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1,700 | 26,666,858 | In conclusion , on the basis of the best available data , the strength of evidence is grade B ( consistent , low- quality evidence ) for full-mouth ( with or without antiseptics ) and quadrant scaling and root planing for treatment of chronic periodontitis | Previous studies have not resolved whether scaling and root planing with a full-mouth ( with or without antiseptics ) or quadrant approach is better for treatment of chronic periodontitis . | A classical treatment for chronic adult periodontitis consists of four to six consecutive sessions of scaling and root planing at a 1- to 2-week interval . Such a so-called " quadrant or sextant therapy " might result in a reinfection of a previously disinfected area by bacteria from an untreated region . The purpose of this study was to investigate , over an 8-month period , the clinical benefits of full-mouth disinfection within a 24-hour period in the control of chronic periodontitis . Ten adult patients with advanced chronic periodontitis were r and omly assigned to a test and a control group . The control group received the st and ard scheme of initial periodontal therapy , consisting of scaling and root planing of the four quadrants was performed within 24 hours and immediately followed by a thorough supra- and subgingival chlorhexidine application to limit any transfer of bacteria . The latter involved tongue brushing with a 1 % chlorhexidine gel for 60 seconds , mouthrinsing with a 0.2 % chlorhexidine solution twice for 60 seconds , repeated subgingival irrigation of all pockets with a 1 % chlorhexidine gel ( 3 times within 10 minutes ) , and mouthrinsing twice daily with a 0.2 % chlorhexidine solution during 2 weeks . In addition , both groups received thorough oral hygiene instructions . The plaque index , gingival index , probing depth , gingival recession , and bleeding on probing were recorded prior to professional cleaning and at 1 , 2 , 4 , and 8 months afterwards . Although the test group scored higher plaque indices than the control group , especially at months 2 and 4 , the gingival index and bleeding tendency showed similar improvements with time . However , when the gingival/plaque ratio was considered , the latter was lower in the test group at all follow-up visits . For pockets > or = 7 mm , full-mouth disinfection showed a significantly ( P = 0.01 ) higher reduction in probing depth at each follow-up visit with , at month 8 , a reduction of 4 mm ( from 8 mm to 4 mm ) , in comparison to 3 mm ( from 8 mm to 5 mm ) for the classical therapy . The increase in gingival recession in the full-mouth disinfection group remained below 0.7 mm , while in the control group it reached 1.9 mm after 8 months . This result ed in a gain of clinical attachment level of 3.7 mm for the test group versus 1.9 mm for the control group . A radiographical examination also indicated a superior improvement for the test group when compared to the control group . This pilot study suggests that a full-mouth disinfection in one day results in an improved clinical outcome in chronic periodontitis as compared to scalings per quadrant at 2-week intervals over several weeks To clarify the source of re-emerging periodontal pathogens after treatment , we compared the ribotypes of Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , Prevotella intermedia/Prevotella nigrescens group and Campylobacter rectus before and after treatment in 7 periodontitis patients and in 6 of the spouses . The patients harbored A. actinomycetemcomitans , P. gingivalis , P. intermedia/P. nigrescens group or C. rectus in their subgingival or salivary sample s before treatment . The respective bacterial species were not detected 1 month after treatment , but reappeared by 6 months later . When available , 4 r and om colonies of each of the 4 species were isolated from both subgingival and salivary sample s at each sampling occasion , the isolates were subcultured , identified and typed applying pheno- and genotypic intraspecies characterization methods . Altogether 90 strains of A. actinomycetemcomitans , P. gingivalis , P. intermedia/P. nigrescens group and C. rectus were available from 2 , 3 , 2 and 4 patients , respectively . The pre- and post-treatment ribotypes of A. actinomycetemcomitans- , P. gingivalis- and P. intermedia/P. nigrescens group-isolates were identical in all respective patients . The pre- and post-treatment ribotypes of C. rectus were identical in 1 of 4 patients , whereas 2 patients harbored a previously not detected post-treatment ribotype and 1 patient harbored the initial and a previously not detected post-treatment ribotype . To study the possibility that periodontitis patients may acquire strains from the spouse after treatment , isolates of A. actinomycetemcomitans , P. gingivalis , P. intermedia/P. nigrescens group and C. rectus ( n = 95 ) from the patients ' spouses were ribotyped and compared with those of the patients . The patient exhibited his own post-treatment ribotypes , different from those of the spouse , of A. actinomycetemcomitans and P. gingivalis in 1 couple and of P. intermedia/P. nigrescens group and C. rectus in 1 couple . In the 2 patients who harbored a previously not detected post-treatment ribotype of C. rectus , one patient shared the new ribotype with the spouse , whereas the other one did not . Although an exogenous source can not be fully ruled out , the patient 's own oral flora seems to be the main source of re-emerging periodontal pathogens after treatment A treatment for periodontal infections often consists of consecutive rootplanings ( per quadrant , at a 1- to 2-week interval ) , without a proper disinfection of the remaining intra-oral niches ( untreated pockets , tongue , saliva , mucosa and tonsils ) . Such an approach , could theoretically lead to a reinfection of previously-treated pockets . The present study aims to examine the effect of a full-mouth disinfection on the microbiota in the above-mentioned niches . Moreover , the clinical benefit of such an approach was investigated . 16 patients with severe periodontitis were r and omly allocated to a test and a control group . The patients from the control group were scaled and rootplaned , per quadrant , at 2-week intervals and obtained oral hygiene instructions . The patients from the test group received a full-mouth disinfection consisting of : scaling and rootplaning of all pockets in 2 visits within 24 h , in combination with tongue brushing with 1 % chlorhexidine gel for 1 min , mouth rinsing with a 0.2 % chlorhexidine solution for 2 min and subgingival irrigation of all pockets ( 3x in 10 min ) with 1 % chlorhexidine gel . Besides oral hygiene , the test group rinsed 2x daily with 0.2 % chlorhexidine and sprayed the tonsils with a 0.2 % chlorhexidine for 2 months . Plaque sample s ( pockets , tongue , mucosa and saliva ) were taken at baseline and after 2 and 4 months , and changes in probing depth , attachment level and bleeding on probing were reported . The full-mouth disinfection result ed in a statistically significant additional reduction/elimination of periodontopathogens , especially in the subgingival pockets , but also in the other niches . These microbiological improvements were reflected in a statistically-significant higher probing depth reduction and attachment gain in the test patients . These findings suggest that a disinfection of all intra-oral niches within a short time span leads to significant clinical and microbiological improvements for up to 4 months AIM To test recolonization of periodontal lesions after full-mouth scaling and root planing ( FM-SRP ) or multiple session-SRP ( MS-SRP ) in a r and omized clinical trial and whether FM-SRP and MS-SRP result in different clinical outcomes . MATERIAL S AND METHODS Thirty-nine subjects were r and omly assigned to FM-SRP or MS-SRP groups . At baseline and after 3 months , probing pocket depth ( PPD ) , plaque index ( PlI ) and bleeding on probing ( BoP ) were recorded . At baseline , immediately after treatment , after 1 , 2 , 7 , 14 and 90 days , paper point sample s from a single site from the maxillary right quadrant were collected for microbiological analysis of five putative pathogens by polymerase chain reaction . RESULTS FM-SRP and MS-SRP result ed in significant reductions in PPD , BoP and PlI and the overall detection frequencies of the five species after 3 months without significant differences between treatments . Compared with MS-SRP , FM-SRP result ed in less recolonization of the five species , significantly for Treponema denticola , in the tested sites . CONCLUSION FM-SRP and MS-SRP result in overall clinical ly and microbiologically comparable outcomes where recolonization of periodontal lesions may be better prevented by FM-SRP OBJECTIVES The beneficial effects of the one-stage , full-mouth disinfection remain controversial in the scientific literature . This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing . This parallel , single blind RCT study aim ed to compare several full-mouth treatment strategies with each other . MATERIAL AND METHODS Seventy-one patients with moderate periodontitis were r and omly allocated to one of the following treatment strategies : scaling and root planing , quadrant by quadrant , at two-week intervals ( negative control , NC ) , full-mouth scaling and root planing within 2 consecutive days ( FRP ) , or three one-stage , full-mouth disinfection ( FM ) protocol s within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics : chlorhexidine ( FMCHX ) for 2 months , amine fluoride/stannous fluoride for 2 months ( FMF ) , or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months ( FMCHX+F ) . At baseline and after 2 , 4 , and 8 a series of periodontal parameters were recorded . RESULTS All treatment strategies result ed in significant ( p<0.05 ) improvements of all clinical parameters over the entire duration of the study . Inter-treatment differences were often encountered . The NC group nearly always showed significant smaller improvements than the two CHX groups . The differences between the FRP or FM groups , and the two CHX groups only sporadically reached a statistical significance . CONCLUSION These observations indicate that the benefits of the " OSFMD " protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time BACKGROUND One-stage full-mouth scaling and root planing ( FM-SRP ) in combination with systemically administered azithromycin was shown to be clinical ly and bacteriologically effective in the treatment of chronic periodontitis . However , FM-SRP requires 2 hours for completion . Azithromycin has a long half-life . Therefore , if SRP of the full mouth is performed within 7 days while an effective concentration of azithromycin remains in the gingiva , the effects may be the same as FM-SRP . The aim of this study was to compare the clinical and bacteriologic effects of FM-SRP and partial-mouth scaling and root planing ( PM-SRP ) in patients with chronic periodontitis , which was performed in three sessions within 7 days , during the effective half-life of systemically administrated azithromycin . METHODS Thirty adult subjects with chronic periodontitis were r and omly divided into three groups ( FM-SRP , PM-SRP , and control ) . A clinical examination was conducted to record the probing depth , clinical attachment level gain , bleeding on probing , gingival index , and volume of gingival crevicular fluid ; bacterial sample s were obtained before treatment and 1 , 3 , 6 , 9 , and 12 months thereafter . Quantitative and qualitative analyses were performed using the polymerase chain reaction-Invader method . RESULTS All clinical parameters showed better improvement in FM-SRP and PM-SRP groups compared to the control group , with no significant differences between the two test groups . Periodontal bacteria were well controlled in the two test groups , but they tended to increase gradually 3 months after treatment in the control group . CONCLUSION PM- and FM-SRP demonstrated comparable clinical and bacteriologic results BACKGROUND / AIMS Recent studies reported significant additional clinical and microbiological improvements when severe adult periodontitis was treated by means of a " one-stage full-mouth " disinfection instead of a st and ard treatment strategy with consecutive root planings quadrant per quadrant . The one stage full-mouth disinfection procedure involves scaling and root planing of all pockets within 24 h in combination with an extensive application of chlorhexidine to all intra-oral niches such as periodontal pockets , tongue dorsum , tonsils ( chairside , and at home for 2 months ) . This study aims to examine the relative importance of the use of chlorhexidine in the one stage full-mouth disinfection protocol . METHODS Therefore , 3 groups of 12 patients each with advanced periodontitis were followed , both from a clinical and microbiological point of view , over a period of 8 months . The patients from the control group were scaled and root planed , quadrant per quadrant . at two-week intervals . The 2 other groups underwent a one stage full-mouth scaling and root planing ( all pockets within 24 h ) with ( Fdis ) or without ( FRp = full-mouth root planing ) the adjunctive use of chlorhexidine . At baseline and after 1 , 2 , 4 and 8 months , the following clinical parameters were recorded : plaque and gingivitis indices , probing depth , bleeding on probing and clinical attachment level . Microbiological sample s were taken from different intra-oral niches ( tongue , mucosa , saliva and pooled sample s from single- and multi-rooted teeth ) . The sample s were cultured on selective and non-selective media in order to evaluate the number of CFU/ml for the key-periodontopathogens . At baseline , an anonymous question naire was given to the patients to record the perception of each treatment ( post operative pain , fever , swelling etc . ) . RESULTS All 3 treatment strategies result ed in significant improvements for all clinical parameters , but the Fdis and FRp patients reacted always significantly more favourably than the control group , with an additional probing depth reduction of + /- 1.5 mm and an additional gain in attachment of + /- 2 mm ( for pockets > or = 7 mm ) . Also from a microbiological point of view both the FRp and Fdis patients showed additional improvements when compared to the control group , as well in the reduction of spirochetes and motile organisms as in the number of CFU/ml of the key-pathogens , especially when the subgingival plaque sample s were considered . The differences between FRp and Fdis patients were negligible . CONCLUSIONS These findings suggest that the benefits of a " one-stage full-mouth disinfection " in the treatment of patients suffering from severe adult periodontitis probably results from the full-mouth scaling and root planing within 24 h rather than the beneficial effect of chlorhexidine . The raise in body temperature the second day after the full-mouth scaling and root planing seems to indicate a Shwartzman reaction OBJECTIVES The aim of this study was to determine whether same-day full-mouth scaling and root planing ( FM-SRP ) and quadrant scaling and root planing ( Q-SRP ) result ed in variations in the systemic humoral immune response dynamics ( antibody titres and avidity ) during active treatment and 3 and 6 months post-therapy . MATERIAL S AND METHODS Forty patients with chronic periodontitis were recruited into this study . Subjects were r and omised into two groups and received either scaling and root planing quadrant by quadrant at 2-weekly intervals ( Q-SRP group ) or same-day full-mouth scaling and root planing ( FM-SRP group ) . Clinical measurements and serum sample s were obtained at baseline and approximately 6 weeks after the last clinical intervention ( R1 ) and 6 months after the initiation of therapy ( R2 ) . Furthermore , serum sample s were obtained from each patient undergoing therapy ( Q-SRP and FM-SRP ) at 3 bi-weekly instances so as to determine the short-term effects of each session of scaling and root planing on the dynamics of the humoral immune response . Serum antibody titre was assayed by enzyme-linked immunosorbent assay ( ELISA ) and antibody avidity was measured by thiocyanate dissociation against five putative periodontal pathogens : Porphyromonas gingivalis ; Actinobacillus actinomycetemcomitans ; Prevotella intermedia ; Treponema denticola and Bacteroides forsythus . RESULTS Both therapies result ed in similar antibody titre reductions against the majority of the organisms tested and although there was a distinct trend for antibody avidity to increase following therapy , this was not found to be statistically significant , reflecting marked inter-individual variation . In addition , no evidence emerged from this study to support increased antibody titres following the active phases of both treatment approaches due to an inoculation effect . Nevertheless , significant short-term increases in antibody avidity to most test bacteria were noted for both treatment strategies . CONCLUSION Both therapies were associated with a reduction in antibody titres and an increase in the binding ability or avidity of antibodies , but there was a marked inter-subject variability and statistical significance was reached for only some of the test bacteria . No significant differences in the humoral antibody dynamics were found between the two treatment approaches AIM This clinical trial investigates the effectiveness of full-mouth disinfection ( FMD ) versus conventional etiological therapy in patients with chronic periodontitis ( CP ) . METHODS The therapy effectiveness was assessed by a r and omized trial , performed over 20 adult periodontitis ( AP ) patients , divided into two groups . Patients were recruited undergoing strict inclusion /exclusion criteria . The following parameters were considered to evaluate and compare the two procedures : bleeding on probing ( BOP ) , Plaque Index ( PLI ) , probing depth ( PD ) , clinical attachment level ( CAL ) . These clinical data were collected at baseline and at three follow-ups ( three months , six months and twelve months from baseline ) . Each parameter was averaged within each group ; then statistic comparisons were performed within groups and between groups . RESULTS In the test-group statistically significant improvements ( P<0.001 ) were found for all parameters between baseline and every following review . The same result was reported in the control group ( with a further significant difference between first and second review ) . Finally , the comparison between groups did not show any difference at any time for every parameter considered . CONCLUSION FMD outcomes are similar to those of the conventional therapy and improvements can be achieved more quickly . FMD does not cause remarkable side effects and reduces the number of therapy sessions . Some aspects about this treatment need further research : maybe FMD could give an extra reduction of bacterial load , in comparison with traditional therapy , result ing in a longer free-infection period ; that could allow a decrease in the frequency of supporting periodontal treatment BACKGROUND The aim of the present study was to evaluate the clinical effects of one-stage periodontal debridement with an ultrasonic instrument , associated with 0.5 % povidone (pvp)-iodine irrigation in patients with chronic periodontitis . METHODS Forty-five patients were r and omly assigned into three groups : the control group ( CG ) received quadrant root planing at 1-week intervals over four consecutive sessions ; the periodontal debridement plus pvp-iodine group ( PD-PIG ) received a 45-minute full-mouth debridement with an ultrasonic instrument , associated with 0.5 % pvp-iodine irrigation ; and the periodontal debridement group ( PDG ) received a 45-minute full-mouth periodontal debridement with an ultrasonic instrument , associated with NaCl irrigation . RESULTS At the 3-month evaluation , the mean probing depth ( PD ) reduction in CG was 2.51+/-0.52 mm , 2.53+/-0.50 mm in PD-PIG , and 2.58+/-0.60 mm in PDG ( P<0.05 ) . The clinical attachment level ( CAL ) analysis showed a statistically significant gain in all groups compared to baseline ( 1.87+/-0.56 mm [ CG ] , 1.94+/-0.70 mm [ PD-PIG ] , and 1.99+/-0.92 mm [ PDG ] ) . Intergroup analysis of PD and CAL at 1 and 3 months showed no differences ( P>0.05 ) . The N-benzoyl-L-arginine-p-nitroanilide ( BAPNA ) test showed a significant reduction in trypsin activity only during the first month ( P<0.05 ) ; at 3 months there were no differences compared to baseline ( P=0.80 ) . CONCLUSION This study provides no evidence that pvp-iodine is effective as an adjunct for one-stage periodontal debridement The aim of this r and omized clinical study was to compare full-mouth scaling and root planing ( FM-SRP ) in two sessions within 24 hours with quadrant-wise scaling and root planing ( Q-SRP ) in four sessions within 4 - 6 weeks and evaluate ( I ) clinical outcome , ( II ) treatment efficiency , and ( III ) treatment discomfort of patients and therapists . Twenty individuals , aged 28 - 65 years , with severe chronic periodontitis were r and omly assigned to treatment with FM-SRP or Q-SRP . At baseline and after 6 months , there were no between-group differences in clinical findings , treatment discomfort , or post-treatment body temperature . The therapists , however , felt that FM-SRP was more physically and psychologically dem and ing than Q-SRP . Mean effective scaling and root planing ( SRP ) time was 165.5 min during the two FM-SRP sessions and 202.1 min during the four Q-SRP sessions . FM-SRP 's initial time savings of 36.6 min compared with Q-SRP diminished to 30.8 min at the 6-month follow-up due to rescaling needs . Total mean treatment time ( comprising SRP and patient reinformation and reinstruction in oral hygiene ) during the first 6 months post-treatment was 321.2 min for FM-SRP and 353.0 min for Q-SRP . Thus , mean savings in total treatment time with FM-SRP was 31.8 min compared with Q-SRP . In conclusion , this study found that both treatment modalities may be recommended for chronic periodontitis patients . Although time saving is possible with FM-SRP , the modality may compromise the therapist 's well-being if practice d frequently due to the risk of musculoskeletal problems The Journal of Evidence -Based Dental Practice ( JEBDP ) is adopting the SORT as its method to better evaluate guideline recommendations and the results from systematic review s ( Fig. 1 ) . The quality rating scores for individual studies also changes to a simpler 3-tier grade that deemphasizes observational studies because the evidence from observational studies is normally too weak to support clinical recommendations . For some years , the st and ard approach to evaluate the quality of individual studies was based on a hierarchical grading system of research design in which r and omized control trials ( RCTs ) received the highest score . The JEBDP has published many articles and evaluations using these methods . For single clinical trials , the quality grade is still very useful and JEBDP will continue to provide a grade of its analysis of these publications ( see later in this article ) . The widespread acceptance of good critical appraisal techniques has also drawn attention to the limitations of these evaluation methods in providing guidance for clinical decision making . An important reason to move from just a quality grade to strength of recommendation is that there is no consensus on how to assign a weight to each of the individual study ’s major and minor defects . Without this , there is large variation in how evaluators assign a grade on a consistent basis . The ‘ ‘ new ’ ’ system to be used by JEBDP is as follows In a st and ard periodontal treatment strategy with consecutive root planings ( per quadrant at a one- to two-week interval ) , re-infection of a disinfected area might occur before completion of the treatment . This study examines , both clinical ly and microbiologically , whether a full-mouth disinfection within 24 hours significantly improves the outcome of periodontal treatment . Ten patients with advanced chronic periodontitis were r and omly allocated to a test and a control group . The patients from the control group received scalings and root planings as well as oral hygiene instructions per quadrant at two-week intervals . Full-mouth disinfection in the test group was sought by the removal of all plaque and calculus ( in two visits within 24 hours ) . In addition , at each of these visits , the tongue was brushed with a 1 % chlorhexidine gel for one min and the mouth rinsed with a 0.2 % chlorhexidine solution for two min . Furthermore , subgingival chlorhexidine ( 1 % ) irrigation was performed in all pockets . The recolonization of the pockets was retarded by oral hygiene and 0.2 % chlorhexidine rinses during two weeks . The clinical parameters were recorded , and plaque sample s were taken from the right upper quadrant at baseline and after one and two months . The test group patients showed a significantly higher reduction in probing depth for deep pockets at both follow-up visits ( p < 0.05 ) . At the one-month visit , differential phase-contrast microscopy revealed significantly lower proportions of spirochetes and motile rods in the test group ( p = 0.01 ) . Culturing showed that the test group harbored significantly fewer pathogenic organisms at one month ( p = 0.005 ) . At two months , the same sites harbored singificantly more " beneficial " bacteria ( p = 0.02 ) . Moreover , all sites of the test group initially harboring P. gingivalis ( 6/10 ) became negative after treatment . These findings suggest that it is possible to achieve a significant improvement of the treatment outcome ( both microbiologically and clinical ly ) with a one-stage full-mouth disinfection BACKGROUND The aim of this r and omized controlled clinical trial was to determine the effects of single-visit full-mouth ultrasonic debridement versus quadrant-wise therapy . MATERIAL AND METHODS Thirty-six subjects with chronic periodontitis , were r and omly allocated to three groups -- quadrant-wise ultrasonic debridement , single-visit full-mouth ultrasonic debridement with povidone iodine and single-visit full-mouth ultrasonic debridement with water . Whole-mouth plaque , bleeding on probing ( BOP ) , pocket depth and attachment level were recorded before treatment and 1 , 3 and 6 months post-treatment . Plaque and saliva sample s were collected for microbiological analysis . RESULTS After treatment , all groups showed significant improvement in clinical parameters . Full-mouth treatments result ed in similar improvements in full-mouth mean plaque percentage , probing pocket depth and probing attachment level as conventional therapy . When data were analysed based on pocket depth and tooth type , there was no difference between groups in probing depth reduction or attachment gains . The full-mouth groups demonstrated greater reduction in BOP% and number of pockets > or = 5 mm and the total treatment time was significantly shorter . The detection frequencies of periodontal pathogens in plaque and saliva showed slight changes with no difference between groups . CONCLUSION Single-visit full-mouth mechanical debridement may have limited additional benefits over quadrant-wise therapy in the treatment of periodontitis , but can be completed in a shorter time AIM To evaluate the clinical efficacy of ( i ) a single session of " full-mouth ultrasonic debridement " ( Fm-UD ) as an initial periodontal treatment approach and ( ii ) re-instrumentation of periodontal pockets not properly responding to initial subgingival instrumentation . METHODS Forty-one patients , having on the average 35 periodontal sites with probing pocket depth ( PPD ) > or = 5 mm , were r and omly assigned to two different treatment protocol s following stratification for smoking : a single session of full-mouth subgingival instrumentation using a piezoceramic ultrasonic device ( EMS PiezonMaster 400 , A+PerioSlim tips ) with water coolant ( Fm-UD ) or quadrant scaling/root planing ( Q-SRP ) with h and instruments . At 3 months , all sites with remaining PPD > or = 5 mm were subjected to repeated debridement with either the ultrasonic device or h and instruments . Plaque , PPD , relative attachment level ( RAL ) and bleeding following pocket probing ( BoP ) were assessed at baseline , 3 and 6 months . Primary efficacy variables were percentage of " closed pockets " ( PPD < or = 4 mm ) , and changes in BoP , PPD and RAL . RESULTS The percentage of " closed pockets " was 58 % at 3 months for the Fm-UD approach and 66 % for the Q-SRP approach ( p>0.05 ) . Both treatment groups showed a mean reduction in PPD of 1.8 mm , while the mean RAL gain amounted to 1.3 mm for Fm-UD and 1.2 mm for Q-SRP ( p>0.05 ) . The re-treatment at 3 months result ed in a further mean PPD reduction of 0.4 mm and RAL gain of 0.3 mm at 6 months , independent of the use of ultrasonic or h and instruments . The efficiency of the initial treatment phase ( time used for instrumentation/number of pockets closed ) was significantly higher for the Fm-UD than the Q-SRP approach : 3.3 versus 8.8 min . per closed pocket ( p<0.01 ) . The efficiency of the re-treatment session at 3 months was 11.5 min . for ultrasonic and 12.6 min . for h and instrumentation ( p>0.05 ) . CONCLUSION The results demonstrated that a single session of Fm-UD is a justified initial treatment approach that offers tangible benefits for the chronic periodontitis patient OBJECTIVES To determine the clinical effects of full mouth compared with quadrant wise scaling and root planing . METHOD Twenty patients with chronic periodontitis ( > or = 2 teeth per quadrant with probing pocket depths ( PPD ) > or = 5 mm and bleeding on probing ( BOP ) were r and omized into a test group treated in two sessions with subgingival scaling and root planing within 24 h ( full-mouth root planing ( FMRP ) ) and a control group treated quadrant by quadrant in four sessions in intervals of 1 week ( quadrant root planing ( QRP ) ) . PPD , relative attachment level ( RAL ) and BOP were recorded at baseline , 3 and 6 months . RESULTS Analysing first quadrant data , in moderately deep pockets ( 5 mm < or = PPD < 7 mm ) there was no evidence for a difference ( FMRP-QRP ) between both groups for PPD reduction ( mean : -0.128 mm ; CI : [ -0.949 , 0.693 ] ; p=0.747 ) , RAL gain ( mean : 0.118 mm ; CI : [ -0.763 , 1.000 ] ; p=0.781 ) , and BOP reduction ( mean : -20.1 % ; CI : [ -44.3 , 4.2 ] ; p=0.099 ) . Likewise , no significant differences between treatments were found for initially deep pockets ( PPD > or = 7 mm ) , neither for first quadrant nor for whole mouth data . CONCLUSION The results of the present study demonstrated equally favourable clinical results following both treatment modalities BACKGROUND A st and ard treatment strategy for periodontal infections often consists of 4 consecutive sessions of scaling and root planing ( per quadrant , at 1- to 2-week intervals ) , without proper disinfection of the remaining intra-oral niches for periodontopathogens . This could theoretically lead to a reinfection of previously disinfected pockets by bacteria from an untreated region/niche . This study aim ed to investigate , over an 8-month period , the clinical benefits of a one stage full-mouth disinfection in the control of severe periodontitis . METHODS Sixteen patients with early-onset periodontitis and 24 patients with severe adult periodontitis were r and omly assigned to test and control groups . The control group was scaled and root planed , per quadrant , at 2-week intervals and given st and ard oral hygiene instructions . A one stage full-mouth disinfection ( test group ) was sought by scaling and root planing the 4 quadrants within 24 hours in combination with the application of chlorhexidine to all intra-oral niches for periodontopathogens . Besides oral hygiene , the test group also rinsed twice daily with a 0.2 % chlorhexidine solution and sprayed the tonsils with a 0.2 % chlorhexidine spray , for 2 months . The plaque index , gingival index , probing depth , bleeding on probing , gingival recession , and clinical attachment level were recorded at baseline and at 1 , 2 , 4 , and 8 months afterwards . RESULTS The one stage full-mouth disinfection result ed , in comparison to the st and ard therapy , in a significant ( P < 0.001 ) additional probing depth reduction and gain in attachment up to 8 months . For initial pockets > or = 7 mm , the " additional " probing depth reduction at the 8 month follow-up was 1.2 mm for single-rooted and 0.9 mm for multi-rooted teeth , with corresponding additional gains in attachment of 1.0 mm and 0.8 mm , respectively . The additional improvements were observed for all subgroups ( adult periodontitis , generalized early-onset cases , smokers ) , with the largest differences in the non-smoking adult periodontitis patients . CONCLUSIONS These findings suggest that a one stage full-mouth disinfection results in an improved clinical outcome for the treatment of chronic adult or early-onset periodontitis as compared to scaling and root planing per quadrant at 2-week intervals BACKGROUND Recent studies showed the clinical benefits of a one stage full-mouth disinfection , when compared to the worldwide st and ard treatment strategy of consecutive root planings per quadrant without proper disinfection of the remaining intraoral niches . The purpose of this study was to investigate the microbiological benefits of such a one stage full-mouth disinfection with special attention to all intraoral niches for periodontopathogens and to evaluate the perception by the patients of the new treatment strategy . METHODS Sixteen patients with early-onset periodontitis and 24 patients with severe adult periodontitis were r and omly assigned to test and control groups . The control group was scaled and root planed , per quadrant , at 2-week intervals and given oral hygiene instructions . The test group received the one stage full-mouth disinfection treatment . At baseline and after 1 , 2 , 4 , and 8 months , microbiological sample s were taken from all niches ( tongue , mucosa , saliva , and pooled sample s from single- and multi-rooted teeth ) . The sample s were cultured on selective and non-selective media . Patient perception of the treatment was evaluated using a question naire . RESULTS In comparison to the st and ard therapy , the one stage full-mouth disinfection result ed in significant additional microbial improvements . The test group showed larger reductions in the proportions of spirochetes and motile organisms in the subgingival flora , and more significant reductions in the density of key pathogens , with even the eradication of P. gingivalis . The beneficial effects in the other niches were primarily restricted to the number of colony-forming units/ml of black-pigmented bacteria , especially on the mucosa and in the saliva and to a lesser extent on the tongue . Both treatments were well tolerated by the patients and the overall severity rating for both therapies was comparable , although 4 quadrants were treated within 24 hours in the test group versus only 1 in the control group . The full-mouth disinfection approach result ed more frequently in a slight increase of body temperature , especially after the second day . CONCLUSIONS These findings support the benefit of a one stage full-mouth disinfection in the treatment of patients with either chronic adult or early-onset periodontitis OBJECTIVE To compare the clinical and microbiological effects of three protocol s for nonsurgical periodontal therapy , including full-mouth scaling and root planing plus systemic antibiotics , on the treatment of chronic periodontitis patients . METHODS Twenty-nine patients diagnosed with moderate to severe chronic periodontitis , selected according to specific criteria , were r and omly assigned to one of three treatment groups : quadrant scaling , full-mouth scaling , and full-mouth scaling supplemented by systemic antibiotics . Antibiotic selection was based on the results of individual susceptibility testing . Oral hygiene instructions and reinforcement were given during the study . All patients received a clinical periodontal and microbiological examination at baseline and at reexamination , 4 - 6 weeks after therapy . Means and st and ard deviations were calculated and differences between groups were analyzed via the Kruskal-Wallis test , p < 0.05 . RESULTS The mean age of the study sample was 49.1 + 11.6 years old , and there were 17 men and 12 women . Patients treated with antibiotics showed antimicrobial susceptibility for amoxicillin and doxycycline . All study groups showed a similar significant improvement in periodontal parameters . Plaque scores were reduced in a range of 29.0 % to 42.6 % . Bleeding on probing was reduced by 34.8 % to 55.0 % ; the reduction for the full-mouth scaling group was larger . Mean reduction in pocket depth was 1.2 to 1.3 mm in all groups . Mean bacterial counts were reduced in the groups receiving full-mouth treatment , but not in the quadrant treatment group . CONCLUSION The three protocol s for non-surgical periodontal treatment demonstrated a similar positive effect on clinical parameters ; however , only full-mouth treatment groups showed a reduction in anaerobic microbial counts at re-examination |
1,701 | 27,820,499 | No beneficial effects were found from self management interventions with improving quality of life .
We also found the exercise component of self management ( four trials ) demonstrated a benefit with reducing pain , improving function and quality of life .
Exercise also offered a benefit over no exercise .
DISCUSSION Pooled results indicate evidence of a beneficial effect from self management strategies with reducing pain and improving function .
The exercise component of self management programmes appears to contribute a significant benefit .
There is encouraging evidence of a small benefit from exercise in self management programs . | BACKGROUND Osteoarthritis ( OA ) is a common cause of pain and disability , and is the most common form of arthritis in the Western world .
The most common joint to be affected is the knee .
Pain and functional disability are common symptoms , which can lead to reduced quality of life and increase the risk of further morbidity .
Current treatment aims to educate patients about the management of OA , reduce pain , improve function , decrease disability and reduce the progression of the disease .
Education with clients has been described as a set of planned educational activities design ed to improve patients ' health behaviours and /or health status .
The purpose of self-education is to maintain or improve health , or , in some cases , to slow deterioration by increasing participant 's perception of self efficacy defined as an ability to control or manage various aspects of OA .
To date , there is no systematic review of the literature undertaken to identify the effectiveness of self-management educational activities for osteoarthritis of the knee .
OBJECTIVE The objective of this systematic review is to evaluate the effectiveness of self-management educational interventions on function and quality of life for adult subjects with OA of the knee . | OBJECTIVE Studies have suggested that the Arthritis Self-Management Program ( ASMP ) course is effective at reducing arthritis pain and health care costs in volunteer participants . There have been no reports of trials of the ASMP in the context of primary care physicians ' practice s , where the potential for spreading the program may be greatest . We conducted a r and omized controlled trial of the ASMP course in a large primary care physician network . METHODS Patients with osteoarthritis , rheumatoid arthritis , or fibromyalgia were recruited for the study . Subjects in the intervention practice s received the 6 week course and those in the control practice s received only the ASMP book , without course . Disability , pain , self-efficacy , mental health , and satisfaction were measured using vali date d instruments at baseline and at 4 months . RESULTS One hundred thirteen patients were recruited for the ASMP course ( intervention ) and completed baseline and 4 month followup question naires . Eighty-four percent completed at least 4 of 6 classes . Seventy-four patients received the ASMP manual ( controls ) and completed both question naires . Patients in the intervention and control groups had similar baseline pain ( p = 0.94 ) , self-efficacy to control pain ( p = 0.90 ) , mental health ( p = 0.10 ) , and vitality scores ( p = 0.21 ) , but those in the intervention arm had slightly less disability ( p = 0.04 ) . At 4 months , there was no significant improvement from baseline in any endpoint and no difference between patients in the intervention and control groups ( all p > 0.2 ) . Patient satisfaction with arthritis care and outcomes was no different for intervention and control patients ( all p > 0.3 ) . All types of health care re source use were similar at baseline and followup for both intervention and control groups ( all p > 0.2 ) . CONCLUSION While the ASMP course has been found to be effective in other patient groups , there were no significant clinical benefits noted at 4 months in patients recruited from primary care practice OBJECTIVE To evaluate the effects of isokinetic exercise versus a program of patient education on pain and function in older persons with knee osteoarthritis . DESIGN A r and omized , comparative clinical trial , with interventions lasting 8 weeks and evaluations of 12 weeks . SETTING An outpatient Veterans Affairs Medical Center clinic and an affiliated university hospital . PATIENTS One hundred thirteen men and women between 50 and 80 years old with diagnosed osteoarthritis of the knee ; 98 completed the entire assigned treatment . INTERVENTION Patients received either a regimen of isokinetic exercise of the quadriceps muscle three times weekly over 8 weeks or a series of 4 discussion s and lectures led by health care professionals . MAIN OUTCOME MEASURES Variables studied for change were isokinetic and isometric quadriceps strength , pain and function determined by categorical and visual analog scales , and overall status using physician and patient global evaluations by the Arthritis Impact Scale , version 2 , Western Ontario McMaster 's Arthritis Index , and Medical Outcome Study Short Form 36 . RESULTS Both treatment groups showed significant strength gains ( p < .05 ) , which occurred over a wider velocity spectrum for the exercise group . Exercised patients also had improved pain scores for more of the variables measured than those receiving education . Both groups had positive functional outcomes and slightly improved measures of overall status . CONCLUSIONS Isokinetic exercise is an effective and well-tolerated treatment for knee osteoarthritis , but a much less costly education program also showed some benefits BACKGROUND Diary recording of pain and disabling activities in osteoarthritis ( OA ) is widely recommended , but , to our knowledge , its impact on symptoms has not been investigated . Exercise programmes have been shown to be effective when patients are closely supervised by nurses or physiotherapists ; however , data are lacking on the efficacy of an unsupervised home based exercise regimen in patients with OA . OBJECTIVES To evaluate the clinical efficacy of patient administered assessment tools and an unsupervised home based exercise programme alone or in combination in patients with OA . METHODS The study was a 24 week , open cluster r and omised controlled trial with a factorial design . Rheumatologists ( n = 867 ) were assigned to four groups according to the treatment given : st and ardised tools ( ST ; n = 220 ) , exercises ( EX ; n = 213 ) , both tools and exercises ( ST+EX ; n = 213 ) , or usual care ( n = 221 ) . Each rheumatologist was to enroll four patients who met the American College of Rheumatology criteria for OA ( three with knee OA , one with hip OA ) . " Tools " consisted of weekly recording of pain and disabling activities in a diary . A home based exercise programme was performed daily at least four times per week with the aid of videotape and booklet . In addition to exercise and assessment , all patients received 12.5 mg or 25 mg of the non-steroidal anti-inflammatory drug rofecoxib once daily . Outcome variables were : pain ( measured on a visual analogue scale , 0 - 100 ) ; Western Ontario and McMaster Universities Osteoarthritis Index , function subscale ( 0 - 100 ) ; and patient assessment of the quality of care ( 0 - 100 ) . RESULTS Overall , 2957 patients with OA ( 2216 knee , 741 hip ) were included . After 24 weeks , both pain and function improved in the ST , EX , ST+EX , and usual care groups ( mean ( SD ) -17 ( 27 ) , -20 ( 29 ) , -15 ( 27 ) , -19 ( 29 ) ; and -11 ( 19 ) , -12 ( 19 ) , -10 ( 19 ) , -11 ( 20 ) , respectively ) , without significant differences between groups . However , patients in the EX and ST+EX groups were more likely to agree that their rheumatologist had done his best to preserve their functional and physical activities . CONCLUSION Although patients ' assessment s favoured the exercise programme , results from this study failed to demonstrate a short term symptomatic effect of the two non-pharmacological treatments ( weekly recording of condition and exercise ) in patients with OA concurrently receiving nonsteroidal anti-inflammatory drugs Implementation studies are recommended to assess the feasibility and effectiveness in real-life of programmes which have been tested in r and omized controlled trials ( RCTs ) . We report on an implementation study of two evidence -based exercise and health education programmes for older adults with osteoarthritis ( OA ) of the knee or hip . Three types of primary health-care providers ( n = 18 ) delivered the OA Knee programme ( n = 20 ) and the OA Hip programme ( n = 20 ) , supported by programme manuals and implementation guidelines , in four regions . The outcome measures were pain and mobility . The Knee programme had OA knowledge and self-efficacy as additional outcome measures . Differences in outcome measures and background variables of participants were assessed between the RCTs and the implementation study . Positive effects ( P < 0.05 ) were found for OA knowledge , pain and self-efficacy in the Knee programme ( n = 157 ) , and for pain in the Hip programme ( n = 132 ) . No effect was found for mobility . Effect sizes of the RCTs and the present study were comparable . Background variables did not explain the variance in the outcome measures . The outcomes of the previous RCTs and the implementation study were comparable , and indicated the ecological validity of the two programmes . The implication s for nationwide dissemination and implementation in The Netherl and s are discussed Objectives To evaluate the effectiveness of two primary care strategies for delivering evidence based care to people aged 55 or over with knee pain : enhanced pharmacy review and community physiotherapy . Design Pragmatic multicentre r and omised clinical trial . Setting 15 general practice s in North Staffordshire . Participants 325 adults aged 55 years or over ( mean 68 years ) consulting with knee pain ; 297 ( 91 % ) reached six month follow-up . Interventions Enhanced pharmacy review ( pharmacological management in accordance with an algorithm ) ; community physiotherapy ( advice about activity and pacing and an individualised exercise programme ) ; control ( advice leaflet reinforced by telephone call ) . Main outcome measure Change in Western Ontario and McMaster Universities osteoarthritis index ( WOMAC ) at 3 , 6 , and 12 months . Results Mean baseline WOMAC pain score was 9.1 ( SD 3.7 ) , and mean baseline function score was 29.9 ( SD 12.8 ) . At three months , the mean reductions in pain scores were 0.41 ( SD 2.8 ) for control , 1.59 ( 3.2 ) for pharmacy , and 1.56 ( 3.4 ) for physiotherapy ; reductions in function scores were 0.80 ( 8.5 ) , 2.61 ( 9.8 ) , and 4.79 ( 10.8 ) . Compared with control , mean differences in change scores for physiotherapy were 1.15 ( 95 % confidence interval 0.2 to 2.1 ) for pain and 3.99 ( 1.2 to 6.8 ) for function ; those for pharmacy were 1.18 ( 0.3 to 2.1 ) for pain and 1.80 ( −0.8 to 4.5 ) for function . These differences were not sustained to six or 12 months . Significantly fewer participants in the physiotherapy group reported consulting their general practitioner for knee pain in the follow-up period , and use of non-steroidal anti-inflammatory drugs was lower in the physiotherapy and pharmacy groups than in the control group . Conclusions Evidence based care for older adults with knee pain , delivered by primary care physiotherapists and pharmacists , result ed in short term improvements in health outcomes , reduced use of non-steroidal anti-inflammatory drugs , and high patient satisfaction . Physiotherapy seemed to produce a shift in consultation behaviour away from the traditional general practitioner led model of care . Trial registration UK National Research Register N0286046917 ; Current Controlled Trials IS RCT N55376150 OBJECTIVE To test the effects of a high intensity home-based progressive strength training program on the clinical signs and symptoms of osteoarthritis ( OA ) of the knee . METHODS Forty-six community dwelling patients , aged 55 years or older with knee pain and radiographic evidence of knee OA , were r and omized to a 4 month home based progressive strength training program or a nutrition education program ( attention control ) . Thirty-eight patients completed the trial with an adherence of 84 % to the intervention and 65 % to the attention control . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index pain and physical function subscales . Secondary outcomes included clinical knee examination , muscle strength , physical performance measures , and question naires to measure quality of life variables . RESULTS Patients in the strength training group who completed the trial had a 71 % improvement in knee extension strength in the leg reported as most painful versus a 3 % improvement in the control group ( p < 0.01 ) . In a modified intent to treat analysis , self-reported pain improved by 36 % and physical function by 38 % in the strength training group versus 11 and 21 % , respectively , in the control group ( p = 0.01 for between group comparison ) . In addition , those patients in the strength training group who completed the trial had a 43 % mean reduction in pain ( p = 0.01 vs controls ) , a 44 % mean improvement in self-reported physical function ( p < 0.01 vs controls ) , and improvements in physical performance , quality of life , and self-efficacy when compared to the control group . CONCLUSION High intensity , home based strength training can produce substantial improvements in strength , pain , physical function and quality of life in patients with knee OA We conducted a pilot study of a nurse-run telephone self-management programme for elderly people with osteoarthritis ( OA ) . Thirty-two subjects , aged 60 years or more , with a diagnosis of OA were recruited from two hospital rheumatology clinics and were r and omized to a control or intervention group . The intervention group received six weekly mailings of OA health education modules , a relaxation audio-tape and six weekly 45 min follow-up telephone self-management sessions . There was a 100 % compliance rate in the intervention group , and all subjects completed baseline and three-month interviews ; one subject in each group was lost to six-month follow-up . There were no significant differences in self-management between the control and intervention groups . However , at three months there were improvements in the intervention group ( relative to baseline ) on some outcome measures . The results suggest that the telephone may be a useful tool for reinforcing health-promoting activities for patients Abstract Objectives : To determine whether a home based exercise programme can improve outcomes in patients with knee pain . Design : Pragmatic , factorial r and omised controlled trial of two years ' duration . Setting : Two general practice s in Nottingham . Participants : 786 men and women aged—45 years with self reported knee pain . Interventions : Participants were r and omised to four groups to receive exercise therapy , monthly telephone contact , exercise therapy plus telephone contact , or no intervention . Patients in the no intervention and combined exercise and telephone groups were r and omised to receive or not receive a placebo health food tablet . Main outcome measures : Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities ( WOMAC ) osteoarthritis index at two years . Secondary outcomes included knee specific physical function and stiffness ( scored on WOMAC index ) , general physical function ( scored on SF-36 question naire ) , psychological outlook ( scored on hospital anxiety and depression scale ) , and isometric muscle strength . Results : 600 ( 76.3 % ) participants completed the study . At 24 months , highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups ( mean difference -0.82 , 95 % confidence interval -1.3 to -0.3 ) . Similar improvements were observed at 6 , 12 , and 18 months . Regular telephone contact alone did not reduce pain . The reduction in pain was greater the closer patients adhered to the exercise plan . Conclusions : A simple home based exercise programme can significantly reduce knee pain . The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist The objective of this study was to determine whether the Arthritis Self-Management Programme ( ASMP ) improves perceptions of control , health behaviours and health status , and changes use of health care re sources . The design was a pragmatic r and omized controlled study ; participants were allocated to ASMP ( Intervention Group ) or a 4-month waiting-list Control Group . The Intervention Group completed a 12-month follow-up . In total , 544 people with arthritis were recruited from the community--311 in the Intervention Group and 233 in the Control Group . Main outcome measures included : arthritis self-efficacy , health behaviours ( exercise , cognitive symptom management , diet and relaxation ) and health status ( pain , fatigue , anxiety , depression and positive affect ) . At 4 months follow-up , the ASMP had a significant effect on arthritis self-efficacy for other symptoms and pain subscales . Performance of a range of health behaviours ( cognitive symptom management , communication with physicians , dietary habit , exercise and relaxation ) was significantly greater among the Intervention Group . The Intervention Group were significantly less depressed and had greater positive mood . In addition , trends towards decreases on fatigue and anxiety were noted . Physical functioning , pain and GP visits remained stable at 4 months . A similar pattern of findings was found at 12 months follow-up for the Intervention Group . Furthermore , a significant improvement was found on pain and visits to GPs had decreased . Apart from a small improvement on physical functioning among the Intervention Group participants with osteoarthritis 12 months , all effects were independent of the type of arthritis . The findings suggest that the ASMP is effective in promoting improvements in perception of control , health behaviours and health status , when delivered in UK setting This study evaluated a novel intervention for older osteoarthritis ( OA ) patients and their spousal caregivers that consisted of st and ard patient education supplemented by information related to effectively managing arthritis as a couple . Twenty-four female OA patients and their husb and s were r and omly assigned to either an educational intervention that was targeted at both patient and spouse or to a patient education intervention that was targeted at only the patient . Findings revealed that both interventions were evaluated favorably but the couple intervention was better attended than the patient intervention . In addition , patients in the couple intervention experienced greater increased efficacy in managing arthritis pain and other symptoms . The findings of this pilot study point to the utility of a dyadic intervention approach to management of OA in late life OBJECTIVE To examine the effects of aerobic and resistance exercise on self-efficacy beliefs in older adults with knee osteoarthritis ( OA ) and to determine whether self-efficacy and knee pain mediated the effects of the treatments on stair time performance and health perceptions . METHODS Measures of self-efficacy , knee pain , stair climbing performance , and health perceptions were collected prior to r and omization and again at an 18-month followup in older adults with knee OA who were assigned to 1 of 3 treatment conditions : aerobic exercise , resistance training , or health education control . All analyses were conducted on the intention-to-treat principle . RESULTS Both exercise treatments increased self-efficacy for stair climbing in comparison to the health education control group . Both knee pain and self-efficacy mediated the effect of the treatments on stair climb time , whereas only knee pain mediated health perceptions . CONCLUSIONS The findings suggest that control beliefs and changes in physical symptoms such as knee pain are important outcomes in physical activity programs with patients who have OA of the knee . Moreover , these variables mediate the effects that such programs have on disability and health perceptions BACKGROUND AND PURPOSE The knee is the weight-bearing joint most commonly affected by osteoarthritis ( OA ) . The symptoms of pain , morning stiffness of short duration and physical dysfunction in the activities of daily living ( ADL ) can have an effect on many aspects of health , affecting quality of life . Regular and moderate physical activity adapted to individuals ' life-styles and education , and joint protection strategies have been advocated as conservative management . The purpose of the present study was to assess the impact of an exercise and walking protocol on the quality of life of elderly people with knee OA . METHOD The study design was a r and omized controlled clinical trial . The subjects comprised 50 elderly people , aged 65 or more , with knee OA who had been referred to the geriatric outpatient unit for rehabilitation . Changes in severity of pain and quality of life were compared between a control group ( CG ) and an experimental group ( EG ) . Both groups participated in an educational session and the EG also received a 12-week exercise and walking protocol . Both groups were assessed at baseline and after three and six months by an independent observer . The Lequesne Index of Knee OA Severity ( LI ) , the Health Assessment Question naire ( HAQ ) and the Medical Outcomes Short-Form Health Survey ( SF-36 ) were used as measurement instruments . RESULTS In the CG , the measures of quality of life ( SF-36 ) , the HAQ and the LI between subjects did not yield statistically significant differences over the three measurement points . For the EG , there was a significant improvement in function , measured by HAQ , and decreasing OA symptom severity , measured by LI . For the SF-36 there were significant improvements in physical function , functional role limitation and pain . Comparisons between the groups showed statistically significant differences after three and six months for all measures , except for the SF-36 emotional domains . CONCLUSION The exercise protocol and walking programme had a positive effect on the quality of life of elderly individuals with knee OA OBJECTIVES To determine whether a home-based pedometer-driven walking program with arthritis self-management education ( Walk + ) would increase physical activity , muscle strength , and functional performance in older adults with osteoarthritis ( OA ) of the knee as opposed to arthritis self-management education alone ( EDU ) . DESIGN A r and omized two-by-three ( group-by-time ) design with participants assigned to Walk + ( n = 17 , mean age + /- st and ard deviation = 69.6 + /- 6.7 ) or EDU ( n = 17 , age = 70.8 + /- 4.7 ) . SETTING Community located in the Baltimore-Washington area . PARTICIPANTS Thirty-four community-dwelling adults , aged 60 and older with symptomatic knee OA and self-reported functional impairment . INTERVENTIONS Both groups received 12 hours of the Arthritis Self-Management program over 12 weeks and were followed for an additional 12 weeks . In addition , the Walk + group received individualized instruction in the use of a pedometer , with the goal of increasing their step count by 30 % of their baseline step count . MEASUREMENTS The outcome measures were physical activity ( daily step counts and total activity vector magnitude as measured by a pedometer and Tritrac-R3D accelerometer ) , quadriceps femoris strength ( isometric peak torque ) , and functional performance tasks ( 100-foot walk-turn-walk , timed stair climb , timed chair rise , and pain status ) . RESULTS Daily steps walked showed a significant group-by-time interaction ( P = .04 ) after controlling for age . From baseline to completion of training , a 23 % increase in daily steps occurred in the Walk + group and a 15 % decrease in the EDU group . Although steps increased in the Walk + group , total activity vector magnitude was maintained , suggesting a more efficient gait . The Walk + group became quicker than the EDU group in the normal-pace walk-turn-walk ( P = .04 ) . An isometric strength gain of 21 % postintervention was seen in the Walk + group , compared with a loss of 3.5 % in the EDU group . CONCLUSION In older adults with symptomatic knee OA , Walk + appears to increase walking , with improvements in muscle strength and walking performance . The use of a home-based pedometer-driven program to increase physical activity , strength , and function in this population warrants further research OBJECTIVE To evaluate the long-term effects of a spouse-assisted coping skills intervention in patients with osteoarthritis ( OA ) of the knees , and to evaluate how pre- to posttreatment changes in marital adjustment and self-efficacy relate to long-term improvements in pain , psychological disability , physical disability , pain coping , and pain behavior . METHODS A followup study was conducted with 88 OA patients who had been r and omly assigned to 1 of 3 treatment conditions : 1 ) spouse-assisted coping skills training ( spouse-assisted CST ) , 2 ) a conventional CST intervention with no spouse involvement , and 3 ) an arthritis education-spousal support ( AE-SS ) control condition . To evaluate long-term outcome , comprehensive measures of self-efficacy , marital adjustment , pain , psychological disability , physical disability , pain coping , and pain behavior were collected from these individuals at 6 and 12 months posttreatment . RESULTS Data analysis revealed that , at 6-month followup , patients in the spouse-assisted CST condition scored higher on measures of coping and self-efficacy than those in the AE-SS control group . At 6-month followup , patients who received CST without spouse involvement showed a significantly higher frequency of coping attempts and reported higher levels of marital adjustment than those in the AE-SS control group . At 12-month followup , patients in the spouse-assisted CST condition had significantly higher overall self-efficacy than those in the AE-SS control condition . In addition , patients in both the spouse-assisted CST and CST only conditions tended to show improvements in physical disability at the 12-month followup . Individual differences in outcome were noted at the 12-month followup . Patients in the spouse-assisted CST condition who reported initial ( pre- to posttreatment ) increases in marital adjustment had lower levels of psychological disability , physical disability , and pain behavior at 12-month followup . However , for patients in the conventional CST and AE-SS control conditions , increases in marital adjustment occurring over the initial phase of treatment were related to increases in pain and decreases in scores on the Pain Control in Rational Thinking factor of the Coping Strategies Question naire . Finally , patients in the spouse-assisted CST condition who showed pre- to posttreatment increases in self-efficacy were more likely to show decreases in pain , psychological disability , and physical disability at 12-month followup . CONCLUSIONS These findings suggest that spouse-assisted CST can enhance self-efficacy and improve the coping abilities of OA patients in the long term . Individual differences in the long-term outcome of spouse-assisted CST were noted , with some patients ( those showing increases in marital satisfaction and self-efficacy ) showing much better outcomes than others Osteoarthritis ( OA ) is the commonest cause of locomotor disability and forms a major element of the workload of the primary care team . There is evidence that patient education may improve quality of life , physical functioning , mental health and coping as well as reducing health service use . The aim of this study was to evaluate the effectiveness of a primary care-based patient education programme ( PEP ) using a r and omised controlled trial . A cluster r and omised controlled trial , involving 22 practice s , was used to determine the efficacy of a nurse-led education programme . The programme consisted of a home visit and four 1-h teaching sessions . Patients were assessed at baseline and then 1 , 3 , 6 and 12 months post intervention using 36-item Short Form ( SF-36 ) , Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , arthritis helplessness index and a patient knowledge question naire . Direct interviews were used at baseline and at the 12-month follow-up . There were no differences in depression , OA knowledge , pain or physical ability at either 1 month or 1 year between the two groups . Control practice s ( 65 patients from 12 practice s ) recruited significantly fewer patients than intervention practice s ( 105 patients from ten practice s , p=0.02 ) . Control practice s had more doctors ( p=0.02 ) , more non-white patients ( p=0.007 ) , fewer patients living alone ( p=0.005 ) and lower levels of disability ( p=0.008 ) . We detected a lack of benefit of PEP for people with OA of the knee . This was thought to be due in part to the short intervention time employed and the heterogeneous nature of the disease and the population studied OBJECTIVE To determine whether gains in functioning observed immediately following participation in an 8-week program of supervised fitness walking for patients with knee osteoarthritis were sustained at 1-year followup . METHODS Twenty-nine ( 61.1 % ) of 47 original intervention program patients and 23 ( 51.1 % ) of 45 original control patients were interviewed by telephone at 1-year followup . Patients completed the Arthritis Impact Measurement Scales physical activity , arthritis impact , pain , medication use , and general health perceptions subscales , as well as a separate visual analog pain scale and measures of perceived self-efficacy to cope with arthritis pain and other symptoms . RESULTS Adherence to walking was low , and there were no statistically significant differences between intervention and control patients at one year . CONCLUSIONS The failure of intervention patients to maintain regular walking result ed in loss of functional benefits that were observed at 8 weeks in the original study . Long-term adherence to walking is critical to maintenance of initial gains in functional outcomes Osteoarthritis ( OA ) is a common , chronic condition that affects most older adults . Adults with OA must deal with pain that leads to limited mobility and may lead to disability and difficulty maintaining independence . A longitudinal , r and omized clinical trial pilot study was conducted to determine whether Guided Imagery ( GI ) with Progressive Muscle Relaxation ( PMR ) would reduce pain and mobility difficulties of women with OA . Twenty-eight older women with OA were r and omly assigned to either the treatment or the control group . The treatment consisted of listening twice a day to a 10-to-15-minute audiotaped script that guided the women in GI with PMR . Repeated- measures ANOVA revealed a significant difference between the two groups in the amount of change in pain and mobility difficulties they experienced over 12 weeks . The treatment group reported a significant reduction in pain and mobility difficulties at week 12 compared to the control group . Members of the control group reported no differences in pain and non-significant increases in mobility difficulties . The results of this pilot study justify further investigation of the effectiveness of GI with PMR as a self-management intervention to reduce pain and mobility difficulties associated with OA OBJECTIVE To compare 16 weeks of isometric versus dynamic resistance training versus a control on knee pain and functioning among patients with knee osteoarthritis ( OA ) . DESIGN R and omized clinical trial . SETTING Outpatient setting . PARTICIPANTS A total of 102 volunteer subjects with OA of the knee r and omized to isometric ( n=32 ) and dynamic ( n=35 ) resistance training groups or a control ( n=35 ) . INTERVENTIONS Strength exercises for the legs , 3 times weekly for 16 weeks . Dynamic group : exercises across a functional range of motion ; isometric : exercises at discrete joint angles . MAIN OUTCOME MEASURES The time to descend and ascend a flight of 27 stairs and to get down and up off of the floor . Knee pain was assessed immediately after each functional task . The Western Ontario and McMaster Universities Osteoarthritis Index was used to assess perceived pain , stiffness , and functional ability . RESULTS In the isometric group , time to perform all 4 functional tasks decreased ( P<.05 ) by 16 % to 23 % . In the dynamic group , time to descend and ascend stairs decreased by 13 % to 17 % . Both groups decreased knee pain while performing the functional tasks by 28 % to 58 % . Other measures of pain and functioning were significantly and favorably affected in the training groups . The improvements in the 2 training groups as a result of their respective therapies were not significantly different . The control group did not change over the duration of the study . CONCLUSION Dynamic or isometric resistance training improves functional ability and reduces knee joint pain of patients with knee OA & NA ; This study tested the separate and combined effects of spouse‐assisted pain coping skills training ( SA‐CST ) and exercise training ( ET ) in a sample of patients having persistent osteoarthritic knee pain . Seventy‐two married osteoarthritis ( OA ) patients with persistent knee pain and their spouses were r and omly assigned to : SA‐CST alone , SA‐CST plus ET , ET alone , or st and ard care ( SC ) . Patients in SA‐CST alone , together with their spouses , attended 12 weekly , 2‐h group sessions for training in pain coping and couples skills . Patients in SA‐CST+ET received spouse‐assisted coping skills training and attended 12‐weeks supervised ET . Patients in the ET alone condition received just an exercise program . Data analyses revealed : ( 1 ) physical fitness and strength : the SA‐CST+ET and ET alone groups had significant improvements in physical fitness compared to SA‐CST alone and patients in SA‐CST+ET and ET alone had significant improvements in leg flexion and extension compared to SA‐CST alone and SC , ( 2 ) pain coping : patients in SA‐CST+ET and SA‐CST alone groups had significant improvements in coping attempts compared to ET alone or SC and spouses in SA‐CST+ET rated their partners as showing significant improvements in coping attempts compared to ET alone or SC , and ( 3 ) self‐efficacy : patients in SA‐CST+ET reported significant improvements in self‐efficacy and their spouses rated them as showing significant improvements in self‐efficacy compared to ET alone or SC . Patients receiving SA‐CST+ET who showed increased self‐efficacy were more likely to have improvements in psychological disability . An intervention that combines spouse‐assisted coping skills training and exercise training can improve physical fitness , strength , pain coping , and self‐efficacy in patients suffering from pain due to osteoarthritis OBJECTIVE To assess in a primary healthcare setting the efficacy of a self-management program in middle-aged patients with osteoarthritis ( OA ) . METHODS This was a 2-group r and omized controlled trial , with 273 patients aged 40 to 60 years with OA of the hip(s ) and /or knee(s ) . The experimental intervention was compared with care-as-usual . Treatments and followup measurements were performed in a general healthcare setting by general practitioners . Duration of followup was 21 months after start of the intervention . Instruction in self-management techniques was given by physiotherapists . The main outcome measures were pain severity in hips and knees , other significant complaints , and functional limitations . RESULTS To begin , 297 patients were r and omized : 149 as self-management and 148 controls ; before the intervention 24 withdrew for practical reasons ( 17 self-management , 7 controls ) . At 3-month followup the intervention group was significantly improved on a visual analog scale ( VAS ) for knee pain ( score 0.67 ; SD 2.10 ) and the WOMAC ( score 2.46 ; SD 9.49 ) , while the control group showed stable VAS knee pain ( 0.01 ; SD 2.00 ) and deterioration on WOMAC ( -0.53 ; SD 9.47 ) . At 21-month followup the differences between the groups increased in favor of the intervention group ( VAS pain knee : p values from 0.023 at 3 mo to 0.004 at 21 mo ; WOMAC : p values from 0.030 to 0.022 ) . CONCLUSION The self-management program positively influenced knee pain and self-reported functional level in this sample of patients with OA . Differences between the study groups increased during followup in favor of the intervention group Abstract Objective To evaluate clinical effectiveness of a self management programme for arthritis in patients in primary care with osteoarthritis . Design R and omised controlled trial . Setting 74 general practice s in the United Kingdom . Participants 812 patients aged 50 and over with osteoarthritis of hips or knees ( or both ) and pain or disability ( or both ) . Intervention Participants were r and omised to six sessions of self management of arthritis and an education booklet ( intervention group ) or the education booklet alone ( control group ) . Main outcome measures Primary outcome was quality of life , as assessed by the short form health survey ( SF-36 ) . Several other physical and psychosocial secondary outcomes were assessed . Data were collected at baseline , four months , and 12 months . Results Response rates were 80 % and 76 % at four and 12 months . The two groups showed significant differences at 12 months on the anxiety subscore of the hospital anxiety and depression scale ( mean difference −0.62 , 95 % confidence interval −1.08 to −0.16 ) , arthritis self efficacy scale for pain ( 0.98 , 0.07 to 1.89 ) , and self efficacy for other aspects of management ( 1.58 , 0.25 to 2.90 ) . Results were similar for intention to treat and per protocol analyses . No significant difference was seen in number of visits to the general practitioner at 12 months . Conclusions The self management of arthritis programme reduced anxiety and improved participants ' perceived self efficacy to manage symptoms , but it had no significant effect on pain , physical functioning , or contact with primary care . Trial registration Current Controlled Trials IS RCT N79115352 [ controlled-trials.com ] OBJECTIVE Both the Arthritis Self-Management Program ( ASMP ) and the generic Chronic Disease Self-Management Program ( CDSMP ) have been shown to be successful in improving conditions in patients with arthritis . This study compared the relative effectiveness of the 2 programs for individuals with arthritis . METHODS Patients whose primary disease was arthritis were r and omized to the ASMP ( n = 239 ) or to the CDSMP ( n = 116 ) . Analyses of covariance were used to compare the outcome measures for the 2 programs at 4 months and 1 year . Measures included quality of life outcomes ( self reported , health distress , disability , activity limitation , global health , pain , and fatigue ) , health behaviors ( practice of mental stress management , stretching and strength exercise , aerobic exercise ) , self efficacy , and health care utilization ( physician visits and hospitalizations ) . RESULTS Both programs showed positive results . The disease-specific ASMP appeared to have advantages over the more generic CDSMP for patients with arthritis at 4 months . These advantages had lessened slightly by 1 year . CONCLUSION The disease-specific ASMP should be considered first where there are sufficient re sources and participants . However , both programs had positive effects , and the CDSMP should be considered a viable alternative OBJECTIVE To determine whether the effects of an exercise programme in patients with osteoarthritis of hip or knee are sustained at six and nine months ' follow up . METHODS A r and omised , single blind , clinical trial was conducted in a primary care setting . Patients with osteoarthritis of hip or knee ( ACR criteria ) were selected . Two intervention groups were compared . Both groups received treatment from their general practitioner , including patient education and drug treatment if necessary . The experimental group also received exercise treatment from a physiotherapist in primary care . The treatment period was 12 weeks , with an ensuing 24 week follow up . The main outcome measures were pain , drug use ( non-steroidal anti-inflammatory drugs ) , and observed disability . RESULTS 201 patients were r and omly allocated to the exercise or control group , and 183 patients completed the trial . At 24 weeks exercise treatment was associated with a small to moderate effect on pain during the past week ( difference in change between the two groups −11.5 ( 95 % CI −19.7 to −3.3 ) . At 36 weeks no differences were found between the groups . CONCLUSIONS Beneficial effects of exercise decline over time and finally disappear OBJECTIVE To assess the effect of a program of supervised fitness walking and patient education on functional status , pain , and use of medication in patients with osteoarthritis of the knee . DESIGN An 8-week r and omized , controlled trial . SETTING Inpatient and outpatient services of an orthopedic hospital in an academic medical center . PATIENTS A total of 102 patients with a documented diagnosis of primary osteoarthritis of one or both knees participated in the study . Data were obtained on 47 of 51 intervention patients and 45 of 51 control patients . INTERVENTIONS An 8-week program of supervised fitness walking and patient education or st and ard routine medical care . MEASUREMENTS Patients were evaluated and outcomes assessed before and after the intervention using a 6-minute test of walking distance and scores on the physical activity , arthritis impact , pain , and medication subscales of the Arthritis Impact Measurement Scale ( AIMS ) . RESULTS Patients r and omly assigned to the walking program had a 70-meter increase in walking distance relative to their baseline assessment , which represents an improvement of 18.4 % ( 95 % Cl , 9.8 % to 27.0 % ) . In contrast , controls showed a 17-meter decrease in walking distance relative to their baseline assessment ( P less than 0.001 ) . Improvements in functional status as measured by the AIMS physical activity subscale were also observed in the walking group but not in the control group ( P less than 0.001 ) ; patients assigned to the walking program improved 39 % ( Cl , 15.6 % to 60.4 % ) . Although changes in scores on the arthritis impact subscale were similar in the two groups ( P = 0.093 ) , the walking group experienced a decrease in arthritis pain of 27 % ( Cl , 9.6 % to 41.4 % ) ( P = 0.003 ) . Medication use was less frequent in the walking group than in the control group at the post-test ( P = 0.08 ) . CONCLUSIONS A program of supervised fitness walking and patient education can improve functional status without worsening pain or exacerbating arthritis-related symptoms in patients with osteoarthritis of the knee OBJECTIVE Evaluation of a self-management program for patients with osteoarthritis ( OA ) of the hip or knee . The program , which consisted of 6 weekly sessions of 2 hours , included health education by a peer and physical exercises taught by a physical therapist . METHODS R and omized controlled trial . Inclusion criteria were diagnosis of OA of the hip or knee according to ACR clinical and radiographic criteria and age 55 to 75 years . EXCLUSION CRITERIA on waiting list for joint replacement . There were pretest , posttest , and followup ( 6 months ) assessment s. The experimental group consisted of 56 patients , the control group 49 . Outcome variables were pain , quality of life , activity restrictions , knowledge about OA , self-efficacy , body mass index ( BMI ) , and mobility measures . Attention was also paid to effects on health care utilization and lifestyle behavior . RESULTS Significant MANOVA group x time effects ( p < 0.05 , one-sided ) were found for pain , quality of life , strength of the left M. quadriceps , knowledge , self-efficacy , BMI , physically active lifestyle , and visits to the physical therapist . Most effects were moderate at posttest assessment and smaller at followup . No effects were found for range of motion and functional tasks . CONCLUSION The program was reasonably effective , but more attention should be paid to proactive followup interventions and to the selection of participants OBJECTIVE To assess the effect of a home based exercise programme , design ed to improve quadriceps strength , on knee pain and disability . Methods —191 men and women with knee pain aged 40–80 were recruited from the community and r and omised to exercise ( n=113 ) or no intervention ( n=78 ) . The exercise group performed strengthening exercises daily for six months . The primary outcome measure was change in knee pain ( Western Ontario McMaster Osteoarthritis index ( WOMAC ) ) . Secondary measures included visual analogue scales ( VAS ) for pain on stairs and walking and WOMAC physical function scores . Results —WOMAC pain score reduced by 22.5 % in the exercise group and by 6.2 % in the control group ( between group difference p<0.05 , unpairedt test).VAS scores for pain also reduced in the exercise group compared with the control group ( p<0.05 ) . Physical function scores reduced by 17.4 % in the exercise group and were unchanged in controls ( p<0.05 ) . Conclusion —A simple programme of home quadriceps exercises can significantly improve self reported knee pain and function & NA ; This study examined the relationship of pain coping strategies to osteoarthritis patients ’ ratings of self‐efficacy and to spouses ’ ratings of the patients ’ self‐efficacy . Subjects , 130 individuals having osteoarthritis of the knees and persistent knee pain , completed a pain coping strategies measure ( the Coping Strategies Question naire ) , a measure of self‐efficacy ( the Arthritis Self‐Efficacy Scale ) , and a measure of pain ( the McGill Pain Question naire ) . Two sets of regression analyses were conducted , one examining the degree to which pain coping strategies predicted patients ’ self‐efficacy ratings , and the other examining the degree to which coping strategies predicted spouses ’ ratings of the patients ’ self‐efficacy . Several pain coping strategies were found to predict a significant proportion of variance in patients ’ ratings of self‐efficacy : ( i ) ignoring pain sensations was related to higher self‐efficacy for pain ; ( ii ) coping self statements were related to higher self‐efficacy for controlling other arthritis symptoms ( e.g. , fatigue or mood symptoms ; and ( iii ) catastrophizing was related to lower self‐efficacy for pain , and self‐efficacy for other arthritis symptoms . Pain coping strategies were also found to predict a significant proportion of variance in spouses ’ ratings of the patients ’ self‐efficacy . Specifically : ( i ) diverting attention was related to lower spousal ratings of self‐efficacy for pain ; ( ii ) praying or hoping was related to lower spousal ratings of self‐efficacy for function ; and ( iii ) catastrophizing was related to lower spousal ratings of self‐efficacy for control of fatigue or mood symptoms . The findings regarding coping strategies were particularly interesting in that they were obtained even after controlling for pain intensity and demographic variables . The pain coping strategies identified are potentially important targets for cognitive‐behavioral assessment and treatment efforts . Interventions design ed to increase the use of adaptive pain coping strategies and decrease the use of maladaptive pain coping strategies could enhance self‐efficacy , reduce pain , and improve the physical and psychological functioning of individuals having osteoarthritis After we assessed the functional status of 439 patients with osteoarthritis , we r and omly assigned them to 1 of 3 intervention groups or to a control group . The interventions consisted of providing information , and differed only in the method of delivery : by phone , in person at the clinic , or both . Physical health improved ( P = 0.02 ) , pain was reduced ( P = 0.02 ) , and psychological health improved marginally ( P = 0.10 ) in patients contacted by phone compared with those not contacted by phone . In those contacted only at the clinic , physical health worsened ( P = 0.02 ) , but neither pain ( P = 0.80 ) nor psychological health ( P = 0.90 ) differed from the values in patients not contacted at the clinic . We conclude that telephone contact is a useful intervention that can enhance the functional status of patients with osteoarthritis We compared a cognitive-behavior modification and a traditional education intervention for adults with osteoarthritis ( OA ) . Forty OA patients were r and omly assigned to one of two groups : cognitive-behavior modification or didactic lectures . During ten weekly sessions , the cognitive-behavior group learned methods for coping with pain and the disabilities associated with OA . The traditional education group experienced a series of lectures from health care professionals . Prior to the interventions and following 2 , 6 , and 12 months , patients in both groups were evaluated with a general Quality of Well-being ( QWB ) scale , the Arthritis Impact Measurement Scales ( AIMS ) , the Beck Depression Inventory ( BDI ) , and other measures . Although there were some differences between the two groups at 2-month follow-up , by the end of 1 year , physical and psychological functioning did not differ significantly between the two groups . In comparison to baseline , both groups demonstrated initial changes on QWB , depression , and the pain component of the AIMS . Improvements in depression remained through the 1-year follow-up . Multiple regression analysis demonstrated that the mobility and physical activity aspects of the AIMS were significant long-term predictors of outcome ( 1 year ) for general quality -of-life measures . One-year outcomes for depression were significantly predicted from scores on social support and mobility measures from the AIMS . We conclude that cognitive-behavior modification and education produce similar effects on long-term physical and psychological functioning in OA patients |
1,702 | 22,419,284 | There was no evidence of a benefit with depot administration of progestagens versus other treatments ( low dose oral contraceptive or leuprolide acetate ) for reduced symptoms .
There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy .
Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups .
There was no evidence of a benefit of anti-progestagens ( gestrinone ) compared with danazol .
There is only limited evidence to support the use of progestagens and anti-progestagens for pain associated with endometriosis | BACKGROUND Endometriosis is a chronic inflammatory condition defined by the presence of gl and s and stroma outside the uterine cavity .
It occurs in 7 % to 10 % of all women of reproductive age and may present as pain or infertility .
The pelvic pain may be in the form of dysmenorrhoea , dyspareunia or pelvic pain .
Initially a combination of estrogens and progestagens was used to create a pseudopregnancy and alleviate the symptoms associated with endometriosis .
Progestagens alone or anti-progestagens have been considered as alternatives because they are inexpensive and may have a better side effect profile than other choices .
OBJECTIVES To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis . | A new drug , gestrinone , was subjected to the first double blind , r and omised placebo controlled trial of any treatment of endometriosis . The disease deteriorated in eight ( 47 % ) of the 17 patients prescribed placebo ( 95 % confidence limits 23 % and 71 % ) compared with none of the 18 patients prescribed gestrinone ( p = 0.002 ) . There was a difference in elimination of the endometriosis in the gestrinone group compared with placebo but this was not statistically significant ( p = 0.057 ) . There was a significant difference in improvement of the disease in the gestrinone group compared with placebo ( p = 0.004 ) , confirming that gestrinone is an effective treatment of endometriosis . Endometriosis deteriorates in at least 23 % of patients ; as it is impossible to predict in whom this will happen , treatment appears to be warranted in all cases OBJECTIVE To compare the efficacy and safety of SC depot medroxyprogesterone acetate ( DMPA-SC 104 ) with that of leuprolide acetate in treatment of endometriosis . DESIGN Phase 3 , multicenter , r and omized , evaluator-blinded , comparator-controlled trial . SETTING Clinical trial sites in Canada and United States . PATIENT(S ) Two hundred seventy-four women with surgically diagnosed endometriosis . INTERVENTION(S ) Intramuscular injections of DMPA-SC ( 104 mg ) or leuprolide acetate ( 11.25 mg ) , given every 3 months for 6 months , with 12 months of posttreatment follow-up . MAIN OUTCOME MEASURE(S ) Reduction in five endometriosis symptoms or signs ( dysmenorrhea , dyspareunia , pelvic pain , pelvic tenderness , pelvic in duration ) ; change in bone mineral density ( BMD ) , hypoestrogenic symptoms , bleeding , and weight . RESULT ( S ) The depot medroxyprogesterone acetate given SC was statistically equivalent to leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment ( month 6 ) and in reducing all five symptoms after 12 months ' follow-up ( month 18 ) . Patients in the DMPA-SC 104 group showed significantly less BMD loss than did leuprolide patients at month 6 , with scores returning to baseline at 12 months ' follow-up . No statistically significant differences in median weight changes were observed between groups . Compared with leuprolide , DMPA-SC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding . CONCLUSION ( S ) Efficacy of DMPA-SC 104 was equivalent to that of leuprolide for reducing endometriosis-associated pain , with less impact on BMD and fewer hypoestrogenic side effects but more bleeding OBJECTIVE To compare the efficacy of Dienogest versus Decapeptyl at 3.75 mg as consolidation therapy for surgery in the treatment of endometriosis . DESIGN Multicenter , open , r and omized , parallel-group clinical trial . SETTING Volunteer patients in an academic research environment . PATIENT(S ) Women with grade 2 , 3 , and 4 ( < /=70 ) endometriosis at initial laparoscopy . INTERVENTION(S ) We provided 16 weeks of treatment with Dienogest , 1 mg tablet daily ; or with Decapeptyl , 3.75 mg IM injection every 4 weeks . MAIN OUTCOME MEASURE(S ) A change in the patient 's Revised American Fertility Society score at the post-treatment laparoscopy . RESULT ( S ) From June 1994 to July 1998 , 142 patients were enrolled in the trial . After exclusion for major protocol deviations , 59 patients were included in the Dienogest group and 61 in the Decapeptyl group . This study group was comparable to the first inclusion group . The patient demographic and clinical characteristics , median duration of endometriosis , Revised American Fertility Society scores , and Visual Analogic Squale ( VAS ) scores were comparable in both groups . Statistical analysis of efficacy was not significantly different between the two groups . Adverse events were reported by 87.7 % of patients in the Dienogest group and 85.1 % in the Decapeptyl group . Neither treatment affected patient body weight or vital signs . CONCLUSION ( S ) Dienogest is as effective as Decapeptyl for consolidation therapy after surgery for the treatment of endometriosis . The safety profile of dienogest differed from Decapeptyl ( 3.75 mg ) . Dienogest constitutes a new therapeutic alternative to the GnRH analogues OBJECTIVE To assess the effect of a new progestin progestogen only pill ( desogestrel ) versus an oral contraceptive in the treatment of recurrent endometriosis . STUDY DESIGN A r and omized prospect i ve clinical study . A group of women with endometriosis ( n=40 ) who showed recurrent dysmenorrhea and /or pelvic pain after conservative surgery , and did not desire a pregnancy . Continuous treatment for 6 months with desogestrel ( 75 microg/d ) ( n=20 ) versus a combined oral contraceptive ( ethinyl estradiol 20 microg plus desogestrel 150 microg ) ( n=20 ) was performed . RESULTS A significant improvement of both pelvic pain and dysmenorrhea was observed following each type of treatment ( P<0.001 ) . The use of desogestrel progestogen only pill was associated with a breakthrough bleeding in 20 % patients , while a significant body weight increase was observed in 15 % after oral contraceptive . CONCLUSIONS Both desogestrel and an oral estro-progestinic were effective , safe and low cost therapy of pain symptoms after endoscopic surgery for endometriosis , the former showing an impact on breakthrough bleeding , the later an incidence on body weight increase BACKGROUND Dienogest is a selective progestin that has been investigated in a clinical trial programme for the treatment of endometriosis . The current non-inferiority trial compared the efficacy and safety of dienogest against leuprolide acetate ( LA ) for treating the pain associated with endometriosis . METHODS Patients with confirmed endometriosis were r and omized to treatment with dienogest ( 2 mg/day , orally ) or LA ( 3.75 mg , depot i.m . injection , every 4 weeks ) for 24 weeks . The primary efficacy variable was absolute change in pelvic pain from baseline to end of treatment , assessed by visual analogue scale ( VAS ) . Safety variables included adverse event profile , laboratory parameters , bone mineral density ( BMD ) , bone markers and bleeding patterns . RESULTS A total of 252 women were r and omized to treatment with dienogest ( n = 124 ) or LA ( n = 128 ) ; 87.9 and 93.8 % of the respective groups completed the trial . Absolute reductions in VAS score from baseline to Week 24 were 47.5 mm with dienogest and 46.0 mm with LA , demonstrating the equivalence of dienogest relative to LA . Hypoestrogenic effects ( e.g. hot flushes ) were reported less frequently in the dienogest group . As expected , bleeding episodes were suppressed less with dienogest than with LA . Changes in mean lumbar BMD between screening and final visit were + 0.25 % with dienogest and -4.04 % with LA subgroups ( P = 0.0003 ) . Markers of bone resorption increased with LA but not dienogest . CONCLUSIONS Dienogest 2 mg/day orally demonstrated equivalent efficacy to depot LA at st and ard dose in relieving the pain associated with endometriosis , although offering advantages in safety and tolerability Danazol ( 200 mg three times a day ) and medroxyprogesterone acetate ( MPA , 100 mg a day ) were compared with placebo in the treatment of infertility of patients with endometriosis . Twenty-seven patients had medical therapy alone for 6 months , and 22 patients received it after conservative surgery . The clinical characteristics of the patients in the danazol group ( n = 18 ) , the MPA group ( n = 17 ) , and the placebo group ( n = 14 ) were comparable to each other . The follow-up time was 30 months . The cumulative pregnancy rates , 33 % in the danazol group ( n = 6 ) , 42 % in the MPA group ( n = 7 ) , and 46 % in the placebo group ( n = 6 ) , did not differ significantly from each other . The time to pregnancy after the start of therapy was 17.7 + /- 8.4 ( st and ard deviation [ SD ] ) months in the danazol group , 18.0 + /- 9.0 months in the MPA group and 10.0 + /- 5.8 months in the placebo group with no significant difference between the groups . The abortion rate was 26 % , and there was no significant difference among the groups . Cox multivariant analysis did reveal ovarian endometriosis a prognostically significant negative indicator as regards fecundation in endometriosis ( P less than 0.05 ) . In summary , correction of infertility alone does not appear to be an indication for the use of danazol or MPA in the treatment of endometriosis , and ovarian endometriotic lesions but not peritoneal ones do make a worse prognosis as regards fecundation in endometriosis OBJECTIVE To evaluate the efficacy , safety , and tolerability of an estrogen-progestogen combination versus low-dose norethindrone acetate in the treatment of persistent pain after surgery for symptomatic rectovaginal endometriosis . DESIGN R and omized controlled trial . SETTING Academic center . PATIENT(S ) Ninety women with recurrent moderate or severe pelvic pain after unsuccessful conservative surgery for symptomatic rectovaginal endometriosis . INTERVENTION(S ) Twelve-month , continuous treatment with oral ethinyl E2 , 0.01 mg , plus cyproterone acetate , 3 mg/day , or norethindrone acetate , 2.5 mg/day . MAIN OUTCOME MEASURE(S ) Degree of satisfaction with therapy . RESULT ( S ) Seven women in the ethinyl E2 plus cyproterone acetate arm and five in the norethindrone acetate arm withdrew because of side effects ( n=5 ) , treatment inefficacy ( n=6 ) , or loss to follow-up ( n=1 ) . At 12 months , dysmenorrhea , deep dyspareunia , nonmenstrual pelvic pain , and dyschezia scores were substantially reduced without major between-group differences . Both regimens induced minor unfavorable variations in the serum lipid profile . According to an intention-to-treat analysis , 28 ( 62 % ) out of 45 patients in the ethinyl E2 plus cyproterone acetate group and 33 ( 73 % ) out of 45 in the norethindrone acetate group were satisfied with the treatment received . CONCLUSION ( S ) Low-dose norethindrone acetate could be considered an effective , tolerable , and inexpensive first-choice medical alternative to repeat surgery for treating symptomatic rectovaginal endometriotic lesions in patients who do not seek conception A prospect i ve , double-blind , placebo-controlled study was design ed to evaluate the clinical efficacy and tolerance of danazol and high-dose medroxyprogesterone acetate ( MPA ) in the treatment of mild-moderate endometriosis . After laparoscopical confirmation of endometriosis , 59 patients were r and omized to receive danazol ( 200 mg 3 times daily ) , MPA ( 100 mg daily ) or placebo for 6 months . Clinical examinations were done before and 1 , 3 , 6 and 12 months after the beginning of the study , and a 2nd laparoscopy 6 months after termination of the medication . Eighteen patients in the danazol group , 16 in the MPA group and 17 in the placebo group completed the trial . Total or partial resolution of peritoneal implants was observed in 60 % of the patients receiving danazol and in 63 % of the patients receiving MPA . In the placebo group , resolution was observed in 18 % , while the size of the implants was estimated to be increased in 23 % of the patients . In relation to placebo , danazol and MPA significantly alleviated endometriosis-associated pelvic pain , lower back pain and defecation pain , but they did not differ from each other in these actions . The appearance of acne , muscle cramps , edema , weight gain and spotting bleeding complicated MPA treatment . The present results indicate that because of good efficacy and tolerance , high-dose MPA is a useful alternative in the hormonal treatment of endometriosis The purpose of this r and omized double blind prospect i ve trial was to study the efficacy and safety of two doses of oral gestrinone in the treatment of endometriosis . Six patients received gestrinone 1.25 mg twice weekly ( group I ) and six patients received gestrinone 2.5 mg twice weekly ( group II ) . Patients underwent pretreatment and post-treatment laparoscopies and their endometriosis scores were recorded . The mean total endometriosis scores declined significantly from 20.0 + /- 5.2 ( mean + /- st and ard error of the mean ) pretreatment to 9.5 + /- 3.9 post-treatment in group I and from 19.1 + /- 4.8 pretreatment to 7.1 + /- 2.1 post-treatment in group II . A total of 67 % of patients reported side effects . This study suggests that oral gestrinone 1.25 mg or 2.5 mg twice weekly is efficacious and safe in the treatment of endometriosis The medium‐ and long‐term effects of gestrinone and danazol on the endometrium were examined in 36 patients with endometriosis . Endometrial biopsies were taken from each patient before treatment and after 3 and 6 months of treatment with 600 mg danazol daily ( n= 17 ) or with 2.5 mg gestrinone twice weekly ( n= 19 ) . Endometrial sample s were analysed by light , scanning and transmission electron microscopy . At 3 months ' treatment the endometria of patients treated with danazol appeared more atrophic than those of the women treated with gestrinone ; some cell organelle involution was evident in all patients . After 6 months of treatment a marked atrophy was observed in patients of both treatment groups . A complete involution of cytoplasmic organelles with cytoplasmic collapse and a shift of nucleoplasmic ratio in favour of the nucleus occurred in patients treated with danazol ; the cytoplasmic organelle involution was less marked in patients treated with gestrinone . Compared with gestrinone , danazol induces more rapid endometrial atrophy , with greater impairment of the cytoplasm and cell secretory activity The circulating concentration of endometrial protein PP14 varied during the menstrual cycle in patients with endometriosis . The highest levels were found on days 1 to 4 of the cycle ( 176 + /- 123 micrograms/L ; mean + /- SD ) , and the lowest on days 5 to 20 ( 44.1 + /- 29.7 micrograms/L ) . Rising levels were observed on days 21 to 30 ( 58.3 + /- 62.6 micrograms/L ) . On days 5 to 20 ( i.e. , during period of the lowest levels ) patients with advanced endometriosis had higher PP14 levels ( 63.9 + /- 39.0 micrograms/L ) than those with mild endometriosis ( 29.3 + /- 18.2 micrograms/L ; p less than 0.01 ) . Patients with mild endometriosis had slightly higher serum PP14 levels than apparently healthy control subjects ( p less than 0.05 ) , but overlapping of values between the two groups is remarkable . Conservative surgical elimination of endometriosis significantly decreased the serum PP14 levels . Treatment with danazol ( 600 mg/day ) , or with medroxyprogesterone acetate ( 100 mg/day ) after laparoscopy also result ed in significant decreases in the serum PP14 concentration . After 6 months of treatment , conservative surgery in combination with danazol or with medroxyprogesterone acetate , yielded more pronounced declines in serum PP14 level than conservative surgery plus placebo . No significant difference was observed between the effects of danazol and medroxyprogesterone acetate . We conclude that endometriosis tissue contributes to the circulating PP14 level , and the decline in PP14 level during danazol and medroxyprogesterone acetate treatments reflects regression of intrauterine and ectopic endometrial tissues OBJECTIVE To determine the efficacy of medroxyprogesterone acetate ( MPA ) , 50 mg/d for 3 months , in treating endometriosis , with a follow-up of 6 months . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled trial . SETTING Academic infertility unit in a teaching hospital . PATIENT(S ) One hundred infertile women found to have endometriosis at laparoscopy , with 50 recruited to each treatment arm . INTERVENTION(S ) Laparoscopy within 3 months of finishing therapy . MAIN OUTCOME MEASURE(S ) Initial and second-look laparoscopy for revised American Fertility Society stages and scores , pregnancies achieved , effects on well-being via symptomatic improvement , and side effects . RESULT ( S ) Whether initially high or low , both MPA and placebo therapy achieved similar statistically significant reductions in stages and scores at second-look laparoscopy . MPA was rated more effective in improving overall well-being . Side effects were minimal in both groups ( 10 % MPA ; 2 % placebo ) . Six pregnancies occurred without other endometriosis therapy being instituted in the placebo group ( 3 during therapy ) , and one with MPA ( 0 during therapy ) . CONCLUSION ( S ) Both MPA and placebo appear equally and significantly effective in treating endometriosis over a 3-month period , as judged by comparative laparoscopy . Therefore , not only must the use of MPA at 50 mg/d over 3 months be question ed , but the performance of placebo also suggests the need to review whether therapy should be instituted at all as well as the present concept that endometriosis is frequently a spontaneously progressive phenomenon OBJECTIVE Our purpose was to evaluate the efficacy and safety of depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol in the long-term treatment of pelvic pain in women with endometriosis . STUDY DESIGN Eighty patients with endometriosis and moderate or severe pelvic pain were r and omized to treatment for 1 year with intramuscular depot medroxyprogesterone acetate 150 mg every 3 months or a cyclic monophasic oral contraceptive ( ethinyl estradiol 0.02 mg , desogestrel 0.15 mg ) combined with oral danazol 50 mg a day for 21 days of each 28-day cycle . The women were asked to grade the degree of their satisfaction at the end of therapy . Variations in severity of symptoms during treatment were determined by a 10 cm visual analog and a 0- to 3-point verbal rating scale . RESULTS Twenty nine of 40 subjects ( 72.5 % ) in the depot medroxyprogesterone acetate group were satisfied after 1 year of therapy compared with 23 of 40 ( 57.5 % ) in the oral contraceptive plus danazol group ( chi 2(1 ) = 1.37 , p = 0.24 , odds ratio 1.95 , 95 % confidence interval 0.76 to 4.97 ) . A significant decrease was observed in all symptom scores in both study groups . At 1-year assessment dysmenorrhea was significantly greater in women allocated to oral contraceptive plus danazol . CONCLUSION Depot medroxyprogesterone acetate seems to be an effective , safe , and convenient low-cost treatment for pelvic pain associated with endometriosis . However , women should be carefully counseled regarding menstrual changes and the potential prolonged delay in the return of ovulation Endometriosis is thought to be an ovarian-dependent benign disease that affects up to 12 % of women during their reproductive life . For the past ten years the gonadotropin-releasing hormone (GnRH)-agonists have been proved effective and safe drugs in the treatment of endometriosis . Nevertheless , gestagens such as lynestrenol still remain the most often used hormonal drugs for the treatment of this disease . The primary objective of this study was to compare the efficacy of the GnRH-agonist leuprorelin acetate depot ( LAD ) ( Enantone ® -Gyn ) 3.75 mg subcutaneously per month with that of the gestagen lynestrenol ( LYN ) ( Orgametril ® ) 5 mg orally twice per day in women with severe endometriosis , in terms of postoperative revised American Fertility Society ( r-AFS ) scores I-IV at first-look laparoscopy ( score after removal of endometriotic lesions or adhesions ) to the r-AFS score after six months ' treatment . Secondary objectives were the improvement of clinical symptoms and the side-effect profile . Forty-eight women with postoperative r-AFS scores I-IV were evaluated in an open prospect i ve r and omized study between 1996 and 1998 . All the participants underwent a first-look laparoscopy with resection of endometriotic lesions and six months ' therapy with one of the above mentioned drugs , and a further second-look laparoscopy . The six months ' treatment with LAD or LYN led to a significant reduction of the r-AFS score points in both groups . The mean r-AFS score in points for the LAD group after the first-look laparoscopy was 21.8 and was 27.2 for the LYN group . After the medical treatment a mean value of 11.5 points was observed in the LAD group compared with a mean value of 25.5 in the LYN group . This difference was statistically significant ( p = 0.000014 , Wilcoxon test ) . The improvement in the symptoms of dysmenorrhea , chronic pelvic pain and dyspareunia was also more pronounced in the LAD-treated group . LAD was more effective than LYN in the suppression of circulating serum 17β-estradiol levels after 6 months of treatment ( mean 27.7 ± 9.3 pg/ml versus 42.6 ± 59.3 pg/ml ) . All the observed side-effects were deemed tolerable by the women who participated in this study . As the reduction of the r-AFS score in points was much more pronounced in the LAD group than in the LYN group , GnRH-agonists should therefore be used as first-choice drugs in the treatment of endometriosis . Due to the limited treatment of 6 months ' duration of GnRHagonists , gestagens might be used as second-line drugs for long-term and continuous treatment in the management of endometriosis to maintain the primary beneficial effect of GnRH-agonist treatment in patients who have completed their families Serum concentrations of CA-125 were determined in association with 6-month medical ( n = 48 ) or surgical and medical therapy ( n = 40 ) of endometriosis . The concentration of CA-125 was significantly higher in stages III + IV ( 66.6 + /- 22.0 [ st and ard deviation ] U/ml ) than in stage I ( 20.9 + /- 2.3 U/ml ) or II ( 28.4 + /- 2.8 U/ml ) ; in stage II , the concentration was higher than in stage I. Surgical elimination of endometriosis significantly decreased the level of CA-125 , as did danazol , but not medroxyprogesterone acetate ( MPA ) , although these drugs were equal in clinical efficacy . The CA-125 changes during hormonal treatment did not correlate with the clinical response . Postoperatively , CA-125 responses to danazol , MPA , or placebo did not differ significantly from each other . During the 6-month follow-up after medication , the CA-125 concentrations tended to increase , especially in danazol-treated women . The determination of CA-125 is useful in estimating the extent of the disease , but it is less valuable in monitoring the treatment effect . The ability of danazol to suppress CA-125 expression emphasizes the specific properties of this drug OBJECTIVES To evaluate the efficacy of gestrinone versus leuprolide acetate ( LA ) in improving pelvic pain in women with endometriosis and to compare their effects on bone mineral density and serum lipid profile . DESIGN Multicenter , double-blind , double-dummy , r and omized clinical trial . SETTING Six academic departments specialized in the study of endometriosis . PATIENT(S ) Fifty-five women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis . INTERVENTION(S ) Six-month treatment with oral gestrinone ( n = 27 ) or IM depot LA ( n = 28 ) followed by 6-month follow-up . MAIN OUTCOME MEASURE(S ) Variations in severity of dysmenorrhea , deep dyspareunia , and nonmenstrual pain as shown by a visual analog scale and a verbal rating scale , modifications in bone mineral content as shown by dual-roentgenogram absorptiometry , and variations in serum cholesterol subfractions and lipoprotein(a ) concentrations . RESULT ( S ) Significant improvements were observed in all three symptoms considered in both treatment arms . Moderate or severe pain symptoms recurrence on both pain scales was observed in 2 of 17 ( 11.8 % ) patients given gestrinone compared with 9 of 17 ( 52.9 % ) of those given LA ( odds ratio , 0.12 ; 95 % confidence interval , 0.02 to 0.69 ) . Lumbar bone mineral density increased slightly in the gestrinone group but decreased by 3 % in the LA one . High-density-lipoprotein cholesterol fell by 25 % and lipoprotein(a ) decreased by approximately 40 % in the gestrinone-treated women but did not vary in those receiving LA . CONCLUSION ( S ) Oral gestrinone is at least as effective as depot LA for pain relief in women with symptomatic endometriosis . A tendency to prolonged pain reduction was observed after gestrinone compared with LA treatment . Gestrinone does not negatively affect bone density but variations in serum lipids need further evaluation OBJECTIVE To compare the efficacy , tolerance and recurrence rate of endometriosis after 5-year follow-up of treatment with Gestrinone and Buserelin , respectively . STUDY DESIGN A prospect i ve study with r and omized follow-up of 5 years duration ( minimum ) for each patient was done . We included 43 cases of endometriosis diagnosed by laparoscopy or laparotomy and treated them with Gestrinone ( Group G , n = 25 cases ) or Buserelin intranasal spray ( Group B , n = 18 ) for 6 months . RESULTS General data : Age , height , weight of patients and AFS score of endometriosis were without significant differences in either group . Specific data : A ) Global clinical efficacy was good or excellent in 74 % ( 16/25 ) of group G and in 78 % ( 14/18 ) of group B without significant differences . B ) Global clinical tolerance was good in 50 % of the patients in group G and in 0 % in group B ( p < 0.001 ) . C ) Global evaluation after 5-year follow-up showed " success " only for 36 % of patients in group G and in 33 % in group B ( no significant differences ) , with " failure " in 40 % and 33 % , respectively ( no significant differences ) . CONCLUSIONS 1 ) Gestrinone and Buserelin intranasal spray are valid treatments for the remission of endometriosis , with " success " , " failure " and " clinical recurrence " rates similar after a follow-up of 5 years of initial treatment . 2 ) The most significant and rogenic effect of Gestrinone was the presence of acne . Vascular effects were also considered as very undesirable effects according to the comments of patients . On the contrary , the effects of analogs are generally better tolerated OBJECTIVE To compare the efficacy and safety of dienogest ( DNG ) with intranasal buserelin acetate ( BA ) in patients with endometriosis . DESIGN Phase III , r and omized , double-blind , multicenter , controlled trial . SETTING Twenty-four study centers in Japan . PATIENT(S ) Two hundred seventy-one patients with endometriosis . INTERVENTION(S ) Dienogest ( 2 mg/day , orally ) or BA ( 900 microg/day , intranasally ) for 24 weeks . MAIN OUTCOME MEASURE(S ) The pre- to posttreatment changes in the scores of five subjective symptoms during nonmenstruation ( lower abdominal pain , lumbago , defecation pain , dyspareunia , and pain on internal examination ) and two objective findings ( in duration in the pouch of Douglas and limited uterine mobility ) . RESULT ( S ) Dienogest reduced the scores of all symptoms and findings at the end of treatment , and the mean changes in the scores of all symptoms and findings except in duration in the pouch of Douglas were comparable to those obtained with BA . Compared with BA , DNG was associated with irregular genital bleeding more frequently and with fewer hot flushes . The reduction in bone mineral density ( BMD ) during DNG treatment was significantly lower than that during BA treatment . CONCLUSION ( S ) DNG is as effective as intranasal BA in alleviating endometriosis , and causes less BMD loss Thirty-nine infertile patients with laparoscopic diagnosis of endometriosis were allocated r and omly to treatment with gestrinone 2.5 mg twice weekly ( 20 patients ) or danazol 600 mg/day ( 19 patients ) for 6 months . If amenorrhea was not obtained after 1 month of treatment , the gestrinone dose was increased to 2.5 mg three times a week ( 7 patients ) and the danazol dose to 800 mg/day ( 2 patients ) . One month after the end of the treatment , a repeat laparoscopy was performed only in the women who agreed ( 7 of the gestrinone treated group , 9 of the danazol group ) . All of the patients were followed for at least 12 months after the end of the treatment , during which time they attempted to conceive . There was a marked improvement of pain symptoms during the treatment in the patients of both groups . The repeat laparoscopy did not reveal significant differences between the two groups in the reduction of the disease extent . Eighteen months after treatment suspension , the cumulative pregnancy rate was 33 % in the patients treated with gestrinone and 40 % in those treated with danazol . Pain symptoms recurred during the follow-up in 57 % of the gestrinone and 53 % of the danazol group . The side effects were more frequent and severe with the danazol treatment , whereas those caused by gestrinone were mostly weight gain and acne . The results of this study suggest that gestrinone is as effective as danazol in the treatment of infertility associated with endometriosis and is better tolerated Background . To assess whether hormonal treatment of endometriosis improves quality of life for women with endometriosis OBJECTIVE To evaluate the efficacy and safety of cyproterone acetate versus an oral contraceptive in the treatment of endometriosis-associated recurrent pelvic pain . DESIGN R and omized controlled trial . SETTING Academic center . PATIENT(S ) Ninety women with recurrent moderate or severe pelvic pain after conservative surgery for symptomatic endometriosis . INTERVENTION(S ) Six months of continuous treatment with oral cyproterone acetate , 12.5 mg/d , or an oral contraceptive containing ethinyl estradiol , 0.02 mg , and desogestrel , 0.15 mg . MAIN OUTCOME MEASURE(S ) Degree of satisfaction with therapy . RESULT ( S ) Six patients in the cyproterone acetate arm and nine in the oral contraceptive arm withdrew because of side effects ( n = 9 ) , treatment inefficacy ( n = 4 ) , or loss to follow-up ( n = 2 ) . At 6 months , dysmenorrhea , deep dyspareunia , and nonmenstrual pelvic pain scores were substantially reduced , and significant improvements were observed in health-related quality -of-life , psychiatric profile , and sexual satisfaction ; no major between-group differences were seen . Subjective and metabolic side effects were limited . According to an intention-to-treat analysis , 33 of 45 ( 73 % ) of patients in the cyproterone acetate group and 30 of 45 ( 67 % ) in the oral contraceptive group were satisfied with the treatment received . CONCLUSIONS Both cyproterone acetate and a continuous monophasic oral contraceptive were effective , safe , and inexpensive therapy for recurrent pain after conservative surgery for endometriosis In a study on endometriosis , ten patients were treated with danazol ( 200 mg three times a day ) and ten patients with high-dose medroxyprogesterone acetate ( MPA ) ( 100 mg a day ) for 6 months . The circulating high-density lipoprotein-cholesterol concentration decreased significantly in the danazol ( 53 % ) and in the MPA groups ( 26 % ) ; the change in the danazol group was significantly higher than that in the MPA group . Danazol also significantly increased the low-density lipoprotein-cholesterol levels ( 37 % ) , whereas MPA had no significant effect . Danazol ( 29 % ) and MPA ( 12 % ) decreased the apolipoprotein A-1 levels significantly . The decrease caused by danazol was significantly greater . Danazol also significantly decreased the apolipoprotein A-2 levels ( 12 % ) and significantly increased the apolipoprotein B levels ( 17 % ) , whereas MPA had no significant effects on them . Three months after the end of medication , all values were at the pretreatment levels . The circulating cholesterol , triglyceride , and very low-density lipoprotein concentrations remained unchanged during both treatments . Danazol and high-dose MPA induced a similar significant regression of peritoneal endometriotic implants in relation to placebo . Our present results , showing that danazol , to a greater extent than high-dose MPA , is associated with changes in lipoprotein metabolism that expose the individual to an increased risk of cardiovascular diseases , suggest that high-dose MPA is preferable to danazol in the long-term treatment of endometriosis BACKGROUND Implanon has been reported to be effective in the treatment of dysmenorrhea . We compared the therapeutic efficacies of depot medroxyprogesterone acetate ( DMPA ) and Implanon with regard to pain relief in women with endometriosis . STUDY DESIGN In a clinical research center at a university hospital , 41 patients with dysmenorrhea , nonmenstrual pelvic pain and dyspareunia associated with histologically proven endometriosis were included in an open , prospect i ve , r and omized , controlled clinical trial . Twenty-one women were assigned by computer-generated r and omization to receive Implanon , and 20 women to receive DMPA . As main outcome measures of this pilot study , we evaluated pain improvement quantified according to visual analog scale score , side effects , vaginal bleeding patterns , withdrawal rate and overall degree of satisfaction . RESULTS During a follow-up period of 1 year , we ascertained a clear improvement in pain intensity for both treatment options . After 6 months , the average decrease in pain was 68 % in the Implanon group and 53 % in the DMPA group . The side-effects profile and the overall degree of satisfaction after study termination were comparable for both treatment options . CONCLUSION Concerning pain relief , the therapeutic efficacy of the contraceptive implant Implanon is not inferior to that of DMPA in symptomatic endometriosis |
1,703 | 29,982,868 | Conclusion The outcome of immediate arthroscopic repair of primary anterior shoulder dislocation is superior and encouraging with significant reduction in failure and revision rates compared to conservative treatment .
Nevertheless , the failure and revision rates are statistically insignificant compared to arthroscopic reconstruction of recurrent dislocation .
Hence , there is evidence to support immediate arthroscopic repair option for primary anterior shoulder dislocations over conservative treatment in young active patients , in order to reduce the risk of failure and revision rates .
However , the evidence is inconclusive compared to arthroscopic reconstruction of recurrent dislocation | Background The ideal treatment of acute anterior shoulder dislocation remains one of the topics that spark debate over the value of primary repair for the first-time anterior shoulder dislocation .
The high rate of complications especially in young adults , such as recurrent instability , residual pain , and inability to return to sports , has led to the quest for an ideal management of such injuries .
Objective In this meta- analysis , we compare between the immediate arthroscopic repair and conservative treatment of primary anterior shoulder dislocation as well as arthroscopic reconstruction of recurrent anterior shoulder dislocation . | Shoulder joint dislocations collected from a r and omized population were investigated in Sweden , wherein nearly 50 % of people with primary dislocations never visit hospitals nor are treated by a physician . Thus information obtained from surgically treated patients is of limited value because cases requiring operative repair represent only a small and selected percentage of the population . The incidence of shoulder dislocation in people from 18 to 70 years of age was at least 1.7 % and was three times more common in males . Spontaneous healing of recurrent dislocations in a period of many years was not uncommon . Shoulder joint dislocation was more common among children than was generally appreciated , with the prognosis usually good . Recurrences of primary dislocations in people 15 to 25 years of age were not as frequent as was expected BACKGROUND Anterior dislocation of the glenohumeral joint in younger patients is associated with a high risk of recurrence and persistent functional deficits . The aim of this study was to assess the efficacy of a primary arthroscopic Bankart repair , while controlling for the therapeutic effects produced by the arthroscopic intervention and joint lavage . METHODS In a single-center , double-blind clinical trial , eighty-eight adult patients under thirty-five years of age who had sustained a primary anterior glenohumeral dislocation were r and omized to receive either an arthroscopic examination and joint lavage alone or together with an anatomic repair of the Bankart lesion . Assessment of the rate of recurrent instability , functional outcome ( with use of three scores ) , range of movement , patient satisfaction , direct health-service costs , and treatment complications was completed for eighty-four of these patients ( forty-two in each group ) during the subsequent two years . RESULTS In the two years after the primary dislocation , the risk of a further dislocation was reduced by 76 % and the risk of all recurrent instability was reduced by 82 % in the Bankart repair group compared with the group that had arthroscopy and lavage alone . The functional scores were also better ( p < 0.05 ) , the treatment costs were lower ( p = 0.012 ) , and patient satisfaction was higher ( p < 0.001 ) after arthroscopic repair . The improved functional outcome appeared to be mediated through the prevention of instability since the functional outcome in patients with stable shoulders was similar , irrespective of the initial treatment allocation . The patients who had a Bankart repair and played contact sports were also more likely to have returned to their sport at two years ( relative risk = 3.4 , p = 0.007 ) . CONCLUSIONS Following a first-time anterior dislocation of the shoulder , there is a marked treatment benefit from primary arthroscopic repair of a Bankart lesion , which is distinct from the so-called background therapeutic effect of the arthroscopic examination and lavage of the joint . However , primary repair does not appear to confer a functional benefit to patients with a stable shoulder at two years after the dislocation Background Nonoperative treatment of traumatic shoulder dislocations leads to a high rate of recurrent dislocations . Hypothesis Early arthroscopic treatment for shoulder dislocation will result in a lower recurrence rate than nonoperative treatment . Study Design Prospect i ve , r and omized clinical trial . Methods Two groups of patients were studied to compare nonoperative treatment with arthroscopic Bankart repair for acute , traumatic shoulder dislocations in young athletes . Fourteen nonoperatively treated patients underwent 4 weeks of immobilization followed by a supervised rehabilitation program . Ten operatively treated patients underwent arthroscopic Bankart repair with a bioabsorbable tack followed by the same rehabilitation protocol as the nonoperatively treated patients . The average follow-up was 36 months . Results Three patients were lost to follow-up . Twelve nonoperatively treated patients remained for follow-up . Nine of these ( 75 % ) developed recurrent instability . Six of the nine have required subsequent open Bankart repair for recurrent instability . Of the nine operatively treated patients available for follow-up , only one ( 11.1 % ) developed recurrent instability . Conclusions Arthroscopic stabilization of traumatic , first-time anterior shoulder dislocations is an effective and safe treatment that significantly reduces the recurrence rate of shoulder dislocations in young athletes when compared with conventional , nonoperative treatment BACKGROUND An initial anterior dislocation of the shoulder becomes recurrent in 66 % to 94 % of young patients after immobilization of the shoulder in internal rotation . Magnetic resonance imaging and studies of cadavera have shown that coaptation of the Bankart lesion is better with the arm in external rotation than it is with the arm in internal rotation . Our aim was to determine the benefit of immobilization in external rotation in a r and omized controlled trial . METHODS One hundred and ninety-eight patients with an initial anterior dislocation of the shoulder were r and omly assigned to be treated with immobilization in either internal rotation ( ninety-four shoulders ) or external rotation ( 104 shoulders ) for three weeks . The primary outcome measure was a recurrent dislocation or subluxation . The minimum follow-up period was two years . RESULTS The follow-up rate was seventy-four ( 79 % ) of ninety-four in the internal rotation group and eighty-five ( 82 % ) of 104 in the external rotation group . The compliance rate was thirty-nine ( 53 % ) of seventy-four in the internal rotation group and sixty-one ( 72 % ) of eighty-five in the external rotation group ( p = 0.013 ) . The intention-to-treat analysis revealed that the recurrence rate in the external rotation group ( twenty-two of eighty-five ; 26 % ) was significantly lower than that in the internal rotation group ( thirty-one of seventy-four ; 42 % ) ( p = 0.033 ) with a relative risk reduction of 38.2 % . In the subgroup of patients who were thirty years of age or younger , the relative risk reduction was 46.1 % . CONCLUSIONS Immobilization in external rotation after an initial shoulder dislocation reduces the risk of recurrence compared with that associated with the conventional method of immobilization in internal rotation . This treatment method appears to be particularly beneficial for patients who are thirty years of age or younger Purpose The purpose of this study was to compare clinical outcomes between a primary dislocation group ( group P ) and a recurrent dislocation group ( group R ) with combined lesion of Bankart and type II SLAP lesions ( type V SLAP lesion ) and to evaluate incidence of type V SLAP lesion . In addition , the authors evaluated clinical outcomes of these patients by dividing two groups according to the sequence for Bankart and SLAP lesion suture . Methods From May 2000 to May 2005 , 310 patients who gave informed consent , underwent the diagnostic arthroscopy and magnetic resonance arthrography ( MRA ) . One hundred and ten patients met the following criteria : ( 1 ) post-traumatic primary or recurrent anterior shoulder instability , ( 2 ) a normal contralateral shoulder , ( 3 ) a type V SLAP lesion , and ( 4 ) minimum follow-up of two years . Group P included 42 patients , and group R , 68 patients . Among all patients , 58 patients who had Bankart lesions sutured first were included in group B , and 52 who had their SLAP lesions sutured beforeh and , group S. Visual analogue scale , range of motion , Rowe and Constant score were used to compare results between group P and group R , also group B and group S. Results The incidence rates of type V SLAP lesion were 42.8 % in group P and 32.0 % in group R. The overall treatment results in our study were good . Even if the difference between the two groups was statistically insignificant , group P showed greater recovery of range of motion than group R in external rotation . No significant difference was found between the two different operative methods according to suture sequence . Conclusion The incidence rates of type V SLAP lesion were 42.8 % in the primary dislocation group and 32.0 % in the recurrent dislocation group . The overall treatment results in our study were good . Although there was no statistical significance in surgical time between the two groups , when both SLAP and Bankart lesions are present , the Bankart lesion must be sutured first to reduce surgical time Background : There is no consensus on the optimal treatment of in-season athletes with anterior shoulder instability , and limited data are available to guide return to play . Purpose : To examine the likelihood of return to sport and the recurrence of instability after an in-season anterior shoulder instability event based on the type of instability ( subluxation vs dislocation ) . Additionally , injury factors and patient-reported outcome scores administered at the time of injury were evaluated to assess the predictability of eventual successful return to sport and time to return to sport during the competitive season . Study Design : Cohort study ( prognosis ) ; Level of evidence , 2 . Methods : Over 2 academic years , 45 contact intercollegiate athletes were prospect ively enrolled in a multicenter observational study to assess return to play after in-season anterior glenohumeral instability . Baseline data collection included shoulder injury characteristics and shoulder-specific patient-reported outcome scores at the time of injury . All athletes underwent an accelerated rehabilitation program without shoulder immobilization and were followed during their competitive season to assess the success of return to play and recurrent instability . Results : Thirty-three of 45 ( 73 % ) athletes returned to sport for either all or part of the season after a median 5 days lost from competition ( interquartile range , 13 ) . Twelve athletes ( 27 % ) successfully completed the season without recurrence . Twenty-one athletes ( 64 % ) returned to in-season play and had subsequent recurrent instability including 11 recurrent dislocations and 10 recurrent subluxations . Of the 33 athletes returning to in-season sport after an instability event , 67 % ( 22/33 ) completed the season . Athletes with a subluxation were 5.3 times more likely ( odds ratio [ OR ] , 5.32 ; 95 % CI , 1.00 - 28.07 ; P = .049 ) to return to sport during the same season when compared with those with dislocations . Logistic regression analysis suggests that the Western Ontario Shoulder Instability Index ( OR , 1.05 ; 95 % CI , 1.00 - 1.09 ; P = .037 ) and Simple Shoulder Test ( OR , 1.03 ; 95 % CI , 1.00 - 1.05 ; P = .044 ) administered after the initial instability event are predictive of the ability to return to play . Time loss from sport after a shoulder instability event was most strongly and inversely correlated with the Simple Shoulder Test ( P = .007 ) at the time of initial injury . Conclusion : In the largest prospect i ve study evaluating shoulder instability in in-season contact athletes , 27 % of athletes returned to play and completed the season without subsequent instability . While the majority of athletes who return to sport complete the season , recurrent instability events are common regardless of whether the initial injury was a subluxation or dislocation BACKGROUND During 1978 and 1979 , we initiated a prospect i ve multicenter study to evaluate the results of nonoperative treatment of primary anterior shoulder dislocation . In the current report , we present the outcome after twenty-five years . METHODS Two hundred and fifty-five patients ( 257 shoulders ) with an age of twelve to forty years who had a primary anterior shoulder dislocation were managed with immobilization ( achieved by tying the arm to the torso with use of a b and age ) or without immobilization . All 227 living patients ( 229 shoulders ) completed the follow-up question naire , and 214 patients completed the Disabilities of the Arm , Shoulder and H and ( DASH ) question naire . RESULTS Ninety-nine ( 43 % ) of 229 shoulders had not redislocated , and seventeen ( 7 % ) redislocated once . Thirty-three recurrent dislocations had become stable over time ( 14.4 % ) , and eighteen were considered to be still recurrent ( 7.9 % ) . Sixty-two shoulders ( 27 % ) had undergone surgery for the treatment of recurrent instability . Immobilization after the primary dislocation did not change the prognosis . Only two of twenty-four shoulders with a fracture of the greater tuberosity at the time of the primary dislocation redislocated ( p < 0.001 ) . When shoulders with a fracture of the greater tuberosity were excluded , forty-four ( 38 % ) of 115 shoulders in patients who had been twelve to twenty-five years of age at the time of the original dislocation and sixteen ( 18 % ) of ninety shoulders in patients who had been twenty-six to forty years of age had undergone surgical stabilization . At twenty-five years , fourteen ( 23 % ) of sixty-two shoulders that had undergone surgical stabilization were in patients who subsequently had a contralateral dislocation , compared with seven ( 7 % ) of ninety-nine shoulders in patients in whom the index dislocation had been classified as solitary ( p = 0.01 ) . Gender and athletic activity did not appear to affect the redislocation rate ; however , women had worse DASH scores than men did ( p = 0.006 ) . CONCLUSIONS After twenty-five years , half of the primary anterior shoulder dislocations that had been treated nonoperatively in patients with an age of twelve to twenty-five years had not recurred or had become stable over time Background : Conservative treatment of posttraumatic antero-inferior shoulder instability leads to a high failure rate in a young and active population . However , treatment in an adolescent age group is not well documented . Methods : We conducted a prospect i ve study with adolescent patients ( age 15 to 18 y ) who suffered a first traumatic anterior dislocation of the shoulder . Two groups of patients were formed . The first group was treated with early arthroscopic stabilization and the second was treated conservatively . There were 43 shoulders in the operative group and 29 shoulders in the conservative group . The rehabilitation protocol was the same for both groups . All patients were followed up prospect ively after 12 , 24 , and 36 months using Rowe Score . Results : A total of 38 shoulders in the surgical group and 27 shoulders in the conservative group could be completely evaluated . From the conservative group , 19 patients ( 70.3 % ) suffered a recurrence of the instability . From the arthroscopic group , 5 patients ( 13.1 % ) suffered a recurrence of the instability . Conclusions : In an adolescent population ( 15 to 18 y ) , conservative treatment after first traumatic shoulder dislocation including immobilization in internal rotation leads to a significantly higher and unacceptable high failure rate compared with early arthroscopic stabilization . Level of Evidence : Level II— prospect i ve comparative study PURPOSE To compare the results of arthroscopic repair in acute anterior shoulder traumatic dislocation with those of nonoperative treatment . TYPE OF STUDY A prospect i ve nonr and omized study was performed . METHODS Between August 1989 and April 1997 , 46 patients were seen after a first episode of traumatic anterior shoulder dislocation . The average age was 21 years ( range , 17 to 27 years ) . Most dislocations were in rugby players ( 36 patients ) . There were 18 patients treated by nonoperative methods and 28 patients treated by acute arthroscopic repair ; 22 patients using transglenoid suture and 6 patients with bone anchor suture fixation . RESULTS Of the patients treated nonoperatively , 94.5 % suffered a redislocation between 4 and 18 months ( average , 6 months ) . In the operative group , 96 % of the patients ( 27 ) obtained excellent results according to the Rowe scale . Only 1 patient suffered a redislocation 1 year after surgery . Three different types of lesions were found during surgery : group I , capsular tear with no labrum lesion ( 4 % ) ; group II , capsular tear with partial labrum detachment ( 32 % ) ; and group III , capsular tear and full anterior labrum detachment ( 64 % ) . The average follow-up was 67.4 months ( range , 28 to 120 ) . There were no surgical complications . CONCLUSIONS The operative group obtained 96 % excellent results , but the nonoperative group only obtained 5.5 % excellent results , according to the Rowe scale . The nonoperative group showed a high incidence of redislocation ( 94.5 % ) compared with the operative group ( 4 % ) . Based on the findings of this study , we recommend using an arthroscopic evaluation and repair after an initial anterior traumatic shoulder dislocation in young athletes A prospect i ve study evaluating nonoperative treatment versus arthroscopic Bankart suture repair for acute , ini tial dislocation of the shoulder was undertaken in young athletes . All patients met the following criteria : 1 ) sus tained an acute first-time traumatic anterior dislocation , 2 ) no history of impingement or occult subluxation , 3 ) the dislocation required a manual reduction , and 4 ) no concomitant neurologic injury . Thirty-six athletes ( average age , 20 years ) met the criteria for inclusion . Group I patients were immobilized for 1 month followed by rehabilitation ; they were allowed full activity at 4 months . Group II patients underwent arthroscopic Bankart repair followed by the same protocol as Group I. Group I consisted of 15 athletes . Twelve patients ( 80 % ) developed recurrent instability ; 7 of the 12 have required open Bankart repair for recurrent instability . Group I consisted of 21 patients ; 18 patients ( 86 % ) had no recurrent instability at last followup ( average , 32 months ; range , 15 to 45 ) ( P = 0.001 ) . One patient in Group II has required a subsequent open Bankart repair to treat symptomatic recurrence ( P = 0.005 ) . In this study , arthroscopic Bankart repair significantly reduced the recurrence rate in young athletes who sustained an acute , initial anterior dislocation of the shoulder INTRODUCTION Early treatment of initial anterior glenohumeral dislocation in young patients is controversial and the interest of surgery , and notably arthroscopic stabilization , has not been demonstrated . A prospect i ve study was therefore performed to assess ( 1 ) short-to-medium-term recurrence rate , ( 2 ) functional outcome , and ( 3 ) and medium-term osteoarthritis rate . HYPOTHESIS Early arthroscopic stabilization by anterior capsule-labrum reinsertion after initial anterior shoulder dislocation is associated with low recurrence rate . MATERIAL S AND METHODS Twenty-one patients with initial anterior dislocation were included between June 2002 and February 2004 . All patients underwent arthroscopic Bankart repair within 30 days of dislocation . Patients were followed up prospect ively , with clinical ( Duplay and Constant scores ) and radiological assessment ( osteoarthritis ) . RESULTS There were 5 recurrent dislocations ( 25 % ) ; 2 patients reported sensations of subluxation : i.e. , 7 failures ( 35 % ) . Mean Walch-Duplay score at 10 years was 88±1 ( range , 30 - 100 ) and mean Rowe score 86±22 ( range , 35 - 100 ) . There was significant internal rotation deficit of one vertebral level between operated and contralateral shoulder ( P < 0.005 ) . At 10 years , 3 shoulders ( 15 % ) showed Samilson grade 1 centered glenohumeral osteoarthritis . CONCLUSION Early arthroscopic capsule-labrum reinsertion by the Bankart technique in the month following initial anterior dislocation of the shoulder in patients under 25 years of age provided a low recurrence rate ( 35 % ) compared to the literature , including dislocation ( 25 % ) and subluxation ( 10 % ) . Functional outcome was satisfactory , and osteoarthritis rate was low ( 15 % Samilson grade 1 ) . LEVEL OF EVIDENCE IV , prospect i ve non-comparative study Background The literature provides little information detailing the incidence of traumatic shoulder instability in young , healthy athletes . Hypothesis Shoulder instability is common in young athletes . Study Design Descriptive epidemiologic study . Methods We prospect ively captured all traumatic shoulder instability events at the United States Military Academy between September 1 , 2004 , and May 31 , 2005 . Throughout this period , all new traumatic shoulder instability events were evaluated with physical examination , plain radiographs , and magnetic resonance imaging . Instability events were classified according to direction , chronicity , and type ( subluxation or dislocation ) . Subject demographics , mechanism of injury , and sport were evaluated . Results Among 4141 students , 117 experienced new traumatic shoulder instability events during the study period ; 11 experienced multiple events . The mean age of these 117 subjects was 20.0 years ; 101 students were men ( 86.3 % ) , and 16 were women ( 13.7 % ) . The 1-year incidence proportion was 2.8 % . The male incidence proportion was 2.9 % and the female incidence proportion was 2.5 % . Eighteen events were dislocations ( 15.4 % ) , and 99 were subluxations ( 84.6 % ) . Of the 99 subluxations , 45 ( 45.5 % ) were primary events , while 54 ( 54.5 % ) were recurrent . Of the 18 dislocations , 12 ( 66.7 % ) were primary events , while 6 ( 33.3 % ) were recurrent . The majority of the 117 events were anterior in nature ( 80.3 % ) , while 12 ( 10.3 % ) were posterior , and 11 ( 9.4 % ) were multidirectional . Forty-four percent ( 43.6 % ) of the instability events experienced were as a result of contact injuries , while 41.0 % were a result of noncontact injuries , including 9 subluxations caused by missed punches during boxing ; information was unavailable for the remaining 15 % . Conclusion Glenohumeral instability is a common injury in this population , with subluxations comprising 85 % of instability events PURPOSE To report the long-term results of a prospect i ve r and omized clinical trial comparing the effectiveness of immediate arthroscopic stabilization versus immobilization and rehabilitation after a first traumatic anterior dislocation of the shoulder . TYPE OF STUDY R and omized clinical trial . METHODS Forty subjects younger than 30 years with a first traumatic anterior shoulder dislocation were r and omized to receive immediate anterior stabilization plus rehabilitation or immobilization followed by rehabilitation . Patients completed the American Shoulder and Elbow Surgeons ( ASES ) , Disabilities of the Arm , Shoulder and H and ( DASH ) , and the Western Ontario Shoulder Instability Index ( WOSI ) question naires . RESULTS At an average follow-up of 75 months , there was a significant difference in the rate of redislocation between the groups but no statistical significant difference in shoulder function with the ASES or the DASH . The mean difference between the 2 groups with the WOSI estimates a small , but clinical ly significant difference . CONCLUSIONS It is recommended that immediate arthroscopic stabilization is the treatment of choice in a subset of patients who are younger than 30 years and are higher level athletes , and the timing for surgery is good or their sport is risky , i.e. , rugby , football , kayaking , rock climbing . LEVEL OF EVIDENCE Level II Our purpose was to compare the effectiveness of traditional treatment with immediate arthroscopic stabilization in young patients who have sustained a first traumatic anterior dislocation of the shoulder . Forty skeletally mature patients younger than 30 years of age were r and omly allocated to immobilization for 3 weeks followed by rehabilitation ( group T ) or arthroscopic stabilization ( within 4 weeks of injury ) followed by an identical immobilization and rehabilitation protocol ( group S ) . A blinded research assistant performed all follow-up evaluations . The dominant arm was involved in 35 % of subjects . The injury occurred in a sporting event in 70 % of subjects . At 24 months , there was a statistically significant difference in the rate of redislocation ( T = 47 % , S = 15.9 % , P = .03 ) . An intention-to-treat analysis comparing disease-specific quality of life using the vali date d Western Ontario Shoulder Instability ( WOSI ) index showed statistically significantly better results in the surgically treated group at the 33 months ( T = 633.93 v S = 287.1 , P = .03 ) and no significant difference in range of motion . At an average 32 months follow-up , a significant reduction in redislocation and improvement in disease-specific quality of life is afforded by early arthroscopic stabilization in patients less than 30 year of age with a first , traumatic , anterior dislocation of the shoulder BACKGROUND Shoulder dislocation may cause arthropathy , but the natural history of this evolution is not well described . We therefore conducted a radiographic follow-up 25 years after the primary shoulder dislocation . METHODS A prospect i ve Swedish multicenter study ( 1978 - 1979 ) included 257 shoulders in 255 patients ( age , 12 - 40 years ) with a first-time anterior shoulder dislocation . After 25 years , 227 patients ( 229 shoulders ) were alive and had follow-up . Radiographic imaging was performed in 223 shoulders ( 97 % ) . RESULTS Shoulders were normal in 44 % . Arthropathy was mild in 29 % , moderate in 9 % , and severe in 17 % . Of the shoulders without a recurrence , 18 % had moderate/severe arthropathy . The corresponding figures were 39 % for shoulders that recurred once or more ( without surgery ) and 26 % ( 16 of 62 ) for surgically stabilized shoulders . Seven of 221 patients ( 7 of 223 shoulders ) were considered alcoholic at 25 years and all had severe arthropathy ( P < .001 ) . Other factors that correlated with moderate/severe arthropathy were age older than 25 years at primary dislocation ( P = .01 ) and primary dislocation caused by high-energy sports activity ( P = .009 ) . Shoulders that had not recurred had less arthropathy than shoulders classified as recurrent ( P = .047 ) or stabilized over time ( P = .007 ) . Sixty-two surgically stabilized shoulders had less arthropathy than those that became stable over time ( P = .047 ) . Mild arthropathy at 10 years was associated with moderate/severe arthropathy at 25 years in 19 of 30 shoulders ( 63 % ) compared with 13 of 146 ( 9 % ) classified as normal at 10 years ( P < .001 ) . Joint incongruence at 10 years was associated with moderate/severe arthropathy at 25 years ( P = .001 ) . CONCLUSION Age at primary dislocation , recurrence , high-energy sports , and alcohol abuse were factors associated with the development of arthropathy . Also shoulders without a recurrence were associated with arthropathy |
1,704 | 30,132,304 | In CKD G5D sevelamer may lead to lower death ( all causes ) ( RR 0.53 , CI 0.30 to 0.91 , low certainty ) and induce less hypercalcaemia ( RR 0.30 , CI 0.20 to 0.43 , low certainty ) when compared with calcium-based binders , and has uncertain or inestimable effects on cardiovascular death , myocardial infa rct ion , stroke , fracture , or coronary artery calcification .
It is uncertain whether the effects of binders on clinical ly-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses .
In studies of adults with CKD G5D treated with dialysis , sevelamer may lower death ( all causes ) compared to calcium-based binders and incur less treatment-related hypercalcaemia , while we found no clinical ly important benefits of any phosphate binder on cardiovascular death , myocardial infa rct ion , stroke , fracture or coronary artery calcification .
In patients with CKD G2 to G5 , the effects of sevelamer , lanthanum , and iron-based phosphate binders on cardiovascular , vascular calcification , and bone outcomes compared to placebo or usual care , are also uncertain and they may incur constipation , while iron-based binders may lead to diarrhoea | BACKGROUND Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease ( CKD ) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder ( CKD-MBD ) .
This is an up date of a review first published in 2011 .
OBJECTIVES The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points , musculoskeletal and cardiovascular morbidity , hospitalisation , and death . | Background : Ferric citrate ( FC ) is a new phosphorus binder shown to increase serum iron stores while reducing intravenous iron and erythropoiesis-stimulating agent usage . Such reductions could lower hospitalization rates and associated costs . Methods : Hospitalizations during a Phase III trial were compared between FC and active control ( AC ) . Hospitalization costs were estimated using the 2013 US Renal Data System Annual Data Report . Results : 34.6 % of FC patients were hospitalized at least once versus 45.6 % of the AC group ( risk reduction 24.2 % ; p = 0.02 ) . There were 181 unique hospitalizations in the FC group versus 239 in the AC group , for a difference of 58 hospitalizations . Total potential savings was US$ 867,622 in hospitalization costs in the FC group . If the hospitalization reduction in our study was applied to the general end-stage renal disease population , this could translate into a savings of US$ 3002/patient/year . Conclusions : Patients receiving FC experienced fewer hospitalizations with the potential for significant savings BACKGROUND AND OBJECTIVES Vascular calcification and endothelial dysfunction contribute to the development of cardiovascular disease in patients with chronic kidney disease ( CKD ) . Sevelamer , a non-calcium-based phosphate binder , has been shown to attenuate cardiovascular calcification in CKD patients , although the exact mechanism has not been clarified . This study was design ed to investigate the effect of short-term sevelamer treatment on both serum fetuin-A concentrations and endothelial dysfunction seen in CKD patients . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Fifty nondiabetic stage 4 CKD patients whose phosphate levels were > or = 5.5 mg/dl were enrolled in this 8-wk r and omized prospect i ve study . Thirty-six healthy volunteers served as matched controls . Patients were treated with either sevelamer ( n = 25 , 12 males ) or calcium acetate ( n = 25 , 13 males ) . Fetuin-A , high-sensitivity C-reactive protein , Ca x PO4 product , flow-mediated dilation ( FMD ) , insulin , and homeostasis model assessment ( HOMA ) were obtained at baseline and after the treatment period . RESULTS As expected , CKD patients had significantly lower levels of fetuin-A and FMD , and significantly higher levels of intact parathyroid hormone , Ca x PO4 product , and high-sensitivity C-reactive protein than controls ( P < 0.001 for all ) . The use of sevelamer led to a significant increase in the fetuin-A concentration with improvement in FMD , whereas no significant difference was observed in the calcium acetate group . In a multiple regression analysis , FMD levels were independently related to fetuin-A both before ( beta = 0.63 , P < 0.001 ) and after ( beta = 0.38 , P = 0.004 ) treatment . CONCLUSIONS This small , r and omized , prospect i ve study shows that short-term sevelamer treatment significantly increases fetuin-A levels and improves FMD in nondiabetic stage 4 CKD patients Background Fetuin-A is known as a circulating inhibitor of vascular calcification . Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients is still uncertain . Methods In the post-hoc study , we analyzed serum fetuin-A and biochemical factors ( Ca , P , i-PTH , hsCRP , TG , LDL-C ) in 50 hemodialysis patients , who completed a 48-week , open-Label , controlled r and omized parallel-group study . 23 patients received sevelamer and 27 patients received calcium carbonate . Results After the 48-week treatment , the sevelamer group had less serum calcium increment , less iPTH decrement , more ALK-P increment , more hsCRP decrement and more LDL-C decrement . There was no significant difference in the serum fetuin-A decrement between two groups . Decreased serum fetuin-A levels were found after 48-week treatment in both groups : from 210.61 ( 104.73 ) to 153.85 ( 38.64 ) ug/dl , P = 0.003 in sevelamer group , from 203.95 ( 107.87 ) to 170.90 ( 58.02 ) ug/mL , P = 0.002 in calcium group . The decrement in serum fetuin-A ( Δfetuin-A ) levels was associated with ΔCa ( ρ = - 0.230 , P = 0.040 ) , ΔiPTH ( ρ = 0.306 , P = 0.031 ) and Δalbumin ( ρ = 0.408 , P = 0.003 ) , not associated with sevelamer use , ΔP and ΔhsCRP . Conclusion After long-term sevelamer or calcium carbonate treatment , both groups of maintenance HD patients had lower serum fetuin-A levels . Serum levels of increased calcium , decreased iPTH and decreased albumin were associated with the serum fetuin-A decrement The objective of the study was to evaluate the phosphate-binding efficacy , side effects , and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis . The study design used was a r and omized , crossover open trial , and the main outcome measurements were plasma ionized calcium levels , plasma phosphate levels , plasma intact parathyroid hormone ( PTH ) levels , requirements for supplemental aluminum-aminoacetate therapy , patient tolerance , and cost of therapy . Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months . All had previously tolerated therapy with calcium carbonate . Of the 19 patients included , 10 completed both treatment arms . After 12 weeks of therapy , the mean ( + /-SEM ) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm ( 4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL ; P = 0.004 ) , whereas the mean plasma phosphate ( 4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL ) and PTH levels ( 266+/-125 pg/mL v 301+/-148 pg/mL ) did not differ significantly between the two treatment arms . Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment , while two patients needed this supplement when treated with calcium carbonate . Five of 17 ( 29 % ) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance ( anorexia , vomiting , diarrhea , general uneasiness ) , whereas the remaining 12 patients did not experience any side effects at all . The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms ; four of them had received treatment with cimetidine or omeprazol before inclusion into the study . Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate ( US$ 6.00/d v US$ 0.65/d ) . Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia . However , care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort . Due to the high cost of the therapy , calcium ketoglutarate should be used only for selected patients Background . Sevelamer carbonate is an improved , buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients . Sevelamer carbonate formulated as a powder for oral suspension presents a novel , patient-friendly alternative to tablet phosphate binders . This study compared the safety and efficacy of sevelamer carbonate powder with sevelamer hydrochloride tablets in CKD patients on haemodialysis . Methods . This was a multi-centre , open-label , r and omized , crossover design study . Thirty-one haemodialysis patients were r and omly assigned to either sevelamer carbonate powder or sevelamer hydrochloride tablets for 4 weeks followed by a crossover to the other regimen for an additional 4 weeks . Results . The mean serum phosphorus was 1.6 ± 0.5 mmol/L ( 5.0 ± 1.5 mg/dL ) during sevelamer carbonate powder treatment and 1.7 ± 0.4 mmol/L ( 5.2 ± 1.1 mg/dL ) during sevelamer hydrochloride tablet treatment . Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus ; the geometric least square mean ratio was 0.95 ( 90 % CI 0.87–1.03 ) . No statistically significant or clinical ly meaningful differences were observed in calcium × phosphorus product and lipid levels between sevelamer carbonate powder and sevelamer hydrochloride tablets . Serum bicarbonate levels increased 2.7 ± 3.7 mmol/L ( 2.7 ± 3.7 mEq/L ) during sevelamer carbonate treatment . No statistically significant change in bicarbonate was observed during sevelamer hydrochloride treatment . Sevelamer carbonate powder and sevelamer hydrochloride were well tolerated during this study . Conclusions . Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus and well tolerated in CKD patients on haemodialysis . Bicarbonate levels improved only during sevelamer carbonate treatment . Sevelamer carbonate powder should provide a welcomed new option for the treatment of hyperphosphataemia for CKD patients on dialysis Background / Aims : Colestilan is a new non-calcium-based phosphate binder licensed in Europe for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis ( CKD 5D ) . This study was conducted to evaluate efficacy in a North American patient population and also to examine secondary actions of colestilan on lipid profile and glycated hemoglobin ( HbA1c ) . Methods : This was a multicenter , r and omized , double-blind , placebo-controlled withdrawal study , after an initial open-label titration period . Patients ( n = 245 ) with stable phosphate control received 6 - 15 g/day colestilan during a 12-week , flexible titration period after which 169 were r and omized to continue the same dose ( n = 85 ) or switch to placebo ( n = 84 ) for 4 weeks . The primary endpoint was the change in serum phosphorus level during the placebo-controlled withdrawal period . Results : A significant difference of -1.01 mg/dl ( -0.33 mmol/l ) in mean change in serum phosphorus , favoring colestilan , was seen during the placebo-controlled withdrawal period ( p < 0.001 ) . Colestilan reduced serum phosphorus significantly from baseline to week 12 ( -1.54 mg/dl ( -0.50 mmol/l ) ; p < 0.001 ) . Serum calcium levels were not affected . Colestilan significantly reduced and maintained reductions in calcium × phosphorus ion product ( Ca × P ) , parathyroid hormone , total cholesterol , low-density lipoprotein cholesterol , uric acid and also HbA1c in patients with elevated baseline HbA1c . Colestilan was generally well tolerated ; most adverse events were gastrointestinal . Conclusion : In this first clinical trial with colestilan in a North American patient population , colestilan demonstrated significant efficacy in controlling serum phosphorus levels in CKD 5D patients with hyperphosphatemia , without increasing calcium levels BACKGROUND Colestilan is a non-absorbed , non-calcium-based , phosphate binder . It also binds bile acids and reduces serum levels of low-density lipoprotein cholesterol ( LDL-C ) . This study evaluated the efficacy of a range of fixed doses of colestilan compared with placebo for the control of serum phosphorus and LDL-C levels in patients with CKD stage 5 on dialysis . METHODS This was a multicentre , r and omized , double-blind , placebo-controlled , multiple fixed-dose trial in which 642 patients with CKD stage 5 on dialysis who had both hyperphosphataemia and dyslipidaemia , were r and omized to treatment with colestilan 3 , 6 , 9 , 12 or 15 g/day or placebo for 12 weeks . The co- primary endpoints were the mean changes in serum phosphorus and the mean per cent change in LDL-C from baseline to Week 12 . RESULTS A significantly greater mean reduction in serum phosphorus level from baseline to Week 12 than seen with placebo was seen with 9 g ( -0.28 mmol/L ) and pooled colestilan 12/15 g ( -0.34 mmol/L ) . The per cent reduction in LDL-C level was significantly greater with colestilan 3 , 6 and 9 g and pooled colestilan 12/15 g than with placebo ( reduction ranged from 15.9 to 27.6 % dependent on dose ) . Colestilan also reduced total cholesterol , oxidized LDL-C , HbA1c and uric acid levels , and did not increase serum calcium levels . Colestilan was generally well tolerated ; the most common adverse events affected the gastrointestinal system . CONCLUSIONS Colestilan is an effective treatment for hyperphosphataemia , and provides beneficial effects on other metabolic parameters associated with cardiovascular risk , notably Background This study compared the effects of short-term titrated colestilan ( a novel non-absorbable , non-calcium , phosphate binder ) with placebo , and evaluated the safety and efficacy of colestilan over 1 year compared with sevelamer , in patients with chronic kidney disease ( CKD ) 5D . Methods This prospect i ve multicentre study comprised a 4-week phosphate binder washout period , a 16-week short-term , flexible-dose , treatment period ( including a 4-week placebo-controlled withdrawal period ) and a 40-week extension treatment phase . Results At Week 16 ( the end of the 4-week placebo-controlled withdrawal period ) , serum phosphorus level was 0.43 mmol/L ( 1.32 mg/dL ) lower with colestilan than placebo ( P < 0.001 ; primary end point ) . Serum LDL-C level was also lower with colestilan than with placebo ( P < 0.001 ) . Both colestilan and sevelamer produced significant reductions from baseline in serum phosphorus levels ( P < 0.001 ) , maintained for 1 year , and the proportion of patients achieving target levels of ≤1.78 mmol/L ( 5.5 mg/dL ) or ≤1.95 mmol/L ( 6.0 mg/dL ) at study end were similar ( 65.3 and 73.3 % , respectively , for colestilan , and 66.9 and 77.4 % , respectively , for sevelamer ) . Serum calcium level remained stable in the colestilan group but tended to increase slightly in the sevelamer group ( end-of- study increase of 0.035 mmol/L over baseline ) . Both binders produced similar reductions from baseline in LDL-C level ( P < 0.001 ) , and responder rates after 1 year , using a target of < 1.83 mmol/L ( 70 mg/dL ) or < 2.59 mmol/L ( 100 mg/dL ) were similar in both groups ( 50.7 and 85.3 % for colestilan and 54.0 and 80.6 % for sevelamer ) . Colestilan was generally well tolerated . Conclusions Colestilan is effective and safe for the treatment of hyperphosphataemia in patients with CKD 5D , and affords similar long-term phosphorus and cholesterol reductions/responder rates to sevelamer Background —Aortic pulse wave velocity ( PWV ) is a predictor of mortality in patients with end-stage renal failure ( ESRF ) . The PWV is partly dependent on blood pressure ( BP ) , and a decrease in BP can attenuate the stiffness . Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated . Methods and Results —One hundred fifty ESRF patients ( aged 52±16 years ) were monitored for 51±38 months . From entry until the end of follow-up , the changes of PWV in response to decreased BP were measured ultrasonographically . BP was controlled by adjustment of “ dry weight ” and , when necessary , with ACE inhibitors , calcium antagonists , and /or & bgr;-blockers , in combination if necessary . Fifty-nine deaths occurred , including 40 cardiovascular and 19 noncardiovascular events . Cox analyses demonstrated that independent of BP changes , the predictors of all-cause and cardiovascular mortality were as follows : absence of PWV decrease in response to BP decrease , increased left ventricular mass , age , and preexisting cardiovascular disease . Survival was positively associated with ACE inhibitor use . After adjustment for all confounding factors , the risk ratio for the absence of PWV decrease was 2.59 ( 95 % CI 1.51 to 4.43 ) for all-cause mortality and 2.35 ( 95 % CI 1.23 to 4.41 ) for cardiovascular mortality . The risk ratio for ACE inhibitor use was 0.19 ( 95 % CI 0.14 to 0.43 ) for all-cause mortality and 0.18 ( 95 % CI 0.06 to 0.55 ) for cardiovascular mortality . Conclusions —These results indicate that in ESRF patients , the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes BACKGROUND The significant incremental expense in the use of conventional sevelamer dose prompted us to evaluate the role of prescribing a lower dose of sevelamer . METHODS To determine the optimum strategy for prescribing sevelamer in peritoneal dialysis patients , we conducted an open-label r and omized study comparing the treat-to- goal strategy ( 4.0-g daily sevelamer dose ) with lower sevelamer dose ( 1.2-g daily dose ) . RESULTS Twenty-seven peritoneal dialysis patients with serum calcium x phosphorus product above 55 mg2/dL2 were recruited . Eighteen were r and omized to the low-dose treatment group ( 1.2 g daily ) , and 9 to the treat-to- goal ( 4.0 g daily ) group . Overall , significantly lower calcium x phosphorus product and serum phosphorus levels at 6 months were achieved by the treat-to- goal treatment . The proportions of patients who attained the Kidney Disease Outcomes Quality Initiative ( K/DOQI ) treatment target , however , did not differ significantly between the treat-to- goal and low-dose treatment groups ( 66.7 % + /- 30.8 % vs. 33.3 % + /- 21.8 % , p=0.10 ) . The numbers needed to treat to benefit 1 patient who attains the K/DOQI recommendation are 1.5 patients ( 95 % confidence interval [ 95 % CI ] , 1.0 - 2.8 ) in the 4.0-g daily dose and 3 patients ( 95 % CI , 1.8 - 8.7 ) in the 1.2-g daily dose group . Therefore , an extra 66.7 % of subjects would be able to attain the treatment recommendation within the same budget if the daily dose of sevelamer used was 1.2 g instead of the usual 4.0 g. Compared with a 1.2-g daily dose of sevelamer , the 4.0-g daily dose had an incremental cost-effectiveness ratio ( ICER ) of US $ 2,353 per additional patient achieving the K/DOQI target . Multivariate analysis showed that only the calcium x phosphorus product after 1 month of sevelamer treatment was predictive of treatment response . CONCLUSIONS Low-dose sevelamer treatment might be a cost-effective approach , which is " good for many rather than best for a few . BACKGROUND Lanthanum carbonate ( LC ) , an effective non-calcium phosphate binder is widely used to manage hyperphosphatemia in patients with chronic kidney disease ( CKD ) on dialysis . Recently , the additional indication for control of hyperphosphatemia in CKD patients not on dialysis has been approved . METHODS A multicenter , r and omized , double-blind , placebo-controlled trial to confirm the efficacy and safety of LC in Japanese hyperphosphatemic stage 4 - 5 CKD patients not on dialysis . After a 4-week run-in period , 143 eligible subjects with serum phosphate levels of 5.6 - 11.0 mg/dL were r and omized ( 2 : 1 ) to receive LC or placebo ( 88 vs. 55 ) for 8 weeks ; 119 subjects completed the study ( 76 vs. 43 ) . The starting LC dose was 750 mg/day , which was then up-titrated to 2,250 mg/day as needed while tolerated . Primary efficacy analysis was performed on the intent-to-treat ( ITT ) population of 141 patients ( 86 vs. 55 ) . RESULTS LC produced a significantly greater reduction in serum phosphate level compared with placebo after 8 weeks of treatment ( difference , 0.97 ( 95 % CI : 0.58 , 1.37 ) mg/ dL ; p < 0.0001 ) . The cumulative proportion of subjects with controlled phosphate levels ≤ 4.6 mg/dL was higher in the LC group than the placebo group ( 59.56 % vs. 10.46 % ) . LC caused significantly greater reductions in serum Ca × P product and urinary phosphate excretion compared with placebo . The safety profile of LC was similar to that of placebo . CONCLUSIONS This study demonstrated the effectiveness of LC to control hyperphosphatemia in pre-dialysis CKD patients We conducted a r and omized unblinded parallel clinical trial to compare the effectiveness , side effects and tolerance between calcium acetate ( CA ) and calcium carbonate ( CC ) in 80 stable chronic hemodialysis patients selected on the basis of their acceptable control of serum phosphorus ( P ) levels with aluminum hydroxide ( AH ) . All patients were dialyzed against the same calcium dialyzate ( 1.62 mmol/l ) . The serum analytical tests included : calcium corrected to total protein , P , PTH ( intact molecule ) and bicarbonate . The study was divided into the following periods : P0 : baseline measurements ; P1 : washout ( withdrawal of AH for 15 days ) ; P2 : r and om allocation to CA and CC treatment at doses equivalent to 75 mEq of elemental calcium , stratified according to previous doses of AH ( 2 months ) ; P3 : adjustment of doses until control P ( 2 months ) . CA was poorly tolerated in 7 patients and CC in 2 ( NS ) . The changes in serum P levels between P0 and P2 periods were lower in the CA group ( 1.73 + /- 0.25 vs. 1.80 + /- 0.50 mmol/l ; p = 0.26 ) than in the CC group ( 1.77 + /- 0.35 vs. 1.93 + /- 0.48 mmol/l ; p = 0.03 , paired t test ) . Serum calcium was hardly modified by CA ( 2.42 + /- 0.20 vs. 2.47 + /- 0.17 mmol/l ; NS ) while in the CC group , it rose significantly ( 2.40 + /- 0.12 vs. 2.55 + /- 0.22 mmol/l ; p = 0.0004 ) . There were no differences in the control of PTH or bicarbonate . ( ABSTRACT TRUNCATED AT 250 WORDS Recent in vitro and in vivo studies have shown that calcium acetate ( CaAC ) is a more effective phosphorus binder than , among other calcium salts , calcium carbonate ( CaCO3 ) . More efficient binding allows serum phosphorus to be controlled with a lower dose ; moreover , less calcium seems to be absorbed when CaAC is used . These properties could reduce the incidence of hypercalcemia ; however , in clinical practice few reports have compared these two calcium salts , and results disagree . We evaluated in a 24-week prospect i ve cross-over study the clinical efficiency of CaCO3 and CaAC in 10 selected chronic hemodialysis patients . Only 7 patients completed the study period . The patients were r and omly assigned to start treatment with one of the two calcium salts ; after 12 weeks they shifted to the other treatment . Serum analytical tests included weekly control of calcium , phosphorus , and alkaline phosphatase . PTH values ( intact molecule ) were obtained initially and at the end of every study period . The same good control of the phosphorus level ( 4.79 + /- 0.6 vs. 4.94 + /- 0.8 mg/dl ) was obtained with CaAC ( mean doses 4.1 + /- 0.3 g/day ) as with CaCO3 ( mean doses 4.01 + /- 0.8 g/day ) . The mean serum calcium levels were similar ( 10.36 + /- 0.5 vs. 10.20 + /- 0.5 mg/dl ) . The dose of elemental calcium administered was significantly less with CaAC ( 957 + /- 83 mg/day ) than with CaCO3 ( 1,590 + /- 317 mg/day ) . However , the incidence of hypercalcemia ( Ca > 11 mg/dl ) was similar during the two treatment periods ( 13 % with CaAC vs. 14 % with CaCO3 ) . Also the incidence of Ca x P products 765 was comparable ( 9.5 vs. 11.9 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS It has been shown that calcium carbonate ( CaCO3 ) is an effective phosphate binder which is less toxic than Al(OH)3 . However , given that its use with st and ard calcium dialysate ( CaD ) levels may lead to hypercalcemia , a decrease in CaD levels has been proposed . The aim of the present study was to elevate the acute clinical and biochemical consequences of a lowering of CaD in HD patients . Dialysate composition was otherwise the same . ( 1 ) Blood pressure levels ( BP ) during short hemodialysis were measured in a group of 12 patients who underwent alternate hemodialyses with dialysate calcium of 1.75 and 1.25 mmol/l . ( 2 ) Ca2 + and PTH kinetics during short hemodialysis were studied in a group of 6 patients who were sequentially treated with 1.75 and 1.25 mmol/l CaD. The results show : ( 1 ) that cardiovascular stability in chronic HD patients during short HD sessions with low CaD ( LCaD ) may be good ; ( 2 ) that a single treatment with st and ard CaD ( SCaD ) produces positive calcium balances ( JCa2 + ) with Ca2 + plasma increase and PTHi inhibition at the end of HD sessions ; during HD with LCaD there were neutral mean JCa2 + and no changes in post-dialysis mean Ca2 + and PTHi plasma levels ; furthermore 2 patients showed a small PTHi increase during HD with LCaD and neutral JCa2 + because of a high positive bicarbonate balance during HD . In conclusion , as with several aspects of dialysis treatment , dialysate calcium levels should also be individualized to avoid hypercalcemic crises or PTHi stimulation BACKGROUND JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient . METHODS In this Phase 3 , multicenter , r and omized , open-label , parallel-group study , we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis . A total of 230 patients with a serum phosphate ≥1.97 and < 3.23 mmol/L were r and omized to JTT-751 ( dose adjusted between 1.5 and 6.0 g/day ) or sevelamer hydrochloride ( dose adjusted between 3.0 and 9.0 g/day ) for 12 weeks . The primary outcome was change in serum phosphate from baseline to end of treatment . Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone ( PTH ) . The changes in ferritin , transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes . RESULTS Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group , establishing non-inferiority of JTT-751 compared with sevelamer ( least squares mean , -0.03 mmol/L ; 95 % confidence interval , -0.13 to 0.07 mmol/L ) . Corrected serum calcium increased and PTH decreased from baseline within both groups ; changes between groups were similar . Gastrointestinal disorders were the most common adverse events in both groups ; the incidence of diarrhea was higher in the JTT-751 group , while constipation occurred frequently in the sevelamer group . Treatment with JTT-751 result ed in significant relative increases in serum ferritin and transferrin saturation . CONCLUSIONS Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia . Differential adverse effects were observed ; biochemical markers of iron status increased in patients treated with JTT-751 . TRIAL REGISTRATION NUMBER CTI-111433 ( The Japan Pharmaceutical Information Center at : http//www . clinical trials.jp ) . Date of registration : 7 March 2011 BACKGROUND AND OBJECTIVES The primary goals were to re-examine whether sevelamer carbonate ( SC ) reduces advanced glycation end products ( AGEs ) ( methylglyoxal and carboxymethyllysine [ CML ] ) , increases antioxidant defenses , reduces pro-oxidants , and improves hemoglobin A1c ( HbA1c ) in patients with type 2 diabetes mellitus ( T2DM ) and diabetic kidney disease ( DKD ) . Secondary goals examined albuminuria , age , race , sex , and metformin prescription . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This two-center , r and omized , intention-to-treat , open-label study evaluated 117 patients with T2DM ( HbA1c > 6.5 % ) and stages 2 - 4 DKD ( urinary albumin/creatinine ratio ≥200 mg/g ) treated with SC ( 1600 mg ) or calcium carbonate ( 1200 mg ) , three times a day , without changing medications or diet . Statistical analyses used linear mixed models adjusted for r and omization levels . Preselected subgroup analyses of sex , race , age , and metformin were conducted . RESULTS SC lowered serum methylglyoxal ( 95 % confidence interval [ CI ] , -0.72 to -0.29 ; P<0.001 ) , serum CML ( 95 % CI , -5.08 to -1.35 ; P≤0.001 ) , and intracellular CML ( 95 % CI , -1.63 to -0.28 ; P=0.01 ) . SC increased anti-inflammatory defenses , including nuclear factor like-2 ( 95 % CI , 0.58 to 1.29 ; P=0.001 ) , AGE receptor 1 ( 95 % CI , 0.23 to 0.96 ; P=0.001 ) , NAD-dependent deacetylase sirtuin-1 ( 95 % CI , 0.20 to 0.86 ; P=0.002 ) , and estrogen receptor α ( 95 % CI , 1.38 to 2.73 ; P ≤0.001 ) . SC also decreased proinflammatory factors such as TNF receptor 1 ( 95 % CI , -1.56 to -0.72 ; P≤0.001 ) and the receptor for AGEs ( 95 % CI , -0.58 to 1.53 ; P≤0.001 ) . There were no differences in HbA1c , GFR , or albuminuria in the overall group . Subanalyses showed that SC lowered HbA1c in women ( 95 % CI , -1.71 to -0.27 ; P=0.01 , interaction P=0.002 ) , and reduced albuminuria in those aged < 65 years ( 95 % CI , -1.15 to -0.07 ; P=0.03 , interaction P=0.02 ) and non-Caucasians ( 95 % CI , -1.11 to -0.22 ; P=0.003 , interaction P≤0.001 ) , whereas albuminuria increased after SC and calcium carbonate in Caucasians . CONCLUSIONS SC reduced circulating and cellular AGEs , increased antioxidants , and decreased pro-oxidants , but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD . Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD , further studies may be warranted Background The accumulation of p-cresol , a metabolic product of aromatic amino acids generated by intestinal microbiome , increases the cardiovascular risk in chronic kidney disease ( CKD ) patients . Therefore , therapeutic strategies to reduce plasma p-cresol levels are highly dem and ed . It has been reported that the phosphate binder sevelamer ( SEV ) sequesters p-cresol in vitro , while in vivo studies on dialysis patients showed controversial results . Aim of our study was to evaluate the effect of SEV on p-cresol levels in non-dialysis CKD patients . Methods This was a single-blind , r and omized placebo-controlled trial ( Registration number NCT02199444 ) carried on 69 CKD patients ( stage 3–5 , not on dialysis ) , r and omly assigned ( 1:1 ) to receive either SEV or placebo for 3 months . Total p-cresol serum levels were evaluated at baseline ( T0 ) , and 1 ( T1 ) and 3 months ( T3 ) after treatment start . The primary end-point was to evaluate the effect of SEV on p-cresol levels . Results Compared to baseline ( T0 , 7.4 ± 2.7 mg/mL ) , p-cresol mean concentration was significantly reduced in SEV patients after one ( − 2.06 mg/mL , 95 % CI − 2.62 to − 1.50 mg/mL ; p < 0.001 ) and 3 months of treatment ( − 3.97 mg/mL , 95 % CI − 4.53 to − 3.41 mg/mL ; p < 0.001 ) ; no change of plasma p-cresol concentration was recorded in placebo-treated patients . Moreover , P and LDL values were reduced after 3 months of treatment by SEV but not placebo . Conclusions In conclusion , our study represents the first evidence that SEV is effective in reducing p-cresol levels in CKD patients in conservative treatment , and confirms its beneficial effects on inflammation and lipid pattern Background Sucroferric oxyhydroxide is a noncalcium , iron-based phosphate binder that demonstrated sustained serum phosphorus control , good tolerability and lower pill burden compared with sevelamer carbonate ( sevelamer ) in a Phase 3 study conducted in dialysis patients . This sub analysis examines the efficacy and tolerability of sucroferric oxyhydroxide and sevelamer in the peritoneal dialysis ( PD ) patient population . Methods The initial study ( NCT01324128 ) and its extension ( NCT01464190 ) were multicenter , Phase 3 , open-label , r and omized ( 2:1 ) , active-controlled trials comparing sucroferric oxyhydroxide ( 1.0 - 3.0 g/day ) with sevelamer ( 2.4 - 14.4 g/day ) in dialysis patients over 52 weeks in total . Results In the overall study , 84/1055 ( 8.1 % ) patients received PD and were eligible for efficacy analysis ( sucroferric oxyhydroxide , n = 56 ; sevelamer , n = 28 ) . The two groups were broadly comparable to each other and to the overall study population . Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 ( mean change from baseline - 0.6 mmol/L ) . Over 52 weeks , sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as sevelamer ; 62.5 % and 64.3 % of patients , respectively , were below the Kidney Disease Outcomes Quality Initiative target range ( ≤1.78 mmol/L ) . This was achieved with a lower pill burden ( 3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day ) with sucroferric oxyhydroxide compared with sevelamer . Treatment adherence rates were 91.2 % with sucroferric oxyhydroxide and 79.3 % with sevelamer . The proportion of patients reporting at least one treatment-emergent adverse event was 86.0 % with sucroferric oxyhydroxide and 93.1 % with sevelamer . The most common adverse events with both treatments were gastrointestinal : diarrhea and discolored feces with sucroferric oxyhydroxide and nausea , vomiting and constipation with sevelamer . Conclusions Sucroferric oxyhydroxide is noninferior to sevelamer for controlling serum phosphorus in patients undergoing PD , while providing a relatively low pill burden and a high rate of adherence Abstract Background Sucroferric oxyhydroxide is a non-calcium , iron-based phosphate binder indicated for the treatment of hyperphosphataemia in adult dialysis patients . This post hoc analysis of a r and omized , 24-week Phase 3 study and its 28-week extension was performed to evaluate the long-term effect of sucroferric oxyhydroxide on iron parameters . Methods A total of 1059 patients were r and omized to sucroferric oxyhydroxide 1.0–3.0 g/day ( n = 710 ) or sevelamer carbonate ( ‘ sevelamer ’ ) 2.4–14.4 g/day ( n = 349 ) for up to 52 weeks . The current analysis only included patients who completed 52 weeks of continuous treatment ( n = 549 ) . Changes in iron-related parameters and anti-anaemic product use during the study were measured . Results Some changes in iron-related parameters across both treatment groups were observed during the first 24 weeks of the study , and to a lesser extent with longer-term treatment . There were small , but significantly greater increases in mean transferrin saturation ( TSAT ) and haemoglobin levels with sucroferric oxyhydroxide versus sevelamer during the first 24 weeks ( change in TSAT : + 4.6 % versus + 0.6 % , P = 0.003 ; change in haemoglobin : + 1.6 g/L versus −1.1 g/L , P = 0.037 ) . Mean serum ferritin concentrations also increased from Weeks 0 to 24 with sucroferric oxyhydroxide and sevelamer ( + 119 ng/mL and + 56.2 ng/mL respectively ; no statistically significant difference between groups ) . In both treatment groups , ferritin concentrations increased to a greater extent in the overall study population [ > 70 % of whom received concomitant intravenous ( IV ) iron ] , compared with the subset of patients who did not receive IV iron therapy during the study . The pattern of anti-anaemic product use was similar in both treatment groups , with a trend towards higher use of IV iron and erythropoiesis-stimulating agents with sevelamer . Conclusions Initial increases in some iron-related parameters were observed in both treatment groups but were more pronounced with sucroferric oxyhydroxide . These differences between treatment groups with respect to changes in iron parameters are likely due to minimal iron absorption from sucroferric oxyhydroxide INTRODUCTION Oral phosphate binders are the main stay of treatment of hyperphosphatemia . Adherence rates to ferric citrate , a recently approved phosphate binder , are unknown . METHODS We conducted a post-hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease ( ESKD ) who were r and omized to ferric citrate vs. active control ( sevelamer carbonate and /or calcium acetate ) . Adherence was defined as percent of actual number of pills taken to total number of pills prescribed . FINDINGS There were no significant differences in baseline characteristics including gender , race/ethnicity , and age between the ferric citrate and active control groups . Baseline phosphorus , calcium , and parathyroid hormone levels were similar . Mean ( SD ) adherence was 81.4 % ( 17.4 ) and 81.7 % ( 15.9 ) in the ferric citrate and active control groups , respectively ( P = 0.88 ) . Adherence remained similar between both groups after adjusting for gender , race/ethnicity , age , cardiovascular disease ( CVD ) , and diabetic nephropathy ( mean [ 95 % CI ] : 81.4 % [ 78.2 , 84.6 ] and 81.5 % [ 77.7 , 85.2 ] for ferric citrate and active control , respectively ) . Gender , race/ethnicity , age , and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder . Subjects with CVD had lower adherence rates to phosphate binder ; this was significant only in the active control group . DISCUSSION Adherence rates to the phosphate binder , ferric citrate , were similar to adherence rates to active control . Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label . Gender , race/ethnicity , nor age influenced adherence Background Hyperphosphatemia is common in chronic kidney disease ( CKD ) and associated with mortality and morbidity . We aim ed to evaluate the dose-dependent efficacy and safety of PA21 ( sucroferric oxyhydroxide ) , an iron-based phosphate binder , in Japanese hemodialysis patients with hyperphosphatemia . Methods In this double-blind , multicenter , Phase II study , 183 patients were r and omized to placebo or PA21 at doses of 250 , 500 , 750 , or 1000 mg ( based on iron content ) three times/day for 6 weeks . The primary efficacy endpoint was the mean change in serum phosphorus levels from baseline to end of treatment in each group . Adverse reactions were evaluated . Results The change in serum phosphorus level was significantly greater in each PA21 group than in the placebo group ( analysis of covariance : P < 0.001 for all groups ) . A dose-dependent change in serum phosphorus levels was observed in the PA21 groups . A notable decrease in mean serum phosphorus levels to the target level of ≤6 mg/dL was shown starting at Week 1 in all PA21 groups . The cumulative achievement rates for target serum phosphorus level at the end of treatment were generally > 80 % in all PA21 groups . The major adverse reaction reported was diarrhea ; however , most cases were mild . Conclusions PA21 was an effective and safe treatment that decreased serum phosphorus levels starting at 1 week of treatment when administered as one 250-mg tablet three times/day . PA21 demonstrated a dose-dependent phosphorus lowering effect up to 3000 mg/day . PA21 may be a new treatment alternative with relatively low pill burden for Japanese hemodialysis patients with hyperphosphatemia Background Calcium (Ca)-based phosphate ( P ) binders , compared to non-Ca-based P binders , contribute to vascular calcification , which is associated with cardiovascular events . Methods The L AND MARK study is a multicenter , r and omized , open-label , parallel comparative study of lanthanum carbonate ( LC ) and calcium carbonate ( CC ) in hemodialysis patients . Stable hemodialysis patients with intact parathyroid hormone ≤240 pg/mL meeting ≥1 of the following criteria ( age > 65 years , postmenopause , diabetes mellitus ) were r and omized into the LC and CC groups . LC group patients initially received LC 750 mg/day or the previously used dose and were titrated up to a maximum 2250 mg/day to achieve serum P levels of 3.5–6.0 mg/dL. CC group patients received CC 3 g/day or the previously used dose and were titrated to achieve the same P range . If the target serum P level was not achieved , non-Ca-based P binders ( other than LC ) could also be added . The primary endpoint is survival time free of cardiovascular events , including cardiovascular death , non-fatal myocardial infa rct ion or stroke , and unstable angina . Results Overall , 2309 patients were allocated to the LC ( N = 1154 ) or CC group ( N = 1155 ) . At baseline , the mean age was 68.4 years , 40.4 % were women , 55.9 % had diabetes , 18.3 % had a history of ischemic heart disease , and 13.9 % had cerebrovascular disease . A total of 184 patients ( 8.4 % ) had undergone coronary intervention procedures . Baseline characteristics were well balanced between groups . Conclusions The L AND MARK study will determine whether LC , a non-Ca-based P binder , reduces cardiovascular mortality and morbidity in chronic hemodialysis patients Currently , calcium- or metal-containing phosphate binders are available to treat hyperphosphatemia in predialysis patients with chronic kidney disease . Bixalomer , a non-calcium , metal-free phosphate binder , has not been studied in these patients . We evaluated the efficacy and safety of bixalomer versus placebo for treatment of hyperphosphatemia in Japanese predialysis patients with chronic kidney disease . This multicenter , r and omized , double-blind , phase 3 trial , r and omized eligible patients 1:1 to receive bixalomer or placebo for 12 weeks . Bixalomer was started at 1500 mg/day and adjusted up to 7500 mg/day depending on serum phosphorus concentrations . The primary endpoint was change in serum phosphorus concentration from baseline to end of treatment . After a 4-week pre-investigational period , 163 patients ( bixalomer : N = 81 ; placebo : N = 82 ) were r and omized . The adjusted mean change ( 95 % confidence interval ) from baseline to end of treatment in serum phosphorus was significantly greater with bixalomer ( -0.78 [ -0.98 , -0.57 ] mg/dL ) versus placebo ( 0.20 [ -0.00 , 0.41 ] mg/dL ) ; mean difference : -0.98 ( -1.27 , -0.69 ) , P < 0.001 . At end of treatment , 57.5 % of bixalomer-treated patients achieved target serum phosphorus concentrations , mean serum intact parathyroid hormone and fibroblast growth factor-23 decreased , and there were no significant changes in corrected serum calcium . The safety and tolerability of bixalomer was similar to placebo . The most common drug-related adverse events were gastrointestinal ( > 24 % patients per group ) . There was a significant increase in bicarbonate concentrations with bixalomer versus placebo ( P = 0.003 ) . Bixalomer was superior to placebo for hyperphosphatemia in Japanese predialysis patients with chronic kidney disease and may constitute a new treatment option BACKGROUND Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer , which may be suited to once-daily dosing . STUDY DESIGN R and omized parallel open-label study . SETTING & PARTICIPANTS Hemodialysis patients . INTERVENTION After a 2-week phosphate-binder washout , patients were r and omly assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer hydrochloride tablets . OUTCOMES Assessment of noninferiority with respect to change from baseline in serum phosphorus levels . MEASUREMENTS Serum phosphorus to 24 weeks . RESULTS After washout , mean serum phosphorus level decreased 2.0 + /- 1.8 mg/dL ( from 7.3 + /- 1.3 mg/dL ) for sevelamer carbonate and 2.9 + /- 1.3 mg/dL ( from 7.6 + /- 1.3 mg/dL ) for sevelamer hydrochloride ( both P < 0.001 ) . The upper CI bound was 1.50 mg/dL ; therefore , noninferiority was not shown . 54 % of sevelamer carbonate powder-treated patients and 64 % of sevelamer hydrochloride tablet-treated patients had serum phosphorus levels within the National Kidney Foundation 's Kidney Disease Outcomes Quality Initiative ( KDOQI ) target ( > or = 3.5 and < or = 5.5 mg/dL ) . Overall , the percentage of patients with treatment-emergent adverse events was similar between groups . However , a greater percentage of treatment-related upper gastrointestinal events , including nausea ( 10 % vs 3 % ) and vomiting ( 6 % vs 1 % ) , were noted with sevelamer carbonate powder once daily . In addition , 4 ( 3 % ) sevelamer carbonate-treated patients experienced stimulation of the gag reflex and 2 ( 1 % ) experienced dislike of the taste with sevelamer carbonate powder . A greater percentage of sevelamer carbonate powder-treated patients discontinued treatment because of these treatment-related events or consent withdrawal . LIMITATIONS Study was not blinded . Once-daily dose may not have been with the highest phosphate content meal ; further exploration of alternative dosing schemes is warranted . CONCLUSIONS Once-daily administration of sevelamer carbonate powder was not as effective in decreasing serum phosphorus levels as thrice-daily administration of sevelamer hydrochloride tablets . Nevertheless , once-daily sevelamer carbonate powder decreased serum phosphorus levels significantly , reaching the KDOQI phosphorus target in most patients . Therefore , once-daily dosing of sevelamer carbonate may be a reasonable alternative Hyperphosphatemia is a significant risk factor for the development of ectopic calcification and coronary artery diseases in patients on hemodialysis ( HD ) , and must be controlled with the use of phosphate binders . Studies comparing the effects of sevelamer and nicotinic acid , both similar non-calcium and non-aluminum phosphate binders , are not available . In this study , 40 patients on HD with a serum phosphorus level of more than 6 mg/dL were enrolled . After a two week washout period without phosphate binders , the patients were r and omly divided into two equal groups ( n = 20 ) and were started on nicotinic acid or sevelamer for a period of four weeks . The dose of nicotinic acid used was 500 mg and that of sevelamer was 1600 mg daily . Blood sample s were drawn for the measurement of the total calcium ( Ca ) , phosphorus ( P ) , alkaline phosphatase ( ALP ) , triglyceride ( TG ) , total cholesterol ( Chol ) , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , uric acid and parathyroid hormone ( PTH ) . Patients receiving sevelamer showed a significant reduction in serum P level ( 2.2 ± 0.69 mg/dL ; P < 0.0001 ) in comparison with the nicotinic acid group ( 1.7 ± 1.06 mg/dL ; P = 0.004 ) . Reduction in the Ca-P product was significantly different in the two groups ; in the sevelamer group , it was 21 ± 7 ; ( P < 0.0001 ) while in the nicotinic acid group , it was 16 ± 11 ( P = 0.007 ) . Also , patients on sevelamer showed greater reduction in the mean TG level ( 38.9 ± 92 mg/dL ; P = 0.005 ) . No significant changes were observed in the mean serum Ca , total Chol , HDL , LDL , ALP and iPTH levels in the two study groups . Our short-term study suggests that although nicotinic acid reduced hyperphosphatemia , sevelamer showed higher efficacy in controlling hyperphosphatemia as well as the Ca-P product Objective . To evaluate the influence of sevelamer hydrochloride and calcium acetate on biomarkers of bone turnover in patients with hyperphosphatemia receiving hemodialysis . Methods . In this prospect i ve , open-label , r and omized , active-controlled study , 70 patients ( 38 men and 32 women ) with hyperphosphatemia ( serum phosphorus level > 6.0 mg/dL ) underwent a two-week washout period and were r and omly selected to receive sevelamer hydrochloride ( n = 37 ) or calcium acetate ( n = 33 ) for eight weeks . Changes in serum levels of intact parathyroid hormone ( iPTH ) , alkaline phosphatase ( Alk-P ) , phosphorus , and calcium were measured and compared . Results . After eight weeks of treatment , calcium acetate lowered iPTH levels significantly more than sevelamer hydrochloride did ( −178.0 vs. −69.0 pg/mL , p = 0.0019 ) . Levels of Alk-P were significantly elevated in patients given sevelamer hydrochloride compared with levels in those given calcium acetate treatment ( 24.09 vs. 7.45 U/L , p = 0.0014 ) . Changes in serum phosphorus levels did not differ between sevelamer hydrochloride ( −1.93 mg/dL ) and calcium acetate ( −2.5 mg/dL ) at the end of the study ( p = 0.0514 ) . Changes in the calcium and phosphorous product did not significantly differ between the sevelamer-hydrochloride group ( −18.06 mg2/dL2 ) and the calcium-acetate group ( −19.05 mg2/dL2 , p = 0.6764 ) . Fifteen patients ( 45.5 % ) treated with calcium acetate had hypercalcemia ( serum-adjusted calcium level > 10.5 mg/dL ) ; the rate was significantly higher than that of patients treated with sevelamer ( five [ 13.5 % ] of 37 , p = 0.0039 ) . Conclusion . Treatment with sevelamer hydrochloride had the advantage of maintaining stable iPTH levels and elevating Alk-P levels while lowering serum phosphorus levels and calcium-phosphorous product The Dialysis Clinical Outcomes Revisited ( DCOR ) trial was a large r and omized , multicenter 3-year trial comparing the effects of sevelamer with calcium-based binders on mortality , hospitalization , morbidity , and medical costs in hemodialysis subjects . Dialysis Clinical Outcomes Revisited was prospect ively design ed to link subjects to the Centers for Medicare & Medicaid Services End-Stage Renal Disease ( CMS ESRD ) data base to collect additional baseline characteristic data and to enhance outcome evaluation . Subjects were linked to the CMS ESRD data base by means of an algorithm using several patient identifiers . Some baseline characteristic data were collected exclusively from the CMS ESRD data base . Mortality and hospitalization end points were obtained from the CMS ESRD data base and compared with similar data collected prospect ively into a case-report form ( CRF ) data base . Of the 2103 patients who participated in the DCOR study , 2101 were successfully linked to the CMS ESRD data base . Patient baseline data showed that treatment groups were well-balanced , except that a higher proportion of subjects in the calcium-based binder group had atherosclerotic heart disease . Calculated mortality rates were similar between data bases , but more deaths were identified in the CMS than in the CRF data base . These additional deaths were verified through several sources . More hospitalizations were also detected in the CMS than in the CRF data base . The CMS data base was a good source of death end points and hospitalization occurrence . Linking patients to the data -rich CMS ESRD data base allowed assessment of additional important secondary end points at a relatively low cost compared with prospect i ve data collection AIMS No conventional phosphate binder is entirely satisfactory for the treatment of hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . Consequently , there is a need for new agents . One such agent is lanthanum carbonate ( La ) . This large-scale study compares the safety of La with st and ard therapy ( any approved phosphate binder ) in patients who were treated for up to 2 years . Efficacy , having previously been demonstrated , was a secondary endpoint . MATERIAL S AND METHODS After washout , patients were r and omized to receive La ( n=682 ) or their pre- study phosphate binder ( n=677 ) . Over a 6-week period , La was titrated to a maximum daily dose of 3000 mg elemental lanthanum ( serum phosphorus target levels for titration were < or = 5.9 mg/dl ( 1.90 mmol/l ) ) . Safety assessment s included adverse events ( AEs ) , full laboratory parameters and blood profiles . Efficacy assessment s included serum phosphorus , calcium , calcium x phosphorus product and parathyroid hormone ( PTH ) levels . RESULTS Average treatment exposure was greater in the st and ard therapy group ( 501.4 days ) than in the La group ( 370.3 days ) because st and ard therapy patients who switched or combined treatments were allowed to continue in the study . The most common AEs were gastrointestinal . The incidences of AEs in the La and treatment exposure-corrected st and ard therapy groups were nausea , 37 versus 29 % ; vomiting , 27 versus 22 % and diarrhea ( 24 % in each group ) . Hypercalcemia that was reported as an AE ( La versus treatment exposure-corrected st and ard therapy ) occurred in 4.3 % and 8.4 % of patients , respectively . There was no indication of liver toxicity , suppression of erythropoiesis or changes in the mini-mental state examination . Over 2 years , phosphorus control was similar in both groups ; in the La group , however , serum calcium was lower and serum PTH levels were maintained in the range recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative ( K/DOQI ) . CONCLUSIONS The 2-year tolerability and efficacy of La are similar to those seen with st and ard therapy , although lower serum calcium levels and improved PTH levels were observed in the La group . These results support La as a viable new option for the management of hyperphosphatemia in ESRD 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 Abstract Background and Objective : Hyperphosphataemia in end-stage renal disease ( ESRD ) is a major contributor to the development of cardiovascular disease . It has been proposed that the phosphate binder sevelamer has pleiotropic properties . The aim of this study was to evaluate the effects of sevelamer compared with calcium acetate on serum lipid profiles , uric acid and reactive oxygen species in haemodialysis patients with hyperphosphataemia . Methods : An 8-week , r and omized , open-label , parallel-group study was conducted after a 2-week washout period . A total of 52 patients with ESRD on maintenance haemodialysis were screened for enrolment ; 26 patients were r and omized to each of the sevelamer and calcium acetate groups . Reactive oxygen species ( ROS ) production , i.e. superoxide and hydrogen peroxide (H2O2)-related radicals , were detected by chemiluminescence measurement with lucigenin and luminol , respectively . Results : There were no significant differences between treatment groups in changes in serum phosphorus ( p = 0.378 ) and adjusted serum calcium levels ( p = 0.980 ) , but there were more hypercalcaemic events in the calcium acetate group ( 12.0 % vs 3.7 % ) during treatment . Total serum cholesterol ( p < 0.001 ) and low-density lipoprotein ( LDL ) cholesterol ( p < 0.001 ) levels decreased significantly compared with baseline in the sevelamer group . The decreases in total serum cholesterol and LDL cholesterol were correlated with the reductions in serum phosphorus levels during sevelamer treatment ( correlation coefficient [ r ] = 0.266 and 0.386 , respectively ) . Serum uric acid decreased significantly in the sevelamer group ( p = 0.020 ) , and this change was correlated with serum phosphorus changes ( r = 0.458 ) . Decreases in plasma H2O2-related radicals , the major oxidative stressor in ROS ( p < 0.001 ) , but not superoxide ( p = 0.593 ) , were observed after sevelamer treatment . Conclusion : The improvements in multiple lipid surrogates , uric acid and ROS seen in this study show that sevelamer is a promising therapy for treatment of hyperphosphataemia in maintenance haemodialysis patients with a high risk of cardiovascular disease Background The contribution of pro-inflammatory markers to cardiovascular ( CV ) risk and vascular calcification in chronic kidney disease ( CKD ) remains largely to be eluci date d. We investigated the association between plasma levels of several biomarkers and calcification volume in three different vascular beds in CKD Stages 3 and 4 patients . Methods This is a cross-sectional , exploratory study in patients with an estimated glomerular filtration rate ( eGFR ) ≥20 and ≤45 mL/min/1.73 m2 and serum phosphorus ≥3.5 and < 6.0 mg/dL enrolled in a previously published r and omized , double blind , placebo-controlled single-centre trial . Ethylenediaminetetraacetic acid ( EDTA ) plasma sample s were collected at baseline before patients received study medication and analysed for the presence of a number of biomarkers . Coronary artery calcium ( CAC ) , thoracic aortic calcification ( TAC ) and abdominal aortic calcification ( AAC ) volumes were measured using st and ard electron-beam computed tomography protocol s. Associations were adjusted for age , sex , smoking , body mass index , diabetes mellitus status , low-density lipoprotein cholesterol ( LDL-C ) , systolic blood pressure and eGFR . Results Associations with CAC were found for β2-microglobulin ( B2 M ) , fibroblast growth factor 23 ( FGF23 ) , interleukin-8 ( IL-8 ) and IL-18 . AAC was associated with : B2 M , FGF23 and IL-2 receptor alpha ( IL-2 RA ) . TAC was associated with : B2 M , FGF23 , IL-2 RA , IL-18 and tumour necrosis factor receptor type I. For most of the analysed biomarkers , there were non-significant trends of associations with calcification . Conclusions This exploratory study found that elevated plasma levels of several inflammatory biomarkers are significantly associated with arterial calcification in CKD Stages 3 and 4 patients . A greater underst and ing of inflammation and calcification in CKD patients may help the development of CV risk- assessment algorithms for better management of these patients Abstract Aim We aim ed to investigate the non‐inferiority of PA21 ( sucroferric oxyhydroxide ) to sevelamer hydrochloride ( sevelamer ) in terms of efficacy and safety in Japanese haemodialysis patients with hyperphosphataemia . Methods In this Phase III , open‐label , multicentre study , 213 haemodialysis patients with hyperphosphataemia were r and omized to PA21 or sevelamer treatment for 12 weeks . The primary outcome was adjusted serum phosphorus concentration at the end of treatment ; the non‐inferiority of PA21 was confirmed if the upper limit of the two‐sided 95 % confidence interval ( CI ) is ≤0.32 mmol/L. Secondary outcomes were corrected serum calcium and intact‐parathyroid hormone concentrations . Adverse events ( AEs ) and adverse drug reactions ( ADRs ) were evaluated . Results The adjusted mean serum phosphorus concentration at the end of treatment confirmed the non‐inferiority of PA21 for lowering serum phosphorus compared with sevelamer ( 1.62 vs 1.72 mmol/L ; difference , −0.11 mmol/L ; 95 % CI , −0.20 to −0.02 mmol/L ) . The mean daily tablet intake was 5.6 ± 2.6 and 18.7 ± 7.1 tablets in the PA21 and sevelamer groups , respectively . The incidences of AEs and ADRs were not significantly different between the two groups . Conclusion The non‐inferiority of PA21 to sevelamer was confirmed for the treatment of Japanese haemodialysis patients with hyperphosphataemia . PA21 was effective , safe , and well tolerated , while having a considerably lower pill burden than sevelamer Background Hyperphosphatemia is a common problem in patients with end-stage renal disease ( ESRD ) who are on maintenance hemodialysis ( HD ) and contributes to the development of secondary hyperparathyroidism and cardiovascular complications . Nicotinamide ( NAM ) has been shown in some studies to inhibit intestinal and renal sodium/phosphorus co-transporters and reduce serum phosphorus levels . We have therefore evaluated the efficacy and safety of NAM as adjunctive therapy to calcium-based phosphate binders to control hyperphosphatemia in hemodialysis patients . Methods Sixty pediatric HD out patients were r and omly divided into two equally sized groups ( 30 children each ) . One group received calcium-based phosphate binder ( control group ) , and the other received both the calcium-based phosphate binder + NAM at a dose of 100 mg twice or three times daily ( nicotinamide group ) . Both groups were followed for a 6-month period . Results Over the 6-month treatment period , children in the NAM group showed a significant decline in the levels of serum phosphorus ( p = 0.0001 ) , serum calcium – phosphorus ( Ca × P ; p = 0.0001 ) product and parathyroid hormone ( p = 0.02 ) versus baseline values and those of the control group . After 6 months of NAM treatment , the mean serum high-density lipoprotein cholesterol levels had increased significantly ( p = 0.01 ) , and the median serum triglyceride levels had decreased ( p = 0.009 ) . There was no significant change in any of these parameters among the children of the control group . The major adverse events associated with the NAM therapy were diarrhea , flushing and nausea . Conclusion The addition of NAM to therapy with phosphate binders is effective in lowering phosphorus levels and has a beneficial effect on the lipid profile with only mild side effects Background In the general population and in hemodialysis patients epicardial adipose tissue ( EAT ) has been associated with increased mortality and cardiovascular events . Weight loss and lipid lowering therapies reduced EAT in the general population . It is unknown whether sevelamer , a phosphate ( Pi ) binder that lowers cholesterol and reduces inflammation in dialysis patients also affects EAT progression . Methods Post-hoc analysis of a r and omized trial of sevelamer ( SVL ) versus calcium-based Pi binders ( CPiB ) in incident hemodialysis patients . EAT was measured on cardiac computed tomography scans performed at enrollment , 6 , 12 and 18 months from baseline . Results Of 109 patients , 54 received SVL and 55 CPiB ; the median LDL change was −16.4 % ( IQR : −67.5 , 142.3 % ) and 12.1 % ( IQR : −51.9 , 193.8 % ) with SVL and CPiB respectively ( p < 0.001 ) . At baseline EAT correlated significantly with gender , body mass index and total coronary artery calcium score ( all p < 0.02 ) . At the end of follow-up , EAT progressed significantly from baseline in the CPiB treated patients but not in the SVL treated patients [ median increase 9.1 % ( p = 0.005 ) vs 3.9 % ( p = 0.25 ) ] . However , there was no significant difference in the degree of progression between treatment groups ( p = 0.34 ) . There was no correlation between LDL or CRP change and EAT change . There were insufficient events in either arm to assess the impact of EAT change on mortality . Conclusion EAT progression from baseline was significantly smaller with SVL than with CPiB , although the difference between treatments was not statistically significant , probably due to the small sample size . Change in serum lipids and markers of inflammation did not predict EAT progression Background Genz-644470 is a new , nonabsorbed phosphate binding polymer . In an in vitro competitive phosphate binding assay , Genz-644470 bound significantly more phosphate per gram than sevelamer . As a consequence , this clinical study evaluated the ability of Genz-644470 to lower serum phosphorus in patients on hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer carbonate and placebo . Because three different fixed doses of Genz-644470 and sevelamer carbonate were used , phosphate-lowering dose-responses of each agent were also analyzed . Methods A r and omized , double-blind , dose-ranging study was conducted . After a 2-week phosphate binder washout , 349 hyperphosphatemic ( serum phosphorus > 5.5 mg/dL ) hemodialysis patients were r and omized to one of seven fixed-dose groups : placebo , Genz-644470 2.4 g/day , Genz-644470 4.8 g/day , Genz-644470 7.2 g/day , sevelamer carbonate 2.4 g/day , sevelamer carbonate 4.8 g/day , or sevelamer carbonate 7.2 g/day . Indicated total daily doses were administered in fixed divided doses three times a day with meals for 3 weeks . The change in serum phosphorus during the treatment period and its dose-response patterns were assessed . Results Dose-dependent reductions in serum phosphorus were observed with both Genz-644470 and sevelamer carbonate . Serum phosphorus-lowering responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in a roughly linear fashion with increasing doses over a threefold range after 3 weeks of treatment . Genz-644470 did not show any advantage in phosphorus lowering per gram of binder compared with sevelamer carbonate . Overall toler-ability was similar between active treatment groups . The tolerability of sevelamer carbonate was consistent with prior studies and with the established safety profile of sevelamer . Conclusion Both Genz-644470 and sevelamer carbonate effectively lowered serum phosphate levels in a dose-dependent fashion in patients with chronic kidney disease on hemodialysis . However , Genz-644470 did not provide any advantage over sevelamer carbonate in phosphate lowering in vivo , as had been demonstrated in vitro AIMS High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment . Lanthanum carbonate ( Fosrenol ) is a new non-aluminum , non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . We report data from a recent trial , which , for the first time , assessed the efficacy and tolerability of lanthanum carbonate treatment , compared with placebo , in Chinese patients with ESRD . PATIENTS AND METHODS Following a one- to three-week washout phase and a four-week , open-label lanthanum carbonate dose-titration phase , male and female hemodialysis patients were r and omized ( 1:1 ) to receive either lanthanum carbonate or placebo for four weeks . The primary efficacy parameter of the study was the control of serum phosphorus levels ( < or = 1.8 mmol/l [ < or = 5.6 mg/dl ] ) . Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone , calcium , and calcium x phosphorus ( Ca x P ) product levels . The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study . RESULTS Mean serum phosphorus level at the end of washout was 2.5 + /- 0.5 mmol/l ( 7.7 + /- 1.5 mg/dl ; n=73 ) , and there was no evidence of a difference in levels between the treatment groups pre-r and omization . At the end of the study , lanthanum carbonate-treated patients had significantly lower phosphorus levels ( 1.6 + /- 0.5 mmol/l [ 5.1 + /- 1.5 mg/dl ] ; n=30 ) than those receiving placebo ( 2.3 + /- 0.4 mmol/l [ 7.2 + /- 1.3 mg/dl ] ; n=31 ; p < 0.001 ) . In addition , a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels ( 60 % ) compared with the placebo group ( 10 % ; p < 0.001 ) . Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of r and omized treatment ( p < 0.001 ) . Lanthanum carbonate was well tolerated ; only one serious adverse event was reported , which was unrelated to treatment . CONCLUSIONS Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD . This finding supports the results of previous US and European studies , which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels BACKGROUND Recently , nicotinamide has been suggested as an effective drug for hyperphosphatemia in hemodialysis patients . The authors assessed the efficacy and safety of nicotinamide in these patients with lower doses and longer duration than other studies . METHODS Forty eight patients with fasting serum phosphorus > 5 mg/dl enrolled in this r and omized clinical trial study and were r and omly assigned to two equal-sized groups of nicotinamide or placebo . The study lasted 8 weeks . In the first four weeks , nicotinamide was administered at 500 mg/day , and in the second four weeks at 1,000 mg/day . Blood sample s were tested at baseline , week 4 , and week 8 . RESULTS In nicotinamide group , the mean phosphorus level decreased from 5.9 ± 0.58 mg/dl to 4.77 ± 1.43 mg/dl in week 4 ( P = 0.002 ) and to 4.66 ± 1.06 mg/dl in week 8 ( P = 0.000 ) . The mean calcium-phosphorus product decreased significantly with the same pattern as phosphorus . High-density lipoprotein level increased from 42.46 ± 8.01 mg/dl to 55.71 ± 11.88 mg/dl in week 4 ( P = 0.000 ) and to 65.25 ± 20.18 mg/dl in week 8 ( P = 0.000 ) . Levels of serum calcium , uric acid , SGOT , SGPT , and iPTH did n't change significantly . Compared to baseline , the platelet counts were decreased in both week 4 and week 8 . No significant changes were observed in placebo group . CONCLUSIONS In our patients , nicotinamide effectively decreased phosphorus , increased high-density lipoprotein , and caused thrombocytopenia . Since nicotinamide lowered platelet counts and caused thrombocytopenia in lower doses than other studies in these patients , it is necessary to plan other studies for assessing the safety of the drug especially in different population Background / Aims : JTT-751 ( ferric citrate hydrate ) is a novel oral , iron-based phosphate binder being developed for the treatment of hyperphosphatemia among chronic kidney disease patients who are on dialysis . This study investigated the dose-response and safety of JTT-751 among Japanese hemodialysis patients . Methods : This was a multicenter , r and omized , placebo-controlled , double-blind , parallel-group , comparative study . A total of 192 subjects with serum phosphorus ( P ) levels between 6.1 and 10.0 mg/dl were r and omized to JTT-751 ( 1.5 , 3 or 6 g/day ) or to placebo treatment for 28 days . Changes in serum P level from baseline were examined . Results : In the full analysis set , the mean change in serum P level at week 4 was 0.04 , –1.28 , –2.16 and –4.10 mg/dl in the placebo , 1.5-grams , 3-grams and 6-grams/day groups , respectively , demonstrating a dose-response relationship up to 6 g/day . Overall , a reduction in serum P levels to ≤5.5 mg/dl was achieved in 2.5 , 16.7 , 50.0 and 92.6 % of subjects , in the placebo , 1.5-grams , 3-grams and 6-grams/day groups , respectively . The most common adverse events ( AEs ) were gastrointestinal disorders . Most AEs were mild . In 25 patients , treatment was discontinued due to increased transferrin saturation ≥50 % ; however , this was not considered to be a safety issue . Conclusions : When hemodialysis subjects received JTT-751 at doses between 1.5 and 6 g/day for 28 days , serum P levels were significantly reduced in a dose-dependent manner ( p < 0.001 ) . JTT-751 was found to be efficacious and safe , with the majority of subjects in the 6-grams/day group achieving a serum P level of ≤5.5 mg/dl BACKGROUND Hyperphosphataemia in patients with advanced chronic kidney disease ( CKD ) is associated with adverse outcomes , including vascular calcification and higher mortality rates . While phosphate lowering is an integral aspect of CKD management , the efficacy and safety of phosphate binders in a contemporary cohort of Chinese haemodialysis patients ( who have different genetics and dietary patterns than other population s ) has not been previously described . Moreover , sparse data are available on strategies for optimal dose titration when transitioning from a calcium-based to a polymer-based phosphate binder . METHODS This r and omized , double-blind , dose-titration study compared sevelamer carbonate ( starting dose 800 mg three times daily ) with placebo over 8 weeks ' duration in Chinese CKD patients on haemodialysis . Patients were required to be using calcium-based binders prior to study start . RESULTS In all , 205 patients were r and omized ( sevelamer , n = 135 ; placebo , n = 70 ) ; mean age was 48.6 years , 61 % were male and the mean time on dialysis was 4.4 years . The mean serum phosphorus decreased significantly in patients treated with sevelamer carbonate [ change -0.69 ± 0.64 mmol/L ( -2.14 ± 1.98 mg/dL ) ] but remained persistently elevated with placebo [ change -0.06 ± 0.57 mmol/L ( -0.19 ± 1.76 mg/dL ) ] ( P < 0.0001 ) . When compared with placebo , sevelamer carbonate treatment result ed in statistically significant greater mean reductions from baseline in serum total ( -17.1 versus -3.3 % ) and low-density lipoprotein cholesterol ( -33.5 versus-7.6 % ) ( P < 0.0001 for both ) . Sevelamer carbonate was well tolerated with 96 % adherence compared with 97 % adherence in the placebo arm . Overall , adverse events experienced by patients in the sevelamer carbonate and placebo treatment groups were similar and consistent with their underlying renal disease . CONCLUSIONS This study demonstrated that hyperphosphataemia developed quickly following the cessation of phosphate binders and remained persistently elevated in end-stage CKD in the placebo-treated group . Gradually titrating up sevelamer carbonate from an initial dose of 2.4 g/day to an average daily dose of 7.1 ± 2.5 g/day was well tolerated , safe and efficacious in contemporary Chinese haemodialysis patients BACKGROUND Fibroblast growth factor 23 ( FGF-23 ) is a marker of endothelial dysfunction and atherosclerotic complications in patients with chronic kidney disease ( CKD ) . Because previous studies suggested that sevelamer may exert effects on FGF-23 level and endothelial function independently of its phosphate-lowering action , we tested the effect of sevelamer versus calcium acetate on vascular function and FGF-23 levels . STUDY DESIGN R and omized prospect i ve open-label trial . SETTING & PARTICIPANTS Patients with stage 4 CKD with hyperphosphatemia ( n = 100 ) . INTERVENTION An 8-week intervention with sevelamer ( n = 47 ) and calcium acetate ( n = 53 ) . OUTCOMES The primary study outcome was change in flow-mediated vasodilatation in the forearm . The secondary outcome was change in FGF-23 levels . RESULTS Serum phosphate levels decreased in both treatment arms ( P < 0.001 ) , but more markedly in the sevelamer group ( P < 0.001 ) . Flow-mediated vasodilatation increased from 6.1 % to 7.1 % ( P < 0.001 ) in sevelamer-treated patients , whereas it was unchanged in the calcium-acetate group ( 6.0 % vs 6.0 % ) . In a combined analysis , treatment-induced changes in flow-mediated vasodilatation were ( P < 0.001 ) associated with simultaneous changes in FGF-23 levels ( -27.1 % [ -33.2 % to -8.8 % ] for the sevelamer group ; 3.5 % [ -8.4 % to 12.1 % ] for the calcium acetate group ) , as well as with C-reactive protein and fetuin A levels . These relationships were confirmed in multiple regression analysis adjusting for changes in serum phosphate levels and other factors . LIMITATIONS Unblinded r and omized controlled study that can not establish mechanisms of effect . CONCLUSIONS In hyperphosphatemic patients with stage 4 CKD , treatment with phosphate lowering induces measurable improvements in flow-mediated vasodilatation . Furthermore , independently of serum phosphate level , FGF-23 level changes induced by phosphate binders are associated with simultaneous changes in flow-mediated vasodilatation . These observations are compatible with the hypothesis that FGF-23 may contribute to vascular dysfunction in this population Chronic kidney disease profoundly disturbs calcium-phosphate metabolism and predisposes to premature atherosclerosis . Both coronary artery calcification ( CAC ) and endothelial dysfunction are common in hemodialysis ( HD ) patients . We hypothesized that a calcium-free phosphate binder would improve endothelial function and delay progression of vascular calcification in HD patients . Methods : This was a r and omized parallel-group trial in HD patients comparing lanthanum carbonate ( LC ) with a non-LC phosphorus binders control group ( non-LC ) at a 1 : 1 r and omization . CAC was obtained at baseline , 6 , and 12 months , and endothelial function ( brachial artery flow-mediated dilation – FMD ) at baseline and 6 months . Results : 13 patients were r and omized ( LC n = 7 and non-LC n = 6 ) . CAC scores ( Log ± SE ) at baseline were 7.21 ± 0.62 ( LC ) and 6.07 ± 0.73 ( control ) . CAC increased in the non-LC group ( 33 ± 17 % and 77 ± 22 % at 6 and 12 months ) , but tended to decrease in the LC group ( –10 ± 11 % and –2 ± 11 % at 6 and 12 months ) . There was statistically less progression in CAC in the LC group compared to control at 6 ( p = 0.002 ) and 12 months ( p = 0.003 ) . There was no difference between groups in FMD ( p = 0.7 ) . Markers of inflammation did not change significantly . Conclusion : A slower rate of progression of CAC occurred in the LC group , independent of changes in FMD . This is the first study showing dissociation between progression of CAC and FMD in HD patients . Larger studies are warranted to eluci date the impact of different phosphate sequestration therapies on atherosclerosis in HD patients Amino-terminally truncated parathyroid hormone ( PTH ) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays ( PTH-IMAs ) , and acute changes in serum calcium affect the proportion of these fragments in circulation . However , the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined . In this study , 60 pediatric dialysis patients , aged 13.9 ± 0.7 years , with secondary hyperparathyroidism were r and omized to 8 months of therapy with oral vitamin D combined with either calcium carbonate ( CaCO3 ) or sevelamer . Serum phosphorus levels did not differ between groups . Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO3 therapy ( p < 0.01 from baseline ) but remained unchanged during sevelamer therapy . In the CaCO3 and sevelamer groups , baseline serum PTH levels ( 1st PTH-IMA ; Nichols Institute Diagnostics , San Clemente , CA ) were 964 ± 75 and 932 ± 89 pg/ml , and levels declined to 491 ± 55 and 543 ± 59 pg/ml , respectively ( nonsignificant between groups ) . Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO3 . The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs , despite differences in serum calcium levels BACKGROUND Sevelamer hydrochloride is a recently approved calcium- and aluminium-free phosphate binder . A r and omized study comparing sevelamer and calcium acetate was performed to assess the control of hyperphosphatemia in hemodialysis patients . METHODS Administration of phosphate binders was discontinued during a two-week washout period . The patients were then r and omized to receive sevelamer or calcium acetate . The laboratory tests were performed monthly for 34 weeks . RESULTS There was a statistically significant decrease of serum phosphorus in both sevelamer and calcium acetate treatments . In addition , sevelamer improved the lipid profile . CONCLUSION This study confirms that sevelamer is effective at lowering serum phosphorus in hemodialysis patients and that it has several striking properties that could be beneficial in atherosclerosis in dialysis patients BACKGROUND We determined recently that targeted treatment with calcium-based phosphate binders ( calcium acetate and carbonate ) led to progressive coronary artery and aortic calcification by electron beam tomography ( EBT ) , while treatment with the non-calcium-containing phosphate binder , sevelamer , did not . Aside from the provision of calcium , we hypothesized that other factors might be related to the likelihood of progressive calcification in both or either treatment groups . METHODS We explored potential determinants of progressive vascular calcification in 150 r and omized study subjects who underwent EBT at baseline and at least once during follow-up ( week 26 or 52 ) . RESULTS Among calcium-treated subjects , higher time-averaged concentrations of calcium , phosphorus and the calcium-phosphorus product were associated with more pronounced increases in EBT scores ; no such associations were demonstrated in sevelamer-treated subjects . The relation between parathyroid hormone ( PTH ) and the progression of calcification was more complex . Lower PTH was associated with more extensive calcification in calcium-treated subjects , whereas higher PTH was associated with calcification in sevelamer-treated subjects . Serum albumin was inversely correlated with progression in aortic calcification . Sevelamer was associated with favourable effects on lipids , although the link between these effects and the observed attenuation in vascular calcification remains to be eluci date d. CONCLUSION Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification , especially when mineral metabolism is not well controlled . Calcium may directly or indirectly ( via PTH ) adversely influence the balance of skeletal and extraskeletal calcification in haemodialysis patients BACKGROUND Hyperphosphataemia in patients on haemodialysis ( HD ) can lead to , or worsen , secondary hyperparathyroidism ( with associated bone disease ) and extra-skeletal calcifications associated with increased cardiovascular morbidity and mortality . MCI-196 is a new , non-absorbed , non-calcium-based phosphate binder . The aim of this study was to determine the effect of three fixed doses of MCI-196 , on serum phosphorus level and other parameters relevant to HD patients . METHODS A total of 120 chronic kidney disease ( CKD ) stage 5 patients on HD and with the serum phosphorus level > 2.1 mmol/l were r and omized to receive double-blind treatment with either 3 , 6 and 9 g/day MCI-196 or placebo for 3 weeks . RESULTS Serum phosphorous decreased in all three treatment groups ( -0.038 , -0.268 and -0.257 mmol/l in the 3 , 6 and 9 g/day groups , respectively ) . The difference between treatment and placebo groups was significant for the 6 and 9 g/day groups ( P < 0.05 in both cases ) . Changes in the mean serum calcium were minimal and without relevant differences between groups . However , calcium-phosphorus product ( Ca x P ) was significantly reduced in the 6 and 9 g/day groups P < 0.05 ) . MCI-196 at all doses decreased serum intact PTH between baseline and endpoint , and differences between treatment groups and placebo were statistically significant for the 3 and 9 g/day groups ( P < 0.02 in both cases ) . Both serum total and LDL cholesterol decreased significantly in all treatment groups compared to placebo ( by 0.71 - 1.05 mmol/l , for total cholesterol and 0.68 - 0.94 mmol/l for LDL cholesterol P < 0.001 in all cases ) . There was minimal change in serum HDL cholesterol . MCI-196 at all doses decreased significantly serum uric acid between baseline and endpoint compared to placebo ( P < 0.005 in all cases ) . The drug was well tolerated . CONCLUSION MCI-196 significantly reduced serum phosphorus , Ca x P and PTH , without effecting serum calcium levels . The additional reduction in total cholesterol and LDL cholesterol indicates a possible dual mechanism of action of MCI-196 that has the potential to reduce cardiovascular morbidity in CKD stage 5 patients Background : Many patients with chronic kidney disease are prescribed vitamin D receptor agonists ( VDRAs ) for the management of secondary hyperparathyroidism . Oral phosphate binders may interact with , and potentially reduce the therapeutic activity of , oral VDRAs . This post hoc analysis of a Phase 3 study evaluated the pharmacodynamic effects of the iron-based phosphate binder sucroferric oxyhydroxide ( SFOH ) and sevelamer ( SEV ) carbonate on VDRA activity in dialysis patients . Methods : One thous and and fifty nine patients were r and omized to SFOH 1.0 - 3.0 g/day ( n = 710 ) or SEV 2.4 - 14.4 g/day ( n = 349 ) for up to 52 weeks . Potential interactions of SFOH and SEV with VDRAs were assessed using serum intact parathyroid hormone ( iPTH ) concentrations as a pharmacodynamic biomarker . Three population s of SFOH- and SEV-treated patients were analyzed : Population 1 ( n = 187 ) , patients taking concomitant stable doses of oral VDRAs only ; Population 2 ( n = 250 ) , patients taking no concomitant VDRAs ; Population 3 ( n = 68 ) , patients taking concomitant stable doses of intravenous paricalcitol only . Population s were compared using a mixed-effects model to obtain the least squares mean change in iPTH from baseline to Week 52 . Differences between treatment groups were also compared . Results : In Population 1 , iPTH decreased from baseline to Week 52 in the SFOH group ( -25.3 pg/ml ) but increased in the SEV group ( 89.8 pg/ml ) ( p = 0.02 ) . In Population 2 , iPTH increased to a similar extent in both treatment groups . In Population 3 , iPTH concentrations in both treatment groups decreased to a similar degree ( -29.6 and -11.4 pg/ml for SFOH and SEV , respectively ; p = 0.87 ) . Conclusions : In contrast with SEV , SFOH did not appear to impact the iPTH-lowering effect of oral VDRAs There is no guideline regarding the concomitant or distant administration of sevelamer and calcium carbonate . Our aim was to determine whether serum phosphate varied when sevelamer and calcium carbonate were administered concomitantly in comparison to administration at separate meals . Fourteen chronic hemodialysis patients were enrolled in this cross-over , r and omized trial . Each subject underwent two four-week study periods . During the " concomitant " period , subjects were instructed to take both sevelamer and calcium carbonate together at each meal , whereas in the " separate " period , they were required to take them at separate meals . The order of the " concomitant " and " separate " periods was r and omized . Phosphate-binding agents were stopped for a one-week washout period before each study period . The total dose of sevelamer and calcium carbonate for each subject remained the same for the whole duration of the study and had been determined according to their usual dose of phosphate binders . Patients were instructed to keep their usual eating habits constant and a nutritionist evaluated the daily phosphate intake three times per week . Dialysis parameters were kept constant . Pre-dialysis serum phosphate , calcium , bicarbonate , and albumin were measured at the end of each week . The average daily dietary phosphate intake remained unchanged throughout the study . At the end of the two study periods there was no significant difference in serum phosphate ( 1.50 + /- 0.46 mmol/L in the " concomitant " period vs. 1.51 + /- 0.31 mmol/L in the " separate " period , P = 0.97 ) , calcium ( 2.26 + /- 0.19 mmol/L in the " concomitant " period vs. 2.27 + /- 0.15 mmol/L in the " separate " period , P = 0.64 ) , calcium x phosphate product ( 3.36 + /- 0.94 mmol(2)/L(2 ) in the " concomitant " period vs. 3.41 + /- 0.71 mmol(2)/L(2 ) in the " separate " period , P = 0.84 ) and bicarbonate levels ( 21.5 + /- 3.3 mmol/L for the " concomitant " period vs. 21.6 + /- 3.1 mmol/L for the " separate " period , P = 0.81 ) . Our results show that simultaneous administration of calcium carbonate and sevelamer does not decrease phosphate-binding capacity . Hence , patients can choose to take their phosphate binders concomitantly or at separate meals , according to their preference Background High levels of circulating fibroblast growth factor 23 ( FGF23 ) are associated with chronic kidney disease ( CKD ) progression and high mortality . In the Phosphate Reduction Evaluation of FGF23 in Early CKD Treatment ( PREFECT ) study , we assessed the effect of reducing intestinal phosphate absorption using lanthanum carbonate on FGF23 levels in normophosphatemic patients with CKD stage 3 . Methods Thirty-five individuals were r and omized to lanthanum carbonate 3000 mg/day ( n = 23 ) or placebo ( n = 12 ) for 12 weeks . Levels of intact FGF23 ( iFGF23 ) , C-terminal FGF23 , serum and urinary phosphate and calcium , intact parathyroid hormone and 1,25-dihydroxyvitamin D were assessed . Results The median age was 65 years in the lanthanum group and 73 years in the placebo group ; 58.8 % and 41.7 % were men , respectively . No significant difference was seen in mean iFGF23 between groups at week 12 . There was , however , a transient reduction from baseline in iFGF23 in the lanthanum group at week 1 , from 70.5 pg/ml to 51.9 pg/ml , which was not seen in the placebo group ; this between-group difference in percentage change from baseline was significant in post hoc analyses ( p = 0.0102 ) . Urinary phosphate decreased after 1 week of lanthanum treatment and remained low at week 12 . Conclusions Reducing intestinal phosphate absorption with lanthanum carbonate did not lead to sustained reductions in iFGF23 in patients with CKD stage 3 , although phosphaturia decreased . This suggests that factors other than phosphate burden may be responsible for driving increases in circulating FGF23 in patients with CKD.Trial registration Clinical Trials.gov NCT01128179 , 20 May 2010 BACKGROUND Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function , cardiovascular events , and mortality . STUDY DESIGN Double-blind , placebo-controlled , r and omized trial . SETTING & PARTICIPANTS 149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2 ) , iron deficiency anemia ( hemoglobin , 9.0 - 12.0 g/dL ; transferrin saturation [TSAT]≤ 30 % , serum ferritin ≤ 300 ng/mL ) , and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited . INTERVENTION R and omization to treatment for 12 weeks with ferric citrate coordination complex ( ferric citrate ) or placebo . OUTCOMES & MEASUREMENTS Co primary end points were change in TSAT and serum phosphate level from baseline to end of study . Secondary outcomes included change from baseline to end of treatment in values for ferritin , hemoglobin , intact fibroblast growth factor 23 ( FGF-23 ) , urinary phosphate excretion , and estimated glomerular filtration rate . RESULTS Ferric citrate treatment increased mean TSAT from 22 % ± 7 % ( SD ) to 32 % ± 14 % and reduced serum phosphate levels from 4.5 ± 0.6 to 3.9 ± 0.6 mg/dL , while placebo exerted no effect on TSAT ( 21 % ± 8 % to 20 % ± 8 % ) and less effect on serum phosphate level ( 4.7 ± 0.6 to 4.4 ± 0.8 mg/dL ; between-group P<0.001 for each ) . Ferric citrate increased hemoglobin levels ( from 10.5 ± 0.8 to 11.0 ± 1.0 g/dL ; P<0.001 vs placebo ) , reduced urinary phosphate excretion 39 % ( P<0.001 vs placebo ) , and reduced serum intact FGF-23 levels from a median of 159 ( IQR , 102 - 289 ) to 105 ( IQR , 65 - 187 ) pg/mL ( P=0.02 vs placebo ) . The incidence and severity of adverse effects were similar between treatment arms . LIMITATIONS The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes . CONCLUSIONS Short-term use of ferric citrate repletes iron stores , increases hemoglobin levels , and reduces levels of serum phosphate , urinary phosphate excretion , and FGF-23 in patients with chronic kidney disease stages 3 to 5 Iron stores assuring optimal efficacy/safety for erythropoiesis are unknown in the dialysis population . Using multicenter trial data , we related safety profiles , erythropoiesis-stimulating agent ( ESA ) , and intravenous iron dosing to achieved iron stores in 441 subjects r and omized 2 : 1 to ferric citrate or active control as their phosphate binder over 52 weeks . Intravenous iron was given at each site 's discretion if ferritin ≤ 1,000 ng/mL and transferrin saturation ≤ 30 % . Multivariable time-dependent Cox regression jointly related the primary safety outcome ( composite of cardiac , infection , gastrointestinal , and hepatobiliary serious adverse events ) to moving averages of ferritin and transferrin saturation over the preceding 90 days with covariate adjustment . Multivariable generalized estimating equations related elevated ESA and intravenous iron doses to trailing 90-day averages of ferritin and transferrin saturation with covariate adjustment . The adjusted hazard ratio for the safety composite per 10 % increase in transferrin saturation was 0.84 ( 95 % confidence interval 0.68 - 1.02 , p = 0.08 ) and 1.09 ( 0.86 - 1.35 , p = 0.48 ) per 400 ng/mL increase in ferritin . The adjusted hazard ratio for the safety composite was 0.50 ( 0.29 - 0.88 , p = 0.016 ) for the highest transferrin saturation tertile vs. the lowest . Adjusted odds ratios for higher intravenous iron dose were lower in the highest ( 0.23 [ 0.16 - 0.35 ] , p < 0.001 ) and middle transferrin saturation tertile ( 0.42 [ 0.31 - 0.57 ] , p < 0.001 ) vs. lowest . Incidence of elevated ESA dose was lower in the highest transferrin saturation tertile ( p = 0.01 ) . Ferritin did not predict clinical events or ESA dose . Transferrin saturation may be a better marker than serum ferritin to judge optimal iron stores in dialysis patients . Transferrin saturations > 34 % are safe and provide maximal efficacy . BACKGROUND Most dialysis patients require phosphate binders to control hyperphosphatemia . Ferric citrate has been tested in phase 2 trials as a phosphate binder . This trial was design ed as a dose-response and efficacy trial . STUDY DESIGN Prospect i ve , phase 3 , multicenter , open-label , r and omized clinical trial . SETTING & PARTICIPANTS 151 participants with hyperphosphatemia on maintenance hemodialysis therapy . INTERVENTION Fixed dose of ferric citrate taken orally as a phosphate binder for up to 28 days ( 1 , 6 , or 8 g/d in 51 , 52 , and 48 participants , respectively ) . OUTCOMES Primary outcome is dose-response of ferric citrate on serum phosphorus level ; secondary outcomes are safety and tolerability . MEASUREMENTS Serum chemistry tests including phosphorus , safety data . RESULTS 151 participants received at least one dose of ferric citrate . Mean baseline phosphorus levels were 7.3 ± 1.7 ( SD ) mg/dL in the 1-g/d group , 7.6 ± 1.7 mg/dL in the 6-g/d group , and 7.5 ± 1.6 mg/dL in the 8-g/d group . Phosphorus levels decreased in a dose-dependent manner ( mean change at end of treatment , -0.1 ± 1.3 mg/dL in the 1-g/d group , -1.9 ± 1.7 mg/dL in the 6-g/d group , and -2.1 ± 2.0 mg/dL in the 8-g/d group ) . The mean difference in reduction in phosphorus levels between the 6- and 1-g/d groups was 1.3 mg/dL ( 95 % CI , 0.69 to 1.9 ; P < 0.001 ) , between the 8- and 1-g/d groups was 1.5 mg/dL ( 95 % CI , 0.86 to 2.1 ; P < 0.001 ) , and between the 8- and 6-g/d groups was 0.21 mg/dL ( 95 % CI , -0.39 to 0.81 ; P = 0.5 ) . The most common adverse event was stool discoloration . LIMITATIONS Sample size and duration confirm efficacy , but limit our ability to confirm safety . CONCLUSIONS Ferric citrate is efficacious as a phosphate binder in a dose-dependent manner . A phase 3 trial is ongoing to confirm safety and efficacy BACKGROUND AND OBJECTIVES Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A phase 3 , multicenter , r and omized , double blind , placebo-controlled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD . Starting in April of 2011 , 90 CKD patients ( eGFR=9.21±5.72 ml/min per 1.73 m(2 ) ) with a serum phosphate≥5.0 mg/dl were r and omized 2:1 to ferric citrate hydrate or placebo for 12 weeks . The primary end point was change in serum phosphate from baseline to the end of treatment . Secondary end points included the percentage of patients achieving target serum phosphate levels ( 2.5 - 4.5 mg/dl ) and change in fibroblast growth factor-23 at the end of treatment . RESULTS The mean change in serum phosphate was -1.29 mg/dl ( 95 % confidence interval , -1.63 to -0.96 mg/dl ) in the ferric citrate hydrate group and 0.06 mg/dl ( 95 % confidence interval , -0.20 to 0.31 mg/dl ) in the placebo group ( P<0.001 for difference between groups ) . The percentage of patients achieving target serum phosphate levels was 64.9 % in the ferric citrate hydrate group and 6.9 % in the placebo group ( P<0.001 ) . Fibroblast growth factor-23 concentrations were significantly lower in patients treated with ferric citrate hydrate versus placebo ( change from baseline [ median ] , -142.0 versus 67.0 pg/ml ; P<0.001 ) . Ferric citrate hydrate significantly increased serum iron , ferritin , and transferrin saturation compared with placebo ( P=0.001 or P<0.001 ) . Five patients discontinued active treatment because of treatment-emergent adverse events with ferric citrate hydrate treatment versus one patient with placebo . Overall , adverse drug reactions were similar in patients receiving ferric citrate hydrate or placebo , with gastrointestinal disorders occurring in 30.0 % of ferric citrate hydrate patients and 26.7 % of patients receiving placebo . CONCLUSION In patients with nondialysis-dependent CKD , 12-week treatment with ferric citrate hydrate result ed in significant reductions in serum phosphate and fibroblast growth factor-23 while simultaneously increasing serum iron parameters This study proposes [ corrected ] to evaluate the impact of different phosphate binders on the slowing of [corrected]cardiovascular calcification [ corrected ] and QT dispersion in incident haemodialysis patients with a follow-up of [ corrected ] 36 months . This is to be a [ corrected ] r and omized , multicenter , perspective , [ corrected ] interventional study . Inclusion criteria are age over 18 years and being an [ corrected ] incident patient [ corrected ] on hemodialysis . Exclusion criteria are congenital prolongation of QT segment syndrome , QT-c > 440 ms , bradycardia < 50 beats per minute , symptomatic [ corrected ] arrhythmia or any other significant heart problems ; electrolyte imbalances [ corrected ] ( especially hypokalemia , hypomagnesemia or [ corrected ] hypocalcemia ) ; abnormal liver function tests and [ corrected ] hypothyroidism . An informed consent will be taken at study entry . The patients will be r and omized to 2 cohorts : [ corrected ] 180 patients in the sevelamer [ corrected ] group and 180 patients in calcium-binder phosphate group . Related vascular calcification mortality is the principal end point [ corrected ] and will be evaluated at 36 months 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 Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders . The patients were r and omised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication . Vitamin D ( dihydrotachysterol ) dosage was unchanged . Serum parathyroid hormone concentrations were reduced to within the normal range , urinary cyclic adenosine monophosphate values fell , plasma phosphate concentrations decreased , and the theoretical renal phosphate threshold increased significantly . Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations , deteriorated in two patients who were not compliant , and did not change in five patients in whom initial bone disease was mild . Growth velocity improved significantly . There was no difference in the clinical response , biochemical changes , or incidence of complications during treatment with the two agents . In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure Vascular calcification ( VC ) contributes to cardiovascular disease in hemodialysis ( HD ) patients , especially with diabetes mellitus ( DM ) complications . No r and omized studies have been published regarding the effect of lanthanum carbonate ( LC ) on VC progression in DM patients . The aim of this study was to evaluate the effects of lanthanum carbonate on the progression of VC in HD patients with type 2 DM . We conducted a r and omized controlled trial comparing LC with calcium carbonate ( CC ) in 43 HD patients at a single dialysis center . Estimations of aortic calcification index ( ACI ) by abdominal computed tomography were performed twice for each patient ( at baseline and 12 months ) . Forty-one patients completed the study ( 19 LC , 22 CC ) . When ACI at baseline was ≦0.48 ( median of baseline ACI ) , median change in ACI ( Δ%ACI ) was 20.44 ( 11.50 - 36.80 % ) in the LC group , and 40.00 ( 33.30 - 92.60 % ) in the CC group ( P = 0.026 ) . On the other h and , when ACI at baseline was > 0.48 , the median change in ACI ( Δ%ACI ) was 6.42 ( 3.13 - 24.40 % ) in the LC group , and 8.08 ( 5.68 - 12.20 % ) in the CC group ( P = 1.000 ) . Serum markers of chronic kidney disease-mineral and bone disorder ( CKD-MBD ) , HbA1c , dose of vitamin D analogues , and side-effects of medications did not change in either group throughout the study except int-PTH increased in the LC group . This study indicated that administration of LC inhibited the progression of VC in patients receiving HD for type 2 DM , only in cases of slight VC compared with CC The use of calcium carbonate ( CaCO3 ) to bind phosphorus ( P ) in chronic hemodialysis patients has been a popular tactic in the past decade . Nonetheless , problems with hypercalcemia decrease its usefulness , particularly in patients treated with calcitriol . A P binder not containing calcium ( Ca ) would be of value in these circumstances . In short-term studies , we showed that magnesium carbonate ( MgCO3 ) was well-tolerated and controlled P and Mg levels when given in conjunction with a dialysate Mg of 0.6 mg/dl . We , therefore , performed a prospect i ve , r and omized , crossover study to evaluate if the chronic use of MgCO3 would allow a reduction in the dose of CaCO3 and yet achieve acceptable levels of Ca , P , and Mg . We also assessed whether the lower dose of CaCO3 would facilitate the use of larger doses of calcitriol . The two phases were MgCO3 plus half the usual dose of CaCO3 and CaCO3 alone given in the usual dose . It was found that MgCO3 ( dose , 465 + /- 52 mg/day elemental Mg ) allowed a decrease in the amount of elemental Ca ingested from 2.9 + /- 0.4 to 1.2 + /- 0.2 g/day ( P < 0.0001 ) . The Ca , P , Mg levels were the same in the two phases . The maximum dose of i.v . calcitriol without causing hypercalcemia was 1.5 + /- 0.3 micrograms/treatment during the MgCO3 phase and 0.8 + /- micrograms/treatment during the Ca phase ( P < 0.02 ) . If these studies are confirmed , the use of MgCO3 and a dialysate Mg of 0.6 mg/dl may be considered in selected patients who develop hypercalcemia during treatment with i.v . calcitriol and CaCO3 Chronic kidney disease ( CKD ) patients are given calcium carbonate to bind dietary phosphorus and reduce phosphorus retention , and to prevent negative calcium balance . Data are limited on calcium and phosphorus balance in CKD to support this . The aim of this study was to determine calcium and phosphorus balance and calcium kinetics with and without calcium carbonate in CKD patients . Eight stage 3/4 CKD patients , eGFR 36 mL/min , participated in two 3-week balances in a r and omized placebo-controlled cross-over study of calcium carbonate ( 1500 mg/d calcium ) . Calcium and phosphorus balance were determined on a controlled diet . Oral and intravenous 45calcium with blood sampling and urine and fecal collection s were used for calcium kinetics . Fasting blood and urine were collected at baseline and end of each week of each balance period for biochemical analyses . Results showed that patients were in neutral calcium and phosphorus balance while on placebo . Calcium carbonate produced positive calcium balance , did not affect phosphorus balance , and produced only a modest reduction in urine phosphorus excretion compared with placebo . Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance suggesting tissue deposition . Fasting biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate . If they can be extrapolated to effects of chronic therapy , these data caution against the use of calcium carbonate as a phosphate binder BACKGROUND Hyperphosphatemia underlies development of hyperparathyroidism , osteodystrophy , extraosseous calcification , and is associated with increased mortality in hemodialysis patients . METHODS To determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus < /=5.5 mg/dL and Ca x P product < /=55 mg(2)/dL(2 ) , we conducted an 8-week r and omized , double-blind study in 100 hemodialysis patients . RESULTS Comparisons of time-averaged concentrations ( weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus ( 1.08 mg/dL difference , P= 0.0006 ) , higher serum calcium ( 0.63 mg/dL difference , P < 0.0001 ) , and lower Ca x P ( 6.1 mg(2)/dL(2 ) difference , P= 0.022 ) than sevelamer recipients . At each week , calcium acetate recipients were 20 % to 24 % more likely to attain goal phosphorus [ odds ratio ( OR ) 2.37 , 95 % CI 1.28 - 4.37 , P= 0.0058 ] , and 15 % to 20 % more likely to attain goal Ca x P ( OR 2.16 , 95 % CI 1.20 - 3.86 , P= 0.0097 ) . Transient hypercalcemia occurred in 8 of 48 ( 16.7 % ) calcium acetate recipients , all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate ( OR 6.1 , 95 % CI 2.8 - 13.3 , P < 0.0001 ) . Week 8 intact PTH levels were not significantly different . Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment ( P < 0.0001 ) . CONCLUSION Calcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride . Cost-benefit analysis indicates that in the absence of hypercalcemia , calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients Summary Calcium carbonate has been successfully used as a phosphate binder in patients with chronic renal failure ; however , a high frequency of hypercalcaemia has been reported . To study the effects of calcium carbonate preparations with different dissolution characteristics on the incidence of this side effect , we conducted a double-blind , crossover trial in 21 patients undergoing chronic haemodialysis . Aluminium hydroxide therapy was replaced with calcium carbonate . The subjects then r and omly received either an enteric-coated or a gastric-coated preparation . Calcium carbonate ( 3.1–3.6 g/d ) controlled serum phosphate concentrations as effectively as aluminium hydroxide ( 2.9 g/d ) . Concurrently , there was a significant rise in mean serum calcium and a fall in serum concentrations of both parathyroid hormone and osteocalcin , the latter suggesting a decrease in bone turnover . Overall , hypercalcaemic episodes developed in 9 patients ( 43 % ) and occurred at a considerable frequency ( 33 episodes per 100 patient-months ) during treatment with the gastric-coated formulation . Following conversion to enteric-coated calcium carbonate ( 3.6 g/d ) patients had fewer occurrences of hypercalcaemia ( 12 episodes per 100 patient-months , P<0.05 ) and , as compared to the gastric-coated preparation , increases in serum calcium > 3.00 mmol/l were not observed at all . Hyperaluminaemia was regressive during therapy with calcium carbonate , but addition of small doses of aluminium hydroxide caused a large rise in serum aluminium concentrations after infusion of desferrioxamine , indicating an enhanced rate of absorption or aberrant compartmentalization of aluminium . We conclude that calcium carbonate can control hyperphosphataemia in dialysis patients . However , undesirable hypercalcaemic episodes may occur , the frequency and severity of which can be lowered by the use of an enteric-coated preparation . Concomitant use of aluminium hydroxide and calcium carbonate should be restricted to patients in whom the degree of aluminium accumulation is monitored by serial desferrioxamine tests Background Fibroblast growth factor 23 ( FGF23 ) is a phosphaturic hormone that is secreted from bone and serum level increases as renal function declines . Higher levels of FGF23 are associated with increased mortality in hemodialysis- patients and in patients with chronic kidney disease ( CKD ) stage 2 - 4 . The use of active vitamin D and phosphate binders as recommended in international guidelines , may affect the level of FGF23 and thereby clinical outcome . We investigated the effects of a phosphate binder and active vitamin D on the serum levels of intact FGF23 ( iFGF23 ) and intact parathyroid hormone ( iPTH ) in patients with CKD stage 3b ( glomerular filtration rate ( GFR ) 30–44 ml/min/1.73 m2 ) . Methods Seven women and 14 men were included , mean age 65.6 ± 12.2 years . They were r and omized in a 1:1 ratio to receive one of two treatment sequences . Group-1 ( the alphacalcidol-sevelamer carbonate group ) : alphacalcidol 0.25 μg once daily for two weeks followed by sevelamer carbonate 800 mg TID with meals for two weeks after a two-week washout period . Group-2 ( the sevelamer carbonate-alphacalcidol group ) : vice versa . Nineteen patients completed the study . The 25-hydroxyvitamin D level at baseline was 97.6 ± 25.0 nmol/l . Results There were no treatment effects on the iFGF23 and iPTH levels overall . In group-1 the iFGF23 level was higher after treatment with alphacalcidol compared with sevelamer carbonate ( mean 105.8 ± 41.6 vs. 79.1 ± 36.5 pg/ml , p = 0.047 ( CI : 0.4 - 52.9 ) , and the iPTH level was lower ( median : 26.5 , range : 14.6 - 55.2 vs. median 36.1 , range 13.4 - 106.9 pg/ml , p = 0.011 ) . In group-2 the iFGF23 level increased non-significantly after treatment with sevelamer carbonate and throughout the washout period . Conclusions In this crossover trial with alphacalcidol and sevelamer carbonate in patients with CKD stage 3b , the levels of iFGF23 were not significantly different after the two treatments . However , in the group of patients initiating therapy with sevelamer carbonate the iFGF23 levels seemed to increase while this response was mitigated in the group of patients given alphacalcidol followed by sevelamer carbonate . This may have therapeutic implication s on choice of first line therapy . The number of patients is small and this conclusion is in part based on subgroup analysis . It is therefore important that these results are confirmed in larger studies .Trial registration Trial Registration Number : European Clinical Trial Data base ( EudraCT ) 2010 - 020415 - 36 and Clinical Trials.gov Background . Phosphate binders are required to control serum phosphorus in dialysis patients . A phosphate binder combining calcium and magnesium offers an interesting therapeutic option . Methods . This controlled r and omized , investigator-masked , multicentre trial investigated the effect of calcium acetate/magnesium carbonate ( CaMg ) on serum phosphorus levels compared with sevelamer hydrochloride ( HCl ) . The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative ( K/DOQI ) target level range after 24 weeks . Three hundred and twenty-six patients from five European countries were included . After a phosphate binder washout period , 255 patients were r and omized in a 1:1 fashion . Two hundred and four patients completed the study per protocol ( CaMg , N = 105 ; dropouts N = 18 ; sevelamer-HCl , N = 99 ; dropouts N = 34 ) . Patient baseline characteristics were similar in both groups . Results . Serum phosphorus levels had decreased significantly with both drugs at week 25 , and the study hypothesis of CaMg not being inferior to sevelamer-HCl was confirmed . The area under the curve for serum phosphorus ( P = 0.0042 ) and the number of visits above K/DOQI ( ≤1.78 mmol/L , P = 0.0198 ) and Kidney disease : Improving global outcomes ( KDIGO ) targets ( ≤1.45 mmol/L , P = 0.0067 ) were significantly lower with CaMg . Ionized serum calcium did not differ between groups ; total serum calcium increased in the CaMg group ( treatment difference 0.0477 mmol/L ; P = 0.0032 ) but was not associated with a higher risk of hypercalcaemia . An asymptomatic increase in serum magnesium occurred in CaMg-treated patients ( treatment difference 0.2597 mmol/L , P < 0.0001 ) . There was no difference in the number of patients with adverse events . Conclusion . CaMg was non-inferior to the comparator at controlling serum phosphorus levels at Week 25 . There was no change in ionized calcium ; there was minimal increase in total serum calcium and a small increase in serum magnesium . It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia BACKGROUND High levels of fibroblast growth factor 23 ( FGF23 ) are associated with mortality and progression of chronic kidney disease ( CKD ) . Reducing dietary phosphorus intake lowers FGF23 secretion in healthly individuals , but there is little data on its effects in patients with pre-dialysis CKD . METHODS Using a 2 × 2 factorial design , we r and omly assigned 16 normophosphataemic CKD stage 3 - 4 patients to receive a 2-week treatment with either lanthanum carbonate 1000 mg three times daily or placebo , and to ingest a tightly controlled diet containing 750 or 1500 mg of dietary phosphorus daily . We analysed serial measurements of FGF23 , parathyroid hormone , serum phosphate and calcium , and 24-h urinary phosphate and calcium excretion using repeated- measures analyses . RESULTS Compared with the 1500-mg phosphorus diet , patients assigned to the 750-mg diet had greater reduction in 24-h urinary phosphate excretion ( 66 % vs. 29 % ; P<0.0001 ) . Lanthanum-treated patients experienced a significant reduction in 24-h urinary phosphate excretion compared with baseline ( 64 % ; P<0.0001 ) , but the difference compared with placebo did not reach significance ( 64 % vs. 31 % ) . Despite the significant reductions in 24-h urinary phosphate excretion , no group demonstrated a significant reduction in FGF23 levels ; FGF23 levels actually increased significantly in the 1500-mg diet plus placebo group , suggesting dietary phosphorus loading . CONCLUSIONS Although dietary phosphorus restriction and lanthanum lowered urinary phosphate excretion consistent with a rapid decrease in phosphorus absorption , inducing a reduction in FGF23 levels in CKD patients may require interventions with a longer duration than in healthy volunteers Background Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients . Long-term efficacy and tolerability of the iron-based phosphate binder , sucroferric oxyhydroxide ( previously known as PA21 ) , was compared with that of sevelamer carbonate ( sevelamer ) in an open-label Phase III extension study . Methods In the initial Phase III study , hemo- or peritoneal dialysis patients with hyperphosphatemia were r and omized 2:1 to receive sucroferric oxyhydroxide 1.0−3.0 g/day ( 2−6 tablets/day ; n = 710 ) or sevelamer 2.4−14.4 g/day ( 3−18 tablets/day ; n = 349 ) for 24 weeks . Eligible patients could enter the 28-week extension study , continuing the same treatment and dose they were receiving at the end of the initial study . Results Overall , 644 patients were available for efficacy analysis ( n = 384 sucroferric oxyhydroxide ; n = 260 sevelamer ) . Serum phosphorus concentrations were maintained during the extension study . Mean ± st and ard deviation ( SD ) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02 ± 0.52 mmol/L with sucroferric oxyhydroxide and 0.09 ± 0.58 mmol/L with sevelamer . Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range ( 1.13–1.78 mmol/L ) for both treatment groups . Mean ( SD ) daily tablet number over the 28-week extension study was lower for sucroferric oxyhydroxide ( 4.0 ± 1.5 ) versus sevelamer ( 10.1 ± 6.6 ) . Patient adherence was 86.2 % with sucroferric oxyhydroxide versus 76.9 % with sevelamer . Mean serum ferritin concentrations increased over the extension study in both treatment groups , but transferrin saturation ( TSAT ) , iron and hemoglobin concentrations were generally stable . Gastrointestinal-related adverse events were similar and occurred early with both treatments , but decreased over time . Conclusions The serum phosphorus-lowering effect of sucroferric oxyhydroxide was maintained over 1 year and associated with a lower pill burden , compared with sevelamer . Sucroferric oxyhydroxide was generally well tolerated long-term and there was no evidence of iron accumulation Background Serum phosphorus control is critical for chronic kidney disease ( CKD ) 5D patients . Currently , clinical profile for an oral phosphorus binder in the mainl and Chinese population is not available . Objective To establish the efficacy , safety , and tolerability of lanthanum carbonate in CKD 5D patients . Design Multicenter , r and omized , double blind , placebo-controlled study . A central r and omization center used computer generated tables to allocate treatments . Setting Twelve tertiary teaching hospitals and medical university affiliated hospitals in mainl and China . Participants Overall , 258 hemodialysis or continuous ambulatory peritoneal dialysis ( CAPD ) adult patients were enrolled . InterventionAfter a 0–3-week washout period and a 4-week lanthanum carbonate dose-titration period , 230 patients were r and omized 1:1 to receive lanthanum carbonate ( 1500 mg-3000 mg ) or placebo for a further 4-week maintenance phase . Main outcome measures Efficacy and safety of lanthanum carbonate to achieve and maintain target serum phosphorus concentrations were assessed . Results In the titration phase , serum phosphorus concentrations of all patients decreased significantly . About three-fifths achieved target levels without significantly disturbing serum calcium levels . At the end of the maintenance period , the mean difference in serum phosphorus was significantly different between the lanthanum carbonate and placebo-treated groups ( 0.63±0.62 mmol/L vs. 0.15±0.52 mmol/L , P < 0.001 ) . The drug-related adverse effects were mild and mostly gastrointestinal in nature . Conclusion Lanthanum carbonate is an efficacious and well-tolerated oral phosphate binder with a mild AE profile in hemodialysis and CAPD patients . This agent may provide an alternative for the treatment of hyperphosphatemia in CKD 5D patients in mainl and China . Trial registration No. Background HS219 ( 40 mg chitosan-loaded chewing gum ) is design ed to bind salivary phosphorus as an add-on to available phosphorus binders . We performed a r and omized , placebo-controlled , double-blind study to evaluate the efficacy and safety of HS219 in hemodialysis ( HD ) patients with hyperphosphatemia as an add-on to phosphorus binders . Methods Sixty-eight HD patients who were maintained on calcium carbonate ( n = 33 ) or sevelamer hydrochloride ( n = 35 ) were enrolled . The primary end point was a change in serum phosphorus levels . Secondary end points included changes in levels of salivary phosphorus , serum calcium , parathyroid hormone ( PTH ) , and intact fibroblast growth factor ( iFGF ) 23 . Results Sixty-three patients chewed either HS219 ( n = 35 ) or placebo ( n = 28 ) for 30 min , three times a day , for 3 weeks . HS219 was well tolerated and safe . However , HS219 was not superior to placebo with additional reduction of serum phosphorus with respect to phosphorus binders at the end of the chewing period . There were no significant effects of HS219 on reduction of salivary phosphorus , serum calcium , iPTH , or iFGF23 levels . Conclusions The chitosan-loaded chewing gum HS219 does not affect serum and salivary phosphorus levels in Japanese HD patients with hyperphosphatemia . Our findings do not support previous findings that 20 mg of chitosan-loaded chewing gum reduces serum and salivary phosphorus levels . Trail registration Clinical Trials.gov NCT01039428 , 24 December , 2009 BACKGROUND Epicardial adipose tissue ( EAT ) has been described in the general population as an independent risk marker for incident coronary artery disease . In hemodialysis patients , it correlates with other markers of cardiovascular disease , but it is unknown if it is associated with adverse events . METHODS post hoc analysis of the Renagel in New Dialysis ( RIND ) patients study , a r and omized trial of sevelamer versus calcium-based phosphate binders in 109 incident hemodialysis patients , followed for all-cause mortality for a median of 49.3 months . Patients underwent baseline cardiac computed tomography imaging within 120 days of dialysis initiation . RESULTS Baseline EAT measurements were available in 95 patients ; EAT was positively correlated with age , body mass index , triglycerides , C-reactive protein , coronary artery calcium and aortic calcium , and negatively correlated with systolic and diastolic blood pressure , serum high density lipoprotein ( HPL ) cholesterol and serum phosphate ( all P < 0.05 ) . During follow-up , a total of 27 ( 28.4 % ) patients expired [ mortality per 1000 patients /year : 95 % confidence interval ( 95 % CI ) = 77 ( 64 - 94 ) ] . Five-year survival rate was 44 . 6 % ( 95 % CI : 21.1 - 65.7 ) and 71.2 % ( 95 % CI : 45.95 - 86.25 ) in patients with EAT above or below the median , respectively . Each 10 cc increase in EAT volume was associated with a significant 6 % increase in the risk of death during follow-up [ hazard ratio ( HR ) : 1.060 ; 95 % CI : 1.013 - 1.109 ; P-value = 0.012 ] . CONCLUSIONS In this sub analysis of a r and omized trial , EAT was an independent predictor of mortality in incident hemodialysis patients after ~4 years of follow-up . These hypothesis-generating findings will need confirmatory evidence 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 This short-term study assessed the efficacy and safety of lanthanum carbonate in the treatment of hyperphosphatemia in dialysis patients ; here , we report a prespecified subgroup analysis of patients undergoing peritoneal dialysis . Methods Men and women ( n = 39 ) who had received continuous ambulatory peritoneal dialysis for chronic kidney disease for 6 months or more were enrolled in eight renal medicine departments in the United Kingdom . A 2-week washout period was followed by a 4-week dose-titration phase during which patients received lanthanum carbonate titrated up to 2250 mg/day . This was followed by a 4-week , r and omized , placebo-controlled , parallel-group phase during which patients continued to receive either lanthanum carbonate at the titrated dose , or a matched dose of placebo . The main outcome measure was control of serum phosphate levels ( 1.3 - 1.8 mmol/l ) at the end of the parallel-group phase . Results Serum phosphate was controlled in 3/39 ( 8 % ) patients at the beginning of the dose-titration phase ( after washout ) and in 18/31 ( 58 % ) patients treated with lanthanum carbonate at its end . After the parallel-group phase , 60 % of lanthanum carbonate-treated patients and 10 % of those receiving placebo had controlled serum phosphate . There was no difference in mean ( 95 % confidence interval ) serum phosphate levels between groups at r and omization : lanthanum carbonate , 1.57 ( 1.34 - 1.81 ) mmol/l ; placebo , 1.58 ( 1.40 - 1.76 ) mmol/l ( p = 0.96 ) . However , a difference was seen at the end of the parallel-group phase : lanthanum carbonate , 1.56 ( 1.33 - 1.79 ) mmol/l ; placebo , 2.25 ( 1.81 - 2.68 ) mmol/l ( p = 0.0015 ) . There were no clinical ly important changes in nutritional parameters and no serious treatment-related adverse events were recorded . Conclusions At doses up to 2250 mg/day , lanthanum carbonate is well tolerated and controls hyperphosphatemia effectively . Treatment with higher doses of lanthanum carbonate may allow patients undergoing peritoneal dialysis the potential to increase their dietary protein intake without compromising their phosphate control Background Magnesium salts bind dietary phosphorus , but their use in renal patients is limited due to their potential for causing side effects . The aim of this study was to evaluate the efficacy and safety of magnesium carbonate ( MgCO3 ) as a phosphate-binder in hemodialysis patients . Methods Forty-six stable hemodialysis patients were r and omly allocated to receive either MgCO3 ( n = 25 ) or calcium carbonate ( CaCO3 ) , ( n = 21 ) for 6 months . The concentration of Mg in the dialysate bath was 0.30 mmol/l in the MgCO3 group and 0.48 mmol/l in the CaCO3 group . Results Only two of 25 patients ( 8 % ) discontinued ingestion of MgCO3 due to complications : one ( 4 % ) because of persistent diarrhea , and the other ( 4 % ) because of recurrent hypermagnesemia . In the MgCO3 and CaCO3 groups , respectively , time-averaged ( months 1–6 ) serum concentrations were : phosphate ( P ) , 5.47 vs. 5.29 mg/dl , P = ns ; Ca , 9.13 vs. 9.60 mg/dl , P < 0.001 ; Ca × P product , 50.35 vs. 50.70 (mg/dl)2 , P = ns ; Mg , 2.57 vs. 2.41 mg/dl , P = ns ; intact parathyroid hormone ( iPTH ) , 285 vs. 235 pg/ml , P < 0.01 . At month 6 , iPTH levels did not differ between groups : 251 vs. 212 pg/ml , P = ns . At month 6 the percentages of patients with serum levels of phosphate , Ca × P product and iPTH that fell within the Kidney Disease Outcomes Quality Initiative ( K/DOQI ) guidelines were similar in both groups , whereas more patients in the MgCO3 group ( 17/23 ; 73.91 % ) than in the CaCO3 group ( 5/20 , 25 % ) had serum Ca levels that fell within these guidelines , with the difference being significant at P < 0.01 . Conclusion Our study shows that MgCO3 administered for a period of 6 months is an effective and inexpensive agent to control serum phosphate levels in hemodialysis patients . The administration of MgCO3 in combination with a low dialysate Mg concentration avoids the risk of severe hypermagnesemia Background Different phosphate binders exert differing effects on bone mineral metabolism and levels of regulating hormones . The objective of this post hoc evaluation of the CALcium acetate MAGnesium carbonate ( CALMAG ) study was to compare the effects of calcium acetate/magnesium carbonate ( CaMg ) and a calcium-free phosphate binder , sevelamer-hydrochloride ( HCl ) , on serum levels of fibroblast growth factor-23 ( FGF-23 ) and markers of bone turnover . Methods This secondary analysis of the controlled , r and omized CALMAG study , comparing the effect of CaMg and sevelamer-HCl on serum phosphorus ( P ) , aim ed to investigate the parameters described above . The analysis included 204 patients who completed the initial study per protocol ( CaMg , n = 105 ; sevelamer-HCl , n = 99 ) . Results The study showed that serum levels of FGF-23 were significantly reduced with CaMg and sevelamer-HCl , with no difference between groups at Week 25 [ analysis of covariance ( ANCOVA ) ; log-intact FGF-23 ( iFGF-23 ) , P = 0.1573 ] . FGF-23 levels strongly correlated with serum P levels at all time points in both groups . The bone turnover parameters alkaline phosphatase ( AP ) , bone AP ( BAP ) , procollagen type 1 amino-terminal propeptide 1 ( P1NP ) , osteoprotegerin ( OPG ) , beta-crosslaps ( β-CTX ) and tartrate-resistant acid phosphatase 5b ( TRAP 5b ) increased significantly in the sevelamer-HCl group ; they remained almost unchanged in the CaMg group , after the initial phase of P lowering ( ANCOVA , P < 0.0001 for all except OPG , P = 0.1718 ) . Conclusions CaMg and sevelamer-HCl comparably lower serum levels of iFGF-23 . Changes in bone parameters were dependent on characteristics of the phosphate binder ; in contrast with sevelamer-HCl , CaMg had no influence on bone turnover markers Background Hyperphosphatemia in patients with chronic kidney disease ( CKD ) contributes to secondary hyperparathyroidism , soft tissue calcification , and increased mortality risk . This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD . Methods In this r and omized , double-blind , placebo-controlled trial , 110 nondialyzed patients from 34 sites with estimated GFR < 30 mL/min/1.73 m2 and serum phosphorus > 4.5 mg/dL were r and omized to calcium acetate or placebo for 12 weeks . The dose of study drugs was titrated to achieve target serum phosphorus of 2.7 - 4.5 mg/dL. Serum phosphorus , calcium , iPTH , bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period . The primary efficacy endpoint was serum phosphorus at 12 weeks . Secondary endpoints were to measure serum calcium and intact parathyroid hormone ( iPTH ) levels . Results At 12 weeks , serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group ( 4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL ; p = 0.04 ) . The albumin-adjusted serum calcium concentration was significantly higher ( 9.5 ± 0.8 vs. 8.8 ± 0.8 ; p < 0.001 ) and iPTH was significantly lower in the calcium acetate group compared to placebo ( 150 ± 157 vs. 351 ± 292 pg/mL respectively ; p < 0.001 ) . At 12 weeks , the proportions of subjects who had hypocalcemia were 5.4 % and 19.5 % for the calcium acetate and the placebo groups , respectively , while the proportions of those with hypercalcemia were 13.5 % and 0 % , respectively . Adverse events did not differ between the treatment groups . Conclusions In CKD patients not yet on dialysis , calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period . Trial Registration www . clinical trials.gov NCT00211978 Background Patients with end-stage renal disease ( ESRD ) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents ( ESAs ) and intravenous ( IV ) iron for anemia . Ferric citrate ( FC ) is a novel , iron-based phosphate binder that increases iron stores and decreases IV iron and ESA usage while maintaining hemoglobin levels , and may decrease the cost of ESRD care . The study objectives were to ( 1 ) quantify differences in ESA and IV iron usage among ESRD patients receiving FC compared with active control ( AC ) ( sevelamer carbonate and /or calcium acetate ) on the basis of data from a 52-week phase III clinical trial and ( 2 ) st and ardize trial data to the general United States ( US ) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA . Study Design The study was a r and omized , controlled clinical trial . Setting and Population A total of 441 adult subjects with ESRD who received FC or AC for 52 weeks were included . Model , Perspective , and TimelineDifferences in ESA and IV iron usage between the treatment groups were modeled over time using generalized linear mixed models and zero-inflated Poisson models . Trends were modeled via logarithmic curves , and utilization patterns were applied to the general dialysis population to estimate expected re source savings . Outcomes Study outcomes were costs saved/patient/year using FC versus AC ( US dollars ) . Results Our model suggests an annual decrease of 129,106 U of ESAs and 1960 mg of IV iron per patient in the second year after a switch from AC to FC . Applying 2013 Medicare pricing , this would save $ 1585 in ESAs and $ 516 in IV iron : a total of $ 2101/patient/year ; these savings would be expected to double for managed care plans . Limitations The projections were made on 1 year of trial data . Conclusions Phosphate binding with FC reduces IV iron and ESA usage . Given the high cost burden of ESRD , our model demonstrates significant potential cost savings . Trial Registration Clinical Trials.gov ( NCT01191255 ) http:// clinical trials.gov/ct2/show/NCT01191255 Efficacy of PA21 ( sucroferric oxyhydroxide ) , a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder , was compared with that of sevelamer carbonate in an open-label , r and omized , active-controlled phase III study . Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0–3.0 g per day and 348 received sevelamer 4.8–14.4 g per day for an 8-week dose titration , followed by 4 weeks without dose change , and then 12 weeks maintenance . Serum phosphorus reductions at week 12 were −0.71 mmol/l ( PA21 ) and −0.79 mmol/l ( sevelamer ) , demonstrating non-inferiority of , on average , three tablets of PA21 vs. eight of sevelamer . Efficacy was maintained to week 24 . Non-adherence was 15.1 % ( PA21 ) vs. 21.3 % ( sevelamer ) . The percentage of patients that reported at least one treatment-emergent adverse event was 83.2 % with PA21 and 76.1 % with sevelamer . A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 ( 15.7 % ) vs. sevelamer ( 6.6 % ) . Mild , transient diarrhea , discolored feces , and hyperphosphatemia were more frequent with PA21 ; nausea and constipation were more frequent with sevelamer . After 24 weeks , 99 hemodialysis patients on PA21 were re-r and omized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose ( 250 mg per day ( ineffective control ) ) in 49 patients . The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control . Thus , PA21 was effective in lowering serum phosphorus in dialysis patients , with similar efficacy to sevelamer carbonate , a lower pill burden , and better adherence Since dietary restrictions and phosphorus removal by haemodialysis ( HD ) are not sufficient to control serum phosphate ( s-phosphate ) levels in dialysis patients the use of oral phosphate binders is m and atory . Calcium ketoglutarate ( CaKE ) is an analogue of glutamic acid exerting phosphate binding properties . Therefore we compared this substance to calcium acetate ( CaAC ) in a 24-weeks open cross-over trial in 28 maintenance HD patients . Medications and HD prescriptions were kept unchanged during the trial . Following 2 weeks of withdrawal of phosphate binders , patients were r and omly assigned to one of the calcium salts for 12 weeks ; after a second withdrawal of 2 weeks , all patients were shifted to the other treatment for another 12 weeks . All patients received equimolar doses of CaKE and CaAC with respect to the amount of prescribed elemental calcium . Treatment with CaAC and CaKE significantly reduced s-phosphate levels after 4 weeks ( CaAC 1.95+/-0.6 vs. 2.4+/-0.53 mmol/l , P = 0.004 ; CaKE 1.95+/-0.4 vs. 2.47+/-0.63 mmol/l , P = 0.0001 ) reaching a virtually stable plateau over the remaining observation time without significant differences between the groups . The incidence of hypercalcaemia defined as a serum calcium level > or = 2.8 mmol/l was significantly higher in CaAC than in CaKE treated patients ( n = 8 vs. n = 1 , P = 0.03 ) . There were no significant differences in serum intact parathyroid hormone ( PTH ) bicarbonate , albumin or calcitriol levels between the groups after 12 weeks treatment . We conclude that CaKE is as effective as CaAC for treatment of hyperphosphataemia in chronic HD patients and may be particularly helpful in patients who are prone to develop hypercalcaemia INTRODUCTION Coronary artery calcification ( CAC ) is highly prevalent among chronic kidney disease ( CKD ) patients and its strong association with mortality has been recognized early in the course of CKD . The aim of the present study was to test the effect of rosuvastatin and sevelamer hydrochloride on the progression of CAC in nondialyzed CKD patients . METHODS An open-label , r and omized and controlled pilot study was conducted including 117 CKD patients ( 62 % men , 56.9 ± 11.2 years , eGFR 36 ± 16.5 ml/min ) . Patients were r and omly assigned to rosuvastatin ( n = 38 ; 10 mg/day ) , to sevelamer hydrochloride ( n = 38 ; 2,400 mg/day ) and to control ( n = 41 ) groups . CAC ( by multislice computed tomography ) and biochemical analyses were performed at baseline and after 24 months . RESULTS At baseline , CAC was observed in 55 % , 58 % and 61 % of patients in the rosuvastatin , sevelamer hydrochloride and control groups , respectively ( p = 0.87 ) . Calcium score at baseline as well as its absolute and relative changes during 24 months were similar among the groups . Low density lipoprotein cholesterol ( LDL-c ) was higher and decreased significantly in the rosuvastatin group ( p < 0.01 ) . The analysis adjusting for LDL-c showed that the drug regimens were not associated with the progression of CAC ( drug effect p = 0.85 ; time-effect p < 0.001 ; interaction p = 0.76 ) . CONCLUSIONS Treatment with rosuvastatin and sevelamer hydrochloride may not delay the progression of CAC in non-dialysis dependent CKD patients 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 Ferric citrate ( FC ) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous ( iv ) iron and erythropoiesis-stimulating agents ( ESAs ) . We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international r and omized clinical trial . In all , 441 subjects were r and omized ( 292 to FC and 149 to sevelamer carbonate and /or calcium acetate [ active control ( AC ) ] ) and followed for 52 weeks . Subjects on FC had increased ferritin and transferrin saturation ( TSAT ) levels compared with subjects on AC by week 12 ( change in ferritin , 114.1±29.35 ng/ml ; P<0.001 ; change in TSAT , 8.62%±1.57 % ; P<0.001 ) . Change in TSAT plateaued at this point , whereas change in ferritin increased through week 24 , remaining relatively stable thereafter . Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks ( median [ interquartile range ] dose=12.9 [ 1.0 - 28.9 ] versus 26.8 [ 13.4 - 47.6 ] mg/wk ; P<0.001 ) , and the percentage of subjects not requiring iv iron was higher with FC ( P<0.001 ) . Cumulative ESA over 52 weeks was lower with FC than AC ( median [ interquartile range ] dose=5303 [ 2023 - 9695 ] versus 6954 [ 2664 - 12,375 ] units/wk ; P=0.04 ) . Overall , 90.3 % of subjects on FC and 89.3 % of subjects on AC experienced adverse events . In conclusion , treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks , with a safety profile similar to that of available binders CONTEXT Hyperphosphatemia has an important role in the development of bone and mineral abnormalities in end-stage renal disease ( ESRD ) . OBJECTIVE To compare the phosphorus binding power and the hypercalcemic effect of calcium acetate and calcium carbonate in hemodialysis patients . TYPE OF STUDY Crossover , r and omized , double-blind study . PLACE A private hospital dialysis center . PARTICIPANTS Fifty-two patients who were undergoing regular hemodialysis three times a week ( [ Ca++ ] dialysate = 3.5 mEq/L ) . PROCEDURES Half of the patients were started on 5.6 g/day of calcium acetate and , after a 2 week washout period , received 6.2 g/day of calcium carbonate . The other half followed an inverse protocol . MAIN MEASUREMENTS Clinical interviews were conducted 3 times a week to monitor for side effects . Determinations of serum urea , calcium , phosphorus , hematocrit , Kt/V and blood gas analysis were obtained before and after each treatment . RESULTS Twenty-three patients completed the study . A significant increase in calcium plasma levels was only observed after treatment with calcium carbonate [ 9.34 mg/dl ( SD 0.91 ) vs. 9.91 mg/dl ( SD 0.79 ) , P < 0.01 ] . The drop in phosphorus levels was substantial and significant for both salts [ 5.64 mg/dl ( SD 1.54 ) vs. 4.60 mg/dl ( SD 1.32 ) , P < 0.01 and 5.89 mg/dl ( SD 1.71 ) vs. 4.56 mg/dl ( SD 1.57 ) , P < 0.01 , for calcium acetate and calcium carbonate respectively ] . The percentage reduction in serum phosphorus ( at the end of the study ) per milliequivalent of salt administered per day tended to be higher with calcium acetate but statistical significance was not found . CONCLUSION Calcium acetate can be a good alternative to calcium carbonate in the h and ling of hyperphosphatemia in ESRD patients . When calcium acetate is used , control of hyperphosphatemia can be achieved with a lower administration of calcium , perhaps with a lower risk of hypercalcemia Secondary hyperparathyroidism ( SHPT ) is one of the serious complications in patients with chronic kidney disease . Parathyroid gl and s secrete parathyroid hormone ( PTH ) , stimulated partly by hyperphosphatemia and hypocalcemia complicating chronic kidney disease ( CKD ) . Use of a calcium-based phosphate binder might be sufficient to reduce serum PTH levels in mild SHPT , while the recent K/DOQI clinical guidelines recommended vitamin D therapy for dialysis patients with serum level of intact parathyroid hormone of 300 pg/mL or more . We conducted a 6-month prospect i ve controlled trial of 50 patients initiating hemodialysis therapy who were r and omized to receive oral calcium carbonate alone or the drug plus oral vitamin D sterol , calcitriol or alfacalcidol . The primary end point was the proportion of r and omized patients who had a mean PTH level of 300 pg/mL or less at the end of this study . The secondary end point included the percent change in the values for corrected calcium , phosphorus , the calcium-phosphorus product , and PTH . Eighty percent of patients receiving calcium carbonate without vitamin D sterols ( 20 of 25 ) reached the primary end point-a mean PTH level of 300 pg/mL or less after the period-as compared with 84 % of those receiving calcium carbonate and vitamin D sterol ( 21 of 25 ) ( Mantel-Haenszel odds ratio 0.76 , 95 % confidence interval : 0.18 - 3.25 , P = 0.71 ) . The other effects of the two regimens on the secondary end points were not significantly different after 6 months . In SHPT of dialysis patients initiating hemodialysis , oral calcium carbonate use alone was not inferior to additional vitamin D sterol use with calcium carbonate in reducing serum PTH levels . Our result indicated that , if serum calcium and phosphorus levels are controlled primarily regardless of used agents , it will be followed by reduction of serum PTH level in these patients OBJECTIVE Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia . The use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis ( sevelamer ) disclosed efficacy in the short and long-term studies . However , due to race differences we performed a short-term study on the Saudi hemodialysis patients and compared sevelamer with a st and ard calcium-based phosphate binder . METHODS An open-label , r and omized , cross-over 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 given either sevelamer or calcium carbonate , and the dosages were titrated to achieve phosphate control over an 8-week period . After a 2-week washout period , patients crossed over to the alternate agent for 8 weeks . Twenty patients from the Dialysis Unit of King Fahd Hospital , Jeddah , Kingdom of Saudi Arabia , were recruited for the study between March 2003 and June 2003 . RESULTS There was a similar decrease in serum phosphate values over the course of the study with both sevelamer ( -3.3 + /-2.2 mg/dL ) and calcium carbonate ( -3.9 + /-2.8 mg/dL ) . Fifty-two percent of patients developed serum calcium greater than 2.75 mmol/L ( 11.0 mg/dL ) while receiving calcium carbonate versus 26 % of patients receiving sevelamer ( p<0.05 ) . 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 13 % mean decrease in serum cholesterol levels . CONCLUSION Sevelamer was effective in controlling hyperphosphatemia without result ing in an increase in the incidence of hypercalcemia seen with calcium carbonate . 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 Abstract Objective : Epidemiological data link elevated levels of serum phosphorus with increased mortality among patients with chronic kidney disease . Recent data also suggest improved survival with the use of dietary phosphate binders in patients on dialysis . However , few studies have comprehensively evaluated the survival benefit associated with different phosphate binders . A post-hoc survival analysis was undertaken of lanthanum carbonate ( Fosrenol * Fosrenol is a registered trademark of Shire Pharmaceuticals , Basingstoke , UK . ) versus st and ard therapy . Research design and methods : Patients on dialysis enrolled in a phase 3 , 2-year , comparative safety study were r and omized 1:1 to lanthanum carbonate or st and ard therapy to treat serum phosphorus to a target of ≤5.9 mg/dL ( 1.90 mmol/L ) . Patients ( N = 1354 ) were followed up for survival status during , or after completion of or discontinuation from the study . Main outcome measures : Survival was measured by time from first dose of study medication to all-cause mortality or last contact . Results : The distribution of follow-up time was similar in the lanthanum carbonate and st and ard therapy groups ( mean 23.7 versus 23.9 months [ median 27.0 versus 26.0 months ] , respectively ) . Serum phosphorus levels were similar across treatment groups , as patients were treated to target . At follow-up , 19.9 % ( 135/680 ) of patients treated with lanthanum carbonate had died versus 23.3 % ( 157/674 ) on st and ard therapy ( log-rank p = 0.18 ) . In the subgroup of patients aged > 65 years ( n = 336 ) , 27.0 % ( 44/163 ) of lanthanum-carbonate-treated patients had died compared with 39.3 % ( 68/173 ) on st and ard therapy ( log-rank p = 0.04 ) . Conclusion : In these survival analyses , overall mortality was similar in the lanthanum carbonate and st and ard therapy groups , but results suggest that there was a survival benefit associated with lanthanum carbonate treatment for patients aged > 65 years , who are likely to carry the greatest burden of vascular calcification . These results were similar to those observed in the Dialysis Clinical Outcomes Revisited study , a prospect i ve trial of sevelamer hydrochloride design ed to assess survival The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known . We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from r and omization . This was a predetermined secondary end point of a r and omized clinical trial design ed to assess progression of coronary artery calcium ( CAC ) scores in the two treatment arms . Thirty-four deaths occurred during the follow-up period : 23 in subjects r and omized to calcium-containing phosphate binders and 11 in subjects r and omized to sevelamer . Baseline CAC score was a significant predictor of mortality after adjustment for age , race , gender , and diabetes with increased mortality proportional to baseline score ( P=0.002 ) . Mortality was borderline significantly lower in subjects r and omized to sevelamer ( 5.3/100 patient years , confidence interval ( CI ) ( 2.2 - 8.5 ) compared to those r and omized to calcium-containing binders ( 10.6/100 patient years , CI 6.3 - 14.9 ) ( P=0.05 ) . The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment ( P=0.016 , hazard ratio 3.1 , CI 1.23 - 7.61 ) . In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality . Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders BACKGROUND Lanthanum carbonate ( LC ) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients . LC also contributes to a reduced oral calcium load compared with calcium carbonate ( CaC ) treatment . However , no crossover studies which compare the influence on serum calcium level between treatments with LC and CaC in hemodialysis ( HD ) patients have been carried out . METHODS After washout for 2 weeks , 50 patients on HD were r and omized ( 1 : 1 ) to receive LC or CaC for 3 months . Thereafter , patients underwent a second 2-week washout period and were switched to the alternative binder for the next 3 months . Mineral and bone metabolism markers were measured with the changes of vitamin D doses . RESULTS The serum phosphate level showed a similar decrease from baseline to 3 months in both groups . During the study periods , hypercalcemia was observed only in patients taking CaC. The dose of vitamin D analogue was increased more frequently in the patients of the LC group compared with LC group . The iPTH level showed a significant decrease in the CaC group , but not in the LC group . Serum levels of BAP , TRAP5b , and ALP were significantly elevated in the LC group , whereas the FGF-23 level showed a significant decrease . CONCLUSION LC effectively reduced the serum phosphate level ( like CaC ) and allowed the vitamin D analogue dosage to be increased without hypercalcemia in HD patients . LC is one of the useful phosphate binders without hypercalcemia . ( UMIN-CTR registration number : UMIN000002331 ) Chronic kidney disease associated mineral and bone disorders arise as a result of aberrant bone mineral metabolism in patients with advancing levels of renal dysfunction and end-stage renal disease . One of the cornerstones of treatment is the use of phosphate-binding agents . We describe the rationale and study design for a clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder . This trial is a three-period , international , multicenter , r and omized , controlled clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder , consisting of a 2-week washout period , a 52-week safety assessment period in which subjects are r and omized to ferric citrate or active control , and a 4-week efficacy assessment period in which subjects r and omized to ferric citrate in the safety assessment period are r and omized to ferric citrate or placebo . Eligible subjects include end-stage renal disease patients who have been treated with thrice-weekly hemodialysis or peritoneal dialysis for at least 3 months in dialysis clinics in the United States and Israel . Primary outcome measure will be the effect of ferric citrate vs. placebo on the change in serum phosphorus . Safety assessment s will be performed by monitoring adverse events , concomitant medication use , and sequential blood chemistries ( including iron parameters , phosphorus , and calcium ) . This three-period trial will assess the efficacy of ferric citrate as a phosphate binder . If proven safe and efficacious , ferric citrate will likely provide an additional phosphate binder to treat chronic kidney disease associated mineral and bone disorders Background Dietary phosphorus restriction , oral administration of phosphorus binders , and dialysis are the main strategies to control hyperphosphatemia in patients with stage 5 chronic kidney disease . Aluminum hydroxide ( AH ) and calcium carbonate , the most commonly used phosphorus binders , have serious disadvantages , such as aluminum toxicity and hypercalcemia . Sevelamer hydrochloride ( SH ) is a relatively new nonabsorbed calcium- and aluminum-free phosphorus binder . The present study was design ed to evaluate the efficacy of SH in the control of hyperphosphatemia and its effect , compared to AH , on serum lipid parameters in patients on continuous ambulatory peritoneal dialysis ( CAPD ) . Methods 30 stable patients on CAPD were included in an open-label , r and omized crossover study . After a 2-week phosphorus binder washout period , 15 patients ( group I ) were administered SH for 8 weeks and in the remaining patients ( group II ) , AH was introduced ( phase A ) . After a new 2-week washout period , patients crossed over to the alternate agent for another 8 weeks ( phase B ) . Results There were similar reductions in serum phosphorus levels over the course of the study with both agents : by 1.18 ± 0.07 mg/dL ( 0.38 ± 0.03 mmol/L ) with SH and by 1.25 ± 0.15 mg/dL ( 0.40 ± 0.05 mmol/L ) with AH in phase A ( p = NS ) , and by 1.35 ± 0.25 mg/dL ( 0.43 ± 0.08 mmol/L ) with AH and by 1.23 ± 0.80 mg/dL ( 0.39 ± 0.25 mmol/L ) with SH in phase B ( p = NS ) . Moreover , SH administration was associated with a 10.5 % ± 9.4 % and a 20.1 % ± 6.8 % fall in total cholesterol ( p < 0.05 ) and low-density lipoprotein cholesterol ( p < 0.001 ) in phase A , and 11.9 % ± 7.2 % ( p < 0.05 ) and 21.5 % ± 2.4 % ( p < 0.001 ) , respectively , in phase B. In both phases of the study , AH administration was not followed by a significant change in serum lipid parameters . Conclusion Sevelamer hydrochloride is a well-tolerated alternative to calcium- or aluminum-containing phosphorus binder in the control of serum phosphorus in CAPD patients . Furthermore , SH improves the lipid profile in these patients This open label , multicentric , comparative clinical trial was done to compare the efficacy and tolerability of two sevelamer formulations , sevelamer carbonate , and sevelamer hydrochloride , in the treatment of hyperphosphatemia in Indian end stage renal disease ( ESRD ) patients . A total of 97 ESRD patients on hemodialysis , were enrolled . Patients were r and omized to receive either sevelamer carbonate or sevelamer hydrochloride . All patients were evaluated every week for 6 weeks for efficacy and safety variables . Total 88 patients completed the study . After 6 weeks of therapy , there were similar reductions ( P<0.0001 ) in mean serum phosphorus and the CaxP product both the groups . The responder rates for test and reference groups were 75 % , 68.18 % respectively ( P=0.3474 ) . The adverse events reported were nausea , abdominal pain/discomfort , heartburn , constipation , diarrhea , increased prothrombin time , and severe arthritis . No serious adverse events were reported . There was no significant difference between the groups for adverse events and the laboratory parameters . From the results of this multicentric , comparative , r and omized clinical study on sevelamer carbonate we can recommend that sevelamer carbonate may be used as a phosphate binder in Indian chronic kidney disease patients Little is known about the impact of various phosphate binders on the skeletal lesions of secondary hyperparathyroidism ( 2 degrees HPT ) . The effects of calcium carbonate ( CaCO3 ) and sevelamer were compared in pediatric peritoneal dialysis patients with bone biopsy-proven 2 degrees HPT . Twenty-nine patients were r and omly assigned to CaCO3 ( n = 14 ) or sevelamer ( n = 15 ) , concomitant with either intermittent doses of oral calcitriol or doxercalciferol for 8 mo , when bone biopsies were repeated . Serum phosphorus , calcium , parathyroid hormone ( PTH ) , and alkaline phosphatase were measured monthly . The skeletal lesions of 2 degrees HPT improved with both binders , and bone formation rates reached the normal range in approximately 75 % of the patients . Overall , serum phosphorus levels were 5.5 + /- 0.1 and 5.6 + /- 0.3 mg/dl ( NS ) with CaCO3 and sevelamer , respectively . Serum calcium levels and the Ca x P ion product increased with CaCO3 ; in contrast , values remained unchanged with sevelamer ( 9.6 + /- 01 versus 8.9 + /- 0.2 mg/dl ; P < 0.001 , respectively ) . Hypercalcemic episodes ( > 10.2 mg/dl ) occurred more frequently with CaCO3 ( P < 0.01 ) . Baseline PTH levels were 980 + /- 112 and 975 + /- 174 pg/ml ( NS ) ; these values decreased to 369 + /- 92 ( P < 0.01 ) and 562 + /- 164 pg/ml ( P < 0.01 ) in the CaCO3 and the sevelamer groups , respectively ( NS between groups ) . Serum alkaline phosphatase levels also diminished in both groups ( P < 0.01 ) . Thus , treatment with either CaCO3 or sevelamer result ed in equivalent control of the biochemical and skeletal lesions of 2 degrees HPT . Sevelamer , however , maintained serum calcium concentrations closer to the lower end of the normal physiologic range , thereby increasing the safety of treatment with active vitamin D sterols BACKGROUND AND AIM OF THE STUDY Valvular calcification is common in patients with end-stage renal disease , and is associated with an unfavorable prognosis . It was hypothesized that sevelamer , a non-calcium-based phosphorus binder , might attenuate the progression of valvular calcification . METHODS Two hundred subjects on maintenance hemodialysis received either sevelamer or calcium-based phosphorus binders . To assess the extent of calcification , 186 subjects underwent baseline electron beam tomography ( EBT ) of the coronary arteries , aorta and mitral and aortic valves , and 132 had follow up EBT scans at week 52 . Changes in valvular calcification and combined valvular/vascular calcification were monitored and compared . RESULTS At baseline , mitral valve calcification was seen in 46 % of subjects , aortic valve calcification in 33 % . Most subjects with zero values at baseline failed to progress over one year . Aortic valve calcification was significantly increased in calcium-treated subjects . Changes in mitral valve calcification , and combined mitral + aortic valve calcification were less in sevelamer-treated than in calcium-treated subjects , but not significantly so . When combining valvular and vascular calcification , the median ( 10 % , 90 % ) change in sevelamer-treated subjects was significantly lower than in calcium-treated subjects ( 6 , -5084 to 1180 versus 81 , -1150 to 2944 , p = 0.04 ) . The effect of sevelamer remained significant after adjustment for baseline calcification and the time-averaged calcium-phosphorus product , and was independent of the calcium preparation ( acetate versus carbonate ) , geographic region ( US versus Europe ) , LDL- or HDL-cholesterol , C-reactive protein and statin use . Significantly more sevelamer-treated subjects experienced an arrest ( 45 versus 28 % , p = 0.047 ) or regression ( 26 versus 10 % , p = 0.02 ) in total valvular and vascular calcification . CONCLUSION Sevelamer arrested the progression of valvular and vascular calcification in almost 50 % of hemodialysis subjects . Sevelamer treatment , plus intensive control of calcium and phosphorus levels , may attenuate progression of , or achieve regression in , cardiac valvular calcification Since hyperphosphatemia in hemodialysis patients can cause secondary hyperparathyroidism and promotes vascular calcification , serum phosphate ( Pi ) levels must be controlled by phosphate binders . Although sevelamer and colestimide are known as similar non-calcium , non-aluminum phosphate binders in hemodialysis patients , there are no studies that compare the effects of the two agents as either a monotherapy or in combination with calcium carbonate ( CaCO3 ) . We r and omly allocated 62 hemodialysis patients with hyperphosphatemia to treatment with sevelamer ( 3.0 g/day ) and colestimide ( 3.0 g/day ) . During the study , 35 subjects dropped out , leaving 13 in the sevelamer group and 14 in the colestimide group . After a 2-week CaCO3 washout , all subjects received the monotherapy for 4 weeks and then CaCO3 ( 3.0 g/day ) was added for another 4 weeks . Serum corrected calcium levels tended to decrease in both groups during the washout period and monotherapy , but there was no significant difference between the two groups after the addition of CaCO3 . Although the calcium x phosphorus product ( Ca x P ) in the two groups increased during the washout period , there was no significant change or difference between the two groups during monotherapy . However , the addition of CaCO3 significantly reduced serum Pi at Week 8 compared to that at Week 0 in both groups , and significantly lowered Ca x P only in the sevelamer group , but not in the colestimide group ( . ) In this short-term study , sevelamer and colestimide similarly ameliorated hyperphosphatemia , but the combination of sevelamer and CaCO3 was more effective than colestimide with CaCO3 in controlling the Ca x P product , and it may improve cardiovascular mortality in hemodialysis patients Two r and omized , placebo-controlled trials conducted in patients with nondialysis-dependent ( NDD ) chronic kidney disease ( CKD ) , iron deficiency anemia , and normal or elevated serum phosphorus demonstrated that ferric citrate ( FC ) significantly increased hemoglobin and decreased serum phosphate concentrations . Pooling these trial results could provide a more robust evaluation of the safety and efficacy of FC in this population . We pooled results of a phase 2 ( n = 149 ) and 3 trial ( n = 233 ) of patients r and omized and treated for up to 12 and 16 weeks , respectively . The starting dose in both trials was three 1-g ( elemental iron 210 mg ) tablets/day with food , up to 12 tablets/day . Doses were titrated in the phase 2 and 3 trials to lower serum phosphate concentrations to a target range ( 0.97–1.13 mmol/L ) and to achieve a ≥10-g/L hemoglobin increase , respectively . Safety was assessed in all patients who received ≥1 dose of FC ( n = 190 ) and placebo ( n = 188 ) . Treatment-emergent adverse events ( AEs ) were reported in 143 of 190 ( 75.3 % ) FC-treated and 116 of 188 ( 61.7 % ) placebo-treated patients ; gastrointestinal AEs were the most frequent ( 94 [ 49.5 % ] vs. 52 [ 27.7 % ] , respectively ) . Specific events reported in > 5 % of patients ( FC vs. placebo , respectively ) included discolored feces ( 41 [ 21.6 % ] vs. 0 [ 0.0 % ] ) , diarrhea ( 39 [ 20.5 % ] vs. 23 [ 12.2 % ] ) , constipation ( 35 [ 18.4 % ] vs. 19 [ 10.1 % ] ) , and nausea ( 18 [ 9.5 % ] vs. 8 [ 4.3 % ] ) . Twenty FC-treated ( 10.5 % ) and 21 placebo-treated patients ( 11.2 % ) experienced a serious AE . Two patients ( 1.1 % ) died in each group . A pooled efficacy assessment demonstrated a consistent hemoglobin rise and modest serum phosphate decline , with few excursions below the normal range . When used for treatment of patients with NDD-CKD , FC contributes to gastrointestinal AEs at higher rates than placebo , while simultaneously correcting two of the principal metabolic manifestations of CKD ( iron deficiency anemia and relative hyperphosphatemia ) BACKGROUND Patients affected by end-stage renal disease ( ESRD ) demonstrate a very high cardiovascular risk mediated by traditional cardiovascular risk factors as well as abnormal mineral metabolism and a state of chronic inflammation . Sevelamer is a nonabsorbable non-calcium-based hydrogel with potential antiatherosclerotic properties . METHOD AND RESULTS One hundred eight patients undergoing maintenance hemodialysis were r and omized to sevelamer or calcium acetate as treatment for hyperphosphatemia . A coronary artery calcium score , as a measure of plaque burden , was calculated at baseline and 1 year , along with serial measurements of serum lipoproteins , beta2-microglobulin , and high-sensitivity C-reactive protein ( hs-CRP ) . At 1 year , coronary artery calcium score progressed significantly from baseline in calcium acetate-treated subjects ( P < .001 ) but not in sevelamer-treated patients ( P = NS ) . Total cholesterol ( P < .0001 ) , low-density lipoprotein cholesterol ( P < .0001 ) , apolipoprotein B ( P < .0001 ) , beta2-microglobulin ( P = .018 ) , and hs-CRP ( P < .002 ) decreased , and high-density lipoprotein increased significantly ( P = .036 ) from baseline in the sevelamer-treated subjects but not in subjects treated with calcium acetate despite the more frequent use of statins in the latter group ( 46 % vs 22 % , P < .05 ) . The changes in total and low-density lipoprotein cholesterol , apolipoprotein B , and hs-CRP were significantly different between treatment groups ( all P < .01 ) . CONCLUSIONS Sevelamer leads to favorable changes in lipids and inflammatory markers with potentially useful antiatherogenic effects in hemodialysis patients Treating hyperphosphatemia without increasing the calcium load in chronic kidney disease patients on dialysis is important , as conventional treatment frequently results in ectopic calcification . Sevelamer , a monotherapy for hyperphosphatemia is frequently associated with gastrointestinal disorders , often result ing in discontinuation of treatment . Lanthanum carbonate is a novel non-calcium-based phosphate binder for the treatment of chronic kidney disease . Here , its clinical efficacy and safety were assessed in Japanese dialysis patients . A placebo-controlled , r and omized , double-blind , parallel group , multicenter study was performed in Japanese dialysis patients . Patients were treated with various dosages of lanthanum carbonate or a placebo daily for six weeks . The primary efficacy endpoint was the change in serum phosphate level from the baseline . Secondary endpoints included achievement rates to target serum phosphate levels and changes in serum calcium levels . Safety was evaluated by the incidence of drug-related and treatment-emergent adverse events . A significant reduction in serum phosphate level was demonstrated for all dosages from Week 1 . This dose-dependent effect was also observed in the changes in serum calcium x phosphate product , yet there was no notable difference in serum calcium or serum intact parathyroid hormone levels . The incidence of drug-related adverse events was dose-dependent , with the most common being gastrointestinal symptoms . Lanthanum carbonate effectively controls serum phosphate levels and is generally tolerable to Japanese chronic kidney disease patients on dialysis , as reported for the Caucasian population . The optimal dosage in Japanese patients needs to be confirmed using a flexible-dose titration schedule BACKGROUND Patients with renal failure require complex regimens of renal replacement therapies and medications , including ingestion of phosphate-binding agents 3 times daily . Previous studies suggested that sevelamer may provide extended phosphate binding and be effective with once-daily dosing , thus simplifying the phosphate-binder regimen . METHODS Twenty-four patients were enrolled in this study , 21 of whom were r and omly assigned to sevelamer administration at their previously prescribed dose , either once daily with the largest meal or thrice daily with meals , with crossover to the other regimen after 4 weeks . Eighteen patients completed both treatment periods . The primary efficacy measure for which the study was powered is comparison of the effect of once-daily versus st and ard thrice-daily sevelamer dosing on serum phosphorus level control , determined by using equivalence testing . Secondary efficacy measures are the effects of the 2 regimens on serum calcium level corrected for albumin level ; calcium x phosphorus product ; albumin ; intact parathyroid hormone ; total , low-density lipoprotein , high-density lipoprotein , and non-high-density lipoprotein cholesterol ; and triglyceride levels . RESULTS Once-daily sevelamer was as effective as thrice-daily dosing of sevelamer in controlling serum phosphorus , calcium , calcium x phosphorus product , serum albumin , and serum lipid levels . Bioequivalence was not shown for intact parathyroid hormone , likely because of high variability . Mean serum phosphorus levels were 4.6 + /- 0.3 mg/dL ( 1.49 + /- 0.10 mmol/L ) during thrice-daily dosing and 5.0 + /- 0.3 mg/dL ( 1.61 + /- 0.10 mmol/L ) during once-daily dosing . The average prescribed dose of sevelamer during both treatment regimens was 6.7 + /- 2.4 g. Routine laboratory measures were similar in the 2 groups . Both regimens were well-tolerated . CONCLUSION Despite concerted patient-directed educational efforts , phosphorus level control in patients with renal failure is suboptimal and contributes to increased mortality risk . Once-daily sevelamer could simplify these regimens and encourage medication compliance , perhaps improving hyperphosphatemia management BACKGROUND / PURPOSE Sevelamer hydrochloride is a recently developed phosphate binder , which is a quaternary amine anion exchanger without calcium or aluminum . Sevelamer is effective in controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis ( HD ) patients . We investigated whether sevelamer restored bone metabolism in chronic HD patients . METHODS An 8-week , prospect i ve , open-label , r and omized study was conducted after a 2-week washout period in chronic hyperphosphatemic HD patients . This study compared the effect of sevelamer on markers of bone turnover with that of calcium acetate , as stratified by baseline serum intact parathyroid hormone ( iPTH ) level . RESULTS There was no difference in the changes of serum phosphorus , calcium-phosphorus product and serum iPTH between the sevelamer and the calcium acetate groups . However , more hypercalcemic events ( 12 % ) were documented under calcium acetate treatment . In patients with hypoparathyroidism , calcium acetate treatment decreased serum iPTH at the end of the study , while sevelamer did not . Increased serum alkaline phosphatase levels were found among patients receiving sevelamer treatment compared with those who received calcium acetate treatment . In those patients receiving sevelamer , the serum alkaline phosphatase level was also positively correlated to the sevelamer dosage ( r = 0.246 , p = 0.013 ) . CONCLUSION Sevelamer effectively reduces serum phosphorus with a lower incidence of hypercalcemic effects in HD patients . Sevelamer is an effective means of treatment for chronic hyperphosphatemic HD patients , especially those with hypoparathyroidism BACKGROUND Lanthanum carbonate ( LC ) has been proposed as a new phosphate binder . Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate ( CC ) on the evolution of renal osteodystrophy in dialysis patients . Bone biopsies were performed at baseline , after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma . METHODS Twenty new dialysis patients were r and omized to receive LC ( median dose 1250 mg ) for 1 year ( n = 10 ) , followed by 2 years of CC treatment or CC ( n = 10 ) during the whole study period ( 3 years ) . RESULTS After 36 weeks of treatment , steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml . Six weeks after cessation of 1 year of treatment , the plasma lanthanum levels declined to a value of 0.17 + /- 0.12 ng/ml ( P < 0.05 ) and after 2 years to 0.09 + /- 0.03 ng/ml . Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point . The mean bone concentration in patients receiving LC increased from 0.05 + /- 0.03 to 2.3 + /- 1.6 microg/g ( P < 0.05 ) after 1 year and slightly decreased at the end of the study to 1.9 + /- 1.6 microg/g ( P < 0.05 ) . CONCLUSIONS Bone deposition after 1 year of treatment with LC is low ( highest concentration : 5.5 microg/g ) . There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity BACKGROUND MCI-196 ( colestilan ) , an anion exchange resin , is widely used as an anti-hypercholesterolaemic drug in Japan . To evaluate the efficacy and safety of MCI-196 as a phosphate binder , a double-blind , r and omized , placebo-controlled prospect i ve trial was conducted in Japanese end-stage renal disease patients with hyperphosphataemia on intermittent haemodialysis treatment . METHODS Phosphate binders were discontinued during a 2-week washout period . Subsequently , patients whose serum phosphorus levels were > or = 6.5 mg/dl , but < 10 mg/dl were eligible to enter the treatment protocol . Patients were r and omized to either MCI-196 6 g/day or placebo for 2 weeks . The efficacy and safety of MCI-196 were assessed in 33 and 46 patients , respectively . RESULTS Serum phosphorus in the placebo group increased by 0.84+/-0.95 mg/dl ( mean+/-SD ) , while serum phosphorus in the MCI-196 group decreased by 0.55+/-1.23 mg/dl . The difference between the two groups was statistically significant ( P = 0.002 ) . A reduction of > or = 1 mg/dl in serum phosphorus was observed in 43 % in the MCI-196 group and 0 % of patients in the placebo group ( P = 0.0122 ) . Calcium-phosphorus ( Ca x P ) product , intact parathyroid hormone ( iPTH ) and low-density lipoprotein (LDL)-cholesterol in the MCI-196 group also decreased significantly compared with the placebo group , while serum calcium was unchanged . Adverse reactions were observed in 51.7 % of the MCI-196 group and 29.4 % of the placebo group ( P = 0.2186 ) . The most frequent adverse reactions in the MCI-196 group were gastrointestinal symptoms and signs , including constipation . CONCLUSIONS The present findings suggest that the short-term administration of MCI-196 is effective in decreasing serum phosphorus in haemodialysis patients . Its long-term efficacy needs to be evaluated BACKGROUND Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5 . Although phosphate binders are often used in patients on peritoneal dialysis ( PD ) , no large r and omized controlled studies evaluating their use solely in this population have previously been reported . METHODS In this multicentre , open-label study , adult patients on PD with serum phosphorus > 5.5 mg/dl were r and omized ( 2:1 ) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate . Doses were titrated to achieve serum phosphorus of 3.0 - 5.5 mg/dl . Changes in serum phosphorus , calcium , intact parathyroid hormone ( iPTH ) , lipids and plasma biomarkers were assessed . RESULTS A total of 253 patients were screened , 143 of whom were r and omized ( sevelamer hydrochloride , n = 97 ; calcium acetate , n = 46 ) . Treatment groups were well balanced with regard to baseline demographics . Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate ( P < 0.001 ) . Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group ( P = 0.001 ) but not in the sevelamer hydrochloride group . Sevelamer hydrochloride was also associated with decreases in total cholesterol , low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase ( all P < 0.001 versus baseline ) . Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients . Hypercalcaemia was experienced by more calcium acetate-treated patients ( 18 versus 2 % ; P = 0.001 ) . CONCLUSIONS In summary , sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients . The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis population This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients . Patients ( n=64 ) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were r and omized ( 1:1 ) to receive calcium carbonate combined with calcitonin ( Group I ) or lanthanum carbonate ( Group II ) for 12 weeks . Blood levels of calcium , phosphorus and intact parathyroid hormone ( iPTH ) were measured every month , bone mass density ( BMD ) and coronary artery calcium scores ( CACS ) were measured at 3 months . During the study period , serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL ( P < 0.05 ) , serum phosphorus decreased from 6.79 ± 1.05 to 5.46 ± 1.18 mg/dL ( P < 0.05 ) , and serum iPTH levels in the Group I and Group II were not significantly different from the baseline . There were no significant differences in CACS in either group . There were no significant differences in the BMD values between Group I and baseline . In Group II , the BMD values at the lumbar spine and femoral neck were significantly lower than those before the trial and significantly lower than the corresponding values of Group I ( P<0.05 ) . Calcium carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients . There were no serious treatment-related adverse events in treatment with calcium carbonate combined with calcitonin AIM The Australian Pharmaceutical Benefits Scheme ( PBS ) commenced cost subsidization for haemodialysis patients of sevelamer in December 2007 , cinacalcet in July 2008 and lanthanum in May 2009 . To determine the impact of PBS listing of these medications , we performed a single centre cross-sectional , longitudinal study . METHODS Dialysis parameters and biochemistry were prospect ively collected at 6 monthly intervals for all prevalent haemodialysis patients from October 2007 to April 2010 . Medications prescribed to manage chronic kidney disease mineral and bone disorder were recorded . Univariate regression analysis was undertaken for each variable against time . RESULTS Patient numbers ranged from 87 to 114 in each period . At baseline , mean age was 68.8 ± 14.3 years , 71 % male , 15.1 ± 3.5 haemodialysis hours/week and urea reduction ratio 71.9 ± 9.8 % . These variables were unchanged over time . The use of sevelamer , cinacalcet and lanthanum increased ( P < 0.001 ) . There was a decrease in the use of aluminium- and calcium-based phosphate binders ( P < 0.001 ) but no change in the use of magnesium based phosphate binders ( P = 0.09 ) or calcitriol ( P = 0.11 ) . Serum phosphate ( P = 0.13 ) and parathyroid hormone ( PTH ) ( P = 0.87 ) were unchanged . Mean ' bone pill ' burden fell from 60.3/week to 51.9/week ( P = 0.02 ) . Mean pill cost increased from Australian dollars ( AUD ) 12.85/patient per week to AUD 59.85/patient per week ( P < 0.001 ) . CONCLUSION The PBS subsidization of sevelamer , cinacalcet and lanthanum has changed prescribing patterns , although serum phosphate and PTH remain unchanged . These changes have been at an additional cost of AUD 2444/patient per year . Data to address clinical end-points of mortality and hospitalization is needed to determine if the cost of these newer agents is warranted Hyperphosphataemia plays a key role in the pathogenesis of renal osteodystrophy , and phosphate-binding agents are required in many chronic dialysis patients . Aluminium hydroxide and calcium carbonate are well-established phosphate binders , but their use is associated with toxicity or poor efficacy . Calcium acetate is known to be a potent phosphate binder , and has recently been used successfully in chronic dialysis patients . In this r and omized cross-over trial in 31 chronic haemodialysis patients , equimolar doses of calcium acetate and calcium carbonate were administered for 6 weeks each . Compliance was estimated from tablet counts , and biochemical parameters were measured at the end of each treatment period . Of the 31 patients 23 completed both treatment arms ; of the remainder , three withdrew due to adverse symptoms , hypercalcaemia necessitated treatment withdrawal in two , and three died . Non-compliance was significantly higher with acetate ( 18.3 % tablets not taken ) than with carbonate ( 8.7 % ) . Serum phosphate was significantly lower after treatment with acetate ( 1.51 mmol/l ) than with carbonate ( 1.80 ) , as was the Ca x PO4 product ( 3.59 vs 4.18 respectively ) and PTH ( 17.8 vs 25.4 pmol/l respectively ) . Serum calcium was significantly higher after acetate therapy ( 2.40 vs 2.32 mmol/l ) . No significant difference was found for sodium , potassium , bicarbonate , urea , creatinine , and haemoglobin . This study confirms that the treatment of hyperphosphataemia is more effective with calcium acetate than with calcium carbonate . For the first time an associated beneficial effect on secondary hyperparathyroidism has also been demonstrated . Patient tolerability of calcium acetate was considerably poorer , probably due in part to tablet formulation and bulkiness , as well as possible direct gastrointestinal effects of the acetate salt Observational data suggest that elevated magnesium levels in dialysis patients may prevent vascular calcification and in vitro magnesium can prevent hydroxyapatite crystal growth . However , the effects of magnesium on vascular calcification and bone mineral density have not been studied prospect ively . Seven chronic hemodialysis patients participated in this open label , prospect i ve pilot study to evaluate the effects of a magnesium-based phosphate binder on coronary artery calcification ( CAC ) scores and vertebral bone mineral density ( V-BMD ) in patients with baseline CAC scores > 30 . Magnesium carbonate/calcium carbonate ( elemental Mg : 86 mg/elemental Ca 100 mg ) was administered as the principal phosphate binder for a period of 18 months and changes in CAC and V-BMD were measured at baseline , 6 , 12 , and 18 months . Serum magnesium levels averaged 2.2+/-0.4 mEq/L ( range : 1.3 - 3.9 mEq/L ) . Phosphorus levels ( 4.5+/-0.6 mg/dL ) were well controlled throughout the 18 months study . Electron beam computed tomography results demonstrated a small not statically significant increase in absolute CAC scores , no significant change in median percent change , and a small none significant change in V-BMD . Magnesium may have a favorable effect on CAC . The long-term effect on bone mineral density remains unclear . Larger studies are needed to confirm these findings Calcium salts are increasingly used as phosphorus binders in patients with chronic renal failure . Calcium carbonate is the principal salt presently utilized , however , other calcium salts may be more effective and safer phosphorus binders . Theoretical calculations , in vitro experiments , and in vivo studies in normal subjects have shown calcium acetate to be a more effective phosphorus binder than other calcium salts . This salt has not previously been studied in patients with chronic renal failure . We used a one-meal gastrointestinal balance technique to measure phosphorus absorption , calcium absorption and phosphorus binding in six patients with chronic renal failure . Calcium acetate was compared with calcium carbonate and placebo . Equivalent doses ( 50 mEq Ca++ ) of calcium acetate bound more than twice as much phosphorus ( 106 + /- 23 mg ) as calcium carbonate ( 43 + /- 39 mg ) P less than 0.05 . When phosphorus binding was factored for calcium absorption , calcium acetate bound 0.44 mEq HPO4 = /mEq absorbed Ca++ compared with 0.16 mEq HPO4 = bound/mEq Ca++ absorbed with calcium carbonate . More efficient phosphorus binding permits serum phosphorus concentration to be controlled with lower doses of calcium salts . The higher phosphorus binding/calcium absorption ratio coupled with a lower dose indicates that less calcium will be absorbed when calcium acetate is used for phosphorus control . Markedly positive calcium balance , hypercalcemia and ectopic calcification should be less likely to occur with this drug than other calcium salts 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 AIM The aim of this study was to develop a novel approach to the analysis of bone histomorphometric data and outcomes presentation that would simplify the characterization of renal osteodystrophy and facilitate clinical decision-making . METHODS AND MATERIAL S Data were derived from a r and omized trial of dialysis patients treated for one year with a dose of lanthanum carbonate or calcium carbonate ( up to 3750 mg/day and 9000 mg/day , respectively ) . Histomorphometric analyses of baseline and end-of- study bicortical transiliac bone biopsies were performed . Activation frequency , bone formation rate/bone surface , osteoclast surface/ bone surface , osteoblast surface/bone surface , mineralization lag time , and osteoid thickness were determined to provide a measure of overall bone cell activity ( bone formation , bone resorption , bone turnover ) and risk of developing osteopenia ( bone balance ) . A novel approach of qualitatively grouping these numerical data as " improved " , " unchanged " , or " worsened " based on deviation from normal was used to facilitate interpretation of clinical relevance . RESULTS Using our method , lanthanum carbonate was shown to improve histomorphometric parameters measured . These improvements were superior to those produced by calcium carbonate . These data add valuable clinical relevance to the previously published qualitative data from the same cohort [ D'Haese et al. 2003 ] . Lanthanum carbonate moderated extreme forms of renal osteodystrophy , whereas calcium carbonate treatment increased the incidence of adynamic and predominant hyperparathyroid bone disease . CONCLUSIONS This study provides an approach to the prospect i ve evaluation of bone disease progression with therapy , and its application supports the safety and greater efficacy of one-year lanthanum carbonate versus calcium carbonate therapy as a means to normalize bone turnover in dialysis patients BACKGROUND AND OBJECTIVES Cinacalcet , a novel calcimimetic , targets the calcium-sensing receptor to lower parathyroid hormone ( PTH ) , calcium , and phosphorus levels in dialysis patients with secondary hyperparathyroidism ( SHPT ) . This study compared the efficacy of a cinacalcet-based regimen with unrestricted conventional care ( vitamin D and phosphate binders ) for achieving the stringent National Kidney Foundation Kidney Disease Outcomes Quality Initiative ( KDOQI ) targets for dialysis patients . STUDY DESIGN In this multicenter , open-label study , hemodialysis patients with poorly controlled SHPT were r and omized to receive conventional care ( n = 184 ) or a cinacalcet-based regimen ( n = 368 ) . Doses of cinacalcet , vitamin D sterols , and phosphate binders were adjusted during a 16-wk dose-optimization phase with the use of algorithms that allowed cinacalcet to be used with adjusted doses of vitamin D. The primary end point was the proportion of patients with mean intact PTH < or = 300 pg/ml during a 7-wk efficacy assessment phase . RESULTS A higher proportion of patients receiving the cinacalcet-based regimen versus conventional care achieved the targets for PTH ( 71 % versus 22 % , respectively ; P < 0.001 ) , Ca x P ( 77 % versus 58 % , respectively ; P < 0.001 ) , calcium ( 76 % versus 33 % , respectively ; P < 0.001 ) , phosphorus ( 63 % versus 50 % , respectively ; P = 0.002 ) , and PTH and Ca x P ( 59 % versus 16 % , respectively , P < 0.001 ) , and allowed a 22 % reduction in vitamin D dosage in patients receiving vitamin D at baseline . Achievement of targets was greatest in patients with less severe disease ( intact PTH range , 300 to 500 pg/ml ) and the cinacalcet dose required was lower in these patients ( median = 30 mg/d ) . CONCLUSIONS Compared with conventional therapy , a cinacalcet-based treatment algorithm increased achievement of KDOQI treatment targets in dialysis patients in whom conventional therapy was no longer effective in controlling this disease BACKGROUND Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients . Sevelamer , a phosphate-binding polymer , attenuates the progression of arterial calcification ; it is unknown whether this improves outcomes . PATIENTS AND INTERVENTIONS A r and omized comparison of sevelamer and calcium-based phosphate binders was performed in hemodialysis patients treated up to 45 months . The primary endpoint was mortality . Secondary endpoints included cause-specific mortality and hospitalization ; 2103 patients were r and omized , 2040 received treatment , and 1065 completed treatment . RESULTS Overall mortality was not significantly reduced by sevelamer ( adjusted relative risk = 0.92 ; 95 % confidence interval , 0.78 to 1.09 ; log-rank P = .40 ) . Among patients > or = 65 years of age , sevelamer reduced the risk of death ( adjusted relative risk = 0.77 ; 95 % confidence interval , 0.62 to 0.97 ; log-rank P = .02 ) . Sevelamer patients had a trend toward fewer hospitalizations ( P = .06 ) and fewer hospital days ( P = .09 ) . CONCLUSIONS A statistically significant reduction in mortality in the overall study population was not observed . Sevelamer was associated with a survival benefit among patients > or = 65 years of age ABSTRACT Background : Lanthanum carbonate , a new phosphate binder , is effective in reducing serum phosphorus levels in patients with end-stage renal disease . A 1-year extension study to two r and omized controlled studies was conducted to evaluate the long-term safety of lanthanum carbonate in patients who received hemodialysis . Research design and methods : Patients from two previous lanthanum carbonate studies were eligible to continue treatment in a 1-year open-label extension . A total of 77 patients ( N = 77 ; 11 from Study 1 , 66 from Study 2 ) were enrolled in this extension . The mean age of patients was 60.9 years ( SD ± 12.5 years ) ; 65 % were male and 35 % were female . All patients received lanthanum carbonate at the optimal dose for phosphorus control , determined in their previous study . Safety and tolerability were assessed by monitoring adverse events , laboratory parameters , and vital signs . The number of patients who maintained serum phosphorus levels at ≤ 5.9 mg/dL ( 1.9 mmol/L ) was recorded , along with serum calcium , calcium × phosphorus product , and parathyroid hormone levels . Results : Lanthanum carbonate was well tolerated and was associated with few treatment-related adverse events . The most commonly reported adverse events were nausea ( 26.0 % ) , peripheral edema ( 23.4 % ) , and myalgia ( 20.8 % ) . No treatment-related serious adverse events occurred . By Week 4 , the mean serum phosphorus level had decreased by approximately 1 mg/dL to 5.7 ± 2.0 mg/dL ( 1.84 ± 0.7 mmol/L ) . At the end of the study , the mean pre-dialysis serum phosphorus level was 5.7 ± 1.4 mg/dL ( 1.84 ± 0.5 mmol/L ) ; 53 % of patients had controlled phosphorus levels . Calcium × phosphorus product decreased during Week 1 and remained within a clinical ly acceptable range thereafter . There were no clinical ly significant changes in serum calcium , or parathyroid hormone levels . Conclusion : Lanthanum carbonate is well tolerated and is effective for the long-term maintenance of serum phosphorus control in patients with end-stage renal disease Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton , little is known about this compartment from bone biopsy studies , particularly in CKD patients . In addition , there is no prospect i ve data on the effects of CKD-MBD therapy on cortical porosity ( Ct . Po ) . This is a post hoc analysis on data from a r and omized controlled trial on the effects of different phosphate binders on bone remodelling . Therapy was adjusted according to the first biopsy , and included sevelamer or calcium acetate , calcitriol and changes in calcium dialysate concentration . We measured Ct . Po at baseline and one year after . Fifty-two patients ( 46±13years old , 67 % women and 60 % white ) were enrolled . Ct . Po was already high at baseline in 85 % of patients [ 30 % ( 17 , 46 ) ] and correlated with PTH ( p=0.001 ) . Low bone turnover was seen in 28 patients ( 54.9 % ) . After one-year treatment , PTH increased in patients with low turnover , as intended . However , increased Ct . Po was seen in 49 patients ( 94 % ) . This increase correlated with the delta of phosphate ( p=0.015 ) and the delta of PTH ( p=0.03 ) ; it was also higher among non-white patients than in white patients ( p=0.039 ) . The risk of increase in Ct . Po was 4.5 higher among non-white patients . Adjusted multiple regression analysis showed that the delta of Ct . Po was dependent on delta PTH and race ( r(2)=0.193 ) . We concluded that in an attempt to increase bone turnover , the increase in PTH levels might be associated with higher cortical porosity , particularly in non-white patients . Whether this finding leads to a high risk of fracture deserves further investigation BACKGROUND Hyperphosphatemia is commonly found in dialysis patients , which can lead to fatal cardiovascular diseases . The objective of this study was to evaluate the effectiveness and safety of extended-release nicotinic acid for reducing serum phosphorus in hemodialysis patients . METHODS A r and omized placebo-controlled trial was conducted , and 28 hemodialysis patients with hyperphosphatemia after 4 weeks of diet control were r and omized to receive extended-release nicotinic acid ( treatment group ) once daily for 12 weeks . The initial daily dose was 375 mg , which was then titrated once weekly to 500 , 750 and 1,000 mg , as tolerated . The control group received placebo . All patients in each group still received their phosphate-binding medication as st and ard treatment . RESULTS At the 12th week , mean serum phosphorus of the treatment group significantly decreased from 7.13 ± 1.09 mg/dL to 5.65 ± 1.22 mg/dL ( p<0.001 ) . However , there was no statistically significant difference between the control and treatment groups . Nine out of the 14 patients ( 64.29 % ) in the treatment group achieved the K/DOQI serum phosphorus goal . Serum high-density lipoprotein cholesterol of patients in the treatment group increased by 30.22 % from baseline ( p=0.037 ) . There were no significant changes in serum calcium or parathyroid hormone level in any of the patients . Hot flushes were observed in all patients of the treatment group . There were no significant changes in the fasting blood glucose level , uric acid or liver function enzymes in any of the patients . CONCLUSIONS Extended-release nicotinic acid is effective and safe in reducing serum phosphorus as an add-on st and ard therapy in hemodialysis patients It has been suggested that phosphate binders may reduce the inflammatory state of hemodialysis ( HD ) patients . However , it is not clear whether it has any effect on oxidative stress . The objective of this study was to evaluate the effect of sevelamer hydrochloride ( SH ) and calcium acetate ( CA ) on oxidative stress and inflammation markers in HD patients . Hemodialysis patients were r and omly assigned to therapy with SH ( n=17 ) or CA ( n=14 ) for 1 year . Before the initiation of therapy ( baseline ) and at 12 months , we measured in vitro reactive oxygen species ( ROS ) production by stimulated and unstimulated polymorphonuclear neutrophils and serum levels of tumor necrosis factor alpha , interleukin-10 , C-reactive protein , and albumin . There was a significant reduction of spontaneous ROS production in both groups after 12 months of therapy . There was a significant decrease of Staphylococcus aureus stimulated ROS production in the SH group . There was a significant increase in albumin serum levels only in the SH group . In the SH group , there was also a decrease in the serum levels of tumor necrosis factor alpha and C-reactive protein . Our results suggest that compared with CA treatment , SH may lead to a reduction in oxidative stress and inflammation . Therefore , it is possible that phosphate binders exert pleiotropic effects on oxidative stress and inflammation , which could contribute toward decreasing endothelial injury in patients in HD BACKGROUND Hyperphosphataemia contributes to secondary hyperparathyroidism and renal osteodystrophy in patients with end-stage renal disease ( ESRD ) . Calcium salts are widely employed to bind dietary phosphate ( P ) but they may promote positive net calcium balance and metastatic calcification . We recently reported that ferric compounds bind intestinal phosphate in studies of normal and azotemic rats . METHODS To extend this observation , we performed an open-label , r and om order , crossover comparison study of ferric citrate and calcium carbonate in haemodialysis patients from two teaching hospitals . The study sample consisted of 23 women and 22 men with an average age of 52.5 + /- 11.8 ( SD ) years and an average weight of 54.5 + /- 10.7 kg . All forms of iron therapy were discontinued . Two weeks before the study , patients were instructed to discontinue all P-binding agents . The patients were r and omly assigned to receive either calcium carbonate ( 3 g/day ) or ferric citrate ( 3 g/day ) for 4 weeks followed by a 2 week washout period , and then crossed over to the other P-binding agent for 4 weeks . RESULTS From a baseline concentration of 5.6 + /- 1.5 mg/dl , the serum P increased during the washout period to 7.2 + /- 1.9 mg/dl prior to calcium carbonate treatment , and to 6.7 + /- 1.9 mg/dl prior to ferric citrate treatment . The serum P concentration fell significantly during treatment with both calcium carbonate ( 7.2 + /- 1.9 to 5.2 + /- 1.5 mg/dl , P<0.0001 ) and ferric citrate ( 6.7 + /- 1.9 to 5.7 + /- 1.6 mg/dl , P<0.0001 ) . The results were not influenced by order of treatment . Under the conditions of the study protocol , ferric citrate was less effective than calcium carbonate at lowering the serum phosphate concentration . The serum Ca concentration increased during treatment with calcium carbonate but not ferric citrate . Ferric citrate treatment did not affect the serum concentration of aluminium . Ferric citrate treatment was associated with mild and generally tolerable gastrointestinal symptoms . CONCLUSION Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients . Further studies are needed to find the optimal dose Sevelamer hydrochloride is an ionic exchange resin with high affinity for phosphate . This phosphate-binding agent has few serious adverse reactions with the advantage of reducing total and low density lipoprotein ( LDL ) cholesterol levels . However , it is controversial as to whether sevelamer hydrochloride can modulate the inflammatory response via endotoxin reduction . Therefore , a single-center , open-label , prospect i ve and r and omized study was performed to compare the clinical efficacy , safety and anti-inflammatory activity of two sevelamer hydrochloride tablet forms – a br and ed tablet form , Renagel ® ( Genzyme manufacturer ) and its generic equivalent ( EMS manufacturer ) . Twenty-eight chronic kidney disease volunteer patients at stage 5 ( CDK 5D ) , on chronic low-flux hemodialysis carried out in 4-hour sessions , three times a week , were studied . The serum phosphorus , ionic calcium , total cholesterol and fractions , bicarbonate , blood pH , interleukin (IL)-6 , IL-10 , IL-1 beta and tumor necrosis factor-alpha ( TNF-α ) levels were collected prior to dialysis at mid-week . The incidence of gastrointestinal adverse effects were determined at the end of the phosphate-binder washout period as well as at the end of the fourth and eighth weeks of use of both tablet forms . The same magnitude of reduction in serum phosphorus was observed with both sevelamer tablet forms . Only the Renagel ® group showed lower total cholesterol and lower LDL cholesterol levels at the fourth and eighth week versus baseline . No significant differences in serum cytokine levels were identified in either drug group . However , the incidence of intestinal obstipation was higher among patients who used the generic equivalent form . In conclusion , Renagel ® and its EMS generic equivalent tablet forms have a similar clinical efficacy in reducing phosphorus in CKD 5D patients on low-flux hemodialysis and a similar safety profile BACKGROUND Vascular calcification and low bone turnover with a relatively low parathyroid hormone ( PTH ) often coexist in diabetic patients undergoing haemodialysis . Since calcium salts ( CaS ) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification , we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients . METHODS We measured the change in coronary artery calcium scores ( CACS ) with sequential electron beam computed tomography ( EBCT ) in 64 diabetic and 45 non-diabetic patients , r and omized to CaS or sevelamer within 90 days of starting haemodialysis . CACS measurements were repeated after 6 , 12 and 18 months . Serum intact PTH ( iPTH ) , calcium and phosphorus were serially tested . RESULTS During the study period , serum phosphate was similar in diabetic and non-diabetic patients . Serum calcium levels were similar at baseline ( 2.3+/-0.25 mmol/l for both ) and increased significantly with CaS treatment ( P<0.05 ) both in diabetic and non-diabetic patients but not with sevelamer . Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients ( median increase 177 vs 27 ; P=0.05 ) . During follow-up , diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer ( 33 % vs 6 % , P=0.005 ) and had a lower mean iPTH level ( 24+/-16 vs 31+/-14 pmol/l ; P=0.038 ) . CONCLUSIONS The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer . These effects are accompanied by iPTH changes suggestive of low bone turnover Background The aim of the study was to evaluate the impact of magnesium ( Mg ) on the evolution of arterial calcifications in hemodialysis patients . Patients and methods Seventy-two stable hemodialysis patients were r and omly allocated to two groups : 36 administered a regimen containing magnesium carbonate plus calcium acetate as a phosphate binder ( Mg group ) , while the rest 36 received calcium acetate alone ( Ca group ) . The presence and the progression of arterial calcifications were evaluated in plain X-rays using a simple vascular calcification score . The duration of the follow-up period was 12 months . Results Thirty-two patients of the Mg group and 27 of the Ca group completed the study . The mean time average values of the biochemical laboratories did not differ between the two groups , except serum Mg : 2.83 + 0.38 in the Mg group versus 2.52 + 0.27 mg/dl in the Ca group , p = 0.001 . In 9/32 ( 28.12 % ) patients of the Mg group and in 12/27 ( 44.44 % ) patients of the Ca group , the arterial calcifications were worsened , p = 0.276 . Moreover , in 4/32 ( 15.6 % ) patients of the Mg group and in 0/27 ( 0 % ) patients of the Ca group , they were improved , p = 0.040 . The multivariate logistic regression analysis revealed that serum magnesium was an independent predictor for no progression of the arterial calcifications , p = 0.047 . Conclusions Magnesium probably retards the arterial calcifications in hemodialysis patients . Further clinical studies are needed to clarify whether magnesium provides cardiovascular protection to this group of patients Fibroblast growth factor 23 ( FGF23 ) is a member of the fibroblast growth factor superfamily which displays a strong phosphaturic action and an inhibition of vitamin D 1-alpha hydroxylase activity . Fourty-six patients undergoing maintenance hemodialysis therapy participated in the study . They were r and omly divided into 2 groups , and treated with either 3 g sevelamer hydrochloride+3 g of calcium bicarbonate ( CaCO3 ) , or 3 g of CaCO3 alone . Serum FGF23 levels were determined by a s and wich enzyme-linked immunosorbent assay ( ELISA ) system that detects the intact form of FGF23 molecules . Although the serum inorganic phosphate ( Pi ) levels were comparable before treatment , the levels were significantly lower in the patients treated with sevelamer hydrochloride+CaCO3 than those with CaCO3 alone after 4 weeks of treatment ( P<0.05 ) . Serum FGF23 levels significantly decreased after 4 weeks of the treatment with sevelamer hydrochloride+CaCO3 from the pretreatment levels ( P<0.05 ) , while no changes were found in the patients treated with CaCO3 alone . Thus , the use of sevelamer hydrochloride and CaCO3 reduced serum FGF23 levels in dialysis patients presumably through inhibiting phosphate load into the intestine BACKGROUND AND OBJECTIVES Management of hyperphosphatemia , a predictor of mortality in chronic kidney disease , is challenging . Nonadherence to dietary phosphate binders , in part , contributes to uncontrolled serum phosphorus levels . This phase IIIb trial assessed the efficacy of increased dosages ( 3000 to 4500 mg/d ) of reformulated lanthanum carbonate ( 500- , 750- , and 1000-mg tablets ) in nonresponders to dosages of up to 3000 mg/d . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis . Patients who achieved serum phosphorus control at week 4 with < or=3000 mg/d lanthanum carbonate entered cohort A ; nonresponders were r and omly assigned to receive 3000 , 3750 , or 4500 mg/d ( cohort B ) . The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8 , among patients in cohort B. RESULTS At the end of week 4 , 54 % of patients achieved serum phosphorus control at dosages < or=3000 mg/d administered as one tablet per meal . Among patients who entered cohort B , control rates of 25 , 38 , and 32 % for patients who were r and omly assigned to 3000 , 3750 , or 4500 mg/d lanthanum carbonate , respectively , were achieved , with no increase in adverse events . Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders , partly because of reduced tablet burden with higher dosage strengths . Physicians and patients also expressed a preference for lanthanum carbonate over previous medication . CONCLUSIONS Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden BACKGROUND Renal osteodystrophy is a common complication of end-stage renal disease ( ESRD ) and is a major cause of morbidity in patients with ESRD . High serum levels of phosphorus , calcium and parathyroid hormone are associated with the development of this disease . The effects on bone of treatment with lanthanum carbonate , a new phosphate binder , and calcium carbonate were assessed in patients with ESRD . METHODS This was an open-label , multicenter , parallel-group study . Patients were recruited within 12 weeks of commencing dialysis . Following screening , phosphate binder administration was stopped , tetracycline labeling administered and a transiliac bone biopsy taken . After r and omization to lanthanum carbonate or calcium carbonate , patients were titrated to an optimum dose for 8 weeks and maintained at this dose for 44 weeks . The bone was then labeled and a second biopsy taken . Biopsy sample s were analyzed histomorphometrically . RESULTS Paired bone biopsies from 33 lanthanum carbonate- and 30 calcium carbonate-treated patients were suitable for analysis . None of the patients on either treatment developed osteomalacia . Assessment of activation frequency changes showed that 41 % of biopsies from lanthanum carbonate-treated patients moved towards normal ( observed values at the follow-up biopsy were closer to expected values than were the baseline values , so patients were considered to be improved ) compared with 23 % of calcium carbonate-treated patients ( p = 0.15 ) . CONCLUSIONS This study indicates that there was no evidence of aluminum-like toxicity with lanthanum carbonate after 1 year of treatment in ESRD patients commencing dialysis , and there appeared to be a beneficial effect on bone-cell function and activity compared with calcium carbonate Calcium acetate has many characteristics of an ideal phosphorus binder . It is a readily soluble salt that avidly binds phosphorus in vitro at pH 5 and above . One-dose/one-meal balance studies show it to be more potent than calcium carbonate or calcium citrate . We studied chronic ( 3-month ) phosphorus binding with calcium acetate in 91 hyperphosphatemic dialysis patients at four different centers . All phosphorus binders were stopped for 2 weeks . Calcium acetate at an initial dose of 8.11 mmol ( 325 mg Ca2 + ) per meal was then used as the only phosphorus binder . Dose was adjusted to attempt control of predialysis phosphorus level less than 1.78 mmol/L ( 5.5 mg/100 mL ) . Final calcium acetate dose was 14.6 mmol ( 586 mg ) Ca2 + per meal . Sixteen patients developed mild transient hypercalcemia ( mean , 2.84 mmol/L [ 11.4 mg/dL ] . Initial phosphorus values in mmol/L ( mg/dL ) were 2.39 ( 7.4 ) ; at 1 month , 1.91 ( 5.9 ) ; and at 3 months , 1.68 ( 5.2 ) . Initial calcium values in mmol/L ( mg/dL ) were 2.22 ( 8.9 ) ; at 1 month , 2.37 ( 9.5 ) ; and at 3 months , 2.42 ( 9.7 ) . Initial aluminum values in mumol/L ( micrograms/L ) were 2.99 ( 80.7 ) ; and at 3 months were 2.54 ( 68.4 ) . Initial C-terminal parathyroid hormone ( C-PTH ) values in ng/mL were 14.6 ; at 1 month , 11.9 ; and at 3 months , 13.2 . Sixty-nine patients then entered a double-blind study . Phosphorus binders were stopped for 1 week . Calcium acetate ( at a dose established in a prior study ) or placebo was then administered for 2 weeks . Next , patients were crossed to the opposite regimen for 2 weeks . Initial phosphorus was 2.36 mmol/L ( 7.3 mg/100 mL ) and calcium 2.22 mmol/L ( 8.9 mg/100 mL ) . ( ABSTRACT TRUNCATED AT 250 WORDS AIMS The aim of this crossover study was to compare the reduction of serum phosphorus ( SP ) with fixed doses of the non-calcium-containing phosphate binders lanthanum carbonate ( LC ) and sevelamer hydrochloride ( SH ) in hemodialysis patients . METHODS Following washout ( 2 - 3 weeks ) , 182 patients with SP > or= 6.0 mg/dl and calcium > or= 8.4 mg/dl were r and omized ( 1:1 ) to receive LC ( 2,250 to 3,000 mg/day ) or SH ( 4,800 to 6,400 mg/day ) for 4 weeks . Patients underwent a second washout ( 2 weeks ) and switched to the alternative binder for 4 weeks . RESULTS At the end of treatment , LC had reduced SP by 1.7 + /- 0.1 mg/dl , compared with 1.4 + /- 0.1 mg/dl for SH ; the difference was not statistically significant in the primary analysis ( LOCF , p = 0.133 ) . However , the reduction with LC was significantly greater than with SH in a prespecified key secondary analysis of patients who completed 4 weeks of treatment with each binder ( 0.5 mg/dl difference , p = 0.007 ) . The reduction of SP was also greater with LC than SH after 1 week of treatment ( p = 0.024 ) . CONCLUSIONS Although the primary analysis found no difference between LC and SH in the reduction of SP , a significant difference in favor of LC was observed in patients who completed treatment . The results of this study show interesting trends with respect to onset and duration of action that warrant further investigation in longer-term studies BACKGROUND Lanthanum carbonate is a highly effective phosphate binder with significant potential as a treatment for hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . Here , the results of a placebo-controlled , dose-ranging study are presented . METHODS 196 patients ( > or = 18 years ) receiving hemodialysis for at least 6 months entered a 1- to 3-week , single-blind , placebo run-in phase . Of these , 145 patients were r and omized to a double-blind phase in which they received placebo or lanthanum carbonate in daily lanthanum doses of 225 , 675 , 1,350 or 2,250 mg for 6 weeks . Serum levels of phosphorus , calcium and parathyroid hormone , and adverse events were monitored throughout the study . RESULTS The intent-to-treat analysis ( n = 144 ) showed significant dose-related reductions in serum phosphorus at lanthanum doses of 675 , 1,350 and 2,250 mg . After 6 weeks of treatment , phosphorus levels were significantly lower in the lanthanum groups receiving 1,350 mg/day and 2,250 mg/day , compared with the placebo group ( respective changes from r and omization : -0.95 + /- 1.39 mg/dl ( -0.31 + /- 0.45 mmol/l ) , -1.13 + /- 2.01 mg/dl ( -0.36 + /- 0.65 mmol/l ) , 0.75 + /- 1.47 mg/dl ( 0.24 + /- 0.47 mmol/l ) , p < 0.001 ) . Significant reductions in serum phosphorus , compared with placebo , occurred in the lanthanum 1,350 mg/day group from the second week of treatment and in the 2,250 mg/day group from the first week of treatment . Adverse events were mainly gastrointestinal ( e.g. nausea and vomiting ) . Treatment-related adverse events occurred in 39 % of patients treated with lanthanum carbonate and 44 % of the placebo group . CONCLUSION Lanthanum carbonate is an effective and well-tolerated agent for the short-term treatment of hyperphosphatemia in patients with ESRD BACKGROUND Abnormalities in serum calcium , phosphorus , and parathyroid hormone ( PTH ) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality . No clinical trials have been conducted to clearly identify categories of calcium , phosphorus , and PTH levels associated with the lowest mortality risk . Current clinical practice guidelines are based largely on expert opinions , and clinical ly relevant differences exist among guidelines across countries . We sought to describe international trends in calcium , phosphorus , and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) , an international study of hemodialysis practice s and associated outcomes . STUDY DESIGN Prospect i ve cohort study . PARTICIPANTS 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I ( 1996 - 2001 ) , DOPPS II ( 2002 - 2004 ) , or DOPPS III ( 2005 - 2007 ) . PREDICTORS Serum calcium , albumin-corrected calcium ( Ca(Alb ) ) , phosphorus , and PTH levels . OUTCOMES Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models . RESULTS Distributions of mineral metabolism markers differed across DOPPS countries and phases , with lower calcium and phosphorus levels observed in the most recent phase of DOPPS . Survival models identified categories with the lowest mortality risk for calcium ( 8.6 to 10.0 mg/dL ) , Ca(Alb ) ( 7.6 to 9.5 mg/dL ) , phosphorus ( 3.6 to 5.0 mg/dL ) , and PTH ( 101 to 300 pg/mL ) . The greatest risk of mortality was found for calcium or Ca(Alb ) levels greater than 10.0 mg/dL , phosphorus levels greater than 7.0 mg/dL , and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium , phosphorus , and PTH . LIMITATIONS Because of the observational nature of DOPPS , this study can only indicate an association between mineral metabolism categories and mortality . CONCLUSIONS Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade . The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism BACKGROUND Elevated levels of fibroblast growth factor 23 ( FGF23 ) are associated with increased risk of adverse outcomes in patients with CKD . Reducing dietary phosphate intake or absorption may decrease FGF23 levels , but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In this 2 × 2 factorial , single-blinded , placebo-controlled , 3-month study , conducted between July 2009 and March 2012 , 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were r and omly assigned to one of four groups : ad libitum diet plus lanthanum carbonate ( LC ) placebo ( n=10 ) , 900-mg phosphate diet plus LC placebo ( n=10 ) , ad libitum diet plus LC ( n=11 ) , or 900-mg phosphate diet plus LC ( n=8 ) . The dose of LC was 1000 mg three times daily with meals . Dietary restriction was accomplished with outpatient counseling . The primary end point was change in FGF23 levels from baseline . RESULTS Compared with ad libitum diet , the 900-mg phosphate diet did not significantly reduce FGF23 levels ( diet × time interaction , P=0.05 ) . Compared with placebo , LC alone also did not significantly reduce FGF23 levels ( LC × time interaction , P=0.21 ) . However , the dual intervention significantly decreased FGF23 levels throughout the study period ( diet × LC × time interaction , P=0.02 ) , result ing in a 35 % ( 95 % confidence interval , 8%-62 % ) reduction by study end . CONCLUSION The combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 3 - 4 and normal serum phosphate levels BACKGROUND AND OBJECTIVES Epidemiologic studies suggest that higher serum phosphaturic hormone fibroblast growth factor 23 levels are associated with increase morbidity and mortality . The aim of the FGF23 Reduction Efficacy of a New Phosphate Binder in CKD Trial was to evaluate the effect of sevelamer carbonate on serum C-terminal fibroblast growth factor 23 levels in normophosphatemic patients with CKD stage 3b/4 . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Patients with CKD , eGFR between 45 and 15 ml/min per 1.73 m2 , fasting serum phosphate concentration > 3.1 mg/dl , and serum C-terminal fibroblast growth factor 23 > 80 relative units/ml were included in our double-blind , placebo-controlled , r and omized multicenter study . All patients received 100,000 IU cholecalciferol at time of r and omization . Participants received either placebo or sevelamer carbonate 4.8 g daily during a 12-week period . Biologic parameters , including serum C-terminal fibroblast growth factor 23 , intact fibroblast growth factor 23 , and α-klotho , were evaluated at baseline and 12 weeks after inclusion . RESULTS Of 96 screened patients , 78 ( mean±SD age : 63±13 years old ; 70 % men ; mean eGFR : 27±9 ml/min per 1.73 m2 ) met the inclusion criteria . At baseline , mean eGFR was 27±9 ml/min per 1.73 m2 , mean serum phosphate level was 3.8±0.5 mg/dl , and median ( interquartile range ) serum C-terminal fibroblast growth factor 23 level was 157 ( 120 - 241 ) relative units/ml . After 12 weeks of treatment , urinary phosphate-to-creatinine ratio fell significantly in the sevelamer group . The sevelamer and placebo groups did not differ significantly in terms of median change in serum C-terminal fibroblast growth factor 23 levels : the median ( interquartile range ) change was 38 ( -13 - 114 ) relative units/ml in the placebo group and 37 ( -1 - 101 ) relative units/ml in the sevelamer group ( P=0.77 ) . There was no significant difference in serum intact fibroblast growth factor 23 , α-klotho , or phosphate levels changes between the two groups . Serum total and LDL cholesterol levels fell significantly in the sevelamer group . CONCLUSIONS In our double-blind , placebo-controlled , r and omized study performed in normophosphatemic patients with CKD , a 12-week course of sevelamer carbonate significantly reduced phosphaturia without changing serum phosphorus but did not significantly modify serum C-terminal fibroblast growth factor 23 and intact fibroblast growth factor 23 or α-klotho levels BACKGROUND The Dialysis Clinical Outcomes Revisited ( DCOR ) trial , a large , r and omized , multicenter , open-label study , compared effects of sevelamer with calcium-based phosphate binders on mortality and hospitalization in hemodialysis patients . Many patients were lost to follow-up , precluding intent-to-treat analysis by using prospect i ve data collection . STUDY DESIGN Preplanned secondary analysis , intent-to-treat design for all outcomes , using Centers for Medicare & Medicaid Services ( CMS ) data . SETTING & PARTICIPANTS Participants were 18 years or older and on hemodialysis therapy for more than 3 months , with Medicare as primary payor . The trial was completed at the end of 2004 . INTERVENTION Sevelamer , calcium-based phosphate binders . OUTCOMES Mortality , morbidity , and hospitalization end points . MEASUREMENTS DCOR subjects were linked to the CMS End-Stage Renal Disease data base . Outcomes were evaluated through the CMS End-Stage Renal Disease enrollment and cl aims data base ; baseline characteristics and comorbid conditions were evaluated using CMS and case-report data . RESULTS Groups were well balanced except for a greater percentage of calcium-group patients with atherosclerotic heart disease . Analyses were adjusted by using 10 baseline characteristics . All-cause ( 17.7 versus 17.4 deaths/100 patient-years ; P = 0.8 unadjusted ; P = 0.9 adjusted ) and cardiovascular mortality ( 9.0 versus 8.2 deaths/100 patient-years ; P = 0.3 unadjusted ; P = 0.4 adjusted ) did not differ significantly between treatment groups . First hospitalization , cause-specific multiple hospitalizations , first morbidity , and multiple morbidity rates also did not differ significantly . Multiple all-cause hospitalization rate ( 1.7 versus 1.9 admissions/patient-year ; P = 0.03 unadjusted ; P = 0.02 adjusted ) and hospital days ( 12.3 versus 13.9 days/patient-year ; P = 0.05 unadjusted ; P = 0.03 adjusted ) were lower in the sevelamer group . LIMITATIONS Outcome parameters and cardiovascular comorbidity assessment s were derived from Medicare cl aims data ; only subjects with Medicare-as- primary -payor status were included in hospitalization and morbidity analyses . CONCLUSIONS In this secondary analysis , treatment with sevelamer versus calcium-based binders did not affect overall mortality ( primary outcome ) , cause-specific mortality , morbidity , or first or cause-specific hospitalization ( secondary outcomes ) , but there was evidence for a beneficial effect on multiple all-cause hospitalizations and hospital days ( secondary outcomes ) BACKGROUND Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular ( CV ) survival in patients receiving dialysis remains to be eluci date d. STUDY DESIGN Open-label r and omized controlled trial with parallel groups . SETTING S & PARTICIPANTS 466 incident hemodialysis patients recruited from 18 centers in Italy . INTERVENTION Study participants were r and omly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder ( although not required by the protocol , all patients in this group received calcium carbonate ) for 24 months . OUTCOMES All individuals were followed up until completion of 36 months of follow-up or censoring . CV death due to cardiac arrhythmias was regarded as the primary end point . MEASUREMENTS Blind event adjudication . RESULTS At baseline , patients allocated to sevelamer had higher serum phosphorus ( mean , 5.6 ± 1.7 [ SD ] vs 4.8 ± 1.4 mg/dL ) and C-reactive protein levels ( mean , 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL ) and lower coronary artery calcification scores ( median , 19 [ IQR , 0 - 30 ] vs 30 [ IQR , 7 - 180 ] ) . At study completion , serum phosphate levels were lower in the sevelamer arm ( median dosages , 4,800 and 2,000 mg/d for sevelamer and calcium carbonate , respectively ) . After a mean follow-up of 28 ± 10 months , 128 deaths were recorded ( 29 and 88 due to cardiac arrhythmias and all-cause CV death ) . Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate ( HR , 0.06 ; 95 % CI , 0.01 - 0.25 ; P < 0.001 ) . Similar results were noted for all-cause CV mortality and all-cause mortality , but not for non-CV mortality . Adjustments for potential confounders did not affect results . LIMITATIONS Open-label design , higher baseline coronary artery calcification burden in calcium carbonate-treated patients , different mineral metabolism control in sevelamer-treated patients , overall lower than expected mortality . CONCLUSIONS These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of incident hemodialysis patients . However , the better outcomes in the sevelamer group may be due to better phosphate control rather than reduction in calcium load Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality , but their safety and efficacy in this population are not well understood . Here , we aim ed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD . We r and omly assigned 148 patients with estimated GFR=20 - 45 ml/min per 1.73 m(2 ) to calcium acetate , lanthanum carbonate , sevelamer carbonate , or placebo . The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3 , 6 , and 9 . Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo ( P=0.03 ) . Phosphate binders , but not placebo , decreased mean 24-hour urine phosphorus by 22 % . Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo ( P=0.002 ) . Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels . Active therapy did , however , significantly increase calcification of the coronary arteries and abdominal aorta ( coronary : median increases of 18.1 % versus 0.6 % , P=0.05 ; abdominal aorta : median increases of 15.4 % versus 3.4 % , P=0.03 ) . In conclusion , phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus ; however , they also promote the progression of vascular calcification . The safety and efficacy of phosphate binders in CKD remain uncertain AIMS To investigate the evolution of renal osteodystrophy in patients on maintenance dialysis , treated with lanthanum carbonate ( LC ) vs. st and ard phosphate-binder therapy ( Stx ) . MATERIAL S AND METHODS This was a 2-year , r and omized , prospect i ve , open-label study during which patients on dialysis received LC titrated to a maximum of 3,000 mg/day or their previous phosphate binder treatment with the aim to achieve target phosphorus levels of < or = 5.9 mg/dl . Paired bone biopsy sample s for histomorphometric analysis were available at baseline and 1 year ( LC 32 , Stx 33 ) , and at baseline and 2 years ( LC 32 , Stx 24 ) . RESULTS With similar phosphorus control , Stx was associated with numerically higher serum calcium levels at most visits . Results of osteocalcin and bone-specific alkaline phosphatase in LC patients were higher throughout the study and correlated with parameters of bone formation ; however , the differences were not significant . Histological changes in bone turnover and volume were analyzed with respect to normal ranges . There was an improvement in bone turnover in the LC group , which was significant in the 1-year group , and an improvement in bone volume which was significant in the 2-year group . No significant changes in bone turnover or bone volume were observed in the Stx groups . In the 2-year LC group , 1 patient had osteomalacia at baseline and end of therapy , and a mineralization defect developed in 2 other patients . Several possible factors for a mineralization defect were present in these patients , but no single cause could be clearly identified . Histomorphometric parameters of bone , including formation and mineralization , did not correlate with bone lanthanum . No mineralization defect was observed in the Stx groups . CONCLUSION These findings show that similar phosphorus control with Stx and LC results in higher bone turnover after 1 year and higher bone volume after 2 years with LC BACKGROUND The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported , but not from a double-blind , comparator-controlled comparative study . METHODS The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a r and omized , double-blind , comparator-controlled , parallel group , multicenter study . This study is the first study using a r and omized , double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders . RESULTS In the double-blind phase , the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups . The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant . However , the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group . The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group . CONCLUSION Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner . However , lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia Background Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality . Current treatment options include dietary restriction , dialysis , and phosphate binders . Treatment using the latter is frequently limited by cost , tolerability , and calcium loading . One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients . Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis ( PD ) patients already receiving st and ard phosphorus-lowering therapies . Methods An 8 week , r and omized , double blind , placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients . Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were r and omized to niacinamide or placebo and prescribed 250 mg twice daily , with titration to 750 mg twice daily , as long as safety parameters were not violated . Phosphate binders , active vitamin D , and cinacalcet were kept constant during the study . The primary end point was change in plasma phosphorus . Secondary end points included changes in lipid parameters . Results 15 patients started on the study drug ( 8 niacinamide , 7 placebo ) and 7 in each arm had at least one on- study phosphorus measurement . The niacinamide treatment group experienced an average 0.7 ± 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 ± 0.8 mg/dL increase . The treatment effect difference ( 1.1 mg/dL ) was significant ( p = 0.037 ) . No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated . Two of the 8 patients r and omized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects . Adverse effects may limit the use of niacinamide in PD patients . Conclusion Niacinamide , when added to st and ard phosphorus-lowering therapies , result ed in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks . [ Clinical Trials.gov number NCT00508885 ( Clinical Trials.gov ) AIMS Whether differences in outcomes of calcium-free vs. calcium-containing phosphate binder treatments can be amplified by concurrent treatment with a calcium-sensing receptor agonist or vitamin D remains to be eluci date d. MATERIAL AND METHODS A post-hoc analysis of the INDEPENDENT study , an open-label r and omized controlled trial design ed to evaluate the impact of sevelamer ( SV ) vs. calcium salts ( CS ) on survival in incident dialysis patients . RESULTS We recruited 466 middle-aged men and women . Cinacalcet ( CC ) and vitamin D ( VD ) were administered to a portion of patients as part of their routine care . We tested the impact of CC and VD on survival in the overall and in both treatment arms of the original study cohort . Overall SV , but not CC or VD , administration was associated with a survival benefit ( mean follow-up : 28 ( 10 ) months ) . However , a significant ( p = 0.006 ) interaction of SV and CC on mortality was observed . CC use was associated with improved survival if administered in combination with SV ( HR 0.34 , 95 % CI 0.14 - 0.81 , p = 0.01 for subjects receiving or not CC ) but not CS ( HR 1.28 , 95 % CI 0.82 - 2.00 ; p = 0.26 for subjects receiving or not CC ) . No effect on mortality or interaction of phosphate binder use with VD was noted . CONCLUSIONS Though hypothesis generating , these results lend support to the idea that use of a CC may increase survival in incident hemodialysis patients when used with a calcium-free phosphate binder A prospect i ve , r and omized open-label trial of sevelamer hydrochloride with or without calcium carbonate ( CC ) involved 86 hemodialysis patients in Japan . The dosage of CC was fixed at 3.0 g/day for the 12-week study . After the first 4 weeks all subjects were changed from CC to sevelamer 3.0 g/day for another 4 weeks , then allocated r and omly to three groups for the final 4 weeks : group A , sevelamer 6.0 g/day ; group B , sevelamer 3.0 g/day and CC 3.0 g/day ; group C , CC 3.0 g/day . The target serum phosphorous concentration (P)=5.5 mg/dL and the corrected calcium concentration ( Ca ) was 9.0 - 10.0 mg/dL. Of the 86 patients , 62 finished the study without a change of dosage and their data were analyzed ( group A , N=16 ; group B , N=26 ; group C , N=20 ) . At week 8 compared with week 4 , the concentration of P increased from 5.7+/-1.4 to 6.4+/-1.7 mg/dL in group A , and decreased significantly in groups B and C , and in group B compared with groups A and C ; groups A and C had similar concentrations at week 8 . The Ca concentration decreased significantly from 9.7+/-1.0 to 9.1+/-0.7 mg/dL after the change to sevelamer . At week 8 Ca was not significantly changed in group A , whereas a significant increase occurred in groups B and C. Side-effects with sevelamer administration occurred in 34 of the 86 patients and 24 dropped out of the study , with a high frequency in group A ( 13/29 ; 44.8 % ) . In conclusion , there was an additive effect of sevelamer for the treatment of hyperphosphatemia with CC . The combination therapy was better tolerated and showed higher patient compliance than CC or sevelamer monotherapy BACKGROUND The management of hyperphosphatemia in patients with moderate to severe chronic kidney disease ( CKD ) includes dietary phosphate restriction and /or prescription of phosphate binders . Measuring phosphate intake in CKD is important for monitoring dietary adherence and for the effectiveness of therapeutic interventions . The 24-hour urine collection is the gold st and ard method for determining phosphate intake ; however , timed urine collection s are cumbersome and prone to error . We investigated the precision and accuracy of spot urine phosphate measurements , compared to 24-hour urine phosphate ( 24hUrP ) collection . STUDY DESIGN , SETTING , AND PARTICIPANTS We evaluated simultaneous spot and 24hUrP measurements , collected on multiple occasions , from 143 participants in the Phosphate Normalization Trial , a r and omized trial of phosphate binders versus placebo among persons with an estimated glomerular filtration rate between 20 - 45 mL/minute per 1.73 m2 . We used residual analyses and graphical methods to model the functional relationship of spot urine phosphate and creatinine measurements with 24hUrP. We used multiple linear regression to test whether additional covariates improved model prediction , including treatment assignment , age , sex , height , weight , urine collection time , and last meal time . We internally vali date d results using leave-one-out cross-validation , and externally vali date d in an independent replication cohort . RESULTS A log-log relation between the spot urine phosphate-to-creatinine ratio and 24hUrP excretion yielded the best model fit . In addition to spot urine phosphate and creatinine concentrations , inclusion of age , sex , and weight significantly improved prediction of 24hUrP. Compared with a spot urine phosphate-to-creatinine ratio alone ( r2 = 0.12 , P < .001 ) , the new equation more accurately predicted 24hUrP ( leave-one-out validation r2 = 0.43 , P < .001 , independent validation r2 = 0.39 , P < .001 ) . CONCLUSION We describe a novel equation to predict 24hUrP excretion using spot urine phosphate and creatinine , age , sex , and weight . The equation is more accurate and precise than the urine phosphate-to-creatinine ratio alone , and it provides a simple method for estimating 24hUrP excretion in patients with nondialysis-requiring CKD OBJECTIVE We have previously shown sevelamer hydrochloride ( RenaGel ) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients . PATIENTS AND METHODS We performed a r and omized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium , using the serum phosphorus concentration and intact parathyroid hormone ( PTH ) as the principal outcomes of interest . Calcium ( 900 mg elemental ) was provided as a once-nightly dose on an empty stomach . 71 patients were r and omized and included in the intent-to-treat population ; 55 completed the 16-week study period ( 2 weeks washout , 12 weeks treatment , 2 weeks washout ) . 49 % of subjects were taking vitamin D metabolites . RESULTS Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods . RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus ( mean change -2.4 mg/dL vs. -2.3 mg/dL ) . RenaGel with calcium was associated with a small increase in serum calcium ( mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group , P = 0.09 ) that was not statistically significant . During the treatment phase , the reduction in PTH tended to be greater in the RenaGel with calcium group ( median change -67.0 vs. -22.5 pg/mL in RenaGel group , P = 0.07 ) . Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH ( median change -114.5 vs. -22 pg/mL in RenaGel group , P = 0.006 ) . Adverse events were seen with equal frequency in both groups , being generally mild in intensity , and rarely attributable to the drugs . CONCLUSION We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia . Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism OBJECTIVE This study was design ed to evaluate the efficacy of magnesium carbonate as a phosphate binder in hemodialysis patients . DESIGN This study was a prospect i ve , r and omized , open-label trial comparing magnesium carbonate/calcium carbonate versus calcium acetate as a sole phosphate binder . SETTING This study involved outpatient hemodialysis . PARTICIPANTS We recruited 30 stable hemodialysis patients without a history of frequent diarrhea . INTERVENTION After receiving informed consent , we r and omized patients 2:1 to magnesium carbonate versus calcium acetate . The dose of each binder was titrated to achieve the Kidney Disease Outcomes Quality Initiative ( K/DOQI ) phosphate target of < 5.5 mg/dL. MAIN OUTCOME MEASURE The efficacy-phase serum phosphorus concentration and the percentage of patients meeting K-DOQI targets for phosphorus , along with the daily elemental calcium intake , were the primary outcome measures . RESULTS Magnesium carbonate provided equal control of serum phosphorus ( 70.6 % of the magnebind group and 62.5 % of the calcium acetate group had their average serum phosphorus within the K-DOQI target during the efficacy phase ) , while significantly reducing daily elemental calcium ingestion from phosphate binders ( 908 + /- 24 vs. 1743 + /- 37 mg/day , P < .0001 ) . CONCLUSION Magnesium carbonate was generally well-tolerated in this selected patient population , and was effective in controlling serum phosphorus while reducing elemental calcium ingestion Elevated serum phosphorus is a predictable accompaniment of end-stage renal disease ( ESRD ) in the absence of dietary phosphate restriction or supplemental phosphate binders . The consequences of hyperphosphatemia include the development and progression of secondary hyperparathyroidism and a predisposition to metastatic calcification when the product of serum calcium and phosphorus ( Ca x PO4 ) is elevated . Both of these conditions may contribute to the substantial morbidity and mortality seen in patients with ESRD . We have analyzed the distribution of serum phosphorus in two large national , r and om , cross-sectional sample s of hemodialysis patients who have been receiving dialysis for at least 1 year . Data were obtained from two special studies of the United States Renal Data System , the Case Mix Adequacy Study ( 1990 ) and the Dialysis Morbidity and Mortality Study Wave 1 ( 1993 ) . The relative risk of death by serum phosphorus quintiles is described after adjusting for age at onset of ESRD , race , sex , smoking status , and the presence of diabetes , the acquired immunodeficiency syndrome , and /or neoplasm . Logistic regression analysis is then used to describe the demographic , comorbid , and laboratory parameters associated with high serum phosphorus . Serum phosphorus was similar in these two study population s and averaged 6.2 mg/dL. Ten percent of patients had levels greater than 9 mg/dL and at least 30 % of each group had serum phosphorus levels greater than 7 mg/dL. The adjusted relative risk of death by serum phosphorus level was not uniform across all quintiles , being constant below a level of 6.5 mg/dL and increasing significantly above this level . The relative risk of death for those with a serum phosphorus greater than 6.5 mg/dL was 1.27 relative to those with a serum phosphorus of 2.4 to 6.5 mg/dL. This increased risk was not diminished by statistical adjustment for coexisting medical conditions , delivered dose of dialysis , nutritional parameters , or markers of noncompliance . Evaluation of predictors of serum phosphorus greater than 6.5 mg/dL revealed in multivariate analysis that younger age at onset of ESRD , female sex , white race , diabetes , active smoking , and higher serum creatinine levels were all significant predictors . Analysis of serum calcium revealed no correlation with relative risk of death . The Ca x PO4 product , however , showed a mortality risk trend similar to that seen with serum phosphorus alone . Those in the highest quintile of the Ca x PO4 product ( > 72 mg2/dL2 ) had a relative mortality risk of 1.34 relative to those with products of 42 to 52 mg2/dL2 . The relative mortality risk by log parathyroid hormone ( PTH ) level was elevated for patients with higher levels , but the mortality risk associated with hyperphosphatemia was independent of PTH . For hemodialysis patients who have been receiving dialysis for at least 1 year , we conclude that a large percentage have a serum phosphorus level above 6.5 mg/dL and that this places them at increased risk of death . This increased risk is independent of PTH . The mechanism(s ) responsible for death is unknown , but may be related to an abnormally high Ca x PO4 product . Although mechanisms are not clearly established , this study supports the need for vigorous control of hyperphosphatemia to improve patient survival Background Hyperphosphatemia is a common complication in dialysis patients that can be treated by oral phosphate binders . We investigated the efficacy and safety of oral ferric citrate as a phosphate binder for Taiwanese patients with end stage renal disease and with hyperphosphatemia who were undergoing hemodialysis . Methods This was a prospect i ve , double-blind , placebo-controlled , r and omized trial carried out in 5 hospitals in Taiwan . Ferric citrate ( 4 or 6 g/day ) or placebo was administered for 56 days . Serum calcium , phosphorous levels , calcium × phosphorus product , serum ferritin level , transferrin saturation , and adverse events were recorded . Results A total of 166 patients completed the trial . The placebo group had relatively constant serum data . Serum phosphorus declined significantly in the 6 g/day group ( p < 0.05 for 4 and 8 weeks ) and the 4 g/day group ( p < 0.05 for 4 and 8 weeks ) . There were similar changes in the calcium × phosphorus product . The serum ferritin level increased significantly in the 6 g/day group ( p < 0.05 ) and the 4 g/day group ( p < 0.05 ) . There were similar changes in transferrin saturation . Most adverse events were mild to moderate and were comparable among the three groups . Conclusions A 56-day treatment with ferric citrate effectively controlled hyperphosphatemia and was well tolerated in maintenance hemodialysis patients . There were also moderate increases in serum ferritin and transferrin saturation BACKGROUND Vascular calcification is common and constitutes a prognostic marker of mortality in the hemodialysis population . Derangements of mineral metabolism may influence its development . The aim of this study is to prospect ively evaluate the association between bone remodeling disorders and progression of coronary artery calcification ( CAC ) in hemodialysis patients . STUDY DESIGN Cohort study nested within a r and omized controlled trial . SETTING & PARTICIPANTS 64 stable hemodialysis patients . PREDICTOR Bone-related laboratory parameters and bone histomorphometric characteristics at baseline and after 1 year of follow-up . OUTCOMES Progression of CAC assessed by means of coronary multislice tomography at baseline and after 1 year of follow-up . Baseline calcification score of 30 Agatston units or greater was defined as calcification . Change in calcification score of 15 % or greater was defined as progression . RESULTS Of 64 patients , 38 ( 60 % ) of the patients had CAC and 26 ( 40 % ) did not [ corrected ] . Participants without CAC at baseline were younger ( P < 0.001 ) , mainly men ( P = 0.03 ) and nonwhite ( P = 0.003 ) , and had lower serum osteoprotegerin levels ( P = 0.003 ) and higher trabecular bone volume ( P = 0.001 ) . Age ( P = 0.003 ; beta coefficient = 1.107 ; 95 % confidence interval [ CI ] , 1.036 to 1.183 ) and trabecular bone volume ( P = 0.006 ; beta coefficient = 0.828 ; 95 % CI , 0.723 to 0.948 ) were predictors for CAC development . Of 38 participants who had calcification at baseline , 26 ( 68 % ) had CAC progression in 1 year . Progressors had lower bone-specific alkaline phosphatase ( P = 0.03 ) and deoxypyridinoline levels ( P = 0.02 ) on follow-up , and low turnover was mainly diagnosed at the 12-month bone biopsy ( P = 0.04 ) . Low-turnover bone status at the 12-month bone biopsy was the only independent predictor for CAC progression ( P = 0.04 ; beta coefficient = 4.5 ; 95 % CI , 1.04 to 19.39 ) . According to bone histological examination , nonprogressors with initially high turnover ( n = 5 ) subsequently had decreased bone formation rate ( P = 0.03 ) , and those initially with low turnover ( n = 7 ) subsequently had increased bone formation rate ( P = 0.003 ) and osteoid volume ( P = 0.001 ) . LIMITATIONS Relatively small population , absence of patients with severe hyperparathyroidism , short observational period . CONCLUSIONS Lower trabecular bone volume was associated with CAC development , whereas improvement in bone turnover was associated with lower CAC progression in patients with high- and low-turnover bone disorders . Because CAC is implicated in cardiovascular mortality , bone derangements may constitute a modifiable mortality risk factor in hemodialysis patients BACKGROUND AND OBJECTIVES Levels of parathyroid hormone ( PTH ) and the phosphaturic hormone FGF23 , a fibroblast growth factor ( FGF ) family member , increase early in chronic kidney disease ( CKD ) before the occurrence of hyperphosphatemia . This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4 . DESIGN , SETTING , PARTICIPANTS , AND MEASUREMENTS Patients were r and omized to receive over a 6-wk period either calcium acetate ( n = 19 ) or sevelamer hydrochloride ( n = 21 ) . RESULTS At baseline , patients presented with elevated fractional excretion of phosphate , serum PTH , and FGF23 . During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate , but no change in serum calcium or serum phosphate . Significant changes were observed for FGF23 only in sevelamer-treated patients . CONCLUSIONS This study confirms the positive effects of early prescription of phosphate binders on PTH control . Prospect i ve and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient . We studied ferric citrate as a phosphorus binder and iron source . In this sequential , r and omized trial , 441 subjects on dialysis were r and omized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period , in which subjects on ferric citrate who completed the active control period were rer and omized to ferric citrate or placebo . The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period . A sequential gatekeeping strategy controlled study -wise type 1 error for serum ferritin , transferrin saturation , and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period . Ferric citrate controlled phosphorus compared with placebo , with a mean treatment difference of -2.2±0.2 mg/dl ( mean±SEM ) ( P<0.001 ) . Active control period phosphorus was similar between ferric citrate and active control , with comparable safety profiles . Subjects on ferric citrate achieved higher mean iron parameters ( ferritin=899±488 ng/ml [ mean±SD ] ; transferrin saturation=39%±17 % ) versus subjects on active control ( ferritin=628±367 ng/ml [ mean±SD ] ; transferrin saturation=30%±12 % ; P<0.001 for both ) . Subjects on ferric citrate received less intravenous elemental iron ( median=12.95 mg/wk ferric citrate ; 26.88 mg/wk active control ; P<0.001 ) and less erythropoietin-stimulating agent ( median epoetin-equivalent units per week : 5306 units/wk ferric citrate ; 6951 units/wk active control ; P=0.04 ) . Hemoglobin levels were statistically higher on ferric citrate . Thus , ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin The purpose of this study was to evaluate the effect of high-dose oral calcium on biochemical indices of bone formation , bone bisphosphonate clearance ( BBC ) and bone mineral content ( BMC ) of the distal forearm in patients undergoing hemodialysis . Eighteen patients agreed to participate and were r and omized in a double-blind manner to receive either 2 g elemental calcium/day ( n = 9 ) or placebo ( n = 9 ) for 6 months . Previous treatment with aluminum-containing phosphate binders was continued unchanged throughout the study . In the placebo group , serum alkaline phosphatase and osteocalcin tended to increase by 8.0 and 10.2 % , respectively , while BBC changed significantly by 49.5 % ( p < 0.05 ) . In the calcium group the opposite was observed with small decreases in alakline phosphatase and osteocalcin by 8.2 and 11.0 % , respectively , and no change in BBC . BMC decreased by 5.0 % in the placebo group , but increased by 5.2 % in the calcium group , result ing in a difference of 10.2 % ( p < 0.05 ) . The present study demonstrates that high-dose oral calcium tends to reduce bone turnover and seems able to prevent bone loss in hemodialyzed patients AIMS Fibroblast growth factor 23 ( FGF23 ) and Klotho are associated with vascular calcification and cardiovascular disease in dialysis patients . Sevelamer has been shown to reduce progression of vascular calcification . This study aim ed to determine the long-term effect of sevelamer treatment on serum FGF23 and Klotho levels in chronic haemodialysis ( HD ) patients . METHODS In the post-hoc analysis , we measured serum FGF23 , Klotho and other biochemical factors ( Ca , P , i-PTH , hsCRP , LDL-C ) in 50 haemodialysis patients , who completed a 48-week , open-Label , controlled r and omized parallel-group study . Twenty-three patients received sevelamer and 27 patients received calcium carbonate . RESULTS After 48-week sevelamer treatment , there were significant changes with lower LDL-C ( from 2.82 ± 0.78 to 1.65 ± 0.53 mmol/L , P = 0.000 ) , lower FGF23 ( from 2465.97 ( 2568.88 ) to 795.61 ( 1098.39 ) , P = 0.000 ) and higher s-Klotho levels ( from 189.35 ( 161.88 ) to 252.94 ( 517.80 ) pg/mL , P = 0.000 ) . In calcium carbonate group , there were no significant changes of LDL-C and FGF23 , but with a borderline significant increase of s-Klotho level ( from 142.34 ( 265.24 ) to 188.57 ( 252.38 ) pg/mL , P = 0.054 ) . Multivariate analysis showed that FGF23 decrement was associated with sevelamer treatment ( β = -0.277 , P = 0.005 ) , change of serum phosphate ( β = 0.609 , P = 0.000 ) and calcium levels ( β = 0.635 , P = 0.000 ) . The increase of serum Klotho was associated with the decrease of serum phosphate ( β = 0.490 , P = 0.019 ) . CONCLUSION Maintenance HD patients had lower serum FGF23 levels , accompanied with significantly increased serum Klotho levels , after 48-week sevelamer treatment . The FGF23 decrement was associated with sevelamer use , the change of serum phosphate and calcium levels . The serum Klotho increment was proportional to the phosphate-lowering power of the binders Dietary phosphate restriction and the oral administration of calcium and aluminum salts have been the principal means of controlling hyperphosphatemia in individuals with end-stage renal disease over the past decade . Although relatively well-tolerated , a large fraction of patients treated with calcium develop hypercalcemia , particularly when administered concurrently with calcitriol , despite a lowering of the dialysate calcium concentration . We evaluated the efficacy of cross-linked poly[allylamine hydrochloride ] ( RenaGel ; Geltex Pharmaceuticals , Waltham , MA ) , a nonabsorbable calcium- and aluminum-free phosphate binder , in a r and omized , placebo-controlled , double-blind trial of 36 maintenance hemodialysis patients followed over an 8-week period . RenaGel was found to be as effective as calcium carbonate or acetate as a phosphate binder . The reduction in serum phosphorus was significantly greater after 2 weeks of treatment with RenaGel ( 6.6 + /- 2.1 mg/dL to 5.4 + /- 1.5 mg/dL ) compared with placebo ( 7.0 + /- 2.1 mg/dL to 7.2 + /- 2.4 mg/dL ; P = 0.037 ) . There was no significant change in serum calcium concentration in either treatment group . The total serum cholesterol and low-density lipoprotein cholesterol fraction were significantly reduced in RenaGel-treated patients compared with placebo-treated patients ( P = 0.013 and P = 0.003 , respectively ) without a concomitant reduction in high-density lipoprotein cholesterol ( P = 0.93 ) . There was no difference among recipients of RenaGel and placebo in terms of adverse events . RenaGel is a safe and effective alternative to oral calcium for the management of hyperphosphatemia in end-stage renal disease AIMS Sevelamer carbonate is an anion exchange resin with the same polymeric structure as sevelamer hydrochloride in which carbonate replaces chloride as the anion . The study investigated the effects of sevelamer carbonate and sevelamer hydrochloride on serum phosphorus , lipids and bicarbonate levels in hemodialysis patients . MATERIAL S AND METHODS This was a double-blind , r and omized , crossover study . 79 hemodialysis patients were r and omly assigned to either sevelamer carbonate or sevelamer hydrochloride for 8 weeks followed by a crossover to the other regimen for an additional 8 weeks of treatment . RESULTS The mean serum phosphorus was 4.6+/-0.9 and 4.7+/-0.9 mg/dl during sevelamer carbonate and sevelamer hydrochloride treatment , respectively . Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus , the geometric least square mean ratio was 0.99 ( 90 % CI , 0.95 - 1.03 ) . Mean total and LDL cholesterol were 144.0+/-33.9 and 59.5+/-24.9 mg/dl , respectively , during sevelamer carbonate treatment and 139.0+/-33.6 and 56.0+/-23.3 mg/dl , respectively , during sevelamer hydrochloride treatment . Serum bicarbonate levels increased by 1.3+/-4.1 mEq/l during sevelamer carbonate treatment . There were fewer gastrointestinal adverse events with sevelamer carbonate . CONCLUSIONS Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus and serum bicarbonate levels increased with sevelamer carbonate . Lipid profiles for both were well-below the levels suggested by KDOQI . Sevelamer carbonate may have advantages over sevelamer hydrochloride in the treatment of hyperphosphatemia in hemodialysis patients BACKGROUND Hyperphosphatemia is common in end-stage renal disease patients . Objective of this study is to compare the hypercalcaemic effect and phosphate binding power of calcium acetate and calcium carbonate in end-stage renal disease patients on maintenance haemodialysis . METHODS This r and omised control trial was conducted in four phases with calcium acetate or calcium carbonate . Sixty-four patients on haemodialysis were r and omly divided into 2 groups . After a washout period of 2 weeks , each group was given calcium acetate or calcium carbonate for 2 months . After another washout period the patients were crossed over and again received these drugs for 2 months . Serum Calcium , phosphate , and albumin were analysed on Selectra E auto analyser at completion of each phase of study . Hypercalcaemic effect was defined as serum calcium > 2.54 mmol/l , and phosphate binding power as serum phosphate < 1.61 mmol/l . RESULTS Forty-one patients completed the study . Though lower dose of calcium acetate was used , it result ed in equally good control of hyperphosphatemia as compared with calcium carbonate therapy [ 1.37 mmol/l ( SD 0.33 ) vs. 1.46 mmol/l ( SD 0.34 ) , p = 0.16 ] . Incidence of hypercalcaemia was higher with calcium carbonate therapy ( 2.73 + /- 0.67 mmol/l vs. 2.32 + /- 0.28 mmol/l , p < 0.01 ) . Both drugs were well tolerated , but patients more frequently complained of muscle cramps while taking calcium acetate . CONCLUSIONS It is concluded that calcium acetate has similar effect on serum phosphate levels as compared to calcium carbonate in patients on maintenance haemodialysis . However , calcium acetate results in lesser frequency of hypercalcaemia as compared to calcium carbonate . Tolerance to both drugs was similar , though patients complained of more muscle cramps while taking calcium acetate Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease . Bixalomer is a nonabsorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract . This study compared the efficacy and safety of bixalomer versus sevelamer hydrochloride for controlling hyperphosphatemia in hemodialysis patients . This was a multicenter , r and omized open-label , non-inferiority study . The primary endpoint was serum phosphate on completion of treatment . Administration of bixalomer was started at 1.5 g/day and adjusted to a maximum of 7.5 g/day depending on the serum phosphate level . Sevelamer hydrochloride was started at 3.0 or 6.0 g/day and adjusted to a maximum of 9.0 g/day . Treatment was continued for 12 weeks . Fifty-five patients were r and omized to each treatment group . After 12 weeks , the baseline adjusted mean serum phosphate level was 5.87 mg/dL in the bixalomer group and 5.55 mg/dL in the sevelamer group , with a difference of 0.31 mg/dL and 95 % confidence interval ( CI ) of [ -0.13 to 0.76 ] . The upper limit of the 95%CI for the difference of the mean serum phosphate level between the two groups was < 1.0 mg/dL , which was the non-inferiority margin in this study . Thus , non-inferiority of bixalomer to sevelamer was confirmed . The incidence of adverse events was lower in the bixalomer group , and bixalomer did not promote acidosis . Bixalomer achieved a similar reduction of serum phosphate to sevelamer , while causing fewer adverse reactions . Consequently , the usefulness of bixalomer for treating hyperphosphatemia was confirmed INTRODUCTION The hyperphosphatemia , hypocalcemia and low calcitriol levels are pathogenic factors for secondary hyperparathyroidism in chronic renal failure . The phosphorus control is essential to prevent secondary hyperparathyroidism . There are not comparatives studies to test the efficacy of control of phosphorus binders in predialysis patients . AIM To compare the efficacy of calcium carbonate vs calcium acetate as phosphate binder in predialysis patients . MATERIAL AND METHODS The present study includes 28 patients with chronic renal failure ( mean clearance of creatinine 21 ml/min ) . Patients were separated into two groups : Group 1 : ( n = 14 ) received calcium carbonate 2,500 mg/day ( 1,000 mg of calcium ) ; Group 2 : ( n = 14 ) receives calcium acetate 1,000 mg ( 254 mg of calcium ) . Calcium and phosphorus were determined every 4 months ; i-PTH , alkaline phosphatase and clearance of creatinine were determined every six months . RESULTS Both groups were comparable regarding age , renal function , calcium , phosphorus , alkaline phosphatase and i-PTH on basal situation and the end of study were not different . The serum calcium increased , not significantly , in the calcium carbonate group ( group 1 ) [ from 9.2 to 9.8 mg/dl ( p = 0.05 ) ] , however it was not modified in the calcium acetate group ( group 2 ) . The serum phosphorus decreased significantly ( p < 0.05 ) in both groups , independently of the calcium levels . Alkaline phosphatase and i-PTH not was modified during the study period . CONCLUSIONS 1 ) Both calcium carbonate and calcium acetate are similarly effective as phosphate binder . 2 ) The carbonate group required four fold greater doses of calcium that acetate group . 3 ) The calcium acetate has less hypercalcemic effect than calcium carbonate Background SBR759 , an iron (III)-based oral phosphate binder , was developed for the treatment of hyperphosphataemia in chronic kidney disease stage V patients receiving maintenance renal replacement therapy ( RRT ) . Serum phosphate-lowering efficacy and dose response of SBR759 ( 3- , 6- , 9- and 12-g/day doses ) were compared with placebo . Methods Japanese patients with hyperphosphataemia ( P ≥ 5.5 mg/dL [ ≥1.78 mmol/L ] ) receiving maintenance RRT ( N = 63 ) were r and omised to receive either SBR759 ( 3- , 6- , 9- , 12-g/day dose ) or placebo ( 12-g/day dose ) for 4 weeks . The primary endpoint was change from baseline in 72-h post-dialysis serum phosphate levels at week 4 for different doses of SBR759 versus placebo . Secondary endpoints were change from baseline in serum phosphate levels and dose-dependent efficacy of SBR759 during the 4-week treatment period . Results SBR759 showed significant reduction in serum phosphate levels compared with placebo at week 4 , demonstrating a significant linear dose response ( P < 0.001 ) . Incidence of adverse events was comparable between the SBR759 treatment groups ( 7/13 and 5/12 in the 3- and 12-g/day groups , respectively , and 8/13 in the 6- and 9-g/day groups ) and was 6/12 in the placebo group . Discoloured faeces and diarrhoea were the most frequently reported adverse events . Two serious adverse events were reported — one in the SBR759 3-g/day group ( 1/13 , skin ulcer ) and one in the SBR759 12-g/day group ( 1/12 , arthralgia ) . Conclusions SBR759 showed significant phosphate-lowering efficacy and dose-dependent response compared with placebo in patients with chronic kidney disease receiving RRT Bone mineral content , estimated by single-photon absorptiometry of the forearm , serum values of intact parathyroid hormone ( PTH(1 - 84 ] , osteocalcin , alkaline phosphatase , 1,25-dihydroxycholecalciferol ( 1,25(OH)2D3 ) , and aluminium were determined during treatment with calcium carbonate ( CaCO3 ) or aluminium hydroxide ( Al(OH)3 ) in 11 dialysis patients participating in a r and omised cross-over study . Each treatment period lasted 6 months . Serum phosphorus was maintained in the range 1.5 - 2.0 mmol/l . During Al(OH)3 treatment bone mineral content ( BMC ) decreased by 11 % per half-year ( mean ) , but only by 3 % per half-year during CaCO3 treatment ( P less than 0.05 ) . Comparing the CaCO3 and Al(OH)3 periods the following differences were found : serum calcium increased during CaCO3 treatment , PTH(1 - 84 ) decreased ( 79 % of initial values during CaCO3 versus 196 % during Al(OH)3 , mean area under curve , P less than 0.05 ) , osteocalcin decreased ( 89 % versus 117 % , P less than 0.01 ) , alkaline phosphatase decreased ( 92 % versus 116 % , P less than 0.05 ) , and aluminium decreased ( 56 % versus 189 % , P less than 0.05 ) . 1,25(OH)2D3 remained unchanged in both periods . No increase in soft-tissue calcification was demonstrated on X-ray of the shoulders in any of the periods . Thus , CaCO3 treatment seems to slow down loss of bone mineral content , and using CaCO3 as phosphate binder may have a more beneficial effect on the progression of uraemic bone disease than Al(OH)3 due to the reduction of hyperparathyroidism and bone turnover BACKGROUND AND OBJECTIVES Lanthanum carbonate ( FOSRENOL , Shire Pharmaceuticals ) is an effective noncalcium , nonresin phosphate binder for the control of hyperphosphatemia in chronic kidney disease ( CKD ) stage 5 patients undergoing dialysis . DESIGN , SETTING , PARTICIPANTS AND MEASUREMENTS A Phase 2 , r and omized , double-blind , placebo-controlled trial evaluating the efficacy and safety of lanthanum carbonate in CKD stage 3 and 4 patients . Of 281 patients screened , 121 were r and omized ( 2:1 ) to lanthanum carbonate or placebo ( 80 versus 41 ) . The modified intent-to-treat population included 90 patients ( 56 versus 34 ) ; 71 ( 43 versus 28 ) completed the study . After run-in , when any current phosphate binders were discontinued and dietary counseling reinforced , patients with serum phosphorus > 4.6 mg/dl received lanthanum carbonate ( titrated up to 3000 mg/d ) or matching placebo for 8 wk . RESULTS At the end of treatment , 25 ( 44.6 % ) versus nine ( 26.5 % ) patients had serum phosphorus < or = 4.6 mg/dl ( difference 18.1 % , P = 0.12 ) in the lanthanum carbonate and placebo groups , respectively . Statistically significant differences were observed between groups in change from baseline to end of treatment for serum phosphorus ( P = 0.02 ) , intact parathyroid hormone ( P = 0.02 ) , and urinary phosphorus excretion ( P = 0.04 ) . The safety profile and tolerability of lanthanum carbonate were similar to that of placebo . CONCLUSIONS Because < 1 % of phosphorus is in the extracellular fluid , serum measurements may not accurately reflect total body burden in patients with CKD stages 3 and 4 . However , lanthanum carbonate is an effective phosphate binder in this patient population , with a safety profile and tolerability similar to that of placebo OBJECTIVE Gout affects a large fraction of persons with advanced chronic kidney disease , and hyperuricemia may increase the risk of cardiovascular disease . Several hypouricemic agents are contraindicated in patients with end-stage renal disease . Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract . Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid , another organic anion . We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term , r and omized , clinical trial comparing sevelamer with calcium-based phosphate binders . METHODS Two hundred subjects undergoing maintenance hemodialysis were r and omly assigned to receive either sevelamer or calcium-based phosphorus binders in an international , multicenter , clinical trial . Data on baseline and end-of- study uric acid concentrations were available in 169 subjects ( 85 % ) ; the change in uric acid concentration from baseline to the end of the study was the outcome of interest . RESULTS Baseline clinical characteristics , including mean uric acid concentrations , were similar in subjects r and omly assigned to receive sevelamer and calcium-based phosphate binders . The mean change in uric acid concentration ( from baseline to the end of the study ) was significantly larger in sevelamer-treated subjects ( -0.64 mg/dl versus -0.26 mg/dl ; P = 0.03 ) . The adjusted mean change in uric acid concentration was more pronounced when the effects of age , sex , diabetes , vintage ( time since initiation of dialysis ) , dialysis dose , and changes in blood urea nitrogen and bicarbonate concentrations were considered ( -0.72 mg/dl versus -0.15 mg/dl ; P = 0.001 ) . Twenty-three percent of sevelamer-treated subjects experienced a study -related reduction in the concentration of uric acid equal to -1.5 mg/dl or more , compared with 10 % of calcium-treated subjects ( P = 0.02 ) . CONCLUSION In a r and omized clinical trial comparing sevelamer and calcium-based phosphate binders , treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations BACKGROUND AND OBJECTIVES Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification ( CAC ) that may contribute to high mortality of dialysis patients . CAC has been found in patients in early stages of nondialysis-dependent CKD . In this population , no study has evaluated the potential role of phosphorus binders on mortality . This study aim ed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients r and omized to different phosphate binders ; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This is a r and omized , multicenter , nonblinded pilot study . Consecutive out patients ( n=212 ; stage 3 - 4 CKD ) were r and omized to either sevelamer ( n=107 ) or calcium carbonate ( n=105 ) . Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3 - 4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD . The CAC score was assessed by computed tomography at study entry and after 6 , 12 , 18 , and 24 months . All-cause mortality , dialysis inception , and the composite end point were recorded for up to 36 months . RESULTS In patients r and omized to sevelamer , all-cause mortality and the composite end point were lower ; a nonsignificant trend was noted for dialysis inception . CONCLUSIONS Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception . Larger studies are needed to confirm these results Sucralfate has been reported to reduce serum phosphate concentration in patients with chronic renal failure . To evaluate whether sucralfate could be used to treat hyperphosphatemia secondary to chronic renal failure and whether this treatment result ed in a reduced exposure to aluminum , an open-label crossover study was design ed to determine the efficacy , relative potency , safety , and cost of sucralfate v aluminum hydroxide . Of the 21 hemodialysis patients completing both phases of the crossover study , serum phosphate could be maintained below 4.5 mg/dL ( 1.45 mmol/L ) in 16 with sucralfate and in 14 with aluminum hydroxide . The 16 patients controlled on sucralfate consumed 1,694 + /- 190 mg/d of aluminum to maintain a serum phosphate concentration of 3.91 + /- 0.17 mg/dL ( 1.27 + /- 0.05 mmol/L ) compared with the 14 patients controlled on aluminum hydroxide with an aluminum intake of 2,678 + /- 294 mg/d ( P less than 0.025 ) and a serum phosphate concentration of 3.94 + /- 0.13 mg/dL ( 1.27 + /- 0.04 mmol/L ) . Thus sucralfate was an effective , albeit expensive , alternative to aluminum hydroxide for the treatment of hyperphosphatemia associated with chronic renal failure . Although the difference in aluminum intake was significant , use of sucralfate did not result in lower serum aluminum concentrations BACKGROUND Previous clinical trials showed that progression of coronary artery calcification ( CAC ) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders . Because sevelamer decreases low-density lipoprotein cholesterol ( LDL-C ) levels , we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients . STUDY DESIGN R and omized , controlled , open-label , noninferiority trial with an upper bound for the noninferiority margin of 1.8 . SETTING & PARTICIPANTS 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL , LDL-C levels greater than 80 mg/dL , and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography . INTERVENTIONS 103 patients were r and omly assigned to calcium acetate , and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups . OUTCOMES & MEASUREMENTS The primary end point was change in CAC score assessed by means of electron-beam computed tomography . RESULTS After 12 months , mean serum LDL-C levels decreased to 68.8 + /- 22.0 mg/dL in the calcium-acetate group and 62.4 + /- 23.0 mg/dL in the sevelamer group ( P = 0.3 ) . Geometric mean increases in CAC scores were 35 % in the calcium-acetate group and 39 % in the sevelamer group , with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 ( 95 % confidence interval , 0.851 to 1.161 ) . LIMITATIONS Treatment assignment was not blinded . The 1.8 a priori margin is large , CAC is a surrogate outcome , duration of treatment was short , and dropout rate was high . CONCLUSIONS With intensive lowering of LDL-C levels for 1 year , hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC The first reported double-blind cross-over comparison between the phosphorus binders calcium carbonate and calcium acetate was undertaken in 15 stable patients on chronic maintenance haemodialysis . Detailed registration of diet and analysis of the protein catabolic rate suggested an unchanged phosphorus intake during the study . It was found that predialytic serum phosphate concentration was significantly decreased by 0.11 mmol/l ( 0.34 mg/dl ) ( P = 0.021 , 95 % confidence limits 0.02 - 0.21 mmol/l ; 0.06 - 0.65 mg/dl ) during calcium acetate treatment . The calcium phosphate product was insignificantly decreased during treatment with calcium acetate whereas we could not exclude the possibility that calcium concentration had increased BACKGROUND AND OBJECTIVES This phase II study tested the safety and efficacy of fermagate , a calcium-free iron and magnesium hydroxycarbonate binder , for treating hyperphosphatemia in hemodialysis patients . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A r and omized , double-blind , three-arm , parallel-group study compared two doses of fermagate ( 1 g three times daily or 2 g three times daily with placebo ) . Sixty-three patients who had been on a stable hemodialysis regimen for > or =3 mo were r and omized to the treatment phase . Study medication was administered three times daily just before meals for 21 d. The primary endpoint was reduction in serum phosphate over this period . RESULTS In the intention-to-treat analysis , mean baseline serum phosphate was 2.16 mmol/L. The fermagate 1- and 2-g three-times-daily treatment arms were associated with statistical reductions in mean serum phosphate to 1.71 and 1.47 mmol/L , respectively . Adverse event ( AE ) incidence in the 1-g fermagate arm was statistically comparable to the placebo group . The 2-g arm was associated with a statistically higher number of patients reporting AEs than the 1-g arm , particularly gastrointestinal AEs , as well as a higher number of discontinuations , complicating interpretation of this dose 's efficacy . Both doses were associated with elevations of prehemodialysis serum magnesium levels . CONCLUSIONS The efficacy and tolerability of fermagate were dose dependent . Fermagate showed promising efficacy in the treatment of hyperphosphatemia in chronic hemodialysis patients as compared with placebo in this initial phase II study . The optimal balance between efficacy and tolerability needs to be determined from future dose-titration studies , or fixed-dose comparisons of more doses Background and Objectives : Coronary artery calcification ( CAC ) is associated with future cardiovascular events and /or death of patients on hemodialysis ( HD ) . We investigated whether progression of CAC in patients on HD could be delayed by switching from a calcium (Ca)-based phosphate ( Pi ) binder to lanthanum carbonate . Design , Setting , Participants , and Measurements : The CAC scores were evaluated at study enrollment and after 6 months in 52 patients on HD using calcium carbonate ( CC ) as a Pi binder . Patients were r and omly divided into 2 groups assigned to receive either CC or lanthanum carbonate ( LC ) , and the CAC scores were evaluated after a 6-month treatment period . Progression of CAC was assessed , as were serum levels of Ca , Pi , and intact parathyroid hormone ( iPTH ) . Results : Forty-two patients completed the study ( 23 receiving CC and 19 receiving LC ) . In the 6 months prior to r and omization , all patients were treated with CC . During this 6-month period , the CAC scores increased significantly in all 42 patients . Once r and omized , there was significantly less progression in the group treated with LC than with CC . Changes in CAC scores from 6 to 12 months were significantly smaller in the LC group than the CC group ( −288.9 ± 1176.4 vs 107.1 ± 559.6 , P = .036 ) , and percentage changes were also significantly different ( −6.4 % vs 41.2 % , P = .024 ) . Serum Ca , Pi , and iPTH levels were similar in both groups during the study period . Conclusions : This pilot study suggested that LC delayed progression of CAC in patients on HD compared with CC BACKGROUND Vascular calcification ( VC ) contributes to cardiovascular disease in haemodialysis ( HD ) patients . Few controlled studies have addressed interventions to reduce VC but non-calcium-based phosphate binders may be beneficial . No published r and omized study to date has assessed the effect of lanthanum carbonate ( LC ) on VC progression . METHODS We conducted a pilot r and omized controlled trial to determine the effect of LC on VC . Forty-five HD patients were r and omized to either LC or calcium carbonate ( CC ) . Primary outcome was change in aortic VC after 18 months . Secondary outcomes included superficial femoral artery ( SFA ) VC , bone mineral density ( BMD ) of lumbar spine and serum markers of mineral metabolism . At baseline , 6 and 18 month computed tomography was performed to measure VC and BMD . A r and om effect linear regression model was performed to assess differences . RESULTS Thirty patients completed the study ( 17 LC , 13 CC ) ; baseline median age 58 years , 38 % diabetic , 64 % male . Ninety-three per cent had aortic VC at commencement and 87 % showed progression . At 18 months , there was significantly less aortic VC progression with LC than CC ( adjusted difference -98.1 ( -149.4 , -46.8 ) Hounsfield units ( HU ) , P < 0.001 ) . There was also a non-significant reduction with LC in left SFA VC ( -25.8 ( -67.7 , 16.1 ) HU , P = 0.2 ) and right SFA VC ( -35.9 ( -77.8 , 5.9 ) HU , P = 0.09 ) . There was no difference in lumbar spine BMD and serum phosphate , calcium and parathyroid hormone levels between groups . Limitations to the study include small sample size and loss to follow up . CONCLUSIONS Lanthanum carbonate was associated with reduced progression of aortic calcification compared with CC in HD patients over 18 months BACKGROUND AND OBJECTIVES A secondary analysis of the Dialysis Clinical Outcomes Revisited ( DCOR ) trial suggested that sevelamer reduced hospitalizations relative to calcium-based phosphate binders . However , whether changed medical costs associated with reduced hospitalizations or other medical services offset the higher cost of sevelamer is unclear . This DCOR secondary analysis aim ed to ( 1 ) evaluate Medicare total , inpatient , outpatient , skilled nursing facility , and other costs in sevelamer-treated versus calcium-treated patients ; ( 2 ) examine Medicare costs in specific categories to determine cost drivers ; and ( 3 ) estimate and incorporate sevelamer and calcium binder costs . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS DCOR trial participants were linked to the Centers for Medicare & Medicaid Services ESRD data base . Medicare costs for 1895 dosed Medicare- primary -payer participants were evaluated . Phosphate binder costs were incorporated . Costs were indexed to 2001 ( study base year ) . Sensitivity analyses were performed with r and omized participants , two follow-up periods , and 2004 as index year . RESULTS Inflation-adjusted Medicare per member per month ( PMPM ) costs were lower for sevelamer-treated than for calcium-treated participants by a mean differential of $ 199 PMPM ( mean , $ 5236 versus $ 5435 ; median , $ 4653 versus $ 4933 ) , mainly because of lower inpatient costs for the sevelamer group ( mean , $ 1461 versus $ 1644 ; median , $ 909 versus $ 1144 ) . However , after phosphate binder costs were incorporated , costs trended lower for calcium-treated than for sevelamer-treated patients ( differential -$81 , 95 % confidence interval -$321 to $ 157 PMPM , using average wholesale price ; -$25 , -$256 to $ 213 PMPM , using wholesale acquisition cost ) . CONCLUSIONS Sevelamer reduced inpatient Medicare costs compared with calcium binders . However , when binder costs were added , overall PMPM costs favored calcium-treated over sevelamer-treated participants A study has cl aim ed that at an equal elemental calcium dose , CaCO3 was not less but equally as efficient in controlling predialysis hyperphosphatemia as calcium acetate , provided both calcium salts were ingested 5 min before meals instead of during meals because the higher acidity of the fasting gastric juice would allow for better dissociation of CaCO3 . However , this study did not directly demonstrate that the efficiency of CaCO3 in controlling hyperphosphatemia was actually greater when it was administered before a meal than during a meal . To examine this point , we performed a 3 month r and omized crossover trial in 12 reliable and stable patients maintained on chronic hemodialysis . Their plasma concentrations of calcium , protein , phosphate , bicarbonate , urea , and creatinine were measured before the first dialysis of each week and the amount of intact parathyroid hormone ( PTH ) at the beginning and at the end of each of the 3 months . Comparison of the plasma concentrations measured during the 2 modes of administration showed no significant differences in creatinine , urea , bicarbonate , or intact PTH . The mean ( + /-SD ) plasma concentration of PO4 was not significantly lower ( 1.88+/-0.50 vs. 1.74+/-0.41 mM ) whereas the corrected level of plasma Ca was significantly lower ( 2.30+/-0.17 vs. 2.38+/-0.16 mM ; p < 0.04 ) when CaCO3 was given before meals than during meals . In conclusion , the administration of CaCO3 before a meal does not increase its efficiency in controlling hyperphosphatemia because the level of plasma PO4 was actually slightly higher with this timing of administration whereas the comparison of the creatinine and urea levels suggested a stability of phosphate intake and the comparison of the PTH and bicarbonate levels suggested the stability of osteolysis and of the transcellular membrane shift of phosphate . Also , administration of CaCO3 before a meal is associated with significantly lower plasma corrected calcium , suggesting less absorption of calcium , which may be an advantage but only in hypercalcemic patients . There is no reason other than the prevention of its hypercalcemic effect to recommend the administration of CaCO3 just before meals rather than during meals BACKGROUND Hyperphosphataemia is a known independent risk factor for cardiovascular mortality . The objective of the study was to compare the effects of two phosphate binders , sevelamer carbonate and calcium carbonate on endothelial function ( EF ) and inflammation in patients on peritoneal dialysis ( PD ) with Type 2 diabetes mellitus ( T2DM ) . METHODS Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks . After a second two-week washout period , subjects crossed over to either of the alternate treatments for another eight weeks . At the beginning and end of each treatment , biomarkers of EF , pro-inflammatory cytokines , serum albumin , calcium , phosphate and lipids were measured . RESULTS Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate . Amongst the EF and pro-inflammatory biomarkers , sevelamer carbonate decreased serum endothelin-1 , plasminogen activator inhibitor-1 , C-reactive protein and interleukin-6 . Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF . CONCLUSIONS Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD BACKGROUND Patients receiving dialysis therapy for end-stage kidney failure have a high cardiovascular mortality that can only be partially explained by traditional risk factors . METHODS This study was a post hoc analysis of a prospect ively gathered data set from a r and omized trial comparing outcomes in new haemodialysis patients treated with sevelamer or calcium-containing phosphate binders . Patients were followed from the time of enrollment until death or censor on 31 December 2005 . Median follow-up was 3.6 years . Demographics , cardiovascular risk factors , laboratory data , medication use and severity of vascular calcification were available at baseline and over the first 18 months of dialysis . RESULTS Baseline predictors of mortality included age , creatinine , heart rate , iPTH , C-reactive protein ( CRP ) , coronary and aortic calcium scores and the presence of aortic valve calcification . Over the first 18 months , averages of diastolic blood pressure , BUN , creatinine , albumin , phosphorus , iPTH and CRP were all significantly different between survivors and non-survivors . A stepwise multivariable adjusted Cox regression model demonstrated that low BUN and albumin and high CRP along with the use of calcium-containing phosphate binders ( rather than sevelamer ) were the strongest predictors of mortality in patients new to haemodialysis . CONCLUSIONS These findings suggest that non-traditional risk factors , such as inflammation and malnutrition measured during the first 18 months of dialysis , are important determinates of survival in new dialysis patients . In addition , the unique risk factor for dialysis patients , the use of calcium-containing phosphate binders , was associated with a higher mortality rate in patients new to dialysis OBJECTIVE To assess phosphate-binding efficacy of a new food product , bread with unusually high calcium content ( Ca-bread ) . DESIGN AND SETTING A r and omized parallel group trial in the university hospital outpatient dialysis unit . PATIENTS Fifty-three r and omly selected uremic patients who met the following inclusion criteria : ( 1 ) required maintenance hemodialysis treatment , ( 2 ) were not to receive vitamin D throughout the study , ( 3 ) were nondiabetic , and ( 4 ) were diagnosed with hyperphosphatemia . INTERVENTION Fifty-three patients were r and omized into 2 groups : control group ( n = 26 ) , which received calcium acetate as a phosphate binder throughout the study , and Ca-bread group ( n = 27 ) , which , after a 2-week washout period , received Ca-bread containing 2.5 % of elemental calcium ( by weight ) , which served as a phosphate binder . Bread was made using wheat flour , calcium carbonate , and fermented buttermilk . The amount of elemental calcium used as a phosphate binder was similar in both groups . Observation of both groups lasted 14 weeks . RESULTS Mean serum phosphate concentration at r and omization was 2.11 + /- 0.14 mmol/L in the control group and 2.20 + /- 0.13 mmol/L in the Ca-bread group . Mean serum calcium concentration at r and omization was 2.12 + /- 0.21 mmol/L in the control group and 2.14 + /- 0.11 mmol/L in the Ca-bread group . The Ca-bread group patients ' predialysis phosphate concentration decreased to a mean of 1.67 + /- 0.18 mmol/L ( P < .05 ) , and their mean calcium concentration increased to 2.27 + /- 0.11 mmol/L ( P = NS ) . In the control group , neither value changed significantly from the original readings . After the hemodialysis session , the mean serum calcium concentration in the control group and the Ca-bread group increased by 7.5 % and 7.9 % , respectively ( P = NS ) . Mean phosphate concentration simultaneously decreased to nearly 1/2 its original predialysis value in both groups . Ca-bread group patients saw a decrease in the mean phosphate concentration ( from predialysis to postdialysis values ) that was 13.8 % greater than that of the control group ( P = NS ) . CONCLUSION A new form of calcium-containing phosphate binder was developed : Ca-bread with an elemental calcium content of 2.5 % . Ca-bread allows for effective amelioration of hyperphosphatemia without inducing hypercalcemia . Furthermore , patient compliance may increase if hyperphosphatemia can be treated by consuming bread with an elevated calcium content 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 Background The recent multicenter , r and omized , open-label INDEPENDENT study demonstrated that sevelamer improves survival in new to hemodialysis ( HD ) patients compared with calcium carbonate . The objective of this study was to determine the cost-effectiveness of sevelamer versus calcium carbonate for patients new to HD , using patient-level data from the INDEPENDENT study . Study design Cost-effectiveness analysis . Setting and population Adult patients new to HD in Italy . Model , perspective , timeframeA patient-level cost-effectiveness analysis was conducted from the perspective of the Servizio Sanitario Nazionale , Italy ’s national health service . The analysis was conducted for a 3-year time horizon . The cost of dialysis was excluded from the base case analysis . InterventionS evelamer was compared to calcium carbonate . Outcomes Total life years ( LYs ) , total costs , and the incremental cost per LY gained were calculated . Bootstrapping was used to estimate confidence intervals around LYs , costs , and cost-effectiveness and to calculate the cost-effectiveness acceptability curve . Results Sevelamer was associated with a gain of 0.26 in LYs compared to calcium carbonate , over the 3-year time horizon . Total drug costs were € 3,282 higher for sevelamer versus calcium carbonate , while total hospitalization costs were € 2,020 lower for sevelamer versus calcium carbonate . The total incremental cost of sevelamer versus calcium carbonate was € 1,262 , result ing in a cost per LY gained of € 4,897 . The bootstrap analysis demonstrated that sevelamer was cost effective compared with calcium carbonate in 99.4 % of 10,000 bootstrap replicates , assuming a willingness-to-pay threshold of € 20,000 per LY gained . Limitations Data on hospitalizations was taken from a post hoc retrospective chart review of the patients included in the INDEPENDENT study . Patient quality of life or health utility was not included in the analysis . Conclusions Sevelamer is a cost-effective alternative to calcium carbonate for the first-line treatment of hyperphosphatemia in new to HD patients in Italy 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 BACKGROUND AND OBJECTIVES Hyperphosphatemia and sub clinical endotoxemia are important sources of inflammation in HD . Proinflammatory cytokines are strong correlates of soluble CD14 ( sCD14 ) concentrations , an independent predictor of mortality in this population . We evaluated the effects of calcium acetate and sevelamer hydrochloride on serum inflammatory profile , endotoxin concentrations , and sCD14 levels in HD patients . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Prospect i ve , r and omized , open-label , parallel design trial . Fifty-nine stable HD patients , 30 receiving sevelamer , and 29 receiving calcium acetate were evaluated . Serum levels of inflammatory parameters ( high-sensitivity C-reactive protein [ hs-CRP ] , TNF-α , interleukin (IL)-1 , -6 , -10 , and -18 ) , as well as endotoxin and sCD14 concentrations , were measured at baseline and after 3 months of therapy . RESULTS Serum IL-6 increased in patients receiving calcium acetate , whereas hs-CRP and IL-6 significantly decreased in subjects treated with sevelamer , with IL-10 experiencing a trend to increase ( P = 0.052 ) . Serum endotoxin and sCD14 levels did not change after treatment with calcium acetate . However , these parameters decreased by 22.6 % and 15.2 % , respectively ( P < 0.01 ) , in patients receiving sevelamer . Multiple regression analysis showed that variation in serum endotoxin concentrations was the strongest factor associated with IL-6 change , whereas the only variables independently associated with changes in sCD14 levels were the variations in serum IL-6 and endotoxin concentrations . CONCLUSIONS Administration of the noncalcium phosphate binder sevelamer to maintenance HD patients is associated with a significant decrease in hs-CRP , IL-6 , serum endotoxin levels and sCD14 concentrations BACKGROUND Hyperphosphatemia is a common complication in end-stage renal disease ( ESRD ) patients . Reducing the serum phosphate level is crucial in management of ESRD . METHODS This study was a r and omized prospect i ve study , design ed to compare patients with hyperphosphatemia undergoing peritoneal dialysis while taking lanthanum carbonate or calcium carbonate . We divided 72 continuous ambulatory peritoneal dialysis ( CAPD ) patients whose serum phosphate levels were over 5.6 mg/dl into two groups to receive either lanthanum carbonate or calcium carbonate . Serum calcium , phosphate and PTH levels were examined serially for 24 weeks . RESULTS Both lanthanum carbonate and calcium carbonate reduced serum phosphate levels , from 6.79 ± 1.05 to 5.44 ± 1.44 and from 6.31 ± 1.13 to 4.74 ± 0.78 mg/dl , respectively . The calcium × phosphate product level was reduced in the lanthanum carbonate and calcium carbonate groups from 60.23 ± 10.23 to 46.97 ± 16.42 and from 57.92 ± 11.05 to 44.50 ± 7.74 mg2/dl2 , respectively . The serum parathyroid hormone ( PTH ) level in the lanthanum carbonate group did not change significantly compared to baseline during the study , but in the calcium carbonate group , the serum PTH level decreased significantly . Gastrointestinal complications were the main adverse effects of lanthanum carbonate and 11 out of 35 patients dropped out of the study due to this complication . CONCLUSIONS Lanthanum carbonate was as effective as calcium carbonate in reducing serum phosphate level , and serum PTH level tended to be steadier in the lanthanum carbonate group compared to the calcium carbonate group . Though the ifference was not significant , lanthanum carbonate tended not to elevate serum calcium level in CAPD patients compared to calcium carbonate . The high incidence of gastrointestinal adverse effect in the lanthanum carbonate group will need further evaluation Lanthanum carbonate , a chewable noncalcium‐containing phosphorus ( P ) binder , is useful for treating secondary hyperparathyroidism in patients who have hypercalcemia and can not swallow whole tablets . However , some patients can not chew tablets or prefer to crush and mix them with food . This study was conducted to determine the P‐binding efficacy of crushed lanthanum and compare it with chewed lanthanum in hemodialysis ( HD ) patients . After a 1‐week washout period , 11 hemodialysis patients ( 7 men , 4 women ) were r and omized to receive , in a crossover fashion , lanthanum 1000 mg 3 times daily chewed with meals and lanthanum 1000 mg 3 times daily crushed into a fine powder , mixed with applesauce and taken with meals , for 4 weeks each . Serum P was measured at the end of each washout ( baseline ) and weekly during treatment . Changes in serum P from baseline for crushed lanthanum were compared with chewed lanthanum using paired sample t test . Administration of crushed lanthanum result ed in a significant reduction in serum P from baseline ( P reduction [ mg/dL ] for crushed lanthanum in week 1 : 2.1 ± 0.4 , week 2 : 1.7 ± 0.5 , week 3 : 1.7 ± 0.5 , week 4 : 1.7 ± 0.4 , P<0.05 ) . No statistically significant differences were observed in serum P reduction from baseline and serum P attained during treatment with crushed when compared with chewed lanthanum . Crushed lanthanum is effective in reducing serum P and have similar P‐binding efficacy to chewed lanthanum . Crushing lanthanum and mixing it with food can thus be an option for patients who are unable to chew or swallow whole tablets A comparative study of long-term haemodialysis patients investigated the effects of calcium acetate and calcium carbonate on concentrations of serum phosphate , calcium , and parathyroid hormone . It was demonstrated that both substances led to a significant decrease in phosphate and serum parathyroid hormone . Administration of calcium acetate reduced the serum phosphate concentration in 7 weeks from an initial value of 2.08 + /- 0.53 mmol/l to 1.51 + /- 0.39 mmol/l ( P less than 0.01 ) . Following a 1-week wash-out period , calcium carbonate reduced the serum phosphate concentration in the same patients from 1.99 + /- 0.62 mmol/l to 1.34 + /- 0.40 mmol/l ( P less than 0.01 ) . Of particular significance , however , is the fact that in relation to daily elementary calcium intake , calcium acetate was a considerably more effective binder of intestinal phosphate than calcium carbonate . During administration of calcium acetate only 1.02 g of elementary calcium were required daily in order to reduce the serum phosphate concentration . The same patients , however , required 1.88 g of elementary calcium during calcium carbonate therapy . Complementary studies investigated the influence of an accompanying calcitriol medication . In this instance , too , calcium acetate was shown to be more effective ; although the patients developed hypercalcaemia with calcium acetate , this happened more often with calcium carbonate . In summary it can be said that daily calcium loading of the uraemic organism under calcium acetate therapy is reduced by nearly half as compared to calcium carbonate therapy , and that this can be achieved with the same effective decrease of the serum phosphate concentration INTRODUCTION The phosphate-binders presently used in the treatment of calcium-phosphorus disorders in dialysis patients remain a crucial element of cardio-vascular protection . The aim of the study was to assess short-time magnesium carbonate treatment efficacy in hemodialysis patients with hyperphosphatemia . MATERIAL AND METHODS The study involved 64 participants ( 32 male and 32 female ) aged 29 - 84 years , with end-stage renal disease , hyperphosphatemia ( > 1.78 mmol/l ) , dialysis 3 times a week , mean session time 4 hours 15 minutes . All the patients were divided into three groups : I--30 patients treated with magnesium carbonate 3 x 1 g ; group II--10 patients treated with sevelamer hydrochloride 0.8 g--3 x 2 tabl ( 3 x 1.6 g ) ; group III--24 patients treated with calcium carbonate 3 x 2 g. Participants were categorized r and omly to groups I and II and to group III only patients with decreased serum calcium concentration ( < 2.1 mmol/1 ) were assigned . The doses stayed constant within 12 weeks of therapy . RESULTS In group treated with magnesium carbonate after 3 months of the treatment the decrease of plasma parathormon ( iPTH ) from 526.1 + /- 463.3 to 443.2 + /- 223.1 ( pg/ml ) , calcium ( Ca ) from 2.4 + /- 0.2 to 2.3 + /- 0.1 ( mmol/1 ) ; the highest reduction of phosphate ( P ) 2.1 + /- 0.5 to 1.6 + /- 0.4 ( mmol/1 ) and calcium phosphate product ( Cax P ) from 4.6 + /- 2.3 to 3.5 + /- 1.1 ( mmol2/ l2 ) were observed . In group II , iPTH slightly increased from initial 425.26 + /- 192.5 to 445.6 + /- 222.3 ( pg/ml ) ; serum calcium decreased from 2.23 + /- 0.17 to 2.0 + /- 0.2 ( mmol/l ) ; phosphates dropped from 2.35 + /- 0.43 to 2.0 + /- 0.3 ( mmol/l ) and Ca x P index from 5.1 + /- 1.2 to 4.1 + /- 0.7 ( mmol2/l2 ) . In group treated with calcium carbonate iPTH decreased from 308.2 + /- 196.6 to 301.9 + /- 188.5 ( pg/ml ) . Calcium , phosphate and Ca x P dropped during the treatment from 2.06 + /- 0.23 to 2.05 + /- 0.2 ( mmol/l ) , 2.17 + /- 0.36 to 1.86 + /- 0.45 ( mmol/l ) and from 4.7 + /- 0.8 to 3.7 + /- 0.9 ( mmol2/l2 ) , respectively . Calcium-phosphorus disorders were normalized to actual guidelines only in participants treated with magnesium carbonate . CONCLUSIONS Magnesium carbonate seems to be the effective treatment of calcium-phosphorus disorders in hemodialysis patients . However its administration , similarly to other non-calcium phosphate-binders , is limited and dedicated to patients with normal serum calcium concentration Serum phosphate independently predicts cardiovascular mortality in the general population and CKD , even when levels are in the normal range . Associations between serum phosphate , arterial stiffness , and left ventricular ( LV ) mass suggest a possible pathophysiological mechanism , potentially mediated by the phosphaturic hormone fibroblast growth factor-23 ( FGF-23 ) . To what extent the phosphate binder sevelamer modulates these effects is not well understood . In this single-center , r and omized , double-blind , placebo-controlled trial , we enrolled 120 patients with stage 3 nondiabetic CKD . After a 4-week open-label run-in period , during which time all patients received sevelamer carbonate , we r and omly assigned 109 patients to sevelamer ( n=55 ) or placebo ( n=54 ) for an additional 36 weeks . We assessed LV mass and systolic and diastolic function with cardiovascular magnetic resonance imaging and echocardiography , and we assessed arterial stiffness by carotid-femoral pulse wave velocity . The mean age was 55 years , and the mean eGFR was 50 ml/min per 1.73 m(2 ) . After 40 weeks , we found no statistically significant differences between sevelamer and placebo with regard to LV mass , systolic and diastolic function , or pulse wave velocity . Only 56 % of subjects took ≥ 80 % of prescribed therapy ; in this compliant subgroup , treatment with sevelamer associated with lower urinary phosphate excretion and serum FGF-23 but not serum phosphate , klotho , vitamin D , or cardiovascular-related outcomes of interest . In conclusion , this study does not provide evidence that sevelamer carbonate improves LV mass , LV function , or arterial stiffness in stage 3 nondiabetic CKD 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 Disturbances in mineral metabolism play a central role in the development of renal bone disease . In a 54-wk , r and omized , open-label study , 119 hemodialysis patients were enrolled to compare the effects of sevelamer hydrochloride and calcium carbonate on bone . Biopsy-proven adynamic bone disease was the most frequent bone abnormality at baseline ( 59 % ) . Serum phosphorus , calcium , and intact parathyroid hormone were well controlled in both groups , although calcium was consistently lower and intact parathyroid hormone higher among patients who were r and omly assigned to sevelamer . Compared with baseline values , there were no changes in mineralization lag time or measures of bone turnover ( e.g. , activation frequency ) after 1 yr in either group . Osteoid thickness significantly increased in both groups , but there was no significant difference between them . Bone formation rate per bone surface , however , significantly increased from baseline only in the sevelamer group ( P = 0.019 ) . In addition , of those with abnormal microarchitecture at baseline ( i.e. , trabecular separation ) , seven of 10 in the sevelamer group normalized after 1 yr compared with zero of three in the calcium group . In summary , sevelamer result ed in no statistically significant changes in bone turnover or mineralization compared with calcium carbonate , but bone formation increased and trabecular architecture improved with sevelamer . Further studies are required to assess whether these changes affect clinical outcomes , such as rates of fracture We compared the effects of calcitriol and doxercalciferol , in combination with either calcium carbonate or sevelamer , on bone , mineral , and fibroblast growth factor-23 ( FGF-23 ) metabolism in patients with secondary hyperparathyroidism . A total of 60 pediatric patients treated with peritoneal dialysis were r and omized to 8 months of therapy with either oral calcitriol or doxercalciferol , combined with either calcium carbonate or sevelamer . Bone formation rates decreased during therapy and final values were within the normal range in 72 % of patients . A greater improvement in eroded surface was found in patients treated with doxercalciferol than in those given calcitriol . On initial bone biopsy , a mineralization defect was identified in the majority of patients which did not normalize with therapy . Serum phosphate concentrations were controlled equally well by both binders , but serum calcium levels increased during treatment with calcium carbonate , and serum parathyroid hormone levels were decreased by 35 % in all groups . Baseline plasma FGF-23 values were significantly elevated and rose over fourfold with calcitriol and doxercalciferol , irrespective of phosphate binder . Thus , doxercalciferol is as effective as calcitriol in controlling serum parathyroid hormone levels and suppressing the bone formation rate . Sevelamer allows the use of higher doses of vitamin D. Implication s of these changes on bone and cardiovascular biology remain to be established BACKGROUND Some trials have indicated that coronary artery calcification progresses more slowly in sevelamer-treated dialysis patients than in those using calcium-based binders . Effects of phosphate binders on circulating advanced glycation end products ( AGEs ) are unknown . STUDY DESIGN R and omized trial with parallel-group design . SETTING & PARTICIPANTS 183 adult ( aged > 20 years ) patients on maintenance hemodialysis therapy at 12 dialysis facilities with a mean vintage of 118 ± 89 ( median , 108 ) months . Dialysate calcium concentration was 2.5 mEq/L , and dietary calcium was not controlled . INTERVENTION Patients were r and omly assigned to 12 months of treatment with sevelamer ( n = 91 ) or calcium carbonate ( n = 92 ) . OUTCOMES & MEASUREMENTS Primary outcome measures were change from baseline in coronary artery calcification score ( CACS ) determined at study entry and completion using multislice computed tomography and the proportion of patients with a ≥ 15 % increase in CACS . Blood parameters were determined at study entry and 2-week intervals , and levels of plasma pentosidine , a representative AGE , were determined at study entry , 6 months , and study completion . RESULTS 79 ( 86.8 % ) and 84 ( 91.3 % ) patients in the sevelamer and calcium-carbonate arms completed the treatment , respectively . Both binders were associated with an increase in mean CACS : 81.8 ( 95 % CI , 42.9 - 120.6 ) and 194.0 ( 139.7 - 248.4 ) , respectively ( P < 0.001 for both ) . After adjustment for baseline values , the increase in the sevelamer group was 112.3 ( 45.8 - 178 ) less ( P < 0.001 ) . Percentages of patients with a ≥ 15 % increase in CACS were 35 % of the sevelamer group and 59 % of the calcium-carbonate group ( P = 0.002 ) . Plasma pentosidine levels increased with calcium carbonate but not [ corrected ] sevelamer treatment ( P < 0.001 ) . Sevelamer use was associated with decreased risk of a ≥ 15 % increase in CACS regardless of baseline blood parameters , pentosidine level , and CACS . LIMITATIONS Treatment duration was relatively short , some sevelamer-treated patients ( 7 of 79 ) received calcium carbonate , and washout could not be performed . CONCLUSIONS The data suggest that sevelamer treatment slowed the increase in CACS and suppressed AGE accumulation BACKGROUND AND OBJECTIVES Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies . A prospect i ve , r and omized , double-blind , placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Hemodialysis patients with phosphorus levels > or = 5.0 mg/dl were r and omly assigned to 8 wk of niacinamide or placebo , titrated from 500 to 1500 mg/d . After a 2-wk washout period , patients switched to 8 wk of the alternative therapy . Vitamin D analogs and calcimimetics were held constant ; phosphorus binders were not changed unless safety criteria were met . RESULTS Thirty-three patients successfully completed the trial . Serum phosphorus fell significantly from 6.26 to 5.47 mg/dl with niacinamide but not with placebo ( 5.85 to 5.98 mg/dl ) . A concurrent fall in calcium-phosphorus product was seen with niacinamide , whereas serum calcium , intact parathyroid hormone , uric acid , platelet , triglyceride , LDL , and total cholesterol levels remained stable in both arms . Serum HDL levels rose with niacinamide ( 50 to 61 mg/dl but not with placebo . Adverse effects were similar between both groups . Among patients who were > or = 80 % compliant , results were similar , although the decrease in serum phosphorus with niacinamide was more pronounced ( 6.45 to 5.28 mg/dl ) and the increase in HDL approached significance ( 49 to 58 mg/dl ) . CONCLUSIONS In hemodialysis patients , niacinamide effectively reduces serum phosphorus when co-administered with binders and results in a potentially advantageous increase in HDL cholesterol . Further study in larger r and omized trials and other chronic kidney disease population s is indicated BACKGROUND AND OBJECTIVES A dose-finding study was undertaken to investigate the efficacy of PA21 , a novel polynuclear iron(III)-oxyhydroxide phosphate binder . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In a r and omized , active-controlled , multicenter , open-label study at 50 clinical sites in Europe and the United States , hemodialysis patients were r and omized to PA21 at dosages of 1.25 , 5.0 , 7.5 , 10.0 , or 12.5 g/d or sevelamer-HCl 4.8 g/d for 6 weeks . The primary efficacy endpoint was the change in serum phosphorus concentration from baseline . RESULTS There were 154 participants who were r and omized and received the study drug . All groups except PA21 1.25 g/d showed a significant decrease in serum phosphorus . Mean decreases in serum phosphorus in PA21 10 g/d and 12.5 g/d were -2.00±1.71 mg/dl and -1.69±1.81 mg/dl , respectively . A similar decrease to sevelamer-HCl ( -1.06±1.35 mg/dl ) was seen with PA21 5.0 g/d ( -1.08±2.12 mg/dl ) and 7.5 g/d ( -1.25±1.21 mg/d ) . Overall , 60.9 % of participants r and omized to PA21 and 57.7 % r and omized to sevelamer-HCl reported ≥1 adverse event . The most frequent adverse events were hypophosphatemia ( 18.0 % ) and discolored feces ( 11.7 % ) for the pooled PA21 dose groups , and diarrhea , hypophosphatemia , and hypotension ( each 11.5 % ) for sevelamer-HCl . Discontinuation due to adverse events occurred at a similar rate in PA21-treated ( 21.1 % ) and sevelamer-HCl-treated ( 23.1 % ) participants . CONCLUSIONS PA21 5 - 12.5 g/d significantly reduces serum phosphorus in hemodialysis patients . The 5 g/d and 7.5 g/d dosages showed similar efficacy to 4.8 g/d of sevelamer-HCl . The adverse events rate was similar for PA21 and sevelamer-HCl Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease . Bixalomer ( Kiklin ® Capsules ) is a non-absorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract . This study was a multicenter , double-blind , r and omized , placebo-controlled study to confirm the superiority of bixalomer to placebo for a 4-week treatment period in patients with chronic kidney disease on hemodialysis with hyperphosphatemia . Sevelamer hydrochloride ( HCl ) , a similar non-absorbable polymer , was used as an active comparator for open-label as a reference without statistical comparison for efficacy and safety . The primary endpoint was the change in serum phosphorus level from baseline . The safety profile was also investigated . The number of subjects was 32 in the placebo group and 31 in each bixalomer group ( 1.5 , 3.0 and 4.5 g/day ) , respectively . The baseline serum phosphorus level was 7.95 to 8.25 mg/dL. Bixalomer showed a significant decrease in serum phosphorus level at all doses compared with placebo , and the adjusted mean change in serum phosphorus level from the baseline to the end of treatment ( at Week 4 or at the time of discontinuation ) was + 0.24 mg/dL in the placebo group , -0.75 mg/dL in the 1.5 g/day group , -1.32 mg/dL in the 3.0 g/day group , and -1.80 mg/dL in the 4.5 g/day group , showing a dose-dependent decrease in serum phosphorus level . The mean change in serum phosphorus level was -2.32 mg/dL in the sevelamer HCl group under the mean dose of 4.8 g/day . Major adverse events included constipation , hard feces , vomiting , etc . ; however , none of the adverse events were serious or severe . Consequently , the superiority of bixalomer to placebo and its dose-dependency for treating hyperphosphatemia were confirmed ( Clinical trial registration : NCT00505037 ) 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 Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients . Unlike calcium-based binders , sevelamer attenuates arterial calcification but it is unknown whether sevelamer affects mortality or morbidity . In a multicenter , r and omized , open-label , parallel design trial we compared sevelamer and calcium-based binders on all-cause and cause-specific mortality ( cardiovascular , infection , and other ) in prevalent hemodialysis patients . A total of 2103 patients were initially r and omized to treatment and 1068 patients completed the study . All-cause mortality rates and cause-specific mortality rates were not significantly different . There was a significant age interaction on the treatment effect . Only in patients over 65 years of age was there a significant effect of sevelamer in lowering the mortality rate . There was a suggestion that sevelamer was associated with lower overall , but not cardiovascular-linked , mortality in older patients . We suggest that further research is needed to confirm these findings The objective of this study was to eluci date the effect of oral calcium supplement upon the severity of secondary hyperparathyroidism and hyperphosphatemia in patients undergoing hemodialysis . Twenty-three accepted to participate and were r and omly allocated to receive in a double-blind manner either 2 g elemental calcium per day ( n = 12 ) or placebo ( n = 11 ) for 6 months . Three patients dropped out leaving 10 patients in each group . In the calcium group serum ionized calcium increased significantly during the 1st month from 1.15 + /- 0.02 to 1.29 + /- 0.04 mmol/l ( mean + /- SE ) and was then stabilized at an average of 1.26 + /- 0.02 mmol/l for the remaining 5 months . Serum intact parathyroid hormone ( PTH ) decreased in average by 54 % within the 1st month and remained at that level for the following months . Hyperphosphatemia remained stable throughout . On the contrary , in the placebo group , serum concentrations of ionized calcium and intact PTH remained unchanged , while serum phosphate increased significantly . The present study demonstrates that oral calcium reduces secondary hyperparathyroidism and prevents the progression of hyperphosphatemia in patients undergoing hemodialysis Summary The effect of lanthanum carbonate on abdominal aortic calcification ( AAC ) in the elderly maintenance hemodialysis ( MHD ) patients was investigated . Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and r and omly divided into case group ( n=28 ) and control group ( n=26 ) . The control group was given routine MHD alone . The case group was given lanthanum carbonate additionally on the basis of routine MHD . The changes of itching degrees at first and third month , and serum calcium , phosphorus , calcium-phosphorus products , intact parathyroid hormone ( iPTH ) levels and AAC scores at third month after treatments were compared between the two groups . The correlation between calcium-phosphorus products and AAC scores was also analyzed . There was no significant difference in the baseline of blood urea nitrogen ( BUN ) , serum creatinine ( Scr ) , uric acid , albumin , hemoglobin , C reactive protein ( CRP ) , low density lipoprotein ( LDL ) , high density lipoprotein ( HDL ) , triglyceride , total cholesterol between case group and control group ( P>0.05 for all ) . There was also no significant difference in the baseline itching scores between the case group and the control group ( P>0.05 ) . At 1st and 3rd month after treatment , the itching scores in the case group were 14.2±3.2 and 10.5±2.3 , respectively , which were significantly lower than the baseline and those in the control group ( P<0.05 for all ) . At 1st and 3rd month after treatment , the itching scores in the control group were 23.6±5.9 and 24.8±6.3 , respectively , which were significantly higher than the baseline ( P<0.05 ) . There was no significant difference in the baseline of serum calcium , phosphorus , calcium-phosphorus products , iPTH levels between the case group and control group ( P>0.05 ) . At 3rd month after treatment , serum phosphorus , calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline ( P<0.05 ) , and the serum calcium , phosphorus , calcium-phosphorus products , and iPTH levels were statistically decreased as compared with those in the control group ( P<0.05 ) . The AAC scores showed statistically significant difference between the case group and the control group ( P<0.05 ) . The serum phosphorus and AAC scores showed a positive correlation in both two groups . It was suggested that the administration of lanthanum carbonate in the elderly MHD patients can effectively relieve itching , and simultaneously reduce serum phosphorus and iPTH levels , result ing in the attenuation of vascular calcification BACKGROUND Fibroblast growth factor 23 ( FGF-23 ) is a hormone that increases the rate of urinary excretion of phosphate and inhibits renal production of 1,25-dihydroxyvitamin D , thus helping to mitigate hyperphosphatemia in patients with kidney disease . Hyperphosphatemia and low 1,25-dihydroxyvitamin D levels are associated with mortality among patients with chronic kidney disease , but the effect of the level of FGF-23 on mortality is unknown . METHODS We examined mortality according to serum phosphate levels in a prospect i ve cohort of 10,044 patients who were beginning hemodialysis treatment and then analyzed FGF-23 levels and mortality in a nested case-control sample of 200 subjects who died and 200 who survived during the first year of hemodialysis treatment . We hypothesized that increased FGF-23 levels at the initiation of hemodialysis would be associated with increased mortality . RESULTS Serum phosphate levels in the highest quartile ( > 5.5 mg per deciliter [ 1.8 mmol per liter ] ) were associated with a 20 % increase in the multivariable adjusted risk of death , as compared with normal levels ( 3.5 to 4.5 mg per deciliter [ 1.1 to 1.4 mmol per liter ] ) ( hazard ratio , 1.2 ; 95 % confidence interval [ CI ] , 1.1 to 1.4 ) . Median C-terminal FGF-23 ( cFGF-23 ) levels were significantly higher in case subjects than in controls ( 2260 vs. 1406 reference units per milliliter , P<0.001 ) . Multivariable adjusted analyses showed that increasing FGF-23 levels were associated with a monotonically increasing risk of death when examined either on a continuous scale ( odds ratio per unit increase in log-transformed cFGF-23 values , 1.8 ; 95 % CI , 1.4 to 2.4 ) or in quartiles , with quartile 1 as the reference category ( odds ratio for quartile 2 , 1.6 [ 95 % CI , 0.8 to 3.3 ] ; for quartile 3 , 4.5 [ 95 % CI , 2.2 to 9.4 ] ; and for quartile 4 , 5.7 [ 95 % CI , 2.6 to 12.6 ] ) . CONCLUSIONS Increased FGF-23 levels appear to be independently associated with mortality among patients who are beginning hemodialysis treatment . Future studies might investigate whether FGF-23 is a potential biomarker that can be used to guide strategies for the management of phosphorus balance in patients with chronic kidney disease Insufficient control of serum calcium and phosphate levels in patients undergoing hemodialysis is associated with increased mortality . As commonly used calcium-containing phosphate binders can cause arterial calcification , newly developed calcium-free phosphate binders , such as sevelamer hydrochloride ( SH ) and lanthanum carbonate ( LC ) , have received much attention . We assessed the efficacy and safety of SH and LC treatment in Japanese patients undergoing hemodialysis in a prospect i ve r and omized open blinded endpoint ( PROBE ) crossover study . Forty-two patients were r and omized to receive SH or LC for 13 weeks , with the dosages adjusted every 2 weeks , followed by treatment with the other drug for another 13 weeks . The average daily doses of SH and LC were 2971 ± 1464 mg and 945 ± 449 mg , respectively . The mean dosage ratio of SH to LC was 3.05 , which was maintained throughout the treatment period . SH and LC were similarly effective at controlling serum calcium and phosphate levels in the majority of patients ( 78 - 93 % ) . A few serious adverse events ( AEs ) involving the biliary system occurred during the LC treatment period , but they were not considered to be treatment-induced . Although the incidence of constipation , the most common treatment-related AE , was higher during the SH period ( 27 % vs. 5 % ; P < 0.05 ) , no difference was observed in total treatment-related AEs . This study demonstrates that SH and LC are comparable treatments for controlling serum phosphate and calcium levels , and that both compounds are safe and well-tolerated in Japanese patients undergoing hemodialysis BACKGROUND AND OBJECTIVES Increased inflammation and oxidative stress may be caused by proteins and lipids modified by cytotoxic advanced glycation end products ( AGEs ) in food . Restricting food containing elevated AGEs improves these risk factors in diabetic CKD . Because diet adherence can be problematic , this study aim ed to remove cytotoxic AGEs from food already ingested and to determine whether sevelamer carbonate sequesters cytotoxic AGEs in the gut , preventing their uptake and thereby reducing AGE-induced abnormalities . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This single-center , r and omized , 2-month , open-label , intention-to-treat , crossover study compared sevelamer carbonate with calcium carbonate treatment in stage 2 - 4 diabetic CKD . Participants received 2 months of treatment with one drug , had a 1-week washout , and then received the opposite drug for 2 months . RESULTS Sevelamer carbonate reduced HbA1c , serum methylglyoxal , serum (ε)N-carboxymethyl-lysine , triglycerides , and 8-isoprostanes . Total cholesterol and fibroblast growth factor 23 were reduced by sevelamer carbonate , relative to calcium carbonate . AGE receptor 1 and sirtuin 1 mRNA were increased and PMNC TNFα levels were decreased by sevelamer carbonate , but not calcium carbonate . Medications and caloric and AGE intake remained unchanged . Sevelamer carbonate reversibly bound AGE-BSA at intestinal , but not stomach , pH. CONCLUSIONS Sevelamer carbonate significantly reduces HbA1c , fibroblast growth factor 23 , lipids , and markers of inflammation and oxidative stress , and markedly increases antioxidant markers , independently of phosphorus in patients with diabetes and early kidney disease . These novel actions of sevelamer carbonate on metabolic and inflammatory abnormalities in type 2 diabetes mellitus may affect progression of early diabetic CKD Objectives : The tolerability and efficacy of lanthanum carbonate has not been studied in the Indian population . This study was , therefore , undertaken to compare the efficacy and tolerability of lanthanum carbonate with calcium acetate in patients with stage 4 chronic kidney disease . Design : A r and omized open label two group cross-over study . Material s and Methods : Following Institutional Ethics Committee approval and valid consent , patients with stage 4 chronic kidney disease were r and omized to receive either lanthanum carbonate 500 mg thrice daily or calcium acetate 667 mg thrice daily for 4 weeks . After a 4-week washout period , the patients were crossed over for another 4 weeks . Serum phosphorous , serum calcium , serum alkaline phosphatase , and serum creatinine were estimated at fixed intervals . Results : Twenty-six patients were enrolled in the study . The mean serum phosphorous concentrations showed a declining trend with lanthanum carbonate ( from pre-drug levels of 7.88 ± 1.52 mg/dL-7.14 ± 1.51 mg/dL ) and calcium acetate ( from pre-drug levels of 7.54 ± 1.39 mg/dL-6.51 ± 1.38 mg/dL ) . A statistically significant difference was seen when comparing the change in serum calcium produced by these drugs ( P < 0.05 ) . Serum calcium levels increased with calcium acetate ( from pre-drug levels of 7.01 ± 1.07 - 7.46 ± 0.74 mg dL ) , while it decreased with lanthanum carbonate ( from pre-drug levels 7.43 ± 0.77 - 7.14 ± 0.72 mg/dL ) . The incidence of adverse effects was greater with lanthanum carbonate . Conclusion : Lanthanum carbonate and calcium acetate are equally effective phosphate binders with trends obvious in the first 4 weeks of therapy . The decrease in serum calcium levels with lanthanum carbonate when compared to the increase in serum calcium levels due to calcium acetate is statistically significant . The drawback of lanthanum carbonate is its high cost and relatively higher incidence of adverse events during treatment Background Phosphorus is associated with mortality in patients with chronic kidney disease ( CKD ) not on dialysis , possibly through phosphorus-dependent vascular calcification . Although a phosphorus-restricted diet reduces serum phosphorus , it is unlikely that it reduces vascular calcification progression in CKD . This study evaluated whether a combined strategy of phosphorus-restricted diet and phosphate-binding therapy can reduce the risk of all-cause mortality and /or dialysis initiation by attenuating coronary artery calcification ( CAC ) progression in non-dialysis CKD patients . Methods This was a post hoc analysis of a subgroup of patients from a study that evaluated the impact of two phosphorus binder regimens on hard outcomes in CKD . Patients ( n = 113 ) with stage 3–4 CKD and evidence of CAC on a phosphorus-restricted diet were r and omized to receive either calcium carbonate or sevelamer added to their phosphorus-restricted diet . End-points were death for any cause and initiation of dialysis . Patients were monitored to the first event or to conclusion of the 36-month follow-up . Results Overall , treatment with calcium carbonate was associated with increased CAC progression and occurrence of all-cause mortality , dialysis initiation , and the composite end-point . After adjustment for confounders , sevelamer use was the only independent predictive factor of reduced risk of each endpoint but only if CAC progression was either absent or moderate . Accelerated progression ( annual CAC increase > 75th percentile of the study cohort ) increased the risk of all-cause mortality and composite end-point ( p = 0.01 ) independently of the use of sevelamer . Conclusions A significant reduction in all-cause mortality , dialysis initiation , and composite end-point risk was achieved by combining phosphorus-restricted diet and sevelamer in non-dialysis CKD patients with absent or moderate but not accelerated CAC progression . Future studies should investigate the role of serum phosphorus , the usefulness of a phosphorus-restricted diet , and the appropriateness of current normal ranges of serum phosphorus concentration in relation to events in non-dialyzed CKD patients Background / Aims : Cardiovascular disease ( CVD ) is increased in chronic kidney disease ( CKD ) , and contributed to by the CKD-mineral bone disorder ( CKD-MBD ) . CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness ( cIMT ) and vascular calcification ( VC ) . Phosphorus is associated with this progression and is considered a CVD risk factor in CKD . We hypothesized that modifying phosphorus balance with lanthanum carbonate ( LaCO3 ) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD . Methods : We r and omized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month r and omized , double-blind , pilot and feasibility study . The primary outcome was the change in serum phosphorus . Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity ( PWV ) , cIMT and VC over 12 months . Results : There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus , urinary phosphorus , tubular reabsorption of phosphorus , PWV , cIMT , or VC . Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23 , Dickkopf-related protein 1 ( DKK1 ) , and sclerostin were increased 2- to 3-fold at baseline , but were not affected by LaCO3 . Conclusion : Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis , PWV , cIMT , VC , or biomarkers of CKD-MBD |
1,705 | 30,636,891 | Conclusion There is limited available evidence on treatments for oral cancer .
The main beneficial treatment reported by authors for patients with resectable oral cancer is surgery alone or in combination with radiotherapy or chemotherapy .
Evidence about the benefits of the treatments for unresectable oral cancer is lacking . | Purpose This evidence mapping aims to describe and assess the quality of available evidence in systematic review s ( SRs ) on treatments for oral cancer . | BACKGROUND Data on preoperative chemotherapy in resectable oral cavity cancer are conflicting . We present the long-term results of a r and omized trial of induction chemotherapy in resectable oral cavity cancer . PATIENTS AND METHODS A r and omized , parallel , multicentre trial evaluated the impact of three cycles of cisplatin 100 mg/m2 and fluorouracil 1000 mg/m2 ( 120-h infusion administered every 21 days ) in stage T2-T4 , N0-N2 , previously untreated patients with advanced disease . Control group received upfront surgery . Postoperative radiation was offered to both arms when pathologic risk features were identified . The co- primary end points were the occurrence of locoregional or distant tumour relapse , and death . RESULTS Among the 198 enrolled patients , with a median follow-up of 11.5 years , there was no difference in the incidence of locoregional relapse between chemotherapy and control group ( P=0.6337 ) , nor in distant metastasis development ( P=0.1527 ) . There was also no difference between groups in overall survival ( P=0.3402 ) . Patients with a pathological complete response ( pCR ) had higher probability of survival than those without ( 10-year OS : 76.2 % versus 41.3 % , P=0.0004 ) . Late toxicities in patients with a minimum follow-up of 60 months ( 42 in each group ) were similar between arms , except from fibrosis ( cumulative incidence 40 % versus 22 % in chemotherapy arm ) and grade 2 dysphagia ( 14 % versus 5 % ) . CONCLUSIONS Long-term follow-up of this r and omized trial confirmed the absence of survival benefit with preoperative chemotherapy in oral cavity cancer . Late toxicity was similar in the two arms except for fibrosis and dysphagia , which were less in the chemotherapy arm . The survival benefit for patients achieving a pCR was maintained PURPOSE To date , consensus has not been reached on which treatment modality , that is , in-continuity neck dissection or discontinuous neck dissection , is more appropriate for managing patients with squamous cell carcinoma ( SCC ) of the tongue and floor of the mouth . This study aim ed to perform a meta- analysis to compare discontinuous neck dissection with in-continuity neck dissection as a treatment modality for SCC of the tongue and floor of the mouth . MATERIAL S AND METHODS The PubMed , Web of Science , China National Knowledge Infrastructure , and Wanfang data bases were search ed for articles that compared discontinuous neck dissection with in-continuity neck dissection in SCC of the tongue and floor of the mouth until March 1 , 2017 . The predictor variable was whether discontinuous neck dissection or in-continuity neck dissection was performed in each group . The primary outcome variable was the incidence of locoregional recurrence . Two authors individually extracted the data and assessed the study quality . The meta- analysis was performed using Stata ( version 13.0 ; StataCorp , College Station , TX ) . RESULTS We included 8 studies with 796 patients in our meta- analysis . The results showed that in-continuity neck dissection had a statistically significantly lower incidence of locoregional recurrence than discontinuous neck dissection ( r and om-effects model : relative risk , 0.459 ; 95 % confidence interval , 0.240 to 0.877 ; P = .019 ) . Because significant heterogeneity among studies ( I2 = 74.5 % , P < .001 ) was found in the heterogeneity evaluation , a separate analysis was performed . However , the results still showed that in-continuity neck dissection had a statistically significantly lower rate of locoregional recurrence than discontinuous neck dissection in patients with T2 and T3 SCC of the tongue and floor of the mouth ( fixed-effects model : relative risk , 0.281 ; 95 % confidence interval , 0.183 to 0.433 ; P < .001 ) . CONCLUSIONS Compared with discontinuous neck dissection , in-continuity neck dissection can significantly reduce the rate of locoregional recurrence in patients with SCC of the tongue and floor of the mouth The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions The current r and omized , multicenter , Phase III trial was conducted to determine whether the disease free interval and overall survival of patients with T2–T4,N0–N3,M0 squamous cell carcinoma ( SCC ) of the oral cavity or oropharynx could be extended through the combination of surgery ( and radiotherapy , if required ) with perilymphatic recombinant IL‐2 ( rIL‐2 ) Either intra-arterial infusions of MTX ( 500 mg over 10 days ) or intra-arterial infusions of BLM ( 95 mg over 13 days ) were administered as initial treatment to 85 patients with untreated squamous cell carcinomas of the oral cavity . Tumour regression was assessed 10 - 15 days after the end of chemotherapy . A sequential analysis was used , and BLM demonstrated a significantly greater local efficacy after the 32nd matched pair was assessed . The same results were observed when tumour response rates were compared , ignoring the matching , on the 85 patients , ( P less than 0.001 ) . The response rate for patients with neck nodes was low ( 10/38 ) . Catheter management problems , toxic effects and lethal reactions were 2.5 times more frequent in the MTX group Between February 1978 and January 1984 , 222 eligible patients were r and omised in a multicentre trial of preoperative intra-arterial chemotherapy in the treatment of oral cavity and oropharynx carcinoma . Patients were r and omised between either surgery or preoperative chemotherapy . This latter group received vincristine and bleomycin for 12 days . Patients were stratified according to the primary site : floor of the mouth ( FM ) versus posterior oral cavity or oropharynx ( POC ) and institution . The FM group received postoperative radiotherapy depending upon quality of the margins and lymph-node pathological involvement , when it was systematic ally applied in the POC group . Tumour regression after chemotherapy either complete ( CR ) or partial ( PR greater than 50 % ) was observed in 48 % in the FM group and 41 % in the POC group , and lymph-node regression ( CR + PR ) was respectively 15 % and 23 % . Some discrepancies appeared between clinical regression and pathological response , and the number of cases without histological response was clearly higher than the number of cases without clinical response . The overall survival showed a statistically significant difference ( P = 0.048 ) between FM and POC groups . In the FM group , median survival in the chemotherapy arm was estimated at 7 years compared with 3 years in the surgery arm . In the POC group , median survival was estimated at 3 years in both treatment arms . Chemotherapy lowered the uncontrolled disease and local recurrence in the FM group . These differences do not exist in the POC group , which may be due to the systematic ally postoperative radiotherapy PURPOSE To evaluate induction chemotherapy with docetaxel , cisplatin , and fluorouracil ( TPF ) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma ( OSCC ) . PATIENTS AND METHODS A prospect i ve open-label phase III trial was conducted . Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC . Patients received two cycles of TPF induction chemotherapy ( docetaxel 75 mg/m(2 ) on day 1 , cisplatin 75 mg/m(2 ) on day 1 , and fluorouracil 750 mg/m(2 ) on days 1 to 5 ) followed by radical surgery and postoperative radiotherapy ( 54 to 66 Gy ) versus up-front radical surgery and postoperative radiotherapy . The primary end point was overall survival ( OS ) . Secondary end points included local control and safety . RESULTS Of the 256 patients enrolled onto this trial , 222 completed the full treatment protocol . There were no unexpected toxicities , and induction chemotherapy did not increase perioperative morbidity . The clinical response rate to induction chemotherapy was 80.6 % . After a median follow-up of 30 months , there was no significant difference in OS ( hazard ratio [ HR ] , 0.977 ; 95 % CI , 0.634 to 1.507 ; P = .918 ) or disease-free survival ( HR , 0.974 ; 95 % CI , 0.654 to 1.45 ; P = .897 ) between patients treated with and without TPF induction . Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response ( ≤ 10 % viable tumor cells ) had superior OS and locoregional and distant control . CONCLUSION Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC PURPOSE Prognosis of patients with advanced oral cavity cancer is worth improving . Chemotherapy has been reported to be especially active in oral cavity tumors . Here we repeat the results of a r and omized , multicenter trial enrolling patients with a resectable , stage T2-T4 ( > 3 cm ) , N0-N2 , M0 untreated , squamous cell carcinoma of the oral cavity . PATIENTS AND METHODS Patients were r and omly assigned to three cycles of cisplatin and fluorouracil followed by surgery ( chemotherapy arm ) or surgery alone ( control arm ) . In both arms , postoperative radiotherapy was reserved to high-risk patients , and surgery was modulated depending on the tumor 's closeness to the m and ible . Patients ' accrual was opened in 1989 and closed in 1999 . It included 195 patients . RESULTS In the chemotherapy arm , three toxic deaths were recorded . No significant difference in overall survival was found . Five-year overall survival was , for both arms , 55 % . Postoperative radiotherapy was administered in 33 % of patients in the chemotherapy arm , versus 46 % in the control arm . A m and ible resection was performed in 52 % of patients in the control arm , versus 31 % in the chemotherapy arm . CONCLUSION The addition of primary chemotherapy to st and ard surgery was unable to improve survival . However , in this study , primary chemotherapy seemed to play a role in reducing the number of patients who needed to undergo m and ibulectomy and /or radiation therapy . Variations in the criteria used to select patients for these treatment options may make it difficult to generalize these results , but there appears to be room for using preoperative chemotherapy to spare destructive surgery or radiation therapy in patients with advanced , resectable oral cavity cancer Tumours of the oral cavity/oropharynx occur relatively infrequently in the UK . The management of such lesions , especially the squamous cell carcinomas , is still a little controversial . Some centres advocate radiotherapy while others adopt surgery and radiotherapy . In an attempt to resolve the question of which approach gives the better results , a multicentre r and omized trial was established to compare surgery plus postoperative radiotherapy with radical radiotherapy alone . It was anticipated that 350 patients would be required to give a statistically significant result , but , after 35 patients had been entered , the trial was closed prematurely with a marked difference in overall survival in favour of the combination arm ( P = 0.0006 ) . At this analysis , carried out 23 months after trial closure , the survival difference between the two arms remains statistically significant for all causes of mortality ( P = 0.001 ; relative death rate = 0.24 ; 95 % CI 0.10 - 0.59 ) In the final report of a prospect i ve , r and omized controlled clinical trial , we report the results of using adjuvant perioperative chemotherapy in patients with oral cancer . Our study is based on the hypothesis of Goldie and Coldman . A total of 135 patients with alveolobuccal carcinoma , classified as clinical ly stage III and IV , were entered on the protocol . After a curative resection , they were r and omized . The patients in the test arm of the study received methotrexate 50 mg/m2 on the 3rd , 10th , and 17th postoperative days . The patients in the control arm underwent observation . This analysis at 24 months showed a disease-free survival rate of 61 % in the test arm versus 37 % in the control arm , which is statistically highly significant ( P < 0.01 ) . Analysis of the recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months ( P = 0.002 ) . Our study provided further clinical evidence in support of the concepts of Goldie and Coldman that the timing of chemotherapeutic drugs is critical for a successful end result |
1,706 | 29,524,110 | This meta- analysis suggests that physical activity and moderate alcohol intake were associated with a reduced risk for CVD and mortality .
Smoking and higher BMI were associated with an increased risk of these endpoints .
Adherence to a healthy lifestyle may substantially lower the burden of CVD and reduce the risk of mortality among middle-aged and elderly women . | Cardiovascular disease ( CVD ) risk factors , incidence and death increases from around the time of menopause comparing to women in reproductive age .
A healthy lifestyle can prevent CVD , but it is unclear which lifestyle factors may help maintain and improve cardiovascular health for women after menopausal transition .
We conducted a systematic review and meta- analysis of prospect i ve cohort studies to evaluate the association between modifiable lifestyle factors ( specifically smoking , physical activity , alcohol intake , and obesity ) , with CVD and mortality in middle-aged and elderly women . | Importance It is not clear to what extent the higher incidence of coronary heart disease ( CHD ) in men vs women is explained by differences in risk factor levels because few studies have presented adjusted risk estimates for sex . Moreover , the increase in risk of CHD in postmenopausal women , possibly hormone related , may eventually eliminate the sex contrast in risk , but age-specific risk estimates are scarce . Objective To quantify the difference in risk of incident myocardial infa rct ion ( MI ) between men and women . Design , Setting and Participants Population -based prospect i ve study from Tromsø , Norway , comprising 33 997 individuals ( 51 % women ) . Median follow-up time during ages 35 to 102 years was 17.6 years . Incidence rates ( IRs ) and incidence rate ratios ( IRRs , relative risk ) of MI were calculated in Poisson regression analysis of person-years at risk . The data analysis was performed in November 2015 . Exposures Sex , age , birth cohort , serum lipid levels , blood pressure , lifestyle factors , diabetes . Main Outcomes and Measures Incident MI . Results A total of 2793 individuals ( 886 women ) received a diagnosis of MI during follow-up in the period 1979 through 2012 . The IR increased with age in both sexes , with lower rates for women until age 95 years . Adjusted for age and birth cohort , the overall IRR for men vs women was 2.72 ( 95 % CI , 2.50 - 2.96 ) . Adjustment for high-density lipoprotein cholesterol and total cholesterol levels had the strongest impact on the risk estimate for sex , followed by diastolic blood pressure and smoking . However , the sex difference remained substantial even after adjustment for these factors ( IRR , 2.07 ; 95 % CI , 1.89 - 2.26 ) . Men had higher risk throughout life , but the IRRs decreased with age ( 3.64 [ 95 % CI , 2.85 - 4.65 ] , 2.00 [ 95 % CI , 1.76 - 2.28 ] , and 1.66 [ 95 % CI , 1.42 - 1.95 ] for age groups 35 - 54 , 55 - 74 , and 75 - 94 years , respectively ) . Adjustment for systolic blood pressure , diabetes , body mass index , and physical activity had no notable impact . Conclusions and Relevance The observed sex contrast in risk of MI can not be explained by differences in established CHD risk factors . The gender gap persisted throughout life but declined with age as a result of a more pronounced flattening of risk level changes in middle-aged men . The minor changes in IRs when moving from premenopausal to postmenopausal age in women make it unlikely that changes in female hormone levels influence the risk of MI Background and Purpose The purpose of the present analysis was to determine how lifestyle influences the risk of cerebrovascular disease in women participating in the Copenhagen City Heart Study . Methods A r and om sample of a white , lower and middle-class , urban population selected in 1976 was invited to two cardiovascular examinations at 5-year intervals . The present analysis was based on 7060 women invited to an initial examination from 1976 through 1978 , aged 35 years or more , and without previous stroke or transient ischemic attack . At the initial examination , potential risk factors were recorded . The 265 first cases of stroke and transient ischemic attack were ascertained at a second examination 5 years later and through hospital records and death certificates through 1988 . The Cox regression model was used to estimate the influence of the factors recorded on the risk of cerebrovascular disease . Results The relative risks of cigarette smoking and lack of physical activity were 1.4 and 1.45 ; 95 % confidence limits , 1.02 to 1.94 and 1.01 to 2.08 , respectively ) . The relative risk of daily consumption of tranquilizers was 1.25 ( 95 % confidence limits , 0.96 to 1.62 ) . No significant influence was found for number of cigarettes , body mass index , or alcohol intake . In postmenopausal women , there was a statistically significant interaction ( P < .041 ) between smoking and hormone replacement therapy . Smokers receiving this therapy had a 28 % lower risk of cerebrovascular disease than smokers not receiving it . Conclusions The statistically significant and equally potent effects on the risk of cerebrovascular disease were found for cigarette smoking and lack of physical activity . The risk associated with smoking seemed to be influenced by hormonal replacement therapy Objective To evaluate the impact of combinations of lifestyle factors on mortality in middle aged women . Design Prospect i ve cohort study . Setting Nurses ’ health study , United States . Participants 77 782 women aged 34 to 59 years and free from cardiovascular disease and cancer in 1980 . Main outcome measure Relative risk of mortality during 24 years of follow-up in relation to five lifestyle factors ( cigarette smoking , being overweight , taking little moderate to vigorous physical activity , no light to moderate alcohol intake , and low diet quality score ) . Results 8882 deaths were documented , including 1790 from cardiovascular disease and 4527 from cancer . Each lifestyle factor independently and significantly predicted mortality . Relative risks for five compared with zero lifestyle risk factors were 3.26 ( 95 % confidence interval 2.45 to 4.34 ) for cancer mortality , 8.17 ( 4.96 to 13.47 ) for cardiovascular mortality , and 4.31 ( 3.51 to 5.31 ) for all cause mortality . A total of 28 % ( 25 % to 31 % ) of deaths during follow-up could be attributed to smoking and 55 % ( 47 % to 62 % ) to the combination of smoking , being overweight , lack of physical activity , and a low diet quality . Additionally considering alcohol intake did not substantially change this estimate . Conclusions These results indicate that adherence to lifestyle guidelines is associated with markedly lower mortality in middle aged women . Both efforts to eradicate cigarette smoking and those to stimulate regular physical activity and a healthy diet should be intensified BACKGROUND Moderate alcohol consumption is inversely associated with cardiovascular diseases . Changes in hormone levels might in part help explain the positive health effect . This study was performed to examine the effect of moderate alcohol consumption on plasma dehydroepi and rosterone sulfate ( DHEAS ) , testosterone , and estradiol levels . METHODS In a r and omized , diet-controlled , crossover study , 10 middle-aged men and 9 postmenopausal women , all apparently healthy , nonsmoking , and moderate alcohol drinkers , consumed beer or no-alcohol beer with dinner during two successive periods of 3 weeks . During the beer period , alcohol intake equaled 40 and 30 g per day for men and women , respectively . The total diet was supplied and had essentially the same composition during these 6 weeks . Before each treatment there was a 1 week washout period , in which the subjects were not allowed to drink alcoholic beverages . At the end of each of the two experimental periods , fasting blood sample s were collected in the morning . RESULTS Moderate alcohol consumption increased plasma DHEAS level by 16.5 % ( 95 % confidence interval , 8.0 - 24.9 ) , with similar changes for men and women . Plasma testosterone level decreased in men by 6.8 % ( 95 % confidence interval , -1.0- -12.5 ) , but no effect was found in women . Plasma estradiol level was not affected . Serum high-density lipoprotein cholesterol level increased by 11.7 % ( 95 % confidence interval , 7.3 - 16.0 ) , with similar changes for men and women . The overall alcohol-induced relative changes in DHEAS , testosterone , and estradiol correlated positively with the relative increase in high-density lipoprotein cholesterol ( adjusted for the relative change in body weight ) ; however , findings were only borderline significant for DHEAS and estradiol ( r = 0.44 , p = 0.08 ; r = 0.32 , p = 0.21 ; and r = 0.46 , p = 0.06 , respectively ) . CONCLUSIONS A protective effect of moderate alcohol consumption for cardiovascular disease risk may in part be explained by increased plasma DHEAS level CONTEXT Obesity is a well-established risk factor for coronary heart disease ( CHD ) , but whether regional fat distribution contributes independently to risk remains unclear . OBJECTIVE To compare waist-hip ratio ( WHR ) and waist circumference in determining risk of CHD in women . DESIGN AND SETTING Prospect i ve cohort study among US female registered nurses participating in the Nurses ' Health Study conducted between 1986 , when the nurses completed a question naire , and follow-up in June 1994 . PARTICIPANTS A total of 44702 women aged 40 to 65 years who provided waist and hip circumferences and were free of prior CHD , stroke , or cancer in 1986 . MAIN OUTCOME MEASURES Incidence of CHD ( nonfatal myocardial infa rct ion or CHD death ) . RESULTS During 8 years of follow-up 320 CHD events ( 251 myocardial infa rct ions and 69 CHD deaths ) were documented . Higher WHR and greater waist circumference were independently associated with a significantly increased age-adjusted risk of CHD . After adjusting for body mass index ( BMI ) ( defined as weight in kilograms divided by the square of height in meters ) and other cardiac risk factors , women with a WHR of 0.88 or higher had a relative risk ( RR ) of 3.25 ( 95 % confidence interval [ CI ] , 1.78 - 5.95 ) for CHD compared with women with a WHR of less than 0.72 . A waist circumference of 96.5 cm ( 38 in ) or more was associated with an RR of 3.06 ( 95 % CI , 1.54 - 6.10 ) . The WHR and waist circumference were independently strongly associated with increased risk of CHD also among women with a BMI of 25 kg/m2 or less . After adjustment for reported hypertension , diabetes , and high cholesterol level , a WHR of 0.76 or higher or waist circumference of 76.2 cm ( 30 in ) or more was associated with more than a 2-fold higher risk of CHD . CONCLUSIONS The WHR and waist circumference are independently associated with risk of CHD in women OBJECTIVES The aim of our study was to determine the effect of the menopause on various coronary heart disease ( CHD ) risk factors and on the global risk of CHD in a population based sample of women , making the difference between menopause and age related effects . STUDY DESIGN The Third French MONICA cross-sectional survey on cardiovascular risk included 1730 r and omly selected women , aged 35 - 64 years , representative from the general population . MAIN OUTCOME MEASURES Women were defined as post-menopausal ( postM ; n=696 ) , peri-menopausal ( periM ; n=183 ) or pre-menopausal ( preM ; n=659 ) based on the date of last menses . Socio-demographic , clinical and biological data were collected . Analyses of variance were used to compare means . RESULTS PostM women had significantly higher age-adjusted levels of total cholesterol ( 6.0mmol/L in postM vs. 5.7mmol/L in preM , p<0.05 ) and LDL cholesterol ( 3.9mmol/L vs. 3.6mmol/L , p<0.05 ) . There was no difference in HDL cholesterol or triglyceride levels , glycemia or blood pressure . Further adjustment on body mass index and hormonal treatments did not modify the results . No risk factor was significantly different between periM and postM. However , the Framingham 10-year risk of CHD was higher in postM , as compared with periM ( 5.1 % vs. 5.0 % , p<0.05 ) . In postM women , lipids and the Framingham risk were not associated with elapsed time since menopause . CONCLUSIONS The CHD risk increases during the sixth decade could be explained not only by estrogen deprivation but also by an effect on lipid profile , which is likely to occur in the peri-menopause period OBJECTIVES This prospect i ve study examined whether changes in traditional and novel coronary heart disease ( CHD ) risk factors are greater within a year of the final menstrual period ( FMP ) , relative to changes that occur before or after that interval , in a multiethnic cohort . BACKGROUND Underst and ing the influence of menopause on CHD risk remains elusive and has been evaluated primarily in Caucasian sample s. METHODS SWAN ( Study of Women 's Health Across the Nation ) is a prospect i ve study of the menopausal transition in 3,302 minority ( African American , Hispanic , Japanese , or Chinese ) and Caucasian women . After 10 annual examinations , 1,054 women had achieved an FMP not due to surgery and without hormone therapy use before FMP . Measured CHD risk factors included lipids and lipoproteins , glucose , insulin , blood pressure , fibrinogen , and C-reactive protein . We assessed which of 2 models provided a better fit with the observed risk factor changes over time in relation to the FMP : a linear model , consistent with chronological aging , or a piecewise linear model , consistent with ovarian aging . RESULTS Only total cholesterol , low-density lipoprotein cholesterol , and apolipoprotein B demonstrated substantial increases within the 1-year interval before and after the FMP , consistent with menopause-induced changes . This pattern was similar across ethnic groups . The other risk factors were consistent with a linear model , indicative of chronological aging . CONCLUSIONS Women experience a unique increase in lipids at the time of the FMP . Monitoring lipids in perimenopausal women should enhance primary prevention of CHD Objective : We examined whether circulating concentrations of sex hormones , including estradiol , testosterone , sex hormone – binding globulin ( SHBG ) , and dehydroepi and rosterone sulfate ( DHEAS ) , were associated with alcohol intake or mediated the alcohol – type 2 diabetes ( T2D ) association . Methods : Among women not using hormone replacement therapy and free of baseline cardiovascular disease , cancer , and diabetes in the Women 's Health Study , 359 incident cases of T2D and 359 matched controls were chosen during 10 years of follow-up . Results : Frequent alcohol intake ( ≥1 drink/day ) was positively and significantly associated with higher plasma estradiol concentrations in an age-adjusted model ( β = 0.14 , 95 % confidence interval [ CI ] , 0.03 , 0.26 ) , compared to rarely/never alcohol intake . After adjusting for additional known covariates , this alcohol – estradiol association remained significant ( β = 0.19 , 95 % CI , 0.07 , 0.30 ) . Testosterone ( β = 0.13 , 95 % CI , −0.05 , 0.31 ) , SHBG ( β = 0.07 , 95 % CI , −0.07 , 0.20 ) , and DHEAS ( β = 0.14 , 95 % CI , −0.04 , 0.31 ) showed positive associations without statistical significance . Estradiol alone or in combination with SHBG appeared to influence the observed protective association between frequent alcohol consumption and T2D risk , with a 12%–21 % reduction in odds ratio in the multivariate-adjusted models . Conclusions : Our cross-sectional analysis showed positive associations between alcohol intake and endogenous estradiol concentrations . Our prospect i ve data suggested that baseline concentrations of estradiol , with or without SHBG , might influence the alcohol – T2D association in postmenopausal women Several population studies from different countries have shown a J-shaped relation between intake of alcohol and mortality from all causes ( 1 - 6 ) . Studies comparing different countries have found a strong inverse relation between incidence rates of coronary heart disease and wine consumption but a weak or nonexistent relation for consumption of beer or spirits ( 7 - 9 ) . The findings that different types of alcoholic beverages have different effects on mortality are indirectly supported by several clinical and experimental studies ( 10 - 12 ) . In contrast , prospect i ve studies have shown that beer ( 13 ) , spirits ( 14 ) , and wine ( 15 ) may have protective effects . However , most of these investigations were based on population s with one predominant type of alcohol consumption ; this precluded valid comparison of the effects of the three different types of alcohol . We sought to analyze the effect of intake of different types of alcohol on mortality from all causes , coronary heart disease , and cancer in several large Danish cohort studies . Methods The Copenhagen Centre for Prospect i ve Population Studies is based on three study sample s : that of the Copenhagen City Heart Study ; that of the Copenhagen County Centre of Preventive Medicine ( the former Glostrup Population Studies ) , which includes six cohorts ; and that of the Copenhagen Male Study ( 16 - 18 ) . The study sample s of the Copenhagen City Heart Study , initiated in 1976 , and the Copenhagen County Centre of Preventive Medicine , initiated in 1964 , were r and omly selected within age strata from the population s residing in defined areas in greater Copenhagen . For the Copenhagen Male Study , initiated in 1971 , employees of 14 large companies in Copenhagen were invited to participate . The mean participation rate in all studies was 80 % ( range , 69 % to 88 % ) . The combined study sample comprises 13 064 men and 11 459 women for whom information on alcohol intake and lifestyle-related variables , described below , was complete . Alcohol Intake Participants of the Copenhagen City Heart Study and the studies in the Copenhagen County Centre of Preventive Medicine were asked about their current average weekly intake of beer , wine , and spirits . In the Copenhagen Male Study , participants were asked about their average daily intake of beer , wine , and spirits on weekdays ( Monday through Thursday ) and weekends ( Friday through Sunday ) ; these reports were combined to estimate weekly alcohol consumption . Persons in our study who did not drink alcohol because they were receiving disulfiram or other medication were excluded from the analysis . One bottle of beer contains 11.6 g of alcohol , and 12 g is an approximate average for one serving of wine or spirits . We grouped participants into five categories on the basis of total intake of alcohol : less than 1 drink/wk ( nondrinkers ) , 1 to 7 drinks/wk , 8 to 21 drinks/wk , 22 to 35 drinks/wk , and more than 35 drinks/wk . Intake of beer , wine , and spirits was categorized similarly ; however , because of the frequency of end point data , more than 21 drinks/wk is the highest intake category for the individual types of beverages . Smoking Status Participants reported whether they were never-smokers , former smokers , or current smokers . Current smokers reported grams of tobacco smoked per day in the form of cigarettes ( 1 g/d ) , small cigars ( 3 g/d ) , cigars ( 5 g/d ) , and pipe tobacco ( 50 g/package ) . Five groups were defined : never-smokers , former smokers , smokers of 1 to 14 g of tobacco daily , smokers of 15 to 24 g of tobacco daily , and smokers of more than 24 g of tobacco daily . Education Participants reported the number of years that they attended school . Three groups were defined : fewer than 8 years , 8 to 11 years , and 12 or more years of school education . Physical Activity Participants reported whether they were physically active during leisure time . Four groups were defined : sedentary ( < 2 h/wk ) , light activity ( 2 to 4 h/wk ) , moderate activity ( > 4 h/wk , noncompetitive ) and heavy activity ( > 4 h/wk , competitive ) . Body Mass Index Body weight and height were measured while the participant was wearing light clothes and no shoes . Body mass index was calculated as weight in kg divided by height in meters squared . Five categories of body mass index were defined : less than 20.0 kg/m2 , 20.0 to 24.9 kg/m2 , 25.0 to 29.9 kg/m2 , 30.0 to 34.9 kg/m2 , and 35.0 kg/m2 or more . Changes in Lifestyle-Related Variables When participants were re-examined during follow-up , the newly obtained values for alcohol intake , smoking status , physical activity , and body mass index were used to replace the old values in the statistical analyses . Observation time and vital status were included in the modeling accordingly . Follow-up Participants were followed from date of entry into the study to date of death , loss to follow-up , emigration , or end of follow-up , whichever came first . The vital status of population s was followed by using each participant 's unique identification number in the national Central Person Register until 9 January 1995 . Fewer than 1 % of the participants were lost to follow-up . Causes of death were obtained from the National Board of Health and were defined by using codes from International Classifications of Diseases , Eighth Revision ( codes 410.0 to 414.0 for coronary heart disease and codes 140.0 to 209.0 for cancer ) . According to a previous study , the reported diagnoses for these grouped codes have proven to be sufficiently valid ( 20 ) . Statistical Analysis We performed Poisson regression ( 21 ) by using SAS/STAT software ( 22 ) to estimate the effect of alcohol intake on the risk for death . These models generate estimates of relative risk that are adjusted for confounders . Each model included the following potential confounders as categorical variables : age , cohort study , sex , education , body mass index , physical activity , and smoking status . Owing to collinearity , it was impossible to include both the amount by type of beverage ( beer , wine , or spirits ) consumed and total alcohol intake in the same regression . We therefore estimated the influence of alcohol according to number of drinks consumed per week [ 0 , 1 to 7 , 8 to 21 , 22 to 35,>35 ] in three regressions : 1 ) total alcohol consumption in drinks per week , without considering beverage type ; 2 ) alcohol consumption in drinks of each beverage per week , without considering the total intake ; and 3 ) percentage of total alcohol intake consumed as wine ( 0 % , 1 % to 30%,>30 % ) . Effects that were insignificant according to the likelihood ratio test ( 5 % level ) were removed by backward elimination . A term indicating interaction between total alcohol intake and percentage alcohol consumed as beer , wine , or spirits was included in the analyses to assess whether the effects of beer , wine , and spirits differed at different levels of total alcohol intake ; no such effects were identified , as judged from the fit of the model . Likewise , no interaction was found between sex and intake of different types of beverage in terms of mortality . Results A total of 4275 women and 1635 men drank less than 1 drink per week ; 64 women and 1032 men drank 35 or more drinks per week . Of 13 613 participants who drank alcohol , 12 846 ( 69 % ) included wine in their intake ( Table 1 ) . During 257 859 person-years of follow-up , 4833 participants died ; of these , 1075 died of coronary heart disease and 1552 died of cancer . Table 1 . Baseline Characteristics of the Study Participants Baseline Characteristics Compared with participants who drank alcohol but no wine , those for whom wine made up more than 30 % of their total alcohol intake were more likely to be women and have a higher educational level but were less likely to be smokers ( Table 1 ) . Participants for whom wine made up more than 30 % of their alcohol intake were similar to those who drank no alcohol in terms of smoking habits , body mass index , and physical activity . Across categories of total alcohol intake , mean alcohol intake within the different categories of wine drinking was similar ; for example , among participants who drank 8 to 21 drinks/wk , those who drank no wine , those who drank 1 % to 30 % wine , and those who drank more than 30 % wine had a mean alcohol intake of 13.3 , 13.7 , and 12.8 drinks/wk , respectively . However , among light drinkers ( 1 to 7 drinks/wk ) , those who drank 1 % to 30 % of their alcohol as wine had a slightly higher mean intake than did those who avoided wine and those who drank more than 30 % of their alcohol intake as wine . Thus , assessment of the effects of wine intake may not be subject to residual confounding by total alcohol intake when controlled for as specified . Total Alcohol Intake and Mortality We found J-shaped relations between total alcohol intake and all-cause mortality in the three sub studies . Pooled analyses also revealed J-shaped relations ( Table 2 ) . When nondrinkers were used as the reference group ( relative risk , 1.00 ) , intake of 1 to 7 drinks per week carried a relative risk of 0.82 ( 95 % CI , 0.76 to 0.88 ) and intake of more than 35 drinks per week carried a relative risk of 1.10 ( CI , 0.95 to 1.26 ) . Alcohol intake was negatively related to death from coronary heart disease and positively related to death from cancer ( Table 2 ) . Table 2 . Relative Risk for Death with Regard to Total Alcohol Intake and Intake of Beer , Wine , and Spirits Intake of Beer , Wine , and Spirits and Mortality Light to moderate intake of beer or spirits had a small effect on death from all causes ( Table 2 ) . This finding contrasted with the effect of wine intake on mortality : Participants who drank 8 to 21 glasses of wine per week had a relative risk for death from all causes of 0.76 ( CI , 0.67 to 0.86 ) . Intake of fewer than 22 drinks of beer , wine , and spirits per week all carried lower risk for death from coronary heart disease ; the reduction in risk was of the same magnitude for beer and wine drinking but was smaller and not statistically significant for spirits drinking . Furthermore , light to moderate drinkers of wine Physical activity at work and in leisure time was studied by using a question naire in a r and om population sample from two counties of Eastern Finl and in 1972 . Data on age , serum cholesterol , diastolic blood pressure , height , weight and smoking were recorded in a field examination . The study population consisted of 3978 men aged 30 - 59 years and 3688 women aged 35 - 59 years . The participation rate was 92 % in men and 94 % in women in these age groups . During the approximately seven-year follow-up until December 31 , 1978 , 210 men and 63 women had an acute myocardial infa rct ion ( AMI ) , 89 men and 14 women died of acute ischemic heart disease , 71 men and 56 women had a cerebral stroke and 172 men and 75 women died of any disease . The subjects with a history of myocardial infa rct ion , angina or cerebral stroke in the 12 months preceding the baseline survey were excluded in the respective analysis . Low physical activity at work was associated with an increased risk of AMI , cerebral stroke and death due to any disease in both men and women , even when controlling for age , serum total cholesterol , diastolic blood pressure , height , weight and smoking in a multiple logistic model . The relative risk of AMI was 1.5 ( 90 % confidence interval ( CI ) = 1.2 - 2.0 ) in men and 2.4 ( 90 % CI = 1.5 - 3.7 ) in women . Low physical activity in leisure time had a significant association with an increased risk of death , but not with an increased risk of AMI or stroke in the multivariate analysis BACKGROUND Limited data are available on the benefit of combining healthy dietary and lifestyle behaviors in the prevention of myocardial infa rct ion ( MI ) in women . METHODS We used factor analysis to identify a low-risk behavior-based dietary pattern in 24 444 postmenopausal women from the population -based prospect i ve Swedish Mammography Cohort who were free of diagnosed cancer , cardiovascular disease , and diabetes mellitus at baseline ( September 15 , 1997 ) . We also defined 3 low-risk lifestyle factors : nonsmoking , waist-hip ratio less than the 75th percentile ( < 0.85 ) , and being physically active ( at least 40 minutes of daily walking or bicycling and 1 hour of weekly exercise ) . RESULTS During 6.2 years ( 151 434 person-years ) of follow-up , we ascertained 308 cases of primary MI . Two major identified dietary patterns , " healthy " and " alcohol , " were significantly associated with decreased risk of MI . The low-risk diet ( high scores for the healthy dietary pattern ) characterized by a high intake of vegetables , fruit , whole grains , fish , and legumes , in combination with moderate alcohol consumption ( > /= 5 g of alcohol per day ) , along with the 3 low-risk lifestyle behaviors , was associated with 92 % decreased risk ( 95 % confidence interval , 72%-98 % ) compared with findings in women without any low-risk diet and lifestyle factors . This combination of healthy behaviors , present in 5 % , may prevent 77 % of MIs in the study population . CONCLUSION Most MIs in women may be preventable by consuming a healthy diet and moderate amounts of alcohol , being physically active , not smoking , and maintaining a healthy weight OBJECTIVE To determine the relationship between aging , life-style factors and health-related factors and endogenous sex hormone levels . DESIGN Cross-sectional study of 400 independently living men between 40 and 80 Years of age . METHODS After exclusion of subjects who were not physically or mentally able to visit the study center , 400 men were r and omly selected from a population -based sample . Total testosterone ( TT ) , bioavailable testosterone ( BT ) ( i.e. not bound to sex hormone-binding globulin ( SHBG ) ) , SHBG , estradiol ( E(2 ) ) and dehydroepi and rosterone-sulfate ( DHEA-S ) were investigated for their relationship with age , body mass index ( BMI ) , waist circumference , smoking , physical activity and general health status . Multivariate models using ANCOVA analyses were used to examine the contribution of life-style factors to sex hormone variability . RESULTS TT , BT and DHEA-S decreased with age ; 0.2 , 0.7 and 1.2%/Year respectively . SHBG showed an increase with age of 1.1%/Year . No changes with age were found for E(2 ) . General health status modified the association of TT and SHBG with age ( P interaction 0.10 and 0.002 respectively ) . Increased BMI and waist circumference were associated with decreased TT , BT , SHBG and DHEA-S and increased E(2 ) ( all P<0.01 ) . Current smoking , lower alcohol intake and a higher physical activity score were associated with higher TT and SHBG levels . CONCLUSION This study showed the important determinants of sex hormones were age , BMI , waist circumference , smoking , general health status and physical activity . Furthermore , it can be concluded that general health status modified the effect between sex hormones and age . For future observational studies it should be taken into account that the above-mentioned determinants may alter the association between sex hormones and diseases and related conditions BACKGROUND Healthy lifestyle has been associated with decreased risk of coronary heart disease . In contrast , little is known about its association with stroke risk . METHODS This is a prospect i ve cohort study among 37 636 women 45 years or older participating in the Women 's Health Study . Stroke was self-reported and confirmed by means of medical record review . We considered the following self-reported lifestyle factors : smoking , alcohol consumption , exercise , body mass index , and diet . The health index was calculated from these variables by assigning scores from 0 to 4 to the respective variable categories , with a higher score indicating healthier behavior . Healthy behavior was defined as never smoking , alcohol consumption between 4 and 10.5 drinks per week , exercise 4 or more times per week , body mass index ( calculated as weight in kilograms divided by the square of height in meters ) less than 22 , and a diet high in cereal fiber , folate , and omega-3 fatty acids , with a high ratio of polyunsaturated to saturated fat , and low in trans fat and glycemic load . RESULTS During 10 years of follow-up , 450 strokes ( 356 ischemic , 90 hemorrhagic , and 4 undefined ) were confirmed . Compared with participants with 0 to 4 health index points ( 4.3 % ) , women with 17 to 20 health index points ( 4.7 % ) had multivariable-adjusted hazard ratios ( 95 % confidence interval ) of 0.45 ( 0.24 - 0.83 ; P<.001 for trend ) for total stroke , 0.29 ( 0.14 - 0.63 ; P<.001 for trend ) for ischemic stroke , and 1.27 ( 0.37 - 4.29 ; P = .62 for trend ) for hemorrhagic stroke . CONCLUSIONS In this large prospect i ve cohort of apparently healthy women , a healthy lifestyle consisting of abstinence from smoking , low body mass index , moderate alcohol consumption , regular exercise , and healthy diet was associated with a significantly reduced risk of total and ischemic stroke but not of hemorrhagic stroke . Our findings underscore the importance of healthy behaviors in the prevention of stroke BACKGROUND Alcohol consumption has both adverse and beneficial effects on survival . We examined the balance of these in a large prospect i ve study of mortality among U.S. adults . METHODS Of 490,000 men and women ( mean age , 56 years ; range , 30 to 104 ) who reported their alcohol and tobacco use in 1982 , 46,000 died during nine years of follow-up . We compared cause-specific and rates of death from all causes across categories of base-line alcohol consumption , adjusting for other risk factors , and related drinking and smoking habits to the cumulative probability of dying between the ages of 35 and 69 years . RESULTS Causes of death associated with drinking were cirrhosis and alcoholism ; cancers of the mouth , esophagus , pharynx , larynx , and liver combined ; breast cancer in women ; and injuries and other external causes in men . The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers ( relative risk , 1.3 ; 95 percent confidence interval , 1.1 to 1.6 ) . The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men ( relative risk , 0.7 ; 95 percent confidence interval , 0.7 to 0.8 ) and women ( relative risk , 0.6 ; 95 percent confidence interval , 0.6 to 0.7 ) reporting at least one drink daily than among nondrinkers , with little relation to the level of consumption . The overall death rates were lowest among men and women reporting about one drink daily . Mortality from all causes increased with heavier drinking , particularly among adults under age 60 with lower risk of cardiovascular disease . Alcohol consumption was associated with a small reduction in the overall risk of death in middle age ( ages 35 to 69 ) , whereas smoking approximately doubled this risk . CONCLUSIONS In this middle-aged and elderly population , moderate alcohol consumption slightly reduced overall mortality . The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco BACKGROUND The main associations of body-mass index ( BMI ) with overall and cause-specific mortality can best be assessed by long-term prospect i ve follow-up of large numbers of people . The Prospect i ve Studies Collaboration aim ed to investigate these associations by sharing data from many studies . METHODS Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospect i ve studies with 894 576 participants , mostly in western Europe and North America ( 61 % [ n=541 452 ] male , mean recruitment age 46 [ SD 11 ] years , median recruitment year 1979 [ IQR 1975 - 85 ] , mean BMI 25 [ SD 4 ] kg/m(2 ) ) . The analyses were adjusted for age , sex , smoking status , and study . To limit reverse causality , the first 5 years of follow-up were excluded , leaving 66 552 deaths of known cause during a mean of 8 ( SD 6 ) further years of follow-up ( mean age at death 67 [ SD 10 ] years ) : 30 416 vascular ; 2070 diabetic , renal or hepatic ; 22 592 neoplastic ; 3770 respiratory ; 7704 other . FINDINGS In both sexes , mortality was lowest at about 22.5 - 25 kg/m(2 ) . Above this range , positive associations were recorded for several specific causes and inverse associations for none , the absolute excess risks for higher BMI and smoking were roughly additive , and each 5 kg/m(2 ) higher BMI was on average associated with about 30 % higher overall mortality ( hazard ratio per 5 kg/m(2 ) [ HR ] 1.29 [ 95 % CI 1.27 - 1.32 ] ) : 40 % for vascular mortality ( HR 1.41 [ 1.37 - 1.45 ] ) ; 60 - 120 % for diabetic , renal , and hepatic mortality ( HRs 2.16 [ 1.89 - 2.46 ] , 1.59 [ 1.27 - 1.99 ] , and 1.82 [ 1.59 - 2.09 ] , respectively ) ; 10 % for neoplastic mortality ( HR 1.10 [ 1.06 - 1.15 ] ) ; and 20 % for respiratory and for all other mortality ( HRs 1.20 [ 1.07 - 1.34 ] and 1.20 [ 1.16 - 1.25 ] , respectively ) . Below the range 22.5 - 25 kg/m(2 ) , BMI was associated inversely with overall mortality , mainly because of strong inverse associations with respiratory disease and lung cancer . These inverse associations were much stronger for smokers than for non-smokers , despite cigarette consumption per smoker varying little with BMI . INTERPRETATION Although other anthropometric measures ( eg , waist circumference , waist-to-hip ratio ) could well add extra information to BMI , and BMI to them , BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22.5 - 25 kg/m(2 ) . The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal . At 30 - 35 kg/m(2 ) , median survival is reduced by 2 - 4 years ; at 40 - 45 kg/m(2 ) , it is reduced by 8 - 10 years ( which is comparable with the effects of smoking ) . The definite excess mortality below 22.5 kg/m(2 ) is due mainly to smoking-related diseases , and is not fully explained |
1,707 | 29,476,566 | CONCLUSION The application of behavioural change tools appears sub-optimal in this group of patients .
Explicit use of BCTs targeting behavioural components upon which outcomes depend may improve the uptake and effectiveness of rehabilitation interventions | OBJECTIVES International guidelines recommend that rehabilitation be offered to people with thoracic cancer to improve symptoms , function , and quality of life .
When rehabilitation interventions require a change in behaviour , the use of theory and behaviour change techniques ( BCTs ) enhance participation .
Our objective was to systematic ally identify BCTs and examine their use in relation to the Capability , Opportunity , Motivation-Behaviour model and known enablers and barriers to engagement in this population . | CONTEXT Few studies consider patient 's and caregiver 's preferences when developing nonpharmacological interventions . This is important to develop acceptable and accessible nonpharmacological interventions for patients with cancer . OBJECTIVES The objective of this study was to identify the views of patients with lung cancer and their informal caregivers on the desirable components of a novel nonpharmacological intervention for the management of the symptom cluster of cough , breathlessness , and fatigue , and their needs and preferences regarding uptake and delivery of the intervention . METHODS This study was qualitative in orientation , using semistructured interviews and framework analysis to elicit the views of 37 patients with lung cancer and 23 caregivers regarding the issues that were perceived to be important regarding the development and delivery of a nonpharmacological intervention . RESULTS A number of key issues were identified that carried important implication s for patient participation and adherence to the intervention , including the perceived relevance of potential techniques ; appreciable benefits in the short term ; convenience ; variation in patient preferences ; timing of the intervention ; venue ; caregiver involvement ; the provider of the intervention , and contact with other patients . CONCLUSION The data from this study have provided insight into the key issues that are likely to influence the development , uptake , and delivery of a nonpharmacological intervention to help manage the respiratory symptom cluster of cough , breathlessness , and fatigue . It is crucial that these findings are considered when developing and modeling a nonpharmacological symptom management intervention BACKGROUND Lung cancer has high mortality rates , with up to 90 % of patients dying within one to two years of its onset . It is essential to carry out research to attempt to solve the problems . Most patients suffer serious fatigue result ing from various symptoms and its long-term treatment . Furthermore , the other related complications such as underlying disease , anemia , malnutrition , nausea , and vomiting can reduced tolerance of chemotherapy . Study showed that nurses are the only hospital staff involved in managing fatigue . As it remains unclear to how fatigue should be managed , it is important to devise a strategy for providing a better service to help these patients survive longer . OBJECTIVE To examine fatigue scores in patients with lung cancer after chemotherapy treatment , and to compare the scores of the group receiving the multidisciplinary education program in self-care group with those of the control group . MATERIAL AND METHOD A r and omized controlled trial was conducted in two groups . The control group and the trial group were 30 patients in each . Studied aged from 45 to 65 years old who were receiving chemotherapy at the Chemotherapy Unit in the Out- Patients Department , Rajavithi Hospital . For a nine-week period , the control group received the hospital 's normal care program while the trial group received the multidisciplinary education program in self-care on fatigue . Scores were allocated to each individual to reflect their levels of fatigue , nutrition , physical fitness , and depression , compared using Independent t-test , Fisher exact test , and Mann-Whitney U-test . RESULTS Sixty patients were enrolled into the study ( mean age = 56.10 ( 45 - 65 ) , male = 68.33 % ) . The basic characteristics of each individual were not significantly different between the two groups . The mean ( + /- SD ) fatigue scores were 2.98 + /- 1.96 and 3.99 + /- 1.64 for the control and the trial group respectively , and these figures were statistically significant ( p = 0.036 ) . Nutrition scores were significantly higher in the trial group than in the control group ( p = 0.002 ) , but the other scores weight , albumin , physical fitness , and depression were not significantly different between the two groups . CONCLUSION The multidisciplinary education program in self-care results in decreased fatigue in patients with lung cancer who are receiving chemotherapy . Therefore , it is recommended that more health professionals and specialists participate actively inpatient care to respond directly to patients ' needs . This strategy should be adopted as the st and ard guideline for caring for patients with cancer who are receiving chemotherapy , and for patients with other conditions Purpose Patients with advanced cancer frequently experience anxiety , depression and poor quality of life ( QOL ) , as well as physical symptoms such as fatigue and weakness . Physical exercise has potential to help control these symptoms but the optimal training prescription is still not clear . We performed a study comparing medical Qigong ( QG ) and st and ard endurance and strength training ( SET ) in patients with advanced stage non-small cell lung ( NSCLC ) and gastrointestinal ( GI ) cancers . Methods A r and omized , cross-over study was performed in patients with advanced NSCLC and GI cancers receiving or eligible for chemotherapy . Patients received supervised QG or SET twice-weekly for 6 weeks . Psychological functioning , QOL , symptoms and physical functioning were assessed before and after each intervention period . Results Nineteen patients completed both interventions . Comparing interventions revealed no difference between QG and SET on change in anxiety or depression scores or QOL . However , SET treatment was better at improving perceived strength ( P = 0.05 ) and walking distance ( P = 0.02 ) . The order in which interventions were performed had a significant impact on the improvement in certain symptoms ( sleep quality , breathlessness , P < 0.05 ) , QOL ( P = 0.01 ) and walking distance ( P = 0.008 ) . In all cases , the beneficial effects of the exercise interventions were markedly reduced during the second interval . Conclusions QG and SET are equivalent in their impact on many aspects of psychological function in cancer patients . However , SET leads to greater improvements in exercise capacity and helps reduce some symptoms . The reduction in beneficial effect of SET on exercise function when offered as the second intervention is a new finding that warrants further study CONTEXT Physical exercise can alleviate cancer-related fatigue . R and omized controlled trials in patients with advanced cancer are scarce . OBJECTIVES We test the impact of a structured , individual sports program on fatigue in patients with advanced cancer . METHODS Seventy-seven patients were invited to participate in this r and omized controlled trial exploring the effects of physical exercises on fatigue 12 and 24 weeks after baseline . Patients were r and omized into three groups . Group A received treatment as usual , Group B was taught a structured , individual sports program , and Group C received additional ambulatory physiotherapeutical supervision . Primary outcome was general fatigue , secondary outcomes included rate of severe general fatigue , further dimensions of the Multidimensional Fatigue Inventory ( MFI ) , as well as walking distance . RESULTS Mean score of general fatigue as well as other MFI subdimensions differed nonsignificantly between all groups at 12 weeks . However , the mental fatigue score demonstrated a statistically significant difference between the three groups . The rate of severe general fatigue was significantly reduced within Intervention Group C. Significant longitudinal change of MFI-dimension mental fatigue was found and reached the threshold for minimal clinical ly important difference , while all MFI-dimensions increased in Group A. CONCLUSION Our results imply that tumor- patients ' severe general fatigue can be reduced when patients conduct appropriate physical exercise . This study amends previous knowledge , as it describes the impact of outpatient physical exercise on fatigue in a heterogeneous patient cohort with various advanced cancer entities . Furthermore , this trial differentiates between patients with only a self-directed exercise program versus those receiving additional partially professional supervision Background : Few studies have evaluated an individualized home-based exercise prescription during and after cancer treatment . Objective : The purpose of this study was to evaluate the effectiveness of a home-based exercise training intervention , the Pro-self Fatigue Control Program on the management of cancer-related fatigue . Interventions / Methods : Participants ( N = 119 ) were r and omized into 1 of 3 groups : group 1 received the exercise prescription throughout the study ; group 2 received their exercise prescription after completing cancer treatment ; and group 3 received usual care . Patients completed the Piper Fatigue Scale , General Sleep Disturbance Scale , Center for Epidemiological Studies -Depression Scale , and Worst Pain Intensity Scale . Results : All groups reported mild fatigue levels , sleep disturbance , and mild pain , but not depression . Using multilevel regression analysis , significant linear and quadratic trends were found for change in fatigue and pain ( ie , scores increased , then decreased over time ) . No group differences were found in the changing scores over time . A significant quadratic effect for the trajectory of sleep disturbance was found , but no group differences were detected over time . No significant time or group effects were found for depression . Conclusions : Our home-based exercise intervention had no effect on fatigue or related symptoms associated with cancer treatment . The optimal timing of exercise remains to be determined . Implication s for Practice : Clinicians need to be aware that some physical activity is better than none , and there is no harm in exercise as tolerated during cancer treatment . Further analysis is needed to examine the adherence to exercise . More frequent assessment s of fatigue , sleep disturbance , depression , and pain may capture the effect of exercise The authors conducted a r and omized controlled trial to evaluate a nurse practitioner (NP)‐delivered symptom management intervention for patients initiating chemotherapy for nonmetastatic cancer . The aim was to reduce patient‐reported symptom burden by facilitating patient‐NP collaboration and the early management of symptoms Abstract Background . Patients with lung cancer are often burdened by dyspnoea , fatigue , decreased physical ability and loss of weight . Earlier studies of physical exercise of patients with COPD have shown promising results . The aim of this study was to investigate , if a well-documented COPD rehabilitation protocol can improve physical fitness and quality of life ( QoL ) in patients with lung cancer . Material and methods . Forty-five patients , with a minimum walking distance of 50 meters , absence of cognitive deficits or severe heart disease and motivated for physical training were invited to an exercise intervention . The intervention consisted of seven weeks of twice weekly training , focusing on walking training , circuit training , h and ling of dyspnoea and instructions in daily diary-based training at home . Prior to , and after the intervention , Incremental- and Endurance Shuttle Walk Test ( ISWT and ESWT ) were performed , and pulmonary function as well as self-reported QoL ( EORTC-QLQ-C30 and LC13 ) were measured . Results . Fourteen subjects dropped out before commencement of the intervention . Seven were excluded after physiotherapeutic evaluation . Of the remaining 24 , three were excluded because of insufficient attendance ( < 65 % of scheduled exercise sessions ) thus 21 patients completed the intervention . For 17 patients with complete pre- and post intervention data , ISWT increased 9 % ( −77 to 39 % ) ( median and range ) ( p = 0.021 ) , while ESWT increased 109 % ( −70 to 432 % ) ( p = 0.002 ) . Twelve of 17 improved in ISWT , while 15 improved in ESWT . No changes in pulmonary function and improvements in QoL were observed . Conclusion . Patients with pulmonary cancer can achieve significant improvements in physical fitness measured with ISWT and ESWT after completion of the intervention program . No changes in pulmonary function and QoL were observed . In addition , we found that a large number of patients dropped out before intervention and that the patients , who succeeded , often discontinued training at home Purpose 1 ) To determine the effect of a home-based walking exercise program on the sleep quality and quality of life of cancer patients , as well as 2 ) to determine if enhanced sleep quality was associated with improvement in quality of life over time . Methods This is a prospect i ve , longitudinal , two-armed , r and omized clinical trial . Participants were recruited from oncology outpatient clinics in two university-based medical centers and were allocated to either usual care ( n = 35 ) or a home-based walking exercise intervention for 8 weeks ( n = 36 ) . Measurements included the Taiwanese version of the Pittsburgh Sleep Quality Index , the Medical Outcomes Study Short Form-36 , the Taiwanese Version Ratings of the Perceived Exertion Scale , and a walking exercise log . This study was analyzed on an intention-to-treat basis . Effects of the walking exercise program on sleep quality and quality of life were analyzed by the generalized estimating equation method . Results Patients in the exercise group reported significant improvements in sleep quality ( β = −3.54 , p < 0.01 ) and the mental health dimension of quality of life ( β = 10.48 , p < 0.01 ) . Among patients who exercised , enhanced sleep quality also corresponded with reduced bodily pain ( β = 0.98 , p = 0.04 ) and improvements over time in the mental health dimension of quality of life ( β = −3.87 , p < 0.01 ) . Conclusions A home-based walking exercise program can be easily incorporated into care for cancer patients who are suffering from sleep disturbances Background Previous studies showed that exercise in cancer patients is feasible and may reduce fatigue and improve physical fitness and quality of life . However , many previous studies had method ological weaknesses related to trial design , sample size , comparison group , outcome measures , short follow-up duration s and programme content . Purpose This paper aims to present the rationale and design of the clinical research subprogramme of the Alpe d’HuZes Cancer Rehabilitation ( A-CaRe ) programme . Method A-CaRe Clinical Research includes four r and omized controlled trials in patients : ( a ) after chemotherapy , ( b ) during chemotherapy , ( c ) after stem cell transplantation and ( d ) during childhood cancer . These trials compare high-intensity resistance and endurance exercise interventions with usual care or a waiting list control group . In two studies , a second intervention arm consisting of low-to-moderate intensity exercise is included . All four A-CaRe trials use similar methods . Results Outcome measures are carefully chosen based on the International Classification of Functioning Disability and Health model . Measurements will be performed prior to r and omization ( T0 ) , after completion of the intervention ( T1 ) and at follow-up ( T2 ) . The primary outcome measures are cardiorespiratory fitness , muscle strength and fatigue . Secondary outcome measures include health-related quality of life and psychosocial functioning . Furthermore , cost-effectiveness and cost-utility analyses are performed from a societal perspective . Conclusion We hypothesize that exercise is more effective at improving physical fitness and thereby reducing fatigue and more cost-effective compared with usual care or a waiting list control group . If so , the programmes will be implemented in the Dutch clinical practice Purpose A previous study investigated the effects of a well-documented COPD exercise protocol in lung cancer patients . The study showed improvements in physical fitness , but poor adherence to continued exercise after intervention . The aim of the present study was to investigate the effect of a modified exercise intervention on post-intervention adherence , and physical fitness in a broad group of lung cancer patients . Methods Fifty-nine patients enrolled in a 9-week exercise program . Eligibility criteria were limited to presence of motivation , and absence of comorbidities that could jeopardize safety . The intervention included three times 3 weeks of exercise ( 3 weeks supervised , 3 weeks home-based and 3 weeks supervised ) . The patient ’s activities were structured by logbooks during the 3 weeks at home . VO2 max was estimated at baseline and at the end of intervention . Self-reported quality of life was recorded before and after the exercise program . Post-intervention exercise activity was assessed by telephone interviews 4 weeks after intervention . Results Fifty-one patients initiated the exercise intervention and 29 patients successfully completed the exercise program . Full data were available for 25 patients regarding estimated VO2 max . Twenty-six of the 29 were available for follow-up with respect to continuance of physical activity . Among the 26 who completed the 9-week training program , 18 ( 69 % ) continued to be physically active on a daily basis . No change in estimated VO2 max was observed . A trend towards increased quality of life and better symptom control was noted . Conclusions The present study showed an increased level of continuance of physical activity compared to the previous study . The present study could , however , not repeat the significant improvements in estimated VO2 max from the previous study Purpose This r and omized controlled trial tested the effects of a specially design ed strength and endurance training on the independence and quality of life in lung cancer patients in stages IIIA/IIIB/IV during palliative chemotherapy . Methods Between August 2010 and December 2011 , 46 patients were r and omized into two groups receiving either conventional physiotherapy or special physiotherapeutic training . The Barthel Index served as primary endpoint . The secondary endpoints were the European Organization for Research and Treatment of Cancer Quality of Life Question naire Core-30 ( EORTC QLQ C-30/LC-13 ) question naire , the 6-Minute Walk Test ( 6MWT ) , stair walking , the Modified Borg Scale , and muscle strength . Nonparametrical data were analyzed with the Wilcoxon and Mann – Whitney U test . For parametric , data student t tests were used . A p value of ≤.05 was accepted . Results Twenty-nine patients completed the trial ( Intervention group ( IG ) , n = 18 ; control group ( CG ) , n = 11 ) . Significant differences were detectable in the Barthel Index ( IGmean = 92.08 ; CGmean = 81.67 ; p = .041 ) , in single scores of the EORTC QLQ C-30/LC-13 question naire ( physical functioning , p = .025 ; hemoptysis , p = .019 ; pain in arms or shoulder , p = .048 ; peripheral neuropathy , p = .050 ; cognitive functioning , p = .050 ) , in the 6MWT , stair walking , strength capacity , and in the patient ’s dyspnoea perception during submaximal walking activities ( IG > CG ) . Conclusion According to these findings , lung cancer patients should receive enhanced physical activity intervention during palliative chemotherapy Background : Although exercise has been addressed as an adjuvant treatment for anxiety , depression and cancer-related symptoms , limited studies have evaluated the effectiveness of exercise in patients with lung cancer . Methods : We recruited 116 patients from a medical centre in northern Taiwan , and r and omly assigned them to either a walking-exercise group ( n=58 ) or a usual-care group ( n=58 ) . We conducted a 12-week exercise programme that comprised home-based , moderate-intensity walking for 40 min per day , 3 days per week , and weekly exercise counselling . The outcome measures included the Hospital Anxiety and Depression Scale and the Taiwanese version of the MD And erson Symptom Inventory . Results : We analysed the effects of the exercise programme on anxiety , depression and cancer-related symptoms by using a generalised estimating equation method . The exercise group patients exhibited significant improvements in their anxiety levels over time ( P=0.009 and 0.006 in the third and sixth months , respectively ) and depression ( P=0.00006 and 0.004 in the third and sixth months , respectively ) than did the usual-care group patients . Conclusions : The home-based walking exercise programme is a feasible and effective intervention method for managing anxiety and depression in lung cancer survivors and can be considered as an essential component of lung cancer rehabilitation The persistence of negative attitudes towards cancer pain and its treatment suggests there is scope for identifying more effective pain education strategies . This r and omized controlled trial involving 189 ambulatory cancer patients evaluated an educational intervention that aim ed to optimize patients ' ability to manage pain . One week post-intervention , patients receiving the pain management intervention ( PMI ) had a significantly greater increase in self-reported pain knowledge , perceived control over pain , and number of pain treatments recommended . Intervention group patients also demonstrated a greater reduction in willingness to tolerate pain , concerns about addiction and side effects , being a " good " patient , and tolerance to pain relieving medication . The results suggest that targeted educational interventions that utilize individualized instructional techniques may alter cancer patient attitudes , which can potentially act as barriers to effective pain management PURPOSE / OBJECTIVES To evaluate the feasibility of a patient-controlled cognitive-behavioral intervention for pain , fatigue , and sleep disturbance during treatment for advanced cancer and to assess initial efficacy of the intervention . DESIGN One group pre- and post-test design . SETTING Outpatient oncology clinics at a comprehensive cancer center in the midwestern United States . SAMPLE 30 adults with advanced ( recurrent or metastatic ) colorectal , lung , prostate , or gynecologic cancer receiving chemotherapy or radiotherapy . METHODS Participants completed baseline measures ( e.g. , demographics , symptom inventory ) and received education and training to use an MP3 player loaded with 12 cognitive-behavioral strategies ( e.g. , relaxation exercises , guided imagery , nature sound recordings ) . Participants used the strategies as needed for symptom management for two weeks , keeping a log of symptom ratings with each use . Following the two-week intervention , participants completed a second symptom inventory and an evaluation of the intervention . MAIN RESEARCH VARIABLES Feasibility , patient-controlled cognitive-behavioral intervention , pain , fatigue , and sleep disturbance . FINDINGS Thirty of 43 eligible patients ( 73 % ) agreed to participate ; of them , 27 ( 90 % ) completed the study . Most reported that they enjoyed the intervention , had learned useful skills , and perceived improvement in their symptoms . Symptom scores at two weeks did not differ significantly from baseline ; however , significant reductions in pain , fatigue , and sleep disturbance severity were found in ratings made immediately before and after use of a cognitive-behavioral strategy . CONCLUSIONS The patient-controlled cognitive-behavioral intervention appears to be feasible for additional study and could reduce day-to-day severity of co-occurring pain , fatigue , and sleep disturbance . IMPLICATION S FOR NURSING A r and omized , controlled trial is needed to test efficacy of the intervention for co-occurring pain , fatigue , and sleep disturbance . Meanwhile , based on previous efficacy studies , cognitive-behavioral strategies can be recommended for certain individual symptoms 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 Background Palliative care ( PC ) patients experience loss of physical function which usually impedes mobility , autonomy and quality of life . We aim ed at examining the feasibility of a home-based exercise program for patients with advanced , incurable diseases after discharge . Results This was a single-arm pilot study ( WHO-ICTRP : DRKS00005048 ) . The 12-week home-based program comprised strength , balance , flexibility and endurance components . Patients with a presumed life expectancy of 6–12 months were recruited during a 6-months period on a specialized PC and a radiation therapy ward . We chose the De Morton Mobility Index as primary outcome . Secondary outcomes were quality of life , 6-min walk test and others . A total of 145 patients were screened , 103 ( 98 % ) out of 105 patients on the specialized PC ward could not be included , mostly because of a low performance status [ n = 94 ; 90 % ; Eastern Cooperative Oncology Group ( ECOG ) > 2 ] . The only two eligible patients declined to participate . Eleven out of 40 patients ( 28 % ) were eligible on the radiation therapy ward . However , only one patient ( 9 % ) participated but dropped out 2 days later ( upcoming surgery ) . Distance to the hospital ( n = 3 ; 30 % ) and considering additional tasks as “ too much ” ( n = 3 ; 30 % ) were most common reasons for non-participation . Conclusions Establishing a home-based exercise program for in patients after discharge was not feasible mainly due to non- eligibility and lack of dem and . For future trials , we suggest that choosing ( 1 ) out patients with ( 2 ) an ECOG of ≤2 and ( 3 ) an estimated survival of ≥9 months could enhance participation in home-based exercise programs PURPOSE Several guidelines on the treatment of cancer-related fatigue recommend optimizing treatment of accompanying symptoms . However , evidence for this recommendation from r and omized clinical trials is lacking . We investigated whether monitoring and protocol ized treatment of physical symptoms alleviates fatigue . PATIENTS AND METHODS In all , 152 fatigued patients with advanced cancer were r and omly assigned to protocol ized patient-tailored treatment ( PPT ) of symptoms or care as usual . The PPT group had four appointments with a nurse who assessed nine symptoms on a 0 to 10 numeric rating scale ( NRS ) . Patients received a nonpharmacologic intervention for symptoms with a score ≥ 1 and a medical intervention for symptoms with a score ≥ 4 . Fatigue dimensions , fatigue NRS score , interference of fatigue with daily life , symptom burden , quality of life , anxiety , and depression were measured at baseline and after 1 , 2 , and 3 months . Differences between the groups over time were assessed by using mixed modeling . RESULTS Seventy-six patients were r and omly assigned to each study arm . Mean age was 58 ± 10 years , 57 % were female , and 65 % were given palliative chemotherapy . We found significant improvements over time in favor of PPT for the primary outcome general fatigue ( P = .01 ) , with significant group differences at month 1 ( effect size , 0.26 ; P = .007 ) and month 2 ( effect size , 0.35 ; P = .005 ) . Improvements in favor of PPT were also found for the following secondary outcomes : fatigue dimensions " reduced activity " and " reduced motivation , " fatigue NRS , symptom burden , interference of fatigue with daily life , and anxiety ( all P ≤ .03 ) . CONCLUSION In fatigued patients with advanced cancer , nurse-led monitoring and protocol ized treatment of physical symptoms is effective in alleviating fatigue Purpose It has not previously been shown whether there is any benefit to multi-morbid patients with lung cancer who participate in complex interdisciplinary rehabilitation programmes after primary therapy . The purpose of this prospect i ve study was to assess changes in exercise capacity and quality of life before and after an in-patient training programme . Patients and methods Forty-five patients with lung cancer ( WHO I-III after surgery and /or radiotherapy and /or chemotherapy ) were enrolled in a 28-day in-patient rehabilitation programme that included st and ardised aerobic training . Functional status and health-related quality of life ( QLQ-C30 , QLQ-LC13 , SF-36 , and MFI-20 ) were examined at the beginning of the study and at day 28 . Results A substantial increase in work performance ( bicycle ergometry from 68 ± 3 to 86 ± 4 W , p < 0.001 , and 6-minute walk test from 322 ± 11 to 385 ± 13 m , p < 0.001 ) was registered . In addition , heart rate at rest was reduced ( from 84 ± 2 to 80 ± 1 beats per minute , p < 0.05 ) and heart rate variability ( indicator of the efficacy of endurance training ) was significantly increased ( from 9.7 ± 1 to 12.9 ± 1 root mean square of successive differences , p < 0.001 ) . Moreover , there was also a significant improvement in quality of life ( 48 ± 3 to 62 ± 2 , p < 0.001 ) while fatigue was reduced from 66 ± 3 to 41 ± 4 , p < 0.001 . Conclusion A st and ardised , aerobic endurance training programme as part of the in-patient oncological rehabilitation of patients with lung cancer results in improvements in both physiological and psychological parameters after therapy . A follow-on study in order to determine to what extent this benefit persists over the long-term , particularly , in comparison with patients who have not participated in a rehabilitation programme , is currently being conducted Background About 90 % of patients with intra-thoracic malignancy experience breathlessness . Breathing training is helpful , but it is unknown whether repeated sessions are needed . The present study aims to test whether three sessions are better than one for breathlessness in this population . Methods This is a multi-centre r and omised controlled non-blinded parallel arm trial . Participants were allocated to three sessions or single ( 1:2 ratio ) using central computer-generated block r and omisation by an independent Trials Unit and stratified for centre . The setting was respiratory , oncology or palliative care clinics at eight UK centres . Inclusion criteria were people with intrathoracic cancer and refractory breathlessness , expected prognosis ≥3 months , and no prior experience of breathing training . The trial intervention was a complex breathlessness intervention ( breathing training , anxiety management , relaxation , pacing , and prioritisation ) delivered over three hour-long sessions at weekly intervals , or during a single hour-long session . The main primary outcome was worst breathlessness over the previous 24 hours ( ‘ worst ’ ) , by numerical rating scale ( 0 = none ; 10 = worst imaginable ) . Our primary analysis was area under the curve ( AUC ) ‘ worst ’ from baseline to 4 weeks . All analyses were by intention to treat . Results Between April 2011 and October 2013 , 156 consenting participants were r and omised ( 52 three ; 104 single ) . Overall , the ‘ worst ’ score reduced from 6.81 ( SD , 1.89 ) to 5.84 ( 2.39 ) . Primary analysis [ n = 124 ( 79 % ) ] , showed no between-arm difference in the AUC : three sessions 22.86 ( 7.12 ) vs single session 22.58 ( 7.10 ) ; P value = 0.83 ) ; mean difference 0.2 , 95 % CIs ( –2.31 to 2.97 ) . Complete case analysis showed a non-significant reduction in QALYs with three sessions ( mean difference –0.006 , 95 % CIs –0.018 to 0.006 ) . Sensitivity analyses found similar results . The probability of the single session being cost-effective ( threshold value of £ 20,000 per QALY ) was over 80 % . Conclusions There was no evidence that three sessions conferred additional benefits , including cost-effectiveness , over one . A single session of breathing training seems appropriate and minimises patient burden . Trial registration Registry : IS RCT N ; Trial registration number : IS RCT N49387307 ; http://www.is rct n.com/IS RCT N49387307 ; registration date : OBJECTIVE The primary aim of the present article was to identify palliative care patient population s who are willing to participate in and able to complete a group exercise/physical training program design ed specifically for the individual patient . METHOD We conducted a prospect i ve phase II intervention study examining the willingness and ability of palliative care cancer patients to participate in a group exercise physical training program . Patients who were diagnosed with incurable cancer and had a life expectancy of less than 1 year at two outpatient clinics were invited to participate in an exercise program in the hospitals . The groups met twice a week over a 6-week period . RESULTS One hundred one consecutive patients were asked for inclusion . Sixty-three patients agreed to participate . Sixteen ( 25 % ) of the 63 patients dropped out after consent was given , but before the program started due to medical problems , social reasons , or death . Thus , 47 patients started the exercise program . Thirteen patients withdrew during the program due to sudden death , medical problems , or social reasons . The most frequent reasons for withdrawal were increased pain or other symptoms . Thirty-four patients completed the exercise program . SIGNIFICANCE OF RESULTS A high proportion of incurable cancer patients were willing to participate ( 63 % ) in a structured exercise program . The attrition rate was high , but despite being severely ill , 54 % of the patients completed the exercise period . This shows that a physical exercise program tailored to the individual patient is feasible in this population Purpose Peak oxygen consumption ( VO2peak ) is an important predictive factor for long-term prognosis in patients with non-small cell lung cancer ( NSCLC ) . The purpose of this study was to investigate whether 8 weeks of exercise training improves exercise capacity , as assessed by VO2peak , and other related factors in patients with NSCLC receiving targeted therapy . Methods A total of 24 participants with adenocarcinoma were r and omly assigned to either the control group ( n = 11 ) or the exercise group ( n = 13 ) . Subjects in the exercise group participated in individualized , high-intensity aerobic interval training of exercise . The outcome measures assessed at baseline and after 8 weeks were as follows : VO2peak and the percentage of predicted VO2peak ( % predVO2peak ) , muscle strength and endurance of the right quadriceps , muscle oxygenation during exercise , insulin resistance as calculated by the homeostasis model , high-sensitivity C-reactive protein , and quality of life ( QoL ) question naire inventory . Results No exercise-related adverse events were reported . After exercise training , VO2peak and % predVO2peak increased by 1.6 mL kg−1 min−1 and 5.3 % ( p < 0.005 ) , respectively ; these changes were associated with improvements in circulatory , respiratory , and muscular functions at peak exercise ( all p = 0.001 ) . The exercise group also had less dyspnea ( p = 0.01 ) and favorably lower fatigue ( p = 0.05 ) than baseline . Conclusions Patients with NSCLC receiving targeted therapy have quite a low exercise capacity , even with a relatively high QoL. Exercise training appears to improve exercise capacity and alleviate some cancer-related symptoms BACKGROUND Palliative cancer patients suffer from high levels of distress . There are physiological changes in relation to the level of perceived distress . OBJECTIVE To study the efficacy of 5 minutes of mindful breathing ( MB ) for rapid reduction of distress in a palliative setting . Its effect to the physiological changes of the palliative cancer patients was also examined . METHODS This is a r and omized controlled trial . Sixty palliative cancer patients were recruited . They were r and omly assigned to either 5 minutes of MB or normal listening arms . The changes of perceived distress , blood pressure , pulse rate , breathing rate , galvanic skin response , and skin surface temperature of the patients were measured at baseline , after intervention , and 10 minutes post-intervention . RESULTS There was significant reduction of perceived distress , blood pressure , pulse rate , breathing rate , and galvanic skin response ; also , significant increment of skin surface temperature in the 5-minute MB group . The changes in the 5-minute breathing group were significantly higher than the normal listening group . CONCLUSION Five-minute MB is a quick , easy to administer , and effective therapy for rapid reduction of distress in palliative setting . There is a need for future study to establish the long-term efficacy of the therapy PURPOSE / OBJECTIVES To examine the effects of concrete objective information ( COI ) and relaxation instruction ( RI ) on patients undergoing radiation therapy , as well as the contribution of symptom uncertainty and body awareness to the intervention effects . DESIGN Three-group r and omized trial . Assignment was stratified by cancer site . Data collectors were blinded to group assignments . SETTING University medical center radiation therapy department serving both urban and rural communities in the southeastern United States . SAMPLE 76 adults having radiation with curative intent for gynecologic , head and neck , or lung cancer . Most were Caucasian and had in situ to stage II disease . Mean age was 55 years . METHODS COI and RI were delivered by tape recordings . Outcome measures were indicators of usual activities and emotions at treatment week 3 and two and four weeks post-treatment . MAIN RESEARCH VARIABLES Intervention group ; social , household , and recreational activities ; anxiety , depression , and anger ; body awareness ; and symptom uncertainty . FINDINGS Participants receiving either intervention reported more social activity during treatment . Those given RI who were high in body awareness reported more household activity during treatment . No effects were found regarding emotion . Symptom uncertainty partially explained COI effects . CONCLUSIONS The findings provide additional support for the effectiveness of COI in helping patients to maintain more of their usual activities during radiation therapy . Instruction in progressive muscle relaxation also may help in maintaining activities . IMPLICATION S FOR NURSING COI helps patients to cope with treatment by reducing their uncertainty about symptoms . RI effects may vary by activity type and awareness of usual body sensations Background : Individuals with cancer receiving chemotherapy suffer deterioration in physical functioning due to symptoms arising from the cancer disease process and its treatment . Objectives : To determine if age , chronic health conditions ( comorbidity ) , stage of cancer , depressive symptomatology , symptom limitations , sex , and site of cancer moderate the effects of cognitive behavioral intervention on physical function and to determine if symptom limitations mediate the effect of the intervention on physical functioning . Methods : Two hundred thirty-seven individuals with solid tumor cancer ( 118 experimental and 119 control group ) participated in this 10-contact , 18-week r and omized control trial . Cognitive behavioral theory guided the nurse-delivered problem-solving experimental intervention . The control group received conventional care . Interviews occurred at baseline and 10 , 20 , and 32 weeks . Results : Women with breast cancer had significantly better physical functioning than women with lung cancer . Chronic health conditions , symptom limitation , and depressive symptomatology at baseline were found to moderate the effect of intervention on physical function . Symptom limitation , however , was not found to mediate the effect of intervention on physical functioning . Discussion : The intervention was shown to affect physical function trajectories differently for individuals with different personal and health characteristics . Because poor physical functioning is strongly associated with mortality and poor quality of life , this information may be used by health professionals to target interventions to those who might be most responsive Objective . Theory use may enhance effectiveness of behavioral interventions , yet critics question whether theory-based interventions have been sufficiently scrutinized . This study applied a framework to evaluate theory use in physical activity interventions for breast cancer survivors . The aims were to ( 1 ) evaluate theory application intensity and ( 2 ) assess the association between extensiveness of theory use and intervention effectiveness . Methods . Studies were previously identified through a systematic search , including only r and omized controlled trials published from 2005 to 2013 , that addressed physical activity behavior change and studied survivors who were < 5 years posttreatment . Eight theory items from Michie and Prestwich ’s coding framework were selected to calculate theory intensity scores . Studies were classified into three subgroups based on extensiveness of theory use ( Level 1 = sparse ; Level 2 = moderate ; and Level 3 = extensive ) . Results . Fourteen r and omized controlled trials met search criteria . Most trials used the transtheoretical model ( n = 5 ) or social cognitive theory ( n = 3 ) . For extensiveness of theory use , 5 studies were classified as Level 1 , 4 as Level 2 , and 5 as Level 3 . Studies in the extensive group ( Level 3 ) had the largest overall effect size ( g = 0.76 ) . Effects were more modest in Level 1 and 2 groups with overall effect sizes of g = 0.28 and g = 0.36 , respectively . Conclusions . Theory use is often viewed as essential to behavior change , but theory application varies widely . In this study , there was some evidence to suggest that extensiveness of theory use enhanced intervention effectiveness . However , there is more to learn about how theory can improve interventions for breast cancer survivors The efficacy of a relaxation technique involving deep breathing , muscle relaxation , and imagery was tested as a nursing intervention for the promotion of comfort and pain relief in hospitalized oncology patients . The intervention was implemented in accordance with Orem 's self-care approach to nursing practice . Sixty-seven new admissions to an oncology ward were r and omly assigned to receive relaxation training by audio tapes , live relaxation training by nurses , or no relaxation training . Relaxation training was conducted twice weekly over a period of three weeks . All subjects were pretested and post-tested with the McGill Pain Question naire and Visual Analogue Scale for pain . Analgesic medication was monitored throughout the study . Data analysis showed significant reductions in subjective pain ratings by subjects receiving relaxation training . There was also a significant reduction in non-opiate p.r.n . analgesic intake which suggested a reduced incidence of breakthrough pain Background Breathlessness , cough and fatigue are distressing symptoms for patients with lung cancer . There is evidence that these three symptoms form a discreet symptom cluster . This study aim ed to feasibly test a new non-pharmacological intervention for the management of the Respiratory Distress Symptom Cluster ( breathlessness-cough-fatigue ) in lung cancer . Method This was a multi-centre , r and omised controlled non-blinded parallel group feasibility trial . Eligible patients ( patients with primary lung cancer and ‘ bothered ’ by at least two of the three cluster symptoms ) received usual care plus a multicomponent intervention delivered over two intervention training sessions and a follow-up telephone call or usual care only . Follow-up was for 12 weeks , and end-points included six numerical rating scales for breathlessness severity , Dyspnoea-12 , Manchester Cough in Lung Cancer scale , FACIT-Fatigue scale , Hospital Anxiety and Depression scale , Lung Cancer Symptom Scale and the EQ-5D-3L , collected at baseline , week 4 and week 12 . Results One hundred seven patients were r and omised over 8 months ; however , six were removed from further analysis due to protocol violations ( intervention group n = 50 and control group n = 51 ) . Of the ineligible patients ( n = 608 ) , 29 % reported either not experiencing two or more symptoms or not being ‘ bothered ’ by at least two symptoms . There was 29 % drop-out by week 4 , and by week 12 , a further two patients in the control group were lost to follow-up . A sample size calculation indicated that 122 patients per arm would be needed to detect a clinical ly important difference in the main outcome for breathlessness , cough and fatigue . Conclusions The study has provided evidence of the feasibility and acceptability of a new intervention in the lung cancer population and warrants a fully powered trial before we reach any conclusions . The follow-on trial will test the hypothesis that the intervention improves symptom cluster of breathlessness , cough and fatigue better than usual care alone . Full economic evaluation will be conducted in the main trial Objective To assess the effect of a multimodal group exercise intervention , as an adjunct to conventional care , on fatigue , physical capacity , general wellbeing , physical activity , and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease . Design R and omised controlled trial . Setting Two university hospitals in Copenhagen , Denmark . Participants 269 patients with cancer ; 73 men , 196 women , mean age 47 years ( range 20 - 65 ) representing 21 diagnoses . Main exclusion criteria were brain or bone metastases . 235 patients completed follow-up . Intervention Supervised exercise comprising high intensity cardiovascular and resistance training , relaxation and body awareness training , massage , nine hours weekly for six weeks in addition to conventional care , compared with conventional care . Main outcome measures European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) , Medical Outcomes Study Short Form ( MOS SF-36 ) , Leisure Time Physical Activity Question naire , muscular strength ( one repetition maximum ) , maximum oxygen consumption ( Vo2max ) . Statistical methods The general linear model was used for continuous outcome while analysis of associates between categorical outcomes was performed as analysis of marginal homogeneity in contingency tables . Results Adjusted for baseline score , disease , and demographic covariates , the intervention group showed an estimated improvement at six weeks for the primary outcome , fatigue , of −6.6 points ( 95 % confidence interval −12.3 to −0.9 , P=0.02 ; effect size=0.33 , 0.04 to 0.61 ) . Significant effects were seen on vitality ( effect size 0.55 , 95 % CI 0.27 to 0.82 ) , physical functioning ( 0.37 , 0.09 to 0.65 ) , role physical ( 0.37 , 0.10 to 0.64 ) , role emotional ( 0.32 , 0.05 to 0.59 ) , and mental health ( 0.28 , 0.02 to 0.56 ) scores . Improvement was noted in physical capacity : estimated mean difference between groups for maximum oxygen consumption was 0.16 l/min ( 95 % CI 0.1 to 0.2 , P<0.0001 ) and for muscular strength ( leg press ) was 29.7 kg ( 23.4 to 34.9 , P<0.0001 ) . No significant effect was seen on global health status/ quality of life . Conclusion A supervised multimodal exercise intervention including high and low intensity components was feasible and could safely be used in patients with various cancers who were receiving adjuvant chemotherapy or treatment for advanced disease . The intervention reduced fatigue and improved vitality , aerobic capacity , muscular strength , and physical and functional activity , and emotional wellbeing , but not quality of life . Trial registration Current Controlled trials IS RCT N05322922 Background Method ological guidelines for intervention reporting emphasise describing intervention content in detail . Despite this , systematic review s of quality improvement ( QI ) implementation interventions continue to be limited by a lack of clarity and detail regarding the intervention content being evaluated . We aim ed to apply the recently developed Behaviour Change Techniques Taxonomy version 1 ( BCTTv1 ) to trials of implementation interventions for managing diabetes to assess the capacity and utility of this taxonomy for characterising active ingredients . Methods Three psychologists independently coded a r and om sample of 23 trials of healthcare system , provider- and /or patient-focused implementation interventions from a systematic review that included 142 such studies . Intervention content was coded using the BCTTv1 , which describes 93 behaviour change techniques ( BCTs ) grouped within 16 categories . We supplemented the generic coding instructions within the BCTTv1 with decision rules and examples from this literature . Results Less than a quarter of possible BCTs within the BCTTv1 were identified . For implementation interventions targeting providers , the most commonly identified BCTs included the following : adding objects to the environment , prompts/cues , instruction on how to perform the behaviour , credible source , goal setting ( outcome ) , feedback on outcome of behaviour , and social support ( practical ) . For implementation interventions also targeting patients , the most commonly identified BCTs included the following : prompts/cues , instruction on how to perform the behaviour , information about health consequences , restructuring the social environment , adding objects to the environment , social support ( practical ) , and goal setting ( behaviour ) . The BCTTv1 mapped well onto implementation interventions directly targeting clinicians and patients and could also be used to examine the impact of system-level interventions on clinician and patient behaviour . Conclusions The BCTTv1 can be used to characterise the active ingredients in trials of implementation interventions and provides specificity of content beyond what is given by broader intervention labels . Identification of BCTs may provide a more helpful means of accumulating knowledge on the content used in trials of implementation interventions , which may help to better inform replication efforts . In addition , prospect i ve use of a behaviour change techniques taxonomy for developing and reporting intervention content would further aid in building a cumulative science of effective implementation interventions Background / Objectives : Our objective was to investigate effects of an oral nutritional supplement containing n-3 polyunsaturated fatty acids ( FAs ) on quality of life , performance status , h and grip strength and physical activity in patients with non-small cell lung cancer ( NSCLC ) undergoing multimodality treatment . Subjects/ Methods : In a double-blind experiment , 40 patients with stage III NSCLC were r and omised to receive 2 cans/day of a protein- and energy-dense oral nutritional supplement containing n-3 polyunsaturated FAs ( 2.02 g eicosapentaenoic acid+0.92 g docosahexaenoic acid/day ) or an isocaloric control supplement , during multimodality treatment . Quality of life , Karnofsky Performance Status , h and grip strength and physical activity ( by wearing an accelerometer ) were assessed . Effects of intervention were analysed by generalised estimating equations . P-values < 0.05 were regarded as statistically significant . Results : The intervention group reported significantly higher on the quality of life parameters , physical and cognitive function ( B=11.6 and B=20.7 , P<0.01 ) , global health status ( B=12.2 , P=0.04 ) and social function ( B=22.1 , P=0.04 ) than the control group after 5 weeks . The intervention group showed a higher Karnofsky Performance Status ( B=5.3 , P=0.04 ) than the control group after 3 weeks . H and grip strength did not significantly differ between groups over time . The intervention group tended to have a higher physical activity than the control group after 3 and 5 weeks ( B=6.6 , P=0.04 and B=2.5 , P=0.05 ) . Conclusion : n-3 Polyunsaturated FAs may beneficially affect quality of life , performance status and physical activity in patients with NSCLC undergoing multimodality treatment The aim of the present study was to investigate the impact of a multidimensional exercise intervention focusing on physical capacity ; one-repetition maximum ( 1RM ) and maximum oxygen uptake ( VO2Max ) , activity level , general well-being and quality of life in cancer patients undergoing chemotherapy . The intervention comprised resistance and fitness training , massage , relaxation and body-awareness training . Eighty-two cancer patients , with or without evidence of residual disease , were included : 66 patients with 13 different types of solid tumours and 16 patients with 6 types of haematological malignancies . The patients trained in mixed groups for 9 h weekly for 6 weeks . Physical capacity , physical activity level and psychosocial well-being as measured by the Medical Outcomes Study 36-item Short-Form Health Survey and the European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 were assessed pre- and post-intervention . Highly significant increases were achieved in muscular strength ( p<0.001 ) , physical fitness ( p<0.001 ) and physical activity levels ( p<0.001 ) . The patients reported significant reduction in treatment-related symptoms , i.e. , fatigue ( p=0.006 ) and pain ( p=0.03 ) . Highly significant improvements were observed in physical functioning ( p<0.001 ) and role functioning ( p<0.001 ) . Even patients with advanced disease were able to improve their results after 6 weeks . It is concluded that a multidimensional exercise intervention , including resistance training , may be beneficial for cancer patients undergoing chemotherapy . This study indicates significant clinical meaningful improvements . The exact role of the intervention has to be defined in a r and omized controlled design . A clinical ly controlled trial including 250 patients is currently being carried out Background Cancer survivors often experience decreased self-confidence which impacts negatively on their ability to self-manage the practical , social and emotional problems frequently faced as they emerge from end of treatment . This was a feasibility study of a life-coaching intervention , design ed to rebuild confidence of survivors and support transition to life after cancer treatment . Methods A one group pre-test , post-test design was used , recruiting participants from community organisations . Eligibility criteria are as follows : < 1 year of completion of primary cancer treatment , aged > 18 , no metastases , and no mental health problems . Participants received one individualised face-to-face and five telephone coaching sessions over 3 months . Outcome measures are as follows : New General Self-Efficacy Scale , Hope Scale , Personal Well-being Index , Assessment of Survivorship Concerns , Quality of Life in Adult Cancer Survivors , Hospital Anxiety and Depression Scale , Social Difficulties Index , and a goal attainment score . Interviews explored feasibility , acceptability and impact of life-coaching and research design . Results Nine women and two men were recruited , representing varying cancer diagnoses . All outcome measures were sensitive to change and indicated positive trends post-intervention . Participant interviews indicated the intervention was well received and had a positive impact . Lessons were learnt about study design , recruitment and intervention delivery . Conclusions Life-coaching has a potential to enable cancer survivors to manage the transition to life beyond cancer and effect change on a range of outcomes . The intervention was feasible to deliver and acceptable to survivors at a time when many struggle to make sense of life . It merits further evaluation through a r and omised controlled trial CONTEXT Breathlessness , fatigue , and anxiety are distressing symptoms for patients with advanced lung cancer . Usually managed as isolated symptoms , they often can occur simultaneously . Previous research often has addressed management of discrete symptoms rather than considering them as a cluster , which , in reality , is the situation faced by patients . OBJECTIVES This study aim ed to examine the effectiveness of a psychoeducational intervention ( PEI ) on the symptom cluster of anxiety , breathlessness , and fatigue , compared with usual care . METHODS A pretest/post-test , two-group , r and omized , controlled trial was conducted . Education on symptom management and coaching in the use of progressive muscle relaxation were delivered to patients one week prior to commencing radiotherapy ( RT ) , and repeated three weeks after beginning RT . Symptom data were collected at four time points : prior to the intervention , three weeks , six weeks , and 12 weeks postintervention . RESULTS One hundred forty lung cancer patients receiving palliative RT were recruited from a publicly funded hospital in Hong Kong . Doubly multivariate analysis of variance revealed a significant difference ( time × group interaction effect , P=0.003 ) over time between the PEI and usual care control group on the pattern of change of the symptom cluster . Significant effects on the patterns of changes in breathlessness ( P=0.002 ) , fatigue ( P=0.011 ) , anxiety ( P=0.001 ) , and functional ability ( P=0.000 ) also were found . CONCLUSION PEI is a promising treatment for relieving the symptom cluster and each of the individually assessed symptoms . More effort needs to be directed at study ing impact of interventions on common symptom clusters BACKGROUND Breathlessness is a common and distressing symptom , which increases in many diseases as they progress and is difficult to manage . We assessed the effectiveness of early palliative care integrated with respiratory services for patients with advanced disease and refractory breathlessness . METHODS In this single-blind r and omised trial , we enrolled consecutive adults with refractory breathlessness and advanced disease from three large teaching hospitals and via general practitioners in South London . We r and omly allocated ( 1:1 ) patients to receive either a breathlessness support service or usual care . R and omisation was computer generated central ly by the independent Clinical Trials Unit in a 1:1 ratio , by minimisation to balance four potential confounders : cancer versus non-cancer , breathlessness severity , presence of an informal caregiver , and ethnicity . The breathlessness support service was a short-term , single point of access service integrating palliative care , respiratory medicine , physiotherapy , and occupational therapy . Research interviewers were masked as to which patients were in the treatment group . Our primary outcome was patient-reported breathlessness mastery , a quality of life domain in the Chronic Respiratory Disease Question naire , at 6 weeks . All analyses were by intention to treat . Survival was a safety endpoint . This trial is registered with Clinical Trials.gov , number NCT01165034 . FINDINGS Between Oct 22 , 2010 and Sept 28 , 2012 , 105 consenting patients were r and omly assigned ( 53 to breathlessness support service and 52 to usual care ) . 83 of 105 ( 78 % ) patients completed the assessment at week 6 . Mastery in the breathlessness support service group improved compared with the control ( mean difference 0·58 , 95 % CI 0·01 - 1·15 , p=0·048 ; effect size 0·44 ) . Sensitivity analysis found similar results . Survival rate from r and omisation to 6 months was better in the breathlessness support service group than in the control group ( 50 of 53 [ 94 % ] vs 39 of 52 [ 75 % ] ) and in overall survival ( generalised Wilcoxon 3·90 , p=0·048 ) . Survival differences were significant for patients with chronic obstructive pulmonary disease and interstitial lung disease but not cancer . INTERPRETATION The breathlessness support service improved breathlessness mastery . Our findings provide robust evidence to support the early integration of palliative care for patients with diseases other than cancer and breathlessness as well as those with cancer . The improvement in survival requires further investigation . FUNDING UK National Institute for Health Research ( NIHR ) and Cicely Saunders International Objective : To conduct a r and omized controlled trial and compare the effects on cancer survivors ’ quality of life in a 12-week group-based multidisciplinary self-management rehabilitation program , combining physical training ( twice weekly ) and cognitive-behavioral training ( once weekly ) with those of a 12-week group-based physical training ( twice weekly ) . In addition , both interventions were compared with no intervention . Methods : Participants ( all cancer types , medical treatment completed ≥3 months ago ) were r and omly assigned to multidisciplinary rehabilitation ( n = 76 ) or physical training ( n = 71 ) . The nonintervention comparison group consisted of 62 patients on a waiting list . Quality of life was measured using the R AND -36 . The rehabilitation groups were measured at baseline , after rehabilitation , and 3-month follow-up , and the nonintervention group was measured at baseline and 12 weeks later . Results : The effects of multidisciplinary rehabilitation did not outperform those of physical training in role limitations due to emotional problem ( primary outcome ) or any other domains of quality of life ( all p > .05 ) . Compared with no intervention , participants in both rehabilitation groups showed significant and clinical ly relevant improvements in role limitations due to physical problem ( primary outcome ; effect size ( ES ) = 0.66 ) , and in physical functioning ( ES = 0.48 ) , vitality ( ES = 0.54 ) , and health change ( ES = 0.76 ) ( all p < .01 ) . Conclusions : Adding a cognitive-behavioral training to group-based self-management physical training did not have additional beneficial effects on cancer survivors ’ quality of life . Compared with the nonintervention group , the group-based self-management rehabilitation improved cancer survivors ’ quality of life . PT = physical training ; CBT = cognitive-behavioral training ; PT+CBT = physical training plus cognitive-behavioral training ; WLC = waiting-list comparison ; QoL = quality of life ; ANOVA = analysis of variance ; ES = effect size Background A reduced exercise capacity is associated with increased morbidity and mortality in patients with advanced non-small cell lung cancer ( NSCLC ) . Therapeutic exercise can be beneficial and neuromuscular electrical stimulation ( NMES ) of the quadriceps muscles may represent a practical approach . The primary aim of this study was to determine the acceptability of NMES of the quadriceps to patients with NSCLC used alongside palliative chemotherapy . Secondary aims explored aspects of safety and efficacy of NMES in this setting . Methods Patients with advanced NSCLC due to receive first-line palliative chemotherapy were r and omized to usual care with or without NMES . They were asked to undertake 30 minute sessions of NMES , ideally daily , but as a minimum , three times weekly . For NMES to be considered acceptable , it was predetermined that ≥80 % of patients should achieve this minimum level of adherence . Qualitative interviews were held with a subset of patients to explore factors influencing adherence . Safety was assessed according to the Common Terminology Criteria for Adverse Events . Quadriceps muscle strength , thigh lean mass , and physical activity level were assessed at baseline and after three cycles of chemotherapy . Results 49 patients ( 28 male , median ( IQR ) age 69 ( 64−75 ) years ) participated . Of 30 r and omized to NMES , 18 were eligible for the primary endpoint , of whom 9 ( 50 % [ 90 % CI , 29 to 71 ] ) met the minimum level of adherence . Adherence was enhanced by incorporating sessions into a daily routine and hindered by undesirable effects of chemotherapy . There were no serious adverse events related to NMES , nor significant differences in quadriceps muscle strength , thigh lean mass or physical activity level between groups . Conclusions NMES is not acceptable in this setting , nor was there a suggestion of benefit . The need remains to explore NMES in patients with cancer in other setting s. Trial Registration Current Controlled Trials IS RCT N 42944026 www.controlled-trials.com/IS RCT Background Breathlessness is common in advanced cancer . The Breathlessness Intervention Service ( BIS ) is a multi-disciplinary complex intervention theoretically underpinned by a palliative care approach , utilising evidence -based non-pharmacological and pharmacological interventions to support patients with advanced disease . We sought to establish whether BIS was more effective , and cost-effective , for patients with advanced cancer and their carers than st and ard care . Methods A single-centre Phase III fast-track single-blind mixed- method r and omised controlled trial ( RCT ) of BIS versus st and ard care was conducted . Participants were r and omised to one of two groups ( r and omly permuted blocks ) . A total of 67 patients referred to BIS were r and omised ( intervention arm n = 35 ; control arm n = 32 received BIS after a two-week wait ) ; 54 completed to the key outcome measurement . The primary outcome measure was a 0 to 10 numerical rating scale for patient distress due to breathlessness at two-weeks . Secondary outcomes were evaluated using the Chronic Respiratory Question naire , Hospital Anxiety and Depression Scale , Client Services Receipt Inventory , EQ-5D and topic-guided interviews . Results BIS reduced patient distress due to breathlessness ( primary outcome : -1.29 ; 95 % CI -2.57 to -0.005 ; P = 0.049 ) significantly more than the control group ; 94 % of respondents reported a positive impact ( 51/53 ) . BIS reduced fear and worry , and increased confidence in managing breathlessness . Patients and carers consistently identified specific and repeatable aspects of the BIS model and interventions that helped . How interventions were delivered was important . BIS legitimised breathlessness and increased knowledge whilst making patients and carers feel ` not alone ’ . BIS had a 66 % likelihood of better outcomes in terms of reduced distress due to breathlessness at lower health/social care costs than st and ard care ( 81 % with informal care costs included ) . Conclusions BIS appears to be more effective and cost-effective in advanced cancer than st and ard care . Trial registration RCT registration at Clinical Trials.gov NCT00678405 ( May 2008 ) and Current Controlled Trials IS RCT N04119516 ( December 2008 ) Goals of workBased on meta-analyses regarding the preparation of patients for potentially threatening medical procedures , a DVD , incorporating behavioral role modelling , was developed to prepare patients for chemotherapy and assist them to self-manage side effects . It was hypothesized that patients who watched the DVD ( vs those who did not ) would report ( 1 ) lower anxiety ; ( 2 ) higher self-efficacy related to coping with treatment side effects ; ( 3 ) fewer supportive care needs ; and ( 4 ) higher satisfaction with information received . It was further hypothesized that these effects would be stronger in those perceiving their treatment intent to be curative rather than palliative . Material s and methods Quasi-experimental design using a historical control group was employed . Participants were scheduled to receive their first ever chemotherapy treatment . Group 1 ( usual care ; n = 50 ) was prospect ively recruited before the release of the DVD and group 2 ( DVD plus usual care ; n = 50 ) after the release . Before commencing chemotherapy , all patients completed reliable and valid measures of self-efficacy , anxiety , and supportive care needs . Data was stratified according to perceived treatment intent . Independent sample t tests were performed for each group ( curative vs palliative).Main results Significant differences were found between the usual care and intervention groups : for self-perceived curative patients in relation to self-efficacy for seeking social support ( p = 0.044 ) , with increased confidence in those watching the DVD , and for self-perceived palliative patients in relation to their satisfaction with information about side effects ( p = 0.026 ) , with increased satisfaction in those watching the DVD . Overall , significant differences were found between self-perceived curative vs palliative patients on measures of self-efficacy and supportive care needs , with self-perceived curative patients reporting more confidence and fewer needs . Conclusions The educational DVD was considered highly acceptable by patients and was found to increase self-efficacy and reduce supportive care needs . Hence , it is appropriate to give to patients before face-to-face chemotherapy education . Additional pretreatment education is recommended , particularly for self-perceived palliative patients , to reduce their pretreatment anxiety and enhance their confidence in coping with treatment CONTEXT Dyspnea is a common symptom in patients with advanced cancer that interferes with functional ability and quality of life ( QOL ) . Although few evidence -based treatments for dyspnea exist , prior studies show support for nonpharmacological interventions that include elements of cognitive-behavioral therapy . OBJECTIVES To examine the feasibility and utility of delivering a brief behavioral intervention for dyspnea in patients with lung cancer . METHODS For this single-group pilot study , eligible patients included those with advanced lung cancer ( Stage III or IV non-small cell or extensive-stage small cell lung cancer ) receiving outpatient cancer treatment who reported at least moderate breathlessness . The manualized intervention consisted of two sessions in which nurse practitioners taught participants breathing and relaxation techniques within the infusion clinic and encouraged home practice . Participants completed measures of breathlessness ( Modified Medical Research Council Dyspnea Scale ) , QOL ( Functional Assessment of Cancer Therapy-Lung Trial Outcome Index ) , and anxiety and depression symptoms ( Hospital Anxiety and Depression Scale ) at baseline and within six weeks after enrollment . RESULTS Of the 32 patients enrolled in the study ( 56.3 % females ; mean age 63.34 [ SD ] = 7.96 years ) , 84.4 % ( N = 27 ) completed all study procedures . Comparing the baseline to post assessment s , we found significant improvements in Modified Medical Research Council Dyspnea Scale ( P < 0.001 ) , Functional Assessment of Cancer Therapy-Lung Trial Outcome Index ( P = 0.01 ) , and Hospital Anxiety and Depression Scale-depression subscale ( P < 0.001 ) scores . CONCLUSION In this sample of patients with advanced lung cancer and dyspnea , we observed a high completion rate for the two-session behavioral intervention . Patients also reported improvements in dyspnea , QOL , and mood . Follow-up r and omized controlled trials are needed to examine the efficacy of brief behavioral interventions for cancer-related dyspnea OBJECTIVE People with inoperable lung cancer experience higher levels of distress , more unmet needs and symptoms than other cancer patients . There is an urgent need to test innovative approaches to improve psychosocial and symptom outcomes in this group . This study tested the hypothesis that a tailored , multidisciplinary supportive care programme based on systematic needs assessment would reduce perceived unmet needs and distress and improve quality of life . METHODS A r and omised controlled trial design was used . The tailored intervention comprised two sessions at treatment commencement and completion . Sessions included a self-completed needs assessment , active listening , self-care education and communication of unmet psychosocial and symptom needs to the multidisciplinary team for management and referral . Outcomes were assessed with the Needs Assessment for Advanced Lung Cancer Patients , Hospital Anxiety and Depression Scale , Distress Thermometer and European Organization of Research and Treatment of Cancer Quality of Life Q-C30 V2.0 . RESULTS One hundred and eight patients with a diagnosis of inoperable lung or pleural cancer ( including mesothelioma ) were recruited from a specialist facility before the trial closed prematurely ( original target 200 ) . None of the primary contrasts of interest were significant ( all p > 0.10 ) , although change score analysis indicated a relative benefit from the intervention for unmet symptom needs at 8 and 12 weeks post- assessment ( effect size = 0.55 and 0.40 , respectively ) . CONCLUSION Although a novel approach , the hypothesis that the intervention would benefit perceived unmet needs , psychological morbidity , distress and health-related quality of life was not supported overall Purpose Cancer patients often experience diminished cognitive function ( CF ) and quality of life ( QOL ) due to the side effects of treatment and the disease symptoms . This study evaluates the effects of medical Qigong ( MQ ; combination of gentle exercise and meditation ) on CF , QOL , and inflammation in cancer patients . Methods Eighty-one cancer patients recruited between October 2007 and May 2008 were r and omly assigned to two groups : a control group ( n = 44 ) who received the usual health care and an intervention group ( n = 37 ) who participated in a 10-week MQ program . Self-reported CF was measured by the European Organization for Research and Treatment of Cancer ( EORTC-CF ) and the Functional Assessment of Cancer Therapy — Cognitive ( FACT-Cog ) . The Functional Assessment of Cancer Therapy — General ( FACT-G ) was used to measure QOL . C-reactive protein ( CRP ) was assessed as a biomarker of inflammation . Results The MQ group self-reported significantly improved CF ( mean difference ( MD ) = 7.78 , t51 = −2.532 , p = 0.014 ) in the EORTC-CF and all the FACT-Cog subscales [ perceived cognitive impairment ( MD = 4.70 , t43 = −2.254 , p = 0.029 ) , impact of perceived cognitive impairment on QOL ( MD = 1.64 , t45 = −2.377 , p = 0.024 ) , and perceived cognitive abilities ( MD = 3.61 , t45 = −2.229 , p = 0.031 ) ] compared to controls . The MQ group also reported significantly improved QOL ( MD = 12.66 , t45 = −5.715 , p < 0.001 ) and had reduced CRP levels ( MD = −0.72 , t45 = 2.092 , p = 0.042 ) compared to controls . Conclusions Results suggest that MQ benefits cancer patients ’ self-reported CF , QOL , and inflammation . A larger r and omized controlled trial including an objective assessment of CF is planned Cheville AL , Girardi J , Clark MM , Rummans TA , Pittelkow T , Brown P , Hanson J , Atherton P , Johnson ME , Sloan JA , Gamble G : Therapeutic exercise during outpatient radiation therapy for advanced cancer : Feasibility and impact on physical well-being . Objective : To characterize the feasibility of delivering a structured physical therapy ( PT ) program as part of a multidisciplinary intervention to patients undergoing outpatient radiation therapy for advanced cancer . Design : A single-blinded , r and omized , controlled trial at a quaternary medical center outpatient clinic . One hundred three adults undergoing radiation therapy for advanced cancer with prognoses ≥6 mos and 5-yr survival estimates ≤50 % were r and omized to usual care or participation in eight 90-min , multidisciplinary interventional sessions with 30 mins of each session devoted to PT . PT consisted of truncal and limb isodynamic strengthening targeting major upper- and lower-limb muscle groups as well as education and provision with instructional material s. Physical well-being and fatigue were assessed with Linear Analog Scale of Assessment . The Profile of Mood States-Short form , including Fatigue-Inertia and Vigor-Activity subscales , was also administered . Results : PT session attendance was 89.3 % . Relative to baseline , mean physical well-being Linear Analog Self Assessment scores at week 4 improved in the intervention group , 0.4 ( SD , 23.6 ) , and declined significantly in the control group , −10.0 ( SD , 21.5 ) ( P = 0.02 ) . Fatigue and vigor were not significantly different between the groups . All intergroup differences had resolved at 8 and 27 wks . Baseline characteristics were not associated with the magnitude or direction of change in outcomes related to physical functioning . Conclusions : Delivery of a st and ardized resistive exercise PT intervention is feasible during outpatient radiation therapy and is associated with preserved physical well-being . However , benefits were not sustained , and fatigue was not affected OBJECTIVE To compare the effects of resistance and cardiovascular exercise on functional mobility in individuals with advanced cancer . DESIGN Prospect i ve , 2-group pretest-posttest pilot study with r and omization to either resistance or cardiovascular exercise mode . SETTING Comprehensive community cancer center and a hospital-based fitness facility . PARTICIPANTS Volunteer sample of individuals ( N=66 ; 30 men ; 36 women ; mean age , 62y ) with advanced cancer recruited through the cancer center , palliative care service , rehabilitation department , and a local hospice . INTERVENTIONS Ten weeks of individualized resistance or cardiovascular exercise , prescribed and monitored by oncology-trained exercise personnel . MAIN OUTCOME MEASURES Functional mobility was assessed using the Short Physical Performance Battery ( SPPB ) ; self-reported pain and fatigue were assessed secondarily using visual analog scales . Data were analyzed using a split plot 2 × 2 analysis of variance ( α=.05 ) . RESULTS Fifty-two patients ( 78.8 % ) completed the study : 23 ( 67.7 % ) of 34 patients in the resistance arm and 29 ( 90.6 % ) of 32 patients in the cardiovascular arm . No participant withdrew because of study adverse events . Ten-week outcomes ( n=52 ) included a significant increase in SPPB total score ( P<.001 ) , increase in gait speed ( P=.001 ) , and reduction in fatigue ( P=.05 ) . Although cardiovascular exercise participants had a modestly greater improvement in SPPB total score than resistance training participants ( F1,49=4.21 , P=.045 ) , the difference was not confirmed in a subsequent intention-to-treat analysis ( N=66 ) . CONCLUSIONS Individuals with advanced cancer appear to benefit from exercise for improving functional mobility . Neither resistance nor cardiovascular exercise appeared to have a strong differential effect on outcome Objectives Breathlessness in patients with lung cancer is a common and distressing symptom affecting 50–70 % of patients , rising to some 90 % for those with advanced lung cancer . The aim of the current study was to assess how feasible inspiratory muscle training ( IMT ) is in the lung cancer population and explore changes in outcome variables . Material s and methods A pilot feasibility r and omised trial was conducted in patients with clinical ly stable lung cancer . The experimental group received training using a pressure threshold device . Patients were instructed to carry out five IMT sessions weekly for 12 weeks for a total of 30 mins/day . Patients in the control group received st and ard care . Outcome measures were completed at baseline and monthly for 3 months , and included : physiological parameters ( FEV1 , FVC ) ; perceived severity of breathlessness using six 10-point NRS ; modified Borg Scale ; quality of life using the short form Chronic Respiratory Disease Question naire ; Hospital Anxiety and Depression Scale , and safety . Results Forty-six patients ( M = 37 , F = 9 ) at a mean age of 69.5 years old and a mean of 16 months post-diagnosis who were not currently receiving chemotherapy and /or radiotherapy were recruited . Seventy-percent had NSCLC and advanced disease . Statistical ( area under the curve-AUC ) and clinical ly important differences were seen with regard to distress from breathlessness ( p = 0.03 ) , ability to cope with breathlessness ( p = 0.01 ) , satisfaction with breathlessness management ( p = 0.001 ) , fatigue ( p = 0.005 ) , emotional function ( p = 0.011 ) , breathlessness mastery ( p = 0.015 ) and depression ( p = 0.028 ) . The m-Borg difference between the two groups at 3 months was 0.80 , which is borderline clinical ly significant . Changes were more evident in the 3-month assessment where the effect of the intervention came to its peak . Conclusion This trial shows the IMT is feasible and potentially effective in patients with lung cancer . These findings warrant a fully powered larger r and omised controlled trial BACKGROUND Physical exercise can improve cancer patients ' functioning and reduce their symptom levels . A r and omized , controlled trial was launched to test the hypothesis that physical exercise reduces fatigue and improves physical performance in cancer patients with advanced and incurable disease . METHODS Cancer patients ( n = 231 ) with a life expectancy ≤2 years were r and omized to a physical exercise group ( PEG , n = 121 ) or a control usual care group ( UCG , n = 110 ) . The PEG exercised under supervision 60 minutes twice a week for 8 weeks . Assessment s were performed before and after the intervention . The primary outcome was physical fatigue ( PF ) measured by the Fatigue Question naire . Physical performance was a secondary outcome measured by the Shuttle Walk Test ( SWT ) and h and grip strength ( HGS ) test . Analyses were performed after multiple imputations for missing data . The trial is registered with Clinical Trials.gov ( identifier , NCT00397774 ) . FINDINGS Thirty-six percent of the PEG were lost to follow-up compared with 23 % of the UCG , primarily as a result of disease progression . Seventy-eight PEG and 85 UCG patients completed the intervention . Analyses showed no significant between-group effects in PF . However , clinical ly and statistically significant between-group effects were found for the SWT and HGS test . INTERPRETATION Fatigue was not reduced but physical performance ( SWT and HGS test ) was significantly improved after 8 weeks of physical exercise . Physical exercise might therefore be a suitable approach for maintaining physical capacity in cancer patients with incurable and advanced disease CONTEXT Two million people across the U.K. are living with cancer , often experienced as a long-term condition . They may have unmet needs after active treatment . Rehabilitation aims to address these needs , maximize psychological and physical function , and enable minimum dependency regardless of life expectancy . OBJECTIVES We aim ed to test , in a r and omized controlled trial , the clinical and cost effectiveness of a rehabilitation intervention for patients with advanced , recurrent cancer . METHODS We conducted a two-arm , wait-list control , r and omized trial of a complex rehabilitation intervention delivered by a hospice-based multidisciplinary team vs. usual care for active , progressive , recurrent hematological and breast malignancies , with a follow-up at three months . The primary outcome was the psychological subscale of the Supportive Care Needs Survey ( SCNS ) . Secondary outcomes were other domains of the SCNS , psychological status , continuity of care , quality of life , and re source use . RESULTS Forty-one participants were enrolled and 36 completed the trial . The primary outcome was significantly lower in the intervention arm ( adjusted difference -16.8 , 95 % CI -28.34 to -5.3 ; P = 0.006 ) . The SCNS physical and patient care subscales ( -14.2 , 95 % CI -26.2 to -2.2 ; P = 0.02 and -7.4 , 95 % CI -13.7 to -1.1 ; P = 0.02 , respectively ) and self-reported health state ( 12.8 , 95 % CI 3.2 to 22.4 ; P = 0.01 ) also differed significantly . The incremental cost-effectiveness ratio was £ 19,390 per quality -adjusted life year . CONCLUSION This intervention significantly reduced the unmet needs of cancer survivors and it is likely that it is cost-effective . Despite small numbers , the main effect size was robust . We recommend implementation alongside evaluation in wider clinical setting s and patient population PURPOSE To determine whether a nurse navigator intervention improves quality of life and patient experience with care for people recently given a diagnosis of breast , colorectal , or lung cancer . PATIENTS AND METHODS Adults with recently diagnosed primary breast , colorectal , or lung cancer ( n = 251 ) received either enhanced usual care ( n = 118 ) or nurse navigator support for 4 months ( n = 133 ) in a two-group cluster r and omized , controlled trial with primary care physicians as the units of r and omization . Patient-reported measures included the Functional Assessment of Cancer Therapy-General ( FACT-G ) Quality of Life scale , three subscales of the Patient Assessment of Chronic Illness Care ( PACIC ) , and selected subscales from a cancer adaptation of the Picker Institute 's patient experience survey . Self-report measures were collected at baseline , 4 months , and 12 months . Automated administrative data were used to assess time to treatment and total health care costs . RESULTS There were no significant differences between groups in FACT-G scores . Nurse navigator patients reported significantly higher scores on the PACIC and reported significantly fewer problems with care , especially psychosocial care , care coordination , and information , as measured by the Picker instrument . Cumulative costs after diagnosis did not differ significantly between groups , but lung cancer costs were $ 6,852 less among nurse navigator patients . CONCLUSION Compared with enhanced usual care , nurse navigator support for patients with cancer early in their course improves patient experience and reduces problems in care , but did not differentially affect quality of life INTRODUCTION The evidence on the effectiveness of rehabilitation in lung cancer patients is limited . Whole body vibration ( WBV ) has been proposed as an alternative to conventional resistance training ( CRT ) . METHODS We investigated the effect of radical treatment ( RT ) and of two rehabilitation programmes in lung cancer patients . The primary endpoint was a change in 6-min walking distance ( 6MWD ) after rehabilitation . Patients were r and omised after RT to either CRT , WBVT or st and ard follow-up ( CON ) . Patients were evaluated before , after RT and after 12 weeks of intervention . RESULTS Of 121 included patients , 70 were r and omised to either CON ( 24 ) , CRT ( 24 ) or WBVT ( 22 ) . After RT , 6MWD decreased with a mean of 38 m ( 95 % CI 22 - 54 ) and increased with a mean of 95 m ( 95 % CI 58 - 132 ) in CRT ( p<0.0001 ) , 37 m ( 95 % CI -1 - 76 ) in WBVT ( p=0.06 ) and 1 m ( 95 % CI -34 - 36 ) in CON ( p=0.95 ) , respectively . Surgical treatment , magnitude of decrease in 6MWD by RT and allocation to either CRT or WBVT were prognostic for reaching the minimally clinical ly important difference of 54 m increase in 6MWD after intervention . CONCLUSIONS RT of lung cancer significantly impairs patients ' exercise capacity . CRT significantly improves and restores functional exercise capacity , whereas WBVT does not fully substitute for CRT PURPOSE / OBJECTIVES To test the effects of a computer-based nursing intervention design ed to provide patients and family caregivers with concrete , objective information on symptom management ; provide education about disease and treatment ; coordinate medical re sources ; and provide emotional support and counseling . DESIGN Two-site , r and omized clinical trial . SETTING S A large , urban , midwestern , tertiary-cancer center and a community-based cancer center in a medium-sized midwestern city . SAMPLE 109 patients newly diagnosed with breast , colon , or lung cancer who were receiving chemotherapy ; 54 received st and ard care , and 55 participated in the intervention group . METHODS Outcome data were collected via structured telephone interviews at three time points : baseline , midway through the intervention , and one month postintervention . The intervention consisting of nine visits , five in person and four by telephone , was conducted over 18 weeks by advanced practice oncology nurses . MAIN RESEARCH VARIABLES Psychosocial functioning , anxiety , and depression . FINDINGS Patients who received the intervention had significantly less depression between baseline and the midway point , as well as less anxiety and greater improvement in the role-emotional and mental health subscales of the Medical Outcomes Study 36 Short Form . CONCLUSIONS Cancer-care nursing interventions can decrease psychosocial morbidity and improve quality of life for newly diagnosed patients with cancer undergoing treatment . Additional research is needed to underst and who benefited most from the intervention . IMPLICATION S FOR NURSING This nurse-directed intervention result ed in improved mental health for patients ; however , physical subscales were not changed . Further work is needed to determine why depression and mental health were affected yet physical health and symptoms did not differ between groups . Results support the important role of nurses in addressing mental health issues in patients and families experiencing cancer CONTEXT Pain , fatigue , and sleep disturbance commonly co-occur in patients receiving treatment for advanced cancer . OBJECTIVES A pilot r and omized controlled trial was conducted to assess initial efficacy of a patient-controlled cognitive-behavioral ( CB ) intervention for the pain , fatigue , and sleep disturbance symptom cluster . METHODS Eighty-six patients with advanced lung , prostate , colorectal , or gynecologic cancers receiving treatment at a comprehensive cancer center were stratified by recruitment clinics ( chemotherapy and radiation therapy ) and r and omized to intervention or control groups . Forty-three patients were assigned to receive training in and use of up to 12 relaxation , imagery , or distraction exercises delivered via an MP3 player for two weeks during cancer treatment . Forty-three patients were assigned to a waitlist control condition for the same two week period . Outcomes included symptom cluster severity and overall symptom interference with daily life measured at baseline ( Time 1 ) and two weeks later ( Time 2 ) . RESULTS Eight participants dropped out ; 78 completed the study and were analyzed ( 36 intervention and 42 control subjects ) . Participants used the CB strategies an average of 13.65 times ( SD=6.98 ) . Controlling for baseline symptom cluster severity and other relevant covariates , it was found that the symptom cluster severity at Time 2 was lower in the intervention group ( M(Adj)=2.99 , SE=0.29 ) than in the waitlist group ( M(Adj)=3.87 , SE=0.36 ) , F(1 , 65)=3.57 , P=0.032 . Symptom interference with daily life did not differ between groups . No significant adverse events were noted with the CB intervention . CONCLUSION Findings suggest that the CB intervention may be an efficacious approach to treating the pain , fatigue , and sleep disturbance symptom cluster . Future research is planned to confirm efficacy and test mediators and moderators of intervention effects CONTEXT Dyspnea is a disabling distressing symptom that is common in advanced disease affecting millions of people worldwide . Current palliative strategies are partially effective in managing this symptom ; facial cooling has been shown to reduce the sensation of breathlessness when induced in volunteers but has not been formally investigated in dyspnea associated with disease . OBJECTIVE The objective of this study was to investigate whether a h and held fan reduces the sensation of breathlessness in such patients , enhancing palliative approaches . METHODS The effectiveness of a h and held fan ( blowing air across the nose and mouth ) in reducing the sensation of breathlessness was assessed in patients with advanced disease . Fifty participants were r and omized to use a h and held fan for five minutes directed to their face or leg first and then crossed over to the other treatment . The primary outcome measure was a decrease of greater than 1 cm in breathlessness recorded on a 10 cm visual analog scale ( VAS ) . RESULTS There was a significant difference in the VAS scores between the two treatments , with a reduction in breathlessness when the fan was directed to the face ( P=0.003 ) . CONCLUSION This study supports the hypothesis that a h and held fan directed to the face reduces the sensation of breathlessness . The fan was acceptable to participants : it is inexpensive , portable , enhances self-efficacy , and available internationally . It should be recommended as part of a palliative management strategy for reducing breathlessness associated with advanced disease 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 AIM To investigate the safety and feasibility of a six-week supervised structured exercise and relaxation training programme on estimated peak oxygen consumption , muscle strength and health related quality of life ( HRHRQOL ) in patients with inoperable lung cancer , undergoing chemotherapy . METHODS A prospect i ve , single-arm intervention study of supervised , hospital based muscle and cardiovascular group training and individual home-based training . Peak oxygen consumption ( VO(2peak ) ) was assessed using an incremental exercise test . Muscle strength was measured with one repetition maximum test ( 1RM ) . HRQOL was assessed using the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) scale . RESULTS Twenty-five patients with non-small cell cancer ( NSCLC ) stage III-IV and four patients with extensive disease small cell lung cancer ( SCLC-ED ) were recruited . Six patients ( 20.7 % ) dropped out leaving 23 patients for analysis . Exercise adherence in the group training was 73.0 % and 8.7 % in the home-based training . There were improvements in estimated VO(2peak ) and six-minute walk distance ( 6 MWD ) as well as increased muscle strength measurements ( p<0.05 ) . There was significant improvement in the " emotional well-being " parameter ( FACT-L ) while there were no significant changes in HRQOL . CONCLUSION Exercise training produces significant improvements in physiological indices and emotional HRQOL and is safe and feasible in patients with advanced stage lung cancer , undergoing chemotherapy . No analysis on home-based training was done because of low adherence CONTEXT Exercise benefits patients with cancer , but studies of home-based approaches , particularly among those with Stage IV disease , remain small and exploratory . OBJECTIVES To conduct an adequately powered trial of a home-based exercise intervention that can be facilely integrated into established delivery and reimbursement structures . METHODS Sixty-six adults with Stage IV lung or colorectal cancer were r and omized , in an eight-week trial , to usual care or incremental walking and home-based strength training . The exercising participants were instructed during a single physiotherapy visit and subsequently exercised four days or more per week ; training and step-count goals were advanced during bimonthly telephone calls . The primary outcome measure was mobility assessed with the Ambulatory Post Acute Care Basic Mobility Short Form . Secondary outcomes included ratings of pain and sleep quality as well as the ability to perform daily activities ( Ambulatory Post Acute Care Daily Activities Short Form ) , quality of life ( Functional Assessment of Cancer Therapy-General ) , and fatigue ( Functional Assessment of Cancer Therapy-Fatigue ) . RESULTS Three participants dropped out and seven died ( five in the intervention and two in the control group , P=0.28 ) . At Week 8 , the intervention group reported improved mobility ( P=0.01 ) , fatigue ( P=0.02 ) , and sleep quality ( P=0.05 ) compared with the usual care group , but did not differ on the other measures . CONCLUSION A home-based exercise program seems capable of improving the mobility , fatigue , and sleep quality of patients with Stage IV lung and colorectal cancer Objective - To evaluate the effect of non-pharmacological intervention for breathlessness in lung cancer on breathlessness ratings and patient functioning . Design - R and omised controlled pilot study . Setting - A nurse led clinic in a specialist cancer centre . Subjects - 20 patients with advanced small cell and non-small cell lung cancer . Intervention - Weekly sessions with a nurse research practitioner over 3 - 6 weeks using counselling , breathing re-training , relaxation and teaching coping and adaptation strategies . Main outcome measures - Visual analogue scale ratings of breathlessness , distress caused by breathlessness , functional capacity , ability to perform activities of daily living and the Hospital Anxiety and Depression Scale . Results - Improvements in median scores on all measures were observed in the intervention group with the exception of depression , compared with the control group where median scores were static or worsened . Distress from breathlessness was improved by a median of 53 % , breathlessness at worst by 35 % and functional capacity by 21 % . In contrast , distress in the control group worsened by a median of 10 % . Significant improvements compared with the control group were observed in breathlessness at best ( p < 0.02 ) , breathlessness at worst ( p < 0.05 ) , distress caused by breathlessness ( p < 0.01 ) , functional capacity ( p < 0.02 ) and ability to perform activities of daily living ( p < 0.03 ) but were not observed for anxiety or depression . Conclusion - Lung cancer patients suffering from breathlessness benefited from this rehabilitative approach to breathlessness management and strategies employed in this pilot study warrant further multicentre research . Macmillan nurses and palliative care teams are recommended to explore the potential of adopting similar approaches Patients with lung cancer experience muscle wasting and weakness . Therapeutic exercise may be beneficial but is not always practical . An alternative approach may be neuromuscular electrical stimulation ( NMES ) of the quadriceps muscles , but this has not been formally examined in patients with cancer . Thus , we have undertaken this pilot study to assess feasibility and inform the design of future studies . Sixteen patients were r and omized to receive usual care ( control group ) or usual care plus NMES for four weeks . NMES consisted of daily stimulation to both thighs for up to 30minutes ( frequency 50Hz , " on " cycle 11%-25 % ) . Adherence was assessed by a self-report diary and a semistructured evaluation form . Quadriceps muscle strength , exercise endurance , and free-living physical activity were assessed using a Cybex NORM dynamometer , an endurance shuttle walk test , and an ActivPAL accelerometer ( mean daily step count ) , respectively . Changes in outcome from baseline were compared between groups by mean differences and their 95 % confidence intervals using independent t-test ( P=0.05 ) . Median ( range ) adherence to the program was 80 % ( 69%-100 % ) . All patients found the NMES device easy to use . Changes in outcome favored the NMES group , with mean differences of 9.4 Nm ( 21 % ) in quadriceps muscle strength , 768 steps ( 15 % ) in free-living activity , and 138 m ( 8 % ) in exercise endurance , but none of the differences were statistically significant . In conclusion , NMES warrants further study in patients with lung cancer OBJECTIVE To evaluate the effectiveness of nursing intervention for breathlessness in patients with lung cancer . DESIGN Patients diagnosed with lung cancer participated in a multicentre r and omised controlled trial where they either attended a nursing clinic offering intervention for their breathlessness or received best supportive care . The intervention consisted of a range of strategies combining breathing control , activity pacing , relaxation techniques , and psychosocial support . Best supportive care involved receiving st and ard management and treatment available for breathlessness , and breathing assessment s. Participants completed a range of self assessment question naires at baseline , 4 weeks , and 8 weeks . SETTING Nursing clinics within 6 hospital setting s in the United Kingdom . PARTICIPANTS 119 patients diagnosed with small cell or non-small cell lung cancer or with mesothelioma who had completed first line treatment for their disease and reported breathlessness . OUTCOME MEASURES Visual analogue scales measuring distress due to breathlessness , breathlessness at best and worst , WHO performance status scale , hospital anxiety and depression scale , and Rotterdam symptom checklist . RESULTS The intervention group improved significantly at 8 weeks in 5 of the 11 items assessed : breathlessness at best , WHO performance status , levels of depression , and two Rotterdam symptom checklist measures ( physical symptom distress and breathlessness ) and showed slight improvement in 3 of the remaining 6 items . CONCLUSION Most patients who completed the study had a poor prognosis , and breathlessness was typically a symptom of their deteriorating condition . Patients who attended nursing clinics and received the breathlessness intervention experienced improvements in breathlessness , performance status , and physical and emotional states relative to control patients Eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , ( n-3 ) fatty acids from fish oil , have immune-modulating effects and may improve nutritional status in cancer . The objective of this study was to investigate the effects of an oral nutritional supplement containing ( n-3 ) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer ( NSCLC ) undergoing multimodality treatment . In a double-blind experiment , 40 patients with stage III NSCLC were r and omly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing ( n-3 ) fatty acids ( 2.0 g EPA + 0.9 g DHA/d ) or an isocaloric control supplement . EPA in plasma phospholipids , energy intake , resting energy expenditure ( REE ) , body weight , fat free mass ( FFM ) , mid-upper arm circumference ( MUAC ) , and inflammatory markers were assessed . Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients ( B ) . The intervention group ( I ) had a better weight maintenance than the control ( C ) group after 2 and 4 wk ( B = 1.3 and 1.7 kg , respectively ; P < 0.05 ) , a better FFM maintenance after 3 and 5 wk ( B = 1.5 and 1.9 kg , respectively ; P < 0.05 ) , a reduced REE ( B = -16.7 % of predicted ; P = 0.01 ) after 3 wk , and a trend for a greater MUAC ( B = 9.1 ; P = 0.06 ) and lower interleukin-6 production ( B = -27.9 ; P = 0.08 ) after 5 wk . After 4 wk , the I group had a higher energy and protein intake than the C group ( B = 2456 kJ/24 h , P = 0.03 and B = 25.0 g , P = 0.01 , respectively ) . In conclusion , a protein- and energy-dense oral nutritional supplement containing ( n-3 ) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC PURPOSE The primary goal of this study was to evaluate the feasibility and effectiveness of a structured , multidisciplinary intervention targeted to maintain the overall quality of life ( QOL ) , which is more comprehensive than psychosocial distress , of patients undergoing radiation therapy for advanced-stage cancer . PATIENTS AND METHODS Radiation therapy patients with advanced cancer and an estimated 5-year survival rate of 0 % to 50 % were r and omly assigned to either an eight-session structured multidisciplinary intervention arm or a st and ard care arm . The eight 90-minute sessions addressed the five domains of QOL including cognitive , physical , emotional , spiritual , and social functioning . The primary end point of maintaining overall QOL was assessed by a single-item linear analog scale ( Linear Analog Scale of Assessment or modified Spitzer Uniscale ) . QOL was assessed at baseline , week 4 ( end of multidisciplinary intervention ) , week 8 , and week 27 . RESULTS Of the 103 participants , overall QOL at week 4 was maintained by the patients in the intervention ( n = 49 ) , whereas QOL at week 4 significantly decreased for patients in the control group ( n = 54 ) . This change reflected a 3-point increase from baseline in the intervention group and a 9-point decrease from baseline in the control group ( P = .009 ) . Intervention participants maintained their QOL , and controls gradually returned to baseline by the end of the 6-month follow-up period . CONCLUSION Although intervention participants maintained and actually improved their QOL during radiation therapy , control participants experienced a significant decrease in their QOL . Thus , a structured multidisciplinary intervention can help maintain or even improve QOL in patients with advanced cancer who are undergoing cancer treatment CONTEXT Tai Chi is a traditional Chinese health-promoting exercise . It has been shown to enhance mental health and improve psychological condition . OBJECTIVES We aim ed to assess the effectiveness of Tai Chi exercise for cancer-related fatigue in patients with lung cancer undergoing chemotherapy . METHODS We conducted a r and omized trial of Tai Chi exercise as compared with low-impact exercise as a control intervention . Exercises were practice d every other day , a one-hour session for 12 weeks for each of the study groups . The primary end point was a change in total score of the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) . Secondary end points were changes in five subscale scores of the MFSI-SF . All assessment s were repeated at three time points , T0 : before first course of chemotherapy ; T1 : before third course of chemotherapy ; and T2 : at the end of the fourth course of chemotherapy . RESULTS Between January 2012 and December 2014 , 96 patients were enrolled in this trial . At six and 12 weeks , the Tai Chi group had a lower MFSI-SF total score compared with the control group ( 59.5 ± 11.3 vs. 66.8 ± 11.9 , P < 0.05 ; 53.3 ± 11.8 vs. 59.3 ± 12.2 , P < 0.05 ) . At six weeks , the Tai Chi group had lower MFSI-SF general subscale scores ( 18.1 ± 4.6 vs. 20.4 ± 4.5 , P < 0.05 ) and physical subscale scores ( 17.5 ± 4.4 vs. 19.1 ± 4.5 , P < 0.05 ) , and higher MFSI-SF vigor subscale scores ( 14.5 ± 3.3 vs. 11.6 ± 3.4 , P < 0.05 ) , compared with the control group . But no significant differences were found in emotional subscale ( 20.2 ± 3.6 vs. 20.0 ± 3.5 , P > 0.05 ) and mental subscale ( 18.2 ± 4.0 vs. 18.9 ± 3.9 , P > 0.05 ) scores between the Tai Chi group and the control group . At 12 weeks , the MFSI-SF subscale scores showed the same trends as at six weeks . CONCLUSION Tai Chi is an effective intervention for managing cancer-related fatigue in patients with lung cancer undergoing chemotherapy , especially for decreasing general fatigue and physical fatigue , and increasing vigor Objective : Mechanisms for cancer related fatigue suggest that exercise but “ not too much and not too little ” could be effective . This study aim ed to investigate feasibility and estimate the potential effects of a walking exercise program in people with advanced cancer and fatigue . Design : A pilot r and omized trial . Setting : McGill University Health Centre ( MUHC ) , Montreal , Canada . Subjects : People with advanced cancer undergoing interdisciplinary assessment and rehabilitation with a fatigue level of 4 to 10 on a visual analogue scale . Interventions : An 8-week fatigue-adapted , walking intervention , facilitated using a pedometer ( STEPS ) , and offered at the same time as or after rehabilitation . Measures : Measures of fatigue , physical function and well-being were administered at entry , and 8 , 16 and 24 weeks . Generalized estimating equations ( GEE ) estimated the odds of response for people receiving the STEPS program in comparison to the odds of response in the controls ( odds ratio , OR ) . Results : Twenty-six persons were r and omized to three groups : during rehabilitation , after rehabilitation , and usual care . For the fatigue measures the OR for STEPS offered at any time using an intention-to-treat approach was 3.68 ( 95%CI : 1.05 - 12.88 ) ; for the physical function measures , the OR was 1.40 ( 95%CI : 0.41- 4.79 ) and 2.36 ( 95%CI : 0.66 - 8.51 ) for the well-being measures . Conclusion : Fifty percent of eligible people were able to participate . This small trial suggests that a personalized exercise program reduces fatigue and that 100 people are needed in a full strength trial Background : Sleep disturbances and poor rest-activity rhythms , which can reduce the quality of life , are highly prevalent among patients with lung cancer . Methods : This trial investigated the effects of a 12-week exercise intervention including home-based walking exercise training and weekly exercise counseling on 111 lung cancer patients . Participants were r and omly allocated to receive the intervention or usual-care . Outcomes included objective sleep ( total sleep time , TST ; sleep efficiency , SE ; sleep onset latency , SOL ; and wake after sleep onset , WASO ) , subjective sleep ( Pittsburgh Sleep Quality Index , PSQI ) , and rest-activity rhythms ( r24 and I < O ) . Outcomes were assessed at baseline and 3 and 6 months after intervention . Results : The PSQI ( Wald χ2=15.16 , P=0.001 ) and TST ( Wald χ2=7.59 , P=0.023 ) of the patients in the exercise group significantly improved 3 and 6 months after intervention . The moderating effect of I < O on TST was significant ( β of group × I < O=3.70 , P=0.032 ) . Conclusions : The walking program is an effective intervention for improving the subjective and objective sleep quality of lung cancer patients and can be considered an optional component of lung cancer rehabilitation We tested the effects on problem-solving , anxiety and depression of 12-week group-based self-management cancer rehabilitation , combining comprehensive physical training ( PT ) and cognitive-behavioural problem-solving training ( CBT ) , compared with PT . We expected that PT + CBT would outperform PT in improvements in problem-solving ( Social Problem-Solving Inventory-Revised ( SPSI-R ) ) , anxiety and depression ( Hospital Anxiety and Depression Scale ( HADS ) ) , and that more anxious and /or depressed participants would benefit most from adding CBT to PT . Cancer survivors ( aged 48.8 ± 10.9 years , all cancer types , medical treatment completed ) were r and omly assigned to PT + CBT ( n = 76 ) or PT ( n = 71 ) . Measurement occasions were : before and post-rehabilitation ( 12 weeks ) , 3- and 9-month follow-up . A non-r and omised usual care comparison group ( UCC ) ( n = 62 ) was measured at baseline and after 12 weeks . Longitudinal intention-to-treat analyses showed no differential pattern in change between PT + CBT and PT . Post-rehabilitation , participants in PT and PT + CBT reported within-group improvements in problem-solving ( negative problem orientation ; p < 0.01 ) , anxiety ( p < 0.001 ) and depression ( p < 0.001 ) , which were maintained at 3- and 9-month follow-up ( p < 0.05 ) . Compared with UCC post-rehabilitation , PT and PT + CBT only improved in anxiety ( p < 0.05 ) . CBT did not add to the effects of PT and had no extra benefits for higher distressed participants . PT was feasible and sufficient for durably reducing cancer survivors ’ anxiety CONTEXT Encouraging use of hospice and minimizing the use of cure-oriented aggressive interventions that detract from quality of life in the last month of life are specific targets for improvement in cancer care . OBJECTIVES To evaluate the effect of an interdisciplinary cancer support team ( CST ) on quality of care and quality of life in patients with advanced cancers . METHODS A nonr and omized clinical trial was conducted , comparing outcomes before and after the integration of an interdisciplinary CST in routine care of adults with Stage III or IV lung , gastrointestinal , or gynecologic cancer . In the control arm , patients ( n = 332 ) received usual care ; after the initiation of the intervention arm , eligible patients ( n = 278 ) received the CST intervention . The intervention consisted of individualized care coordination , symptom management , education , psychosocial and spiritual supports , and advance care planning throughout the 15-month study period . Quality of end-of-life care was measured through an " aggressiveness of care " index . Health-related quality of life ( HRQOL ) was measured with the Functional Assessment of Cancer Therapy-General . RESULTS There were no statistically significant differences between groups on specific indicators of quality of care . Surviving subjects with higher survival expectancy ( who also reported better baseline quality of life ) in the intervention arm had the greatest improvement in HRQOL scores , compared with the other three groupings of survival expectancy by treatment group ( high vs. low by intervention vs. control ) ( P = 0.044 ) . CONCLUSION Individually tailored supportive services from an interdisciplinary team are associated with improved HRQOL in some patients . This has implication s for the potential benefits that can be accrued from providing intensive support to all patients , even those who may appear to be at less risk for distress . There also are important method ological considerations in using aggressiveness of care indices as a measure of quality of care Systematic review s of high quality r and omized trials generally count as the ‘ best evidence ’ . However , well-conducted r and omized trials are sometimes unavailable , unfeasible , unethical or unnecessary . In such cases other forms of evidence must be considered . Many EBM proponents accept mechanistic reasoning ( ‘ pathophysiologic rationale ’ ) for generalizability , hypothesis generation , ruling out implausible hypotheses , and for supporting efficacy in the absence of other ‘ stronger ’ forms of evidence . Yet because mechanistic reasoning has often led us astray , most EBM proponents are justifiably sceptical about using mechanistic reasoning as evidence for efficacy . We suggest that the scepticism about the value of mechanistic reasoning should not extend to high quality mechanistic reasoning . Just as poor quality r and omized trials ( that are unblinded , underpowered or biased , that employ unconcealed allocation , or otherwise biased ) will not provide high quality evidence for efficacy , so poor quality mechanistic reasoning will be unreliable . In this theoretical exploration we suggest that mechanistic reasoning involving a not incomplete inferential chain and that takes potential complexity into account can and should be used as evidence of efficacy . We support our rules for mechanistic evidence with three examples The purpose of this pilot study was to assess the effects of a physical exercise program on physical performance and quality of life ( QOL ) in a population with incurable cancer and a short life expectancy . Thirty-four patients participated in a 50-minute group exercise program twice a week for 6 weeks . Physical performance was measured by three tests : " 6-minute walk test , " " timed repeated sit to st and , " and " functional reach . " Fatigue was measured by the Fatigue Question naire . QOL was assessed by the European Organization for Research and Treatment of Cancer Core Quality of Life Question naire . The outcome variables were assessed before and after the intervention . The walk length increased and the " timed repeated sit to st and " was reduced ( P < 0.05 ) . Emotional functioning improved and physical fatigue was reduced ( P < 0.05 ) . Physical exercise seems to be a feasible way to improve well-being among patients with incurable cancer . Future r and omized trials are needed to confirm the results Background : Physical activity can confer many benefits on cancer survivors , including relief of persistent symptoms related to cancer treatment . Objectives : To evaluate the effect of a motivational interviewing ( MI ) intervention on increasing physical activity ( Community Healthy Activities Model Program for Seniors question naire ) and improving aerobic fitness ( 6-minute walk ) , health ( Medical Outcomes Study Short-Form 36 ) , and fatigue ( Schwartz Cancer Fatigue Scale ) in cancer survivors . A secondary purpose was to evaluate whether the effect of MI on physical activities depended on self-efficacy . Methods : Fifty-six physically inactive adult cancer survivors ( mean = 42 months since completion of treatment ) were assigned r and omly to intervention and control groups . The MI intervention consisted of one in-person counseling session followed by two MI telephone calls over 6 months . Control group participants received two telephone calls without MI content . Outcomes were measured at baseline , 3 months , and 6 months , and were analyzed using multilevel modeling . Results : The results of the MI intervention explained significant group differences in regular physical activities ( measured in caloric expenditure per week ) , controlling for time since completion of cancer treatment ( p < .05 ) . Aerobic fitness , physical and mental health , and fatigue were not different between groups . In the intervention group , individuals with high self-efficacy for exercise at baseline increased their physical activity more than those with low self-efficacy ( p < .05 ) . In the control group , increases in physical activity did not depend on self-efficacy . Discussion : Use of MI may increase physical activity in long-term cancer survivors , especially in persons with high self-efficacy for exercise . Multilevel modeling analysis revealed individual changes that would not have been shown by analysis of group means . Future studies with larger sample s or more intense MI interventions may show changes in aerobic fitness , physical and mental health , and fatigue PURPOSE / OBJECTIVES To evaluate the effectiveness of a cognitive behavioral intervention in decreasing symptom severity in patients with advanced cancer undergoing chemotherapy . DESIGN Prospect i ve , r and omized clinical trial based on cognitive behavioral theory . SETTING Six urban cancer centers in the midwestern United States . SAMPLE 124 patients 21 years of age or older were recruited and r and omized to receive conventional care or conventional care and an intervention . Participants were newly diagnosed with stage III , stage IV , or recurrent cancer ( solid tumor or non-Hodgkin lymphoma ) , undergoing chemotherapy , cognitively intact , and able to read and speak English . METHODS Data were gathered via telephone interviews at baseline and 10 and 20 weeks after r and omization . Nurses with experience in oncology delivered a five-contact , eight-week intervention aim ed at teaching patients problem-solving techniques to affect symptom severity . MAIN RESEARCH VARIABLES Gender , site of cancer , age , symptom severity and depressive symptoms at baseline , group ( i.e. , experimental versus control ) , and total symptom severity . FINDINGS Patients in the experimental group and those with lower symptom severity at baseline had significantly lower symptom severity at 10 and 20 weeks ; the experimental difference at 20 weeks occurred primarily in those 60 years of age and younger . Depressive symptoms at baseline predicted symptom severity at 20 weeks ; however , age , gender , and site of cancer did not affect symptom severity at either time point . CONCLUSIONS A cognitive behavioral intervention to teach problem-solving skills can be effective for patient symptom self-management during and following an intervention . IMPLICATION S FOR NURSING Problem-solving strategies should be included in educational programs for patients with advanced cancer , particularly those 60 years of age and younger CONTEXT Patients on investigational clinical trials and their caregivers experience poor quality of life ( QOL ) , which declines as the disease progresses . OBJECTIVE To examine the effect of a st and ardized cognitive-behavioral problem-solving educational intervention on the QOL of patients enrolled on investigational clinical trials and their caregivers . DESIGN Prospect i ve , multi-institution , r and omized trial . QOL was measured repeatedly over 6 months . PARTICIPANTS Patients were simultaneously enrolled onto phase 1 , 2 , or 3 Institutional Review Board (IRB)-approved cancer clinical trials . INTERVENTION Intervention arm dyads participated in three conjoint educational sessions during the first month , learning the COPE problem solving model . Nonintervention arm dyads received usual care . OUTCOME MEASURES Global QOL was measured by the City of Hope Quality of Life Instruments for Patients or Caregivers ; problem solving skills were measured by the Social Problem Solving Inventory-Revised . RESULTS The results are reported using the CONSORT statement . The analytic data set included 476 dyads including 1596 patient data points and 1576 care giver data points . Patient QOL showed no significant difference in the rate of change between the intervention and usual care arms ( p = 0.70 ) . Caregiver QOL scores in the intervention arm declined , but at less than half the rate in the control arm ( p = 0.02 ) . CONCLUSIONS The COPE intervention enabled the average caregiver to come much closer to stable QOL over the 6-month follow-up . Future studies should enroll subjects much earlier in the cancer illness trajectory , a common patient/caregiver theme . The maximum effect was seen in caregivers who completed the 6-month follow-up , suggesting that the impact may increase over time OBJECTIVE Our aim was to investigate the feasibility of completing an exercise program in patients with advanced cancer and to obtain preliminary data of its impact on physical and quality of life ( QoL ) outcomes . METHODS We conducted a nonr and omized pilot study . Participants were 26 palliative care patients with advanced cancer ( mean age=54.5 years ; st and ard deviation [ SD ] 8.9 years ) of the outpatient clinic of the medical oncology and the urology departments of a medical center in The Netherl and s. Participants followed an individually grade d group exercise program , consisting of resistance training and aerobic exercise , twice a week during 6 weeks . Feasibility of the training program , muscle strength , aerobic fitness , body composition , QoL , fatigue , and physical role , social , and activities of daily living ( ADL ) functioning were assessed at baseline and immediately after the intervention . RESULTS Dropout rate during the training period was 35 % due to disease progression . After the training period , based on intention to treat analysis , muscle strength and aerobic functional fitness had increased significantly ( p≤0.01 ) . A significant decrease in fat percentage ( p≤0.02 ) was observed . QoL had increased significantly ( p≤0.02 ) , as well as social ( p≤0.04 ) , physical role ( p≤0.01 ) , and ADL functioning ( p≤0.05 ) . Fatigue decreased significantly on the Checklist Individual Strength ( CIS ) and R AND -36 question naires ( p≤0.02 ) , however not on the European Organisation for Research and Treatment of Cancer ( EORTC ) QLQ-C30 ( p=0.48 ) . No change in physical functioning was observed with the EORTC QLQ-C30 and R AND -36 ( respectively , p=0.33 and p=0.09 ) . CONCLUSIONS These preliminary results show that physical exercise in patients with advanced cancer is feasible . A significant impact was observed on physical and QoL outcomes . These findings need to be confirmed with a larger-scale , r and omized controlled trial Introduction . Patients with advanced-stage lung cancer face poor survival and experience co-occurring chronic physical and psychosocial symptoms . Despite several years of research in exercise oncology , few exercise studies have targeted advanced lung cancer patients undergoing chemotherapy . The aim of the present study was to investigate the benefits of a 6-week supervised group exercise intervention and to outline the effect on aerobic capacity , strength , health-related quality of life ( HRQoL ) , anxiety , and depression . Methods . VO2peak was assessed using an incremental exercise test . Muscle strength was measured with one repetition maximum test ( 1RM ) . HRQoL , anxiety , and depression were assessed using Functional Assessment of Cancer Therapy – Lung ( FACT-L ) scale and the Hospital Anxiety and Depression Scale ( HADS ) . Results . One hundred and forthteen patients with advanced stage lung cancer were recruited . Forty-three patients dropped out . No serious adverse events were reported . Exercise adherence in the group training was 68 % . Improvements in VO2peak ( P < .001 ) and 6-minute walk distance ( P < .001 ) and muscle strength measurements ( P < .05 ) were seen . There was a reduction in anxiety level ( P = .0007 ) and improvement in the emotional well-being parameter ( FACT-L ) but no statistically significant changes in HRQoL were observed . Conclusion . The results of the present study show that during a 6-week hospital-based supervised , structured , and group-based exercise program , patients with advanced-stage lung cancer ( NSCLC IIIb-IV , ED-SCLC ) improve their physical capacity ( VO2peak , 1RM ) , functional capacity , anxiety level , and emotional well-being , but not their overall HRQoL. A r and omized controlled trial testing the intervention including 216 patients is currently being carried out OBJECTIVE To describe the proportion and characteristics of patients with late stage cancer that are and are not receptive to receiving rehabilitation services , and the rationale for their level of interest . DESIGN Prospect i ve mixed- methods study . SETTING Comprehensive cancer center in a quaternary medical center . PARTICIPANTS Adults with stage IIIC or IV non-small cell or extensive stage small cell lung cancer ( N=311 ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Telephone-acquired responses to the administration of ( 1 ) the Activity Measure for Post Acute Care Computer Adaptive Test ( AM-PAC-CAT ) ; ( 2 ) numerical rating scales for pain , dyspnea , fatigue , general emotional distress , and distress associated with functional limitations ; ( 3 ) a query regarding receptivity to receipt of rehabilitation services , and ( 4 ) a query about rationale for nonreceptivity . RESULTS Overall , 99 ( 31.8 % ) of the study 's 311 participants expressed interest in receiving rehabilitation services : 38 at the time of enrollment and an additional 61 during at least 1 subsequent contact . Participants expressing interest were more likely to have a child as primary caregiver ( 18.18 % vs 9.91 % , P=.04 ) and a musculoskeletal comorbidity ( 42.4 % vs 31.6 % , P=.05 ) . Function-related distress was highly associated with receptivity , as were lower AM-PAC-CAT scores . Reasons provided for lack of interest in receiving services included a perception of their limited benefit , being too busy , and prioritization below more pressing tasks/concerns . CONCLUSIONS One-third of patients with late stage lung cancer are likely to be interested in receiving rehabilitation services despite high levels of disability and related distress . These findings suggest that patient misperception of the role of rehabilitation services may be a barrier to improved function and quality of life . Efforts to educate patients on the benefits of rehabilitation and to more formally integrate rehabilitation as part of comprehensive care may curb these missed opportunities PURPOSE This study aim ed to evaluate the safety , feasibility , and effects of an 8-wk combined resistance and endurance exercise program in patients with advanced non-small cell lung cancer ( NSCLC ) during in- and outpatient care . METHODS In this intervention study , 40 patients with predominantly advanced NSCLC receiving simultaneous or sequential radiochemotherapy or chemotherapy alone were enrolled . For a period of 8 wk , patients were instructed to exercise at least five times per week during the inpatient setting and at least three times per week in the outpatient setting . Physical performance status ( endurance capacity : 6-min walk test ; strength capacity : h and held dynamometry ) , quality -of-life ( Functional Assessment of Cancer Therapy-Lung ) , fatigue ( Multidimensional Fatigue Inventory ) , and depression ( Patient Health Question naire ) were assessed at baseline ( T0 ) , after the exercise intervention ( T1 ) , and at a follow-up time point 8 wk later ( T2 ) . The primary end point was adequate adherence ( feasibility ) defined as completing at least two training sessions per week during a minimum of 6 wk . RESULTS Of 40 patients , 31 ( 77.5 % ) completed the postexercise assessment ( T1 ) and 22 ( 55 % ) completed follow-up ( T2 ) . The stages were IIA ( 5 % ) , IIIA ( 8 % ) , IIIB ( 20 % ) , and IV ( 67 % ) , and the median age was 63 yr ( range = 22 - 75 yr ) . Overall , adherence was 82 % for those patients who completed T1 , and 55 % of the 40 participating patients fulfilled the adequate adherence criterion . Those who completed the intervention showed a significant improvement in the 6-min walk distance and in knee , elbow , and hip muscle strength after the intervention ( T1 ) . Quality of life , fatigue , and depression scores remained stable or declined slightly . Significant improvements in knee-muscle strength were also observed at T2 . CONCLUSIONS Exercise training is feasible in advanced and metastatic NSCLC patients during anticancer treatment . In this pilot study , endurance and strength capacity improved over time , indicating the rehabilitative importance of the applied intervention . To investigate the potential impact of exercise training in this patient group , a larger r and omized trial is warranted BACKGROUND This study explored the effects of acupressure on fatigue of lung cancer patients undergoing chemotherapy . PATIENTS AND METHODS For this experimental study , 57 subjects were r and omly assigned to three groups : acupressure with essential oils ( n=17 ) , acupressure only ( n=24 ) , and sham acupressure ( n=16 ) . Acupoints were Hegu ( LI4 ) , Zusanli ( ST36 ) , and Sanyingjiao ( SP6 ) . All subjects received acupressure once every morning for 5 months , with each acupoint pressed for 1 min . Fatigue , functional status , anxiety , depression , and sleep quality were measured before initial chemotherapy ( T0 ) , on Day 1 of third chemotherapy ( T1 ) , and on Day 1 of sixth chemotherapy ( T2 ) . Outcome differences between groups were analyzed at T0 , T1 , and T2 by general estimating equations . RESULTS After controlling for baseline outcome values , age , and adherence to acupressure , subjects who received acupressure with essential oils and acupressure had significantly less fatigue in daily living activities and sleep better quality at T1 than subjects who received sham acupressure . Subjects who received acupressure with essential oils had significantly better sleep quality at T2 than the sham acupressure group . Subjects who received acupressure with or without essential oils had greater odds of better functional status at T1 than the sham group . CONCLUSION It is plausible that acupressure with or without essential oils helps lung cancer patients undergoing chemotherapy reduce cancer-related fatigue and increase activity level . Further study is wanted to test this hypothesis A community-based nursing study was conducted in Sydney , Australia , to compare the effects of progressive muscle relaxation and guided imagery on anxiety , depression , and quality of life in people with advanced cancer . In this study , 56 people with advanced cancer who were experiencing anxiety and depression were r and omly assigned to 1 of 4 treatment conditions : ( 1 ) progressive muscle relaxation training , ( 2 ) guided imagery training , ( 3 ) both of these treatments , and ( 4 ) control group . Subjects were tested before and after learning muscle relaxation and guided imagery techniques for anxiety , depression , and quality of life using the Hospital Anxiety and Depression scale and the Functional Living Index — Cancer scale . There was no significant improvement for anxiety ; however , significant positive changes occurred for depression and quality of life Physical exercise has been shown to enhance quality of life ( QOL ) in cancer survivors using pretest-posttest design s and compared to usual care ( i.e. no intervention ) . In the present study , we conducted a r and omized controlled trial to determine if exercise could improve QOL in cancer survivors beyond the known benefits of group psychotherapy ( GP ) . We matched 22 GP classes ( N=108 ) on content and then r and omly assigned 11 ( n=48 ) to GP alone and 11 ( n=60 ) to GP plus home-based , moderate-intensity exercise ( GP+EX ) . Participants completed a physical fitness test and QOL measures ( e.g. Functional Assessment of Cancer Therapy scales ) at the beginning and end of GP classes ( about 10 weeks ) . We had excellent recruitment ( 81 % ) , retention ( 89 % ) , and adherence ( 84 % ) rates and a modest contamination ( 22 % ) rate . Using intention-to-treat repeated measures analyses of variance , we found significant Time by Condition interactions for functional well-being , fatigue , and sum of skinfolds . We also found borderline significant interactions for physical well-being , satisfaction with life , and flexibility . All interactions favored the GP+EX condition . We conclude that a home-based , moderate intensity exercise program may im-prove QOL in cancer survivors beyond the benefits of GP , particularly in relation to physical and functional well-being BACKGROUND Breathlessness remains a refractory symptom in malignant lung disease . Breathing training is an effective , non-pharmacological intervention but it is unclear how this should be delivered . This feasibility study aim ed to assess recruitment and retention , best end point and variability of breathlessness scores in order to calculate sample size for a future study . METHOD This was a single centre , r and omised controlled non-blinded parallel group feasibility study . Eligible participants ( breathless patients with intrathoracic malignancy ) received three breathlessness management training sessions or a single session only . Follow-up was for eight weeks and endpoints were : numerical rating scales ( NRS ) of breathlessness severity ; breathlessness distress ; HADS question naire ; coping ( BriefCOPE and our NRS coping question ) ; EQ-5D and EQ-VAS . RESULTS 22 patients were r and omised over 12 months ; 55 % of expected recruitment from pilot data . Screening logs indicated this result ed , in part , from excluding patients who were receiving or who had recently received chemotherapy or radiotherapy . There was 40 % drop-out by week four . The most useful NRS scores for breathlessness severity were for " worst " and " average " over past 24h . From the variability data for " worst breathlessness " , a sample size of 270 should allow detection of a 30 % improvement in area under the curve in the three-session group compared with single-session , ( 90 % power ; p=0.05 , two-tailed ; 2:1 r and omisation single : three sessions ) allowing 50 % drop out at four weeks . CONCLUSIONS The follow-on study will test the hypothesis that three sessions of training improve breathlessness better than a single session . It will include patients undergoing palliative anti-cancer therapy . Stratification by centre will allow for differences in rates of chemotherapy or radiotherapy and variations in breathlessness service configuration BACKGROUND Self-management is recommended for patients with chronic conditions , but its use with cancer survivors is underexplored . Optimal strategies for achieving lifestyle changes in cancer survivors are not known . OBJECTIVE We aim ed to determine feasibility , acceptability and preliminary efficacy of self-management-based nutrition and physical activity interventions for cancer survivors . DESIGN , SETTING AND PARTICIPANTS Adult survivors ( n = 25 ) during ( Group 1 , n = 11 ) or post ( Group 2 , n = 14)-curative chemotherapy for solid tumours , most ( n = 20 , 80 % ) with breast cancer , were recruited prospect ively from a single clinical centre . INTERVENTION The Flinders Living Well Self-Management Program , a generic self-management care planning programme , was utilized to establish patient-led nutrition and exercise goals within a tailored 12-week intervention . Fortnightly progress review s occurred with assessment s at baseline , 6 and 12 weeks . RESULTS Most participants ( 84 % ) found the intervention acceptable/very acceptable . Both groups showed a trend towards significant improvement in the self-management capability ' knowledge about changing risk factors ' ( P = 0.047 ) ; Group 2 showed a trend towards significantly improved ' psychological impacts ' ( P = 0.007 ) . Goal ratings improved for both groups ( P = 0.001 ) . Quality of life improved for both groups for emotional functioning ( P = 0.03 ) . Physical functioning improved for Group 2 ( P = 0.05 ) ; however , most symptom domains worsened for Group 1 , as expected given their treatment stage . DISCUSSION AND CONCLUSIONS Self-management interventions are feasible for this population . In particular , building self-management capacity during the active phase of patients ' cancer treatment provides health and psychosocial benefits . Larger r and omized controlled trials are required to further determine efficacy . Further translational research is also needed to determine acceptability , feasibility , enablers and barriers for clinicians embedding this approach into routine cancer survivorship care OBJECTIVES The objective of this study was to determine the effects of physical therapy , including massage and exercise , on pain and mood in patients with advanced terminal cancer . DESIGN The design was a r and omized controlled pilot study . SUBJECTS Twenty-four ( 24 ) patients with terminal cancer were r and omly assigned to one of two treatment groups . INTERVENTIONS Group A received a physiotherapy intervention consisting of several massage techniques , mobilizations , and local and global exercises . Group B received a simple h and contact/touch to areas of pain ( cervical area , shoulder , interscapular area , heels , and gastrocnemius ) , which was maintained for the same period of time as the intervention group . All patients received six sessions of 30 - 35 minutes in duration over a 2-week period . OUTCOMES Outcomes were collected at baseline , at 1 week , and at a 2-week follow-up ( after treatment completion ) by an assessor blinded to the treatment allocation of the participants . Outcomes included the Brief Pain Inventory ( BPI , 0 - 10 scale ) , Memorial Pain Assessment Card ( 0 - 10 scale ) , and Memorial Symptom Assessment Scale ( MSAS Physical , Psychological , 0 - 4 scale ) . Baseline between-group differences were assessed with an independent t-test . A two-way repeated- measures analysis of variance was used to examine the effects of the intervention . RESULTS There were no significant between-group baseline differences ( p>0.2 ) . A significant group × time interaction with greater improvements in group A was found for BPI worst pain ( F=3.5 , p=0.036 ) , BPI pain right now ( F=3.94 , p=0.027 ) , and BPI index ( F=13.2 , p<0.001 ) , for MSAS Psychological ( F=8.480 , p=0.001 ) . CONCLUSIONS The combination of massage and exercises can reduce pain and improve mood in patients with terminal cancer . A sustained effect on pain and psychologic distress existed ; however , parameters such as physical distress and the least pain were no greater in the intervention group as compared to the sham CONTEXT Palliative care , including symptom management and attention to quality of life ( QOL ) concerns , should be addressed throughout the trajectory of a serious illness such as lung cancer . OBJECTIVES This study tested the effectiveness of an interdisciplinary palliative care intervention for patients with Stage I-IV non-small cell lung cancer ( NSCLC ) . METHODS Patients undergoing treatments for NSCLC were enrolled in a prospect i ve , quasi-experimental study whereby the usual care group was accrued first followed by the intervention group . Patients in the intervention group were presented at interdisciplinary care meetings , and appropriate supportive care referrals were made . They also received four educational sessions . In both groups , QOL , symptoms , and psychological distress were assessed at baseline and 12 weeks using surveys which included the Functional Assessment of Cancer Therapy-Lung and the Lung Cancer Subscale , the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being , and the Distress Thermometer . RESULTS A total of 491 patients were included in the primary analysis . Patients who received the intervention had significantly better scores for QOL ( 109.1 vs. 101.4 ; P < 0.001 ) , symptoms ( 25.8 vs. 23.9 ; P < 0.001 ) spiritual well-being ( 38.1 vs. 36.2 ; P = 0.001 ) , and lower psychological distress ( 2.2 vs. 3.3 ; P < 0.001 ) at 12 weeks , after controlling for baseline scores , compared to patients in the usual care group . Patients in the intervention group also had significantly higher numbers of completed advance care directives ( 44 % vs. 9 % ; P < 0.001 ) , and overall supportive care referrals ( 61 % vs. 28 % ; P < 0.001 ) . The benefits were seen primarily in the earlier stage patients vs. those with Stage IV disease . CONCLUSION Interdisciplinary palliative care in the ambulatory care setting result ed in significant improvements in QOL , symptoms , and distress for NSCLC patients |
1,708 | 28,099,657 | CONCLUSIONS Non-pharmacological treatment improves the overall quality of life and physical domain of people with arterial hypertension .
Adherence to pharmacological treatment has a positive impact on the mental and physical domains of patients , as it did on the overall quality of life score | ABSTRACT OBJECTIVE To verify the effects of antihypertensive treatment ( pharmacological and non-pharmacological ) on the health-related quality of life of individuals with hypertension . | Background A post-hoc analysis was performed on the data from a 54 weeks phase III study ( Clinical Trials.gov identifier : NCT00923091 ) to measure changes in the health-related quality of life ( HRQoL ) of 2,690 patients aged ≥18 with moderate-to-severe hypertension who received one of six doses of olmesartan/amlodipine/hydrochlorothiazide ( OLM/AML/HCTZ ) , using the MINICHAL and EQ-5D instruments . Methods Descriptive statistics were used to assess blood pressure and HRQoL scores over the study period . Analysis of covariance ( ANCOVA ) was used to identify those factors that could possibly have influenced HRQoL. Linear regression was used to assess the relationship between changes in blood pressure and HRQoL scores . Results Patients ’ baseline MINICHAL mood and somatic domains scores were 5.5 and 2.6 . Over the study period HRQoL improved as both MINICHAL scores decreased by 31 - 33 % . Patients ’ baseline EQ-5D index and VAS scores were 0.9 and 73.4 respectively , increasing by 6 % and 12 % over the study period . Patients ’ QALY gain over the 54 weeks study period was estimated to be 0.029 QALYs . The ANCOVA showed that changes in patients ’ HRQoL was likely to have been influenced by patients ’ achievement of blood pressure control , the amount of concomitant medication and patients ’ last used dosage strength of antihypertensive . Linear regression showed that blood pressure improvement may have been associated with improved HRQoL. Conclusions This study showed that OLM/AML/HCTZ reduced blood pressure and significantly increased blood pressure control whilst improving patients ’ HRQoL. Achieving blood pressure control , amount of concomitant medication and dosage strength of antihypertensive impacted on patients ’ OBJECTIVE The study evaluated whether a pharmaceutical care intervention can result in better underst and ing about hypertension , increase medication adherence to antihypertensive therapy and improve overall health-related quality of life . METHODS A non- clinical r and omized control trial was conducted whereby participants received an educational intervention through hospital pharmacists . Hypertension knowledge , medication adherence and health-related quality of life were measured by means of self-administered question naires . Descriptive statistics were used to describe the demographic and disease characteristics of the patients . Inferential statistics were used for inter- and intragroup comparisons . SPSS 17 was used for data analysis . RESULTS Three hundred and eighty-five hypertensive patients were r and omly assigned ( 192 in the control group and 193 in the intervention group ) to the study . No significant differences were observed in either group for age , gender , income , locality , education , occupation or duration of disease . There was , however , a significant increase in the participants ' levels of knowledge about hypertension and medication adherence among the interventional group after completing the intervention . Significantly lower systolic and diastolic blood pressure levels were also observed among the interventional group after completion of the intervention . The interventional group , however , reported decreased yet significant health-related quality of life at the end of the interventional programme . CONCLUSION Pharmacist intervention can significantly increase disease-related knowledge , blood pressure control and medication adherence in patients with hypertension . However , further research is needed to address the decreased health-related quality of life after completion of the study Changes in coronary risk factors , health behaviours , and health-related quality of life ( HRQOL ) were examined by tertiles of social support group attendance in 440 patients ( 21 % females ) with coronary artery disease . All patients participated in the Multicenter Lifestyle Demonstration Project ( MLDP ; eight hospital sites in the USA ) , an insurance-covered multi-component cardiac prevention program including dietary changes , stress management , exercise and group support for 1 year . Significant improvements in coronary risk factors , health behaviours , and HRQOL were noted at 1 year . Several of these improvements ( i.e. systolic blood pressure , health behaviours , HRQOL ) were related to social support group attendance , favoring those who attended more sessions . The associations between support group attendance to systolic blood pressure and to four HRQOL subscales ( bodily pain , social functioning , mental health , and the mental health summary score ) remained significant when controlling for changes in health behaviours , but dropped to a non-significant level for the HRQOL subscales ‘ physical functioning ’ , ‘ general health ’ and ‘ role-emotional ’ . These results suggest an independent relationship of social support group attendance to systolic blood pressure while improvements in quality of life may be in part due to improved health behaviours facilitated by increased social support group attendance Hypertensive patients may be adversely affected by complications and other concomitant processes such as anxiety , sedation , and drug side effects . It has been suggested that some recently developed antihypertensive agents do not affect quality of life by causing adverse effects . We compared the effects of two antihypertensive drugs on quality of life : atenolol , a st and ard cardioselective β-blocker , and celiprolol , one of a new class of selective β-blockers with vasodilatory properties . One hundred thirty-two patients with mild-to-moderate hypertension were eligible to enter a 28-week , double-blind , parallel-group study . The study protocol consisted of a 4-week period on placebo and a 24-week period of dosage-adjusted treatment with either atenolol or celiprolol . We assessed both systolic and diastolic blood pressure and quality of life perception by a selected test battery that included the Bulpitt and Fletcher Quality of Life Question naire . Supine blood pressure fell from 167/101 ( range 120/95 to 200/116 ) to 150/92 mm Hg ( p < 0.0001 ) during celiprolol treatment . This antihypertensive effect was at least as good with celiprolol as with atenolol . Quality of life perception was comparable for the two drugs although adverse effects were seen more frequently with atenolol than with celiprolol , particularly after prolonged treatment . Patient compliance was better for celiprolol than for atenolol . Our results show that the selective β-blocker with vasodilatory property celiprolol is at least as effective as atenolol and that it is more advantageous in terms of some quality of life variables BACKGROUND The goal of this pilot study was to examine the effects of a structured interdisciplinary education program on blood pressure , knowledge , anthropometric measures , medication compliance , behavioural risk factors and quality of life . METHOD In this quasi-experimental study , participants were assigned to an intervention ( n = 21 ) or a regular care group ( n = 19 ) . The intervention group attended four weekly sessions related to hypertension . Anthropometric measures and blood pressure were recorded at baseline , one , three and six months for all participants . Both groups completed question naires on knowledge , health-related behaviours and quality of life at these same intervals . RESULTS The reduction in systolic blood pressure was greater in the intervention group than in the regular care group ( p = 0.05 ) . However , there were no between group differences with regard to the other variables studied . CONCLUSION Participation in a structured interdisciplinary education program was associated with a reduction of systolic blood pressure , thus contributing to a risk reduction for cardiovascular disease The impact of hostility was examined in relation to the conduct and results of a clinical field trial . Data were derived from a multi-center r and omized double-blind study of the comparative effects of antihypertensive therapy ( captopril , methyldopa and propranolol ) on the quality of life of 620 hypertensive men . Hostility levels were higher in subjects reporting skipping medication dosages compared to those reporting they always complied with the medication schedule . Reporting of symptoms often associated with antihypertensive drug regimens was positively related to hostility scores throughout the study , even during the blinded placebo period . Persons with high hostility scores showed the greatest decline in blood pressure independent of type of antihypertensive medication . However , there was some limited evidence that hostility levels were significantly reduced by one antihypertensive medication . Overall , the present findings suggest that double-blind pharmacologic clinical trials may benefit from using reliable measures of hostility as covariates in the evaluation of symptom reports and amount of blood pressure reduction The aim was to evaluate the effects of a change of treatment from beta-blocker to captopril on the quality of life of hypertensive patients . One hundred forty-nine mild to moderate hypertensive patients who were being treated with beta-blockers were r and omly assigned to receive captopril ( 12.5 to 50 mg twice daily ) , or to continue on beta-blocker treatment ( atenolol : 25 to 100 mg once daily [ n = 121 ] , or propranolol , 10 to 80 mg twice daily [ n = 12 ] ) . When required , 25 mg hydrochlorothiazide was added in each group . The patients were followed over periods ranging from 6 to 12 months . Blood pressure , treatment side effects , and quality of life were monitored . Blood pressure was equally well managed in both groups , though a lower level of treatment was required in the captopril group . The captopril treated patients exhibited favorable changes in several aspects of quality of life : sleep-related , gastrointestinal , and physical activity-related symptoms improved from baseline to end of follow-up . Drowsiness and the ability to concentrate significantly improved in the captopril group only ( P < .01 ) . Change in treatment from beta-blocker to captopril result ed in equally well controlled blood pressure on a lower drug dose . Moreover , the change to captopril had a positive impact on the quality of life In an experimental study , 150 general practitioners studied 468 apparently healthy subjects whose blood pressure ( BP ) level was unknown or had not been measured for 1 year . The study lasted for 10 weeks . If BP was > 95 mm Hg on the first two visits , subjects were r and omized into two experimental groups for 8 weeks , with cross-over from betaxolol to placebo and vice versa after 4 weeks . Quality of life was measured at visits 1 , 3 ( 2 weeks ) , 5 ( 6 weeks ) , and 7 ( 10 weeks ) in five ways : well-being , physical state , sexual functioning , sleep , and cognitive acuity . BP level appeared to be effectively controlled by betaxolol as compared with placebo . The results show that no effects on quality of life could be detected by labeling subjects as hypertensives . Equally , almost no effects of active treatment could be established . Learning effects on the two cognitive acuity measurements used were attenuated by betaxolol , however . Apparently , in a carefully controlled study , the effects of increased medical attention and care outweigh the potentially negative effects of labeling and treatment BACKGROUND Most treated hypertensive patients do not achieve adequate blood pressure ( BP ) control . Initiating therapy with two drugs has been suggested when BP is > 20/10 mm Hg above goal . To ensure patients ' compliance , such treatment needs to be well tolerated and must not compromise health-related quality of life ( HRQL ) . The primary objective of this study was to compare the effects on HRQL of initiating treatment with felodipine + metoprolol ( F+M ) fixed combination tablets , or enalapril ( E ) , or placebo ( P ) . METHODS A total of 947 patients of both sexes with primary hypertension ( diastolic BP 95 to 110 mm Hg ) , aged 20 to 70 years , participated in this r and omized , double-blind , parallel group , 12-week , multicenter trial . Treatment was initiated with F+M 5 + 50 mg , or E 10 mg , or P. Doses were doubled after 4 or 8 weeks if diastolic BP was > 90 mm Hg . The HRQL was measured at baseline and at the last visit using two vali date d question naires : the Psychological General Well-being Index ( PGWB ) and the Subjective Symptom Assessment Profile ( SSA-P ) . Office BP was measured at trough , that is , 24 h after the previous dose . RESULTS The HRQL was high at baseline and generally well maintained during the study . For example , the mean ( SD ) PGWB total score was 104 ( 16 ) at baseline and 105 ( 16 ) at 12 weeks in all three treatment groups . The BP reductions after F+M ( 18/14 mm Hg ) and E ( 12/9 mm Hg ) were significantly greater than after P ( 7/7 mm Hg ) , and the reduction after F+M was significantly greater than after E. CONCLUSIONS The HRQL is maintained in the presence of substantial BP reduction during antihypertensive treatment with F+M fixed combination tablets OBJECTIVE To determine whether pharmaceutical care provided by a pharmacist-managed hypertension clinic results in better treatment outcomes when compared with traditional health care from a primary care physician . DESIGN Prospect i ve , controlled study SETTING Veterans Affairs Medical Center , Philadelphia , Pennsylvania . PATIENTS Fifty six patients with essential hypertension ; 27 were r and omly assigned to the intervention group and 29 to the control group . INTERVENTION Patients in the intervention group were scheduled monthly to meet with a clinical pharmacist who made appropriate changes in prescribed drugs , adjusted dosages , and provided drug counseling in accordance with the hypertension guidelines in the sixth report of the Joint National Committee on the Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) . Patients in the control group received st and ard care from their physicians . The study period was 6 months . MEASUREMENTS AND MAIN RESULTS Treatment outcomes were measured by changes in compliance , blood pressure , and patient satisfaction . The Short Form-36 health survey and a patient satisfaction survey were used to measure changes in patient satisfaction , and a compliance evaluation survey measured compliance . Twenty-one ( 81 % ) patients in the intervention group attained their blood pressure goal of below 140/90 mm Hg at the completion of the study versus only eight ( 30 % ) in the control group ( p < 0.0001 ) . Of 11 patients with diabetes in the intervention group , 10 ( 91 % ) attained their blood pressure goal ( < 130/80 mm Hg ) versus only two ( 12 % ) of 16 patients with diabetes in the control group ( p < 0.0001 ) . No significant differences in patient satisfaction or compliance were reported between the intervention and control groups . CONCLUSIONS Pharmaceutical care improves blood pressure control and results in more patients with hypertension reaching their blood pressure goal |
1,709 | 27,577,677 | AUTHORS ' CONCLUSIONS There was no evidence of a difference in efficacy between the various intravaginal oestrogenic preparations when compared with each other .
However , there was low- quality evidence that intra-vaginal oestrogenic preparations improve the symptoms of vaginal atrophy in postmenopausal women when compared to placebo .
There was low- quality evidence that oestrogen cream may be associated with an increase in endometrial thickness compared to oestrogen ring ; this may have been due to the higher doses of cream used .
However there was no evidence of a difference in the overall body of evidence in adverse events between the various oestrogenic preparations compared with each other or with placebo | BACKGROUND Vaginal atrophy is a frequent complaint of postmenopausal women ; symptoms include vaginal dryness , itching , discomfort and painful intercourse .
Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary .
An alternative choice is oestrogenic preparations administered vaginally ( in the form of creams , pessaries , tablets and the oestradiol-releasing ring ) .
This is an up date of a Chochrane systematic review ; the original version was first published in October 2006 .
OBJECTIVES The objective of this review was to compare the efficacy and safety of intra-vaginal oestrogenic preparations in relieving the symptoms of vaginal atrophy in postmenopausal women . | The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study . They had also been treated for cancer of the cervix ( 27 women ) , endometrium ( 5 ) , ovaries ( 5 ) or breast ( 1 ) . All women presented with sexual troubles , mainly genital discomfort ( dyspareunia or vaginism ) . In a double-blind fashion , gynaecological capsules containing either an oestradiol diether ( ICD : promestriene ) or only the excipient were administered for 40 consecutive days . At the end of the treatment , the FSH , LH , oestrone ( E1 ) and oestradiol ( E2 ) plasma levels were not found to be significantly different from the pre-therapeutic values . These results suggest that promestriene acts on the vaginal mucosa , therefore not being converted back into the hormone from which it was derived . Also , in its dietheroxide form , promestriene is incapable of crossing the malpighian ( vaginal or epidermal ) epithelium and of reaching the general blood circulation . This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated , as in patients who have an oestrogen-sensitive cancer in their medical history Silicone vaginal rings for the continuous release of 17 beta-oestradiol ( E2 ) with 2 constant in vitro release rates were used for the treatment of symptoms of urogenital atrophy in 2 groups of postmenopausal women . The very low dose of 7 micrograms/24 h was found to alleviate atrophic symptoms effectively and to induce significant maturation of vaginal and urethral epithelium . After a brief initial peak , the serum levels of E2 over 3 mth of treatment remained close to the detection limit . The ' undetectable ' E2 release pattern was reflected only in increased levels of oestrone sulphate . There was no evidence of a systemic metabolic response and patient acceptance of the method was excellent . Continuous low-dose release of E2 via vaginal rings consequently offers an alternative means of administering local oestrogen therapy which may be particularly suitable for geriatric patients OBJECTIVE : To evaluate the efficacy of two vaginal doses of estradiol ( E2 ) compared with placebo in the treatment of atrophic vaginitis . METHODS : In a multi-center , r and omized , double-blind , parallel-group study , 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks . Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health . Additional analyses included maturation of vaginal and urethral mucosa . Safety assessment s included endometrial biopsy , adverse events , changes in laboratory tests , and physical examinations . After 12 weeks of treatment , all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52 . RESULTS : Vaginal tablets with 25 mcg and 10 mcg E2 showed significant ( P<.001 ) improvement in composite score of vaginal health . Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2 . Over 12 weeks , both active treatments result ed in greater decreases in vaginal pH than placebo . There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms . The efficacy was maintained to week 52 with 25 mcg E2 . CONCLUSION : Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms , improved urogenital atrophy , decreased vaginal pH , and increased maturation of the vaginal and urethral epithelium . Those improvements were greater with 25 mcg than with 10 mcg E2 . Both doses were effective in the treatment of atrophic vaginitis . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00465192 and NCT00464971 LEVEL OF EVIDENCE : Objective : The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens ( CE ) cream for treatment of atrophic vaginitis . Methods : Postmenopausal women ( N = 423 ) with moderate-to-severe vaginal atrophy were r and omized to CE cream 0.3 mg or placebo once daily ( 21 days on/7 days off ) or twice weekly for 12 weeks , followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen . Primary endpoints were changes in vaginal maturation index ( VMI ; percentage of superficial cells ) , vaginal pH , and severity of participant-reported most bothersome symptom ( vaginal dryness , itching , burning , or dyspareunia ) at week 12 . Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks . Results : At week 12 , improvements in VMI with daily and twice-weekly use of low-dose CE cream ( 27.9 % and 25.8 % , respectively ) were significantly greater compared with placebo ( 3.0 % and 1.0 % , respectively ; P < 0.001 ) . Improvements in vaginal pH with daily and twice-weekly CE cream ( −1.6 for both ) were also significantly greater relative to placebo ( −0.4 and −0.3 , respectively ; P < 0.001 ) . VMI and vaginal pH responses were sustained through 52 weeks . Both CE cream regimens significantly reduced most bothersome symptom scores compared with placebo ( P ≤ 0.001 ) , including those for dyspareunia ( P ≤ 0.01 ) . There was no report of endometrial hyperplasia or carcinoma . Adverse events occurred with similar frequency among the active and placebo groups during the double-blind phase . Conclusions : Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy . Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy Objective To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence , urogenital atrophy , and recurrent urinary tract infections in postmenopausal women . Design Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve , r and omized , placebo-controlled study . Participants were r and omly divided into two groups , with each group consisting of 44 women . Women in the treatment group received intravaginal estriol ovules : 1 ovule ( 1 mg ) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy . Women in the control group received inert placebo vaginal suppositories in a similar regimen . We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles , and urethrocystometry before as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group . Thirty ( 68 % ) of the treated participants , and only seven ( 16 % ) of the control participants registered a subjective improvement of their incontinence . In the treated participants , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra . Urethrocystometry showed positive but not statistically significant modifications . Conclusions Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo st and ard hormone therapy tis trial , placebo controls can be used because the riskbenet ratio of no therapy is only slightly less favorable than the risk-benet ratio of any available therapy , and the result ing knowledge may contribute to the welfare of those who suffer from allergies . On this alternative view , therapeutic benecence is maintained as the moral st and ard for determining whether participation in placebo-controlled trials may be offered to subjects . It can not be dispensed with in any event , because it provides the st and ard against which placebo use must be assessed to determine that the increment of risk to subjects is not excessive . Once this determination is made , subjects may be invited to consider whether r and omization is a matter of “ approximate indifference ” in the light of their own values and goals ( Veatch 2002 ) . However , given the vagaries of assuring adequately informed consent in the real world of clinical research , therapeutic benecence should be maintained as an independent , threshold st and ard for determining whether placebo-controlled trials can be undertaken with proper regard for the welfare of subjects . On the other h and , therapeutic benecence does not constitute an absolute priority . When placebo-controlled trials impose only a modest increment of risk compared to best available therapy , then subjects may be invited to participate if doing so is necessary to contribute to the welfare of patients as a group . Miller and Brody are right about this conclusion but wrong about the underlying rationale . Background : Vaginal atrophy is a common complication in menopause which does not improve with time and , if untreated , can affect the quality of life for women . The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen ( Premarin ) in treatment of vaginal atrophy . Methods : This study was a r and omized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy ; they were r and omly allocated to two groups ( recipient conjugated estrogen and hyaluronic acid ) . The severity of each sign of atrophy was evaluated by visual analog signals ( VAS ) and on the basis of a four point scale . Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0 - 100 . As to the vaginal PH , we used PH marker b and , the rate of which was divided into 4 degrees . Data were analyzed using SPSS , version 20 , and P≤0.05 was considered as significant . Results : The results of this study showed that the symptoms of vaginal atrophy compared with the baseline level were relieved significantly in both groups . Dryness , itching , maturation index , PH and composite score of the vaginal symptoms were relieved significantly in both groups ( P<0.001 ) . Dyspareunia in Premarin ( P<0.05 ) and hyaluronic acid ( P<0.001 ) decreased compared with pre-treatment . Urinary incontinence only showed improvement in the hyaluronic acid group ( P<0.05 ) . Improvement in urinary incontinence , dryness , maturation index ( P<0.05 ) and composite score of vaginal symptoms ( P<0.001 ) in the hyaluronic acid group was better than those in the Premarin group . Conclusion : According to the results of the present study , hyaluronic acid and conjugated estrogen improved the symptoms of vaginal atrophy . But hyaluronic acid was more effective and this drug is suggested for those who do not want to or can not take local hormone treatment . Trial Registration Number : I RCT Fifty-one post-menopausal women suffering from symptoms of oestrogen deficiency-derived atrophic vaginitis were treated intravaginally with two therapeutic regimens based on doses of 25 micrograms 17 beta-oestradiol ( E2 ) in an open , controlled study . All the patients received treatment daily for 2 weeks by way of induction therapy . They were then r and omly allocated to either once-weekly ( 17 patients ) or twice-weekly ( 34 patients ) vaginal administration for a further 50 weeks as maintenance treatment . Endometrial histopathology was evaluated before and after 1 year of treatment . The effects on symptoms and oestrogen/gonadotrophin levels were determined before and after 2 , 12 , 24 , 36 and 52 weeks of therapy . Nine women continued twice-weekly treatment for a further year , meaning that they underwent treatment for a total period of 2 years . Endometrial biopsies were obtained after 2 years of treatment . All the pretreatment endometrial biopsies indicated an atrophic endometrium . One patient out of the 14 who completed 1 year of therapy in the group treated once weekly showed weak proliferation of the endometrium , while the other 13 had an atrophic endometrium . In the group treated twice weekly , 2 out of the 31 patients who completed the study showed weak proliferation of the endometrium . The other 29 had an atrophic endometrium . All 9 women who received treatment for 2 years had an atrophic endometrium at the end of the treatment period . The twice-weekly dosage regimen gave complete relief of symptoms in almost all patients , whereas the majority of the patients in the group treated once weekly still had mild symptoms . No adverse effects were reported . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE We studied the efficacy , safety , and acceptability of an estradiol-releasing ( 6.5 to 9.5 micrograms per 24 hours ) silicone vaginal ring ( Estring ) in postmenopausal women with symptoms and signs of urogenital aging during a treatment period of 1 year . STUDY DESIGN The study was open with blind analysis of vaginal cytologic testing . In addition to gynecologic examination , subjective symptoms were assessed and vaginal pH and urinary sample s ( for bacteriuria ) were obtained before insertion of Estring . This procedure was repeated every 3 months up to 1 year 's treatment , together with requests concerning acceptability and adverse experiences . At inclusion and end of Estring treatment , vaginal smears for evaluation of cytologic results were obtained . RESULTS Estring induced a high maturation value in the vaginal mucosa and restored vaginal pH to levels normality seen in fertile women ( < 5.5 ) . For most variables a 90 % responder rate ( proportion of cured and improved patients ) was found after 3 months and up to 1 year regarding subjective symptoms and objective signs of vaginal mucosal atrophy . Twenty-eight ( 20 % ) of 136 women , withdrew from the study , 8 ( 6 % ) of them because of adverse events . Three women reported vaginal bleeding , none associated with malignancy or endometrial proliferation . Ten ( 7 % ) reported vaginal irritation , and in two cases vaginal ulcers were found . About 90 % did not remove the ring during any of the 3-month treatment periods , and 78 % used the four consecutive rings continuously up to 1 year . The ring was given a strong preference ( p < 0.001 ) by patients with previous experience of other administration forms . CONCLUSION Estring represents a safe , highly effective , and very well-accepted administration form for long-term treatment of urogenital disorders caused by estrogen deficiency in postmenopausal women OBJECTIVE To assess the efficacy , tolerability , and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol ( E2 ) , compared with placebo , for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women . METHODS Women with moderate to severe vasomotor symptoms ( seven or more per day or 56 per week average ) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 ( n = 113 ) or 100 microg per day E2 ( n = 112 ) , or a placebo vaginal ring ( n = 108 ) . Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale . Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology . Participant satisfaction with the vaginal ring was evaluated via question naire . RESULTS Vasomotor symptoms significantly improved in both treatment groups , compared with placebo ( P < .05 ) . There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo . For women with vaginal atrophy at baseline ( n = 60 ) , the maturation index improved significantly in both treatment groups compared with placebo . Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups ( P < .05 ) compared with placebo . The vaginal rings were well tolerated . Most adverse events were mild or moderate and consistent with estrogen therapy . CONCLUSION A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms , compared with placebo . The E2 vaginal ring was well tolerated Vaginal atrophy can be reversed for most women through systemic hormones . Those women who can not take systemic hormones can get relief of symptoms with local estrogen therapy , which ideally should be locally effective without significant systemic absorption and without endometrial stimulation . An estradiol-releasing vaginal ring was therefore tested for efficacy , safety and patient acceptability in a 15-week open-label , r and omized parallel group trial with blinded evaluations of the cytological response data . Conjugated estrogen vaginal cream was used as a reference control . The primary objectives of the study were to evaluate whether the two treatments were equivalent regarding improvement in urogenital atrophy , improvement in physicians 's overall evaluation of product performance on urinary and /or vaginal changes , and improvement in patient 's assessment of urinary and /or vaginal symptoms . A secondary objective was to assess frequency of endometrial overstimulation during estrogen replacement therapy , to be measured by a progestogen challenge test . The ring and cream treatment produced an equivalent effect on the vaginal mucosa , and equivalence was also found in physician 's and patient 's assessment s of both vaginal and urinary symptomatology . Both treatments were equally effective in improving the vaginal pH toward levels normally seen in fertile women ( < 5.0 ) . With regard to endometrial stimulation , significantly more patients had bleedings at progestogen challenge test after 3 months of treatment with cream than with the ring . The ring , however , was given significantly better overall product acceptability ratings by the patients . It can therefore be seen as an equally effective , but significantly more acceptable , new administration form for treatment of urogenital disorders due to estrogen deficiency , with a more favourable safety profile than vaginal cream The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . 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 . Objectives To assess the efficacy of an oestradiol‐releasing vaginal ring and oestriol pessaries in the alleviation of lower urinary tract symptoms occurring after the menopause In a double-blind , placebo-controlled study , 109 patients suffering from local and vasomotor postmenopausal complaints were r and omly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol ( E3 ) or a placebo . The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially , followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period . The effectiveness of the therapy was assessed on the basis of question naires ( Kupperman index for vasomotor complaints and an original urogenital index for local complaints ) and gynaecological examinations which included assessment s of vaginal cytology , vaginal pH and Döderlein bacilli . To rule out induced endometrial proliferation , endometrial biopsies were performed in 50 women before and after the study . The vaginal depot ( E3 ) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints , including hot flushes . Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation . Taking into account the minimal rate of adverse effects , the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints OBJECTIVE Our purpose was to study the efficacy , safety , and acceptability of a new estradiol-releasing ( 6.5 to 9.5 micrograms per 24 hours ) silicone rubber vaginal ring compared with Ovesterin 0.5 mg estriol vaginal pessaries . STUDY DESIGN Gynecologic clinical status , vaginal pH , cytologic characteristics , and occurrence of bacteriuria were determined before starting and after 3 and 12 weeks of treatment in 146 postmenopausal women . RESULTS Both treatments alleviated the subjective and objective symptoms of estrogen deficiency excellently , and both were equally effective at restoring the vaginal pH to levels normally seen in fertile women ( < 5.5 ) . Vaginal cytologic studies showed a significant difference in maturation value in favor of the estradiol-releasing silicone rubber vaginal ring , as measured by the pathologist 's assessment of the proliferation of the vaginal mucosa . A total of 77 % of users were classified as responders , compared with 39 % in the pessary group . Both treatments were well accepted . The administration of the pessary was associated with a significantly higher ( p < 0.001 ) incidence of discomfort than that of the ring , which was given better ( p < 0.001 ) rating by the patients at the 12-week visit . A strong preference ( p < 0.001 ) for the ring was shown by patients with previous experience with pessaries . CONCLUSION Treatment of urogenital symptoms in postmenopausal women with an estradiol-releasing vaginal ring is shown to be an effective and safe method , exhibiting advantages over treatment with estriol vaginal pessaries ABSTRACT Objective The aim of this study was to demonstrate the efficacy of an ultra-low-dose vaginal estriol 0.03 mg in combination with viable Lactobacillus acidophilus KS400 ( Gynoflor ® vaginal tablets ) in the short-term therapy and to investigate the long-term maintenance dose in the treatment of vaginal atrophy . Methods This was a double-blind , r and omized , placebo-controlled study ( Controlled phase – initial therapy ) followed by an open-label follow-up ( Open phase – test medication initial and maintenance therapy ) . Included were postmenopausal women with vaginal atrophy symptoms and Vaginal Maturation Index ( VMI ) of ≤ 40 % . The method of treatment was initial therapy with test medication ( or placebo in first phase ) , one vaginal tablet daily for 12 days , followed by maintenance therapy , one tablet on two consecutive days weekly for 12 weeks . Results A total of 87 women completed the study . The Controlled phase results for a change in VMI demonstrated superiority of the 0.03 mg estriol – lactobacilli combination to placebo ( p < 0.001 ) . In the test group , the positive change in VMI was 35.2 % , compared to 9.9 % in the placebo group . In the Open phase after the initial therapy , the VMI was increased to 55.4 % and , during maintenance therapy , it stayed at a comparable level ( 52.8–49.4 % ) . The maturation of epithelium was followed by improvement of clinical symptoms and normalization of the vaginal ecosystem . Conclusions The ultra-low-dose , vaginal 0.03 mg estriol – lactobacilli combination ( Gynoflor ® ) was superior to placebo with respect to changes in VMI after the 12-day initial therapy , and the maintenance therapy of two tablets weekly was sufficient to prevent the relapse of vaginal atrophy Background : Atrophic vaginitis is a disease , which affects up to 50 % of postmenopausal women . This study compared the effectiveness and user-friendliness of Vagifem ( an estradiol vaginal tablet ) and vaginal estrogen cream in the treatment of atrophic vaginitis . Material s and Methods : One hundred and sixty postmenopausal women with symptoms of atrophic vaginitis were r and omly divided into two groups of treatment with Vagifem or with vaginal estrogen cream for 12 weeks . Patients used the medication daily for the first 2 weeks of the study , and twice weekly . Severity of vaginal atrophy and four main symptoms of atrophic vaginitis including dysuria , dyspareunia , vaginal itching , and dryness were evaluated and compared before and after treatment . In addition , patients were asked regarding user-friendliness and hygienic issues of medications . Results : Both vaginal estrogen cream and Vagifem significantly improved symptoms of atrophic vaginitis but in terms of effectiveness for the treatment symptoms of atrophic vaginitis , there was no significant difference between the two medications . Vagifem compared to estrogen cream result ed in significantly lower rate of hygienic problems ( 0 % versus 23 % , P < 0.001 ) , and was reported by the patients as a significantly easier method of treatment ( 90 % versus 55 % , P < 0.0001 ) . Conclusion : This investigation showed that Vagifem is an appropriate medication for the treatment of atrophic vaginitis , which is as effective as vaginal estrogen creams and is more user-friendly To determine whether the combined contraceptive pill used intravaginally was as effective as the st and ard conjugated estrogen cream for the treatment of urogenital symptoms in postmenopausal Thai women OBJECTIVE Estrogen or combined hormone ( estrogen-progestin ) therapy is highly efficacious for managing the signs and symptoms of urogenital atrophy . A low , effective estrogen dose may enhance patient acceptance and reduce side effects . METHODS In this r and omized , double-blind , multicenter clinical trial , 71 healthy postmenopausal women with vaginal atrophy ( Vaginal Maturation Index < or = 55 ) received either low-dose synthetic conjugated estrogens , A tablets ( Cenestin ) ( SCE-A ) , 0.3 mg once daily , or placebo for 16 weeks . RESULTS Treatment with SCE-A for 16 weeks result ed in a highly significant ( P<0.0001 ) mean increase of 17.7 in the Vaginal Maturation Index compared to a mean increase of 4.1 with placebo treatment . A significant estrogenic improvement was detected as early as 4 weeks ( mean increase 14.6 ) . Superficial cells were significantly increased from 2.1 % at baseline to 15.9 % at week 16 with SCE-A , and parabasal cells were significantly reduced from 23.0 % at baseline to 1.6 % at week 16 ( P<0.01 between treatments for both ) . Vaginal pH was significantly decreased from 6.2 at week -2 to 5.2 at week 16 with SCE-A compared to placebo ( P<0.0001 ) . There were no significant differences between treatment groups in the incidence of treatment-emergent side effects or other measures of safety , except for urinary tract infection , which occurred more frequently in the placebo group . CONCLUSIONS These results confirm the relatively rapid estrogenic effect and safety of a low-dose ( 0.3 mg/day ) of slow-release SCE-A ( Cenestin ) in the treatment of vaginal atrophy in postmenopausal women Objective To evaluate the use and effect of early administration of vaginal estrogen via a continuous low-dose estradiol vaginal ring placed immediately after pelvic reconstructive surgery . Methods This was a r and omized controlled trial of 65 postmenopausal women undergoing vaginal reconstructive surgery . The subjects were r and omly assigned to receive an estradiol-releasing vaginal ring , placebo vaginal ring , or control without vaginal ring for 12 weeks immediately after vaginal reconstructive surgery . The primary outcome was tissue quality based on vaginal maturation 3 months postoperatively . Secondary outcome measures were subjective and objective signs of atrophy ; vaginal pH ; the presence of granulation tissue , microscopic inflammation , and major healing abnormalities ; and the ability to tolerate an intravaginal ring . Results At 12 weeks , the estradiol ring group had a significantly improved maturation value ( P<0.01 ) and objective atrophy assessment ( P<0.01 ) compared with the placebo ring and control arms . Granulation tissue was increased in the placebo ring arm ( P<0.01 ) . Subjective atrophy scores did not differ among the groups ( P=0.39 ) . Conclusions Early administration of vaginal estrogen after vaginal surgery via an estradiol-releasing ring is feasible and results in improved markers of tissue quality postoperatively compared to placebo and controls Abstract : Local estrogen substitution has been shown to be more appropriate than any systemic application for the treatment of urogenital symptoms of hormone defiency . The efficacy , safety and acceptability of a new low-dose drug delivery system consisting of an estradiol-releasing silicone vaginal ring was studied in two multicenter trials . In an open-label comparative trial a total of 219 postmenopausal women were r and omized to the estradiol-releasing vaginal ring or to estriol suppositories . In terms of efficacy both treatment arms were shown to be equivalent ; however , significantly higher rates of acceptability were found for the vaginal ring . In a double-blinded placebo-controlled study a total of 84 patients were r and omized to either treatment arm for a period of 24 weeks . The statistically significant improvement of the vaginal epithelial pH and maturation values demonstrated the efficacy of the estradiol-releasing vaginal ring compared to the placebo ring Twenty-four postmenopausal women with vaginal atrophy due to oestrogen deficiency were treated with 17 beta-oestradiol administered as vaginal tablets containing 10 and 25 micrograms , respectively , in a slow-release system ( Vagifem , Novo Nordisk , Denmark ) . All the women were treated for 2 weeks with each dose in a double-blind , cross-over study . Plasma concentrations of unconjugated oestradiol and unconjugated oestrone were measured at regular intervals for 24 h on days 1 and 14 of each treatment regimen . Cytological and clinical evaluations of the vaginal and urethral epithelium were also carried out . Initially , when the epithelium was still atrophic , dose-dependent absorption of oestradiol was demonstrated . After 14 days of treatment maturation of the vaginal epithelium was seen with both regimens and the absorption of oestradiol then declined significantly on both the 10 and the 25 micrograms dose . Oestrone levels remained unchanged and gonadotrophin levels were unaffected during treatment . Vaginal cytology showed maturation on both the 10 and the 25 micrograms dose , whereas urethral cytology showed a reduction in parabasal cells that was significant only on 25 micrograms . Clinical and subjective improvement was apparent on both doses and acceptance of treatment was good A peculiar aspect of the postmenopausal period is atrophy of the lower genital tract , vagina and vulva . This is due to estrogen deficiency and is accompanied by vaginal pH elevation , lower number of lactobacilli and increased incidence of aspecific vulvovaginitis . We tested a new vaginal douche with an antibacterial-anti-inflammatory ( non antibiotic-nonsteroidal ) principle , cetyltrimethylammonium naproxenate 0.223 % as an adjunct to classical estrogen topical replacement therapy . We treated 34 menopausal patients ( mean age 67 yrs ) in a double parallel controlled ( 15 A only estrogen topical therapy vs 19 B topical estrogen plus cetyltrimethylammonium naproxenate douches uid ) study for 30 days . A significant reduction of symptoms was obtained in both groups although a faster reduction has been seen in the group treated with both drugs (= B ) . In conclusion a better replacement of physiological pH with reappearance of lactobacilli , a selective action on vaginal pathogens , a faster symptom remission and an higher psychophysical welfare can be attributed to the vaginal douche used in adjunct to classical estrogen topical therapy Abstract . Thirty postmenopausal women with vaginal atrophy were treated with a vaginal cream or vaginal suppositories containing 0.5 rag estriol ( OvestinR , Organon , The Netherl and s ) . The preparations were given daily for 14 days and then during the next 6 weeks a maintenance dose was applied twice a week OBJECTIVES Determination of the efficacy and safety of vaginally administered low dose ( 25 microg ) micronized 17beta-estradiol in the management of patients with urogenital symptoms . METHODS A total of 1612 patients with urogenital complaints were r and omized to receive 25 microg of micronized 17beta-estradiol ( n=828 ) or placebo ( n=784 ) in a multicenter double-blind placebo-controlled study running for 12 months . Female patients were treated once a day over a period of 2 weeks , and then twice a week for the remaining of the 12 months with an active or placebo tablet . The assessment included full history- question naire , micturition diary , gynecologic and cystometric examination , transvaginal ultrasound , and serum 17beta-estradiol level determination . It was carried out at the beginning , and after 4 and 12 months of treatment . RESULTS The overall success rate of micronized 17beta-estradiol and placebo on subjective and objective symptoms of postmenopausal women with vaginal atrophy was 85.5 % , and 41.4 % , respectively . A significant improvement of urinary atrophy symptoms was determined in vaginal ERT group as compared with the beginning of the study ( 51.9 % vs. 15.5 % , P=0.001 ) . The maximal cystometric capacity ( 290 ml vs. 200 ml , P=0.023 ) , the volume of the urinary bladder at which patients first felt urgency ( 180 vs. 140 , P=0.048 ) , and strong desire to void ( 170 ml vs. 130 ml , P=0.045 ) were significantly increased subsequent to the micronized 17beta-estradiol treatment . The number of patients with uninhibited bladder contractions significantly decreased following micronized 17beta-estradiol as compared with pretreatment values ( 17/30 , P=0.013 ) . Side effects were observed in 61 ( 7.8 % ) patients treated with low dose micronized 17beta-estradiol . Therapy with 25 microg of micronized 17beta-estradiol did not raise serum estrogen level nor stimulated endometrial growth . CONCLUSIONS Local administration of 25 microg of micronized 17beta-estradiol is an effective and a safe treatment option in the management of women with urogenital complaints Objective : To compare the effects of oral and vaginal estrogen therapy ( ET ) on the vaginal blood flow and sexual function in postmenopausal women with previous hysterectomy . Design : Fifty-seven women were r and omized to receive either oral ( 0.625 mg of conjugated equine estrogens per tablet ; n = 27 ) or topical ( 0.625 mg conjugated equine estrogens per 1 g vaginal cream ; n = 30 ) estrogen administered once daily . All women underwent estradiol measurements , urinalysis , pelvic examination , introital color Doppler ultrasonographies , and personal interviews for sexual symptoms using a vali date d question naire before and 3 months after ET . Results : A higher serum level of estradiol was noted in the oral group compared with the topical group after 3 months of ET . There were significant increases in the number of vaginal vessels and the minimum diastole ( P < 0.01 ) , and marked decreases of pulsatility index values ( P < 0.01 ) in both groups after ET . Regarding the systolic peak , we found a significant decrease only in the topical group ( P < 0.05 ) . Although the post-ET prevalence of anorgasmia decreased significantly in both groups ( P < 0.05 ) , changes in other domains , including the rates of low libido and coital frequency , were not statistically significant ( P > 0.05 ) . In the topical group , ET improved sexual function on the vaginal dryness and dyspareunia domains in a statistically significant manner ( P < 0.05 ) , but this was not the case in the oral group ( P > 0.05 ) . However , the efficacy of oral ET for vaginal dryness and dyspareunia reached 80 % and 70.6 % , respectively . The corresponding figures of the topical ET were 79.2 % and 75 % . Conclusions : The results of our study suggest that ET alone in hysterectomized postmenopausal women increases the vaginal blood flow and improves some domains of sexual function , but it may not have an impact on diminished sexual desire or activity . Compared with systemic therapy , topical vaginal preparations are found to correlate with better symptom relief despite the lower serum level of estradiol Twenty ( 20 ) post-menopausal women , mean age 62.4 yr , presenting with symptoms associated with urogenital atrophy were treated intravaginally with daily doses of 25 and 50 micrograms oestradiol ( E2 ) in a double-blind , cross-over study . After r and omization , the patients started daily treatment with pessaries containing either 25 or 50 micrograms E2 for 3 wk , followed by a maintenance period of 6 wk during which the pessaries were used only twice a week . A 4-wk wash-out period was followed by another treatment period of 9 wk . The effects on the karyopyknotic index ( KPI ) and on endometrial histopathology were assessed before and after 3 , 9 , 16 and 22 wk of treatment . In the case of the 25 micrograms dose the mean KPI values were 34.7 and 20.9 % after 3 and 9 weeks of treatment , respectively , the corresponding figures after treatment with 50 micrograms E2 being 39.2 and 22.7 % . No dose-effect relationship was apparent from the vaginal cytology findings . Endometrial biopsies could not be taken systematic ally in all patients . Weak proliferation of the endometrium was observed in 1 woman after 3 wk of daily treatment with the 50 micrograms dose . No endometrial stimulation was detected in any of the patients after treatment with 25 micrograms daily . Beneficial clinical and cytological effects were obtained with both dosage regimens . Daily intravaginal administration of 25 micrograms E2 can accordingly be advocated for the treatment of urogenital symptoms attributable to oestrogen deficiency in post-menopausal women Objective : To compare serum 17&bgr;-estradiol ( E2 ) , estrone ( E1 ) , estrone sulfate , follicle-stimulating hormone , luteinizing hormone , sex hormone-binding globulin , vaginal pH , and the vaginal maturation indices in women using a low-dose transdermal patch releasing 14 & mgr;g of E2 per day and a vaginal ring releasing 7.5 & mgr;g of E2 per day . Design : Twenty-four postmenopausal women were r and omly assigned to either the patch ( n = 12 ) or the ring ( n = 12 ) for a 12-week study period . Serum E2 , E1 , estrone sulfate , follicle-stimulating hormone , luteinizing hormone , and sex hormone-binding globulin were measured by immunoassay at baseline and 6 and 12 weeks . Vaginal pH was determined at baseline and 6 and 12 weeks . Vaginal cytologic examinations for vaginal maturation index were done at baseline and 12 weeks . Results : Twenty women completed the study . The patch significantly increased serum E1 and E2 levels at 6 and 12 weeks ( P < 0.01 ) ; there was no significant increase in serum E1 and E2 levels with the ring . Both the patch and the ring significantly reduced vaginal pH at 6 ( P < 0.001 ) and 12 ( P < 0.001 ) weeks and significantly reduced the percentage of vaginal parabasal cells at 12 weeks with no significant difference between the two groups . Both preparations increased the proportion of superficial cells ; the increase was significant only with the patch ( P = 0.04 ) . Conclusions : A transdermal E2 skin patch releasing 14 & mgr;g of E2 per day had an effect on vaginal pH and vaginal maturation indices similar to that of a vaginal E2 ring releasing 7.5 & mgr;g of E2 per day . Therefore , this patch is likely to relieve symptoms of vulvovaginal atrophy OBJECTIVE The purpose of this study was to investigate whether the effects of 17beta-estradiol tablets that are design ed for the treatment of postmenopausal urovaginal atrophy are influenced by the site of placement into the vagina . STUDY DESIGN In this controlled crossover trial , 10 postmenopausal women received a single 17beta-estradiol tablet in the outer or inner one third of the vagina . Before and 3 hours after treatment , the pulsatility index , resistance index , and blood flow were evaluated in the uterine and periurethral vessels by Doppler examination . Parallel 17beta-estradiol serum evaluations were performed . RESULTS Comparable and significant increases in 17beta-estradiol were observed . After inner administration , the pulsatility index and resistance index of both uterine arteries decreased ; uterine artery blood flow increased significantly ( P < .0001 ) but decreased in periurethral vessels ( P < .02 ) . After outer administration , the uterine artery pulsatility index , resistance index , and blood flow did not change , and the periurethral blood flow significantly increased ( P < .0001 ) . CONCLUSION For optimizing the efficacy while minimizing the risk of endometrial hyperplasia , 17beta-estradiol tablets must be placed in the outer one third of the vagina OBJECTIVE The aim of the study was to confirm the superior efficacy of estriol containing pessaries compared to placebo in the treatment of vaginal atrophy . STUDY DESIGN In a prospect i ve , multicenter , r and omized , placebo-controlled , double-blind study , 436 postmenopausal women with vaginal atrophy ( vaginal maturation index , VMI<40 % ; vaginal pH>5 ; most bothersome symptom , MBS≥65 on visual analogue scale , VAS ) were treated with pessaries containing either 0.2 mg estriol ( N=142 ) or 0.03 mg estriol ( N=147 ) or with a matching placebo ( N=147 ) for 12 weeks . MAIN OUTCOME MEASURES Primary efficacy endpoints included increase in VMI , decrease of the vaginal pH value and decrease in intensity of MBS after 12 weeks of treatment . RESULTS The increase in VMI was significantly greater under 0.2 mg estriol and 0.03 mg estriol ( 46.3±17.0 and 38.4±19.4 , respectively ) compared to placebo ( 23.9±21.5 ; p values<0.001 ) , vaginal pH decreased significantly more ( -1.6±0.8 and -1.4±0.9 , respectively ) compared to placebo ( -0.6±0.8 ; p values<0.001 ) and MBS intensity ( VAS ) declined significantly more ( -52.2±23.7 and -47.1±23.4 , respectively ) compared to placebo ( -31.8±26.3 ; p values<0.001 ) . Adverse events were rare and occurred at similar rates in all three groups . CONCLUSIONS Superiority of estriol containing pessaries over placebo was shown in the local treatment of vaginal atrophy . Even a very low dose of 0.03 mg estriol proved sufficient for local treatment of vaginal atrophy with excellent tolerability The aim of the study was to investigate the effect of 25 micrograms 17 beta-estradiol administered as a small vaginal tablet ( Vagifem , Novo Nordisk A/S ) on the symptoms of the vagina related to atrophy . The study was design ed as a double-blind r and omized placebo controlled study running for 12 weeks . The women were treated once daily for 2 weeks with the active or the placebo tablet . During the subsequent 10 weeks the women were treated twice a week . One hundred and sixty-four women were included . Ten dropped out for minor reasons , most of these due to lack of effect in the placebo group . In the Vagifem group 78.8 % were suffering from moderate to severe atrophy of the vagina , compared with 81.9 % in the placebo group . After 2 weeks the percentages were 14.3 and 35.3 , respectively . After 12 weeks of treatment , 10.7 % in the Vagifem group compared with 29.9 % in the placebo group had moderate to severe atrophy ( P less than 0.0001 ) . A substantial part of the women complained about subjective symptoms such as vaginal dryness and dyspareunia . After 12 weeks of treatment , a significant improvement was found in the Vagifem group ( P less than 0.002 ) . Before treatment 53.1 % in the treatment group and 41.0 % in the placebo group were suffering from urological symptoms . After 2 weeks , 60.5 % of the women in the Vagifem group underwent a change for the better compared to 35.3 % in the placebo group . After 12 weeks of treatment the percentages in the two groups feeling an improvement were 62.8 % and 32.4 % . In this study local low-dose treatment with 25 micrograms 17 beta-estradiol was found to have a significant effect on the postmenopausal urogenital symptoms related to atrophy Background . Atrophic vaginitis is a common condition . This study compared the usefulness of estradiol vaginal tablets ( EVT ) and estriol vagitories ( EV ) in treatment of atrophic vaginitis OBJECTIVES To determine if the efficacy of continuous low dose estradiol released from a vaginal ring is equivalent to estriol vaginal cream regarding improvement of the patient 's subjective feeling of vaginal dryness and to determine if there is a preference for either of the two study treatments . METHODS Open-label r and omized parallel group trial with active control with a blind evaluation of vaginal cytology and with a cross-over ( change-over ) phase for preference comparison . One hundred and sixty five postmenopausal women with symptoms of vaginal dryness and signs of vaginal atrophy were r and omized to an estradiol ring ( Estring ) or estriol cream ( Synapause ) . The duration of each treatment period was 12 weeks . RESULTS Both study treatments were equally effective regarding the ability to alleviate the symptom feeling of vaginal dryness and the signs of vaginal atrophy . Both treatments were efficient in restoring the vaginal mucosa , recorded as higher maturation values and as decreased vaginal pH. Estring was superior to estriol cream regarding preference of treatment . Both treatments were equivalent for the occurrence of adverse events , including bleeding . CONCLUSION data from this change-over study confirm efficacy and safety of both the vaginal ring and cream in the treatment of postmenopausal women with urogenital atrophy symptoms and signs . The patients had a strong preference for the vaginal ring Sixty-four patients with severe menopausal symptoms completed a four month double-blind placebo trial with conjugated equine oestrogens ( premarin ) . Using a graphic rating scale system of assessment , a statistically significant improvement with premarin was observed in 12 psychological and symptomatic scores ( Table 3 ) . From a comparison between these results and the results of the 20 patients without vasomotor symptoms it would appear that many of these symptomatic improvements result from the relief of hot flushes ( i.e. a domino effect ) . However , the improvement in memory and reduction of anxiety in these 20 patients suggest that oestrogens have a direct tonic effect on the mental state which is independent of vasomotor symptoms . Sixty-one patients with less severe menopausal symptoms completed the second twelve month double-blind placebo trial and , as assessed by graphic rating scales , a significant improvement with premarin was observed in five psychological and symptomatic scores ( Table 3 ) . In both the twelve and four month studies the marked placebo effect of " youthful skin appearance " , and on skin greasiness in the twelve month study , indicate that no reliance can be placed on patient judgement of skin texture and appearance . Despite the lessening of the domino effect there was a slight improvement with premarin over placebo in 15 of the remaining 16 symptoms and it is likely that the cumulative effect of these small improvements results in an overall enhancement of well-being . The relief of atrophic vaginitis by premarin did not result in an improvement in libido and this suggests that the ability and the desire to have sexual intercourse are not related . The strength and duration of the placebo effect were well demonstrated in the three st and ard psychiatric scoring systems , the Beck score ( for depression ) , the General Health Question naire and the Eysenck Personality Index ( formula : see text ) ( for neuroticism ) . We observed a highly significant placebo effect extending for six months in all three , the improvement with premarin over placebo being non-significant . We must conclude that these tests are not sufficiently sensitive to assess psychological or symptomatic changes in menopausal women and that these changes are best assessed by the graphic rating scales . The number of side-effects and complications was assessed in the 61 patients in the long study . A higher incidence of minor side-effects was observed during premarin therapy ; this was most marked in relation to leg cramps but radio-isotope scanning revealed no evidence of leg vein thrombosis in these patients or indeed in any patient in the study . Premarin caused no elevation of systolic or diastolic blood pressure ; indeed there was a progressive fall in blood pressure throughout the study with no significant difference between premarin and placebo OBJECTIVE : To evaluate the efficacy of ultra – low-dose 10-microgram 17&bgr;-estradiol ( E2 ) vaginal tablets for treatment of vaginal atrophy . METHODS : Postmenopausal women ( N=309 ) were r and omly assigned to 10-microgram E2 or placebo vaginal tablets for 52 weeks in a multicenter , double-blind study . Primary efficacy endpoints included change from baseline to week 12 in vaginal cytology , vaginal pH , and most bothersome urogenital symptoms score . Grading of vaginal health was a secondary efficacy assessment . Safety assessment s included endometrial biopsy , physical and gynecologic examinations , and recording adverse events . RESULTS : At week 12 , the change from baseline for 10 micrograms E2 compared with placebo demonstrated significant improvement in vaginal Maturation Index ( proportion of parabasal cells : –37 % compared with –9 % ; superficial cells : 13 % compared with 4 % ; intermediate cells : 24 % compared with 5 % ; P<.001 for each ) , Maturation Value ( 25.0 compared with 6.5 , P<.001 ) , grading of vaginal health ( –0.91 compared with –0.51 , P<.001 ) , vaginal pH grade ( –1.3 compared with –0.4 , P<.001 ) , and most bothersome symptoms score ( –1.23 compared with –0.87 , P=.003 ) . For each component of vaginal Maturation Index , vaginal Maturation Value , grading of vaginal health , and vaginal pH , treatment effects were statistically different from placebo after 2 weeks of treatment . For most bothersome symptoms , treatment effect became apparent after 4 weeks and reached statistical significance at week 8 of therapy . All treatment effects were statistically significant at week 52 . There were no major safety findings regarding physical , gynecologic , or laboratory assessment s. CONCLUSION : After 12 weeks of treatment , an ultra – low-dose 10-microgram E2 vaginal tablet , compared with placebo , demonstrated significant improvement for the primary endpoints : vaginal cytology and pH and most bothersome urogenital symptoms score . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , http:// clinical trials.gov , NCT00108849 LEVEL OF EVIDENCE : Forty post-menopausal women with urogenital disorders who were in patients in the same geriatric hospital were treated with oestriol ( E3 ) for 6 weeks . For the first 2 weeks 0.5 mg E3 ( Leo AB , Sweden ) was administered intravaginally every day . Over the following 4 weeks the patients received the same quantity either once or twice weekly as a maintenance dose . Oestrogen influence on the vaginal and urethral epithelium was assessed by means of the karyopyknotic index ( KPI ) , while the degree of maturation of the vaginal epithelium was estimated visually . Urinary bacteria were cultivated . A pronounced and progressive rise in KPI was seen in both the vaginal and the urethral epithelium following daily E3 treatment . However , neither of the two maintenance dosages was sufficient to sustain the initial maturation of the vaginal and urethral epithelium induced by E3 , since the KPI returned to pretreatment values within 4 weeks . The effect of E3 administration on the vaginal epithelium was overestimated by the visual assessment method . No changes were seen in urinary bacteria . Medroxyprogesterone acetate was given before and after E3 treatment . None of the women suffered from withdrawal bleeding The treatment of postmenopausal symptoms was studied in 26 healthy women using a new synthetic rubber ( Kraton D 2109 ) vaginal ring containing 53 mg of 17 beta-oestradiol . All women were postmenopausal , at least 6 months after the last vaginal bleeding and suffering from daily hot flushes . The study was conducted in a double-blind placebo-controlled intrapatient cross-over fashion , and the study period was 6 months . The rings used give an initial in vitro release rate of 0.4 mg/E2 per day . The in vitro release rate decreases to about 0.2 mg/day after 20 days and levels off asymptotically to about 0.1 mg/day after 50 days . Serum E2 levels equivalent to the follicular phase of the normal menstrual cycle were measured after 1 month 's use , and serum E2 level stayed above postmenopausal levels throughout the study period . FSH was suppressed during use of the E2-releasing vaginal ring , while LH showed no statistically significant suppression in continued use . Postmenopausal complaints were recorded by Visual Analogue Scales ( VAS ) as judged by both the patient and the examining doctor ; all complaints had favourable outcomes during use of the E2-releasing vaginal ring without deterioration of symptoms during use of the placebo ring . No serious side-effects were encountered , and the possibility of managing all postmenopausal complaints with intravaginal oestrogen treatment is discussed OBJECTIVES This study was design ed to evaluate the efficacy of Replens , a non-hormonal moisturizing vaginal gel , on symptoms of vaginal atrophy in postmenopausal women , in comparison with Dienoestrol ( Cilag ) , an oestrogenic vaginal cream . METHODS Thirty-nine patients were r and omly allocated to either of the two treatments . Replens was given three times a week during the 12 weeks of the study , while Dienoestrol was administered daily during the first 2 weeks and thereafter three times a week . Vaginal dryness index , itching , irritation , dyspareunia , pH and safety were evaluated every week the first month and every month thereafter . RESULTS Both treatments had a significant increase on vaginal dryness index as soon as the first week of treatment , and the hormonal compound was significantly better than the non-hormonal one . All symptoms such as itching , irritation and dyspareunia significantly decreased or disappeared without any difference between the two treatments . For pH , no significant difference was seen either in each group or between the two groups . No adverse events related with the two drugs were found . CONCLUSION This study shows that Replens applied vaginally three times a week , is a full therapy for all symptoms of vaginal atrophy as well as local estrogen . No serious adverse event was related . Replens is an alternative treatment to local estrogen and perhaps a good complement of systemic HRT in patient suffering from vaginal dryness Objective We investigated the effects of 2 months of treatment with topical estrogens on atrophic vaginitis and gynecological health in Asian women . Study design Multicenter , open-label trial of 150 postmenopausal women age < 70 years with atrophic vaginitis . Women applied conjugated equine estrogens ( CEE ) vaginal cream ( 0.625 mg/g ) once daily on days 1–21 of two 28-day cycles . Changes in the vaginal maturation index ( VMI ) from baseline to days 21 ( month 1 ) and 49 ( month 2 ) were the primary outcome . Physiological changes were assessed by the Genital Health Clinical Examination ( GHCE ) . Results The VMI was significantly improved ( p < 0.001 ) from baseline at each assessment period . The significant improvement in GHCE from baseline after 1 month ( p < 0.001 ) was maintained at 2 months . Conclusions Vaginal treatment with CEE cream for 21 days of two consecutive 28-day cycles result ed in beneficial changes in the vaginal tissues and induced an overall genital health pattern more characteristic of the premenopausal state Abstract Objectives To investigate the pharmacokinetics , safety and preliminary effectiveness of ultra-low-dose estriol vaginal gel formulations ( 20 μg/g ( T1 ) and 50 μg/g ( T2 ) ) compared to Ovestinon ® ( estriol 500 μg/0.5 g ( R ) ) and placebo in postmenopausal women . Methods Forty-three volunteers were r and omly assigned to received T1 , T2 , R or placebo once daily for 21 days . Absorption of estriol after single and multiple administration was analyzed . Cytological changes in the vagina , tolerability and safety were also investigated . Results Thirty-six women were included in the pharmacokinetic analysis . Systemic absorption was lower with test formulations ( AUC0-t : 171.65 ± 80.18 ( T1 ) and 406.75 ± 199.53 ( T2 ) pg/ml × h ) than with Ovestinon ® ( 1221.97 ± 549.06 pg/ml × h ) . Estriol exposure of the test formulations after multiple administration ( AUCss : 36.33 ± 30.52 ( T1 ) and 73.71 ± 46.86 ( T2 ) pg/ml × h ) was significantly lower than after single-dose administration and not significantly different between them . In contrast , the exposure after repeated administration of Ovestinon ® was considerable and not statistically different from levels after single administration . All estriol formulations produced similar improvement in the vaginal maturation value , while placebo showed a small and not significant change . Overall safety and acceptability were good . Conclusions Estriol 20 and 50 μg/g formulations , while showing a comparable capacity for reversing vaginal atrophy , present a highly favorable safety profile , producing a very low systemic absorption of estriol and significantly lower than that of Ovestinon ® OBJECTIVE To assess efficacy and tolerability of a isoflavone ( Glycine max L. Merr . ) vaginal gel to the treatment of vaginal atrophy in postmenopausal women . METHODS The double-blind , r and omized , placebo-controlled , clinical trial . Ninety women were treated for 12 weeks with isoflavone vaginal gel 4 % ( 1g/day ) and a placebo gel and conjugated equine estrogen cream ( 0.3mg/day ) . After 4 and 12 weeks , the vaginal atrophy symptoms were classified at none , mild , moderate and severe and the vaginal cytology were taken to determine the maturation value . The endometrial safety ( by transvaginal ultrasonography ) was evaluated through at screening and the end of the trial . RESULTS Isoflavone vaginal gel appears to be effective for relief of vaginal dryness and dyspareunia symptoms and an increase in the intermediate and superficial cells was noted . These results were similar to the effects with use of conjugated equine estrogens and superior to placebo gel . No changes in endometrial thickness , sera FSH and estradiol levels were observed at study endpoint . CONCLUSION Glycine max ( L. ) Merr . at 4 % vaginal gel on a daily basis in postmenopausal women led to improvements in vaginal atrophy symptoms and a significant increase in cell maturation values . Isoflavones proved good treatment options for relief of vulvovaginal symptoms especially in women who do not wish to use hormonal therapy or have contra-indications for this treatment Abstract . One thous and two hundred women , aged 61 , r and omly selected from a defined geographical area in South Sweden , were interviewed by an anonymous question naire about their urogenital symptoms . Seventy‐five percent cooperated , of whom 29.2 % admitted to some degree of urinary incontinence and 48.8 % some degree of lower genital tract disorder . Stress incontinence symptoms were reported by 11.8 % of the women , urge incontinence by 7.9 % and both types combined—“mixed ” by 9.5 % . Four percent of all women ( 18 % of stress incontinence ) experienced a loss sufficient to necessitate the wearing of a sanitary napkin or change of under clothing several times a day . Thirteen percent had repeated urinary tract infections . Itch , discharge and smarting pain was reported by 15 % . Thirty‐eight percent had vaginal dryness and dyspareunia . Only 4 % of the women were undergoing estrogen therapy This was an open-label study comparing effects of a nonhormonal drug-free bioadhesive vaginal moisturizer to a local estrogen therapy in the treatment of vaginal dryness symptoms . There were 15 women evaluated in each treatment group during a 12-week period . Results indicated that the bioadhesive vaginal moisturizer was a safe and effective alternative to estrogen vaginal cream , with both therapies exhibiting statistically significant increases in vaginal moisture , vaginal fluid volume , and vaginal elasticity with a return of the premenopausal pH state Objective The aim of this study was to evaluate the efficacy and safety of a new low-concentration estriol formulation ( 0.005 % estriol vaginal gel ) , providing an ultra low dose of estriol per application ( 50 & mgr;g ) , for the local treatment of postmenopausal vaginal atrophy . Methods Postmenopausal women with symptoms and signs of vaginal atrophy were enrolled in a prospect i ve , double-blind , placebo-controlled study . Women received either 1 g of vaginal gel containing 50 & mgr;g of estriol or placebo gel , daily for 3 weeks and then twice weekly up to 12 weeks . A cytological vaginal study , evaluation of vaginal pH , and assessment of symptoms and signs of vaginal atrophy were performed , and changes between baseline and weeks 3 and 12 were assessed . Adverse events were recorded . Results A total of 167 women were included ( 114 received estriol and 53 received placebo ) . After 12 weeks of therapy , a superiority of estriol compared with placebo gel was shown in the change in maturation value and vaginal pH ( P < 0.001 and P < 0.001 , respectively ) . The superiority of estriol was well demonstrated in improvement of vaginal dryness ( P = 0.001 ) and the Global Symptom Score ( P = 0.018 ) . Estriol gel proved also superior in the improvement of several of the most outst and ing vaginal signs of vaginal atrophy evaluated . After 3 weeks , estriol gel also showed a superiority over the placebo gel in most symptoms and signs evaluated . Treatment-related adverse events were similar among groups . Conclusions 0.005 % Estriol vaginal gel , a new formulation providing an ultra low dose of estriol per application , was shown to be safe and effective in the treatment of postmenopausal vaginal atrophy Objective This study aim ed to evaluate the histologic and cytologic effects of preoperative vaginal estrogen in women with atrophic vaginitis and pelvic organ prolapse . Methods Forty-two women with atrophic vaginitis and stage greater than or equal to 2 prolapse were enrolled in this assessor-blinded r and omized controlled trial comparing daily vaginal estrogen cream use for 2 to 12 weeks preoperatively versus no intervention . Data were analyzed using t test and analysis of variance . Results Of these 42 women , 22 received treatment and 20 were controls . After a mean 7 ( 3 ) weeks of use , the vaginal maturity index increased 15.5 % in the treatment group and declined 1.5 % in the control group ( P < 0.001 ) . The vaginal epithelial thickness was 339 ( 96 ) & mgr;m in the treatment group compared to 302 ( 119 ) & mgr;m ( P = 0.275 ) in the controls . Conclusions Preoperative vaginal estrogen application for 2 to 12 weeks restores vaginal cytology to premenopausal levels , but does not increase vaginal epithelial thickness in women with prolapse INTRODUCTION A significant number of postmenopausal women suffer from distressing problems because of urogenital atrophy secondary to the decline in circulating estrogen levels . Treatment with topical hormones may provide relief in such women when used judiciously . AIM To study the effects of local estrogen with or without local testosterone on urogenital and sexual health in postmenopausal women . METHODS Seventy-five postmenopausal women symptomatic for urogenital atrophy and sexual dysfunction were r and omly divided into two study groups and one control group . The women in study group 1 received local estrogen cream ; study group 2 received local estrogen and testosterone cream ; the control group received nonhormonal lubricant KY gel for 12 weeks . The urogenital and sexuality score , along with the vaginal health index and the vaginal maturation index ( VMI ) , was calculated at the beginning of therapy and 12 weeks later . MAIN OUTCOME MEASURES Changes in the urogenital and sexuality score along with vaginal health index and VMI . RESULTS After 12 weeks of therapy , there was a significant improvement in all the four study parameters , which correlated well with the improvement in symptoms of urogenital atrophy and sexual dysfunction in both the study groups as compared with the control group . Improvement in sexuality score was greatest with combined estrogen- and rogen therapy . There were no adverse effects and the therapies were well accepted without any compliance issue . CONCLUSION Local estrogen either alone or with and rogen is highly effective in relieving symptoms of urogenital atrophy and in improving sexual function in symptomatic postmenopausal women INTRODUCTION Female libido is multifactorial and complex . Declining estrogen levels in postmenopausal women affects vaginal function . AIM The aim of this study was to evaluate female sexual function after using topical estrogen , testosterone , or polyacrylic acid as vaginal lubricants with K-Y jelly as a placebo lubricant . METHODS This was a r and omized controlled clinical trial on 80 postmenopausal women between 40 and 70 years of age with follow-up at the Menopause Clinic of the CAISM Unicamp . The women were r and omized to treatment with topical vaginal estrogen , testosterone , polyacrylic acid , or oil lubricant alone , three times a week for a period of 12 weeks from November 2011 to January 2013 . MAIN OUTCOME MEASURE We used the Female Sexual Function Index ( FSFI ) to assess changes in sexual response at baseline , and after 6 and 12 weeks . RESULTS After 12 weeks of treatment , polyacrylic acid and topical testosterone produced improvements in the FSFI domains of sexual desire , lubrication , satisfaction , reduced pain during intercourse , and total score compared with lubricant alone . Treatment with topical estrogen in comparison with lubricant alone showed an improvement in the FSFI field of desire . The intragroup analysis over the time of the treatment showed improvements in the fields of desire , lubrication , and reduced pain for polyacrylic acid , testosterone , and estrogen . Furthermore , women who used testosterone showed improvements over time in the fields of arousal , orgasm , and satisfaction . CONCLUSIONS Treatment of postmenopausal women with symptoms of vaginal atrophy with polyacrylic acid , testosterone , and estrogen for 12 weeks produced improvements in self-reported female sexual function when compared with a placebo lubricant |
1,710 | 27,679,515 | DiskussionDieser Übersichtssartikel zeigt , dass körperliche Aktivität zu einer Verminderung der Symptomatik und einer Steigerung der affektiven Befindlichkeit bei Patienten mit depressiven Erkrankungen führt . | ZusammenfassungZielZiel der Arbeit ist die Darstellung des aktuellen Forschungsst and es zu körperlicher Aktivität als therapeutische Intervention bei Patienten mit Depressionen .
Method ikEs wurde eine systematische Bewertung von i m Zeitraum 1980 bis März 2016 veröffentlichten Fachartikeln , die den Einfluss einer Bewegungsintervention i m Vergleich zu einer Kontrollbedingung in der Beh and lung von Depressionen untersuchen , durchgeführt .
Abstract Aim This article gives a conspectus of the present state of research on the efficiency of exercise as a treatment for patients suffering from depression .
The review focused on studies that examined the effects of exercise compared to control conditions in the treatment of depression . | BACKGROUND Regular physical exercise may improve a variety of physiological and psychological factors in depressive persons . However , there is little experimental evidence to support this assumption for adolescent population s. We conducted a r and omized controlled trial to investigate the effect of physical exercise on depressive state , the excretions of stress hormones and physiological fitness variables in adolescent females with depressive symptoms . METHODS Forty-nine female volunteers ( aged 18 - 20 years ; mean 18.8 + /- 0.7 years ) with mild-to-moderate depressive symptoms , as measured by the Centre for Epidemiologic Studies Depression ( CES-D ) scale , were r and omly assigned to either an exercise regimen or usual daily activities for 8 weeks . The subjects were then crossed over to the alternate regimen for an additional 8-week period . The exercise program consisted of five 50-min sessions per week of a group jogging training at a mild intensity . The variables measured were CES-D rating scale , urinary cortisol and epinephrine levels , and cardiorespiratory factors at rest and during exercise endurance test . RESULTS After the sessions of exercise the CES-D total depressive score showed a significant decrease , whereas no effect was observed after the period of usual daily activities ( ANOVA ) . Twenty-four hour excretions of cortisol and epinephrine in urine were reduced due to the exercise regimen . The training group had a significantly reduced resting heart rate and increased peak oxygen uptake and lung capacity . CONCLUSIONS The findings of this study suggest that a group jogging exercise may be effective in improving depressive state , hormonal response to stress and physiological fitness of adolescent females with depressive symptoms BACKGROUND Depression is common and tends to be recurrent . Alternative treatments are needed that are non-stigmatising , accessible and can be prescribed by general medical practitioners . AIMS To compare the effectiveness of three interventions for depression : physical exercise , internet-based cognitive-behavioural therapy ( ICBT ) and treatment as usual ( TAU ) . A secondary aim was to assess changes in self-rated work capacity . METHOD A total of 946 patients diagnosed with mild to moderate depression were recruited through primary healthcare centres across Sweden and r and omly assigned to one of three 12-week interventions ( trail registry : KCTR study ID : KT20110063 ) . Patients were reassessed at 3 months ( response rate 78 % ) . RESULTS Patients in the exercise and ICBT groups reported larger improvements in depressive symptoms compared with TAU . Work capacity improved over time in all three groups ( no significant differences ) . CONCLUSIONS Exercise and ICBT were more effective than TAU by a general medical practitioner , and both represent promising non-stigmatising treatment alternatives for patients with mild to moderate depression BACKGROUND Depression is a major health problem for community-dwelling elderly adults . Since limited re sources are available to decrease the high prevalence of depressive symptoms among the elderly adults , improved support for them can be provided if we can determine which intervention is superior in ridding depressive symptoms . OBJECTIVE To compare the effectiveness of the physical fitness exercise program and the cognitive behavior therapy program on primary ( depressive symptoms ) and secondary outcomes ( 6-min walk distance , quality of life , and social support ) for community-dwelling elderly adults with depressive symptoms . DESIGN AND SETTING S A prospect i ve r and omized control trial was conducted in three communities in northern Taiwan . PARTICIPANTS The elderly adults in the three communities were invited to participate by mail , phone calls , and posters . There were a total of 57 participants who had depressive symptoms and all without impaired cognition that participated in this trial . None of the participants withdrew during the 9 months of follow-up for this study . METHODS Fifty-seven participants were r and omly assigned to one of the three groups : the physical fitness exercise program group , the cognitive behavior therapy ( CBT ) group , or the control group . The primary ( Geriatric Depression Scale-15 , GDS-15 ) , and secondary outcomes ( 6-min walk distance , SF-36 , and Inventory of Socially Supportive Behaviors scales , ISSB ) were collected immediately ( T2 ) , at 3 months ( T3 ) , and at 6 months after the interventions ( T4 ) . RESULTS After the interventions , the CBT group participants demonstrated significantly lower symptoms of depression ( p=0.009 ) at T2 and perceived more social support from those around them ( p<0.001 , < 0.001 and = 0.004 , respectively ) at three time-point comparisons than the control group . Moreover , after intervention , participants in the physical fitness exercise program group had decreased GDS-15 scores at three time-point comparisons ( p=0.003 , 0.012 and 0.037 , respectively ) , had a substantially greater 6-min walk distance ( p=0.023 ) , a better quality of life ( p<0.001 ) , and a better perceived social support at T2 ( p<0.001 ) . CONCLUSIONS Immediately after a 12-week intervention , there were significant decreases in depressive symptoms and more perceived social support amongst those in the CBT group . When considering the effectiveness in the decrease of depressive symptoms longer term , the increase in the 6-min walk distance and raising the patients ' quality of life , physical fitness exercise program may be a better intervention for elderly adults with depressive symptoms BACKGROUND Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression . However , the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder ( MDD ) has not been systematic ally evaluated . OBJECTIVE To assess the effectiveness of an aerobic exercise program compared with st and ard medication ( ie , antidepressants ) for treatment of MDD in older patients , we conducted a 16-week r and omized controlled trial . METHODS One hundred fifty-six men and women with MDD ( age , > or = 50 years ) were assigned r and omly to a program of aerobic exercise , antidepressants ( sertraline hydrochloride ) , or combined exercise and medication . Subjects underwent comprehensive evaluations of depression , including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria and Hamilton Rating Scale for Depression ( HAM-D ) and Beck Depression Inventory ( BDI ) scores before and after treatment . Secondary outcome measures included aerobic capacity , life satisfaction , self-esteem , anxiety , and dysfunctional cognitions . RESULTS After 16 weeks of treatment , the groups did not differ statistically on HAM-D or BDI scores ( P = .67 ) ; adjustment for baseline levels of depression yielded an essentially identical result . Growth curve models revealed that all groups exhibited statistically and clinical ly significant reductions on HAM-D and BDI scores . However , patients receiving medication alone exhibited the fastest initial response ; among patients receiving combination therapy , those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms . CONCLUSIONS An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons . Although antidepressants may facilitate a more rapid initial therapeutic response than exercise , after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD BACKGROUND Nearly two-thirds of elderly patients treated for depression fail to achieve symptomatic remission and functional recovery with first-line pharmacotherapy . In this study , we ask whether a mind-body exercise , Tai Chi Chih ( TCC ) , added to escitalopram will augment the treatment of geriatric depression design ed to achieve symptomatic remission and improvements in health functioning and cognitive performance . METHODS : One hundred twelve older adults with major depression age 60 years and older were recruited and treated with escitalopram for approximately 4 weeks . Seventy-three partial responders to escitalopram continued to receive escitalopram daily and were r and omly assigned to 10 weeks of adjunct use of either 1 ) TCC for 2 hours per week or 2 ) health education ( HE ) for 2 hours per week . All participants underwent evaluations of depression , anxiety , resilience , health-related quality of life , cognition , and inflammation at baseline and during 14-week follow-up . RESULTS Subjects in the escitalopram and TCC condition were more likely to show greater reduction of depressive symptoms and to achieve a depression remission as compared with those receiving escitalopram and HE . Subjects in the escitalopram and TCC condition also showed significantly greater improvements in 36-Item Short Form Health Survey physical functioning and cognitive tests and a decline in the inflammatory marker , C-reactive protein , compared with the control group . CONCLUSION : Complementary use of a mind-body exercise , such as TCC , may provide additional improvements of clinical outcomes in the pharmacologic treatment of geriatric depression Objective : To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to st and ard antidepressant medication ( sertraline ) and greater reductions in depression compared to placebo controls . Methods : Between October 2000 and November 2005 , we performed a prospect i ve , r and omized controlled trial ( SMILE study ) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital . A total of 202 adults ( 153 women ; 49 men ) diagnosed with major depression were assigned r and omly to one of four conditions : supervised exercise in a group setting ; home-based exercise ; antidepressant medication ( sertraline , 50–200 mg daily ) ; or placebo pill for 16 weeks . Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale ( HAM-D ) . Results : After 4 months of treatment , 41 % of the participants achieved remission , defined as no longer meeting the criteria for major depressive disorder ( MDD ) and a HAM-D score of < 8 . Patients receiving active treatments tended to have higher remission rates than the placebo controls : supervised exercise = 45 % ; home-based exercise = 40 % ; medication = 47 % ; placebo = 31 % ( p = .057 ) . All treatment groups had lower HAM-D scores after treatment ; scores for the active treatment groups were not significantly different from the placebo group ( p = .23 ) . Conclusions : The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD . Placebo response rates were high , suggesting that a considerable portion of the therapeutic response is determined by patient expectations , ongoing symptom monitoring , attention , and other nonspecific factors . BDI = Beck Depression Inventory ; CI = confidence interval ; HAM-D = Hamilton Depression Rating Scale ; ITT = intention-to-treat ; MDD = major depressive disorder ; SD = st and ard deviation ; SSRIs = selective serotonin reuptake inhibitors ; TSH = thyroid stimulating hormone OBJECTIVE The Regenerate pilot study explored whether a 10-week , community-based progressive resistance training ( PRT ) program could reduce depressive symptoms in depressed chronic stroke survivors . METHODS Participants were screened for depressive status using the PHQ-9 and confirmed by psychiatric assessment . Eligible people ( n = 45 ) were r and omised to PRT or a waiting-list comparison group . The PRT program included two high intensity sessions/week for 10 weeks at a community-based gymnasium . Depressive status , physical and mental health and quality of life were measured at baseline , 10 weeks and 6 months . Muscle strength was assessed using 1 repetition maximum ( 1-RM ) for upper and lower limbs . RESULTS The participants ' median age was 69 years : 27 were male . The intervention group had lower depression scores than the comparison group at all time points . At 6-month follow-up , there was a trend for PRT participants to be more likely to be no longer depressed than the comparison group , but the difference was not significant after adjusting for baseline scores . There were modest improvements in health and wellbeing over time , but many scores were lower than reported in non-depressed people . Intervention participants demonstrated significant improvements in strength . Program adherence was good : on average 75 % of the 10-week program was completed . CONCLUSIONS The intervention appeared to be feasible within a community-based setting . To optimize stroke recovery and improve the quality of life of stroke survivors , health professionals should continue to focus on helping survivors ' mental health recovery as well their physical rehabilitation BACKGROUND Interventions including physical exercise may help improve the outcomes of late-life major depression , but few studies are available . AIMS To investigate whether augmenting sertraline therapy with physical exercise leads to better outcomes of late-life major depression . METHOD Primary care patients ( 465 years ) with major depression were r and omised to 24 weeks of higher-intensity , progressive aerobic exercise plus sertraline ( S+PAE ) , lower-intensity , non-progressive exercise plus sertraline ( S+NPE ) and sertraline alone . The primary outcome was remission ( a score of ≤10 on the Hamilton Rating Scale for Depression ) . RESULTS A total of 121 patients were included . At study end , 45 % of participants in the sertraline group , 73 % of those in the S+NPE group and 81 % of those in the S+PAE group achieved remission ( P = 0.001 ) . A shorter time to remission was observed in the S+PAE group than in the sertraline-only group . CONCLUSIONS Physical exercise may be a safe and effective augmentation to antidepressant therapy in late-life major depression Objective : To examine a 1-year follow-up of a 4-month , controlled clinical trial of exercise and antidepressant medication in patients with major depressive disorder ( MDD ) . Methods : In the original study , 202 sedentary adults with MDD were r and omized to : a ) supervised exercise ; b ) home-based exercise ; c ) sertraline ; or d ) placebo pill . We examined two outcomes measured at 1-year follow-up ( i.e. , 16 months post r and omization ) : 1 ) continuous Hamilton Depression Rating Scale score ; and 2 ) MDD status ( depressed ; partial remission ; full remission ) in 172 available participants ( 85 % of the original cohort ) . Regression analyses were performed to examine the effects of treatment group assignment , as well as follow-up antidepressant medication use and self-reported exercise ( Godin Leisure-Time Exercise Question naire ) , on the two outcomes . Results : In the original study , patients receiving exercise achieved similar benefits compared with those receiving sertraline . At the time of the 1-year follow-up , rates of MDD remission increased from 46 % at post treatment to 66 % for participants available for follow-up . Neither initial treatment group assignment nor antidepressant medication use during the follow-up period were significant predictors of MDD remission at 1 year . However , regular exercise during the follow-up period predicted both Hamilton Depression Rating Scale scores and MDD diagnosis at 1 year . This relationship was curvilinear , with the association concentrated between 0 minute and 180 minutes of weekly exercise . Conclusion : The effects of aerobic exercise on MDD remission seem to be similar to sertraline after 4 months of treatment ; exercise during the follow-up period seems to extend the short-term benefits of exercise and may augment the benefits of antidepressant use . Trial Registration : clinical trials.gov Identifier : NCT00331305 . MDD = major depressive disorder ; HAM-D = Hamilton Depression Rating Scale ; SCID = Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition Axis I Disorders ; PSSS = Perceived Social Support Scale BACKGROUND Laughter Yoga founded by M. Kataria is a combination of unconditioned laughter and yogic breathing . Its effect on mental and physical aspects of healthy individuals was shown to be beneficial . OBJECTIVE The objective of this study was to compare the effectiveness of Kataria 's Laughter Yoga and group exercise therapy in decreasing depression and increasing life satisfaction in older adult women of a cultural community of Tehran , Iran . METHODS Seventy depressed old women who were members of a cultural community of Tehran were chosen by Geriatric depression scale ( score>10 ) . After completion of Life Satisfaction Scale pre-test and demographic question naire , subjects were r and omized into three groups of laughter therapy , exercise therapy , and control . Subsequently , depression post-test and life satisfaction post-test were done for all three groups . The data were analyzed using analysis of covariance and Bonferroni 's correction . RESULTS Sixty subjects completed the study . The analysis revealed a significant difference in decrease in depression scores of both Laughter Yoga and exercise therapy group in comparison to control group ( p<0.001 and p<0.01 , respectively ) . There was no significant difference between Laughter Yoga and exercise therapy groups . The increase in life satisfaction of Laughter Yoga group showed a significant difference in comparison with control group ( p<0.001 ) . No significant difference was found between exercise therapy and either control or Laughter Yoga group . CONCLUSION Our findings showed that Laughter Yoga is at least as effective as group exercise program in improvement of depression and life satisfaction of elderly depressed women OBJECTIVE Recent studies have thrown doubt on the true effectiveness of anti-depressants in light and moderate depression . The aim of this study is to evaluate the impact of physical training and music therapy on a sample group of subjects affected by light to moderate depression versus subjects treated with pharmacological therapy only . DESIGN AND SETTING R and omized controlled study . Patients were r and omized into two groups . Subjects in the pharmacotherapy group received a therapy with antidepressant drugs ; the exercise/music therapy group was assigned to receive physical exercise training combined with listening to music . The effects of interventions were assessed by differences in changes in mood state between the two groups . MAIN OUTCOME MEASURES Medically eligible patients were screened with the Hamilton Anxiety Scale and with the Geriatric Depression Scale . We used plasmatic cytokine dosage as a stress marker . RESULTS We recruited 24 subjects ( mean age : 75.5 ± 7.4 , 11 M/13 F ) . In the pharmacotherapy group there was a significant improvement in anxiety only ( p<0.05 ) at 6-months . In the exercise/music therapy was a reduction in anxiety and in depression at 3-months and at 6-months ( p<0.05 ) . We noted an average reduction of the level of TNF-a from 57.67 ( ± 39.37 ) pg/ml to 35.80 ( ± 26.18 ) pg/ml . CONCLUSIONS Our training may potentially play a role in the treatment of subjects with mild to moderate depression . Further research should be carried out to obtain more evidence on effects of physical training and music therapy in depressed subjects OBJECTIVES This report released findings of a r and omized controlled trial conducted in Hong Kong to further our underst and ing of the psychosocial effects of qigong on elderly persons with depression . DESIGN Eighty-two participants with a diagnosis of depression or obvious features of depression were recruited and r and omly assigned into the intervention and comparison group . The intervention group was given a 16-week period of Qigong practice while the comparison group participated in a newspaper reading group with same duration and frequency . RESULTS After eight weeks of qigong practice , the intervention group participants outstripped themselves in improvement in mood , self-efficacy and personal well being , and physical and social domains of self-concept when compared with comparison subjects . After 16 weeks of practice , the improvement generalized to the daily task domain of the self-concept . CONCLUSIONS This report shows that regular qigong practice could relieve depression , improve self-efficacy and personal well being among elderly persons with chronic physical illness and depression The purpose of this study was to compare the effects of 16 weeks of a comprehensive exercise routine to supervised walking and social conversation on depression in nursing home residents with Alzheimer 's disease ( AD ) . Method : This study was a three-group , repeated- measures design with r and om assignment to treatment group . Forty-five nursing home residents with moderate to severe AD were r and omly assigned to a 16-week programme of comprehensive exercise , supervised walking or social conversation . Raters were blinded to treatment group assignment . Major outcome variables were depression measured by the Cornell Scale for Depression in Dementia , mood measured by the Dementia Mood Assessment Scale and the Alzheimer 's Mood Scale , and affect measured by the Observed Affect Scale . Depression was reduced in all three groups with some evidence of superior benefit from exercise . Depression is a common problem with serious and costly consequences for nursing home residents with AD . Exercise as a behavioural approach to treatment of depression in nursing home residents with severe AD evidence d a clear benefit to participants in this study . More research is needed to clarify the relative benefits of different types of exercise in conjunction with or without pharmacological intervention In this article , we examined the antidepressant influence of an 8-week-long aerobic exercise intervention in which two training parameters were manipulated : exercise frequency and group environment . Twenty-three individuals with elevated symptoms of depression were recruited in a sport and fitness facility and agreed to participate in this 8-week study . They were r and omly assigned to three groups : ( a ) low-frequency exercise ( control ) ( n = 7 ) , ( b ) high-frequency exercise ( n = 8) , and ( c ) high-frequency exercise + group-based intervention ( n = 8) . Participants completed the Beck Depression Inventory ( BDI-II ) at study entry , and at 4 and 8 weeks subsequently . The results showed that those in the high-frequency aerobic exercise experimental groups reported lower depression scores than those in the low-frequency ( control ) group at 4 weeks ( 13.2 + /- 7.3 and 11.7 + /- 3.1 vs. 22.4 + /- 7.5 ) and 8 weeks ( 10.9 + /- 8.1 and 9.6 + /- 2.5 vs. 20.7 + /- 6.3 ) . However , alleviation in depressive symptoms was not found to be greater in those participants who received a group-based intervention The effects of two non-drug treatments ( physical exercise and bright light ) on mood , body weight and oxygen consumption were compared in age-matched groups of female subjects with winter depression , non-seasonal depression or without depression . It was found that oxygen consumption in the pre-treatment condition was similar in non-depressed subjects ( n=18 ) and depressed non-seasonals ( n=18 ) , while comparatively lower values were obtained in winter depression ( n=27 ) . Neither mood nor metabolic parameters changed significantly in the group of nine untreated winter depressives . One week of physical exercise ( 1-h pedaling on a bicycle ergometer between 13.00 and 14.00 h ) increased oxygen consumption in the group of nine winter depressives and lowered oxygen consumption in nine-subject groups of depressed and non-depressed non-seasonals . One week of bright light treatment ( 2-h exposure to 2500 lux between 14.00 and 16.00 h ) increased oxygen consumption in nine winter depressives and nine non-depressed subjects , while no significant change in oxygen consumption was found in nine subjects with non-seasonal depression . Weight loss was observed in the groups treated with physical exercise and in the group of light-treated winter depressives . Winter depression responded equally well to exercising and light , while a significant therapeutic difference in favor of exercising was found in non-seasonal depression . Overall , the results of the study suggest that energy-regulating systems are implicated in the antidepressant action of the non-drug treatments Objective The purpose of this study was to assess the status of 156 adult volunteers with major depressive disorder ( MDD ) 6 months after completion of a study in which they were r and omly assigned to a 4-month course of aerobic e-ercise , sertraline therapy , or a combination of e-ercise and sertraline . Methods The presence and severity of depression were assessed by clinical interview using the Diagnostic Interview Schedule and the Hamilton Rating Scale for Depression ( HRSD ) and by self-report using the Beck Depression Inventory . Assessment s were performed at baseline , after 4 months of treatment , and 6 months after treatment was concluded ( ie , after 10 months ) . Results After 4 months patients in all three groups e-hibited significant improvement ; the proportion of remitted participants ( ie , those who no longer met diagnostic criteria for MDD and had an HRSD score < 8) was comparable across the three treatment conditions . After 10 months , however , remitted subjects in the e-ercise group had significantly lower relapse rates ( p = .01 ) than subjects in the medication group . Exercising on one ’s own during the follow-up period was associated with a reduced probability of depression diagnosis at the end of that period ( odds ratio = 0.49 , p = .0009 ) . Conclusions Among individuals with MDD , e-ercise therapy is feasible and is associated with significant therapeutic benefit , especially if e-ercise is continued over time Summary Previous studies have shown that sustained exercise in human subjects causes an increase in the plasma concentration ratio of free tryptophan : other large neutral amino acids [ including the branched-chain amino acids ( BCAA ) ] . This should favour the transport of tryptophan into the brain and also the synthesis of 5-hydroxytryptamine , which is thought to contribute to fatigue during prolonged exercise . A mixture of the three BCAA was given to subjects during a 30-km cross-country race or a marathon ( 42.2 km ) and the effects on mental and physical performances were measured . The mental performance , measured as the performance in the Stroop Colour and Word Test ( CWT ) , was improved after , as compared to before the 30-km cross-country race when a BCAA supplement was given during the race , whereas the CWT scores were similar before and after in the placebo group . The running performance in the marathon was improved for the “ slower ” runners ( 3.05 h–3.30 h ) when BCAA was taken during the race ; however , there was no significant effect on the performance in the “ faster ” runners ( < 3.05 h ) . The results showed that both mental and physical performance was improved by an intake of BCAA during exercise . In addition , the effects of exercise on the plasma concentration of the aromatic amino acids were altered when a BCAA supplement was given during the marathon PURPOSE We wanted to assess the effectiveness of a home-based physical activity program , the Depression in Late Life Intervention Trial of Exercise ( DeLLITE ) , in improving function , quality of life , and mood in older people with depressive symptoms . METHODS We undertook a r and omized controlled trial involving 193 people aged 75 years and older with depressive symptoms at enrollment who were recruited from primary health care practice s in Auckl and , New Zeal and . Participants received either an individualized physical activity program or social visits to control for the contact time of the activity intervention delivered over 6 months . Primary outcome measures were function , a short physical performance battery comprising balance and mobility , and the Nottingham Extended Activities of Daily Living scale . Secondary outcome measures were quality of life , the Medical Outcomes Study 36-item short form , mood , Geriatric Depression Scale ( GDS-15 ) , physical activity , Auckl and Heart Study Physical Activity Question naire , and self-report of falls . Repeated measures analyses tested the differential impact on outcomes over 12 months ’ follow-up . RESULTS The mean age of the participants was 81 years , and 59 % were women . All participants scored in the at – risk category on the depression screen , 53 % had a Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases , Tenth Revision diagnosis of major depression or scored more than 4 on the GDS-15 at baseline , indicating moderate or severe depression . Almost all participants , 187 ( 97 % ) , completed the trial . Overall there were no differences in the impact of the 2 interventions on outcomes . Mood and mental health related quality of life improved for both groups . CONCLUSION The DeLLITE activity program improved mood and quality of life for older people with depressive symptoms as much as the effect of social visits . Future social and activity interventions should be tested against a true usual care control Background A few recent studies have found indications of the effectiveness of inpatient psychotherapy for depression , usually of an extended duration . However , there is a lack of controlled studies in this area and to date no study of adequate quality on brief psychodynamic psychotherapy for depression during short inpatient stay exists . The present article describes the protocol of a study that will examine the relative efficacy , the cost-effectiveness and the cost-utility of adding an Inpatient Brief Psychodynamic Psychotherapy to pharmacotherapy and treatment-as-usual for in patients with unipolar depression . Methods / Design The study is a one-month r and omized controlled trial with a two parallel group design and a 12-month naturalistic follow-up . A sample of 130 consecutive adult in patients with unipolar depression and Montgomery-Asberg Depression Rating Scale score over 18 will be recruited . The study is carried out in the university hospital section for mood disorders in Lausanne , Switzerl and . Patients are assessed upon admission , and at 1- , 3- and 12- month follow-ups . Inpatient therapy is a manualized brief intervention , combining the virtues of inpatient setting and of time-limited dynamic therapies ( focal orientation , fixed duration , re source -oriented interventions ) . Treatment-as-usual represents the best level of practice for a minimal treatment condition usually proposed to in patients . Final analyses will follow an intention – to-treat strategy . Depressive symptomatology is the primary outcome and secondary outcome includes measures of psychiatric symptomatology , psychosocial role functioning , and psychodynamic-emotional functioning . The mediating role of the therapeutic alliance is also examined . Allocation to treatment groups uses a stratified block r and omization method with permuted block . To guarantee allocation concealment , r and omization is done by an independent research er . Discussion Despite the large number of studies on treatment of depression , there is a clear lack of controlled research in inpatient psychotherapy during the acute phase of a major depressive episode . Research on brief therapy is important to take into account current short lengths of stay in psychiatry . The current study has the potential to scientifically inform appropriate inpatient treatment . This study is the first to address the issue of the economic evaluation of inpatient psychotherapy . Trial registration Australian New Zeal and Clinical Trial Registry ( ACTRN12612000909820 Objective To investigate the effectiveness of facilitated physical activity as an adjunctive treatment for adults with depression presenting in primary care . Design Pragmatic , multicentre , two arm parallel r and omised controlled trial . Setting General practice s in Bristol and Exeter . Participants 361 adults aged 18 - 69 who had recently consulted their general practitioner with symptoms of depression . All those r and omised had a diagnosis of an episode of depression as assessed by the clinical interview schedule-revised and a Beck depression inventory score of 14 or more . Interventions In addition to usual care , intervention participants were offered up to three face to face sessions and 10 telephone calls with a trained physical activity facilitator over eight months . The intervention was based on theory and aim ed to provide individually tailored support and encouragement to engage in physical activity . Main outcome measures The primary outcome was self reported symptoms of depression , assessed with the Beck depression inventory at four months post-r and omisation . Secondary outcomes included use of antidepressants and physical activity at the four , eight , and 12 month follow-up points , and symptoms of depression at eight and 12 month follow-up . Results There was no evidence that participants offered the physical activity intervention reported improvement in mood by the four month follow-up point compared with those in the usual care group ; adjusted between group difference in mean Beck depression inventory score −0.54 ( 95 % confidence interval −3.06 to 1.99 ; P=0.68 ) . Similarly , there was no evidence that the intervention group reported a change in mood by the eight and 12 month follow-up points . Nor was there evidence that the intervention reduced antidepressant use compared with usual care ( adjusted odds ratio 0.63 , 95 % confidence interval 0.19 to 2.06 ; P=0.44 ) over the duration of the trial . However , participants allocated to the intervention group reported more physical activity during the follow-up period than those allocated to the usual care group ( adjusted odds ratio 2.27 , 95 % confidence interval 1.32 to 3.89 ; P=0.003 ) . Conclusions The addition of a facilitated physical activity intervention to usual care did not improve depression outcome or reduce use of antidepressants compared with usual care alone . Trial registration Current Controlled Trials IS RCT N16900744 Background No controlled trials have evaluated the long term efficacy of exercise activity to improve the treatment of patients with Major Depressive Disorders . The aim of the present study was to confirm the efficacy of the adjunctive physical activity in the treatment of major depressive disorders , with a long term follow up ( 8 months ) . Methods Trial with r and omized naturalistic control . Patients selected from the clinical activity registries of the Psychiatric Unit of the University of Cagliari , Italy . Inclusion criteria : female , between 40 and 60 years , diagnosis of Major Depressive Disorders ( DSM-IV TR ) resistant to the ongoing treatment . Exclusion criteria : diagnosis of psychotic disorders ; any contraindications to physical activity.30 patients ( 71.4 % of the eligible ) participated to the study .Cases : 10 r and omized patients undergoing pharmacological treatment plus physical activity . Controls : 20 patients undergoing only pharmacological therapy . The following tools were collected from each patient by two different psychiatric physicians at baseline and 8 month after the beginning of exercise program : SCID-I , HAM-D , CGI ( Clinical Global Impression ) , GAF . Results The patients that made physical activity had their HAM-D , GAF and CGI score improved from T0 to T8 , all differences were statistically significant . In the control group HAM-D , GAF and CGI scores do not show any statistically significant differences between T0 and T8.LimitsSmall sample size limited to female in adult age ; control group was not subject to any structured rehabilitation activity or placebo so it was impossible to evaluate if the improvement was due to a non specific therapeutic effect associated with taking part in a social activity . Conclusion Physical activity seems a good adjunctive treatment in the long term management of patients with MDD . R and omized placebo controlled trials are needed to confirm the results Background . Exercise has been suggested to be a viable treatment for depression . This study investigates the effect of supervised aerobic exercise training on depressive symptoms and physical performance among Chinese patients with mild to moderate depression in early in-patient phase . Methods . A r and omized repeated measure and assessor-blinded study design was used . Subjects in aerobic exercise group received 30 minutes of aerobic training , five days a week for 3 weeks . Depressive symptoms ( MADRS and C-BDI ) and domains in physical performance were assessed at baseline and program end . Results . Subjects in aerobic exercise group showed a more significant reduction in depressive scores ( MADRS ) as compared to control ( between-group mean difference = 10.08 ± 9.41 ; P = 0.026 ) after 3 weeks training . The exercise group also demonstrated a significant improvement in flexibility ( between-group mean difference = 4.4 ± 6.13 ; P = 0.02 ) . Limitations . There was lack of longitudinal followup to examine the long-term effect of aerobic exercise on patients with depression . Conclusions . Aerobic exercise in addition to pharmacological intervention can have a synergistic effect in reducing depressive symptoms and increasing flexibility among Chinese population with mild to moderate depression . Early introduction of exercise training in in-patient phase can help to bridge the gap of therapeutic latency of antidepressants during its nonresponse period BACKGROUND Depression in elderly people may be contributed to by the multiple losses of aging . Exercise has the potential to positively impact many of these losses simultaneously . We tested the hypothesis that progressive resistance training ( PRT ) would reduce depression while improving physiologic capacity , quality of life , morale , function and self-efficacy without adverse events in an older , significantly depressed population . METHODS We conducted a 10-week r and omized controlled trial of volunteers aged 60 and above with major or minor depression or dysthymia . Subjects were r and omized for 10 weeks to either a supervised PRT program three times a week or an attention-control group . RESULTS A total of 32 subjects aged 60 - 84 , mean age 71.3 + /- 1.2 yr , were r and omized and completed the study . No significant adverse events occurred . Median compliance was 95 % . PRT significantly reduced all depression measures ( Beck Depression Inventory in exercisers 21.3 + /- 1.8 to 9.8 + /- 2.4 versus controls 18.4 + /- 1.7 to 13.8 + /- 2 , p = .002 ; Hamilton Rating Scale of Depression in exercisers 12.3 + /- 0.9 to 5.3 + /- 1.3 versus controls 11.4 + /- 1.0 to 8.9 + /- 1.3 , p = .008 ) . Quality of life subscales of bodily pain ( p = .001 ) , vitality ( p = .002 ) , social functioning ( p = .008 ) , and role emotional ( p = .02 ) were all significantly improved by exercise compared to controls . Strength increased a mean of 33 % + /- 4 % in exercisers and decreased 2 % + /- 2 % in controls ( p < .0001 ) . In a multiple stepwise regression model , intensity of training was a significant independent predictor of decrease in depression scores ( r2 = .617 , p = .0002 ) . CONCLUSIONS PRT is an effective antidepressant in depressed elders , while also improving strength , morale , and quality of life BACKGROUND While physical exercise as adjunctive treatment for major depression has received considerable attention in recent years , the evidence is conflicting . This study evaluates the effects of two different add-on treatments : exercise and basic body awareness therapy . METHODS R and omized controlled trial with two intervention groups and one control , including 62 adults on antidepressant medication , who fulfilled criteria for current major depression as determined by the Mini International Neuropsychiatric Interview . Interventions ( 10 weeks ) were aerobic exercise or basic body awareness therapy ( BBAT ) , compared to a single consultation with advice on physical activity . Primary outcome was depression severity , rated by a blinded assessor using the Montgomery Asberg Rating Scale ( MADRS ) . Secondary outcomes were global function , cardiovascular fitness , self-rated depression , anxiety and body awareness . RESULTS Improvements in MADRS score ( mean change=-10.3 , 95 % CI ( -13.5 to -7.1 ) , p=0.038 ) and cardiovascular fitness ( mean change=2.4ml oxygen/kg/min , 95 % CI ( 1.5 to 3.3 ) , p=0.017 ) were observed in the exercise group . Per- protocol analysis confirmed the effects of exercise , and indicated that BBAT has an effect on self-rated depression . LIMITATIONS The small sample size and the challenge of missing data . Participants ׳ positive expectations regarding the exercise intervention need to be considered . CONCLUSIONS Exercise in a physical therapy setting seems to have effect on depression severity and fitness , in major depression . Our findings suggest that physical therapy can be a viable clinical strategy to inspire and guide persons with major depression to exercise . More research is needed to clarify the effects of basic body awareness therapy Objective : To evaluate the short-term effects of exercise in patients with major depression . Design : Prospect i ve , r and omised , controlled study . Setting : A university hospital . Patients : A consecutive series of 38 in patients with a major depression episode undergoing st and ard clinical antidepressant drug treatment . Interventions : Patients were r and omly assigned to an exercise ( walking , n = 20 ) or placebo ( low-intensity stretching and relaxation exercises , n = 18 ) group . Training was carried out for 10 days . Main outcome measurements : Severity of depression assessed with the Bech-Rafaelsen Melancholy Scale ( BRMS ) and the Center for Epidemiologic Studies Depression scale ( CES-D ) . Results : After 10 days , reduction of depression scores in the exercise group was significantly larger than in the placebo group ( BRMS : 36 % v 18 % ; CES-D : 41 % v 21 % ; p for both = 0.01 ) ; the proportion of patients with a clinical response ( reduction in the BRMS scores by more than six points ) was also larger for the exercise group ( 65 % v 22 % , p<0.01 ) . Conclusions : Endurance exercise may help to achieve substantial improvement in the mood of selected patients with major depression in a short time BACKGROUND Depression is common in later life . AIMS To determine whether exercise is effective as an adjunct to antidepressant therapy in reducing depressive symptoms in older people . METHOD Patients were r and omised to attend either exercise classes or health education talks for 10 weeks . Assessment s were made " blind " at baseline , and at 10 and 34 weeks . The primary outcome was seen with the 17-item Hamilton Rating Scale for Depression ( HRSD ) . Secondary outcomes were seen with the Geriatric Depression Scale , Clinical Global Impression and Patient Global Impression . RESULTS At 10 weeks a significantly higher proportion of the exercise group ( 55 % v. 33 % ) experienced a greater than 30 % decline in depression according to HRSD ( OR=2.51 , P=0.05 , 95 % CI 1.00 - 6.38 ) . CONCLUSIONS Because exercise was associated with a modest improvement in depressive symptoms at 10 weeks , older people with poorly responsive depressive disorder should be encouraged to attend group exercise activities The Depression Outcomes Study of Exercise ( DOSE ) was a r and omized clinical trial to determine whether exercise is an efficacious treatment for mild to moderate major depressive disorder ( MDD ) in adults ages 20 to 45 years . The specific hypotheses under investigation were ( 1 ) active exercise is an efficacious monotherapy for mild to moderate levels of MDD , and ( 2 ) there is a dose-response relation between the exercise amount and reduction in depressive symptoms . The primary outcome measure was the Hamilton Rating Scale for Depression ( HRSD ) collected weekly over 12 weeks . Secondary outcome measures were the Inventory of Depressive Symptoms ( clinician and self-report ) , HRSD scores at 24 weeks , cardiorespiratory fitness , self-efficacy , and quality of life . Eighty men and women who were diagnosed with a Structured Clinical Interview for Depression and who had mild ( HRSD 12 - 16 ) to moderate ( HRSD 17 - 25 ) MDD were r and omized to one of five doses of exercise : 7.0 kcal/kg/week in 3 days/week ; 7.0 kcal/kg/week in 5 days/week ; 17.5 kcal/kg/week in 3 days/week ; 17.5 kcal/kg/week in 5 days/week ; or 3 days/week of stretching and flexibility exercises for 15 to 20 min/session . Participants exercised under supervision in our laboratory over the course of 12 weeks . Symptoms of depression were measured weekly by trained clinical raters blinded to the participant 's treatment assignment . The design of the study restricted participant characteristics to mild to moderate MDD and controlled exercise features to permit the evaluation of exercise as a sole treatment for depression . This study is the first to examine dose-response effects of exercise in participants diagnosed with MDD Objective To evaluate the efficacy of a home-based exercise programme added to usual medical care for the treatment of depression . Design Prospect i ve , two group parallel , r and omised controlled study . Setting Community-based . Patients 200 adults aged 50 years or older deemed to be currently suffering from a clinical depressive illness and under the care of a general practitioner . Interventions Participants were r and omly allocated to either usual medical care alone ( control ) or usual medical care plus physical activity ( intervention ) . The intervention consisted of a 12-week home-based programme to promote physical activity at a level that meets recently published guidelines for exercise in people aged 65 years or over . Main outcome measurements Severity of depression was measured with the structured interview guide for the Montgomery-Asberg Depression Rating Scale ( SIGMA ) , and depression status was assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders ( SCID-I ) . Results Remission of depressive illness was similar in both the usual care ( 59 % ) and exercise groups ( 63 % ; OR = 1.18 , 95 % CI 0.61 to 2.30 ) at the end of the 12-week intervention , and again at the 52-week follow-up ( 67 % vs 68 % ) ( OR=1.07 , 95 % CI 0.56 to 2.02 ) . There was no change in objective measures of fitness over the 12-week intervention among the exercise group . Conclusions This home-based physical activity intervention failed to enhance fitness and did not ameliorate depressive symptoms in older adults , possibly due to a lack of ongoing supervision to ensure compliance and optimal engagement The purpose of this study was to conduct a pilot clinical trial to test the feasibility and efficacy of an exercise program and anti-depressant treatment compared with usual care in improving the emotional and physical functioning of older adults with minor depression . Participants were 37 older adults with minor depression who were r and omized to exercise , sertraline , or usual care ; 32 participants completed the 16-week study . Outcomes included measures of both emotional ( clinician and self-report ) and physical ( observed and self-report ) functioning . There were trends for the superiority of the exercise and sertraline conditions over usual care in improving SF-36 mental health scores and clinician-rated depression scores . Individuals in the exercise condition showed greater improvements in physical functioning than individuals in the usual care condition . Both sertraline and exercise show promise as treatments for late-life minor depression . However , exercise has the added benefit of improving physical functioning as well OBJECTIVE To assess the benefit and harm of exercise training in adults with clinical depression . METHOD The DEMO trial is a r and omized pragmatic trial for patients with unipolar depression conducted from January 2005 through July 2007 . Patients were referred from general practitioners or psychiatrists and were eligible if they fulfilled the International Classification of Diseases , Tenth Revision , criteria for unipolar depression and were aged between 18 and 55 years . Patients ( N = 165 ) were allocated to supervised strength , aerobic , or relaxation training during a 4-month period . The primary outcome measure was the 17-item Hamilton Rating Scale for Depression ( HAM-D(17 ) ) , the secondary outcome measure was the percentage of days absent from work during the last 10 working days , and the tertiary outcome measure was effect on cognitive abilities . RESULTS At 4 months , the strength measured by 1 repetition maximum for chest press increased by a mean ( 95 % CI ) of 4.0 kg ( 0.8 to 7.2 ; p = .014 ) in the strength training group versus the relaxation group , and maximal oxygen uptake increased by 2.7 mL/kg/min ( 1.2 to 4.3 ; p = .001 ) in the aerobic group versus the relaxation group . At 4 months , the mean change in HAM-D(17 ) score was -1.3 ( -3.7 to 1.2 ; p = .3 ) and 0.4 ( -2.0 to 2.9 ; p = .3 ) for the strength and aerobic groups versus the relaxation group . At 12 months , the mean differences in HAM-D(17 ) score were -0.2 ( -2.7 to 2.3 ; p = .8 ) and 0.6 ( -1.9 to 3.1 ; p = .6 ) for the strength and aerobic groups versus the relaxation group . At 12 months , the mean differences in absence from work were -12.1 % ( -21.1 % to -3.1 % ; p = .009 ) and -2.7 % ( -11.7 % to 6.2 % ; p = .5 ) for the strength and aerobic groups versus the relaxation group . No statistically significant effect on cognitive abilities was found . CONCLUSION Our findings do not support a biologically mediated effect of exercise on symptom severity in depressed patients , but they do support a beneficial effect of strength training on work capacity . TRIAL REGISTRATION ( Clinical Trials.gov ) Identifier : NCT00103415 OBJECTIVE Major depressive disorder ( MDD ) is associated with decreased physical activity and increased rates of the metabolic syndrome ( MetS ) , a risk factor for the development of type 2 diabetes and cardiovascular disorders . Exercise training has been shown to improve cardiorespiratory fitness and metabolic syndrome factors . Therefore , our study aim ed at examining whether patients receiving an exercise program as an adjunct to inpatient treatment will benefit in terms of physiological and psychological factors . METHOD Fourty-two in patients with moderate to severe depression were included . Twenty-two patients were r and omized to additional 3x weekly exercise training ( EXERCISE ) and compared to treatment as usual ( TAU ) . Exercise capacity was assessed as peak oxygen uptake ( VO2peak ) , ventilatory anaerobic threshold ( VAT ) and workload expressed as Watts ( W ) . Metabolic syndrome was defined according to NCEP ATPIII panel criteria . RESULTS After 6 weeks of treatment , cardiorespiratory fitness ( VO2peak , VAT , Watt ) , waist circumference and HDL cholesterol were significantly improved in EXERCISE participants . Treatment response expressed as ≥50 % MADRS reduction was more frequent in the EXERCISE group . CONCLUSIONS Adjunctive exercise training in depressed in patients improves physical fitness , MetS factors , and psychological outcome . Given the association of depression with cardiometablic disorders , exercise training is recommended as an adjunct to st and ard antidepressant treatment We compared the effectiveness of an aerobic and nonaerobic exercise in the treatment of clinical depression in women . A total of 40 women , screened on the Research Diagnostic Criteria for major or minor depressive disorder , were r and omly assigned to an 8-week running ( aerobic ) , weight-lifting ( nonaerobic ) , or wait-list control condition . Subjects were reassessed at mid- and posttreatment , and at 1- , 7- , and 12-month follow-ups . Depression was monitored by the Beck Depression Inventory , Lubin 's Depression Adjective Check List , and the Hamilton Rating Scale for Depression ; fitness level was assessed using submaximal treadmill testing . Results were remarkably consistent across measures , with both exercise conditions significantly reducing depression compared with the waitlist control condition , and generally appearing indistinguishable from each other . No significant between-group fitness changes were noted . These findings indicate that both types of exercise conditions significantly reduce depression and that these results are not dependent on achieving an aerobic effect Rejection of catheters is generally thought to be due to patients pulling out their catheters , but we found circumstantial evidence for this in only one third of cases . Some catheters with smaller balloons drop out spontaneously , perhaps owing to laxity of the pelvic floor or urethral dilatation caused by repeated catheterisation , and others are expelled forcibly , presumably owing to uninhibited contractions of the bladder . Urinary catheters may therefore drop out , be pushed out , or be pulled out . The life expectancy of catheters in this group of patients suggests the type of catheter that should be used . We recommend cheaper latex catheters and think that expensive " long life " silicon catheters are inappropriate in most long stay patients . Rejection of catheters is common in poorly mobile old people with cognitive impairment . It is associated with urethral trauma and may result in septicaemia . Long term catheterisation should therefore be considered only when other methods to promote continence and provide comfort have failed.3 Further work is needed to determine why some patients pull out their catheters and whether bladder stabilising drugs might reduce episodes of spontaneous rejection of catheters OBJECTIVE To examine the effect of exercise intervention on exercise maintenance , depression , quality of life , and mental health at 6 months for people with traumatic brain injury ( TBI ) with at least mild depression . DESIGN Treatment group participants were assessed at baseline , after a 10-week exercise intervention , and 6 months after completion of the intervention . SETTING Community . PARTICIPANTS Participants ( N=40 ) with self-reported TBI from 6 months to 5 years prior to study enrollment and a score of 5 or greater on the Patient Health Question naire-9 . INTERVENTIONS Ten-week exercise intervention program consisting of supervised weekly 60-minute sessions and unsupervised 30 minutes of aerobic exercises 4 times each week . Telephone follow-up was conducted every 2 weeks for an additional 6 months to promote exercise maintenance for individuals r and omized to the intervention group . MAIN OUTCOME MEASURE Beck Depression Inventory ( BDI ) comparing participant outcomes over time . Post hoc analyses included comparison among those who exercised more or less than 90 minutes per week . RESULTS Participants reduced their scores on the BDI from baseline to 10 weeks and maintained improvement over time . Many participants ( 48 % ) demonstrated increased physical activity at 6 months compared with baseline . Those who exercised more than 90 minutes had lower scores on the BDI at the 10-week and 6-month assessment s and reported higher perceived quality of life and mental health . CONCLUSIONS Exercise may contribute to improvement in mood and quality of life for people with TBI and should be considered as part of the approach to depression treatment Two experiments are reported that examine the possibility that exercise selectively influences different types of cognition . To our knowledge , these experiments represent the first attempt to study higher-cognitive processes during exercise . Theoretical thinking was guided by the transient hypofrontality hypothesis . In both experiments , athletes who exercised at a sustained , moderate pace were compared to sedentary controls on two neuropsychological tests , one that is generally regarded as heavily dependent on prefrontal cognition and one that is relatively insensitive to prefrontal operation . Results showed that during exercise performance on tests dem and ing prefrontal-dependent cognition was impaired , while at the same time , cognitive processes requiring little prefrontal activity were unaffected BACKGROUND AND OBJECTIVES Clinical depression affects millions of women annually . Exercise has been studied as a potential antidepressant , with most studies supporting its efficacy . Exercise also has the potential to reduce the risk for physical comorbidities that occur with depression . However , less is known about the types of exercise programs to which women with depressive symptoms will adhere . Our objectives were to ( 1 ) compare two exercise programs , varying in their degree of structure , on improvements in physical activity and ( 2 ) compare the two exercise interventions on depressive symptoms , body composition , and fitness . METHODS Women with depressive symptoms ( physician diagnosed and confirmed with the Beck Depression Inventory ) residing in the greater Boston area were recruited for this 3-month intervention study . Continuous enrollment took place between November 2005 and November 2006 . Women were r and omly assigned to either a clinic-based or home-based exercise intervention , with assessment s at baseline and 3-months . RESULTS Participants ( n=32 ) were predominantly minority ( 81.4 % ) and , at baseline , had moderate symptoms of depression ( Beck Depression Inventory [ BDI ] , mean=25.6 , SD=9.3 ) , and were sedentary ( mean=35.8 min/week of moderate and vigorous activity , SD=31.4 ) . Gain scores for depressive symptoms ( clinic-based mean=-11.7 , home-based mean=-9.7 ) and physical activity ( clinic-based mean=65.4 , home-based mean=39.0 ) indicate strong improvements across time . Intent-to-treat analyses on 3-month data show that both interventions were associated with improvements in time spent in physical activity and depressive symptoms . Neither intervention impacted body composition or fitness . CONCLUSIONS Both exercise programs were associated with reductions in depressive symptoms and increased physical activity participation , suggesting that even a home-based program can benefit women with depressive symptoms Forty clinical ly depressed women were r and omized to a running , weight lifting , or delayed treatment condition . Self-concept was assessed at baseline , pre- , mid- , and posttreatment for all subjects and at 1 , 7 , and 12 months for exercise groups . Significant improvements in self-concept were found for exercise groups relative to control groups . No significant differences between exercise groups were found , and improvements were reasonably well-maintained over time . Differential changes on dimensions of self-concept were not demonstrated . These results suggest that both running and weight lifting exercise programs improve self-concept in clinical ly depressed women BACKGROUND Physical exercise has been extensively research ed as a therapeutic option for treatment of major depression . METHODS In a r and omized controlled trial , we analyze the effects of aerobic physical exercise as an add-on strategy for treatment of severe depressed in patients . The exercise has a " Dose " of 16.5 kcal/kg/week , three times a week during all the hospitalization . RESULTS Our preliminary results show that there is no significant difference in scores of Hamilton in the second week between groups ( Mean[SD]=8.2[5.96 ] × 11.18[5.03 ] , p=0.192 ) . However , there is a significant reduction in Hamilton scores of patients in exercise group at discharge ( Mean[SD]=5.93[4.46 ] × 9.45[3.56 ] , p=0.041 ) . Regarding Quality of Life ( QoL ) , no significant difference were found between groups in the second week in physical domain ( Mean[SD]=56.98[8.96 ] × 54.54[9.18 ] , p=0.511 ) and psychological domain ( Mean[SD]=50.88[13.88 ] × 42.04[12.42 ] , p=0.106 ) . However , there is a significant difference in psychological domain ( Mean[SD]=55.88[9.92 ] v 41.66[13.04 ] , p=0.004 ) and a trend but no statistical significance in the physical ( Mean[SD]=58.80[9.14 ] × 52.12[8.70 ] , p=0.07 ) at discharge . LIMITATIONS Many patients receive different treatment strategies , like ECT ( 1 patient at exercise group × 3 at control group ) . Other limitation is the small number of participants included until this moment . CONCLUSION Our preliminary results suggest that physical exercise could be a feasible and effective add-on strategy for treatment of severe depressed in patients , improving their depressive symptoms and Two clinical trials have been conducted in a sample of depressed patients to determine whether the addition of an aerobic exercise programme to their usual treatment improved outcome after 12 weeks . In the first trial , an aerobic exercise group had a superior outcome compared with a control group in terms of trait anxiety and a st and ard psychiatric interview . A second trial was then conducted to compare an aerobic exercise programme with low intensity exercise . Both groups showed improvement but there were no significant differences between the groups . In neither trial was there any correlation between the extent of change in the subjects ' physical fitness due to aerobic exercise and the extent of the improvement of psychiatric scores BACKGROUND Treatment-resistant major depressive disorder ( MDD ) is a complex condition , with very low remission rates . Physical exercise has been used , with some encouraging results , as an alternative therapy in other depressive disorders . This study assessed the impact on depression and functioning parameters of a moderate intensity exercise program , as an adjuvant to pharmacotherapy , in treatment-resistant MDD patients . METHODS 150 individuals with treatment-resistant MDD , defined as taking combined therapy in doses considered adequate for 9 - 15 months , without showing clinical remission , were initially screened . 33 were r and omized to one of two groups : usual pharmacotherapy ( N = 11 ) and usual pharmacotherapy plus aerobic exercise ( N = 22 ) . The exercise program consisted of home-based 30 - 45 min/day walks , 5 days/week , for 12 weeks , being 1 walk per week supervised . RESULTS The exercise group showed improvement of all depression and functioning parameters , as indicated by lower HAMD17 , BDI and CGI-S and higher GAF ( p < 0.05 ) at last observation compared both to baseline values and to control group . At the end of the study none of the participants in the control group showed response or remission , whilst in the exercise group 21 % of participants showed response and 26 % remission , although these differences were not statistically significant . CONCLUSION A 12 week , home-based exercise program of 30 - 45 min/day walks , 5 days/week , improved depression and functioning parameters in treatment-resistant MDD patients , and contributed to remission of 26 % of these patients . Moderate intensity exercise may be a helpful and effective adjuvant therapy for treatment-resistant MDD OBJECTIVE The onset of action of antidepressants often takes 4 to 6 weeks . The antidepressant effect of wake therapy ( sleep deprivation ) comes within hours but carries a risk of relapse . The objective of this study was to investigate whether a new chronotherapeutic intervention combining wake therapy with bright light therapy and sleep time stabilization could induce a rapid and sustained augmentation of response and remission in major depressive disorder . METHOD 75 adult patients with DSM-IV major depressive disorder , recruited from psychiatric wards , psychiatric specialist practice s , or general medical practice s between September 2005 and August 2008 , were r and omly assigned to a 9-week chronotherapeutic intervention using wake therapy , bright light therapy , and sleep time stabilization ( n = 37 ) or a 9-week intervention using daily exercise ( n = 38 ) . Patients were evaluated at a psychiatric research unit . The study period had a 1-week run-in phase in which all patients began treatment with duloxetine . This phase was followed by a 1-week intervention phase in which patients in the wake therapy group did 3 wake therapies in combination with daily morning light therapy and sleep time stabilization and patients in the exercise group began daily exercise . This phase was followed by a 7-week continuation phase with daily light therapy and sleep time stabilization or daily exercise . The 17-item Hamilton Depression Rating Scale was the primary outcome measure , and the assessors were blinded to patients ' treatment allocation . RESULTS Both groups responded well to treatment . Patients in the wake therapy group did , however , have immediate and clinical ly significantly better response and remission compared to the exercise group . Thus , immediately after the intervention phase ( week 2 ) , response was obtained in 41.4 % of wake therapy patients versus 12.8 % of exercise patients ( odds ratio [ OR ] = 4.8 ; 95 % CI , 1.7 - 13.4 ; P = .003 ) , and remission was obtained in 23.9 % of wake therapy patients versus 5.4 % of exercise patients ( OR = 5.5 ; 95 % CI , 1.7 - 17.8 ; P = .004 ) . These superior response and remission rates obtained by the wake therapy patients were sustained for the whole study period . At week 9 , response was obtained in 71.4 % of wake therapy patients versus 47.3 % of exercise patients ( OR = 2.8 ; 95 % CI , 1.1 - 7.3 ; P = .04 ) , and remission was obtained in 45.6 % of wake therapy patients and 23.1 % of exercise patients ( OR = 2.8 ; 95 % CI , 1.1 - 7.3 , P = .04 ) . All treatment elements were well tolerated . CONCLUSIONS Patients treated with wake therapy in combination with bright light therapy and sleep time stabilization had an augmented and sustained antidepressant response and remission compared to patients treated with exercise , who also had a clinical ly relevant antidepressant response . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00149110 Forty-three depressed women were r and omly assigned to either ( a ) an aerobic exercise treatment condition in which they participated in strenuous exercise , ( b ) a placebo treatment condition in which they practice d relaxation exercises , or ( c ) a no-treatment condition . Aerobic capacity was assessed before and after the 10-week treatment period . Self-reported depression was assessed before , during , and after the treatment period . The results indicated that subjects in the aerobic exercise condition evidence d reliably greater improvements in aerobic capacity than did the subjects in either of the other conditions ( p less than .002 in both cases ) and that the subjects in the aerobic exercise condition evidence d reliably greater decreases in depression than did subjects in the placebo condition ( p = .05 ) or subjects in the no-treatment condition ( p = .001 ) . These results provide the first controlled evidence concerning the effects of strenuous exercise on depression Psychosocial factors predicting treatment dropout or failure to benefit from treatment were identified in a r and omized trial of exercise therapy and pharmacotherapy for major depression . One hundred fifty-six men and women over age 50 diagnosed with major depressive disorder were assigned to a 16-week program of aerobic exercise , medication ( sertraline ) , or a combination of exercise and medication . Thirty-two patients ( 21 % ) failed to complete the program and were considered treatment " dropouts . " At the end of 16 weeks , 83 patients ( 53 % ) were in remission ; the remaining patients not in remission were considered treatment " failures . " Baseline levels of self-reported anxiety and lift satisfaction were the best predictors of both patient dropout and treatment success or failure across all treatment conditions Thirty community-dwelling , moderately depressed elderly were r and omly assigned to 1 of 3 interventions : experimenter-accompanied exercise in the form of walking , a social contact control condition , and a wait-list control . Exercise and social contact both result ed in significant reductions in both the total and the psychological subscale of the Beck Depression Inventory ( BDI ) . The exercise condition , however , unlike the control conditions , result ed in decreased somatic symptoms of the BDI . These results indicate that , at least in the short term , exercise has a broader effect compared with control conditions in reducing depressive symptoms in the moderately depressed elderly BACKGROUND This study , conducted between 1998 and 2001 and analyzed in 2002 and 2003 , was design ed to test ( 1 ) whether exercise is an efficacious treatment for mild to moderate major depressive disorder ( MDD ) , and ( 2 ) the dose-response relation of exercise and reduction in depressive symptoms . DESIGN The study was a r and omized 2x2 factorial design , plus placebo control . SETTING / PARTICIPANTS All exercise was performed in a supervised laboratory setting with adults ( n = 80 ) aged 20 to 45 years diagnosed with mild to moderate MDD . INTERVENTION Participants were r and omized to one of four aerobic exercise treatment groups that varied total energy expenditure ( 7.0 kcal/kg/week or 17.5 kcal/kg/week ) and frequency ( 3 days/week or 5 days/week ) or to exercise placebo control ( 3 days/week flexibility exercise ) . The 17.5-kcal/kg/week dose is consistent with public health recommendations for physical activity and was termed " public health dose " ( PHD ) . The 7.0-kcal/kg/week dose was termed " low dose " ( LD ) . MAIN OUTCOME MEASURES The primary outcome was the score on the 17-item Hamilton Rating Scale for Depression ( HRSD(17 ) ) . RESULTS The main effect of energy expenditure in reducing HRSD(17 ) scores at 12 weeks was significant . Adjusted mean HRSD(17 ) scores at 12 weeks were reduced 47 % from baseline for PHD , compared with 30 % for LD and 29 % for control . There was no main effect of exercise frequency at 12 weeks . CONCLUSIONS Aerobic exercise at a dose consistent with public health recommendations is an effective treatment for MDD of mild to moderate severity . A lower dose is comparable to placebo effect |
1,711 | 20,008,688 | There was no consistent or reproducible treatment effect of any therapy on this outcome measured at 1 year .
The 1-year change in CAC does not appear to be a suitable surrogate end point for treatment trials in patients with CVD or chronic kidney disease | BACKGROUND Coronary artery calcification ( CAC ) measured by computed tomography is radiographic confirmation of atherosclerosis , predicts cardiovascular events , and has been evaluated as a surrogate measure in r and omized trials . | Calcium controls numerous events within the vessel wall . Permeability of the endothelium is calcium dependent , as are platelet activation and adhesion , vascular smooth muscle proliferation and migration , and synthesis of fibrous connective tissue . Double-helix computerized tomography is a noninvasive technique that can detect , measure , and compare coronary calcification in the coronary arteries . Using this method , our objective was to determine whether administration of nifedipine once daily in lieu of diuretics in high-risk hypertensive patients will arrest or slow down the progression of coronary artery calcification . The study was design ed as a side arm of INSIGHT ( International Nifedipine Study : Intervention as Goal for Hypertension Therapy ) , aim ed to show the efficacy of nifedipine once daily versus co-amilozide ( hydrochlorothiazide 25 mg , amiloride 2.5 mg ) in high-risk hypertensive patients . A total of 201 patients with a total calcium score of ≥10 at the onset of study who underwent an annual double-helix computerized tomography for 3 years were analyzed for efficacy . Inhibition of coronary calcium progression was significant in the nifedipine versus the co-amilozide group during the first year ( 3.18 % versus 27 % , respectively , P = 0.02 ) , not significant during the second year ( 28.5 % versus 47 % , respectively , P = 0.14 ) , and significant during the third year ( 40 % versus 78 % , respectively , P = 0.02 ) . The results point to a slower progression of coronary calcification in hypertensive patients on nifedipine once daily versus co-amilozide Background and Aims : Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients . This is a prospect i ve study that compares the effects of calcium acetate and sevelamer on coronary calcification ( CAC ) and bone histology . Methods : 101 hemodialysis patients were r and omized for each phosphate binder and su bmi tted to multislice coronary tomographies and bone biopsies at entry and 12 months . Results : The 71 patients who concluded the study had similar baseline characteristics . On follow-up , the sevelamer group had higher levels of intact parathyroid hormone ( 498 ± 352 vs. 326 ± 236 pg/ml , p = 0.017 ) , bone alkaline phosphatase ( 38 ± 24 vs. 28 ± 15 U/l , p = 0.03 ) and deoxypyridinoline ( 135 ± 107 vs. 89 ± 71 nmol/l , p = 0.03 ) and lower LDL cholesterol ( 74 ± 21 vs. 91 ± 28 mg/dl , p = 0.015 ) . Phosphorus ( 5.8 ± 1.0 vs. 6 ± 1.0 mg/dl , p = 0.47 ) and calcium ( 1.27 ± 0.07 vs. 1.23 ± 0.08 mmol/l , p = 0.68 ) levels did not differ between groups . CAC progression ( 35 vs. 24 % , p = 0.94 ) and bone histological diagnosis at baseline and 12 months were similar in both groups . Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption ( eroded surface , ES/BS = 9.0 ± 5.9 vs. 13.1 ± 9.5 % , p = 0.05 ) , whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate ( BFR/BS = 0.015 ± 0.016 vs. 0.062 ± 0.078 , p = 0.003 for calcium and 0.017 ± 0.016 vs. 0.071 ± 0.084 μm3/μm2/day , p = 0.010 for sevelamer ) . Conclusions : There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups Background — Recent clinical trials have suggested that intensive versus st and ard lipid-lowering therapy provides for additional benefit . Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification ( CAC ) in serial measurements . Methods and Results — In a multicenter , r and omized , double-blind trial , 471 patients ( age 61±8 years ) who had no history of coronary artery disease and no evidence of high- grade coronary stenoses ( > 50 % diameter reduction ) were r and omized if they had ≥2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidence d by a CAC score ≥30 . Patients were assigned to receive 80 mg or 10 mg of atorvastatin per day over 12 months . Progression of CAC volume scores could be analyzed in 366 patients . After pretreatment with 10 mg of atorvastatin for 4 weeks , 12 months of study medication reduced LDL cholesterol from 106±22 to 87±33 mg/dL in the group r and omized to receive 80 mg of atorvastatin ( P<0.001 ) , whereas levels remained stable in the group r and omized to receive 10 mg ( 108±23 at baseline , 109±28 mg/dL at the end of the study , P = NS ) . The mean progression of CAC volume scores , corrected for the baseline CAC volume score , was 27 % ( 95 % CI 20.8 % to 33.1 % ) in the 80-mg atorvastatin group and 25 % ( 95 % CI 19.1 % to 30.8 % ) in the 10-mg atorvastatin group ( P=0.65 ) . CAC progression showed no relationship with on-treatment LDL cholesterol levels . Conclusions — We did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis . Over a period of 12 months , intensive atorvastatin therapy was unable to attenuate CAC progression compared with st and ard atorvastatin therapy . The possibility remains that the time window was too short to demonstrate an effect Background —Women have been underrepresented in statin trials , and few data exist on the effectiveness and safety of statins in this gender . We used sequential electron-beam tomography ( EBT ) scanning to quantify changes in coronary artery calcium ( CAC ) as a measure of atherosclerosis burden in patients treated with statins . Methods and Results —In a double-blind , multicenter trial , we r and omized 615 hyperlipidemic , postmenopausal women to intensive ( atorvastatin 80 mg/d ) and moderate ( pravastatin 40 mg/d ) lipid-lowering therapy . Patients also su bmi tted to 2 EBT scans at a 12-month interval ( mean interval 344±55 days ) to measure percent change in total and single-artery calcium volume score ( CVS ) from baseline . Of the 615 r and omized women , 475 completed the study . Mean±SD percent LDL reductions were 46.6%±19.9 % and 24.5%±18.5 in the intensive and moderate treatment arms , respectively ( P<0.0001 ) , and National Cholesterol Education Program Adult Treatment Panel III LDL goal was reached in 85.3 % and 58.8 % of women , respectively ( P<0.0001 ) . The total CVS% change was similar in the 2 treatment groups ( median 15.1 % and 14.3 % , respectively ; P = NS ) , and single-artery CVS% changes and absolute changes were also similar ( P = NS ) . In both arms , there was a trend toward a greater CVS progression in patients with prior cardiovascular disease , diabetes mellitus , and hypertension , whereas hormone replacement therapy had no effect on progression . Conclusions —In postmenopausal women , intensive statin therapy for 1 year caused a greater LDL reduction than moderate therapy but did not result in less progression of coronary calcification . The limitations of this study ( too short a follow-up period and the absence of a placebo group ) precluded determination of whether progression of CVS was slowed in both arms or neither arm compared with the natural history of the disease BACKGROUND Aged Garlic Extract ( AGE ) reduces multiple cardiovascular risk factors , including blood pressure , cholesterol , platelet aggregation and adhesion , while stimulating nitric oxide generation in endothelial cells . However , no study has evaluated the ability of AGE to inhibit vascular calcification , a marker of plaque formation in human coronary arteries . OBJECTIVE To assess the efficacy of Aged Garlic Extract ( AGE ) on changing the rate of atherosclerosis progression as compared to placebo . DESIGN A placebo-controlled , double-blind , r and omized pilot study to determine whether the atherosclerotic plaque burden detected by electron beam tomography ( EBT ) will change at a different rate under the influence of AGE as compared to placebo . Twenty-three patients were enrolled , and 19 patients completed the study protocol . AGE 4 ml or the equivalent amount of placebo was given to subjects . Duration of the study was 1 year . S-allylcysteine ( SAC ) , one of the active compound of AGE , was measured in the blood as a compliance marker . RESULTS The mean change of the calcium score ( volumetric method ) for the AGE group ( n = 9 ) was 7.5 + /- 9.4 % over 1 year . The placebo group ( n = 10 ) demonstrated an average increase in calcium scores of 22.2 + /- 18.5 % , significantly greater than the treated cohort ( P = 0.046 ) . There were no significant differences in individual cholesterol parameters or C reactive protein between the groups . In patients r and omized to AGE , there was a nonsignificant trend for improving cholesterol/high-density lipoprotein ratio ( P = 0.07 ) and homocysteine level ( P = 0.08 ) . CONCLUSIONS This small pilot study indicates the potential ability of AGE to inhibit the rate of progression of coronary calcification , as compared to placebo over 1 year . Should these findings be extended and confirmed in larger studies , garlic may prove useful for patients who are at high risk of future cardiovascular events Purpose To assess inter-scan reproducibility of coronary calcium measurements obtained from Multi Detector-Row CT ( MDCT ) images and to evaluate whether this reproducibility is affected by different measurement protocol s , slice thickness , cardiovascular risk factors and /or technical variables . Design Cross-sectional study with repeated measurements . Material s and methods The study population comprised 76 healthy women . Coronary calcium was assessed in these women twice in one session using 16-MDCT ( Philips Mx 8000 IDT 16 ) . Images were reconstructed with 1.5 mm slice thickness and 3.0 mm slice thickness . The 76 repeated scans were scored . The Agatston score , a volume measurement and a mass measurement were assessed . Reproducibility was determined by estimation of mean , absolute , relative difference , the weighted kappa value for agreement and the Intra-class correlation coefficient ( ICCC ) . Results Fifty-five participants ( 72.4 % ) had a coronary calcification of more than zero in Agatston ( 1.5 mm slice thickness ) . The reproducibility of coronary calcium measurements between scans in terms of ranking was excellent with Intra-class correlation coefficients of > 0.98 , and kappa values above 0.80 . The absolute difference in calcium score between scans increased with increasing calcium levels , indicating that measurement error increases with increasing calcium levels . However , no relation was found between the mean difference in scores and calcium levels , indicating that the increase in measurement error is likely to result in r and om misclassification in calcium score . Reproducibility results were similar for 1.5 mm slices and for 3.0 mm slices , and equal for Agatston , volume and mass measurements . Conclusion Inter-scan reproducibilility of measurement of coronary calcium using images from MDCT is excellent , irrespective of slice thickness and type of calcium parameter Background —Coronary calcification measured by fast computed tomography techniques is a surrogate marker of coronary atherosclerotic plaque burden . In a cohort study , we prospect ively investigated whether lipid-lowering therapy with a cholesterol synthesis enzyme inhibitor reduces the progression of coronary calcification . Methods and Results —In 66 patients with coronary calcifications in electron beam tomography ( EBT ) , LDL cholesterol > 130 mg/dL , and no lipid-lowering treatment , the EBT scan was repeated after a mean interval of 14 months and treatment with cerivastatin was initiated ( 0.3 mg/d ) . After 12 months of treatment , a third EBT scan was performed . Coronary calcifications were quantified using a volumetric score . Cerivastatin therapy lowered the mean LDL cholesterol level from 164±30 to 107±21 mg/dL. The median calcified volume was 155 mm3 ( range , 15 to 1849 ) at baseline , 201 mm3 ( 19 to 2486 ) after 14 months without treatment , and 203 mm3 ( 15 to 2569 ) after 12 months of cerivastatin treatment . The median annualized absolute increase in coronary calcium was 25 mm3 during the untreated versus 11 mm3 during the treatment period ( P = 0.01 ) . The median annual relative increase in coronary calcium was 25 % during the untreated versus 8.8 % during the treatment period ( P < 0.0001 ) . In 32 patients with an LDL cholesterol level < 100 mg/dL under treatment , the median relative change was 27 % during the untreated versus −3.4 % during the treatment period ( P = 0.0001 ) . Conclusions —Treatment with the cholesterol synthesis enzyme inhibitor cerivastatin significantly reduces coronary calcium progression in patients with LDL cholesterol > 130 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 BACKGROUND Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus . However , the benefit of statins in such patients receiving hemodialysis , who are at high risk for cardiovascular disease and death , has not been examined . METHODS We conducted a multicenter , r and omized , double-blind , prospect i ve study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were r and omly assigned to receive 20 mg of atorvastatin per day or matching placebo . The primary end point was a composite of death from cardiac causes , nonfatal myocardial infa rct ion , and stroke . Secondary end points included death from all causes and all cardiac and cerebrovascular events combined . RESULTS After four weeks of treatment , the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin , and among those receiving placebo it was reduced by 1.3 percent . During a median follow-up period of four years , 469 patients ( 37 percent ) reached the primary end point , of whom 226 were assigned to atorvastatin and 243 to placebo ( relative risk , 0.92 ; 95 percent confidence interval , 0.77 to 1.10 ; P=0.37 ) . Atorvastatin had no significant effect on the individual components of the primary end point , except that the relative risk of fatal stroke among those receiving the drug was 2.03 ( 95 percent confidence interval , 1.05 to 3.93 ; P=0.04 ) . Atorvastatin reduced the rate of all cardiac events combined ( relative risk , 0.82 ; 95 percent confidence interval , 0.68 to 0.99 ; P=0.03 , nominally significant ) but not all cerebrovascular events combined ( relative risk , 1.12 ; 95 percent confidence interval , 0.81 to 1.55 ; P=0.49 ) or total mortality ( relative risk , 0.93 ; 95 percent confidence interval , 0.79 to 1.08 ; P=0.33 ) . CONCLUSIONS Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death , nonfatal myocardial infa rct ion , and stroke in patients with diabetes receiving hemodialysis The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known . We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from r and omization . This was a predetermined secondary end point of a r and omized clinical trial design ed to assess progression of coronary artery calcium ( CAC ) scores in the two treatment arms . Thirty-four deaths occurred during the follow-up period : 23 in subjects r and omized to calcium-containing phosphate binders and 11 in subjects r and omized to sevelamer . Baseline CAC score was a significant predictor of mortality after adjustment for age , race , gender , and diabetes with increased mortality proportional to baseline score ( P=0.002 ) . Mortality was borderline significantly lower in subjects r and omized to sevelamer ( 5.3/100 patient years , confidence interval ( CI ) ( 2.2 - 8.5 ) compared to those r and omized to calcium-containing binders ( 10.6/100 patient years , CI 6.3 - 14.9 ) ( P=0.05 ) . The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment ( P=0.016 , hazard ratio 3.1 , CI 1.23 - 7.61 ) . In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality . Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders 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 Background : Previous studies have described increased vascular calcification in renal dialysis patients . The clinical significance of this finding with respect to outcomes after percutaneous coronary intervention in this population is unknown . Methods : We analysed a prospect i ve interventional data base at a single tertiary center and identified 41 dialysis patients who underwent coronary angioplasty . All studies were review ed for the presence of coronary calcium in the target and reference vessels and compared with respect to baseline clinical factors and cardiovascular outcomes . Results : The mean ages for those with and without coronary calcification were 63.6 ± 11.0 and 67.3 ± 11.0 , respectively , P = 0.30 . The groups were similar in years on dialysis , diabetes , hypertension , smoking , and measures of calcium and phosphate balance . The total cholesterol , LDL-C , HDL-C , and triglycerides were 162.5 ± 42.3 and 202.0 ± 54.5 , P = 0.02 ; 94.9 ± 39.6 and 121.2 ± 48.1 , P = 0.18 ; 39.3 ± 12.4 and 47.3 ± 12.2 , P = 0.15 ; 157.4 ± 100.4 and 181.3 ± 187.4 , P = 0.15 , for those with and without calcification , respectively . The composite of target vessel revascularization , myocardial infa rct ion , or death was 47.4 % and 77.3 % for those with and without calcification , respectively , P = 0.06 . The Cox proportional hazards model , controlling for years on dialysis , showed a significant , event-free survival in those with coronary calcium seen fluoroscopically , P = 0.05 . Conclusions : In dialysis patients , coronary calcification identified in the target or reference vessels is associated with lower total cholesterol and favourable interventional outcomes . J Cardiovasc Risk 8:133 - 137 © 2001 Lippincott Williams & Wilkins OBJECTIVES We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease ( ASCVD ) events . BACKGROUND The electron beam computed tomography-derived coronary calcium score predicts coronary disease events . Small , uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events , but controlled , scientific demonstration of these effects is lacking . METHODS We conducted a double-blind , placebo-controlled r and omized clinical trial of atorvastatin 20 mg daily , vitamin C 1 g daily , and vitamin E ( alpha-tocopherol ) 1,000 U daily , versus matching placebos in 1,005 asymptomatic , apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender . All study participants also received aspirin 81 mg daily . Mean duration of treatment was 4.3 years . RESULTS Treatment reduced total cholesterol by 26.5 % to 30.4 % ( p < 0.0001 ) , low-density lipoprotein cholesterol by 39.1 % to 43.4 % ( p < 0.0001 ) , and triglycerides by 11.2 % to 17.0 % ( p < or = 0.02 ) but had no effect ( p = 0.80 ) on progression of coronary calcium score ( Agatston method ) . Treatment also failed to significantly reduce the primary end point , a composite of all ASCVD events ( 6.9 % vs. 9.9 % , p = 0.08 ) . Event rates were related to baseline calcium score ( pre-specified analysis ) and may have been reduced in a subgroup of participants with baseline calcium score > 400 ( 8.7 % vs. 15.0 % , p = 0.046 [ not a pre-specified analysis ] ) . CONCLUSIONS Treatment with alpha-tocopherol , vitamin C , and low doses of atorvastatin ( 20 mg once daily ) did not affect the progression of coronary calcification . Treatment may have reduced ASCVD events , especially in subjects with calcium scores > 400 , but these effects did not achieve conventional levels of statistical significance Objectives : To evaluate the effect of intensive lipid-lowering treatment on coronary artery calcification in a sub study of a trial recruiting patients with calcific aortic stenosis . Methods : In a double blind r and omised controlled trial , 102 patients with calcific aortic stenosis and coronary artery calcification were r and omly assigned by the minimisation technique to atorvastatin 80 mg daily or matched placebo . Coronary artery calcification was assessed annually by helical computed tomography . Results : 48 patients were r and omly assigned to atorvastatin and 54 to placebo with a median follow up of 24 months ( interquartile range 24–30 ) . Baseline characteristics and coronary artery calcium scores were similar in both groups . Atorvastatin reduced serum low density lipoprotein cholesterol ( −53 % , p < 0.001 ) and C reactive protein ( −49 % , p < 0.001 ) concentrations whereas there was no change with placebo ( −7 % and 17 % , p > 0.95 for both ) . The rate of change in coronary artery calcification was 26%/year ( 0.234 ( SE 0.037 ) log arbitrary units (AU)/year ; n = 39 ) in the atorvastatin group and 18%/year ( 0.167 ( SE 0.034 ) log AU/year ; n = 49 ) in the placebo group , with a geometric mean difference of 7%/year ( 95 % confidence interval −3 % to 18 % , p = 0.18 ) . Serum low density lipoprotein concentrations were not correlated with the rate of progression of coronary calcification ( r = 0.05 , p = 0.62 ) . Conclusion : In contrast to previous observational studies , this r and omised controlled trial has shown that , despite reducing systemic inflammation and halving serum low density lipoprotein cholesterol concentrations , statin treatment does not have a major effect on the rate of progression of coronary artery calcification OBJECTIVE Since its introduction early in the 1990s , helical CT has become the predominant technology for obtaining CT images for medical applications . Recent improvements in the temporal resolution of helical CT ( subsecond ) and the addition of retrospective cardiac gating are combined in this report evaluating cardiac-gated helical CT for quantifying coronary artery calcium . We compare total calcium scores determined on subsecond gated helical CT with the current reference for coronary calcium evaluation , electron beam CT . MATERIAL S AND METHODS We compared total calcium scores obtained using a general purpose , unmodified helical CT scanner with scores obtained using electron beam CT in 36 individuals who were 68+/-11 years old ( age range , 41 - 85 years ) . RESULTS Correlation coefficients ranged from 0.97 to 0.98 ( Pearson 's product moment ) and from 0.95 to 0.96 ( Spearman 's rank order ) , depending on the coronary calcium scoring method used . Agreement in the classification of participants as " healthy " or " diseased " at threshold total calcium scores of 10 , 100 , 160 , 200 , 400 , and 680 was , respectively , 94 % , 97 % , 89 % , 92 % , 94 % , and 100 % using the conventional electron beam CT scoring method and an equivalent method with helical CT . CONCLUSION A general purpose , current generation helical CT scanner equipped for retrospective cardiac gating can accurately quantify coronary calcium , and the results are highly correlated to scores obtained with electron beam CT . As an alternative method for measuring coronary calcium , gated subsecond cardiac helical CT offers greater availability and lower cost , thereby making population -based screening for coronary artery calcium more feasible BACKGROUND Previous clinical trials showed that progression of coronary artery calcification ( CAC ) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders . Because sevelamer decreases low-density lipoprotein cholesterol ( LDL-C ) levels , we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients . STUDY DESIGN R and omized , controlled , open-label , noninferiority trial with an upper bound for the noninferiority margin of 1.8 . SETTING & PARTICIPANTS 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL , LDL-C levels greater than 80 mg/dL , and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography . INTERVENTIONS 103 patients were r and omly assigned to calcium acetate , and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups . OUTCOMES & MEASUREMENTS The primary end point was change in CAC score assessed by means of electron-beam computed tomography . RESULTS After 12 months , mean serum LDL-C levels decreased to 68.8 + /- 22.0 mg/dL in the calcium-acetate group and 62.4 + /- 23.0 mg/dL in the sevelamer group ( P = 0.3 ) . Geometric mean increases in CAC scores were 35 % in the calcium-acetate group and 39 % in the sevelamer group , with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 ( 95 % confidence interval , 0.851 to 1.161 ) . LIMITATIONS Treatment assignment was not blinded . The 1.8 a priori margin is large , CAC is a surrogate outcome , duration of treatment was short , and dropout rate was high . CONCLUSIONS With intensive lowering of LDL-C levels for 1 year , hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC 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 Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients . Unlike calcium-based binders , sevelamer attenuates arterial calcification but it is unknown whether sevelamer affects mortality or morbidity . In a multicenter , r and omized , open-label , parallel design trial we compared sevelamer and calcium-based binders on all-cause and cause-specific mortality ( cardiovascular , infection , and other ) in prevalent hemodialysis patients . A total of 2103 patients were initially r and omized to treatment and 1068 patients completed the study . All-cause mortality rates and cause-specific mortality rates were not significantly different . There was a significant age interaction on the treatment effect . Only in patients over 65 years of age was there a significant effect of sevelamer in lowering the mortality rate . There was a suggestion that sevelamer was associated with lower overall , but not cardiovascular-linked , mortality in older patients . We suggest that further research is needed to confirm these findings |
1,712 | 23,828,442 | This pooled analysis of 12 published studies shows that KRAS wt status is a good prognostic factor for B-based chemotherapy .
Also , KRAS wt CRC is associated with a better RR with B plus chemotherapy than mut counterpart | The significance of KRAS in advanced colorectal cancer ( CRC ) treated with bevacizumab ( B ) is not well understood . | BACKGROUND Polychemotherapy and biological drugs have increased therapeutic options and outcomes of advanced colorectal cancer ( CRC ) . We examined the relation between progression-free survival ( PFS ) , post-progression survival ( PPS ) and overall survival ( OS ) in trials of modern ( oxaliplatin- and irinotecan-based ) chemotherapy alone or with targeted therapies for advanced CRC . We also evaluated surrogacy of PFS and OS . PATIENTS AND METHODS A PubMed search identified 34 r and omized trials . We split the OS , PFS and PPS and evaluated the correlation between OS and either PFS or PPS . RESULTS The median PPS and PFS were 10.75 and 8.4 months , respectively . For all trials , PPS was strongly associated with OS [ regression coefficient (R2)=0.8 ; Spearman 's rank correlation coefficient (r)=0.88 ] , whereas PFS was moderately associated with OS (R2)=0.43 ; r=0.64 ) . In trials with targeted therapies , the correlation of PPS with OS was 0.88 . However , across all trials , correlation between differences in median PFS ( ΔPFS ) and median OS ( ΔOS ) is 0.59 ( P=0.0007 ) , confirming PFS/OS surrogacy . CONCLUSION Our findings indicate that in recent first-line , phase III , trials , OS becomes more associated with PPS than PFS . However , improvements in PFS are strongly associated with improvements in OS . In this setting so , PFS may be an appropriate surrogate for OS PURPOSE Mutations affecting the KRAS gene are established predictive markers of outcome with anti-epithelial growth factor receptor ( EGFR ) antibodies in advanced colorectal cancer ( CRC ) . The relevance of these markers for anti-vascular endothelial growth factor ( VEGF ) therapy is controversial . This analysis was performed to assess the predictive and prognostic impact of KRAS and BRAF gene mutation status in patients receiving capecitabine with bevacizumab ( CG ) or capecitabine without bevacizumab in the phase III AGITG MAX ( Australasian Gastrointestinal Trials Group MAX ) study . PATIENTS AND METHODS Mutation status was determined for 315 ( 66.9 % ) of the original 471 patients . Mutation status was correlated with efficacy outcomes ( response rate , progression-free survival [ PFS ] , and overall survival [ OS ] ) , and a predictive analyses was undertaken . RESULTS Mutations in KRAS and BRAF genes were observed in 28.8 % and 10.6 % of patients , respectively . KRAS gene mutation status ( wild type [ WT ] v mutated [ MT ] ) had no prognostic impact for PFS ( hazard ratio [ HR ] , 0.89 ; CI , 0.69 to 1.14 ) or OS ( HR , 0.97 ; CI , 0.73 to 1.28 ) . BRAF mutation status ( WT v MT ) was not prognostic for PFS ( HR , 0.80 ; CI , 0.54 to 1.18 ) but was prognostic for OS ( HR , 0.49 ; CI , 0.33 to 0.73 ; P = .001 ) . By using the comparison of capecitabine versus capecitabine and bevacizumab ( CB ) and CB plus mitomycin ( CBM ) , KRAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .95 and 0.43 , respectively ) . Similarly , BRAF gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .46 and 0.32 , respectively ) . CONCLUSION KRAS gene mutation status was neither prognostic for OS nor predictive of bevacizumab outcome in patients with advanced CRC . BRAF gene mutation status was prognostic for OS but was not predictive of outcome with bevacizumab We assessed Ki-ras mutations by single-str and conformation polymorphism followed by DNA sequencing , p53 expression by immunohistochemistry , ploidy status , and S-phase fraction in 66 stage II and 163 stage III colon cancer patients enrolled on a r and omized trial of surgery followed by observation or adjuvant levamisole or 5-fluorouracil ( 5FU ) plus levamisole ( Intergroup Trial 0035 ) to see whether these factors were independently associated with survival or with differential effects of adjuvant therapy . A Cox proportional hazards survival model was used to describe marker effects and therapy by marker interactions , with adjustment for the clinical covariates affecting survival . A Bonferroni adjustment was used to account for multiple testing . Mutation of the Ki-ras gene was found in 41 % of the cancers and was associated with a poor prognosis in stage II but not stage III . In stage II , 7-year survival was 86 % versus 58 % in those with wild type versus Ki-ras mutations . After adjustment for treatment and clinical variables , the hazard ratio ( HR ) for death was 4.5 ; 95 % confidence interval ( CI ) , 1.7 - 12.1 ( P = 0.012 ) . p53 overexpression was found in 63 % of cancers and was associated with a favorable survival in stage III but not stage II . Seven-year survival in stage III was 56 % with p53 overexpression versus 43 % with no p53 expression ( HR , 2.2 ; 95 % CI , 1.3 - 3.6 ; P = 0.012 ) . Aneuploidy was more common in stage III than in stage II ( 66 versus 47 % ; P = 0.009 ) but was not independently related to survival in either group . The proliferative rate was greater in aneuploid than in diploid cancers but was not related to survival . There was no benefit of adjuvant therapy in stage II nor in any of the stage II subgroups defined by mutational status . In stage III , adjuvant therapy with 5FU plus levamisole improved 7-year survival in patients with wild-type Ki-ras ( 76 versus 44 % ; HR , 0.4 ; 95 % CI , 0.2 - 0.8 ) and in those without p53 overexpression ( 64 versus 26 % ; HR , 0.3 ; 95 % CI , 0.1 - 0.7 ) . Adjuvant therapy did not benefit those with Ki-ras mutations or p53 overexpression . The effects of adjuvant therapy did not differ according to ploidy status or proliferative rate . Ki-ras mutation is a significant risk factor for death in stage II , and the absence of p53 expression is a significant risk factor for death in stage III colon cancer after adjustment for treatment and clinical covariates . Exploratory analyses suggest that patients with stage III colon cancer with wild-type Ki-ras or no p53 expression benefit from adjuvant 5FU plus levamisole , whereas those with Ki-ras mutations or p53 overexpression do not . An independent study will be required to determine whether response to adjuvant therapy in colon cancer depends on mutational status BACKGROUND Mutations involving the oncogene K-ras in colorectal cancer may be related to tumor aggressiveness . However , the value of K-ras gene determination as a prognostic marker has not been clearly established . PATIENTS AND METHODS The results from 98 patients recruited in a prospect i ve study analyzing the effect of a K-ras mutation as a prognostic factor in colorectal cancer are reported . RESULTS Disease-free ( P = 0.02 ) and overall survival ( P = 0.03 ) were significantly reduced for patients harboring a K-ras mutation . Two specific mutations demonstrated a significantly increased risk of disease recurrence , namely , 12-TGT ( P = 0.04 ) and 13-GAC substitutions ( P = 0.002 ) . Patients with either of these substitutions had a 2-year disease-free survival rate of 37 % compared with that of 67 % for the group of patients harboring any other mutation type or a wild-type status ( P = 0.01 ) . CONCLUSIONS The results herein presented suggest that K-ras acts as a prognostic factor in colorectal cancer and that this effect is probably related to a limited number of defined mutations BACKGROUND Despite the consistent clinical results demonstrated by studies on anti-angiogenic drugs targeted against the vascular endothelial growth factor in metastatic colorectal cancer ( mCRC ) patients , no specific direct/indirect biomarker of their efficacy has been vali date d. In this field , circulating endothelial cells ( CECs ) and endothelial progenitor cells ( CEPs ) have recently been proposed as noninvasive biomarkers . PATIENTS AND METHODS The absolute numbers of CEPs , total CECs ( tCECs ) and their resting ( rCECs ) and activated subsets were evaluated by multiparameter flow cytometry in 40 mCRC patients at baseline and before the administration of the third and sixth course of a bevacizumab-based first-line treatment . Fifty healthy subjects were utilized as control . RESULTS The overall response rate was 80 % , overall clinical benefit was 90 % and median progression-free survival ( PFS ) was 13.8 months . In our patients , tCECs and rCECs were significantly increased compared with healthy subjects . The patients who achieved a radiological response showed , at baseline , a significant decrease of rCECs and a trend in decrease of tCECs in comparison with patients not achieving response . Finally , a baseline absolute number of tCEC and rCEC < 40 cells/ml was evidence d in patients with a longer PFS . No correlation was found regarding CEP . CONCLUSIONS Our study suggests significant correlations between both tCEC and rCEC baseline levels and the antitumor efficacy of a bevacizumab-based combination therapy in mCRC patients , thus confirming that these biomarkers could be used in the clinical setting as an early predictor of tumor response PURPOSE Mutations in the K-ras gene are frequent in human cancer . ras activation in primary cells results in a cellular senescence phenotype that is precluded by inactivation of p16 . At the clinical level , this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways . PATIENTS AND METHODS We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospect ively collected colorectal carcinomas . p53 mutations and p14 alternative reading frame methylation status were also assessed . Associations with survival were investigated . RESULTS K-ras mutations were present in 44 ( 38 % ) of 115 cases , and p16 methylation was present in 42 ( 37 % ) of 113 cases . p53 mutations were detected in 50 % ( 56 of 115 ) and p14 methylation in 29 % ( 32 of 112 ) of cases . K-ras and p16 alterations were independent genetic events . Presence of K-ras or p16 genetic alterations ( analyzed independently ) was associated with shorter survival , although differences were not statistically significant . Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras . Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis . Differences were maintained when cases undergoing radical surgery and without distant metastases were considered . CONCLUSION These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer BACKGROUND Hypertension is associated with antivascular endothelial growth factor treatment , but the clinical implication s of hypertension are uncertain . To assess the prognostic and predictive value of bevacizumab-related hypertension , a comprehensive analysis of whether hypertension and efficacy outcomes are associated was conducted on seven company-sponsored placebo-controlled phase III studies of bevacizumab . METHODS Patient-specific data were available from 6,486 patients with metastatic colorectal , breast , non-small cell lung , pancreatic , and renal cell cancers . Primary hypertension endpoint was a blood pressure ( BP ) increase of > 20 mmHg systolic or > 10 mmHg diastolic within the first 60 days of treatment . Additional endpoints included other predefined thresholds of change in BP and severity of hypertension grade d using the National Cancer Institute 's Common Terminology Criteria for Adverse Events . To analyze the general prognostic importance of an early BP increase , multivariate Cox regression models were used to assess the correlation between BP changes and progression-free ( PFS ) and overall survival ( OS ) outcomes in the control groups . To analyze whether early BP increases could predict for benefit from bevacizumab , similar analyses were conducted in the bevacizumab-treated and control groups . RESULTS In six of seven studies , early BP increase was neither predictive of clinical benefit from bevacizumab nor prognostic for the course of the disease . For study AVF2107 g , early increased BP was associated with longer PFS and OS times in the bevacizumab group but shorter OS time in the control group . CONCLUSIONS Early treatment-related BP increases do not predict clinical benefit from bevacizumab based on PFS or OS outcomes . BP increases do not appear to have general prognostic importance for patients with advanced cancer BACKGROUND Cetuximab ( C ) , alone or with irinotecan , demonstrates activity in irinotecan-refractory colorectal cancer ( CRC ) . Activity of 5-fluorouracil ( 5-FU ) , leucovorin ( L ) , and bevacizumab ( B ) , and preliminary data of cetuximab + bevacizumab , and toxicity profiles suggests that FOLF-CB ( 5-FU , L , C+B ) may have activity with a favorable toxicity profile as first-line therapy . METHODS Eligible patients were r and omized at registration to either arm A ( mFOLFOX6-B ) ( modified , 5-FU . L ( folinic acid ) , oxaliplatin ( O ) + bevacizumab ) , administered days 1 and 15 of each 28-day cycle as bevacizumab 5 mg/kg , oxaliplatin 85 mg/m(2 ) , leucovorin 400 mg/m(2 ) , and 5-FU 400 mg/m(2 ) then 1200 mg/m(2)/day for 48 hours , or arm B ( FOLF-CB ) , which included bevacizumab , leucovorin , and 5-FU as in arm A and cetuximab 400 mg/m(2 ) day 1 cycle 1 ; all other weekly cetuximab doses were 250 mg/m(2 ) . RESULTS Two hundred forty-seven patients ( arm A/arm B 124/123 ) were enrolled , and 239 were treated ( 118/121 ) . Twelve-month progression-free survival ( PFS ) was 45%/32 % , objective response rates ( ORR ) ( complete response [ CR ] + partial response [ PR ] ) were 52%/41 % , disease control rates ( CR+PR+stable disease [ SD ] ) were 87%/83 % , and median overall survival ( OS ) was 21/19.5 months , respectively . Grade 3 - 4 neutropenia was higher in arm A ( 28%/7 % ) , as was grade 3 fatigue ( 12%/3 % ) , and grade 3 neuropathy ( 11%/ < 1 % ) , whereas acneiform rash was confined to arm B. Retrospective analysis of KRAS mutational status did not demonstrate KRAS as a meaningful determinant of activity , except in arm B patients with KRAS-mutated tumors , which result ed in inferior PFS . Patient satisfaction favored the control ( mFOLFOX6-B ) . CONCLUSION FOLF-CB was not superior to mFOLFOX6-B in terms of 12-month PFS and ORR , and was not more acceptable to patients . This trial supports the conclusion of other recently reported trials that concurrent cetuximab+bevacizumab should not be routinely used in metastatic CRC |
1,713 | 28,725,682 | The current review confirms the increasing research being conducted into NMS in DNPD patients as well as the necessity for further investigation into less-studied NMS , such as pain . | Non-motor symptoms ( NMS ) are a key component of Parkinson ’s disease ( PD ) .
A range of NMS , most notably impaired sense of smell , sleep dysfunction , and dysautonomia are present from the ‘ pre-motor ’ phase to the final palliative stage .
Theories as to the pathogenesis of PD such as those proposed by Braak and others also support the occurrence of NMS in PD years before motor symptoms start .
However , research addressing the range and nature of NMS in PD has been confounded by the fact that many NMS arise as part of drug-related side effects .
Thus , drug-naive PD ( DNPD ) patients provide an ideal population to study the differences in the presentation of NMS .
The aim of this paper is therefore to systematic ally review all the available studies of NMS in DNPD patients . | The present study investigated memory for intention in individuals with Parkinson 's disease ( PD ) who were newly diagnosed and not yet treated to avoid the effect of therapy as a potential confounding variable . A comprehensive neuropsychological battery and an event-based prospect i ve memory task were administered to 41 subjects with de novo PD and 40 control subjects . Separate scores were computed for correct execution of intended action ( prospect i ve component ) and recall of intention ( retrospective component ) . PD patients performed marginally worse ( p = .053 ) than controls on the prospect i ve component of the task . On the other h and , the performance of the two groups was comparable for the retrospective component . Neuropsychological findings revealed lower performance of the PD group in episodic memory and in some measures of executive functions . These results suggested a subtle prospect i ve memory dysfunction present at the initial stage of PD , which may be related to disruption of fronto-striatal circuitry BACKGROUND The clinical manifestations of drug-induced parkinsonism ( DIP ) and Parkinson disease ( PD ) are nearly indistinguishable , making it difficult to differentiate DIP from PD , especially in the early stages . We compared non-motor symptoms between patients with DIP and those with drug-naïve PD in the early stages using the Non Motor Symptoms Scale ( NMSS ) . METHODS We prospect ively enrolled 28 patients with DIP , 35 patients with drug-naïve PD , and 32 controls with no history of neurological diseases or related medical problems . We investigated demographic characteristics , medical and drug history , parkinsonian motor symptoms , and non-motor symptoms . We used the NMSS to evaluate non-motor symptoms in all patients . RESULTS The total NMSS scores were higher in patients with PD than those with DIP , as were the scores for certain domains , including the cardiovascular , sleep/fatigue , urinary , sexual , and miscellaneous domains . When controlling for age and gender , the correlation analysis revealed that scores for urinary symptoms ( urgency , frequency and nocturia ) , sleep disturbances ( daytime sleep , restless legs ) , concentration , taste or smell were significantly associated with PD . CONCLUSIONS Our data suggest that non-motor symptoms , particularly urinary symptoms , excessive daytime sleepiness , restless leg syndrome , attention deficit and hyposmia may be helpful to differentiate between DIP and PD in the early stages Background Non-motor symptoms are very common among patients with Parkinson 's disease since the earliest stage , but little is known about their progression and their relationship with dopaminergic replacement therapy . Methods We studied non-motor symptoms before and after 2 years from dopaminergic therapy introduction in ninety-one newly diagnosed previously untreated PD patients . Results At baseline , nearly all patients ( 97.8 % ) referred at least one non-motor symptom . At follow-up , only few non-motor symptoms significantly changed . Particularly , depression and concentration became less frequent , while weight change significantly increased after introduction of dopamine agonists . Conclusions We reported for the first time a 2-year prospect i ve study on non-motor symptoms before and after starting therapy in newly diagnosed PD patients . Even if non-motor symptoms are very frequent in early stage , they tend to remain stable during the early phase of disease , being only few non-motor symptoms affected from dopaminergic therapy and , specifically , by the use of dopamine agonists BACKGROUND It is accepted that orthostatic hypotension is a clinical marker for the diagnosis of multiple system atrophy , but conflicting data indicate that it may also be present in Parkinson disease ( PD ) . OBJECTIVES To evaluate the prevalence of autonomic cardiovascular impairment and orthostatic hypotension in a large group of patients with de novo PD , followed up for at least 7 years , to clinical ly confirm the diagnosis of the disease . METHODS During a 2-year recruiting period , 60 untreated patients diagnosed as having idiopathic PD underwent autonomic cardiovascular function evaluation using the Ewing test . Patients subsequently received dopaminergic therapy and their condition was followed up for at least 7 years . RESULTS Nine ( 15 % ) of 60 patients were excluded from the study because during the follow-up period a parkinsonian syndrome was diagnosed ( 5 had multiple system atrophy and 4 had progressive supranuclear palsy ) . Data from 51 patients with PD underwent final statistical analysis and the results were compared with those of 51 age-matched healthy control subjects who had taken the same battery of autonomic tests . A statistically significant difference was found in postural hypotension ( P = .02 ) and deep breathing test results ( P = .03 ) between patients and controls . Seven ( 14 % ) of 51 patients with PD and 3 ( 60 % ) of 5 patients with multiple system atrophy had a decrease of more than 20 mm Hg in systolic blood pressure on st and ing . CONCLUSIONS Data from this study indicate a high prevalence of sympathetic and parasympathetic failure in patients with de novo PD , and when using a decrease of at least 20 mm Hg in systolic blood pressure , manometric orthostatic hypotension was found in 7 ( 14 % ) of the 51 patients with de novo PD BACKGROUND Gastrointestinal tract ( GIT ) dysfunction is common in Parkinson 's disease ( PD ) patients . However , it remains unclear whether levodopa affects GIT function in PD . OBJECTIVE To perform an open study of levodopa 's effects on anorectal constipation in de novo PD patients by the quantitative lower-gastrointestinal autonomic test ( QL-GAT ) . METHODS Nineteen unselected de novo PD patients ( 10 men , 9 women ; mean age , 66 years ; mean duration of the disease , 2.2 years ) were recruited for the study . Eighteen of the patients reported constipation . These patients were treated with 200/20 mg b.i.d . of levodopa/carbidopa for 3 months . Pre- and post-treatment , objective parameters in the QL-GAT that comprised the colonic transit time ( CTT ) and rectoanal videomanometry were obtained . RESULTS Levodopa was well tolerated by all patients . There was a trend toward subjective improvements in bowel frequency and difficulty defecating . Levodopa did not significantly change CTT of the total colon or any segment of the colon . During rectal filling , levodopa significantly lessened the first sensation ( p < 0.05 ) . It also tended to augment the amplitude of spontaneous phasic rectal contraction ( not statistically significant ) . During defecation , levodopa significantly lessened the amplitude in paradoxical sphincter contraction upon defecation ( PSD ) ( p < 0.01 ) . It also tended to augment the amplitude of rectal contraction and lessen the amplitude of abdominal strain ( not statistically significant ) . Overall , levodopa significantly lessened post-defecation residuals ( p < 0.05 ) . CONCLUSIONS The QL-GAT in the present study showed for the first time that levodopa augmented rectal contraction , lessened PSD , and thereby ameliorated anorectal constipation in de novo PD patients Objective : To determine nonmotor signs ( NMS ) and evaluate the utility of several diagnostic tools in patients with de novo Parkinson disease ( PD ) . Methods : This is a large single-center study of the DeNoPa cohort , including frequency-matched healthy controls . This study covers motor signs , NMS , and a combination of diagnostic tests including olfactory testing , transcranial sonography of substantia nigra ( TCS ) , and polysomnography ( PSG ) . We report the frequency and characteristics of NMS and the outcomes of nonmotor tests at the time of diagnosis . Results : Cross-sectional analyses of baseline investigations identified significant differences in the NMS Question naire ( NMSQuest ) and the Scopa-AUT Gastrointestinal score in 159 drug-naïve PD patients vs 110 controls . In addition , patients with PD showed reduced olfactory function , hyperechogenicity on TCS , and higher frequency of REM sleep behavior disorder ( RBD ) . In exploring predictive markers , we found that the combination of several investigations , i.e. , the NMSQuest , Scopa-AUT Gastrointestinal score , and Smell Identification Test reached an area under the receiver operating characteristic curve ( AUC ) of 0.913 ( 95 % confidence interval [ CI ] 0.878–0.948 ) . With the addition of serum cholesterol and mean heart rate values , the AUC value reached 0.919 ( 95 % CI 886–0.953 ) ; when TCS and PSG were added , the AUC increased to 0.963 ( 95 % CI 0.943–0.982 ) . Conclusions : We show feasibility and utility of st and ardized data acquisition in a large , single-center cohort of patients with de novo PD and matched healthy controls . The baseline results from our prospect i ve investigations reached a value of > 0.9 sensitivity and specificity for biological markers when we added routine laboratory investigations and quantified nonmotor features including sleep Objectives : Fatigue is common in Parkinson 's disease ( PD ) , causing serious negative effects on quality of life . Despite its clinical importance , the nature of fatigue in PD is poorly understood because its underlying neurobiology is unknown . Fatigue can be more complicated in advanced PD because of its chronicity . In order to find features that are innate to fatigue in PD , it would be useful to conduct a study looking at de novo PD . Assessing fatigue in de novo patients allows excluding at least one confounding factor . Methods : We prospect ively investigated 87 drug-naïve PD patients . Thirty-nine patients ( 44.8 % ) were found to have fatigue around the time of diagnosis of PD . Results : We found that depression and difficulties with activities of daily living were independent risk factors for fatigue ; however , motor dysfunction was not related . Clinical ly meaningful responses to dopaminergic medication were observed . Discussion : Our study determined that fatigue occurs in the early stages of PD . It can inform clinical decision-making to significantly benefit PD patients with fatigue Background : Fatigue is a common complaint in Parkinson disease ( PD ) . We investigated fatigue in a cohort of previously untreated patients with early PD enrolled in the Earlier vs Later Levodopa ( ELLDOPA ) clinical trial . Methods : A total of 361 patients were enrolled in the r and omized , double-blind , placebo-controlled ELLDOPA trial and assigned to receive placebo or carbidopa-levodopa 37.5/150 mg , 75/300 mg , or 150/600 mg daily for 40 weeks , followed by a 2-week medication washout period . Subjects who scored > 4 on the Fatigue Severity Scale were classified as fatigued . PD severity was assessed using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Hoehn-Yahr scale , and Schwab-Engl and Activities of Daily Living Scale . A subgroup of subjects underwent [123I]-β-CIT SPECT to measure striatal dopamine transporter density . Results : Of the 349 ELLDOPA subjects who completed fatigue measures , 128 were classified as fatigued at baseline . The fatigued group was significantly more impaired neurologically ( UPDRS , all subscales and Hoehn and Yahr staging ) and functionally ( Schwab-Engl and Scale ) but no significant differences were observed in β-CIT measurements between the two groups . Analysis of covariance showed a greater increase in fatigue score from baseline to the end of the 2-week washout in the placebo group ( 0.75 points ) than in the three groups receiving levodopa ( increases of 0.30 [ 150 mg/day ] , 0.36 [ 300 mg/day ] , and 0.33 [ 600 mg/day ] ; p = 0.03 for heterogeneity ) . Conclusions : Fatigue is a frequent symptom in early , untreated , non-depressed patients with Parkinson disease ( PD ) , affecting over 1/3 of the patients in this cohort at baseline and 50 % by week 42 . Fatigue was associated with the severity of PD , and progressed less in patients treated with levodopa OBJECTIVE Rapid eye movement ( REM ) sleep behavior disorder ( RBD ) is a risk factor for dementia in Parkinson disease ( PD ) patients . The objectives of our study were to prospect ively evaluate the frequency of RBD in a sample of treatment-naïve , newly diagnosed PD patients and compare sleep characteristics and cognition in RBD and non-RBD groups . METHODS Fifty-seven newly diagnosed PD patients were consecutively recruited in a university medical center . All patients underwent two overnight polysomnography ( PSG ) sessions and were diagnosed with RBD according to the International Classification of Sleep Disorders , Second Revision criteria . Daytime sleepiness was measured in a multiple sleep latency test ( MSLT ) . Cognition was assessed in a st and ard neuropsychologic examination . RESULTS Seventeen PD patients ( 30 % ) met the criteria for RBD . The RBD patients and non-RBD patients did not significantly differ in mean age , gender ratio , disease duration , motor symptom subtype and severity , total sleep time , percentage of REM sleep , apnea-hypopnea index , mean oxygen saturation , and importantly cognitive performance . However , non-RBD patients had a significantly shorter mean daytime sleep latency than RBD patients ( 15 vs. 18 min , respectively ; P=.014 ) . CONCLUSION A high frequency of RBD was found in our sample of 57 newly diagnosed PD patients . At this stage in the disease , RBD was not found to be associated with other sleep disorders or cognitive decline . Follow-up is needed to assess the risk for developing dementia in early-stage PD patients with RBD BACKGROUND Delayed gastric emptying is a non-motor symptom of Parkinson 's disease . Few data exist on gastric emptying in early-stage Parkinson 's disease . In idiopathic rapid-eye-movement sleep behavior disorder , a presumable pre-motor stage of Parkinson 's disease , gastric emptying has not yet been investigated . METHODS Twenty healthy controls , 13 patients with idiopathic rapid-eye-movement sleep behavior disorder , and 39 patients with Parkinson 's disease patients underwent st and ardized testing for gastric emptying with the (13)C-octanoate breath test . RESULTS Gastric emptying was significantly delayed in drug-naïve ( P < .001 ) and in treated Parkinson 's disease patients ( P < .001 ) , but normal in patients with idiopathic rapid-eye-movement sleep behavior disorder . CONCLUSIONS Our study confirms delayed gastric emptying in drug-naïve , early-stage Parkinson 's disease . Normal gastric emptying in idiopathic rapid-eye-movement sleep behavior disorder might be explained by the fact that neurodegenerative changes in structures modulating gastric motility are not severe enough to cause a functional deficit that can be detected by the (13)C-octanoate breath test Neuropsychiatric and cognitive symptoms are common in patients with Parkinson ’s disease ( PD ) from the early stage of the disease but their course is still unclear . In this study we investigated prospect ively the progression of affective and cognitive symptoms and disorders in de novo idiopathic PD patients . Twenty-four de novo drug naïve PD patients underwent a comprehensive neurological , psychopathological and neuropsychological evaluation at the first diagnostic visit ( OFF ) , after 4−6 months when the antiparkinsonian therapy regimen was stabilized ( ON-1 ) , and at one year following the ON-1 follow-up visit ( ON-2 ) . Generalized least squares analysis revealed a significant improvement over time in the depressive mood , short and long term episodic verbal memory , visual memory , and the motor symptoms . Pairwise comparisons showed a significant change from OFF to ON-1 for all the aforementioned variables , except for short term episodic verbal memory which approached significance . A significant improvement from ON-1 to ON-2 , however , was shown for short term episodic verbal memory . An ancillary analysis indicated that overall level and change in a number of cognitive variables , but not depression , was conditional upon age of onset , education , and sometime gender . In conclusion , early stage PD is not associated with affective and cognitive deterioration . On the contrary , very specific neuropsychiatric and cognitive symptoms may improve . This study provides Class III evidence that antiparkinsonian treatment commonly used in the clinical practice improves memory performance and depression severity in de novo patients with PD Sleep disturbances and daytime sleepiness are well-known phenomena in Parkinson 's disease ( PD ) . Fifteen previously untreated PD patients underwent clinical evaluation , subjective sleep evaluation and polysomnographic evaluation ( PSG ) before and after a treatment period of mean 8+/-3.1 months with dopaminergic drugs . Both mean Unified Parkinson 's Disease Rating Scale ( UPDRS ) total score and mean subset III of the UPDRS were significantly improved with dopaminergic treatment . PSG revealed that administration of dopaminergic drugs result ed in significant increase in mean percentage of stages 1 and 2 . The mean Epworth Sleepiness Scale ( ESS ) score was significantly increased and mean Multiple Sleep Latency Test ( MSLT ) score was significantly decreased after dopaminergic treatment indicating subjective and objective daytime sleepiness . The differences in MSLT scores were best explained by a higher dose of L-dopa , whereas other variables such as disease duration , treatment duration , Hoehn and Yahr stage , sleep efficiency index or dopamine agonists did not increase the significance . In contrast , any of the variables appeared to explain ESS score variability . This study demonstrates that daytime sleepiness is not present in untreated patients but emerges later during dopaminergic treatment . Total daily L-dopa dose is predictive of objective daytime sleepiness . Furthermore , subjective assessment of sleepiness may cause underestimation of the severity of daytime sleepiness Background and purpose : The aim of this study was to establish the cognitive profile of newly diagnosed untreated ( de novo ) patients with Parkinson ’s disease ( PD ) and more advanced , treated patients , and to determine the effects of dopamine ( DA ) replacement therapy Abstract Autonomic nervous system ( ANS ) involvement is frequently found in Parkinson 's disease ( PD ) , but its causal relationship to the disease itself and its medication is unclear . We evaluated the effects of PD medications on cardiovascular ANS functions . Heart rate ( HR ) responses to normal and deep breathing , the Valsalva manoeuvre and tilting , and blood pressure ( BP ) responses to tilting and isometric work were measured prospect ively in 60 untreated PD patients r and omised to receive either levodopa ( n=20 ) , bromocriptine ( n=20 ) or selegiline ( n=20 ) as their initial treatment . The results were compared with those of 28 healthy controls . The responses were recorded at baseline , after 6 months on medication and following a 6-week washout period . At baseline HR responses to normal breathing , deep breathing and tilting were already lower and the fall in the systolic BP immediately and at 5 min after tilting was more pronounced in the PD patients than in the controls . Six months ' levodopa treatment diminished the systolic BP fall after tilting when compared to baseline , whereas bromocriptine and selegiline increased the fall in systolic BP after tilting and selegiline diminished the BP responses to isometric work . The BP responses returned to the baseline values during the washout period . The drugs induced no change in the HR responses . Thus PD itself causes autonomic dysfunction leading to abnormalities in HR and BP regulation and the PD medications seem to modify ANS responses further . Bromocriptine and selegiline , in contrast to levodopa , increase the orthostatic BP fall and supress the BP response to isometric exercise reflecting mainly impairment of the sympathetic regulation Background : Longitudinal studies on healthy participants have shown that subjective memory impairment ( defined as subjective cognitive complaints with normal cognitive objective performance ) might be a strong predictor of mild cognitive impairment ( MCI ) . Parkinson disease ( PD ) also manifests cognitive disturbances , but whether subjective memory complaints may predict the development of MCI in PD has not yet been explored . Methods : We prospect ively screened newly diagnosed , untreated patients with PD in order to evaluate whether subjective memory complaints may predict development of MCI over a 2-year follow-up evaluation . Results : We enrolled 76 de novo untreated patients with PD . Of the 76 patients , 23 ( 30.3 % ) complained memory issues . Among the patients cognitively unimpaired at baseline , those with subjective complaints were more likely to develop MCI at follow-up . The regression model confirmed that presence of subjective memory complaints at baseline was an independent predictor of development of MCI at follow-up . Discussion : This is the first prospect i ve study to explore the relationship between subjective and objective cognitive deficits in newly diagnosed , untreated patients . Our results provide preliminary evidence that subjective memory complaints might predict future development of MCI |
1,714 | 29,101,131 | Conclusion The results of the eight included studies suggest that CHWs can be trained effectively for CVD prevention and management . | Introduction Community health workers ( CHWs ) are increasingly being tasked to prevent and manage cardiovascular disease ( CVD ) and its risk factors in underserved population s in low-income and middle-income countries ( LMICs ) ; however , little is known about the required training necessary for them to accomplish their role .
This review aim ed to evaluate the training of CHWs for the prevention and management of CVD and its risk factors in LMICs . | Background Lay health workers ( LHWs ) play a pivotal role in addressing the high TB burden in Malawi . LHWs report lack of training to be a key barrier to their role as TB care providers . Given the cost of traditional off-site training , an alternative approach is needed . Our objective was to evaluate the effectiveness of a KT intervention tailored to LHWs needs . Methods The study design is a pragmatic cluster r and omized trial . The study was embedded within a larger trial , PALMPLUS , and compared three arms which included 28 health centers in Zomba district , Malawi . The control arm included 14 health centers r and omized as controls in the larger trial and maintained as control sites . Seven of 14 PALMPLUS intervention sites were r and omized to the LHW intervention ( PALM/LHW intervention arm ) , and the remaining 7 PALMPLUS sites maintained as a PALM only arm . PALMPLUS intervention sites received an educational outreach program targeting mid-level health workers . LHW intervention sites received both the PALMPLUS intervention and the LHW intervention employing on-site peer-led educational outreach and a point-of-care tool tailored to LHWs identified needs . Control sites received no intervention . The main outcome measure is the proportion of treatment successes . Results Among the 28 sites , there were 178 incident TB cases with 46/80 ( 0.58 ) successes in the control group , 44/68 ( 0.65 ) successes in the PALMPLUS group , and 21/30 ( 0.70 ) successes in the PALM/LHW intervention group . There was no significant effect of the intervention on treatment success in the univariate analysis adjusted for cluster r and omization ( p = 0.578 ) or multivariate analysis controlling for covariates with significant model effects ( p = 0.760 ) . The overall test of the intervention-arm by TB-type interaction approached but did not achieve significance ( p = 0.056 ) , with the interaction significant only in the control arm [ RR of treatment success for pulmonary TB relative to non-pulmonary TB , 1.18 , 95 % CI 1.05–1.31 ] . Conclusions We found no significant treatment effect of our intervention . Given the identified trend for effectiveness and urgent need for low-cost approaches to LHW training , further evaluation of tailored KT strategies as a means of LHW training in Malawi and other LMICs is warranted . Trial registration Clinical Trials.gov NCT01356095 Objective To assess the effectiveness of a community based lifestyle intervention on blood pressure in children and young adults in a developing country setting . Design Cluster r and omised controlled trial . Setting 12 r and omly selected geographical census based clusters in Karachi , Pakistan . Participants 4023 people aged 5 - 39 years . Intervention Three monthly family based home health education delivered by lay health workers . Main outcome measure Change in blood pressure from r and omisation to end of follow-up at 2 years . Results Analysed using the intention to treat principle , the change in systolic blood pressure ( adjusted for age , sex , and baseline blood pressure ) was significant ; it increased by 1.5 ( 95 % confidence interval 1.1 to 1.9 ) mm Hg in the control group and by 0.1 ( −0.3 to 0.5 ) mm Hg in the home health education group ( P for difference between groups=0.02 ) . Findings for diastolic blood pressure were similar ; the change was 1.5 mm Hg greater in the control group than in the intervention group ( P=0.002 ) . Conclusions Simple , family based home health education delivered by trained lay health workers significantly ameliorated the usual increase in blood pressure with age in children and young adults in the general population of Pakistan , a low income developing country . This strategy is potentially feasible for up-scaling within the existing healthcare systems of Indo-Asia . Trial registration Clinical trials NCT00327574 BACKGROUND Adherence to drugs and healthy lifestyles is low after acute coronary syndrome . We assessed whether trained community health workers could improve adherence to drugs , lifestyle changes , and clinical risk markers in patients with acute coronary syndrome in India . METHODS In this study done at 14 hospitals in India we r and omly assigned ( 1:1 ) patients with acute coronary syndrome 1 or 2 days before discharge from hospital to a community health worker-based intervention group or a st and ard care group . Patients were r and omly assigned with a telephone r and omisation service . In the intervention group , during four in-hospital and two home visits , community health workers used unstructured discussion s , visual methods , and patient diaries to educate patients on healthy lifestyle and drugs , and measures to enhance adherence . The primary outcome was adherence to proven secondary prevention drugs ( antiplatelet drugs , β blockers , angiotensin-converting enzyme inhibitors or angiotensin receptor blockers , and statins ) estimated using a Composite Medication Adherence Scale at 1 year . The secondary outcomes were difference in lifestyle factors ( diet , exercise , and tobacco and alcohol use ) , and clinical risk markers ( blood pressure , bodyweight , BMI , heart rate , and lipids ) . All analyses were by intention to treat . This trial is registered with the Clinical Trial Registry of India , number REF/2013/03/004737 , and Clinical Trials.gov , number NCT01207700 . RESULTS Between Aug 23 , 2011 , and June 25 , 2012 , 806 participants were r and omly assigned ( 405 to a community health worker-based intervention group and 401 to a st and ard care group ) . At 1 year , 40 patients had died and 15 had discontinued or been lost to follow-up , so 750 ( 93 % ) were included in the analyses ( 375 in each group ) . Secondary prevention drugs prescribed at discharge were 98 % ( 786/803 ) for any antiplatelet drug , 79 % ( 638/803 ) for dual antiplatelet drugs , 69 % ( 555/803 ) for β blockers , 69 % ( 552/803 ) for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers , and 95 % ( 762/803 ) for statins . At one year , overall adherence ( ≥80 % ) to prescribed evidence -based drugs was higher in the intervention group than in the control group ( 97 % vs 92 % , odds ratio [ OR ] 2·62 , 95 % CI 1·32 - 5·19 ; p=0·006 ) . For individual drugs , we recorded significant differences for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers ( 97 % [ 233/240 ] in the intervention group vs 93 % [ 223/240 ] in the control group ; p=0·036 ) and statins ( 97 % [ 346/356 ] vs 93 % [ 321/345 ] ; p=0·011 ) . The intervention group had significantly greater adherence to smoking cessation ( 85 % [ 110/129 ] vs 52 % [ 71/138 ] , OR 5·46 , 95 % CI 3·03 - 9·86 ; p<0·0001 ) , regular physical activity ( 89 % [ 333/375 ] vs 60 % [ 226/375 ] , OR 5·23 , 95 % CI 3·57 - 7·66 ; p<0·0001 ) , and healthy diet ( score 5·0 vs 3·0 , OR 2·47 , 95 % CI 1·88 - 3·25 ; p<0·0001 ) . More patients in the intervention group had stopped alcohol use at 1 year ( 87 % [ 64/74 ] vs 46 % [ 46/67 ] , OR 2·92 , 95 % CI 1·26 - 6·79 ; p = 0·010 ) . At 1 year , the mean systolic blood pressure ( 124·4 mm Hg [ SD 13·5 ] vs 128·0 mm Hg [ 15·9 ] ; p=0·002 ) , weight ( 65·0 kg [ 11·0 ] vs 66·5 kg [ 11·5 ] ; p<0·0001 ) , cholesterol ( 157·0 [ 40·2 ] vs 166·9 [ 48·4 ] ; p=0·184 ) , LDL ( 81·0 [ 20·6 ] vs 87·3 [ 29·9 ] ; p=0·191 ) , HDL ( 42·0 [ 11·4 ] vs 38·2 [ 6·5 ] ; p=0·042 ) , and BMI ( 24·4 kg/m(2 ) [ SD 3·7 ] vs 25·0 kg/m(2 ) [ 3·8 ] ; p<0·0001 ) were lower in the intervention group than in the control group . However , we noted no significant difference in diastolic blood pressure and heart rate . INTERPRETATION A community health worker-based personalised intervention strategy in patients with acute coronary syndrome improved adherence to evidence -based drugs and healthy lifestyles , and result ed in an improvement in clinical risk markers . Integration of trained community health workers can improve secondary prevention in coronary artery disease . FUNDING US National Heart , Lung , and Blood Institute ( NHLBI ) , National Institutes of Health , Department of Health and Human Services , and the UnitedHealth group , USA Background In Africa hypertension is common and stroke is increasing . Detection , treatment and control of high blood pressure ( BP ) is limited . BP can be lowered by reducing salt intake . In Africa salt is added to the food by the consumer , as processed food is rare . A population -wide approach with programmes based on health education and promotion is thus possible . Methods We carried out a community-based cluster r and omised trial of health promotion in 1,013 participants from 12 villages ( 628 women , 481 rural dwellers ) ; mean age 55 years to reduce salt intake and BP . Average BP was 125/74 mmHg and urinary sodium ( UNa ) 101 mmol/day . A health promotion intervention was provided over 6 months to all villages . Assessment s were made at 3 and 6 months . Primary end-points were urinary sodium excretion and BP levels . Results There was a significant positive relationship between salt intake and both systolic ( 2.17 mmHg [ 95 % CI 0.44 to 3.91 ] per 50 mmol of UNa per day , p < 0.001 ) and diastolic BP ( 1.10 mmHg [ 0.08 to 1.94 ] , p < 0.001 ) at baseline . At six months the intervention group showed a reduction in systolic ( 2.54 mmHg [ -1.45 to 6.54 ] ) and diastolic ( 3.95 mmHg [ 0.78 to 7.11 ] , p = 0.015 ) BP when compared to control . There was no significant change in UNa . Smaller villages showed greater reductions in UNa than larger villages ( p = 0.042 ) . Irrespective of r and omisation , there was a consistent and significant relationship between change in UNa and change in systolic BP , when adjusted for confounders . A difference in 24-hour UNa of 50 mmol was associated with a lower systolic BP of 2.12 mmHg ( 1.03 to 3.21 ) at 3 months and 1.34 mmHg ( 0.08 to 2.60 ) at 6 months ( both p < 0.001 ) . Conclusion In West Africa the lower the salt intake , the lower the BP . It would appear that a reduction in the average salt intake in the whole community may lead to a small but significant reduction in population systolic BP OBJECTIVE To evaluate the effectiveness of the Shanghai Chronic Disease Self-Management Program ( CDSMP ) . METHODS A r and omized controlled trial with six-month follow-up compared patients who received treatment with those who did not receive treatment ( waiting-list controls ) in five urban communities in Shanghai , China . Participants in the treatment group received education from a lay-led CDSMP course and one copy of a help book immediately ; those in the control group received the same education and book six months later . FINDINGS In total , 954 volunteer patients with a medical record that confirmed a diagnosis of hypertension , heart disease , chronic lung disease , arthritis , stroke , or diabetes who lived in communities were assigned r and omly to treatment ( n = 526 ) and control ( n = 428 ) groups . Overall , 430 ( 81.7 % ) and 349 ( 81.5 % ) patients in the treatment and control groups completed the six-month study . Patients who received treatment had significant improvements in weekly minutes of aerobic exercise , practice of cognitive symptom management , self-efficacy to manage own symptoms , and self-efficacy to manage own disease in general compared with controls . They also had significant improvements in eight indices of health status and , on average , fewer hospitalizations . CONCLUSION When implemented in Shanghai , the CDSMP was acceptable culturally to Chinese patients . The programme improved participants ' health behaviour , self-efficacy , and health status and reduced the number of hospitalizations six months after the course . The locally based delivery model was integrated into the routine of community government organizations and community health services . Chinese lay leaders taught the CDSMP courses as successfully as professionals Mainstream preventive interventions often fail to reach poor population s with a high risk of cardiovascular diseases ( CVDs ) in Pakistan . A community-based CVD primary prevention project aim ed at developing approaches to reduce risk factors in such population s was established by Heartfile in collaboration with the National Rural Support Program in the district of Lodhran . The project implemented a range of activities integrated with existing social and health service mechanisms during a three year intervention period 2000/01 - 03/04 . These were targeted in 4 key setting s : community health education , mass media interventions , training of health professionals and health education through Lady Health Workers . The project received support from the Department for International Development , UK . At the community level , a pre-test-post-test quasi-experimental design was used for examining project outcomes related to the community component of the intervention . Pre and post-intervention ( training ) evaluations were conducted involving all health care providers in r and omly selected workshops in order to determine baseline levels of knowledge and the impact of training on knowledge level . In order to assess practice s of physician and non-physician health care providers patient interviews , with control comparisons were conducted at each health care facility . Significant positive changes were observed in knowledge levels at a community level in the district of intervention compared with baseline knowledge levels particularly in relation to a heart healthy diet , beneficial level of physical activity , the causes of high blood pressure and heart attack and the effects of high blood pressure and active and passive smoking on health . Significant changes in behaviors at a practice level were not shown in the district of intervention . However the project played a critical role in spurring national action for the prevention and control of non-communicable diseases and introducing sustainable public health interventions for poor communities in Pakistan Abstract Background Diabetes makes a significant contribution to the burden of disease in South Africa . This study assesses a group diabetes education programme using motivational interviewing in public sector health centres serving low socio-economic communities in Cape Town . The programme was delivered by mid-level health promotion officers ( HPOs ) . Objectives The aim of the study was to explore the experience of the HPOs and to observe their fidelity to the educational programme . Methods Three focus group interviews were held with the 14 HPOs who delivered the educational programme in 17 health centres . Thirty-three sessions were observed directly and the audio tapes were analysed using the motivational interviewing ( MI ) integrity code . Results The HPOs felt confident in their ability to deliver group education after receiving the training . They reported a significant shift in their communication style and skills . They felt the new approach was feasible and better than before . The re source material was found to be relevant , underst and able and useful . The HPOs struggled with poor patient attendance and a lack of suitable space at the facilities . They delivered the majority of the content and achieved beginning-level proficiency in the MI guiding style of communication and the use of open questions . The HPOs did not demonstrate proficiency in active listening and continued to offer some unsolicited advice . Conclusion The HPOs demonstrated their potential to deliver group diabetes education despite issues that should be addressed in future training and the district health services . The findings will help with the interpretation of results from a r and omised controlled trial evaluating the effectiveness of the education Despite the high prevalence of diabetes in rural Guatemala , there is little education in diabetes self-management , particularly among the indigenous population . To address this need , a culturally relevant education intervention for diabetic patients was developed and implemented in two rural communities in Guatemala . An evaluative research project was design ed to investigate if the structured , community-led diabetes self-management intervention improved selected health outcomes for participants . A one-group , pretest – posttest design was used to evaluate the effectiveness of the educational intervention by comparing measures of health , knowledge , and behavior in patients pre- and postintervention . A survey instrument assessed health beliefs and practice s and hemoglobin A1c ( HgA1c ) measured blood glucose levels at baseline and 4 months post initiation of intervention ( n = 52 ) . There was a significant decrease ( 1.2 % ) in the main outcome measure , mean HgA1c from baseline ( 10.1 % ) and follow-up ( 8.9 % ; p = .001 ) . Other survey findings were not statistically significant . This study illustrates that a culturally specific , diabetes self-management program led by community health workers may reduce HgA1c levels in rural population s of Guatemala . However , as a r and om sample was not feasible for this study , this finding should be interpreted with caution . Limitations unique to the setting and patient population are discussed in this article OBJECTIVES This study attempted to evaluate clinical outcomes and long-term cost-effectiveness of an intervention involving Community Health Workers ( CHW 's , a.k.a . promotoras de salud in Spanish ) in assisting Mexican-American diabetes type-2 patients with controlling their condition . The intervention has been carried out in Hidalgo County , TX which is situated on the U.S.-Mexico border . STUDY DESIGN The design of the study is experimental . The sample ( n = 30 ) was recruited from Mexican-American diabetes patients aged 30 or above . The intervention group received monthly visits from CHW 's , while the control group did not . METHODS Incremental lifetime health outcomes and related expenditures were calculated using the CDC Diabetes Cost-Effectiveness Model ( DCEM ) which is a probabilistic computer simulation model of disease progression and cost-effectiveness for type 2 diabetes patients . The DCEM allows projection of lifetime healthcare costs and Quality -Adjusted Life-Years ( QALYs ) . RESULTS The intervention group showed a significant improvement in glycemic control and cholesterol management after two years of intervention . The intervention is expected to reduce long-term complications , result ing in an increase in residual life-years and quality -adjusted life-years . The incremental cost-effectiveness ratio has been estimated to be $ 13,810 , which is below the level of comparable studies . CONCLUSIONS Intervention has a substantial impact on the medical costs of type 2 diabetes treatment . The estimates presented in this model may be used to analyse the cost-effectiveness of interventions involving CHW 's for type 2 diabetes BACKGROUND In re source -constrained setting s of developing countries , promotion of community-based health interventions through community health workers ( CHWs ) is an important strategy to improve child health . However , there are concerns about the sustainability of such programmes owing to the high rate of CHW attrition . This study examined factors influencing retention of volunteer CHWs in a cluster r and omised trial on community management of under-5 fever in a rural Ghanaian district . METHODS Data were obtained from structured interviews ( n=520 ) and focus group discussion s ( n=5 ) with CHWs . Factors influencing CHWs ' decisions to remain or leave the programme were analysed using a probit model , and focus group discussion results were used to eluci date the findings . RESULTS The attrition rate among CHWs was 21.2 % . Attrition was comparatively higher in younger age groups ( 25.9 % in 15 - 25 years group , 18.2 % in 26 - 45 years group and 16.5 % in ≥46 years group ) . Approval of a CHW by the community ( p<0.001 ) and the CHW 's immediate family ( p<0.05 ) were significant in influencing the probability of remaining in the programme . Motivation for retention was related to the desire to serve their communities as well as humanitarian and religious reasons . CONCLUSION The relatively moderate rate of attrition could be attributed to the high level of community involvement in the selection process as well as other aspects of the intervention leading to high community approval and support . Attention for these aspects could help improve CHW retention in community-based health interventions in Ghana , and the lessons could be applied to countries within similar setting BACKGROUND There is a need to evaluate and implement cost-effective strategies to improve adherence to treatments in coronary heart disease . There are no studies from low- to middle income countries ( LMICs ) evaluating trained community health worker (CHW)-based interventions for the secondary prevention of coronary heart disease . METHODS We design ed a hospital-based , open r and omized trial of CHW-based interventions versus st and ard care . Patients after an acute coronary syndrome ( ACS ) were r and omized to an intervention group ( a CHW-based intervention package , comprising education tools to enhance self-care and adherence , and regular follow-up by the CHW ) or to st and ard care for 12 months during which study outcomes were recorded . The CHWs were trained over a period of 6 months . The primary outcome measure was medication adherence . The secondary outcomes were differences in adherence to lifestyle modification , physiological parameters ( blood pressure [ BP ] , body weight , body mass index [ BMI ] , heart rate , lipids ) , and major adverse cardiovascular events . RESULTS We recruited 806 patients stabilized after an ACS from 14 hospitals in 13 Indian cities . The mean age was 56.4 ( ± 11.32 ) years , and 17.2 % were females . A high prevalence of risk factors such as hypertension ( 43.4 % ) , diabetes ( 31.9 % ) , tobacco consumption ( 35.4 % ) , and inadequate physical activity ( 70.5 % ) was documented . A little over half had ST-elevation myocardial infa rct ion ( 53.7 % ) , and 46.3 % had non-ST-elevation myocardial infa rct ion or unstable angina . CONCLUSION The CHW interventions and training for SPREAD have been developed and adapted for local use . The results and experience of this study will be important to counter the burden of cardiovascular diseases in low- to middle income countries BACKGROUND Primary prevention of cardiovascular disease (CVD),by identifying individuals at risk is a well-established , but costly strategy when based on measurements that depend on laboratory analyses . A non-laboratory , paper-based CVD risk assessment chart tool has previously been developed to make screening more affordable in developing countries . Task shifting to community health workers ( CHWs ) is being investigated to further scale CVD risk screening . This study aim ed to develop a mobile phone CVD risk assessment application and to evaluate its impact on CHW training and the duration of screening for CVD in the community by CHWs . METHODS A feature phone application was developed using the open source online platform , CommCare ( © ) . CHWs ( n=24 ) were trained to use both paper-based and mobile phone CVD risk assessment tools . They were r and omly allocated to using one of the risk tools to screen 10 - 20 community members and then crossed over to screen the same number , using the alternate risk tool . The impact on CHW training time , screening time and margin of error in calculating risk scores was recorded . A focus group discussion evaluated experiences of CHWs using the two tools . RESULTS The training time was 12.3h for the paper-based chart tool and 3h for the mobile phone application . 537 people were screened . The mean screening time was 36 min ( SD=12.6 ) using the paper-base chart tool and 21 min ( SD=8.71 ) using the mobile phone application , p=<0.0001 . Incorrect calculations ( 4.3 % of average systolic BP measurements , 10.4 % of BMI and 3.8 % of CVD risk score ) were found when using the paper-based chart tool while all the mobile phone calculations were correct . Qualitative findings from the focus group discussion corresponded with the findings of the pilot study . CONCLUSION The reduction in CHW training time , CVD risk screening time , lack of errors in calculation of a CVD risk score and end user satisfaction when using a mobile phone application , has implication s in terms of adoption and sustainability of this primary prevention strategy to identify people with high CVD risk who can be referred for appropriate diagnoses and treatment |
1,715 | 30,260,073 | The administration of perioperative dexmedetomidine effectively prevents JET in pediatric patients undergoing cardiac surgery but has no significant effect on postoperative renal function . | OBJECTIVE We conducted a meta- analysis to evaluate the effects of prophylactic perioperative dexmedetomidine administration on postoperative junctional ectopic tachycardia ( JET ) and acute kidney injury ( AKI ) in pediatric patients having undergone cardiac surgery . | Objectives : Recent data have suggested an association between the use of dexmedetomidine and a decreased incidence of acute kidney injury in adult patients after cardiopulmonary bypass . However , no study has focused on this association among pediatric population s where the incidence of acute kidney injury is particularly high and of critical significance . The primary objective of this study was to assess the relationship between the use of postoperative dexmedetomidine and the incidence of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass . The secondary objective was to determine whether there was an association between dexmedetomidine use and duration of mechanical ventilation or cardiovascular ICU stay . Design : Single-center retrospective matched cohort study . Setting : A 20-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California . Patients : Children less than 18 years old admitted after cardiac surgery with cardiopulmonary bypass between January 1 , 2012 , and May 31 , 2014 . Interventions : None . Measurements and Main Results : Data from a cohort of 102 patients receiving dexmedetomidine during the first postoperative day after cardiac surgery were compared to an age- and procedure-matched cohort not receiving dexmedetomidine . Cohorts had similar baseline and demographic characteristics . Patients receiving dexmedetomidine were less likely to develop acute kidney injury ( 24 % vs 36 % ; odds ratio , 0.54 ; 95 % CI , 0.29–0.99 ; p = 0.046 ) . After adjusting for age , bypass time , nephrotoxin use , and vasoactive inotropic score , the use of dexmedetomidine was associated with a lower incidence of acute kidney injury with adjusted odds ratio of 0.43 ( 95 % CI , 0.27–0.98 ; p = 0.048 ) . There was no difference between the cohorts with respect to the duration of mechanical duration ( 1 d each ; p = 0.98 ) or cardiovascular ICU stays ( 5 vs 6 d ; p = 0.91 ) . Conclusions : The use of a dexmedetomidine infusion in pediatric patients after congenital heart surgery was associated with a decreased incidence of acute kidney injury ; however , it was not associated with changes in clinical outcomes . Further prospect i ve study is necessary to vali date these findings Introduction : Incidence of junctional ectopic tachycardia ( JET ) after repair of tetralogy of Fallot ( TOF ) is 5.6–14 % . Dexmeditomidine is a α-2 adrenoceptor agonist modulates the release of catecholamine , result ing in bradycardia and hypotension . These effects are being explored as a therapeutic option for the prevention of perioperative tachyarrhythmia . We undertook this study to examine possible preventive effects of dexmedetomidine on postoperative JET and its impact on the duration of ventilation time and length of Intensive Care Unit stay . Methods : After obtaining approval from the hospitals ethics committee and written informed consent from parents , this quasi-r and omized trial was initiated . Of 94 patients , 47 patients received dexmedetomidine ( dexmedetomidine group ) and 47 patients did not receive the drug ( control group ) . Results : Dexmedetomidine group had more number of complex variants like TOF with an absent pulmonary valve or pulmonary atresia ( P = 0.041 ) . Hematocrit on cardiopulmonary bypass ( CPB ) , heart rate while coming off from CPB and inotrope score was significantly low in the dexmedetomidine group compared to control group . The incidence of JET was significantly low in dexmedetomidine group ( P = 0.040 ) compared to control group . Conclusions : Dexmedetomidine may have a potential benefit of preventing perioperative JET Objective : The objective of this study was to assess the effectiveness of pre-emptive dexmedetomidine versus amiodarone in preventing junctional ectopic tachycardia ( JET ) in pediatric cardiac surgery . Design : This is a prospect i ve , controlled study . Setting : This study was carried out at a single university hospital . Subjects and Methods : Ninety patients of both sexes , American Society of Anesthesiologists Physical Status II and III , age range from 2 to 18 years , and scheduled for elective cardiac surgery for congenital and acquired heart diseases were selected as the study participants . Interventions : Patients were r and omized into three groups ( 30 each ) . Group I received dexmedetomidine 1 mcg/kg diluted in 100 ml of normal saline intravenously ( IV ) over a period of 20 min , and the infusion was completed 10 min before the induction followed by a 0.5 mcg/kg/h infusion for 72 h postoperative , Group II received amiodarone 5 mg/kg diluted in 100 ml of normal saline IV over a period of 20 min , and the infusion was completed 10 min before the induction followed by a 10–15 mcg/kg/h infusion for 72 h postoperative , and Group III received 100 ml of normal saline IV . Primary outcome was the incidence of postoperative JET . Secondary outcomes included vasoactive-inotropic score , ventilation time ( VT ) , pediatric cardiac care unit stay , hospital length of stay , and perioperative mortality . Measurements and Main Results : The incidence of JET was significantly reduced in Group I and Group II ( P = 0.004 ) compared to Group III . Heart rate while coming off from cardiopulmonary bypass ( CPB ) was significantly low in Group I compared to Group II and Group III ( P = 0.000 ) . Mean VT , mean duration of Intensive Care Unit stay , and length of hospital stay ( day ) were significantly short ( P = 0.000 ) in Group I and Group II compared to Group III ( P = 0.000 ) . Conclusion : Perioperative use of dexmedetomidine and amiodarone is associated with significantly decreased incidence of JET as compared to placebo without significant side effects This study was design ed to evaluate the incidence and risk factors associated with the occurrence of junctional ectopic tachycardia ( JET ) in patients after congenital heart surgery . We prospect ively analyzed cardiac rhythm status in 336 consecutive patients undergoing surgery for congenital heart disease at our institution during a 1-year period . The incidence of JET was 8 % ( 27/336 ) . Repairs with the highest incidence of JET were arterial switch operation ( 3/13 , 23 % ) , atrioventricular ( AV ) canal repair ( 4/19 , 21 % ) , and Norwood repair ( 2/10 , 20 % ) . Compared to patients with no arrhythmias , patients with JET were more likely to be younger ( 2.75 ± 2.44 vs 5.38 ± 7.25 years , p < 0.01 ) , have had longer cardiopulmonary bypass times ( 126 ± 50 vs 85 ± 73 , p < 0.01 ) , and have a higher inotrope score ( 6.26 ± 7.55 vs 2.41 ± 8.11 , p < 0.01 ) . By multivariate analysis , ischemic time was the only factor associated with JET [ odds ratio , 1.01 ( confidence interval , 1.005–1.02 ) ; p = 0.0014 ) . The presence of JET did not correlate with electrolyte abnormalities . JET is not necessarily related to surgery near the His bundle or hypomagnesemia . Longer ischemic time is the best predictor of JET . Patients undergoing arterial switch operation , AV canal repair , and Norwood repair are at highest risk of postoperative JET and should be considered for prophylactic therapy Background : Junctional ectopic tachycardia occurs frequently after congenital cardiac surgery and can be a cause of increased morbidity and mortality . Dexmedetomidine ( DEX ) is an α2 adrenoreceptor agonist , has properties of controlling tachyarrhythmia by regulating the sympatho-adrenal system . Objective : To evaluate the efficacy of DEX for control of junctional ectopic tachycardia after repair of Tetralogy of Fallot ( TOF ) . Material s and Methods : Two hundred and twenty pediatric cardiac patients with TOFs were enrolled in a prospect i ve r and omized control study . Patients underwent correction surgery . They were divided into two groups , i.e. , Group 1 ( DEX ) and Group 2 ( control ) . Heart rate , rhythm , mean arterial pressure ( MAP ) were recorded after the anesthetic induction ( T1 ) , after termination of bypass ( T2 ) , after 04 hours ( T3 ) , and 08 hours after transferring the patient to intensive care unit ( ICU ; T4 ) . Results : Heart rate was comparable between two groups before starting the drug but statistically significant after bypass until 08 hours after transferring the patient to ICU . Junctional ectopic tachycardia occurred more in Group-2 ( 20 % ) as compared to Group-1 ( 9.09 % ; P = 0.022 ) . Junctional ectopic tachycardia occurs early in Group-2 ( 0.14 ± 0.527 hours ) as compared to Group 1 ( 0.31 ± 1.29 hours ; P = 0.042 ) . The duration of junctional ectopic tachycardia was more prolonged in Group-2 ( 1.63 ± 3.64 hours ) as compared to Group-1 ( 0.382 ± 1.60 hours ; P = 0.012 ) . The time to withdraw from mechanical ventilation and ICU stay of Group 1 patient was less than of Group 2 patients ( P = < 0.001 ) . Conclusion : DEX had a therapeutic role in the prevention of junctional ectopic tachycardia in patients undergoing repair for TOF OBJECTIVE Early postoperative arrhythmias are a known complication of cardiac surgery ; however , little data exists specific to pediatrics . The purpose of this study was to determine the incidence and risk factors associated with the development of arrhythmias immediately after surgery in a pediatric population . METHODS Data were collected in a prospect i ve observational format from pediatric patients undergoing cardiac surgery between September 2000 and May 2003 . This format included age , anatomy , surgical repair , and serum magnesium and calcium levels , as well as cardiopulmonary bypass and aortic crossclamp times . Patients were continuously monitored , and hemodynamically significant arrhythmias were recorded . RESULTS Arrhythmias occurred in 28 of the 189 patients enrolled ( 15 % ) including 16 with junctional ectopic tachycardia , 7 with complete atrioventricular block , 4 with ventricular tachycardia , and 1 with re-entrant supraventricular tachycardia . Significant differences were found between the arrhythmia and nonarrhythmia groups with regard to age ( 22 vs 45 months ) , cardiopulmonary bypass time ( 189 vs 109 minutes ) , and aortic crossclamp time ( 105 vs 44 minutes ) ; P < .05 . Magnesium and calcium levels were not significantly different between the groups . Two repairs carried an increased risk : complete atrioventricular septal defect repair , 8 of 11 patients ( 72 % ) , and the arterial switch 5 of 8 patients ( 62.5 % ) ; P < .05 . Atrioventricular septal defects had an even higher incidence when controlled for age , bypass time , and crossclamp time ( odds ratio = 7.65 ) . CONCLUSIONS Hemodynamically significant postoperative arrhythmias are a frequent complication of pediatric cardiac surgery . Younger age and longer bypass and crossclamp times are risk factors for arrhythmia . In addition , the repair of atrioventricular septal defects carries an independent risk of arrhythmias Background : Dexmedetomidine has been reported to have a renal protective effect after adult open heart surgery . The authors hypothesized that intraoperative infusion of dexmedetomidine would attenuate the decrease in renal function after pediatric open heart surgery . Methods : Twenty-nine pediatric patients ( 1–6 years ) scheduled for atrial or ventricular septal defect repair were r and omly assigned to receive either continuous infusion of normal saline ( control group , n = 14 ) or dexmedetomidine ( a bolus dose of 0.5 & mgr;g/kg and then an infusion of 0.5 & mgr;g/kg/h ) ( dexmedetomidine group , n = 15 ) from anesthesia induction to the end of cardiopulmonary bypass . Serum creatinine ( Scr ) was measured before surgery ( T0 ) , 10 minutes after anesthesia induction ( T1 ) , 5 minutes after cardiopulmonary bypass weaning ( T2 ) , 2 hours after T2 ( T3 ) , and after postoperative day 1 ( POD1 ) and postoperative day 2 ( POD2 ) and estimated glomerular filtration rates ( eGFRs ) were calculated . Renal biomarkers were measured at T1 , T2 , and T3 . Acute kidney injury ( AKI ) was defined as an absolute increase in Scr of ≥ 0.3 mg/dL or a percent increase in Scr of ≥50 % . Results : The incidence of AKI during the perioperative period was significantly higher in the control group than in the dexmedetomidine group ( 64 % [ 9/14 ] vs 27 % [ 4/15 ] , P = .042 ) . eGFR was significantly lower in the control group than in the dexmedetomidine group at T2 ( 72.6 ± 15.1 vs 83.9 ± 13.5 , P = .044 ) and T3 ( 73.4 ± 15.4 vs 86.7 ± 15.9 , P = .03 ) . Conclusion : Intraoperative infusion of dexmedetomidine may reduce the incidence of AKI and suppress post-bypass eGFR decline Abstract Postoperative arrhythmia is a common complication after open heart surgery in children . JET is the most common and dangerous arrhythmia . We aim ed to assess safety and efficacy of prophylactic amiodarone in preventing JET in children underwent cardiac surgery and to assess risk factors for JET among our patients . In total , 117 children who underwent cardiac surgery for CHD at Tanta University Hospital from October 2011 to April 2015 were divided in two groups ; amiodarone group ( 65 patients ) was given prophylactic amiodarone intraoperatively and placebo group ( 52 patients ) . Amiodarone is started as loading dose of 5 mg/kg IV in the operating room after induction of anesthesia and continued for 3 days as continuous infusion 10–15 μg/kg/min . Primary outcome and secondary outcomes of amiodarone administration were reported . We studied pre- , intra- and postoperative factors to determine risk factors for occurrence of JET among these children . Prophylactic amiodarone was found to significantly decrease incidence of postoperative JET from 28.9 % in placebo group to 9.2 % in amiodarone group , and symptomatic JET from 11.5 % in placebo group to 3.1 % in amiodarone group , and shorten postoperative intensive care unit and hospital stay without significant side effects . Risk factors for occurrence of JET were younger age , lower body weight , longer cardiopulmonary bypass , aortic cross-clamp time , hypokalemia , hypomagnesemia , acidosis and high dose of inotropes . JET was more associated with surgical repair of right ventricular outlet obstruction as in case of tetralogy of Fallot and pulmonary stenosis . Most of JET 15/21 ( 71.4 % ) occurred in the first day postoperatively , and 6/21 occurred in the second day ( 28.6 % ) . Prophylactic amiodarone is safe and effective in preventing early JET in children after open heart surgery This research determined the safety and efficacy of two small-dose infusions of dexmedetomidine by evaluating sedation , analgesia , cognition , and cardiorespiratory function . Seven healthy young volunteers provided informed consent and participated on three occasions with r and om assignment to drug or placebo . Heart rate , blood pressure , respiratory rate , ETCO2 , O2 saturation , and processed electroencephalogram ( bispectral analysis ) were monitored . Baseline hemodynamic measurements were acquired , and psychometric tests were performed ( visual analog scale for sedation ; observer ’s assessment of alertness/sedation scale ; digit symbol substitution test ; and memory ) . The pain from a 1-min cold pressor test was quantified with a visual analog scale . After a 10-min initial dose of saline or 6 & mgr;g · kg−1 · h−1 dexmedetomidine , volunteers received 50-min IV infusions of saline , or 0.2 or 0.6 & mgr;g · kg−1 · h−1 dexmedetomidine . Measurements were repeated at the end of infusion and during recovery . The two dexmedetomidine infusions result ed in similar and significant sedation ( 30%–60 % ) , impairment of memory ( approximately 50 % ) , and psychomotor performance ( 28%–41 % ) . Hemodynamics , oxygen saturation , ETCO2 , and respiratory rate were well preserved throughout the infusion and recovery periods . Pain to the cold pressor test was reduced by 30 % during dexmedetomidine infusion . Small-dose dexmedetomidine provided sedation , analgesia , and memory and cognitive impairment . These properties might prove useful in a postoperative or intensive care unit setting . Implication s : The & agr;2 agonist , dexmedetomidine , has sedation and analgesic properties . This study quantified these effects , as well as cardiorespiratory , memory and psychomotor effects , in healthy volunteers . Dexmedetomidine infusions result ed in reversible sedation , mild analgesia , and memory impairment without cardiorespiratory compromise BACKGROUND Postoperative tachyarrhythmias remain a common complication after congenital cardiac operations . Dexmedetomidine ( DEX ) , an α-2 adrenoreceptor agonist , can have a therapeutic role in supraventricular tachyarrhythmias for cardioversion to sinus rhythm or heart rate control . Whether routine perioperative use of DEX decreases the incidence of supraventricular and ventricular tachyarrhythmias was studied . METHODS In this prospect i ve cohort study , 32 pediatric patients undergoing cardiothoracic operations received DEX and were compared with 20 control patients who did not receive DEX . RESULTS Dexmedetomidine was started after anesthesia induction and continued intraoperatively and postoperatively for 38±4 hours ( mean dose , 0.76±0.04 μg/kg/h ) . Ten control patients and 2 DEX patients sustained 16 episodes of tachyarrhythmias ( p=0.001 ) , including a 25 % vs 0 % ( p=0.01 ) incidence of ventricular tachycardia and 25 % vs 6 % ( p=0.05 ) of supraventricular arrhythmias in the control and DEX group , respectively . Transient complete heart block occurred in 2 control patients and in 1 DEX patient . Control patients had a higher heart rate ( 141±5 vs 127±3 beats/min , p=0.03 ) , more sinus tachycardia episodes ( 40 % vs 6 % ; p=0.008 ) , required more antihypertensive drugs with nitroprusside ( 20±7 vs 4±1 μg/kg ; p=0.004 ) and nicardipine ( 13±5 vs 2±1 μg/kg ; p=0.02 ) , and required more fentanyl ( 39±8 vs 19±3 μg/kg ; p=0.005 ) . CONCLUSIONS Perioperative use of dexmedetomidine is associated with a significantly decreased incidence of ventricular and supraventricular tachyarrhythmias , without significant adverse effects |
1,716 | 19,821,432 | This retrospective study compared percutaneous cryotherapy with percutaneous radiofrequency .
Both severe and non-severe adverse events were reported , but the true nature and extent of harm was difficult to asses .
At present , there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma . | BACKGROUND Hepatocellular carcinoma is the most common primary malignant cancer of the liver .
Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial .
OBJECTIVES The aim of this review is to evaluate the potential benefits and harms of cryotherapy for the treatment of hepatocellular carcinoma . | BACKGROUND The majority of patients with primary or metastatic malignancies confined to the liver are not c and i date s for resection because of tumor size , location , multifocality , or inadequate functional hepatic reserve . Cryoablation has become a common treatment in select groups of these patients with unresectable liver tumors . However , hepatic cryoablation is associated with significant morbidity . Radiofrequency ablation ( RFA ) is a technique that destroys liver tumors in situ by localized application of heat to produce coagulative necrosis . In this study , we compared the complication and early local recurrence rates in patients with unresectable malignant liver tumors treated with either cryoablation or RFA . PATIENTS AND METHODS Patients with hepatic malignancies were entered into two consecutive prospect i ve , nonr and omized trials . The liver tumors were treated intraoperatively with cryoablation or RFA ; intraoperative ultrasonography was used to guide placement of cryoprobes or RFA needles . All patients were followed up postoperatively to assess complications , treatment response , and local recurrence of malignant disease . RESULTS Cryoablation was performed on 88 tumors in 54 patients , and RFA was used to treat 138 tumors in 92 patients . Treatment-related complications , including 1 postoperative death , occurred in 22 of the 54 patients treated with cryoablation ( 40.7 % complication rate ) . In contrast , there were no treatment-related deaths and only 3 complications after RFA ( 3.3 % complication rate , P<0.001 ) . With a median follow-up of 15 months in both patient groups , tumor has recurred in 3 of 138 lesions treated with RFA ( 2.2 % ) , versus 12 of 88 tumors treated with cryoablation ( 13.6 % , P<0.01 ) . CONCLUSIONS RFA is a safe , well-tolerated treatment for patients with unresectable hepatic malignancies . This study indicates that ( 1 ) complications occur much less frequently following RFA of liver tumors compared with cryoablation of liver tumors , and ( 2 ) early local tumor recurrence is infrequent following RFA OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials HYPOTHESIS The complication and success rates in patients treated with either percutaneous cryosurgery ( PCS ) or percutaneous radiofrequency ( PRF ) for unresectable hepatic malignancies are similar . DESIGN Retrospective study . SETTING University hospital . PATIENTS AND METHODS Sixty-four patients were treated with either PCS ( n = 31 ) or PRF ( n = 33 ) . Patient treatment was based on the r and om availability of the probes . Tumors were evaluated by a blinded comparison of pretreatment and posttreatment helical computed tomographic scans . All living patients had at least a 6-month follow-up . MAIN OUTCOME MEASURES Complication rate , initial treatment success ( complete devascularization of the tumor ) , and local recurrence ( tumor revascularization within or at its periphery ) . RESULTS The distribution of tumor types was similar in the 2 groups ( P = .76 ) . One patient with cirrhosis died of variceal hemorrhage on day 30 after PCS ( mortality , 3.2 % ) , while no mortality was observed after PRF ( P = .48 ) . Complications occurred in 9 ( 29 % ) of the patients following PCS and in 8 ( 24 % ) of the patients following PRF ( P = .66 ) . Initial treatment success was comparable in the 2 treatment groups ( 30 [ 83 % ] of 36 tumors following PCS vs 34 [ 83 % ] of 41 tumors following PRF ) . However , local recurrences occurred more frequently after PCS than after PRF ( 16 [ 53 % ] of 30 vs 6 [ 18 % ] of 34 ; P = .003 ) . The higher rate of local recurrence was identified for metastases ( 10 [ 71 % ] of 14 after PCS vs 3 [ 19 % ] of 16 after PRF ; P = .004 ) , while the difference was not significant for hepatocellular carcinoma ( 6 [ 38 % ] of 16 after PCS vs 3 [ 17 % ] of 18 after PRF ; P = .25 ) . Multivariate analysis demonstrated that the use of PCS ( P = .003 ) and more than 1 treatment ( P = .05 ) were independent risk factors for local tumor recurrence . CONCLUSION While similar initial treatment success and complication rates are observed following either PCS or PRF , local recurrences occur more frequently following PCS , particularly for metastases BACKGROUND Thermal ablation of unresectable hepatic tumors can be achieved by cryosurgical ablation ( CSA ) or radiofrequency ablation ( RFA ) . The relative advantages and disadvantages of each technique have not yet been determined . HYPOTHESIS Radiofrequency ablation of malignant hepatic neoplasms can be performed safely , but is currently limited by size . Cryosurgical ablation , while associated with higher morbidity , is more effective for larger unresectable hepatic malignant neoplasms . DESIGN Retrospective analysis of prospect i ve patient data base . PATIENTS AND METHODS Between July 1992 and September 1999 , 308 patients with liver tumors not amenable to curative surgical resection were treated with CSA and /or RFA ( percutaneous , laparoscopic , celiotomy ) . No patient had preoperative evidence of extrahepatic disease . All patients underwent laparoscopy with intraoperative ultrasound if technically possible . Both RFA and CSA were performed under ultrasound guidance . Resection , as an adjunctive procedure , was combined with ablation in certain patients . RESULTS Laparoscopy identified extrahepatic disease in 12 % of patients , and intraoperative hepatic ultrasound identified additional lesions in 33 % of patients , despite extensive preoperative imaging . Radiofrequency ablation alone or combined with resection or CSA result ed in reduced blood loss ( P<.05 ) , thrombocytopenia ( P<.05 ) , and shorter hospital stay compared with CSA alone ( P<.05 ) . Median ablation times for lesions greater than 3 cm were 60 minutes with RFA and 15 minutes with CSA ( P<.001 ) . Local recurrence rates for lesions greater than 3 cm were also greater with RFA ( 38 % vs 17 % ) . CONCLUSIONS Laparoscopy and intraoperative ultrasound are essential in staging patients with hepatic malignant neoplasms . Radiofrequency ablation when combined with CSA reduces the morbidity of multiple freezes . Although RFA is safer than CSA and can be performed via different approaches ( percutaneously , laparoscopically , or at celiotomy ) , it is limited by tumor size ( <3 cm ) . Percutaneous RFA should be considered in high-risk patients or those with small local recurrences BACKGROUND / AIMS This study aim ed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy , particularly in relation to the presence or absence of underlying cirrhosis , hepatitis virus marker patterns , age of the subjects and alpha-foetoprotein values . METHODS A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study . Both newly diagnosed cases ( incident cases ) and cases diagnosed before May 1996 but still attending the hospitals during the study period ( prevalent cases ) were included . RESULTS We found that 71.1 % of cases were positive for hepatitis C virus antibodies but negative for HBsAg ; in contrast , 11.5 % were negative for anti-HCV but positive for HBsAg ; 5.3 % were positive for both markers ; and 12.1 % were negative for both viruses . The mean age of detection was over 60 years , with a younger mean age in HBsAg-positive compared to anti-HCV-positive patients ( 59.3 years vs. 65.6 years , p<0.01 ) . The male-to-female ratio among HBsAg-positive patients was 10.4:1 , in contrast to 2.8:1 among anti-HCV-positive patients ( p<0.01 ) . The majority of cases ( 93.1 % ) had underlying cirrhosis . Cirrhotic patients were more likely to be anti-HCV positive than non-cirrhotic cases ( 73.2 % vs 43.9 % ; p<0.01 ) ; conversely , absence of hepatitis virus markers was more frequently observed in the non-cirrhotic than in the cirrhotic population ( 40.9 % vs. 10.0 % ; p<0.01 ) . Overall , the alpha-foetoprotein level was altered ( > 20 ng/ml ) in 57.9 % of patients ; only 18 % of cases presented diagnostic ( > 400 ng/ml ) values . Anti-HCV positivity ( O.R. 2.0 ; CI 95%=1.3 - 3.1 ) but not HBsAg positivity ( O.R. 1.0 ; CI 95%=0.6 - 1.8 ) was shown to be an independent predictor of the likelihood of altered alpha-foetoprotein values by multivariate analysis . CONCLUSIONS These findings point to differences in the characteristics of the population s infected by hepatitis B and hepatitis C. Factors other than the hepatitis viruses are important in non-cirrhotic patients . A change in the relative prevalence of hepatitis virus markers among hepatocellular carcinoma cases was demonstrated , reflecting a significant change in the rate of HBV endemicity in the Italian population . Finally , the increased trend in the mortality rate from liver cancer in Italy from 4.8 per 100,000 in 1969 to 10.9 in 1994 may reflect the large cohort of subjects infected with HCV via the iatrogenic route during 1950s and 1960s when glass syringes were commonly used for medical treatment Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . OBJECTIVE The authors evaluate the results of cryosurgery in malignant liver tumors . SUMMARY BACKGROUND DATA The outcome of primary or secondary liver tumors is poor when resection can not be achieved . Encouraging results of cryosurgery have been reported in unresectable liver tumors , but this treatment needs further evaluation of its efficacy in homogeneous groups of patients . METHODS From 63 patients with malignant liver tumors with various histology treated by cryosurgery in a 2.5-year period , the authors evaluated the results of 34 patients with nonresectable hepatocellular carcinoma ( 9 patients ) or nonresectable metastases from colorectal cancer ( 25 patients ) . Cryosurgery was used either as a single treatment ( 4 hepatocellular carcinomas , 5 metastases ) or in association with liver resection ( 5 hepatocellular carcinomas , 20 metastases ) . Systemic chemotherapy was used routinely before surgery and after surgery . RESULTS There was no intraoperative mortality . Mortality within 2 months was 3 % and was unrelated to the procedure . Postoperative morbidity consisted of one sterile fluid collection and one biliary fistula ( 8 % ) . At a mean follow-up of 16 months , ( range , 2 - 27 ) local recurrence rate was 0 % for hepatocellular carcinoma and 44 % for metastases . Cumulative survival at 24 months was 63 % and 52 % , respectively , with 6 patients ( 67 % ) and 5 patients ( 20 % ) currently disease free . In the group of patients with metastases , survival was related to the size of the treated tumor ( p = 0.06 ) and the absence of residual disease ( p = 0.03 ) . CONCLUSIONS Cryosurgery is safe and increases the number of patients with unresectable liver malignancies in whom surgery can aim at eradicating the tumor . Local recurrence is observed more frequently for metastases than for hepatocellular carcinoma . The benefit in survival is related to the complete treatment of the tumoral disease |
1,717 | 23,060,602 | It was found that there was good support for wraparound services and relational interventions , but little support for widely used carer training programmes . | Foster care is a complex setting in which to provide therapeutic interventions due to the high rates of difficulty , poor outcomes and high numbers of professionals and carers involved .
This systematic review aims to examine interventions that have been empirically assessed in foster care . | The current study was design ed to explore the use of behavioral ( i.e. , accuracy and reaction times ) and electrophysiological measures ( i.e. , event-related potentials ) to assess the impact of a family-based preventive intervention for preschool-aged , maltreated children in foster care . These measures were recorded during a computerized flanker task design ed to assess cognitive control and response monitoring . The sample was recruited from a larger r and omized efficacy trial of Multidimensional Treatment Foster Care for Preschoolers ( MTFC-P ) and included foster children assigned to the intervention condition ( n = 10 ) , foster children assigned to a services-as-usual comparison condition ( n = 13 ) , and low-income , nonmaltreated community children ( n = 11 ) . The children ’s behavioral and electrophysiological performance on the task was generally consistent with previous research with adults and older children . There were no group differences on the behavioral measures of cognitive control or response monitoring . Notably , however , group differences were observed on the electrophysiological measures of response monitoring . Specifically , the foster children who received services as usual were significantly less responsive to performance feedback about errors than the foster children who received the intervention and the nonmaltreated children . Applications of this methodology and implication s of the results for future prevention research are discussed The relative effectiveness of group care ( GC ) and multidimensional treatment foster care ( MTFC ) was compared in terms of their impact on criminal offending , incarceration rates , and program completion outcomes for 79 male adolescents who had histories of chronic and serious juvenile delinquency . Results show that boys who participated in MTFC had significantly fewer criminal referrals and returned to live with relatives more often . Multiple regression analyses showed that assignment to a treatment condition ( i.e. , GC or MTFC ) predicted official and self-reported criminality in follow-up beyond other well-known predictors of chronic juvenile offending ( i.e. , age at 1st offense , number of previous offenses , age at referral ) The purpose of this study was to evaluate the effectiveness of a 2-component intervention for biological and foster parent ( pairs ) to improve parenting practice s , co-parenting , and child externalizing problems . Participants were biological and foster parents ( N=128 ) of primarily neglected children ( ages 3 to 10 years ) placed in regular foster homes . Biological and foster parents were r and omly assigned in pairs to the intervention ( n=80 ) or a usual care ( n=48 ) condition . Intervention families received a 12-week parenting course ( Incredible Years ) and a newly developed co-parenting component . Key findings included significant gains in positive parenting and collaborative co-parenting for both biological and foster parents at the end of the intervention . At follow-up , intervention parents sustained greater improvement in positive parenting , showed gains in clear expectations , and reported a trend for fewer child externalizing problems . Findings supported the feasibility of offering joint parenting training to meet the needs of participating families and demonstrated that the co-parenting construct applied to families in the foster care system was amenable to intervention Young children who enter foster care experience disruptions in care and maltreatment at a point when maintaining attachment relationships is a key , biologically based task . In previous research , we have found that young children experience challenges as they form attachments with new caregivers . They tend to push their new caregivers away , even though such children are especially in need of nurturing care . Further , many caregivers do not respond in nurturing ways when their children are distressed , which we have found is problematic for young children in foster care . We developed an intervention that is design ed to help caregivers provide nurturance even when children do not elicit it , and even when it does not come naturally to them . This paper presents preliminary findings of the effectiveness of this intervention on children ’s attachment behaviors . Forty-six children were r and omly assigned to either the experimental intervention or to an educational intervention . For three consecutive days , attachment behaviors were reported across three distress-eliciting situations . Children whose parents had received the experimental intervention showed significantly less avoidance than children whose parents had received the educational intervention . These preliminary results suggest that the intervention is successful in helping children develop trusting relationships with new caregivers Studies with nonhuman primates and rodents , as well as with human children , have suggested that early separations from caregivers are often associated with changes in the functioning of the hypothalamus-pituitary-adrenal ( HPA ) axis . On the basis of these findings , we design ed a relational intervention that was intended to normalize HPA functioning among children in foster care . This paper presents findings from a r and omized clinical trial that assessed the effectiveness of a relational intervention ( Attachment and Biobehavioral Catch-up [ ABC ] ) with regard to HPA functioning . The ABC intervention was intended to enhance children 's ability to regulate physiology and behavior . The control intervention ( Developmental Education for Families ) was intended to enhance children 's cognitive skills . A comparison group of children who had never been in foster care was also included . Children 's cortisol production was assessed upon arrival at the lab , and 15 and 30 min following the Strange Situation . R and om effects analyses of variance were performed to assess differences in initial values and change between children in the two intervention groups . Children in the ABC intervention and comparison group children showed lower initial values of cortisol than children in the treatment control group , considering arrival at lab as initial values ( p < .05 ) . Groups did not differ significantly in change over time . These results suggest that the ABC intervention is effective in helping children regulate biology in ways more characteristic of children who have not experienced early adversity Placement disruptions undermine efforts of child welfare agencies to promote safety , permanency , and child well-being . Child behavior problems significantly contribute to placement changes . The aims of this investigation were to examine the impact of a foster parent training and support intervention ( KEEP ) on placement changes and to determine whether the intervention mitigates placement disruption risks associated with children 's placement histories . The sample included 700 families with children between ages 5 and 12 years , from a variety of ethnic background s. Families were r and omly assigned to the intervention or control condition . The number of prior placements was predictive of negative exits from current foster placements . The intervention increased chances of a positive exit ( e.g. , parent/child reunification ) and mitigated the risk-enhancing effect of a history of multiple placements . Incorporating intervention approaches based on a parent management training model into child welfare services may improve placement outcomes for children in foster care The lack of prepared and available foster parents for children with prenatal substance effects is of increasing concern to the child welfare field . The research study reported here evaluated a multimodal inservice training program design ed to enhance the competency of foster parents caring for infants with prenatal substance effects , and to promote an intent to foster such infants . Findings suggest that future foster parent training efforts in this area should focus on knowledge and skill attainment AIMS To evaluate the impact of training foster carers on children 's emotional and behavioural functioning . METHODS In a r and omised controlled trial in 17 Scottish local council areas , with immediate and nine month follow up , 182 children and their foster families were r and omly allocated to either st and ard services alone or st and ard services plus extra training for foster carers on communication and attachment . Main outcome measures were child psychopathology , attachment disorder , self esteem , and cost of foster care . RESULTS Over 60 % of children had measurable psychopathology at baseline . The training was perceived as beneficial by participants . Scores for parent reported psychopathology and attachment disorders decreased by around 5 % , self esteem increased by 2 % , and costs by 22 % in the intervention group . Results were non-significant . CONCLUSIONS Despite being well received by foster carers , the training was not sufficient to make a useful impact on the high level of psychopathology . This group may warrant more intensive interventions Abstract This study examined change in attachment-related behaviors among foster preschoolers participating in a r and omized trial of the Multidimensional Treatment Foster Care Program for Preschoolers ( MTFC-P ) . Measures of secure , resistant , and avoidant behaviors were collected using a caregiver-report diary at 3-month intervals during the 12 months following a new foster placement . Children r and omly assigned to the MTFC-P intervention condition ( n = 57 ) showed significant increases in secure behavior and significant decreases in avoidant behavior relative to children assigned to a regular foster care condition ( n = 60 ) . Both groups showed significant decreases in resistant behavior over time . Analyses also revealed a significant interaction between treatment condition and age at first foster placement on change in secure behavior . Results are discussed in terms of the importance of early intervention and prevention services for foster preschoolers Parent training for foster parents is m and ated by federal law and supported by state statues in nearly all states ; however , little is known about the efficacy of that training , and recent review s underscore that the most widely used curricula in the child welfare system ( CWS ) have virtually no empirical support ( Grimm , Youth Law News , April – June:3–29 , 2003 ) . On the other h and , numerous theoretically based , developmentally sensitive parent training interventions have been found to be effective in experimental clinical and prevention intervention trials ( e.g. , Kazdin and Wassell , Journal of the American Academy of Child and Adolescent Psychiatry , 39:414–420 , 2000 ; McMahon and Foreh and , Helping the noncompliant child , Guilford Press , New York , USA , 2003 ; Patterson and Forgatch , Parents and adolescents : I. Living together , Castalia Publishing , Eugene , OR , USA , 1987 ; Webster-Stratton et al. , Journal of Clinical Child Pyschology Psychiatry , 42:943–952 , 2001 ) . One of these , Multidimensional Treatment Foster Care ( MTFC ; Chamberlain , Treating chronic juvenile offenders : Advances made through the Oregon Multidimensional Treatment Foster Care model , American Psychological Association , Washington , DC , USA , 2003 ) , has been used with foster parents of youth referred from juvenile justice . The effectiveness of a universal intervention , KEEP ( Keeping Foster Parents Trained and Supported ) based on MTFC ( but less intensive ) was tested in a universal r and omized trial with 700 foster and kinship parents in the San Diego County CWS . The goal of the intervention was to reduce child problem behaviors through strengthening foster parents ’ skills . The trial was design ed to examine effects on both child behavior and parenting practice s , allowing for specific assessment of the extent to which improvements in child behavior were mediated by the parenting practice s targeted in the intervention . Child behavior problems were reduced significantly more in the intervention condition than in the control condition , and specific parenting practice s were found to mediate these reductions , especially for high-risk children in foster families reporting more than six behavior problems per day at baseline Most foster parents in the United States are required to participate in training , yet no empirical support exists for the training 's effectiveness . During the past two decades , high- quality clinical trials have documented that parent management training ( PMT ) programs produce positive outcomes for children and families in clinical and school setting s ; yet , these advances have not transferred to foster/kinship parents . Here , we describe a r and omized control trial testing the effectiveness of a PMT-based treatment with 700 foster/kinship parents in San Diego County . The collaborative processes to engage stakeholders , the strategies for involving parents , and the results of two levels of developer involvement in training and supervision on child behavioral outcomes are also described 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 OBJECTIVE To determine the effectiveness of an intervention design ed to improve outcomes for infants and toddlers in foster care . METHOD Records were review ed for all children who were adjudicated as in need of care in a specific parish in Louisiana between 1991 and 1998 . This period included 4 years before and 4 years after a comprehensive intervention was implemented . Children adjudicated between 1991 and 1994 were the comparison group , and those adjudicated between 1995 and 1998 were the intervention group . RESULTS After the intervention , more children were freed for adoption and fewer children were returned to their birth families than before the intervention . There was no difference in length of time in care before and after the intervention . With regard to the same child returning in a subsequent incident of maltreatment , relative risk reduction for the intervention group ranged from 53 % to 68 % . With regard to the same mother maltreating another child subsequently , relative risk reduction for the intervention group ranged from 63 % to 75 % . CONCLUSIONS A comprehensive preventive intervention for maltreated infants and toddlers in foster care substantially reduced rates of recidivism but had no effect on length of time in care Foster children are at great risk for poor school outcomes . Given that school readiness is a powerful predictor of later school success , the promotion of school readiness skills in foster children is an opportunity for preventive intervention . Results are presented from a preliminary evaluation of a program design ed to improve school readiness in foster children . Twenty-four foster children were r and omly assigned to the intervention or comparison conditions . The intervention consisted of therapeutic playgroups ( twice weekly for 7 weeks during the summer ) focusing on social competence and self-regulation skills . Attendance rates for the playgroups are reported . In addition , group differences on data collected before and after the intervention are reported . Intervention group children exhibited increased social competence and self-regulation . Comparison group children exhibited poorer performance in these domains over time . Results are discussed in terms of how the study has informed a current r and omized efficacy trial of a school-readiness intervention Foster children exhibit high rates of atypical neuroendocrine functioning compared to children in the general population . In particular , alterations in the daytime diurnal activity of the hypothalamic-pituitary-adrenal ( HPA ) axis have been observed in foster children , often characterized by blunted salivary cortisol levels ( i.e. , low morning levels that remain low throughout the day ) . There is emerging evidence that therapeutic interventions for foster children can affect this pattern of HPA axis activity , but the specific intervention components responsible for change have not been fully explicated . Within a r and omized trial to evaluate a therapeutic intervention for foster preschoolers ( n = 57 intervention condition ; n = 60 comparison condition ; n = 60 community comparison condition ) , the present study examined whether diurnal cortisol activity was associated with caregiver self-reported stress in response to child problem behavior . Results showed immediate reductions in caregiver stress that were sustained through 12 months postbaseline in the intervention condition . In contrast , caregivers in the regular foster care condition showed higher rates of stress across time and increased stress sensitivity to child problem behaviors . In addition , among caregivers in regular foster care , higher self-reported stress was associated with lower morning cortisol levels and more blunted diurnal cortisol activity . These results provide evidence that interventions can simultaneously impact caregiver stress and buffer children from the negative impacts of caregiver stress on HPA axis regulation Preschool-aged foster children face multiple risks for poor long-term outcomes . These risks appear to increase with the number of placement changes experienced . The Early Intervention Foster Care Program ( EIFC ) targets the spectrum of challenges that preschool-aged foster children face via a team approach delivered in home and community setting s. In this article , we report on permanent placement outcomes from the EIFC r and omized clinical trial . Children in EIFC had significantly fewer failed permanent placements than children in the regular foster care comparison condition . The number of prior placements was positively associated with the risk of failed permanent placements for children in the comparison condition but not for children in EIFC . Type of prior maltreatment did not predict permanent placement outcomes . These results provide the foundation of an evidence base for the EIFC program as a preventive intervention to improve permanent placement outcomes for preschool-aged foster children The effectiveness of a parenting program with 394 Head Start mothers was examined . Nine Head Start centers were r and omly assigned to either an experimental condition in which parents , teachers , and family service workers participated in the intervention or a control condition in which the regular Head Start program was offered . Mothers in the intervention group were observed at home to have significantly fewer critical remarks and comm and s , to use less harsh discipline , and to be more positive and competent in their parenting when compared with control mothers . Teachers reported that intervention mothers were more involved in their children 's education and that their children were more socially competent . Intervention children were observed to exhibit significantly fewer conduct problems , less noncompliance , less negative affect , and more positive affect than control children . One year later most of the improvements were maintained Atypical diurnal patterns of hypothalamic-pituitary-adrenal ( HPA ) axis activity have been observed in sample s of individuals following early life adversity . A characteristic pattern arising from disrupted caregiving is a low early-morning cortisol level that changes little from morning to evening . Less well understood is the plasticity of the HPA axis in response to subsequent supportive caregiving environments . Monthly early-morning and evening cortisol levels were assessed over 12 months in a sample of 3 - 6-year-old foster children enrolled in a r and omized trial of a family-based therapeutic intervention ( N=117 ; intervention condition , n=57 ; regular foster care condition , n=60 ) , and a community comparison group of same-aged , non-maltreated children from low-income families ( n=60 ) . Latent growth analyses revealed stable and typical diurnal ( morning-to-evening ) cortisol activity among non-maltreated children . Foster children in the intervention condition exhibited cortisol activity that became comparable to the non-maltreated children over the course of the study . In contrast , children in regular foster care condition exhibited increasingly flattened morning-to-evening cortisol activity over the course of the study . In sum , improvements in caregiving following early adversity appear to have the potential to reverse or prevent disruptions in HPA axis functioning Children in foster care have social and emotional problems at rates three to ten times higher than those found in the general population . During the elementary school years ( i.e. 5 - 12 years ) , research indicates that disruptive behavior in children in care can negatively impact social , emotional and academic development , as well as placement stability . Evidence d-based interventions to improve children ’s behavior and reduce parenting stress are necessary . This pilot study augmented an existing evidence d-based intervention ( i.e. the Incredible Years ) developed for birth families for use with foster caregivers . Results from 18 families indicate that foster caregiver-reported conduct symptoms were significantly lower for children whose families participated in the treatment group . A similar trend was found for the overall externalizing behavior . No significant changes were identified in parenting attitudes and stress . Participants reported high levels of satisfaction and acceptability with the program and outcomes . These findings indicate that foster caregiver training should be examined in larger , r and omized control trials Abstract Objective : To see whether a behaviourally based group parenting programme , delivered in regular clinical practice , is an effective treatment for antisocial behaviour in children . Design : Controlled trial with permuted block design with allocation by date of referral . Setting : Four local child and adolescent mental health services . Participants : 141 children aged 3 - 8 years referred with antisocial behaviour and allocated to parenting groups ( 90 ) or waiting list control ( 51 ) . Intervention : Webster-Stratton basic videotape programme administered to parents of six to eight children over 13 - 16 weeks . This programme emphasises engagement with parental emotions , rehearsal of behavioural strategies , and parental underst and ing of its scientific rationale . Main outcome measures : Semistructured parent interview and question naires about antisocial behaviour in children administered 5 - 7 months after entering trial ; direct observation of parent-child interaction . Results : Referred children were highly antisocial ( above the 97th centile on interview measure ) . Children in the intervention group showed a large reduction in antisocial behaviour ; those in the waiting list group did not change ( effect size between groups 1.06 SD ( 95 % confidence interval 0.71 to 1.41 ) , P<0.001 ) . Parents in the intervention group increased the proportion of praise to ineffective comm and s they gave their children threefold , while control parents reduced it by a third ( effect size between groups 0.76 ( 0.16 to 1.36 ) , P=0.018 ) . If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16 % . Conclusions : Parenting groups effectively reduce serious antisocial behaviour in children in real life conditions . Follow up is needed to see if the children 's poor prognosis is improved and criminality prevented . What is already known on this topic Children who persistently display a high level of antisocial behaviour are at high risk of social rejection , juvenile delinquency , and long term unemployment ; the cost to society is high While some behaviourally based parenting programmes have been shown to be effective in university centre trials with volunteers or specially selected cases , most trials of psychological treatments for children in real life setting s have shown no effect What this study adds An evidence based intervention is available for use in regular clinical practice that effectively reduces antisocial behaviour in referred children The intervention works well with children at risk of criminality from a combination of highly antisocial behaviour , multiple psychopathology , and social |
1,718 | 32,271,923 | We confirm the importance of primary taste areas for gustatory processing in human adults .
We also provide tentative evidence for reward-related cau date activity in relation to the sweet taste of caloric sugars . | BACKGROUND The reward value of palatable foods is often cited as an important influence on eating behaviors , including intake of sugars .
However , human neuroimaging studies have generated conflicting evidence on the basic neural representation of taste and reward responses to caloric sweeteners ( sucrose and glucose ) , and most relevant studies have used small subject numbers .
OBJECTIVE We conducted a systematic review and a coordinate-based meta- analysis of studies reporting brain responses to oral sugar solutions . | Background The reward value of food is partly dependent on learned associations . It is not yet known whether replacing sugar with non-caloric sweeteners in food is affecting long-term acceptance . Objective To determine the effect of replacing sugar with non-caloric sweeteners in a nutrient-empty drink ( soft drink ) versus nutrient-rich drink ( yoghurt drink ) on reward value after repeated exposure . Design We used a r and omized crossover design whereby forty subjects ( 15 men , 25 women ) with a mean±SD age of 21±2 y and BMI of 21.5±1.7 kg/m2 consumed a fixed portion of a non-caloric sweetened ( NS ) and sugar sweetened ( SS ) versions of either a soft drink or a yoghurt drink ( counterbalanced ) for breakfast which were distinguishable by means of colored labels . Each version of a drink was offered 10 times in semi-r and om order . Before and after conditioning the reward value of the drinks was assessed using behavioral tasks on wanting , liking , and expected satiety . In a subgroup ( n=18 ) fMRI was performed to assess brain reward responses to the drinks . Results Outcomes of both the behavioral tasks and fMRI showed that conditioning did not affect the reward value of the NS and SS versions of the drinks significantly . Overall , subjects preferred the yoghurt drinks to the soft drinks and the ss drinks to the NS drinks . In addition , they expected the yoghurt drinks to be more satiating , they reduced hunger more , and delayed the first eating episode more . Conditioning did not influence these effects . Conclusion Our study showed that repeated consumption of a non-caloric sweetened beverage , instead of a sugar sweetened version , appears not to result in changes in the reward value . It can not be ruled out that learned associations between sensory attributes and food satiating capacity which developed preceding the conditioning period , during lifetime , affected the reward value of the drinks In this study , the representation of taste in the orbitofrontal cortex was investigated to determine whether or not a pleasant and an aversive taste have distinct or overlapping representations in this region . The pleasant stimulus used was sweet taste ( 1 M glucose ) , and the unpleasant stimulus was salt taste ( 0.1 M NaCl ) . We used an ON/OFF block design in a 3 T fMRI scanner with a tasteless solution delivered in the OFF period to control for somatosensory or swallowing-related effects . It was found that parts of the orbitofrontal cortex were activated ( P < 0.005 corrected ) by glucose ( in 6/7 subjects ) and by salt ( in 6/7 subjects ) . In the group analysis , separate areas of the orbitofrontal cortex were found to be activated by pleasant and aversive tastes . The involvement of the amygdala in the representation of pleasant as well as aversive tastes was also investigated . The amygdala was activated ( region of interest analysis , P < 0.025 corrected ) by the pleasant taste of glucose ( 5/7 subjects ) as well as by the aversive taste of salt ( 4/7 subjects ) . Activation by both stimuli was also found in the frontal opercular/insular ( primary ) taste cortex . We conclude that the orbitofrontal cortex is involved in processing tastes that have both positive and negative affective valence and that different areas of the orbitofrontal cortex may be activated by pleasant and unpleasant tastes . We also conclude that the amygdala is activated not only by an affectively unpleasant taste , but also by a taste that is affectively pleasant , thus providing evidence that the amygdala is involved in effects produced by positively affective as well as by negatively affective stimuli Vision provides a primary sensory input for food perception . It raises expectations on taste and nutritional value and drives acceptance or rejection . So far , the impact of visual food cues varying in energy content on subsequent taste integration remains unexplored . Using electrical neuroimaging , we assessed whether high- and low-calorie food cues differentially influence the brain processing and perception of a subsequent neutral electric taste . When viewing high-calorie food images , participants reported the subsequent taste to be more pleasant than when low-calorie food images preceded the identical taste . Moreover , the taste-evoked neural activity was stronger in the bilateral insula and the adjacent frontal operculum ( FOP ) within 100 ms after taste onset when preceded by high- versus low-calorie cues . A similar pattern evolved in the anterior cingulate ( ACC ) and medial orbitofrontal cortex ( OFC ) around 180 ms , as well as , in the right insula , around 360 ms . The activation differences in the OFC correlated positively with changes in taste pleasantness , a finding that is an accord with the role of the OFC in the hedonic evaluation of taste . Later activation differences in the right insula likely indicate revaluation of interoceptive taste awareness . Our findings reveal previously unknown mechanisms of cross-modal , visual-gustatory , sensory interactions underlying food evaluation Sensory-specific satiety , which is defined as a relative decrease in pleasantness , is increased by greater oro-sensory stimulation . Both sensory-specific satiety and pleasantness affect taste activation in the orbitofrontal cortex . In contrast , metabolic satiety , which results from energy intake , is expected to modulate taste activation in reward areas . The aim of this study was to determine the effects of the amount of oro-sensory stimulation and energy content on consumption-induced changes in taste activation . Ten men participated in a 2 × 2 r and omized crossover study . Subjects were scanned twice using functional magnetic resonance imaging : after fasting for at least 2h and after treatment , on four occasions . Treatment consisted of the ingestion of 450 mL of orangeade ( sweetened with 10 % sucrose or non-caloric sweeteners ) at 150 mL/min , with either small ( 5 mL ) or large ( 20 mL ) sips . During scanning , subjects alternately tasted orangeade , milk and tomato juice and rated its pleasantness . Before and after the scans , subjects rated pleasantness , prospect i ve consumption , desire to eat and sweetness for all tastants . Main findings were that , before treatment , the amygdala was activated more by non-caloric than by caloric orangeade . Caloric orangeade activated part of the striatum before , but not after treatment . We observed no main effects of sip size on taste activation and no interaction between sip size and caloric content . In conclusion , the brain responds differentially to caloric and non-caloric versions of a sweet drink and consumption of calories can modulate taste activation in the striatum . Further research is needed to confirm that the observed differences are due to caloric content and not to ( subliminal ) differences in the sensory profile . In addition , implication s for the effectiveness of non-caloric sweeteners in decreasing energy intake need to be established Research indicates that dysfunctional food reward processing may contribute to pathological eating behaviour . It is widely recognized that both the amygdala and the orbitofrontal cortex ( OFC ) are essential parts of the brain 's reward circuitry . The aims of this fMRI study were ( 1 ) to examine the effects of food deprivation and calorie content on reward processing in the amygdala and the OFC , and ( 2 ) to examine whether an explicit evaluation of foods is necessary for OFC , but not amygdalar activity . Addressing the first aim , healthy females were presented with high and low calorie food pictures while being either hungry or satiated . For the second aim , attention focus was manipulated by directing participants ' attention either to the food or to a neutral aspect . This study shows that hunger interacts with the energy content of foods , modulating activity in the posterior cingulate cortex , medial OFC , insula , cau date putamen and fusiform gyrus . Results show that satiated healthy females show an increased reward processing in response to low calorie foods . Confirming our hypothesis , food deprivation increased activity following the presentation of high calorie foods , which may explain why treatments of obesity energy restricting diets often are unsuccessful . Interestingly , activity in both the amygdala and mOFC was only evident when participants explicitly evaluated foods . However , attention independent activity was found in the mPFC following the high calorie foods cues when participants where hungry . Current findings indicate that research on how attention modulates food reward processing might prove especially insightful in the study of the neural substrates of healthy and pathological eating behaviour BACKGROUND A preference for sweet tastes has been repeatedly shown to be associated with alcohol preference in both animals and humans . In this study , we tested the extent to which recent drinking is related to blood oxygen level-dependent ( BOLD ) activation from an intensely sweet solution in orbitofrontal areas known to respond to primary rewards . METHODS Sixteen right-h and ed , non-treatment-seeking , healthy volunteers ( mean age : 26 years ; 75 % male ) were recruited from the community . All underwent a taste test using a range of sucrose concentrations , as well as functional magnetic resonance imaging ( fMRI ) during pseudor and om , event-driven stimulation with water and a 0.83 M concentration of sucrose in water . RESULTS [ Sucrose > water ] provoked a significant BOLD activation in primary gustatory cortex and amygdala , as well as in the right ventral striatum and in bilateral orbitofrontal cortex . Drinks/drinking day correlated significantly with the activation as extracted from the left orbital area ( r = 0.52 , p = 0.04 after correcting for a bilateral comparison ) . Using stepwise multiple regression , the addition of rated sucrose liking accounted for significantly more variance in drinks/drinking day than did left orbital activation alone ( multiple R = 0.79 , p = 0.002 ) . CONCLUSIONS Both the orbitofrontal response to an intensely sweet taste and rated liking of that taste accounted for significant variance in drinking behavior . The brain response to sweet tastes may be an important phenotype of alcoholism risk |
1,719 | 32,346,645 | Conclusions : CSP and HSP may result in the same complete resection rates for polyps ≤10 mm . | Objectives : Cold polypectomy ( CP ) is widely used because of its safety profile .
This systematic review and meta- analysis aim ed to clarify the indications for CP based on polyp size . | BACKGROUND AND AIMS Small colorectal polyps are encountered frequently and may be incompletely removed during colonoscopy . The optimal technique for removal of small colorectal polyps is uncertain . The aim of this study was to compare the incomplete resection rate ( IRR ) by using EMR or cold snare polypectomy ( CSP ) for the removal of small adenomatous polyps . METHODS This was a prospect i ve r and omized controlled study from a tertiary-care referral center . A total of 358 patients who satisfied the inclusion criteria ( polyp sized 6 - 9 mm ) were r and omized to the EMR ( n = 179 ) and CSP ( n = 179 ) groups , and their polyps were treated with conventional EMR or CSP , respectively . After polypectomy , an additional 5 forceps biopsies were performed at the base and margins of polypectomy sites to assess the presence of residual polyp tissue . The EMR and CSP sample s were compared to assess the IRR . RESULTS Among a total of 525 polyps , 415 ( 79.0 % ) were adenomatous polyps , and 41 ( 16.4 % ) were advanced adenomas . The overall IRR for adenomatous polyps was significantly higher in the CSP group compared with the EMR group ( 18/212 , 8.5 % vs 3/203 , 1.5 % ; P = .001 ) . Logistic regression analysis revealed that the CSP procedure was a stronger risk factor for the IRR ( odds ratio [ OR ] 6.924 ; 95 % confidence interval [ CI ] , 2.098 - 24.393 ; P = .003 ) . In addition , piecemeal resection was the most important risk factor for the IRR ( OR 28.696 ; 95 % CI , 3.620 - 227.497 ; P = .001 ) . The mean procedure time for polypectomy was not significantly different between the EMR and CSP groups ( 5.5 ± 2.7 vs 4.7 ± 3.4 minutes ; P = .410 ) . None of these patients presented with delayed bleeding . There were no severe adverse events related to the biopsies . CONCLUSIONS EMR was significantly superior to CSP for achieving complete endoscopic resection of small colorectal polyps . Patients with piecemeal resection of polyps had a higher risk for incomplete resection . ( Clinical trial registration number : Hongwei-1102 - 12 . ) BACKGROUND AND STUDY AIMS Cold snare polypectomy is an established method for the resection of small colorectal polyps ; however , significant incomplete resection rates still leave room for improvement . We aim ed to assess the efficacy of cold snare endoscopic mucosal resection ( CS-EMR ) , compared with hot snare endoscopic mucosal resection ( HS-EMR ) , for nonpedunculated polyps sized 6 - 10 mm . PATIENTS AND METHODS This study was a dual-center , r and omized , noninferiority trial . Consecutive adult patients with at least one nonpedunculated polyp sized 6 - 10 mm were enrolled . Eligible polyps were r and omized ( 1:1 ) to be treated with either CS-EMR or HS-EMR . Both methods involved submucosal injection of a methylene blue-tinted normal saline solution . The primary noninferiority end point was histological eradication evaluated by postpolypectomy biopsies ( noninferiority margin - 10 % ) . Secondary outcomes included occurrence of intraprocedural bleeding , clinical ly significant postprocedural bleeding , and perforation . RESULTS Among 689 patients screened , 155 patients with 164 eligible polyps were included ( CS-EMR n = 83 , HS-EMR n = 81 ) . The overall rate of histological complete resection was 92.8 % in the CS-EMR group and 96.3 % in the HS-EMR group ( difference 3.5 % ; 95 % confidence interval [ CI ] - 4.15 to 11.56 ) , showing noninferiority of CS-EMR compared with HS-EMR . CS-EMR was shown to be noninferior both for polyps measuring 6 - 7 mm ( CS-EMR 93.3 % ; HS-EMR 100 % ; 95 % CI - 7.95 to 21.3 ) and those of 8 - 10 mm ( 92.5 % vs. 94.7 % , respectively ; 95 % CI - 7.91 to 13.16 ) . Rates of intraprocedural bleeding were similar between the two groups ( CS-EMR 3.6 % , HS-EMR 1.2 % ; P = 0.30 ) . No clinical ly significant postprocedural bleeding or perforation occurred in either group . CONCLUSIONS CS-EMR appears to be a valuable modification of the st and ard cold snare technique , obviating the need to use diathermy for nonpedunculated colorectal polyps sized 6 - 10 mm BACKGROUND AND AIMS Curability is associated with resection width and depth in polypectomy . We evaluated the resection width and depth achieved with hot snare polypectomy ( HSP ) and cold snare polypectomy ( CSP ) for small colorectal polyps . METHODS In this single-center , prospect i ve , r and omized controlled study , patients with rectal or rectosigmoid polyps ≤10 mm in diameter were treated with HSP or CSP . Resection width was evaluated as mucosal defect size , measured immediately postprocedure and 1 day later . Resection depth was histologically evaluated using obtained specimens . RESULTS Fifty-two patients were enrolled . Mean lesion size was 5.6 mm with HSP ( n = 27 ) and 5.8 mm with CSP ( n = 25 ) . Mean mucosal defect diameter immediately after HSP and CSP was 5.1 mm and 7.5 mm , respectively ( P < .001 ) . The diameter 1 day after the procedure increased by 29 % ( 95 % confidence interval [ CI ] , 17%-41 % ) with HSP and decreased by 25 % ( 95 % CI , 18%-32 % ) with CSP ( P < .001 ) . Muscularis mucosa was obtained similarly with HSP and CSP ( 96 % [ 95 % CI , 82%-99 % ] vs 92 % [ 95 % CI , 75%-98 % ] ; P = .603 ) . Submucosal tissue was obtained significantly more frequently with HSP than with CSP ( 81 % [ 95 % CI , 63%-92 % ] vs 24 % [ 95 % CI , 11%-43 % ] ; P < .001 ) . CONCLUSIONS The resection width immediately after CSP was larger than that after HSP but was significantly smaller at day 1 after resection . Although the resection depth after CSP was more superficial , muscularis mucosa was obtained in most specimens . Thus , CSP has sufficient resection width and depth to enable complete polyp resection and potentially has a superior safety profile than HSP BACKGROUND Both cold-only snare and hot polypectomy snare are used for the removal of small colorectal polyps . OBJECTIVE To compare the outcome of cold snare polypectomy of small colorectal polyps with a snare exclusively design ed as a cold snare versus cold snare polypectomy by using a traditional polypectomy snare . DESIGN Prospect i ve , r and omized , controlled study . SETTING Municipal hospital in Japan . INTERVENTIONS Patients with colorectal polyps 10 mm or smaller in diameter were r and omized to dedicated cold snare ( dedicated cold snare group ) or traditional cold snare ( traditional cold snare group ) . The primary outcome measure was complete resection rates by cold snaring based on pathological examination . Secondary outcomes included bleeding within 2 weeks after polypectomy and identification of submucosal arteries and injured arteries in the resected specimens . RESULTS Seventy-six patients having 210 eligible polyps were r and omized : dedicated cold snare group , N = 37 ( 98 polyps ) and traditional cold snare group , N = 39 ( 112 polyps ) . Patient demographic characteristics including the number , size , and shape of the polyps removed were similar in the 2 groups . The complete resection rate was significantly greater with the dedicated cold than with the traditional cold snare ( 91 % [ 89/98 ] vs 79 % [ 88/112 ] , P = .015 ) , with a marked difference with 8- to 10-mm polyps , both flat and pedunculated . Immediate bleeding and hematochezia rates were similar ( 19 % vs 21 % , P = .86 ; 5.4 % vs 7.7 % , P = .69 ) . No delayed bleeding occurred . Histology demonstrated a similar prevalence of arteries and injured arteries in the submucosa ( 33 % [ 32/96 ] vs 30 % [ 31/104 ] , P = .59 ; 3.1 % [ 3/96 ] vs 6.7 % [ 7/104 ] , P = .24 ) . LIMITATIONS Small sample size , single-center study . CONCLUSION Polypectomy by using a dedicated cold snare result ed in complete polyp removal more often than did cold snaring with a traditional snare , especially polyps 8 to 10 mm in diameter , whether flat or pedunculated . ( CLINICAL TRIAL REGISTRATION NUMBER NCT02036047 . BACKGROUND Cold snare techniques are widely used for removal of diminutive and small colorectal polyps . The influence of resection technique on the effectiveness of polypectomy is unknown . We therefore compared st and ard cold snare polypectomy with a newly described suction pseudopolyp technique , for completeness of excision and for complications . PATIENTS AND METHODS In this single-center study , 112 patients were r and omized to cold snare polypectomy or the suction pseudopolyp technique . Primary outcome was endoscopic completeness of excision . Consensus regarding the endoscopic assessment of completeness of excision was st and ardized and aided by chromoendoscopy . Secondary outcomes included : completeness of histological excision , polyp " fly away " and retrieval rates , early bleeding ( 48 hours ) , delayed bleeding ( 2 weeks ) , and perforation . RESULTS 148 polyps were removed , with size range 3 - 7 mm , 60 % in the left colon , and 90 % being sessile . Regarding completeness of excision ( with uncertain findings omitted ) : endoscopically , this was higher with the suction pseudopolyp technique compared with cold snare polypectomy but not statistically significantly so ( 73/74 [ 98.6 % ] vs. 63/68 [ 92.6 % ] ; P = 0.08 ) . A trend towards a higher complete histological excision rate with the suction pseudopolyp technique was also not statistically significant ( 45/59 [ 76.3 % ] vs. 37/58 [ 63.8 % ] ; P = 0.14 ) . Polyp retrieval rate was not significantly different ( suction 68/76 [ 89.5 % ] vs. cold snare 64/72 [ 88.9 % ] ; P = 0.91 ) . No perforation or bleeding requiring hemostasis occurred in either group . CONCLUSION In this study both polypectomy techniques were found to be safe and highly effective , but further large multicenter trials are required . Clinical trial registration at www . clinical trials.gov : NCT02208401 BACKGROUND The bleeding risk after cold snare polypectomy in anticoagulated patients is not known . OBJECTIVE To compare the bleeding risk after cold snare polypectomy or conventional polypectomy for small colorectal polyps in anticoagulated patients . DESIGN Prospect i ve r and omized controlled study . SETTING Municipal hospital in Japan . INTERVENTIONS Anticoagulated patients with colorectal polyps up to 10 mm in diameter were enrolled . Patients were r and omized to polypectomy with either cold snare technique ( Cold group ) or conventional polypectomy ( Conventional group ) without discontinuation of warfarin . The primary outcome measure was delayed bleeding ( ie , requiring endoscopic intervention within 2 weeks after polypectomy ) . Secondary outcome measures were immediate bleeding and retrieval rate of colorectal polyps . RESULTS Seventy patients were r and omized ( 159 polyps ) : Cold group ( n = 35 , 78 polyps ) and Conventional group ( n = 35 ; 81 polyps ) . The patients ' demographic characteristics including international normalized ratio and the number , size , and shape of polyps removed were similar between the 2 techniques . Immediate bleeding during the procedure was more common with conventional polypectomy ( 23 % [ 8/35 ] ) compared with cold polypectomy ( 5.7 % [ 2/35 ] ) ( P = .042 ) . No delayed bleeding occurred in the Cold group , whereas 5 patients ( 14 % ) required endoscopic hemostasis in the Conventional group ( P = .027 ) . Complete polyp retrieval rates were identical ( 94 % [ 73/78 ] vs 93 % [ 75/81 ] ) . The presence of histologically demonstrated injured arteries in the submucosal layer with cold snare was significantly less than with conventional snare ( 22 % vs 39 % , P = .023 ) . LIMITATION Small sample size , single-center study . CONCLUSIONS Delayed bleeding requiring hemostasis occurred significantly less commonly after cold snare polypectomy than conventional polypectomy despite continuation of anticoagulants . Cold snare polypectomy is preferred for removal of small colorectal polyps in anticoagulated patients . ( CLINICAL TRIAL REGISTRATION NUMBER NCT 01553565 . ) 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 Background Cold polypectomy has been widely accepted for removal of small colorectal polyps . However , no large-scale prospect i ve study exists as for its safety in Japan . We investigated this issue in this single-center , prospect i ve cohort study in a total of 1198 colorectal polyps resected with cold polypectomy . Patients and methods Four hundred and seventy-four patients who underwent cold polypectomy for colorectal neoplastic lesions less than 10-mm diameter between September 2014 and October 2016 were enrolled . Primary outcome was the incidence of delayed bleeding within 2 weeks after the procedure . Secondary outcomes were the rate of immediate bleeding , perforation , endoscopic en bloc resection , and advanced histology . Results Cold polypectomy was performed on 1198 polyps in the 474 patients . No delayed bleeding or colonic perforation was observed . Immediate bleeding during the procedure , requiring endoscopic hemostasis , occurred in 97 lesions ( 8.1 % ) , and all of them were successfully managed endoscopically . The endoscopic en bloc resection rate was 97.2 % . Twenty-eight lesions ( 2.3 % ) were histologically diagnosed as advanced neoplasia ; among them , three lesions were well-differentiated adenocarcinomas , and in two of them , a negative margin was not histologically confirmed . Conclusions Cold polypectomy for small colorectal polyps is a safe technique without significant complication , but careful endoscopic diagnosis at cold polypectomy is necessary to identify advanced neoplasia . The reliability of cold polypectomy in excision of polyps with high- grade neoplasia should be established before the procedure becomes st and ard in the excision of small colorectal polyps . Clinical trial registration number : UMIN000014812 AIM To compare the efficacy and safety of cold snare polypectomy ( CSP ) and hot forceps biopsy ( HFB ) for diminutive colorectal polyps . METHODS This prospect i ve , r and omized single-center clinical trial included consecutive patients ≥ 20 years of age with diminutive colorectal polyps 3 - 5 mm from December 2014 to October 2015 . The primary outcome measures were en-bloc resection ( endoscopic evaluation ) and complete resection rates ( pathological evaluation ) . The secondary outcome measures were the immediate bleeding or immediate perforation rate after polypectomy , delayed bleeding or delayed perforation rate after polypectomy , use of clipping for bleeding or perforation , and polyp retrieval rate . Prophylactic clipping after polyp removal was n’t routinely performed . RESULTS Two hundred eight patients were r and omized into the CSP ( 102 ) , HFB ( 106 ) and 283 polyps were evaluated ( CSP : 148 , HFB : 135 ) . The en-bloc resection rate was significantly higher with CSP than with HFB [ 99.3 % ( 147/148 ) vs 80.0 % ( 108/135 ) , P < 0.0001 ] . The complete resection rate was significantly higher with CSP than with HFB [ 80.4 % ( 119/148 ) vs 47.4 % ( 64/135 ) , P < 0.0001 ] . The immediate bleeding rate was similar between the groups [ 8.6 % ( 13/148 ) vs 8.1 % ( 11/135 ) , P = 1.000 ] , and endoscopic hemostasis with hemoclips was successful in all cases . No cases of perforation or delayed bleeding occurred . The rate of severe tissue injury to the pathological specimen was higher HFB than CSP [ 52.6 % ( 71/135 ) vs 1.3 % ( 2/148 ) , P < 0.0001 ] . Polyp retrieval failure was encountered CSP ( 7 ) , HFB ( 2 ) . CONCLUSION CSP is more effective than HFB for resecting diminutive polyps . Further long-term follow-up study is required BACKGROUND Cold polypectomy techniques ( without electrocautery ) by means of biopsy forceps or snare are widely adopted for the removal of subcentimetric polyps . However , few data are available on the safety of this approach . The aim of this study was to assess the safety of cold polypectomy for subcentimetric polyps , as well as the rate of advanced neoplasia in these lesions . PATIENTS AND METHODS In a prospect i ve multicenter trial , consecutive patients with at least one < 10-mm polyp at colonoscopy were prospect ively included . All of the < 10-mm polyps detected within the study period were removed by cold polypectomy . The rates of immediate or delayed bleeding and other complications were assessed at 7 and 30 days after cold polypectomy by telephone calls . The rate of advanced histology was also assessed . Predictive variables of postpolypectomy bleeding or advanced neoplasia were identified by multivariate analysis . RESULTS A total of 1015 < 10-mm polyps in 823 patients ( 15.5 % on antiplatelet agents ) were removed . Of these , 822 ( 81 % ) were ≤ 5 mm and 193 ( 19 % ) were 6 - 9 mm . Immediate postpolypectomy bleeding occurred in 18 patients , corresponding to a per-patient and per-polyp bleeding rate of 2.2 % ( 95 % confidence interval [ CI ] 1.2 % - 3.2 % ) and 1.8 % ( 95 % CI 1 % - 2.6 % ) , respectively . Therapy with antiplatelet agents ( odds ratio [ OR ] 4 ; 95 % CI 1.5 - 10.6 ) and larger polyp size ( OR 2 ; 95 % CI 1.1 - 6.9 ) were independent predictors of bleeding . Bleeding was successfully treated by endoscopic hemostasis in all cases and required no further medical intervention . Advanced neoplasia prevalence in polyps ≤ 5 mm was as high as 8.7 % . CONCLUSIONS The results from this study showed the high safety of a cold polypectomy approach for subcentimetric polyps . This was due to the low rate of postpolypectomy bleeding and to the high efficacy of endoscopic hemostasis in its treatment . The high rate of advanced neoplasia in polyps ≤ 5 mm should prompt some caution on the management of these lesions following detection at computed tomography colonography or colon capsule endoscopy BACKGROUND Polypectomy techniques vary in clinical practice . The aim of this study was to determine patterns of polypectomy practice s in a r and om sample of gastroenterologists . METHODS A total of 300 gastroenterologists were selected r and omly from the membership directory of a professional society . They were asked to complete a st and ardized survey by telephone , electronic mail , or facsimile . RESULTS The offices of 285 physicians were contacted successfully . A total of 189 ( 63 % ) chose to participate . 152 ( 80 % ) of these physicians were in private practice , and 37 ( 20 % ) were in academic practice . The mean number of years in practice was 15.5 ( range 1 - 46 years ) . Forceps techniques ( cold or hot ) dominated other polypectomy methods for polyps 1 to 3 mm in size ( p < 0.0001 ) , whereas electrosurgical snare resection was dominate for polyps 7 to 9 mm in diameter ( p < 0.0001 ) . No method of polypectomy was significantly more likely to be used for polyps 4 to 6 mm in size . The proportion of physicians who had used dye spraying was 8.5 % ; detachable snares , 20.1 % ; clips , 20.1 % ; and submucosal saline solution injection , 82 % . Of those who had used submucosal saline solution injection , 29.7 % had no rules for its use , and , in the remainder , there was marked variation regarding the criteria . For polyp stalks greater than 1 cm in diameter , 69 % used no method to prevent bleeding . Of those who did use preventive techniques , 76 % used epinephrine injection . The electrosurgical current used for polypectomy was pure coagulation in 46 % , blend in 46 % , and pure-cut in 3 % ; 4 % varied the current . CONCLUSIONS At present , polypectomy technique among clinical gastroenterologists is highly variable . Some newer ancillary techniques have had extremely limited use thus far Objective To investigate the success rate of cold snare polypectomy ( CSP ) for complete resection of 4–9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy ( HSP ) . Design A prospect i ve , multicentre , r and omised controlled , parallel , non-inferiority trial conducted in 12 Japanese endoscopy units . Endoscopically diagnosed sessile adenomatous polyps , 4–9 mm in size , were r and omly assigned to the CSP or HSP group . After complete removal of the polyp using the allocated technique , biopsy specimens from the resection margin after polypectomy were obtained . The primary endpoint was the complete resection rate , defined as no evidence of adenomatous tissue in the biopsied specimens , among all pathologically confirmed adenomatous polyps . Results A total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016 . The complete resection rate for CSP was 98.2 % compared with 97.4 % for HSP . The non-inferiority of CSP for complete resection compared with HSP was confirmed by the + 0.8 % ( 90 % CI −1.0 to 2.7 ) complete resection rate ( non-inferiority p<0.0001 ) . Postoperative bleeding requiring endoscopic haemostasis occurred only in the HSP group ( 0.5 % , 2 of 402 polyps ) . Conclusions The complete resection rate for CSP is not inferior to that for HSP . CSP can be one of the st and ard techniques for 4–9 mm colorectal polyps . ( Study registration : UMIN000018328 Background and Aim : The ideal method to remove small colorectal polyps is unknown . We compared removal by colon snare transection without electrocautery ( cold snare polypectomy ) with conventional electrocautery snare polypectomy ( hot polypectomy ) in terms of procedure duration , difficulty in retrieving polyps , bleeding , and post-polypectomy symptoms . Methods : Patients with colorectal polyps up to 8 mm in diameter were r and omized to polypectomy by cold snare technique ( cold group ) or conventional polypectomy ( conventional group ) . The principal outcome measures were abdominal symptoms within 2 weeks after polypectomy . Secondary outcome measures were the rates of retrieval of colorectal polyps and bleeding . Results : Eighty patients were r and omized : cold group , n = 40 ( 101 polyps ) and conventional group , n = 40 ( 104 polyps ) . The patients ’ demographic characteristics and the number and size of polyps removed were similar between the two techniques . Procedure time was significantly shorter with cold polypectomy vs. conventional polypectomy ( 18 vs. 25 min , p < 0.0001 ) . Complete polyp retrieval rates were identical [ 96 % ( 97/101 ) vs. 96 % ( 100/104 ) ] . No bleeding requiring hemostasis occurred in either group . Abdominal symptoms shortly after polypectomy were more common with conventional polypectomy ( i.e. 20 % ; 8/40 ) than with cold polypectomy ( i.e. 2.5 % ; 1/40 ; p = 0.029 ) . Conclusion : Cold polypectomy was superior to conventional polypectomy in terms of procedure time and post-polypectomy abdominal symptoms . The two methods were otherwise essentially identical in terms of bleeding risk and complete polyp retrieval . Cold polypectomy is therefore the preferred method for removal of small colorectal polyps BACKGROUND Polypectomy with cold biopsy forceps is a frequently used technique for removal of small , sessile , colorectal polyps . Jumbo forceps may lead to more effective polypectomy because of the larger size of the forceps cup . OBJECTIVE To evaluate the efficiency of cold jumbo biopsy forceps compared with st and ard forceps for polypectomy of small , sessile , colorectal polyps . DESIGN R and omized , controlled trial . SETTING Outpatient endoscopy center . PATIENTS This study involved 140 patients found to have at least one eligible polyp defined as a sessile polyp measuring ≤6 mm . INTERVENTION Polypectomy with cold biopsy forceps . MAIN OUTCOME MEASUREMENTS Complete visual polyp eradication with one forceps bite . RESULTS In 140 patients , a total of 305 eligible polyps were detected ( 151 removed with jumbo forceps and 154 with st and ard forceps ) . Complete visual eradication of the polyp with one forceps bite was achieved in 78.8 % of the jumbo forceps group and 50.7 % of the st and ard forceps group ( P < .0001 ) . Biopsies from the polypectomy sites of adenomatous polyps thought to be visually completely eradicated with one bite showed a trend toward a higher complete histologic eradication rate with the jumbo forceps ( 82.4 % ) compared with the st and ard forceps ( 77.4 % ) , but the difference did not reach statistical significance ( P = .62 ) . The withdrawal time for visual inspection of the colon and time to perform polypectomies were significantly shorter in the jumbo forceps group ( mean 21.43 vs 18.23 minutes ; P = .02 ) . LIMITATIONS Lack of blinding to the type of forceps used . CONCLUSION The jumbo biopsy forceps is superior to the st and ard forceps in removing small , sessile polyps . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00855790 . ) Background and aim Removal of polyps during colonoscopy effectively prevents the development of colorectal cancer . So far , snare resection with high frequency current with or without prior submucosal saline injection is the method of choice . The aim of this study was to evaluate the feasibility , safety , and outcome of cold snare resection during routine endoscopy . Methods In this prospect i ve study , 522 patients undergoing outpatient colonoscopy were included . Cold snare resection for diminutive ( < 6 mm ) , small ( 6 – 9 mm ) , and larger polyps ( > 9 – 15 mm ) was performed using a dedicated cold snare device ( Exacto ® ) without prior submucosal injection . Outcome parameters included bleeding rate , perforation rate , procedure time , histologic evaluation of polyp margins , and success rates . The data were compared to a group of patients undergoing hot snare resection . Results Overall , 1233 polyps were removed using cold snare resection with an overall success rate of 99.4 % . All failures of cold snare resection occurred in the cecum ( 8/82 , failure rate 9.8 % ) . In the remaining colon , the success rate was 100 % . Immediate post-polypectomy bleeding occurred in 0.49 % of all patients and was most frequently seen in polyps larger than 9 mm . The procedure time was significantly shorter using cold snare resection compared with hot snare resection ( 27.6 min vs. 35.7 min , P < 0.01 ) . Conclusion Cold snare resection can be performed safely in out patients for removal of small polyps in screening colonoscopy . It does not require prior saline injection and reduces procedure time without an increased risk of bleeding OBJECTIVES : There are few data on cold snare polypectomy ( CSP ) in direct comparison with cold forceps polypectomy ( CFP ) for colonoscopic resection of diminutive colorectal polyps ( DCPs ; ≤5 mm ) . The primary aim of this study was to compare the histologic polyp eradication rate of CSP with that of CFP using double-biopsy technique . METHODS : This was a r and omized controlled trial at a single academic hospital . Of the 165 patients invited , 54 consecutive patients having 117 eligible polyps were enrolled in this study . To evaluate histologic eradication of polyps , two or more additional biopsies were taken from the base and edges of the polypectomy site . RESULTS : The mean size of polyps was 3.66 mm ( ±1.13 ) . Most polyps evaluated were tubular adenomas ( 69.9 % ) . The rate of histologic eradication was significantly higher in the CSP group than in the CFP group ( 93.2 % vs. 75.9 % , P=0.009 ) . The time taken for polypectomy was significantly shorter in the CSP group ( 14.29 vs. 22.03 s , P<0.001 ) . Failure of tissue retrieval was noted in 6.8 % of polyps resected by CSP . Multivariate analysis revealed that the method of polypectomy ( CFP ) and the polyp size ( ≥4 mm ) were independent predictors associated with incomplete histologic eradication ( odds ratio ( OR ) 4.750 ( 95 % confidence interval ( CI ) : 1.459–15.466 ) , OR 4.375 ( 95 % CI : 1.345–14.235 ) ; all P<0.05 , respectively ) . CONCLUSIONS : CSP is superior to CFP for the endoscopic removal of DCPs with regard to completeness of polypectomy . CSP technique should be considered the primary method for endoscopic treatment of polyps in the 4–5-mm size range ( Clinical Trials.gov number : NCT01646242 ) BACKGROUND Accurate optical diagnosis of small ( < 10 mm ) colorectal polyps in vivo , without formal histopathology , could make colonoscopy more efficient and cost effective . The aim of this study was to assess whether optical diagnosis of small polyps is feasible and safe in routine clinical practice . METHODS Consecutive patients with a positive faecal occult blood test or previous adenomas undergoing surveillance at St Mark 's Hospital ( London , UK ) , from June 19 , 2008 , to June 16 , 2009 , were included in this prospect i ve study . Four colonoscopists with different levels of experience predicted polyp histology using optical diagnosis with high-definition white light , followed by narrow-b and imaging without magnification and chromoendoscopy , as required . The primary outcome was accuracy of polyp characterisation using optical diagnosis compared with histopathology , the current gold st and ard . Accuracy of optical diagnosis to predict the next surveillance interval was also assessed and compared with surveillance intervals predicted by current guidelines using histopathology . This study is registered with Clinical Trials.gov , NCT00888771 . FINDINGS 363 polyps smaller than 10 mm were detected in 130 patients , of which 278 polyps had both optical and histopathological diagnosis . By histology , 198 of these polyps were adenomas and 80 were non-neoplastic lesions ( of which 62 were hyperplastic ) . Optical diagnosis accurately diagnosed 186 of 198 adenomas ( sensitivity 0.94 ; 95 % CI 0.90 - 0.97 ) and 55 of 62 hyperplastic polyps ( specificity 0.89 ; 0.78 - 0.95 ) , with an overall accuracy of 241 of 260 ( 0.93 , 0.89 - 0.96 ) for polyp characterisation . Using optical diagnosis alone , 82 of 130 patients could be given a surveillance interval immediately after colonoscopy , and the same interval was found after formal histopathology in 80 patients ( 98 % ) using British guidelines and in 78 patients ( 95 % ) using US multisociety guidelines . INTERPRETATION For polyps less than 10 mm in size , in-vivo optical diagnosis seems to be an acceptable strategy to assess polyp histopathology and future surveillance intervals . Dispensing with formal histopathology for most small polyps found at colonoscopy could improve the efficiency of the procedure and lead to substantial savings in time and cost . FUNDING Leigh Family Trust , London , UK BACKGROUND In the National Polyp Study ( NPS ) , colorectal cancer was prevented by colonoscopic removal of adenomatous polyps . We evaluated the long-term effect of colonoscopic polypectomy in a study on mortality from colorectal cancer . METHODS We included in this analysis all patients prospect ively referred for initial colonoscopy ( between 1980 and 1990 ) at NPS clinical centers who had polyps ( adenomas and nonadenomas ) . The National Death Index was used to identify deaths and to determine the cause of death ; follow-up time was as long as 23 years . Mortality from colorectal cancer among patients with adenomas removed was compared with the expected incidence-based mortality from colorectal cancer in the general population , as estimated from the Surveillance Epidemiology and End Results ( SEER ) Program , and with the observed mortality from colorectal cancer among patients with nonadenomatous polyps ( internal control group ) . RESULTS Among 2602 patients who had adenomas removed during participation in the study , after a median of 15.8 years , 1246 patients had died from any cause and 12 had died from colorectal cancer . Given an estimated 25.4 expected deaths from colorectal cancer in the general population , the st and ardized incidence-based mortality ratio was 0.47 ( 95 % confidence interval [ CI ] , 0.26 to 0.80 ) with colonoscopic polypectomy , suggesting a 53 % reduction in mortality . Mortality from colorectal cancer was similar among patients with adenomas and those with nonadenomatous polyps during the first 10 years after polypectomy ( relative risk , 1.2 ; 95 % CI , 0.1 to 10.6 ) . CONCLUSIONS These findings support the hypothesis that colonoscopic removal of adenomatous polyps prevents death from colorectal cancer . ( Funded by the National Cancer Institute and others . ) BACKGROUND AND AIMS A previous study reported that cold snare polypectomy ( CSP ) was superior to cold forceps polypectomy ( CFP ) for the removal of diminutive colorectal polyps ( DCPs ) ( ≤5 mm ) when the techniques were assessed for completeness of resection . However , completeness is expected to be greater with CFP when strict investigation of the remnant polyp is performed . The aim of this study was to assess the efficacy of CFP with narrow-b and imaging ( NBI ) evaluation of polypectomy sites for removal of DCPs , compared with CSP . METHODS This was a r and omized , controlled , noninferiority trial at a tertiary-care referral hospital . Of the 380 patients screened , 146 patients with 231 DCPs were enrolled . CFP was used to resect DCPs until no remnant polyp was visible by NBI endoscopy . The primary noninferiority endpoint was histologic eradication of polyps , with a noninferiority margin of -10 % . RESULTS A size of > 3 mm was seen in 129 polyps ( 55.8 % ) . The overall rates of histologic eradication were 90.5 % in the CFP group and 93.0 % in the CSP group ( difference , 2.5 % ; 95 % confidence interval [ CI ] , -9.67 to 4.62 ) . However , when confined to the polyps > 3 mm , the histologic eradication rate was 86.8 % and 93.4 % ( 95 % CI , -17.2 to 3.6 ) , respectively . Polyp size , histology , location , and time taken for polypectomy did not differ between the groups . The failure rate of tissue retrieval was higher in the CSP than in the CFP group ( 7.8 % vs 0.0 % , respectively ; P = .001 ) . CONCLUSIONS In this study , > 90 % of all DCPs were completely resected by using CFP with NBI evaluation of polypectomy sites , showing noninferiority compared with CSP . However , in polyps measuring > 3 mm , CFP failed to show noninferiority versus CSP . CFP appears to be the proper method for resection of DCPs 1 to 3 mm in size if no remnant polyp is visible by NBI endoscopy , but CFP is likely to be insufficient for larger polyps . ( CLINICAL TRIAL REGISTRATION NUMBER NCT02201147 . ) Background : The optimal method of diminutive polypectomy ( < 6 mm ) is unknown . Objective : To assess the rates of incomplete resection of diminutive polyps of the colon using three st and ard polyp resection techniques ( hot snare , cold snare , and cold biopsy forceps ) . Design : R and omized , pilot study . Setting s : Single-center endoscopy center . Patients : Patients undergoing routine outpatient colonoscopies . Interventions : Polypectomy was performed using the method to which the patient was r and omized . Following retrieval of the polyp , the polypectomy base was lifted by submucosal injection of normal saline and then excised using the cold snare device . If no tissue could be removed , then at least four cold biopsies using forceps of the remaining margin were obtained . Main outcome measures : Adequacy of resection of diminutive polyps , which was defined as no visible adenoma or hyperplastic tissue seen in the base tissue on histology . Results : A total of 60 patients were enrolled ( 57 % male ) , the mean age was 60 ( range 33 – 82 ) , and 62 polyps were r and omized from 37 patients . The mean polyp size was 3.6 mm ( range 2 – 5 mm ) and 37 polyps ( 60 % ) were adenomatous . Overall incomplete polyp resection rate was 9 % ( 95 % CI 3 – 19 % ) , 5 of 37 ( 14 % ) for adenomas . By the study arm , the incomplete resection rates were 1 of 18 ( 6 % ) for hot snare , 2 of 21 ( 10 % ) for cold snare , and 2 of 18 ( 11 % ) for cold biopsy forceps . The majority of polyp bases were removed with cold biopsy forceps since most of the endoscopists did not feel that the saline lift cold snare method was feasible or appropriate . Limitations : Small sample size ; endoscopic mucosal resection ( EMR ) of the polyp base tissue was not routinely performed . Conclusions : Recruiting patients to a pilot study that r and omized polyps to one of three common methods of polypectomy for diminutive polyps was feasible , and approximately 1 in 10 diminutive polyps found on colonoscopy were incompletely resected by st and ard polypectomy methods Background With the aging of the population and rising incidence of thromboembolic events , the clinical use of antithrombotic agents is also increasing . There are few reports yet on the management of antithrombotic agent use in patients undergoing cold snare polypectomy ( CSP ) . Aims The aim of this study was to evaluate whether continued administration of antithrombotic agents in patients undergoing CSP would be associated with an increased rate of delayed post-polypectomy bleeding ( DPPB ) . Methods A total of 1177 colorectal polyps in 501 patients were resected at Omori Red Cross Hospital between October 2017 and March 2018 . The polyps were divided into two groups depending on whether the patients received antithrombotic agent treatment or not : the antithrombotic group ( 911 polyps ) and the no-antithrombotic group ( 266 polyps ) . Results Among the 1177 polyp resections , there was no case of DPPB , including in the antithrombotic group . Immediate bleeding occurred in a total of 63 ( 5.4 % ) cases . Polyp location in the rectum ( OR ( 95 % CI ) 2.64 ( 1.223–5.679 ) ; p = 0.013 ) , polyp size ≥ 6 mm ( OR ( 95 % CI ) 4.64 ( 2.719–7.933 ) ; p < 0.001 ) , polypoid growth pattern ( OR ( 95 % CI ) 2.78 ( 1.607–4.793 ) ; p < 0.001 ) , and antithrombotic agent use ( OR ( 95 % CI ) 2.98 ( 1.715–5.183 ) ; p < 0.001 ) were identified as significant risk factors of immediate bleeding . Conclusions Continued use of antithrombotic agents does not increase the risk of DPPB , even in those receiving multiple antithrombotic agents . Thus , it is safe to perform CSP even in multiple agent users . Prospect i ve , r and omized studies are necessary to confirm our results BACKGROUND AND AIMS Cold snare polypectomy ( CSP ) and jumbo forceps polypectomy ( JFP ) have been shown to be effective for removing diminutive colorectal polyps ( DCPs ) ( ≤5 mm ) . However , no study has compared complete resection rates between CSP and JFP for DCPs . The aim of this study was to compare the efficacy and safety of JFP with CSP for the removal of DCPs . METHODS This was a prospect i ve r and omized controlled trial from 2 tertiary-care referral centers . A total of 1003 patients were screened , and 169 patients with 196 DCPs were enrolled . The main outcome was complete polyp resection rate . RESULTS Of 196 diminutive polyps , 177 ( 90.3 % ) were adenomatous polyps . The overall complete resection rate was 92.1 % ( 163/177 ) . The complete resection rate was not significantly different between JFP and CSP groups ( 92.0 % vs 92.2 % ; P = .947 ) . JFP achieved complete resection rates comparable with CSP for polyps > 3 mm ( 90.3 % vs 89.8 % ; P = .928 ) . Polypectomy procedure time , tissue retrieval rate , and rate of postpolypectomy adverse events were not significantly different between the 2 groups . CONCLUSIONS Both JFP and CSP achieved complete resection rates of > 90 % for DCPs . Thus , JFP may be considered for polypectomy of DCPs . ( International clinical trial registry number : KCT0002805 . ) BACKGROUND AND AIMS The true incidence of incomplete muscularis mucosa resection with cold snare polypectomy ( CSP ) is unknown . We examined the incidence of incomplete muscularis mucosa resection both with and without cold snare defect protrusion ( CSDP ) . PATIENTS AND METHODS We prospect ively enrolled patients undergoing polypectomy for 4 - 9-mm nonpedunculated polyps . We evaluated the presence of CSDP immediately following CSP , and biopsied the CSDP or the center of the mucosal defect without CSDP . The presence of the muscularis mucosa and any residual polyp in the biopsies was evaluated histologically . The primary outcome was the incidence of incomplete mucosal layer resection defined as presence of muscularis mucosa or residual polyp in the biopsies . RESULTS From August 2017 to October 2018 , 188 patients were screened , and 357 polyps were included . CSDP was detected in 122/355 ( 34 % ) evaluated mucosal defects . Excluding five lesions requiring hemostasis immediately following CSP , 352 mucosal defects were biopsied . After excluding 102 biopsies containing normal mucosa , we evaluated 250 biopsies . The overall incidence of incomplete mucosal layer resection was 63 % ( 159/250 ) ; 76 % ( 68/90 ) with CSDP and 57 % ( 91/159 ) without CSDP ( p < 0.01 ) . Both univariate and multivariate analysis showed that size ( ≥ 6 mm ) , resection time ( ≥ 5 sec ) , and serrated lesions were risk factors for CSDP . CONCLUSIONS CSDP , which was present with 36 % , was a good indicator for incomplete mucosal layer resection . Even in nonCSDP polypectomies , 57 % of the mucosal layer was not removed completely . Thus , CSP should be used for intraepithelial lesions , only , and careful pretreatment evaluation is recommended BACKGROUND The optimal technique for removal of diminutive or small colorectal polyps is debatable . OBJECTIVE To compare the complete resection rates of cold snare polypectomy ( CSP ) and cold forceps polypectomy ( CFP ) for the removal of adenomatous polyps ≤7 mm . DESIGN Prospect i ve r and omized controlled study . SETTING A university hospital . PATIENTS A total of 139 patients who were found to have ≥1 colorectal adenomatous polyps ≤7 mm . INTERVENTIONS Polyps were r and omized to be treated with either CSP or CFP . After the initial polypectomy , additional EMR was performed at the polypectomy site to assess the presence of residual polyp tissue . MAIN OUTCOME MEASUREMENTS Absence of residual polyp tissue in the EMR specimen of the polypectomy site was defined as complete resection . RESULTS Among a total of 145 polyps , 128 ( 88.3 % ) were adenomatous polyps . The overall complete resection rate for adenomatous polyps was significantly higher in the CSP group compared with the CFP group ( 57/59 , 96.6 % vs 57/69 , 82.6 % ; P = .011 ) . Although the complete resection rates for adenomatous polyps ≤4 mm were not different ( 27/27 , 100 % vs 31/32 , 96.9 % ; P = 1.000 ) , the complete resection rates for adenomatous polyps sized 5 to 7 mm was significantly higher in the CSP group compared with the CFP group ( 30/32 , 93.8 % vs 26/37 , 70.3 % ; P = .013 ) . LIMITATIONS Single-center study . CONCLUSION CSP is recommended for the complete resection of colorectal adenomatous polyps ≤7 mm . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01665898 . ) |
1,720 | 26,989,684 | CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett 's esophagus , gastric neoplasms and polyps , colorectal cancers in inflammatory bowel disease , malignant pancreatobiliary strictures , and pancreatic cysts . | Confocal laser endomicroscopy ( CLE ) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time .
The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases .
Although CLE has several promising applications , its use has been limited by its low availability , high cost , and need of specific operator training . | BACKGROUND & AIMS Confocal laser endomicroscopy allows subsurface analysis of the intestinal mucosa and in vivo histology during ongoing endoscopy . Here , we have applied this technique to the in vivo diagnosis of Barrett 's epithelium and associated neoplasia . METHODS Fluorescein-aided endomicroscopy was performed by applying the endomicroscope over the whole columnar-lined lower esophagus . Images obtained within 1 cm of the columnar-lined lower esophagus were stored digitally and a targeted biopsy examination or endoscopic mucosal resection of the examined areas was performed . In vivo histology was compared with the histologic specimens . All digitally stored images were re-assessed by a blinded investigator by the confocal Barrett classification system to predict histology . Intraobserver and interobserver variations of the involved endoscopists were evaluated by using kappa statistics . RESULTS Endomicroscopy allowed distinguishing between different types of epithelial cells and detected cellular and vascular changes in Barrett 's epithelium at high resolution during ongoing endoscopy in 63 patients . Barrett 's esophagus and associated neoplasia could be predicted with a sensitivity of 98.1 % and 92.9 % and a specificity of 94.1 % and 98.4 % , respectively ( accuracy , 96.8 % and 97.4 % ) . The mean kappa value for interobserver agreement for the prediction of histopathological diagnosis was .843 , whereas the intraobserver agreement showed a mean kappa value of .892 . CONCLUSIONS Fluorescence-aided endomicroscopy of Barrett 's esophagus allows in vivo histology of the mucosal layer during ongoing endoscopy . Gastric and Barrett 's epithelium and Barrett's-associated neoplastic changes can be diagnosed with high accuracy . Thus , endomicroscopy may be helpful in the management of patients with Barrett 's esophagus Objectives Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease ( IBD ) . Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation . The objectives of the study were ( 1 ) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and ( 2 ) whether these parameters predict relapse of IBD . Methods Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction . A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospect i ve pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn 's disease . Results Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium . Mouse experiments demonstrated inward flow through some leakage-associated shedding events , which was increased when luminal osmolarity was decreased . In IBD patients in clinical remission , increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination ( p<0.001 ) . The sensitivity , specificity and accuracy for the grading system to predict a flare were 62.5 % ( 95 % CI 40.8 % to 80.4 % ) , 91.2 % ( 95 % CI 75.2 to 97.7 ) and 79 % ( 95 % CI 57.7 to 95.5 ) , respectively . Conclusions Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease OBJECTIVES : Epithelial gaps result ing from intestinal cell extrusions can be visualized with confocal laser endomicroscopy ( CLE ) during colonoscopy and increased in normal-appearing terminal ileum of inflammatory bowel disease ( IBD ) patients . Cell-shedding events on CLE were found to be predictive of disease relapse . The aim of this study was to assess the prognostic value of epithelial gap densities for major clinical events ( hospitalization or surgery ) in follow-up . METHODS : We prospect ively followed IBD patients undergoing colonoscopy with probe-based CLE ( pCLE ) for clinical events including symptom flares , medication changes , hospitalization , or surgery . Survival analysis methods were used to compare event times for the composite outcome of hospitalization or surgery using log-rank tests and Cox proportional hazards models . We also examined the relationship of gap density with IBD flares , need for anti-tumor necrosis factor therapy , disease duration , gender and endoscopic disease severity , and location . RESULTS : A total of 21 Crohn 's disease and 20 ulcerative colitis patients with a median follow-up of 14 ( 11–31 ) months were studied . Patients with elevated gap density were at significantly higher risk for hospitalization or surgery ( log-rank test P=0.02 ) . Gap density was a significant predictor for risk of major events , with a hazard ratio of 1.10 ( 95 % confidence interval=1.01 , 1.20 ) associated with each increase of 1 % in gap density . Gap density was also correlated with IBD disease duration ( Spearman 's correlation coefficient rho=0.44 , P=0.004 ) , and was higher in male patients ( 9.0 vs. 3.6 gaps per 100 cells , P=0.038 ) . CONCLUSIONS : Increased epithelial gaps in the small intestine as determined by pCLE are a predictor for future hospitalization or surgery in IBD patients BACKGROUND Confocal endomicroscopy is a newly developed endoscopic imaging technology that produces 1000-fold magnification cross-sectional images of the GI surface and subsurface tissue during routine endoscopy . The gastric pit patterns identified by confocal endomicroscopy and correlation with histopathologic examination have not yet been established . OBJECTIVE Our purpose was to explore the appearance of various kinds of gastric pits and clarify the relationship between gastric pit patterns and the histopathologic findings . DESIGN Descriptive study . SETTING Qilu Hospital , Sh and ong University , Jinan , China . PATIENTS A total of 132 consecutive patients underwent confocal endomicroscopy after 7 healthy volunteers had been examined in vivo and 10 sample s resected from 10 patients with gastric cancer had been examined ex vivo by use of confocal endomicroscopy . The confocal images obtained from the 132 patients were compared with the histopathologic findings of the biopsy specimens from the corresponding confocal imaging sites in a prospect i ve and blinded fashion . MAIN OUTCOME MEASUREMENTS The relationship between the pit patterns and the histopathologic findings . RESULTS Gastric pit patterns were classified into 7 types . Normal mucosa with fundic gl and s mainly showed type A ( round pits ) , and corporal mucosa with histologic gastritis showed type B ( noncontinuous short rod-like ) ; normal mucosa with pyloric gl and s mainly showed type C ( continuous short rod-like ) , and antral mucosa with histologic gastritis showed type D ( elongated and tortuous branch-like ) . Goblet cells were easily distinguished by confocal endomicroscopy in intestinal metaplasia mucosa , which showed type F. The sensitivity and specificity of the type E pattern for predicting gastric atrophy were 83.6 % and 99.6 % , respectively . Corresponding values of the type G pattern for predicting gastric cancer were 90.0 % and 99.4 % . LIMITATIONS No data on interobserver and intraobserver variability . CONCLUSIONS The patterns of gastric pits identified by confocal endomicroscopy correlate well with the histopathologic findings . Confocal endomicroscopy may prove useful in predicting histopathologic diagnoses during routine endoscopic procedures Background Patients with ulcerative colitis and Crohn 's colitis have increased risk of colorectal cancer . Current screening endoscopy protocol s based on white light endoscopy ( WLE ) and r and om biopsies are laborious and of uncertain sensitivity . Novel endoscopic techniques include chromoendoscopy ( CE ) and confocal laser endomicroscopy ( CLE ) . Aim The aim was to compare WLE and CE for the detection of intraepithelial neoplasia ( IEN ) . Furthermore , we analysed the sensitivity and specificity of CE and CLE for the diagnosis of IEN . Methods The cohort consisted of 30 patients examined by WLE , CE with 0.4 % indigocarmine , and by a CLE system Pentax EC-3870CIFK during one examination . Additional 15 patients were examined by conventional protocol only . R and om biopsies and biopsies from all suspicious lesions were taken . We compared the number of IENs detected by WLE and CE and analysed the predictive values of CE and CLE for the histology diagnosis . Results There were 1584 r and om biopsies ( 35.2 per patient ) taken . There were 78 targeted biopsies ( 1.7 per patient ) taken in 24 of 45 patients examined by WLE and an additional 36 biopsies in 16 of 30 patients examined by CE ( 1.17 additional per patient ) . There were no IENs found on r and om biopsies versus six low- grade or high- grade IENs in four patients ( two detected by WLE , four additional by CE ) from targeted biopsies , P=0.02 . A total of 100 suspicious lesions were detected and analysed by CE and histology . CLE could not examine 32 of 100 lesions ( two of 30 flat vs. 30 of 70 pedunculated lesions , P=0.0002 , odds ratio 10.5 ) . The sensitivity of CE/CLE for low- grade or high- grade IEN was 100/100 % , the specificity 96.8/98.4 % , positive predictive value was 62.5/66.7 % and negative predictive value was 100/100 % . Conclusion Targeted biopsies are superior to r and om biopsies in the screening of IEN in patients with inflammatory bowel disease . CE increases the diagnostic yield of WLE . In our study CLE did not provide additional clinical benefits Background : Increased cell shedding with gap formation and local barrier dysfunction can be identified endomicroscopically in the terminal ileum of patients with inflammatory bowel disease . We aim to evaluate whether these changes are also present in the duodenum of patients with inflammatory bowel disease . Methods : Fifteen patients with Crohn 's disease ( CD ) , 10 patients with ulcerative colitis ( UC ) , and 10 controls underwent fluorescein-aided confocal laser endomicroscopy ( CLE ) . CLE was performed on macroscopically normal antral and duodenal ( D1 , D2 , D3 , D4 ) mucosa . Representative CLE images were prospect ively analyzed . Images were scored for the number of epithelial gaps , cell shedding , and the degree of fluorescein leakage into the intestinal lumen . Results : Both CD and UC patients had significantly more epithelial gaps , epithelial cell shedding , and leakage of fluorescein into the duodenal lumen than controls . The degree of cell shedding and epithelial gap formation was similar in CD and UC patients . In all cases , macroscopic endoscopic appearances of the duodenum were normal , and conventional histological analysis showed a mild nonspecific duodenitis in 7 of 15 patients with CD . Patients with UC had a histologically normal duodenum . Gap formation , cell shedding , and fluorescein leakage was similar in CD with active compared with inactive disease , except for D2 shedding . Conclusions : CLE can detect epithelial damage and barrier loss in the duodenum of CD and UC patients that is not apparent on conventional endoscopy or histology BACKGROUND The diagnosis of pancreatic cystic neoplasms ( PCNs ) , which now depends on morphology , cytology , and fluid analysis , is still challenging . A novel confocal laser endomicroscopy probe that can be inserted through a 19-gauge FNA needle allows needle-based confocal laser endomicroscopy ( nCLE ) , and the feasibility of nCLE has been reported in PCNs . The combination of cystoscopy by using a through-the-needle fiberoptic probe in combination with nCLE under EUS guidance may improve the diagnosis of PCNs . OBJECTIVE To assess the feasibility , safety , and diagnostic yield of the combination of cystoscopy and nCLE in the clinical diagnosis of PCNs . DESIGN A prospect i ve feasibility study . SETTING An academic tertiary referral center . PATIENTS Thirty patients with PCNs . INTERVENTIONS EUS-guided dual through-the-needle imaging ( cystoscopy and nCLE ) for PCNs . MAIN OUTCOME MEASUREMENTS Technical feasibility and safety . Associations of cystoscopy and nCLE findings with clinical diagnosis of PCNs . RESULTS The procedure was technically successful with the exception of 1 probe exchange failure . In 2 patients ( 7 % ) , postprocedure pancreatitis developed . Specific features associated with the clinical diagnosis of mucinous cysts were identified : mucin on cystoscopy and papillary projections and dark rings on nCLE . The sensitivity of cystoscopy was 90 % ( 9/10 ) , and that of nCLE was 80 % ( 8/10 ) , and the combination was 100 % ( 10/10 ) in 18 high-certainty patients . LIMITATIONS A single-center study and lack of complete pathologic correlation . CONCLUSION The combination of dual through-the-needle imaging ( cystoscopy and nCLE ) of pancreatic cysts appears to have strong concordance with the clinical diagnosis of PCN . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01447238 . ) Background Most modalities for tissue confirmation during endoscopic retro grade cholangiopancreatography ( ERCP ) suffer from low sensitivity and poor diagnostic accuracy . Probe-based confocal laser endomicroscopy ( pCLE ) was prospect ively evaluated in a multicenter registry including 102 patients with indeterminate strictures and demonstrated excellent sensitivity ( 98 % ) . Yet , several false-positive cases were induced by benign inflammatory conditions result ing in a specificity of 67 % . Aims To evaluate the diagnostic performance of pCLE for the diagnosis of indeterminate biliary stricture ; and to propose interpretation criteria for benign inflammatory conditions to reduce the number of false positives . Methods Sixty cases from the prospect i ve registry were review ed retrospectively ( 27 malignant , 33 benign ) by a panel of three biliary endoscopists . Each case ’s clinical history , ERCP impression , and corresponding pCLE sequences was used to score image quality , propose presumptive diagnoses , and rate level of diagnostic confidence . Results Using the Miami Classification ( MC ) , the overall accuracy in retrospectively diagnosing malignancy in those 60 cases was 85 versus 78 % for the prospect i ve analysis , reducing the number of false positives from 12 to 8 . A second review of the false-positive cases ’ pCLE sequences ( benign inflammatory ) helped refine the existing classification by identifying four descriptive criteria specific to benign inflammatory conditions ( Paris Classification ) : Vascular congestion , dark granular patterns with scales , increased inter-gl and ular space , and thickened reticular structure . Conclusions The Paris Classification is a refinement of the existing Miami Classification to improve the accuracy of pCLE for diagnosing benign inflammatory strictures . Prospect i ve multicenter studies are needed to further vali date this refined classification criteria As antibodies to tumor necrosis factor ( TNF ) suppress immune responses in Crohn 's disease by binding to membrane-bound TNF ( mTNF ) , we created a fluorescent antibody for molecular mTNF imaging in this disease . Topical antibody administration in 25 patients with Crohn 's disease led to detection of intestinal mTNF+ immune cells during confocal laser endomicroscopy . Patients with high numbers of mTNF+ cells showed significantly higher short-term response rates ( 92 % ) at week 12 upon subsequent anti-TNF therapy as compared to patients with low amounts of mTNF+ cells ( 15 % ) . This clinical response in the former patients was sustained over a follow-up period of 1 year and was associated with mucosal healing observed in follow-up endoscopy . These data indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatment and can be used for personalized medicine in Crohn 's disease and autoimmune or inflammatory disorders BACKGROUND AND AIMS Clinical observations suggest that the lymphoid follicles ( LFs ) may play a crucial role in the pathogenesis of inflammatory bowel disease ( IBD ) , especially in Crohn 's disease ( CD ) as the site of initial mucosal inflammation . The aim of this study was to compare the morphology of LFs in CD , ulcerative colitis ( UC ) and control patients using confocal laser endomicroscopy ( CLE ) in correlation to histological and immunohistochemical findings of biopsies . METHODS 79 patients with IBD ( 46 with CD , 32 with UC and 1 patient with indeterminate colitis ) and 67 controls patients were enrolled prospect ively in this study . Median age was 32.5 years ( range 19 - 65 ) and 37.4 years ( range 20 - 65 years ) respectively . To analyze the LFs , st and ardized images from the terminal ileum and the colon were taken using white-light video endoscopes . Additionally , CLE was performed to analyze subsurface structure of LFs . Targeted biopsies of LFs were analyzed using haematoxylin and eosin stain and immunohistochemistry . RESULTS LFs were seen in all parts of the lower GI tract , but mostly in the terminal ileum and cecum . Endoscopy in 15 out of 17 patients with the first manifestation of CD showed LFs surrounded by red ring ( so-called red ring sign , RRS ) . Histologically , LFs with RRS showed hypervascularization at the base of the LFs associated with numerous CD15-positive granulocytes . Similar features were not seen in LFs without RRS and in the control group . In some LFs with RRS early aphthous ulcers were seen . Using CLE , RRS showed abolished normal crypt architecture , crypt distortion , increased cellular infiltrate within the lamina propria , and dilated vessels . CONCLUSION LFs with RRS probably represent an early sign of aphthous ulcers in early CD and , thus , may be considered as early markers of first manifestation and flares in CD 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 BACKGROUND Confocal laser endomicroscopy ( CLE ) enables in vivo microscopic imaging of the GI tract mucosa . However , there are limited data on endoscope-based CLE ( eCLE ) for imaging Barrett 's esophagus ( BE ) . OBJECTIVE To compare high-definition white-light endoscopy ( HDWLE ) alone with r and om biopsy ( RB ) and HDWLE + eCLE and targeted biopsy ( TB ) for diagnosis of BE neoplasia . DESIGN Multicenter , r and omized , controlled trial . SETTING Academic medical centers . PATIENTS Adult patients with BE undergoing routine surveillance or referred for early neoplasia . INTERVENTION Patients were r and omized to HDWLE + RB ( group 1 ) or HDWLE + eCLE + TB ( group 2 ) . Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2 . Blinded expert pathology diagnosis was the reference st and ard . MAIN OUTCOME MEASUREMENTS Diagnostic yield , performance characteristics , clinical impact . RESULTS A total of 192 patients with BE were studied . HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia ( 34 % vs 7 % ; P < .0001 ) , compared with HDWLE + RB but with comparable accuracy . HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia ( 22 % vs 6 % ; P = .002 ) and would have obviated the need for any biopsy in 65 % of patients . The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96 % from 40 % ( P < .0001 ) without significant reduction in specificity . In vivo CLE changed the treatment plan in 36 % of patients . LIMITATIONS Tertiary-care referral centers and expert endoscopists limit generalizability . CONCLUSION Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01124214 . ) BACKGROUND AND STUDY AIMS Advances in endoscopy have led to imaging of the details of the gastric mucosa , but the histological diagnosis usually has to be confirmed by endoscopic biopsy . A method of confocal endomicroscopy that has recently been developed allows the observation of living cells in vivo . Several investigators have reported that the technique is of value , but there have as yet been no studies describing its application in gastric cancer . PATIENTS AND METHODS Twenty-seven patients with early gastric cancer underwent confocal endomicroscopy ( Pentax EG-3870CIK ; Pentax , Tokyo , Japan ) . After intravenous administration of fluorescein sodium , confocal images obtained from the normal mucosa and from cancerous lesions were interpreted by two pathologists independently and compared with the histological findings , including CD34 immunostaining of biopsy specimens or resected specimens from the same sites . RESULTS Fluorescein yielded high- quality confocal images of the gastric mucosa ; if cancer could be targeted ( 59 % ) images were mostly grade d good . The images corresponded to the hematoxylin-eosin staining of transverse sections of specimens from the same sites . In the results for the interpretation by the two pathologists , the accuracy for the diagnosis of gastric cancer was 94.2 % ( pathologist A ) , and 96.2 % ( pathologist B ) , respectively . The accuracy decreased substantially when poor images and inaccessible lesions were included . CONCLUSIONS Confocal endomicroscopy is useful in the diagnosis of gastric cancer but good quality images can not always be obtained . In the future , it may allow virtual biopsy and help reduce unnecessary biopsies Background Clostridium difficile infection ( CDI ) is one of the most dreaded causes of hospital-acquired diarrhea . Main objective was to investigate whether confocal laser endomicroscopy ( CLE ) has the capability for in vivo diagnosis of C. difficile associated histological changes . Second objective was to prove the presence of intramucosal bacteria using CLE . Methods 80 patients were prospect ively included , 10 patients were diagnosed with CDI based on toxigenic culture . To vali date the presence of intramucosal bacteria ex vivo , CLE was performed in pure C. difficile culture ; additionally fluorescence in situ hybridization ( FISH ) was performed . Finally , CLE with fluorescence labelled oligonucleotide probe specific for C. difficile was performed ex vivo in order to prove the presence of bacteria . Results CLE identified CDI-associated histological changes in vivo ( sensitivity and accuracy of 88.9 % and 96.3 % ) . In addition , intramucosal bacteria were visualized . The presence of these bacteria could be proven by CLE with labeled , specific molecular C. difficile probe and FISH-technique . Based on comparison between CLE and FISH analyses , sensitivity and specificity for the presence of intramucosal bacteria were 100 % . Conclusion CLE has the potential for in vivo diagnosis of CDI associated colitis . In addition , CLE allowed the detection of intramucosal bacteria in vivo BACKGROUND & AIMS Accurate histopathology of endoscopic duodenal biopsy specimens is critical in the diagnosis of celiac disease ( CD ) but sampling error and poor quality specimens may generate a false-negative result . Confocal endomicroscopy ( CEM ) is a novel technology allowing real-time in vivo microscopy of the mucosa that may diagnose CD and evaluate its severity and response to treatment more accurately than histopathology . METHODS Subjects with CD and controls prospect ively underwent CEM . Features of villous atrophy and crypt hypertrophy were defined . A CEM score measuring CD severity was devised and vali date d against the diagnosis of CD and blinded histopathology . Receiver operator characteristics , sensitivity to change after treatment , and reliability of findings were assessed . RESULTS From 31 patients ( 6 untreated CD , 11 treated CD , and 14 controls ) , 7019 CEM images paired with 326 biopsy specimens were obtained . The accuracy of CEM in diagnosing CD was excellent ( receiver operator characteristics area under the curve , 0.946 ; sensitivity , 94 % , specificity , 92 % ) and correlated well with the Marsh grading ( R-squared , 0.756 ) . CEM differentiated CD from controls ( P < .0001 ) and was sensitive to change after treatment with gluten-free diet ( 1787 optical biopsies ; P = .012 ) . The intraclass correlation of reliability was high ( 0.759 - 0.916 ) . Of the 17 cases with diagnosed CD , 16 ( 94 % ) were diagnosed correctly using CEM but only 13 ( 76 % ) had detectable histopathology changes . The procedure was safe and well-tolerated . CONCLUSIONS CEM effectively diagnoses and evaluates CD severity in vivo . This promising technique has the potential to improve endoscopy efficiency BACKGROUND AND AIM Current diagnostic modalities for indeterminate biliary strictures offer low accuracy . Probe-based confocal laser endomicroscopy ( pCLE ) permits microscopic assessment of mucosal structures by obtaining real-time high-resolution images of the mucosal layers of the gastrointestinal tract . Previously , an interobserver study demonstrated poor to fair agreement even among experienced confocal endomicroscopy operators . Our objective was to assess interobserver agreement and diagnostic accuracy upon completion of a pCLE training session . METHODS Forty de-identified pCLE video clips of indeterminate biliary strictures were sent to five endoscopists at four tertiary care centers for scoring . Observers subsequently attended a teaching session by an expert pCLE user that included 20 training clips and rescored the same pCLE video clips , which were r and omized and renumbered . RESULTS Pre-training interobserver agreement for all observers was ' fair ' ( Κ : 0.31 , P-value : < 0.0001 ) and diagnostic accuracy was 72 % ( 55 - 80 % ) . Post-training interobserver agreement for all observers was ' substantial ' ( Κ : 0.74 , P-value : < 0.0001 ) and diagnostic accuracy was 89 % ( 80 - 95 % ) . Using a paired t-test , we observed an increase of 17 % ( 95 % CI 7.6 - 26.4 ) in post-training diagnostic accuracy ( t = 5.01 , df = 4 , P-value 0.007 ) . CONCLUSIONS Interobserver agreement and diagnostic accuracy improved after observers underwent training by an expert pCLE user with a specific sequence set . Users should participate in such training programs to maximize diagnostic accuracy of pCLE evaluation Background The preoperative diagnosis of biliary stenosis is associated with low accuracy . As a consequence , probe-based confocal laser endomicroscopy ( pCLE ) , an in-vivo histological imaging technique , was applied in the bile duct . The aim of this study was to establish whether previous inflammation of the bile duct affects confocal interpretation . The findings from pCLE were compared in two groups of patients : those in whom there had been no cholangitis nor stenting and those in whom stents had been used and subsequently retrieved or who had suffered cholangitis . Patients and methods pCLE was performed on 54 patients ( mean age 66 years ; 31 men , 23 women ) from September 2008 to July 2011 . Patients were divided in two groups : group 1 : 39 patients who had not undergone a biliary procedure in the month preceding the pCLE procedure ; and group 2 : 15 patients who had undergone stent placement or presented with cholangitis in the month preceding the pCLE procedure . Endoscopic and pCLE data were collected prospect ively . pCLE results were compared to benchmark histology ( surgery , endoultrasonography , percutaneous biopsy ) . Patients with a benign stricture who did not undergo operation were followed for 1 year . pCLE images of the bile duct were obtained during endoscopic retro grade cholangiopancreatography procedures . pCLE images were interpreted prospect ively using the Miami classification in vivo and in real time . Results In group 1 , sensitivity , specificity , and accuracy were 88 , 83 , and 87 % , respectively . In group 2 , sensitivity , specificity , and accuracy were 75 , 71 , and 73 % , respectively . Diagnostic accuracy of pCLE was lower when applied to group 2 ( p < 0,001 ) . The investigation is less reliable in bile ducts affected by inflammation from cholangitis or previous stenting . Conclusions Inflammatory lesions of the bile duct interfere with interpretation of pCLE . A refined pCLE description of inflammatory lesions should improve accuracy of pCLE in bile duct stenosis BACKGROUND Probe-based confocal laser endomicroscopy ( pCLE ) allows real-time detection of neoplastic Barrett 's esophagus ( BE ) tissue . However , the accuracy of pCLE in real time has not yet been extensively evaluated . OBJECTIVE To compare the sensitivity and specificity of pCLE in addition to high-definition white-light endoscopy ( HD-WLE ) with HD-WLE alone for the detection of high- grade dysplasia ( HGD ) and early carcinoma ( EC ) in BE . DESIGN International , prospect i ve , multicenter , r and omized , controlled trial . SETTING Five tertiary referral centers . PATIENTS A total of 101 consecutive BE patients presenting for surveillance or endoscopic treatment of HGD/EC . INTERVENTIONS All patients were examined by HD-WLE , narrow-b and imaging ( NBI ) , and pCLE , and the findings were recorded before biopsy sample s were obtained . The order of HD-WLE and NBI was r and omized and performed by 2 independent , blinded endoscopists . All suspicious lesions on HD-WLE or NBI and 4-quadrant r and om locations were documented . These locations were examined by pCLE , and a presumptive diagnosis of benign or neoplastic ( HGD/EC ) tissue was made in real time . Finally , biopsies were taken from all locations and were review ed by a central pathologist , blinded to endoscopic and pCLE data . MAIN OUTCOME MEASUREMENTS Diagnostic characteristics of pCLE . RESULTS The sensitivity and specificity for HD-WLE were 34.2 % and 92.7 % , respectively , compared with 68.3 % and 87.8 % , respectively , for HD-WLE or pCLE ( P = .002 and P < .001 , respectively ) . The sensitivity and specificity for HD-WLE or NBI were 45.0 % and 88.2 % , respectively , compared with 75.8 % and 84.2 % , respectively , for HD-WLE , NBI , or pCLE ( P = .01 and P = .02 , respectively ) . Use of pCLE in conjunction with HD-WLE and NBI enabled the identification of 2 and 1 additional HGD/EC patients compared with HD-WLE and HD-WLE or NBI , respectively , result ing in detection of all HGD/EC patients , although not statistically significant . LIMITATIONS Academic centers with enriched population . CONCLUSIONS pCLE combined with HD-WLE significantly improved the ability to detect neoplasia in BE patients compared with HD-WLE . This may allow better informed decisions to be made for the management and subsequent treatment of BE patients . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00795184 . ) Background Confocal endomicroscopy is an emergent technique and allows real optical biopsies in the gastrointestinal ( GI ) tract . The aim of this study was to evaluate a new intraductal confocal miniprobe in patients with a normal common bile duct ( CBD ) or with a suspicion of a malignant stenosis ( cholangiocarcinoma ) . Methods Thirty-seven patients ( 23 males ) underwent endoscopic retro grade cholangiopancreatography ( ERCP ) for bile duct stone removal ( 7 cases ) or bile duct stenosis ( 30 cases ) . Intraductal confocal microscopy ( IDCM ) was performed during the ERCP using a probe-based confocal laser endomicroscopy ( pCLE ) technique . IDCM was done with the CholangioFlex probe with Cellvizio ( Mauna Kea Technologies , Paris , France ) . The depth of penetration of theCholangioFlex probe was 40–70 μm and magnification was 400 × . Images were review ed by an experienced pathologist in GI disease and compared to ERCP findings , CBD biopsies performed during ERCP or EUS , and in 15 patients to the resected specimen ( Wipple resection ) . Results No complications related to the CholangioFlex insertion occurred after the ERCP . Good images were obtained in 33 patients . Final histology diagnosis was a normal CBD in 7 cases , 23 malignant stenoses ( 4 ampullary carcinomas , 13 cholangiocarcinomas , and 6 pancreatic cancer ) , and 7 inflammatory stenoses ( 4 chronic pancreatitis , 1 stenosis of hepaticojejunal anastomosis , 1 postcholecystectomy CBD stenosis , and 1 primary sclerosing cholangitis ) . IDCM of a normal CBD showed a thin black b and ( < 20 μm ) , normal vessels ( thin and regular ) , and no visible gl and s. IDCM of malignant strictures revealed irregular vessels with lack of contrast in the CBD wall , large black b and ( > 20 μm ) , and an aggregate of irregular black cells ( black clumps ) . These aspects were seen in all malignant stenoses and none were seen in benign or normal CBD . The presence of irregular vessels , large black b and s , and black clumps seen with confocal laser microscopy enabled prediction of neoplasia with an accuracy rate of 86 % , sensitivity of 83 % , and specificity of 75 % . The respective numbers for st and ard histopathology were 53 , 65 , and 53 % . Conclusion This phase I – II study on IDCM showed that IDCM is feasible . This new technique will open a new door for optical biopsy of the CBD BACKGROUND & AIMS Colorectal cancer surveillance guidelines rely on clinicohistologic features of adenomas . Unfortunately , in common practice , recording of these features lacks precision and uniformity , which might hamper appropriate follow-up decisions . Confocal laser endomicroscopy ( CLE ) is a novel technology that allows real-time in vivo microscopy of the mucosa and provides accurate histopathology . The aims of this study were ( 1 ) to define and vali date differential features of adenomatous and nonadenomatous colorectal polyps by chromoendoscopy-guided CLE ( C-CLE ) and ( 2 ) to assess predictive value of this technique for diagnosis of colorectal neoplasia . METHODS Patients at risk for colorectal cancer were prospect ively investigated by using CLE . During extubation , fluorescein 10 % was used in conjunction with acriflavine hydrochloride 0.05 % to characterize global tissue architecture as well as cytonuclear features of colorectal epithelium . Ex vivo histology was used as gold st and ard . Reproducibility tests were performed . RESULTS In total , 116 colorectal polyps from 72 patients were examined . Ex vivo histology showed 68 adenomas , 6 invasive carcinomas , 30 hyperplastic polyps , and 12 inflammatory polyps . C-CLE of adenomas revealed lack of epithelial surface maturation , crypt budding , altered vascular pattern , and loss of cell polarity . In contrast , C-CLE of nonadenomatous polyps revealed epithelial surface maturation , and minor abnormalities of crypt architecture and of vascular pattern , and maintained cell polarity . Adenoma dysplasia score reliably discriminated high- grade dysplasia from low- grade dysplasia ( accuracy , 96.7 % ) . Interobserver agreement was high ( K coefficients : pathologist , 0.92 ; endomicroscopist , 0.88 ) . In vivo histology predicted ex vivo data with sensitivity of 97.3 % , specificity of 92.8 % , and accuracy of 95.7 % . CONCLUSIONS C-CLE accurately discriminates adenomatous from nonadenomatous colorectal polyps and enables evaluation of degree of dysplasia during ongoing endoscopy . This technology might offer considerable potential to ultimately fine-tune surveillance programs , particularly in high-risk groups BACKGROUND The diagnosis of GERD is made by using a combination of clinical symptoms , pH study , endoscopy , and histology . Histologic changes include basal cell hyperplasia and papillary elongation . Confocal laser endomicroscopy ( CLE ) enables surface and subsurface imaging of living cells in vivo at ×1000 magnification and up to 250 μm below the tissue surface . In the esophagus , the distance between the surface to papillary ( S-P ) tip can be measured by using CLE . OBJECTIVE To measure the S-P distance in the esophagus in patients with reflux esophagitis and controls by using CLE and comparing with histologic measurements . DESIGN Retrospective analysis of a prospect i ve data base . SETTING Endoscopy unit of a tertiary-care children 's hospital . PATIENTS This study involved 7 patients ( 5 female ) with a median age of 7.6 years ( range 1.8 - 15.5 years ) and median weight of 23 kg ( range 13.2 - 71 kg ) and 16 controls with a median age of 12.0 years ( range 2.2 - 15.3 years ) and median weight of 38.2 kg ( range 10.7 - 83 kg ) . INTERVENTION S-P distance was measured both by CLE and histology and was corrected for height for both patients and controls and the results compared . MAIN OUTCOME MEASUREMENTS To determine if there were significant differences in the S-P distance in patients with esophagitis and controls . RESULTS The median confocal and histologic measurements for S-P distance , corrected for patient height , were 0.19 μm/cm ( range 0.10 - 0.49 μm/cm ) and 0.58 μm/cm ( range 0.29 - 0.76 μm/cm ) and for controls were 0.44 μm/cm ( range 0.20 - 0.93 μm/cm ) and 1.07 μm/cm ( range 0.76 - 0.1.57 μm/cm ) , respectively . LIMITATIONS Small numbers involved in the study , reliance on only papillary elongation in arriving at a diagnosis . CONCLUSION Measurement of the S-P distance by CLE will enable real-time diagnosis of GERD-related esophagitis during ongoing endoscopy BACKGROUND AND AIMS Neoangiogenesis and increased endothelial permeability are observed as results of chronic intestinal inflammation . However , limited data on microvascular and crypt architecture during remission phases is available . The aim of this prospect i ve investigator blinded cohort study was to assess crypt and microvascular architecture and function in ulcerative colitis by probe based confocal laser endomicroscopy ; we also evaluated whether these findings may have the potential to predict disease relapse . METHODS 19 ulcerative colitis patients in clinical and endoscopic remission and 19 controls were studied . A computer based image processing technique was applied to construct 20 mosaicing image sets from each subject . Remitting patients were sub-grouped into either inactive or quiescent disease according to histology . RESULTS Pericrypt fluorescence ( p<0.01 ) , crypt diameter ( p<0.05 ) but not intercrypt distance ( p=0.07 ) were significantly increased in ulcerative colitis patients compared to controls . Patients with inactive disease showed a significant increase in fluorescence leakage ( median fluorescence ( IQR ) , 3888 ( 3560 - 4240 ) vs. 2696 ( 2502 - 3390 ) , p<0.01 ) , crypt diameter ( median diameter ( IQR ) , 92.5 ( 85.5 - 101 ) vs. 73 ( 70 - 77 ) , p<0.05 ) and intercrypt distance ( median distance ( IQR ) , 82.5 ( 70.5 - 91.2 ) vs. 66 ( 59.5 - 73.5 ) , p<0.05 ) compared to those with quiescent disease . A composite outcome score combining fluorescence leakage and crypt diameter was able to predict a disease flare during a 12 month follow-up period ( p<0.01 ) . CONCLUSIONS In vivo intramucosal changes detected by confocal endomicroscopy in ulcerative colitis remittent patients can predict disease relapse . This observation may have further implication s for disease management and medical treatment BACKGROUND AND STUDY AIM The real-time identification and removal of adenomas is a cost-effective strategy to improve the prognosis of colorectal cancer . Confocal laser endomicroscopy ( CLE ) could provide real-time histological-level observation . We aim ed to evaluate the efficacy of CLE diagnosis using a simple classification system that differentiates adenomas from non-neoplastic polyps with intravenous fluorescein staining alone . PATIENTS AND METHODS An endoscope integrated confocal laser microscopy system was used in this study . CLE images of 35 colonic polyps , including 15 hyperplastic polyps and 20 adenomas confirmed by histology , were first evaluated to develop criteria for diagnosis of neoplastic and non-neoplastic polyps . The diagnostic criteria included goblet cell depletion , villous architecture , and microvascular alterations . We then performed a prospect i ve study of colonic polyps found during CLE and classified them according to the established criteria . A total of 115 patients with 115 colonic polyps were included . The real-time CLE diagnosis was compared with that from histology . The stored CLE images were evaluated later by a blinded observer . RESULTS The sensitivity , specificity , positive predictive value , and negative predictive value of real-time CLE in identifying colonic adenomas were 93.9 % ( 95 % confidence interval [ CI ] 85.4 - 97.6 ) , 95.9 % ( 95 % CI 86.2 - 98.9 ) , 96.9 % ( 95 % CI 89 - 99 ) , and 92.2 % ( 95 % CI 81 - 97 ) , respectively , compared with histological results . Interobserver agreement between real-time and post-CLE still-image evaluation was excellent ( kappa = 0.929 ) . Goblet cell depletion alone had a sensitivity of 84.9 % ( 95 % CI 73 - 92 ) and a specificity of 87.8 % ( 95 % CI 75 - 95 ) , as well as excellent interobserver agreement ( kappa = 0.824 ) . CONCLUSIONS Endoscope integrated CLE with fluorescein staining may reliably assist in the real-time identification of colonic adenomas . Among three diagnostic categories , goblet cell depletion can be used to distinguish adenomas and hyperplastic polyps BACKGROUND AND STUDY AIMS Surveillance of Barrett 's esophagus includes endoscopic inspection with biopsy of suspicious lesions followed by four-quadrant biopsy of the remaining mucosa . We assessed the ability of probe-based confocal laser endomicroscopy ( pCLE ) to replace biopsy in the endoscopic evaluation of patients with Barrett 's esophagus in a prospect i ve and controlled setting . PATIENTS AND METHODS A total of 68 patients who were referred for endoscopic assessment of Barrett 's esophagus were included across three centers . pCLE recordings were interpreted live during the examination as well as in a blinded manner at least 3 months after endoscopy . pCLE diagnosis of neoplasia based on pre-defined criteria was compared with histopathology from suspicious as well as four-quadrant biopsies . RESULTS A total of 670 pairs of biopsies and pCLE video sequences were available for analysis , with neoplasia ( high- grade dysplasia or cancer ) being histologically diagnosed in 8.3 % . Specificity and negative predictive value of pCLE in excluding neoplasia was 0.97 ( 90 % CI 0.95 - 0.98 ) and 0.93 ( 0.91 - 0.95 ) for the blinded evaluation , and 0.95 ( 0.90 - 0.98 ) and 0.92 ( 0.90 - 0.94 ) for the on-site assessment . Positive predictive values ( PPVs ) and sensitivity were rather poor for both setting s ( 46 % /28 % [ blinded ] and 18 % /12 % [ on-site ] , respectively ) . CONCLUSIONS pCLE can be regarded as non-inferior to endoscopic biopsy in excluding neoplasia of Barrett 's esophagus mucosa . However , due to its low PPV and sensitivity , pCLE may currently not replace st and ard biopsy techniques for the diagnosis of Barrett 's esophagus and associated neoplasia . Further technical development of pCLE and a better underst and ing of its role in relation to other imaging technologies are necessary Background and Study Aim The incidence of cholangiocarcinoma ( CCA ) in primary sclerosing cholangitis ( PSC ) ranges between 7 and 14 % . Despite using multiple tissue sampling modalities , detection of CCA remains a challenge . Probe-based confocal laser endomicroscopy ( pCLE ) has been utilized to visualize subepithelial biliary mucosa in patients with indeterminate strictures . We assessed the technical feasibility and operating characteristics of pCLE in a cohort of PSC patients with dominant biliary strictures ( DS ) . Patients and Methods This was a chart review of a prospect ively maintained data base at a single tertiary referral center of 15 PSC patients with 21 dominant stenoses undergoing pCLE . A data collection sheet included demographics , ERCP , cholangioscopy , pCLE ( Miami criteria ) , tissue sampling results , and follow-up to 12 months or liver transplantation . Operating characteristics for pCLE and ERCP tissue sampling were calculated . Results Sufficient visualization of DS by pCLE was achieved in 20/21 ( 95 % ) . pCLE sensitivity , specificity , PPV , and NPV were 100 % ( 95 % CI 19.3–100 % ) , 61.1 % ( 95 % CI 35.8–82.6 % ) , 22.2 % ( 95 % CI 3.5–59.9 % ) , and 100 % ( 95 % CI 71.3–100 % ) , respectively , in detecting neoplasia . In comparison , concomitant tissue sampling yielded sensitivity , specificity , PPV , and NPV of 0 % ( 95 % CI 0–80.7 % ) , 94.4 % ( 95 % CI 72.6–99.1 % ) , 0 % ( 95 % CI 0–83.5 % ) , and 89.5 % ( 95 % CI 66.8–98.4 % ) , respectively . Conclusions pCLE achieves a high technical success rate in patients with PSC and DS . This single center , small series , suggests that pCLE may have a high sensitivity and negative predictive value to exclude neoplasia . If verified in larger prospect i ve studies , the technology may be utilized to risk stratify dominant strictures in patients with PSC AIM To evaluate the diagnostic accuracy of confocal laser endomicroscopy ( CLE ) for the detection of dysplasia in long-st and ing ulcerative colitis ( UC ) . METHODS We prospect ively performed a surveillance colonoscopy in 51 patients affected by long-st and ing UC . Also , in the presence of macroscopic areas with suspected dysplasia , both targeted contrasted indigo carmine endoscopic assessment and probe-based CLE were performed . Colic mucosal biopsies and histology , utilised as the gold st and ard , were assessed r and omly and on visible lesions , in accordance with current guidelines . RESULTS Fourteen of the 51 patients ( 27 % ) showed macroscopic mucosal alterations with the suspected presence of dysplasia , needing chromoendoscopic and CLE evaluation . In 5 macroscopically suspected cases , the presence of dysplasia was confirmed by histology ( 3 flat dysplasia ; 2 DALMs ) . No dysplasia/cancer was found on any of the outst and ing r and om biopsies . The diagnostic accuracy of CLE for the detection of dysplasia compared to st and ard histology was sensitivity 100 % , specificity 90 % , positive predictive value 83 % and negative predictive value 100 % . CONCLUSION CLE is an accurate tool for the detection of dysplasia in long-st and ing UC and shows optimal values of sensitivity and negative predictivity . The scheduled combined application of chromoendoscopy and CLE could maximize the endoscopic diagnostic accuracy for diagnosis of dysplasia in UC patients , thus limiting the need for biopsies Objective : The biggest challenge in endoscopic surveillance of Barrett ’s oesophagus is better detection of neoplasia in mucosa of normal macroscopic appearance . We evaluated in vivo miniprobe confocal laser microscopy ( CLM ) for the detection of invisible Barrett ’s neoplasia . Design : Prospect i ve two-centre trial in two phases : phase I to establish criteria of Barrett ’s neoplasia and phase II to test these criteria . Patients and intervention : 296 biopsy sites in 38 consecutive patients with Barrett ’s oesophagus ( mean age 62.1 years , 89.5 % men , median length of the Barrett ’s oesophagus , 3 cm ) were examined with st and ard high-resolution endoscopy and by miniprobe CLM , with precise matching of CLM recordings to biopsy sites . CLM image criteria for normal versus neoplastic Barrett ’s oesophagus were established from 95 biopsies of 15 patients ( phase I ) ; these criteria were then prospect ively tested on 201 biopsies from the remaining patients without visible focal changes ( phase II ) . All 201 CLM video recordings from phase II cases were r and omised and blindly evaluated by two gastroenterologists . Main outcome measure : The primary endpoints were accuracy values in diagnosing HGIN or early carcinoma ( EC ) on a per-biopsy basis . Secondary endpoints included inter-observer agreement . Results : All initially defined miniprobe CLM criteria ( phase I ) were significantly more frequently detected in HGIN/EC sites compared with sites with no or low grade neoplasia ( phase II ) . In a per-biopsy analysis , sensitivity and specificity for two independent investigators were 75.0 % and 88.8 % , and 75.0 % and 91.0 % , respectively , translating at best into a positive predictive value of 44.4 % and a negative predictive value of 98.8 % . Inter-observer agreement was good ( kappa 0.6 ) . Conclusion : Miniprobe CLM showed a high negative predictive value for the diagnosis of endoscopically invisible neoplasia in Barrett ’s oesophagus ; sensitivity , however , has still to be improved BACKGROUND AND STUDY AIMS The accurate diagnosis of indeterminate pancreaticobiliary strictures presents a clinical dilemma . Probe-based confocal laser endomicroscopy ( pCLE ) offers real-time in vivo microscopic tissue examination that may increase sensitivity for the detection of malignancy . the objective of this study was to develop and vali date a st and ard descriptive classification of pcle in the pancreaticobiliary system . PATIENTS AND METHODS A total of 102 patients undergoing endoscopic retro grade cholangiopancreatography ( ERCP ) with pCLE to assess indeterminate pancreaticobiliary strictures were enrolled in a multicenter registry ; 89 of these patients were evaluable . Information and data on the following were collected prospect ively : clinical , ERCP , tissue sampling , pCLE , and follow-up . A uniform classification of pCLE findings ( " Miami Classification " ) was developed , consisting of a set of image interpretation criteria . Thereafter , these criteria were tested through blinded consensus review of 112 r and omized pCLE videos from 47 patients , and inter-observer variability was assessed in 42 patients . RESULTS A consensus definition of the specific criteria of biliary and pancreatic pCLE findings for indeterminate strictures was developed . Single-image interpretation criteria did not have a high enough sensitivity for predicting malignancy . However , combining two or more criteria significantly increased the sensitivity and predictive values . The characteristics most suggestive of malignancy included the following : thick white b and s ( > 20 µm ) , or thick dark b and s ( > 40 µm ) , or dark clumps or epithelial structures . These provided sensitivity , specificity , positive predictive value , and negative predictive value of 97 % , 33 % , 80 % , and 80 % compared with 48 % , 100 % , 100 % , and 41 % for st and ard tissue sampling methods . Inter-observer variability was moderate for most criteria . CONCLUSION The Miami Classification enables a structured , uniform , and reproducible description of pancreaticobiliary pCLE . Combining individual characteristics improves the sensitivity for the detection of malignancy BACKGROUND Characterization of indeterminate biliary strictures remains problematic . Tissue sampling is the criterion st and ard for confirming malignancy but has low sensitivity . Probe-based confocal laser endomicroscopy ( pCLE ) showed excellent sensitivity in a registry ; however , it has not been vali date d in a prospect i ve study . OBJECTIVE To prospect ively vali date pCLE in real time during ERCP for indeterminate biliary strictures . DESIGN Prospect i ve , international , multicenter study . SETTING Six academic centers . PATIENTS A total of 136 patients with indeterminate biliary strictures . INTERVENTIONS Investigators provided a presumptive diagnosis based on the patient history , ERCP impression , and pCLE during the procedure before and after tissue sampling results were available . A presumptive diagnosis also was made separately by a blinded investigator during ERCP and after tissue sampling to estimate care without pCLE . Follow-up was at least 6 months . MAIN OUTCOME MEASUREMENTS Accuracy , sensitivity , and specificity during ERCP alone , ERCP with pCLE , and ERCP with pCLE and tissue sampling . RESULTS A total of 112 patients were evaluated ( 71 with malignant lesions ) . Tissue sampling alone was 56 % sensitive , 100 % specific , and 72 % ( 95 % confidence interval [ CI ] , 63%-80 % ) accurate . pCLE with ERCP was 89 % sensitive , 71 % specific , and 82 % ( 95 % CI , 74%-89 % ) accurate . After tissue sampling returned , strictures could be characterized with 88 % ( 95 % CI , 81%-94 % ) accuracy . LIMITATIONS No r and omization of care maps . pCLE not blinded . CONCLUSION pCLE provided a more accurate and sensitive diagnosis of cholangiocarcinoma compared with tissue sampling alone . Incorporation of pCLE into the diagnostic armamentarium of patients with indeterminate biliary strictures may allow for a more accurate assessment , potentially reducing delays in diagnosis and costly repeat testing . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01392274 . ) BACKGROUND & AIMS We investigated suspected food intolerances in patients with irritable bowel syndrome ( IBS ) using confocal laser endomicroscopy ( CLE ) for real-time visualization of structural/functional changes in the intestinal mucosa after food challenge . Patients with functional changes after food challenge ( CLE+ ) were placed on personalized exclusion diets and followed up for long-term symptom relief . METHODS Thirty-six IBS patients with suspected food intolerance and 10 patients with Barrett 's esophagus ( controls ) without IBS symptoms were examined by CLE at University Hospital Schleswig-Holstein ( Kiel , Germany ) . Diluted food antigens were administered directly to the duodenal mucosa through the working channel of the endoscope . Epithelial breaks , intervillous spaces , and the number of intraepithelial lymphocytes ( IEL ) were measured before and after the food challenge . CLE+ patients were placed on exclusion diets , given symptom score question naires , and followed up for 1 year ; controls resumed their previous diet . RESULTS CLE showed a real-time response to food antigens in 22 of 36 patients ; no responses were observed in 14 of 36 patients ( CLE- ) or any of the controls . Baseline IELs were significantly higher in CLE+ than CLE- subjects ( P = .004 ) ; numbers increased significantly after food challenge ( P = .0008 ) . Within 5 minutes of exposure of CLE+ patients to food antigens , IELs increased , epithelial leaks/gaps formed , and intervillous spaces widened . Epithelial leaks and intervillous spaces also increased significantly in CLE+ vs baseline ( both P < .001 ) . The concordance of IELs measured by CLE and conventional histology was 70.6 % ; they did not correlate ( P = .89 ; r(2 ) = 0.027 ) . Symptom scores improved more than 50 % in CLE+ patients after a 4-week exclusion diet and increased to 74 % at 12 months ; symptoms continued in CLE- patients . CONCLUSIONS Based on CLE analysis of IBS patients with a suspected food intolerance , exposure to c and i date food antigens caused immediate breaks , increased intervillous spaces , and increased IELs in the intestinal mucosa . These changes are associated with patient responses to exclusion diets . Registered at clinical trials.gov ( registration number : NCT01692613 ) BACKGROUND & AIMS A confocal laser endoscopy system has recently been developed that may allow subsurface imaging of living cells in colonic tissue in vivo . The aim of the present study was to assess its potential for prediction of histology during screening colonoscopy for colorectal cancer . METHODS Twenty-seven patients underwent colonoscopy with the confocal endoscope using acriflavine hydrochloride or fluorescein sodium with blue laser illumination . Furthermore , 42 patients underwent colonoscopy with this system using fluorescein sodium . St and ardized locations and circumscript lesions were examined by confocal imaging before taking biopsy specimens . Confocal images were grade d according to cellular and vascular changes and correlated with conventional histology in a prospect i ve and blinded fashion . RESULTS Acriflavine hydrochloride and fluorescein sodium both yielded high- quality images . Whereas acriflavine hydrochloride strongly labeled the superficial epithelial cells , fluorescein sodium offered deeper imaging into the lamina propria . Fluorescein sodium was thus used for the prospect i ve component of the study in which 13,020 confocal images from 390 different locations were compared with histologic data from 1038 biopsy specimens . Subsurface analysis during confocal laser endoscopy allowed detailed analysis of cellular structures . The presence of neoplastic changes could be predicted with high accuracy ( sensitivity , 97.4 % ; specificity , 99.4 % ; accuracy , 99.2 % ) . CONCLUSIONS Confocal laser endoscopy is a novel diagnostic tool to analyze living cells during colonoscopy , thereby enabling virtual histology of neoplastic changes with high accuracy . These newly discovered diagnostic possibilities may be of crucial importance in clinical practice and lead to an optimized rapid diagnosis of neoplastic changes during ongoing colonoscopy BACKGROUND & AIMS Cysts of the pancreas display a wide spectrum of histology , including inflammatory ( pseudocysts ) , benign ( serous ) , premalignant ( mucinous ) , and malignant ( mucinous ) lesions . Endoscopic ultrasonography ( EUS ) may offer a diagnostic tool through the combination of imaging and guided , fine-needle aspiration ( FNA ) . The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cystic lesions . METHODS The results of EUS imaging , cyst fluid cytology , and cyst fluid tumor markers ( CEA , CA 72 - 4 , CA 125 , CA 19 - 9 , and CA 15 - 3 ) were prospect ively collected and compared in a multicenter study using histology as the final diagnostic st and ard . RESULTS Three hundred forty-one ( 341 ) patients underwent EUS and FNA of a pancreatic cystic lesion ; 112 of these patients underwent surgical resection , providing a histologic diagnosis of the cystic lesion ( 68 mucinous , 7 serous , 27 inflammatory , 5 endocrine , and 5 other ) . Receiver operator curve analysis of the tumor markers demonstrated that cyst fluid CEA ( optimal cutoff of 192 ng/mL ) demonstrated the greatest area under the curve ( 0.79 ) for differentiating mucinous vs. nonmucinous cystic lesions . The accuracy of CEA ( 88 of 111 , 79 % ) was significantly greater than the accuracy of EUS morphology ( 57 of 112 , 51 % ) or cytology ( 64 of 109 , 59 % ) ( P < 0.05 ) . There was no combination of tests that provided greater accuracy than CEA alone ( P < 0.0001 ) . CONCLUSIONS Of tested markers , cyst fluid CEA is the most accurate test available for the diagnosis of mucinous cystic lesions of the pancreas BACKGROUND & AIMS Confocal laser endomicroscopy has been shown to allow direct histologic imaging of gastrointestinal tumors in vivo . This study was design ed to assess the potential of endomicroscopy for predicting histology in vivo during routine endoscopy in patients with early squamous cell cancer . METHODS Twenty-one consecutive patients with suspected early squamous cell cancer who had been referred for endoscopic therapy to a tertiary-care academic medical center were included in this prospect i ve study . After staining with 0.5 % Lugol 's solution and injection of 500 mg fluorescein sodium , unstained mucosal areas were examined using confocal imaging . Images of each scanned lesion were acquired and stored digitally , and in vivo diagnosis was performed during ongoing endoscopy . Biopsy specimens were taken from every lesion . The confocal images were review ed by 2 endoscopists , who were blinded to the histology and endoscopic appearance . RESULTS Confocal images were acquired from 43 lesions in 21 patients . Twenty-seven of the 43 lesions ( 63 % ) were proven to be squamous cell cancer on histology . All squamous cell cancers were diagnosed correctly by endomicroscopy and 2 lesions were falsely diagnosed as neoplastic . The overall accuracy was 95 % , and the sensitivity and specificity were 100 % and 87 % , respectively . Intraobserver agreement was almost perfect ( kappa = 0.95 ) and interobserver agreement was substantial ( kappa = 0.79 ) . CONCLUSIONS Confocal laser endomicroscopy is able to provide virtual histology of early squamous cell cancers with a high degree of accuracy and can facilitate rapid diagnosis during routine endoscopy BACKGROUND AND STUDY AIMS Confocal laser endomicroscopy ( CLE ) allows subsurface imaging of gastrointestinal mucosa in vivo . The goal of the present study was to compare the endomicroscopic characteristics of cells and intrapapillary capillary loops ( IPCLs ) in normal and superficial esophageal squamous cell carcinoma ( SESC ) . PATIENTS AND METHODS We recruited consecutive patients with SESC diagnosed by conventional endoscopy and confirmed by histopathology between July 2006 and May 2008 . The confocal endoscopic images of these patients were collected and compared with the corresponding histology . The characteristic patterns of cells and IPCLs was then analyzed from these images of malignant and normal mucosa . The quality of images and interobserver variations of two endoscopists were also evaluated . RESULTS Overall , 64 sample s from 57 subjects ( 27 SESCs , 30 controls ) were examined by CLE . The confocal images corresponded to the hematoxylin and eosin staining from the same sites . The confocal images showed that there was a significantly higher proportion of squamous epithelial cells with irregular arrangement ( 79.4 % vs. 10.0 % , P < 0.001 ) , increased diameter of IPCLs ( 26.0 microm vs. 19.2 microm , P < 0.001 ) , and irregular shape IPCLs ( 82.4 % vs. 36.7 % , P = 0.0002 ) in the SESC group compared with the controls . Massive IPCLs with tortuous vessels ( 44.1 % vs. 0 % , P < 0.0001 ) , and long branching IPCLs ( 23.5 % vs. 3.3 % , P = 0.0204 ) were frequently observed in the SESC group . In this study , about 35.5 % of images were grade d as good quality , and the interobserver agreement for the prediction of cancerous mucosa was grade d as substantial . CONCLUSIONS CLE can be used to distinguish cancerous from normal epithelium , which gives it potential value for early detection of esophageal carcinoma . The difficulty in obtaining good images in the esophagus by CLE is a latent problem BACKGROUND Altered intestinal permeability and mucosal inflammation have been reported in irritable bowel syndrome ( IBS ) patients . Increased cell extrusion in the epithelium as measured by epithelial gaps may be associated with barrier dysfunction and may lead to mucosal inflammation . Confocal laser endomicroscopy can be used to identify and quantitate epithelial gaps in the small intestine . OBJECTIVE To determine the epithelial gap density in IBS and healthy control patients . DESIGN Prospect i ve , controlled cohort study . SETTING A tertiary referral center . PATIENTS In IBS and control patients undergoing routine colonoscopy , probe-based confocal laser endomicroscopy was used to image the terminal ileum . MAIN OUTCOME MEASUREMENTS The primary outcome was the density of epithelial gaps ( gaps/cells counted ) in adequately imaged villi using pCLE . Images were review ed by 2 blinded review ers . RESULTS We recruited 18 healthy controls and 16 IBS patients . The median epithelial gap densities for control and IBS patients were 6 and 32 gaps per 1000 cells , respectively ( P < .001 ) . There was a trend toward higher gap density in female ( P = .07 ) and younger ( ρ = -0.43 , P = .07 ) patients . Using 3 % ( 90 % of the control population ) as the cutoff for abnormal gap density , we found the diagnostic accuracy for IBS to be as follows : 62 % sensitivity , 89 % specificity , 83 % positive predictive value , and 73 % negative predictive value . LIMITATIONS A single-center study , small number of patients . CONCLUSIONS IBS patients have significantly more epithelial gaps in their small intestine compared with healthy controls , which suggests that increased epithelial cell extrusion may be a cause of altered intestinal permeability observed in IBS Background Endoscopic surveillance in patients with long-st and ing inflammatory bowel disease ( IBD ) improves early detection of intraepithelial neoplasia ( IEN ) . We aim ed to compare three different endoscopic surveillance strategies in the detection of IEN . Methods One hundred fifty surveillance colonoscopies ( ulcerative colitis , UC n = 141 ; Crohn 's disease , CD n = 9 ) were carried out . R and om quadrant biopsies were taken ( group I , n = 50 ) . Chromoendoscopy with indigo carmine was performed and subsequently quadrant biopsies were collected ( group II , n = 50 ) . Patients in group III ( n = 50 ) underwent confocal endomicroscopy ( CEM ) , and CEM-guided as well as r and om quadrant biopsies were taken ( group III , n = 50 ) . The findings of CEM were correlated to conventional histology . Patients with high- grade IEN underwent surgery or strict follow-up by patients ' request . Results In group I ( 1531 biopsies ) , no IEN was detected by histology . In group II ( 1,811 biopsies ) , chromoendoscopy-guided biopsies revealed high- grade IEN in two patients ( 4 % detection rate ) . In four patients of group III ( 1477 biopsies ) , areas with high- grade IEN were clearly visible by CEM and confirmed by histology ( 8 % detection rate , p < 0.05 ) . Of six patients with high- grade IEN , five patients underwent proctocolectomy . Colorectal cancer was detected in one out of five patients . Conclusion Targeted biopsy protocol s guided by either chromoendoscopy or CEM led to higher detection rates of IEN and are thus m and atory for surveillance colonoscopies in patients with long-st and ing UC . R and om biopsy protocol s should be replaced by chromoendoscopy-guided protocol BACKGROUND AND STUDY AIMS Probe-based confocal laser endomicroscopy ( pCLE ) is a new imaging modality that enables histological examination of gastrointestinal mucosa during endoscopic procedures . Most studies have evaluated offline interpretation of pCLE images . In clinical practice , real-time interpretation is necessary to assist decision-making during the procedure . The aim of this pilot study was to compare the accuracy of real-time pCLE diagnosis made during the procedure with that of blinded offline interpretation to provide accuracy estimates that will aid the planning of future studies . PATIENTS AND METHODS pCLE was performed in patients undergoing screening and surveillance colonoscopy . Once a polyp had been identified , one endoscopist analyzed pCLE images during the procedure and made a provisional " real-time " diagnosis . Saved video recordings were de-identified , r and omized , and review ed " offline " 1 month later by the same endoscopist , who was blinded to the original diagnoses . RESULTS Images from a total of 154 polyps were recorded ( 80 neoplastic , 74 non-neoplastic ) . The overall accuracy of real-time pCLE diagnosis ( accuracy 79 % , sensitivity 81 % , specificity 76 % ) and offline pCLE diagnosis ( 83 % , 88 % , and 77 % , respectively ) for all 154 polyps were similar . Among polyps < 10 mm in size , the accuracy of real-time interpretation was significantly lower ( accuracy 78 % , sensitivity 71 % , specificity 83 % ) than that of offline pCLE interpretation ( 81 % , 86 % , 78 % , respectively ) . For polyps ≥ 10 mm , the accuracy of pCLE diagnosis in real-time was better ( accuracy 85 % , sensitivity 90 % , specificity 75 % ) than offline pCLE diagnosis ( 81 % , 97 % , and 50 % , respectively ) . CONCLUSIONS These results suggest that real-time and offline interpretations of pCLE images are moderately accurate . Real-time interpretation is slightly less accurate than offline diagnosis , but overall both are comparable . Additionally , there was contrasting accuracy between the two methods for small and large polyps BACKGROUND AND STUDY AIMS Confocal laser endomicroscopy ( CLE ) with intravenous infusion of fluorescein allows noninvasive , real-time in vivo visualization of gastrointestinal mucosa at ~ × 1000 magnification ( " virtual biopsy " ) . Conventional biopsies obtained during these procedures serve as the reference and established diagnostic st and ard . The aim of the present study was to assess whether the st and ard histologic biopsies that are obtained during CLE retain fluorescein in the tissues and allow the visualization of mucosal structures without any additional staining . PATIENTS AND METHODS CLE optical imaging of the mucosa was performed in 16 patients who were undergoing CLE colonoscopy . St and ard conventional biopsies were also obtained from both normal colonic mucosa and colonic polyps . De-paraffinized mucosal sections were examined under a fluorescence microscope for the presence and distribution of fluorescein , and then underwent immunostaining for expression of vascular endothelial growth factor ( VEGF ) . RESULTS St and ard mucosal biopsy sections from patients undergoing CLE displayed a strong fluorescence and showed well-delineated mucosal structures . In colonic adenomas , there was a 4.6-fold increased vascular permeability compared with normal mucosa ( P<0.001 ) , indicated by fluorescein leakage to the extravascular space . Immunostaining demonstrated an aberrantly increased expression of VEGF in the epithelium of colonic adenomas but not in the epithelium of normal mucosa or hyperplastic polyps . CONCLUSIONS This study shows for the first time that st and ard colonic biopsies obtained during CLE retain fluorescein , show excellent delineation of mucosal structures without additional staining , allow the evaluation of mucosal microvasculature and vascular permeability , and are suitable for immunostaining BACKGROUND Confocal laser endomicroscopy ( CLE ) is a novel endoscopic modality that allows subsurface analysis of the gastric mucosa during ongoing endoscopy . Several studies have reported that this technique is of value in the diagnosis of premalignant lesions in the GI tract , but as yet no investigations have reported its application in the analysis of gastric intraepithelial neoplasia ( GIN ) . OBJECTIVE To assess the feasibility of CLE for the identification and grading of GIN . DESIGN Prospect i ve double-blind feasibility study . SETTING Qilu Hospital , Sh and ong University , Jinan , China . PATIENTS CLE images of 33 patients were first evaluated to establish the diagnostic criteria for gastric lesions . Eligible patients were then prospect ively investigated by CLE using the newly established criteria . INTERVENTIONS All endoscopically suspicious lesions were examined by CLE , and CLE diagnoses were compared with corresponding histopathologic results . MAIN OUTCOME MEASUREMENTS Sensitivity , specificity , and positive and negative likelihood ratios of CLE diagnosis of biopsy-proven intraepithelial neoplasia by per-lesion analysis . RESULTS The sensitivity , specificity , and positive and negative likelihood ratios of CLE diagnosis of GIN were 77.8 % , 81.8 % , 4.28 , and 0.27 , respectively . The mean κ value for interobserver agreement for the diagnosis of GIN was 0.70 among endoscopists and 0.71 between endoscopist and GI pathologist . Intraepithelial neoplasia score ≥5 differentiated high- grade from low- grade intraepithelial neoplasia with a sensitivity of 66.7 % and a specificity of 88.0 % . LIMITATIONS Nonr and omized single-center study , limited number of patients . CONCLUSIONS CLE is an acceptable and potentially useful technology for the identification and grading of GIN in vivo . The diagnostic accuracy needs to be improved BACKGROUND Diagnosis and management of Barrett 's oesophagus are controversial . Technical improvements in real-time recognition of intestinal metaplasia and neoplastic foci provide the chance for more effective target biopsies . Confocal laser endomicroscopy allows to analyze living cells during endoscopy . AIMS To assess the diagnostic accuracy , inter- and intra-observer variability of endomicroscopy for detecting in vivo neoplasia ( dysplasia and /or early neoplasia ) in Barrett 's oesophagus . METHODS Prospect i ve pilot study . Patients referred for known Barrett 's oesophagus were screened . Endomicroscopy was carried out in a circular fashion , every 1 - 2 cm , on the whole columnar-lined distal oesophagus . Visible lesions , when present , were analyzed first . Targeted biopsies were taken . Confocal images were classified according to confocal Barrett classification . Endomicroscopic and histological findings were compared . RESULTS Forty-eight out of 50 screened patients underwent endomicroscopy . Visible lesions were observed in 3 patients . In a per-biopsy analysis , Barrett's-oesophagus-associated neoplasia could be predicted with an accuracy of 98.1 % . The agreement between endomicroscopic and histological results was substantial ( κ=0.76 ) . CONCLUSIONS This study suggests that endomicroscopy can provide in vivo diagnosis of Barrett 's oesophagus-associated neoplasia . Because it allows for the study of larger surface areas of the mucosa , endomicroscopy may lead to significant improvements in the in vivo screening and surveillance of Barrett 's oesophagus d t m n d m e D m This is one of a series of statements discussing the use of GI endoscopy in common clinical situations . The St and ards of Practice Committee of the American Society for Gastrointestinal Endoscopy ( ASGE ) prepared this text . This guideline is an up date of a previous ASGE guideline published in 2005.1 In preparing this guideline , a search of the medical literature was performed by using PubMed . Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants . When few or no data exist from well- design ed prospect i ve trials , emphasis is given to results from large series and reports from recognized experts . Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time that the guidelines are drafted . Further controlled clinical studies may be needed to clarify aspects of this guideline . This guideline may be revised as necessary to account for changes in technology , new data , or other aspects of clinical practice . The recommendations are based on review ed studies and are grade d on the strength of the supporting evidence ( Table 1).2 The trength of individual recommendations is based on both he aggregate evidence quality and an assessment of the nticipated benefits and harms . Weaker recommendaions are indicated by phrases such as “ We suggest , ” hereas stronger recommendations are typically stated as We recommend . ” This guideline is intended to be an educational device o provide information that may assist endoscopists in roviding care to patients . This guideline is not a rule and hould not be construed as establishing a legal st and ard of are or as encouraging , advocating , requiring , or discourging any particular treatment . Clinical decisions in any articular case involve a complex analysis of the patient ’s ondition and available courses of action . Therefore , clincal considerations may lead an endoscopist to take a ourse of action that varies from these guidelines BACKGROUND Recent technological advances in miniaturisation have allowed for a confocal scanning microscope to be integrated into trans-endoscopic probes enabling endoscopists to collect in vivo virtual biopsies of the gastrointestinal mucosa during endoscopy . AIMS The aim of the present study was to assess prospect ively the clinical applicability and predictive power of a probe-based confocal laser endomicroscopy for the in vivo diagnosis of colorectal neoplasia . METHODS Patients with evidence of colorectal superficial neoplasia at routine endoscopy , were included prospect ively in this study . Lesions were identified using white-light endoscopy followed by pCLE imaging recorded by a Coloflex UHD-type probe . The images were interpreted as either neoplastic or not according to vascular and cellular changes . pCLE readings were then compared with histopathological results from endoscopically resected lesions and /or targeted biopsy specimens . RESULTS A total of 32 lesions were identified in 20 consecutive patients . Histopathology diagnosis was of adenomas in 19 cases , hyperplastic polyps in 11 cases and adenocarcinoma in 2 cases . For the detection of neoplastic tissue pCLE had a sensitivity of 100 % , a specificity of 84.6 % , an accuracy of 92.3 , a PPV of 90.5 % and a NPV of 100 % . CONCLUSIONS pCLE permits high- quality imaging , enabling prediction of intraepithelial neoplasia with a high level of accuracy BACKGROUND Probe-based confocal laser endomicroscopy enables microscopic examination of the digestive mucosa . AIMS ( 1 ) To identify and vali date quantitative endomicroscopic criteria for evaluation of the colonic mucosa and ( 2 ) to compare these criteria between healthy and Crohn 's disease patients in clinical remission . METHODS Six healthy controls and ten Crohn 's disease patients in clinical remission were included in this prospect i ve study . Methylene blue-stained biopsies of the right colon and corresponding endomicroscopic images were analyzed . Major axis , minor axis , and major axis/minor axis ratio of crypt lumens were quantified . RESULTS Quantitative assessment was performed on 21 ± 4 crypt lumens per patient . Major axis/minor axis ratio values measured with endomicroscopy or methylene blue-stained biopsies were linearly correlated ( r=0.63 , p=0.01 ) . All macroscopically inflamed mucosa had values of major axis/minor axis ratio higher than the median of controls . Interestingly , 50 % ( 3/6 ) of Crohn 's disease patients with macroscopically normal mucosa had also a higher ratio than pooled controls . Histological analysis showed that 6/7 patients with major axis/minor axis ratio superior to 1.7 had microscopic inflammation . CONCLUSION Probe-based confocal laser endomicroscopy allows quantitative analysis of colonic pit structure . Endomicroscopic analysis of major axis/minor axis ratio allows the detection of microscopic residual inflammation with greater accuracy than st and ard endoscopy in Crohn 's disease patients in clinical remission Background The identification of gastric superficial cancerous lesions based on conventional white-light endoscopy ( WLE ) is challenging , and histological analysis remains the ‘ gold st and ard ’ for the final diagnosis . Confocal laser endomicroscopy ( CLE ) can provide in vivo histological observation without the need for biopsy . Objective To develop and evaluate CLE imaging criteria for gastric superficial cancerous lesions and to compare the diagnostic value of real-time integrated CLE ( iCLE ) and WLE alone in distinguishing gastric superficial cancerous lesions . Design Prospect i ve study . Setting Qilu Hospital , Sh and ong University , Jinan , China . Patients A total of 182 patients were enrolled into phase I and 1786 patients were enrolled into phase II . Interventions CLE images were blindly evaluated after endoscopy in phase I , and real-time iCLE diagnosis during endoscopy was compared with WLE diagnosis by using histopathology as a gold st and ard in phase II . Main outcome measurements The validity and reliability of the CLE diagnosis for identifying gastric superficial cancerous lesions . Results Off-line CLE diagnosis for early gastric cancers had a high sensitivity ( 88.1 % ) and specificity ( 98.6 % ) . When the two-tiered CLE classification of non-cancerous lesions and cancer/high- grade intraepithelial neoplasia ( HGIN ) lesions was introduced , CLE diagnosis led to a higher sensitivity ( 90.2 % ) and specificity ( 98.5 % ) ( phase I ) . Real-time iCLE diagnosis had a higher sensitivity ( 88.9 % ) , specificity ( 99.3 % ) and accuracy ( 98.8 % ) for gastric superficial cancer/HGIN lesions than WLE diagnosis ( sensitivity , 72.2 % ; specificity , 95.1 % ; and accuracy , 94.1 % ) ( p<0.05 ) ( phase II ) . Limitations This was a single-centre study . Conclusions CLE can be used to identify gastric superficial cancer/HGIN lesions with high validity and reliability BACKGROUND Residual neoplasia after EMR of colorectal lesions is common . There is a critical need for imaging methods to accurately diagnose residual disease and to guide retreatment in real time . OBJECTIVE The aim was to estimate and compare the accuracy of virtual chromoendoscopy ( VCE ) and probe-based confocal laser endomicroscopy ( pCLE ) for detection of residual neoplastic tissue at the site of prior EMR . DESIGN Prospect i ve , blind , pilot comparison of advanced endoscopic imaging ( VCE and pCLE ) by using matching histology as reference st and ard . SETTING Three tertiary-care referral hospitals . PATIENTS This study involved 92 participants who underwent follow-up colonoscopies for the evaluation of prior EMR sites within 1 year . INTERVENTION The EMR scars were assessed during follow-up high-resolution colonoscopy by using VCE ( narrow-b and imaging/Fujinon Intelligent Color Enhancement [ FICE ] ) , and pCLE . Confocal videos of EMR scars were interpreted in real time and were also stored and review ed offline , blinded to histopathology and endoscopic appearance . Tissue confirmation by biopsies or polypectomy/repeat EMR was performed in all cases . MAIN OUTCOME MEASUREMENTS Sensitivity , specificity , and accuracy for VCE and pCLE alone and in combination against histopathology as the st and ard reference st and ard . RESULTS Among 129 EMR scars , residual neoplasia was confirmed by histology in 29 sites ( 22 % ) . For VCE , the sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and accuracy were 72 % , 77 % , 49 % , 91 % , and 77 % , respectively , and were 97 % , 77 % , 55 % , 99 % , and 81 % for pCLE ( P = .045 for sensitivity ) . When only EMR scars for which VCE and pCLE agreed on the diagnosis were analyzed ( 95/129 scars ) , the accuracy , sensitivity , specificity , PPV , and NPV of pCLE and VCE were 90 % , 100 % , 87 % , 67 % , and 100 % , respectively . LIMITATIONS Small sample size , lack of power , involvement of highly experienced pCLE experts . CONCLUSION Confocal endomicroscopy significantly increases the sensitivity for detecting residual neoplasia after colorectal EMR compared with endoscopy alone . When confocal endomicroscopy is used in combination with VCE , the accuracy is extremely high , and sensitivity approaches that of histopathology . Together , they may reduce the need for histologic examination and allow a highly accurate on-table decision to treat again or not , thus avoiding unnecessary repeat procedures . ( CLINICAL TRIAL REGISTRATION NUMBER 00874263 . ) BACKGROUND & AIMS Confocal fluorescence microscopy ( CFM ) has been mentioned to be a promising tool for in vivo histology . Recently , a portable confocal miniprobe has been developed . Our aim was to evaluate the potential benefit of CFM for detection of gastrointestinal neoplasia . METHODS A total of 47 patients with known or suspected neoplasia in the upper ( n = 34 ) or lower gastrointestinal tract ( n = 13 ) were examined with st and ard endoscopes . After mucolyis with 5 - 10 mL of acetic acid 1.5 % , chromoendoscopy with 2 - 5 mL cresyl violet 0.25 % was performed , with the substance also being used as a fluorophore for CFM . Real-time video sequences were recorded . Thereafter , biopsies were taken or mucosectomy/polypectomy was performed from the same examined area . All stored sequences were put into a r and om order and assessed by a pathologist and a gastroenterologist both blinded to any data . RESULTS A total of 119 CFM video sequences were recorded of 85 benign or 34 neoplastic areas . Quality of CFM images was regarded too low in 24 ( pathologist ) and 14 sequences ( gastroenterologist ) . For the pathologist , accuracy of CFM detecting neoplasia was 92.6 % ( suitable images ) and 73.9 % ( intention to diagnose ) . The respective accuracy values for the gastroenterologist were 92.4 % ( suitable images ) and 81.5 % ( intention to diagnose ) . Agreement between CFM and histopathology was excellent ( kappa values , 0.821 and 0.817 ) . CONCLUSIONS We have demonstrated that CFM with a miniprobe has the potential to diagnose neoplasia during ongoing endoscopy . This system has the advantage that it can be used with st and ard endoscopes . Further studies are warranted for validation OBJECTIVES : Objective ly diagnosing non-erosive reflux disease ( NERD ) is still a challenge . We aim ed to evaluate the use of in-vivo confocal laser endomicroscopy ( CLE ) to examine the microalterations of the esophagus in patients with NERD and its relationship with reflux episodes monitored by multiple intraluminal impedance-pH ( MII-pH ) . METHODS : Patients with gastroesophageal reflux symptoms completed reflux disease question naires . NERD was determined by negative gastroscopy . Patients without reflux symptoms were recruited as controls . Pilot clinical study was followed by prospect i ve controlled blinded study . All subjects were examined by white-light mode of the endoscopy followed by the st and ard CLE mode and then MII-pH monitoring . The microalterations seen on CLE images and the correlation between CLE features and reflux episodes were evaluated , the correlation between CLE and transmission electron microscope ( TEM ) data was also analyzed . RESULTS : On CLE images , NERD patients had more intrapapillary capillary loops ( IPCLs ) per image than did controls ( 8.29±3.52 vs. 5.69±2.31 , P=0.010 ) , as well as the diameter of IPCLs ( 19.48±3.13 vs. 15.87±2.21 μm , P=0.041 ) and intercellular spaces of squamous cells ( 3.40±0.82 vs. 1.90±0.53 μm , P=0.042 ) . The receiver operating characteristic analysis indicated that IPCLs number ( optimal cutoff > 6 per image , area under the curve ( AUC ) 0.722 , 95 % confidence interval ( CI ) 0.592–0.853 , sensitivity 67.7 % , specificity 71.6 % ) , IPCLs diameter ( optimal cutoff > 17.2 μm , AUC 0.847 , 95 % CI 0.747–0.947 , sensitivity 81 % , specificity 76 % ) , and the intercellular spaces of squamous cells ( optimal cutoff > 2.40 μm , AUC 0.935 , 95 % CI 0.875–0.995 , sensitivity 85.7 % , specificity 90.5 % ) diagnosed NERD with reasonable accuracy . Combined features of dilatation of intercellular space plus increased IPCLs provided 100 % specificity in the diagnosis of NERD patients . The intercellular spaces of squamous cells observed on CLE were highly related to that on TEM findings ( r=0.75 , P<0.001 ) . Multivariate progressive regression analysis showed that acidic reflux , especially in the supine position , was related to the increased number and dilation of IPCLs in the squamous epithelium ( β=0.063 , t=2.895 , P=0.038 and β=0.156 , t=1.023 , P=0.04 ) . CONCLUSIONS : CLE represents a useful and potentially significant improvement over st and ard endoscopy to examine the microalterations of the esophagus in vivo . Acidic reflux is responsible for the microalterations in the esophagus of patients with NERD BACKGROUND AND AIMS Because of the large number of biopsy specimens , surveillance colonoscopy in ulcerative colitis ( UC ) is currently time consuming and significant flat lesions still may be missed . In this study we assessed the value of combined chromoscopy and endomicroscopy for the diagnosis of intraepithelial neoplasias in a r and omized controlled trial . METHODS A total of 161 patients with long-term UC in clinical remission were r and omized at a 1:1 ratio to undergo conventional colonoscopy or chromoscopy with endomicroscopy . Eight patients were excluded because of insufficient bowel preparation . In the conventional colonoscopic group ( n = 73 ) , r and om biopsy examinations and targeted biopsy examinations were performed . In the endomicroscopy group ( n = 80 ) , circumscribed mucosal lesions were identified by chromoscopy and evaluated for targeted biopsy examination by endomicroscopy . The primary outcome analysis was based on the detection of neoplasias . RESULTS By using chromoscopy with endomicroscopy , 4.75-fold more neoplasias could be detected ( P = .005 ) than with conventional colonoscopy , although 50 % fewer biopsy specimens ( P = .008 ) were required . If only circumscribed lesions would have been biopsied in the first group , the total number of biopsy specimens could have been reduced by more than 90 % . A total of 5580 confocal endomicroscopic images from 134 circumscribed lesions were compared with histologic results . The presence of neoplastic changes could be predicted by endomicroscopy with high accuracy ( sensitivity , 94.7 % ; specificity , 98.3 % ; accuracy , 97.8 % ) . CONCLUSIONS Endomicroscopy based on in vivo histology can determine if UC lesions identified by chromoscopy should undergo biopsy examination , thereby increasing the diagnostic yield and reducing the need for biopsy examinations . Thus , chromoscopy-guided endomicroscopy may lead to significant improvements in the clinical management of UC BACKGROUND Epithelial gaps created by shedding of epithelial cells in the small intestine can be visualized by using confocal laser endomicroscopy ( CLE ) . The density of epithelial gaps in the small bowels of patients with inflammatory bowel disease ( IBD ) and controls without IBD is unknown . OBJECTIVE To determine whether the epithelial gap density in patients with IBD is different from that in controls . DESIGN Prospect i ve , controlled , cohort study . SETTING A tertiary-care referral center . PATIENTS This study involved patients with IBD and control patients without IBD undergoing colonoscopy . INTERVENTION Probe-based CLE ( pCLE ) was used to image the terminal ileum . MAIN OUTCOME MEASUREMENTS The primary outcome of the study was gap density , defined as the total number of gaps per 1000 cells counted in adequately imaged villi by using pCLE . The pCLE images were blindly review ed , and the number of epithelial gaps and cells were manually counted . The secondary outcomes were correlation of gap density with disease activity , location , and severity of clinical disease . RESULTS There were 30 controls and 28 patients with IBD . Of the patients with IBD , 16 had Crohn 's disease , and 12 had ulcerative colitis . The median epithelial gap densities for controls and patients with IBD were 18 and 61 gaps/1000 cells , respectively ( P < .001 ) . Gap density did not correlate with disease activity . Patients with ulcerative pan-colitis tended toward gap densities lower than those of patients with limited colitis ( 32 versus 97 gaps/1000 cells , P = .06 ) . Patients with IBD with severe clinical disease also had lower median gap densities ( 37 vs 90 gaps/1000 cells , P = .04 ) . LIMITATIONS A single-center study . CONCLUSION The epithelial gap density was significantly increased in patients with IBD compared with controls . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00988273 . ) BACKGROUND Endoscopists with extensive experience with confocal endomicroscopy ( CEM ) have demonstrated that this technology is useful for Barrett 's esophagus ( BE ) surveillance . However , data on endoscopists with minimal experience with this technique are limited . HYPOTHESIS For BE surveillance , an endoscopist with minimal experience in CEM-guided biopsy would achieve a similar diagnostic yield with fewer biopsies when compared to the r and om 4-quadrant biopsy protocol . OBJECTIVE To compare the diagnostic yields of CEM-guided biopsy technique with the r and om 4-quadrant biopsy protocol . DESIGN R and omized controlled trial . SETTING Tertiary care center . PATIENTS Patients with BE . METHODS Out of 18 patients who underwent routine BE surveillance , 11 and 7 were r and omly assigned to group A ( CEM-guided ) and to group B ( r and om 4-quadrant biopsy ) , respectively . The pathologists were blinded to all clinical information . RESULTS Mean length of endoscopic Barrett was similar in both groups , ( 5.1 vs. 6.3 cm , p=0.51 ) . The diagnostic yields for detecting SIM ( 63.6 % vs. 59.5 % , p=0.5 ) , low grade dysplasia ( 11 . 6 % vs. 11.2 % , p = NS ) , high grade dysplasia ( 10.1 % vs. 11.5 % , p=0.88 ) . Although the total number of individual mucosal biopsy performed were 52 % lower in the CEM group ( 129 vs. 269 ) , the overall diagnostic yield ( 85.3 % vs. 82.2 % , p=0.53 ) was similar in both groups . LIMITATIONS Small sample size . CONCLUSIONS For BE surveillance , limited data suggested that endoscopists with minimal experience in CEM can effective use this technology for " smart " biopsy to decrease the need for intense tissue sampling but without lowering the diagnostic yield in detecting dysplasia BACKGROUND Because of the low sensitivity of current ERCP-guided tissue sampling methods , management of patients with indeterminate pancreaticobiliary strictures is a challenge . Probe-based confocal laser endomicroscopy ( pCLE ) enables real-time microscopic visualization of strictures during an ongoing ERCP . OBJECTIVE To document the utility , performance , and accuracy of real-time pCLE diagnosis compared with histopathology . DESIGN Prospect i ve observational study within the framework of a multicenter registry . SETTING Five academic centers . PATIENTS This study involved 102 patients with indeterminate pancreaticobiliary strictures . INTERVENTION Clinical information , ERCP findings , tissue sampling results , and pCLE videos were collected prospect ively . Investigators were asked to provide a presumptive diagnosis based on pCLE during the procedure before pathology results were available . All patients received at least 30 days of follow-up until definitive diagnosis of malignancy was established or 1-year follow-up if index tissue sampling was benign . MAIN OUTCOME MEASUREMENTS Diagnostic accuracy , sensitivity , specificity of ERCP-guided pCLE compared with ERCP with tissue acquisition . RESULTS There were no pCLE-related adverse events in the study . We were able to evaluate 89 patients , of whom 40 were proven to have cancer . The sensitivity , specificity , positive-predictive value , and negative-predictive value of pCLE for detecting cancerous strictures were 98 % , 67 % , 71 % , and 97 % , respectively , compared with 45 % , 100 % , 100 % , and 69 % for index pathology . This result ed in an overall accuracy of 81 % for pCLE compared with 75 % for index pathology . Accuracy for combination of ERCP and pCLE was significantly higher compared with ERCP with tissue acquisition ( 90 % vs 73 % ; P = .001 ) . LIMITATIONS Investigators had access to all relevant clinical information , which may have biased the predictive characteristics of pCLE . CONCLUSION Probe-based CLE provides reliable microscopic examination and has excellent sensitivity and negative predictive value . The significantly higher accuracy of ERCP and pCLE compared with ERCP with tissue acquisition may support supplementing ERCP with pCLE BACKGROUND & AIMS The management of dysplasia-associated lesional mass ( DALM ) and adenoma-like mass ( ALM ) in chronic ulcerative colitis ( CUC ) differs radically , involving total pan-proctocolectomy vs endoscopic resection and surveillance . Such lesions can not be reliably differentiated using conventional colonoscopy . Confocal laser scanning imaging enables in vivo surface and subsurface cellular resolution imaging during ongoing video endoscopy . The aim of this study was to prospect ively assess the clinical applicability and predictive power of the Pentax EC3870 K endomicroscope for the in vivo differentiation of ALM and DALM in CUC during ongoing videocolonoscopy . METHODS Patients were recruited who had a diagnosis of ALM or DALM within the previous 16 weeks . Confocal laser endomicroscopic ( CLE ) imaging of the circumscribed lesion and 4 adjacent mucosal segments was performed . Targeted biopsy with and without tissue sampling with endoscopic mucosal resection was performed and compared with conventional histopathology as the gold st and ard . RESULTS Thirty-six patients with 36 lesions fulfilled the study entry criteria . Using modified Mainz criteria for the in vivo diagnosis of ALM and DALM , the kappa coefficient of agreement between CLE and histopathologic evaluation was 0.91 , and accuracy was 97 % ( 95 % confidence interval = 86%-99 % ) . CONCLUSIONS This is the first study addressing the novel application of the Pentax EC3870 K endomicroscopy system for the in vivo differentiation of ALM and DALM during ongoing video colonoscopy in CUC . We have shown that ALM and DALM can be differentiated with a high overall accuracy , enabling the safe selection of patients suitable for endoluminal resection versus immediate referral for pan-proctocolectomy BACKGROUND Probe-based confocal laser endomicroscopy ( pCLE ) allows real-time in vivo histologic evaluation of GI mucosal lesions . Although pCLE has been used for various GI disorders , the significance of pCLE for gastric lesions is largely unknown . OBJECTIVE We compared the accuracy of conventional endoscopic forceps biopsy and pCLE for the diagnosis of superficial gastric neoplasia before endoscopic resection . DESIGN Prospect i ve comparative study . SETTING Single tertiary referral center . PATIENTS This study involved 54 superficial gastric neoplasias in 46 patients . MAIN OUTCOME MEASUREMENT Accuracy of in vivo and offline pCLE diagnosis and interobserver agreement . METHODS pCLE was performed before endoscopic resection of superficial gastric neoplasias previously diagnosed by endoscopic biopsy . The overall accuracy of endoscopic , in vivo pCLE , and offline pCLE diagnosis was compared with postendoscopic resection histopathology . RESULTS Endoscopic resection was performed on 54 lesions . On final histopathology , there were 3 non-neoplastic lesions , 19 gastric dysplasias , 22 differentiated adenocarcinomas , and 10 undifferentiated adenocarcinomas . The overall agreement with the final histopathology was substantial for conventional biopsies ( κ = 0.617 ) and excellent for in vivo pCLE ( κ = 0.824 ) ( P < .001 ) . The overall accuracy for the diagnosis of adenocarcinoma was 91.7 % for pCLE and 85.2 % for conventional biopsies ( P = .065 ) . The combined accuracy of conventional endoscopic biopsies and pCLE was 98.1 % . The interobserver agreement for offline pCLE diagnosis was excellent ( κ = 0.931 ) . LIMITATIONS Single-center study , small sample size . CONCLUSION Our study showed that pCLE can provide an accurate diagnosis for superficial gastric neoplasia . pCLE has the potential to compensate for the inherent limitations of a conventional endoscopic biopsy BACKGROUND AND STUDY AIMS Advances in endoscopic imaging techniques have enabled more accurate identification of subtle mucosal abnormalities . The aim of the study was to assess the accuracy of predicting high grade dysplasia ( HGD ) and intramucosal cancer ( IMC ) in mucosa predicted as being nondysplastic vs. dysplastic by high definition white light endoscopy ( HD-WLE ) , narrow b and imaging ( NBI ) , and confocal laser endomicroscopy ( CLE ) . PATIENTS AND METHODS A cross-sectional study was performed in a tertiary referral setting between February 2010 and September 2011 . A total of 50 consecutive patients who were referred to St Vincent 's Hospital for management of dysplastic Barrett 's esophagus were included . A prediction of likely histology was made for each mucosal point ( four-quadrant every 1 cm and any visible mucosal abnormality ) , first with HD-WLE , followed by NBI , and finally CLE . Biopsies were taken at all of these points . RESULTS A total of 1190 individual biopsy points were assessed . At histology , 39 biopsy points were found to harbor HGD and 52 biopsy points harbored IMC . For the detection of HGD/IMC the sensitivity , specificity , and accuracy were : HD - WLE , 79.1 % , 83.1 % , and 82.8 % ; NBI , 89.0 % , 80.1 % , and 81.4 % ; and CLE , 75.7 % , 80.0 % , and 79.9 % , respectively . All mucosal points with IMC and all patients with HGD were detected by targeted biopsies guided by HD-WLE and NBI without the need for r and om Seattle protocol biopsies . CONCLUSIONS HD-WLE in combination with NBI is highly accurate in the detection of HGD/IMC . Performing targeted biopsies in the surveillance of Barrett 's esophagus is possible in expert centers BACKGROUND Confocal laser endomicroscopy ( CLE ) is a rapidly emerging method for in vivo imaging of the GI tract . OBJECTIVE To determine the preliminary evaluation accuracy and interobserver agreement of probe-based CLE ( pCLE ) in Barrett 's esophagus ( BE ) . DESIGN Prospect i ve , double-blind review of pCLE images of 40 sites of BE tissue by using matching biopsies as the reference st and ard . A training set of 20 images with known histology was first review ed to st and ardize image interpretation , followed by blinded review of 20 unknown images . SETTING Eleven experts in BE imaging from 4 different endoscopy centers from the United States and Europe evaluated the images . PATIENTS This study involved nonconsecutive patients undergoing BE surveillance or evaluation of high- grade intraepithelial neoplasia or early adenocarcinoma . INTERVENTION Intravenous fluorescein pCLE imaging of each site within the BE segment , followed by matching biopsy . MAIN OUTCOME MEASUREMENTS Sensitivity , specificity , and agreement for the pCLE diagnosis of high- grade intraepithelial neoplasia or carcinoma . RESULTS In the validation set ( n = 20 ) , 11 cases had high- grade intraepithelial neoplasia or invasive carcinoma . The sensitivity for the diagnosis of neoplasia for the 11 endoscopists was 88 % ( range 6 of 11 to 11 of 11 ) , and the specificity was 96 % ( range 7 of 9 to 9 of 9 ) . There was substantial agreement on the pCLE diagnosis ( 86 % , kappa 0.72 ; 95 % confidence interval , 0.58 - 0.86 ) . Endomicroscopists with prior pCLE experience had an overall sensitivity of 91 % ( all 10 of 11 ) , specificity of 100 % ( all 9 of 9 ) , and almost perfect agreement ( 92 % , kappa 0.83 ; 95 % confidence interval , 0.64 - 1.0 ) . LIMITATIONS Small sample size and use of offline video sequences . CONCLUSION Results suggest that pCLE for the diagnosis of neoplasia in BE has very high accuracy and reliability BACKGROUND Confocal laser endomicroscopy ( CLE ) allows real-time in vivo histologic evaluation of GI lesions . To our knowledge , there is no reported prospect i ve study comparing endoscopic and optical biopsy using CLE before endoscopic submucosal dissection ( ESD ) with post-ESD histopathology . OBJECTIVE We compared endoscopic and optical biopsy before ESD and thereby assessed the ability of CLE to effectively diagnose and differentiate gastric epithelial neoplasia . DESIGN Single tertiary-care center , prospect i ve comparative study . SETTING Soonchunhyang University Hospital , between September 2009 and April 2010 . PATIENTS This study involved 31 patients with 35 gastric epithelial neoplasias , previously diagnosed by endoscopic biopsy , who were scheduled for ESD . INTERVENTION Target lesions were imaged in vivo by using CLE . MAIN OUTCOME MEASUREMENTS The overall accuracy of endoscopic and CLE diagnosis was compared with post-ESD histopathology . RESULTS In histopathology after ESD , 11 of 35 lesions ( 31.5 % ) were adenomas and 24 ( 68.5 % ) were adenocarcinomas . The overall accuracy of CLE diagnosis of gastric adenomas and adenocarcinomas was significantly higher at 94.2 % ( 95 % confidence interval [ CI ] , 81.3 - 98.4 ) , versus 85.7 % ( 95 % CI , 70.6 - 93.7 ) for endoscopic biopsy ( P = .031 ) . The overall accuracy of CLE diagnosis of differentiated and undifferentiated adenocarcinomas also was higher ( 95.4 % ; 95 % CI , 78.2 - 99.1 ) than that of endoscopic biopsy ( 84.2 % ; 95 % CI , 62.4 - 94.4 ) but did not differ significantly ( P = .146 ) . LIMITATIONS Single tertiary-care center experience and small patient number . CONCLUSION This study demonstrates the high accuracy of diagnosis of gastric epithelial neoplasia by using CLE . The use of CLE could possibly thus reduce the number of unnecessary biopsies and mistaken diagnoses before ESD BACKGROUND AND AIM Confocal laser endomicroscopy ( CLE ) is a new endoscopy technique for subsurface analysis of the gastric mucosa and in vivo histology examination during endoscopy . We aim ed to compare the clinical applicability and predictive power of CLE with the diagnosis of Helicobacter pylori infection in patients with gastrointestinal symptoms . METHODS A total of 103 consecutive patients scheduled to undergo endoscopy were enrolled . CLE image criteria for H. pylori infection were established in a pilot study of 20 patients , then images for 83 consecutive patients were prospect ively evaluated , and data were correlated with the final diagnosis of H. pylori infection in a blinded manner . RESULTS We found good association between histopathology and CLE findings . H. pylori infection was identified by CLE with any of the following three features : white spots , neutrophils and microabscesses . The accuracy , sensitivity and specificity of CLE diagnosis of H. pylori infection were 92.8 % , 89.2 % and 95.7 % , respectively . The mean kappa-value for interobserver agreement in the prediction of H. pylori infection was 0.78 . Neutrophils were the best diagnostic feature and had good sensitivity ( 83.8 % ) and specificity ( 97.8 % ) . H. pylori-associated changes were more common in the antrum than in the corpus among infected patients ( P < 0.001 ) . CONCLUSIONS H. pylori infection can be identified by specific cellular and subcellular changes of the surface gastric mucosa with CLE . CLE is a novel , useful method for predicting H. pylori infection in vivo during endoscopy Background : Confocal laser endomicroscopy ( CLE ) allows microscopic imaging within the mucosal layer of the gut during ongoing endoscopy . Different studies have addressed the potential of CLE for in vivo diagnosis of ulcerative colitis and microscopic colitis . However , there are no data on the utility of CLE for in vivo diagnosis of Crohn 's disease ( CD ) . The aim was to assess the clinical utility of CLE in patients with CD and to determine whether disease activity can be grade d using CLE . Methods : Consecutive patients with and without CD were enrolled . The colonic mucosa was examined by st and ard white‐light endoscopy followed by CLE . The features seen on CLE were compared between CD patients and controls . Results : In all , 76 patients with CD were screened , of whom 54 patients were included in the present study . Eighteen patients without inflammatory bowel disease ( IBD ) served as controls . A significantly higher proportion of patients with active CD had increased colonic crypt tortuosity , enlarged crypt lumen , microerosions , augmented vascularization , and increased cellular infiltrates within the lamina propria . In quiescent CD , a significant increase in crypt and goblet cell number was detected compared with controls . Based on our findings , we propose a Crohn 's Disease Endomicroscopic Activity Score ( CDEAS ) for assessing CD activity in vivo . Conclusions : CLE has the potential to significantly improve diagnosis of CD compared with st and ard endoscopy . These findings should be evaluated in future prospect i ve trials to assess the value of this newly developed CLE score for prediction of disease course and therapeutic responses . ( Inflamm Bowel Dis 2012 ; BACKGROUND & AIMS Probe-based confocal laser endomicroscopy ( pCLE ) allows in vivo imaging of tissue at micron resolution . Virtual chromoendoscopy systems , such as Fujinon intelligent color enhancement and narrow b and imaging , also have potential to differentiate neoplastic colorectal lesions . The accuracy of these systems in clinical practice is , however , unknown . Our primary aim was to compare sensitivity and specificity of pCLE to virtual chromoendoscopy for classification of colorectal polyps using histopathology as a gold st and ard . A secondary aim was to compare sensitivity and specificity of pCLE to virtual chromoendoscopy using a modified gold st and ard that assumed that all polyps > /=10 mm had malignant potential and were considered neoplastic or high risk . METHODS Patients underwent colonoscopy using high-resolution colonoscopes . The surface pit pattern was determined with NBI or FICE in all patients . Confocal images were recorded and subsequently analyzed offline , blinded to the endoscopic characteristics and histopathology . Each polyp was diagnosed as benign or neoplastic based on confocal features according to modified Mainz criteria . RESULTS A total of 119 polyps ( 81 neoplastic , 38 hyperplastic ) from 75 patients was assessed . The pCLE had higher sensitivity compared to virtual chromoendoscopy when considering histopathology as gold st and ard ( 91 % vs 77 % ; P = .010 ) and modified gold st and ard ( 88 % vs 76 % ; P = .037 ) . There was no statistically significant difference in specificity between pCLE and virtual chromoendoscopy when considering histopathology or modified gold st and ard . CONCLUSIONS Confocal endomicroscopy demonstrated higher sensitivity with similar specificity in classification of colorectal polyps . These new methods may replace the need for ex vivo histological confirmation of small polyps , but further studies are warranted BACKGROUND AND AIMS Surveillance of patients with ulcerative colitis consists of taking targeted and r and om biopsies , which is time-consuming and of doubtful efficiency . The use of probe-based confocal laser endomicroscopy ( pCLE ) may increase efficiency . This prospect i ve pilot study aim ed to evaluate the feasibility and diagnostic accuracy of pCLE in ulcerative colitis surveillance . METHODS In 22 patients with ulcerative colitis , 48 visible lesions and 87 r and om areas were initially evaluated by real-time narrow-b and imaging ( NBI ) and high-definition endoscopy ( HDE ) . Before taking biopsies , fluorescein-enhanced pCLE was performed . All pCLE videos were scored afterwards by two endoscopists who were blinded to histology and endoscopy . Outcome measures were : ( 1 ) the feasibility of pCLE , expressed as pCLE imaging time required , percentage of imaging time with clear pCLE histology , and pCLE video quality as rated by two endoscopists ; and ( 2 ) the diagnostic accuracy of pCLE . RESULTS The median pCLE imaging time required was 98 seconds for lesions vs. 66 seconds for r and om areas ( P = 0.002 ) . The median percentages of imaging time with clear pCLE histology were 61 % vs. 81 % respectively ( P < 0.001 ) . The pCLE video quality was rated as good/excellent in 69 % . Feasibility was significantly poorer for sessile and pedunculated mobile lesions . The sensitivity , specificity , and accuracy of blinded pCLE were 65 % , 82 % , and 81 % , whereas these figures were 100 % , 89 % , and 92 % for real-time endoscopic diagnosis with NBI and HDE . CONCLUSION This study demonstrates that pCLE for ulcerative colitis surveillance is feasible with reasonable diagnostic accuracy . Future research should show whether increased experience with pCLE improves its ease of use and whether real-time pCLE diagnosis is associated with greater diagnostic accuracy BACKGROUND AND STUDY AIMS The differential diagnosis of solitary pancreatic cystic lesions is frequently difficult . Needle-based confocal laser endomicroscopy ( nCLE ) performed during endoscopic ultrasound-guided fine-needle aspiration ( EUS-FNA ) is a new technology enabling real-time imaging of the internal structure of such cysts . The aim of this pilot study was to identify and vali date new diagnostic criteria on nCLE for pancreatic cystic lesions . PATIENTS AND METHODS A total of 31 patients with a solitary pancreatic cystic lesion of unknown diagnosis were prospect ively included at three centers . EUS-FNA was combined with nCLE . The final diagnosis was based on either a stringent gold st and ard ( surgical specimen and /or positive cytopathology ) or a committee consensus . Six nonblinded investigators review ed nCLE sequences from patients with the most stringent final diagnosis , and identified a single feature that was only present in serous cystadenoma ( SCA ) . The findings were correlated with the pathology of archived specimens . After a training session , four blinded independent observers review ed a separate independent video set , and the yield and interobserver agreement for the criterion were assessed . RESULTS A superficial vascular network pattern visualized on nCLE was identified as the criterion . It corresponded on pathological specimen to a dense and subepithelial capillary vascularization only seen in SCA . The accuracy , sensitivity , specificity , positive predictive value , and negative predictive value of this sign for the diagnosis of SCA were 87 % , 69 % , 100 % , 100 % , and 82 % , respectively . Interobserver agreement was substantial ( κ = 0.77 ) . CONCLUSION This new nCLE criterion seems highly specific for the diagnosis of SCA . The visualization of this criterion could have a direct impact on the management of patients by avoiding unnecessary surgery or follow-up . Clinical trials.gov NCT01563133 |
1,721 | 24,936,656 | The results in this meta- analysis support and strengthen the evidence base indicating Behavioural Activation is an effective treatment for depression . | BACKGROUND Depression is a common , disabling condition for which psychological treatments are recommended .
Behavioural activation has attracted increased interest in recent years .
It has been over 5 years since our meta-analyses summarised the evidence supporting and this systematic review up date s those findings and examines moderators of treatment effect . | A tendency toward abstract and overgeneral processing is a cognitive bias hypothesized to causally contribute to symptoms of depression . This hypothesis predicts that training dysphoric individuals to become more concrete and specific in their thinking would reduce depressive symptoms . To test this prediction , 60 participants with dysphoria were r and omly allocated either to ( a ) concreteness training ; ( b ) bogus concreteness training , matched with concreteness training for treatment rationale , experimenter contact , and treatment duration but without active engagement in concrete thinking ; ( c ) a waiting-list , no training control . Concreteness training result ed in significantly greater decreases in depressive symptoms and significantly greater increases in concrete thinking than the waiting-list and the bogus training control , and significantly greater decreases in rumination than the waiting-list control . These findings suggest that concreteness training has potential as a guided self-help intervention for mild-to-moderate depressive symptoms BACKGROUND Behavioural activation appears as effective as cognitive-behaviour therapy ( CBT ) in the treatment of depression . If equally effective , then behavioural activation may be the preferred treatment option because it may be suitable for delivery by therapists with less training . This is the first r and omised controlled trial to look at this possibility . AIMS To examine whether generic mental health workers can deliver effective behavioural activation as a step-three high-intensity intervention . METHOD A r and omised controlled trial ( IS RCT N27045243 ) comparing behavioural activation ( n=24 ) with treatment as usual ( n=23 ) in primary care . RESULTS Intention-to-treat analyses indicated a difference in favour of behavioural activation of -15.79 ( 95 % CI -24.55 to -7.02 ) on the Beck Depression Inventory-II and Work and Social Adjustment Scale ( mean difference -11.12 , 95 % CI -17.53 to -4.70 ) . CONCLUSIONS Effective behavioural activation appears suitable for delivery by generic mental health professionals without previous experience as therapists . Large-scale trial comparisons with an active comparator ( CBT ) are needed OBJECTIVE Depression is highly prevalent among illicit drug users , and this co-occurrence is associated with poorer treatment outcomes . However , there has been limited empirical attention toward developing and assessing behavioral interventions for depression among illicit drug users . The objective of the current study was to test the efficacy of integrating a brief behavioral intervention for depression into st and ard inpatient substance abuse treatment . METHOD Forty-four adult illicit drug users with mild to moderate depressive symptoms ( Beck Depression Inventory-II [ BDI-II ] score > or= 10 ) who were receiving inpatient substance abuse treatment were r and omly assigned to either treatment as usual ( TAU ) alone or TAU plus brief behavioral therapy for depression ( i.e. , Life Enhancement Treatment for Substance Use [ LETS Act ! ] ) . Patients were assessed at baseline for DSM-IV psychiatric diagnoses , depressive symptoms ( Hamilton Rating Scale for Depression , BDI-II ) , anxiety symptoms ( Beck Anxiety Inventory ) , and enjoyment and reward value of activities ( Environmental Reward Observation Scale ) . Patients were again assessed at posttreatment and at 2-week follow-up . Treatment satisfaction and attrition rates also were assessed at posttreatment . Data were collected from November 2005 to March 2006 . RESULTS Patients who received the LETS Act ! intervention ( N = 22 ) evidence d significantly greater improvements than the TAU group ( N = 22 ) in severity of depression , anxiety symptoms , and enjoyment and reward value of activities at posttreatment and in depressive symptoms at 2-week follow-up . The LETS Act ! group also reported significantly higher treatment satisfaction ratings . CONCLUSIONS This study supports the efficacy of LETS Act ! in treating depressive symptoms and improving the enjoyment and reward value of activities among illicit drug users currently receiving inpatient substance use treatment . Data also indicate the intervention may help prevent treatment attrition . LETS Act ! appears to be a feasible and parsimonious intervention to improve the treatment of depression and overall quality of care within inpatient substance abuse treatment setting BACKGROUND Depressed patients are often characterised by marital distress , but few studies investigate the effects of marital therapy on depressed mood and relationship dysfunction . METHOD Twenty-seven depressed patients experiencing marital distress were r and omly assigned to either individual behavioural-cognitive therapy or marital therapy . The individual treatment condition focused on depressed mood , behavioural activity and dysfunctional cognitions , whereas in the marital condition the partner was involved in the treatment and the focus was on the communication process in the marital relationship . MANOVAs revealed that treatment led to statistically significant improvements in depressed mood , behavioural activity and dysfunctional cognitions , an increase in relationship satisfaction and improvement of communication in patients and spouses . A significant interaction effect was found , showing that marital therapy had more impact on relationship variables than the individual treatment . CONCLUSION Both individual cognitive-behaviour therapy and marital therapy lead to less depressive complaints , and both treatment conditions have a positive effect on the relationship , although the effect on the relationship is significantly stronger in couples who were tested by marital therapy compared with patients who were treated individually Background Despite the high prevalence of postnatal depression ( PND ) , few women seek help . Internet interventions may overcome many of the barriers to PND treatment use . We report a phase II evaluation of a 12-session , modular , guided Internet behavioural activation ( BA ) treatment modified to address postnatal-specific concerns [ Netmums Helping With Depression ( NetmumsHWD ) ] . Method To assess feasibility , we measured recruitment and attrition to the trial and examined telephone session support and treatment adherence . We investigated sociodemographic and psychological predictors of treatment adherence . Effectiveness outcomes were estimated with the Edinburgh Postnatal Depression Scale ( EPDS ) , Generalized Anxiety Disorder-7 , Work and Social Adjustment Scale , Postnatal Bonding Question naire , and Social Provisions Scale . Results A total of 249 women were recruited via a UK parenting site , Netmums.com . A total of 83 women meeting DSM-IV criteria for major depressive disorder were r and omized to NetmumsHWD ( n = 41 ) or treatment-as-usual ( TAU ; n = 42 ) . Of the 83 women , 71 ( 86 % ) completed the EPDS at post-treatment , and 71 % ( 59/83 ) at the 6-month follow-up . Women completed an average of eight out of 12 telephone support sessions and five out of 12 modules . Working women and those with less support completed fewer modules . There was a large effect size favouring women who received NetmumsHWD on depression , work and social impairment , and anxiety scores at post-treatment compared with women in the TAU group , and a large effect size on depression at 6 months post-treatment . There were small effect sizes for postnatal bonding and perceived social support . Conclusions A supported , modular , Internet BA programme can be feasibly delivered to postpartum women , offering promise to improve depression , anxiety and functioning BACKGROUND Behavioural activation might be a viable alternative to antidepressant medication for major depressive disorder . AIMS To compare the effectiveness of behavioural activation and treatment as usual ( TAU , antidepressant medication ) for major depressive disorder in routine clinical practice in Iran . METHOD Patients with major depressive disorder ( n = 100 ) were r and omised to 16 sessions of behavioural activation ( n = 50 ) or antidepressant medication ( n = 50 ) ( I RCT 138807192573N1 ) . The main outcome was depression , measured with the Beck Depression Inventory ( BDI ) and the Hamilton Rating Scale for Depression ( HRSD ) , assessed at 0 , 4 , 13 and 49 weeks . RESULTS Symptom reduction was greater in the behavioural activation group than in the TAU group on both the BDI and the HRSD at 13 and 49 weeks in multilevel analysis . Baseline depression severity was a moderator , with relatively better effects for behavioural activation in individuals who were more severely depressed . Also , there was better retention in the behavioural activation than in the TAU group . CONCLUSIONS Behavioural activation is a viable and effective treatment for people with major depressive disorder , especially for those who are more severely depressed , and it can successfully be disseminated into routine practice setting s in a non-Western country such as Iran The purpose of this study was to provide an experimental test of the theory of change put forth by A. T. Beck , A. J. Rush , B. F. Shaw , and G. Emery ( 1979 ) to explain the efficacy of cognitive-behavioral therapy ( CT ) for depression . The comparison involved r and omly assigning 150 out patients with major depression to a treatment focused exclusively on the behavioral activation ( BA ) component of CT , a treatment that included both BA and the teaching of skills to modify automatic thoughts ( AT ) , but excluding the components of CT focused on core schema , or the full CT treatment . Four experienced cognitive therapists conducted all treatments . Despite excellent adherence to treatment protocol s by the therapists , a clear bias favoring CT , and the competent performance of CT , there was no evidence that the complete treatment produced better outcomes , at either the termination of acute treatment or the 6-month follow-up , than either component treatment . Furthermore , both BA and AT treatments were just as effective as CT at altering negative thinking as well as dysfunctional attributional styles . Finally , attributional style was highly predictive of both short- and long-term outcomes in the BA condition , but not in the CT condition This study followed treatment responders from a r and omized controlled trial of adults with major depression . Patients treated with medication but withdrawn onto pill-placebo had more relapse through 1 year of follow-up compared to patients who received prior behavioral activation , prior cognitive therapy , or continued medication . Prior psychotherapy was also superior to medication withdrawal in the prevention of recurrence across the 2nd year of follow-up . Specific comparisons indicated that patients previously exposed to cognitive therapy were significantly less likely to relapse following treatment termination than patients withdrawn from medication , and patients previously exposed to behavioral activation did almost as well relative to patients withdrawn from medication , although the difference was not significantly different . Differences between behavioral activation and cognitive therapy were small in magnitude and not significantly different across the full 2-year follow-up , and each therapy was at least as efficacious as the continuation of medication . These findings suggest that behavioral activation may be nearly as enduring as cognitive therapy and that both psychotherapies are less expensive and longer lasting alternatives to medication in the treatment of depression In a study design ed to maximize the effectiveness of treatment by allowing participants to select the target of treatment , 40 depressed older adults were r and omly assigned to a waiting-list control condition or to conditions in which the target of treatment was either chosen or assigned . All participants received self-management therapy and the choice was between changing behavior or changing cognition . It was found that individually administered self-management therapy was effective in treating depression for older adults . There were no differences in outcome between versions of self-management therapy that targeted behavioral or cognitive change . Among those who completed treatment , there were no differences in outcome between those who received a choice and those who did not . Individuals who were given a choice of treatment options , however , were less likely to drop out of treatment prematurely OBJECTIVE Major depression is the most common psychiatric disorder among breast cancer patients and is associated with substantial impairment . Although some research has explored the utility of psychotherapy with breast cancer patients , only 2 small trials have investigated the potential benefits of behavior therapy among patients with well-diagnosed depression . METHOD In a primarily Caucasian , well-educated sample of women ( age = 55.4 years , SD = 11.9 ) diagnosed with breast cancer and major depression ( n = 80 ) , this study was a r and omized clinical trial testing the efficacy of 8 sessions of behavioral activation treatment for depression ( BATD ) compared to problem-solving therapy . Primary outcome measures assessed depression , environmental reward , anxiety , quality of life , social support , and medical outcomes . RESULTS Across both treatments , results revealed strong treatment integrity , excellent patient satisfaction with treatment protocol s , and low patient attrition ( 19 % ) . Intent-to-treat analyses suggested both treatments were efficacious , with both evidencing significant pre-post treatment gains across all outcome measures . Across both treatments , gains were associated with strong effect sizes , and based on response and remission criteria , a reliable change index , and numbers-needed-to-treat analyses , approximately ¾ of patients exhibited clinical ly significant improvement . No significant group differences were found at posttreatment . Treatment gains were maintained at 12-month follow-up , with some support for stronger maintenance of gains in the BATD group . CONCLUSIONS BATD and problem-solving interventions represent practical interventions that may improve psychological outcomes and quality of life among depressed breast cancer patients . Study limitations and future research directions are discussed Depression presents a significant public health burden for Latinos , the largest and fastest-growing minority group in the United States . The current study performed a r and omized controlled trial of Behavioral Activation ( BA ) for Latinos ( BAL , n=21 ) , with relatively minor modifications , compared to treatment as usual ( TAU , n=22 ) in a community mental health clinic setting with a sample of depressed , Spanish-speaking Latinos . TAU was a strong comparison condition , taking place at the same clinic , under the same guidelines and clinic protocol s , with similar levels of ongoing consultation , and using the same pool of therapists as BAL . Results indicated that BAL performed well with respect to treatment engagement and retention . Regarding acute treatment outcomes , an interaction emerged between number of sessions attended and condition . Specifically , only BAL clients who were engaged in treatment and attended more sessions demonstrated significant reductions in depression and improvements in quality of life and mental health functioning . Results are discussed in terms of the balance of efficacy and effectiveness issues addressed in this trial The current study is a controlled clinical investigation of two nonpharmacological treatments of depression in patients with Alzheimer 's disease . Two active behavioral treatments , one emphasizing patient pleasant events and one emphasizing caregiver problem solving , were compared to an equal- duration typical care condition and a wait list control . Seventy-two patient-caregiver dyads were r and omly assigned to one of four conditions and assessed pre- , post- , and at 6-months follow-up . Patients in both behavioral treatment conditions showed significant improvement in depression symptoms and diagnosis as compared with the two other conditions . These gains were maintained at 6-month follow-up . Caregivers in each behavioral condition also showed significant improvement in their own depressive symptoms , while caregivers in the two other conditions did not . Results indicate that behavioral interventions for depression are important and effective strategies for treating demented patients and their caregivers BACKGROUND AND SIGNIFICANCE The treatment of personality disorders in older adults , particularly those co-morbid with other Axis I disorders ( e.g. , Major Depressive Disorder ) , is an understudied clinical phenomenon . It has also been demonstrated that personality disorders in older adults complicate treatment of other psychopathology , as well as result in heightened interpersonal disturbance and emotional distress . METHODS Two studies utilizing st and ard Dialectical Behavior Therapy ( DBT ) to treat depression and personality disorders in older adults are review ed . Study 1 examined 34 chronically depressed individuals aged 60 and older who were r and omly assigned to receive 28 weeks of antidepressant medication plus clinical management , either alone ( MED ) or with the addition of DBT skills-training and scheduled telephone coaching sessions ( MED + DBT ) . Study 2 had two phases of treatment : Phase I : 8-week open-trial of antidepressant medication ( n = 65 ) ; Phase II : 24-week r and omized trial of DBT + MED versus MED alone for those who prospect ively failed to respond to the Phase I medication trial ( n = 37 ) . RESULTS Study 1 demonstrated that 71 % of MED + DBT patients were in remission at post-treatment , in contrast to 47 % of MED patients . This became a significant difference at the 6-month follow-up ; where 75 % of MED + DBT-D patients were in remission compared with only 31 % of MED patients . Study 2 showed that after 8 weeks of treatment with antidepressant medication alone ( Phase 1 ) only 14 % of the sample had at least a 50 % reduction in HAM-D scores . Phase II results showed on average , the DBT + MED group reached depression remission by the post-group assessment and maintained these gains while the MED group did not reach remission , until the follow-up assessment . Results demonstrated superiority of DBT + MED compared to MED alone on Interpersonal Sensitivity and Interpersonal Aggression at post-treatment and 6-month follow-up . CONCLUSION Results from these two treatment development studies indicate that applying st and ard DBT for the treatment of co-morbid MDD or MDD + PD in older adults is feasible , acceptable , and has clinical promise . Modifications to st and ard DBT and an overview of a new treatment manual for this population are summarized Background and Purpose — Depression after stroke is prevalent , diminishing recovery and quality of life . Brief behavioral intervention , adjunctive to antidepressant therapy , has not been well evaluated for long-term efficacy in those with poststroke depression . Methods — One hundred one clinical ly depressed patients with ischemic stroke within 4 months of index stroke were r and omly assigned to an 8-week brief psychosocial – behavioral intervention plus antidepressant or usual care , including antidepressant . The primary end point was reduction in depressive symptom severity at 12 months after entry . Results — Hamilton Rating Scale for Depression raw score in the intervention group was significantly lower immediately posttreatment ( P<0.001 ) and at 12 months ( P=0.05 ) compared with control subjects . Remission ( Hamilton Rating Scale for Depression < 10 ) was significantly greater immediately posttreatment and at 12 months in the intervention group compared with the usual care control . The mean percent decrease ( 47%±26 % intervention versus 32%±36 % control , P=0.02 ) and the mean absolute decrease ( −9.2±5.7 intervention versus −6.2±6.4 control , P=0.023 ) in Hamilton Rating Scale for Depression at 12 months were clinical ly important and statistically significant in the intervention group compared with control . Conclusion — A brief psychosocial – behavioral intervention is highly effective in reducing depression in both the short and long term BACKGROUND Despite the high prevalence of postnatal depression ( PND ) , few women seek help . The internet may increase timely access to treatment . We report a r and omized controlled trial of a minimal intervention internet Behavioral Activation ( iBA ) treatment modified to address postnatal specific concerns ( Postnatal-iBA ) . METHODS Women ( n=910 ) recruited via a popular UK parenting site , Netmums.com , scoring above 12 on the Edinburgh Postnatal Depression Scale ( EPDS ) were r and omly assigned to receive either Postnatal-iBA delivered or treatment-as-usual ( TAU ) . We investigated the feasibility ( recruitment , trial and treatment adherence ) and effectiveness ( depression status EPDS > 12 ) of the intervention . RESULTS Recruitment was excellent ; 1261 women , 961 of whom met inclusion criteria , signed up to the trial within two 2-week recruitment periods . Thirty-eight percent ( 343/910 ) of women completed the 15-week outcome assessment . Of those who completed 15-week assessment , fewer exceeded the depression cutoff in the Postnatal-iBA group ( n=66/181 ) compared to TAU ( n=91/162 ) . Assuming all non-respondents remained depressed , the Postnatal-iBA effect was reduced . LIMITATIONS The study suffered from high attrition and future trials need to consider strategies for improving outcome completion . Some women reported struggles " keeping up " with the treatment . CONCLUSIONS A minimal support , widely accessible internet Behavioral Activation program for PND is feasible to deliver to community population s when embedded within popular parenting sites . For women who provide outcome data , postnatal-iBA offers promise as an effective treatment for PND . The addition of support may reduce women 's struggles to keep pace with the treatment Objective : This Stage 1b controlled trial sought a preliminary test of the relative efficacy of Behavioral Therapy for Depression in Drug Dependence ( BTDD ) against a structured relaxation intervention ( REL ) for treating DSM-IV depressive disorders and substance abuse . Method : Thirty-eight methadone maintained opiate dependent participants , who met criteria for a DSM-IV depressive disorder , were r and omized to one of two , 24-week treatment conditions ( BTDD or REL ) . Results : Depression response , defined as at least a 50 % reduction in Hamilton Depression Scale score from baseline to the end of study , was high and similar in both BTDD ( 61 % ) and REL ( 65 % ) . Rates of drug use were low overall , both at baseline and at the end of study , and did not differ between treatment groups at study endpoint . Conclusions : The findings suggest that both behavioral- and relaxation-based approaches show promise for treating comorbid depression in drug dependent population s. Future work should examine combining or modifying these interventions to target substance use more directly and include values based methods for increasing more adaptive behavioral patterns Antidepressant medication is considered the current st and ard for severe depression , and cognitive therapy is the most widely investigated psychosocial treatment for depression . However , not all patients want to take medication , and cognitive therapy has not demonstrated consistent efficacy across trials . Moreover , dismantling design s have suggested that behavioral components may account for the efficacy of cognitive therapy . The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a r and omized placebo-controlled design in adults with major depressive disorder ( N = 241 ) . In addition , it examined the importance of initial severity as a moderator of treatment outcome . Among more severely depressed patients , behavioral activation was comparable to antidepressant medication , and both significantly outperformed cognitive therapy . The implication s of these findings for the evaluation of current treatment guidelines and dissemination are discussed Depression causes significant distress , disability and cost within the UK . Behavioural activation ( BA ) is an effective single-str and psychological approach which may lend itself to brief training programmes for a wide range of clinical staff . No previous research has directly examined outcomes of such dissemination . A 5-day training course for 10 primary care mental health workers aim ing to increase knowledge and clinical skills in BA was evaluated using the Training Acceptability Rating Scale . Depression symptom level data collected in a r and omized controlled trial using trainees were then compared to results from meta- analysis of studies using experienced therapists . BA training was highly acceptable to trainees ( 94.4 % , SD 6 % ) . The combined effect size of BA was unchanged by the addition of the results of this evaluation to those of studies using specialist therapists . BA offers a promising psychological intervention for depression that appears suitable for delivery by mental health nurses following brief training This study presents 2-year follow-up data of a comparison between complete cognitive-behavioral therapy for depression ( CT ) and its 2 major components : behavioral activation and behavioral activation with automatic thought modification . Data are reported on 137 participants who were r and omly assigned to 1 of these 3 treatments for up to 20 sessions with experienced cognitive-behavioral therapists . Long-term effects of the therapy were evaluated through relapse rates , number of asymptomatic or minimally symptomatic weeks , and survival times at 6- , 12- , 18- , and 24-month follow-ups . CT was no more effective than its components in preventing relapse . Both clinical and theoretical implication s of these findings are discussed A 12‐week self‐control therapy program based on the self‐control model proposed by Rehm was added to the routine program for depressed patients in a psychiatric day‐treatment center . It was hypothesized that addition of the self‐control therapy would accelerate the recovery of depressed patients . Twenty‐five depressed patients were r and omly assigned to either st and ard treatment or st and ard treatment plus the self‐control therapy program . At post‐test , patients in the self‐control condition showed significant improvement with regard to self‐control , self‐esteem , depression , depressed mood and frequency and potential enjoyability of pleasant events , whereas the control patients did not . On 5 of 6 measures the differences between the groups were significant in the hypothesized direction . Although at the 13‐week follow‐up the positive effects of the self‐control therapy were maintained , between‐group differences were no longer significant , except for self‐control The efficacy of bibliotherapy for mildly and moderately depressed older adults was examined . Cognitive bibliotherapy and behavioral bibliotherapy were compared with a delayed-treatment control condition . Results indicate that the two experimental conditions were superior to the control condition , but that the cognitive and behavioral bibliotherapies were nondifferentially efficacious . Sixty-six percent of the subjects demonstrated clinical ly significant change . There were no specific effects associated with either the cognitive or the behavioral interventions . Treatment gains were maintained at 6-month follow-up . The implication s of bibliotherapy for geriatric depression as an alternative or adjunct to traditional treatments are discussed BACKGROUND Internet-based cognitive behavior therapy for depression has been tested in several trials but there are no internet studies on behavioral activation ( BA ) , and no studies on BA over the internet including components of acceptance and commitment therapy ( ACT ) . The aim of this study was to develop and test the effects of internet-delivered BA combined with ACT against a waiting list control condition as a first test of the effects of treatment . METHODS Selection took place with a computerized screening interview and a subsequent semi-structured telephone interview . A total of 80 individuals from the general public were r and omized to one of two conditions . The treatment lasted for 8 weeks after which both groups were assessed . We also included a 3 month follow-up . The treatment included interactive elements online and a CD-ROM for mindfulness and acceptance exercises . In addition , written support and feedback was given by a therapist every week . RESULTS Results at posttreatment showed a large between group effect size on the Beck Depression inventory II d=0.98 ( 95%CI=0.51 - 1.44 ) . In the treated group 25 % ( 10/40 ) reached remission defined as a BDI score ≤ 10 vs. 5 % ( 2/40 ) in the control group . Results on secondary measures were smaller . While few dropped out from the study ( N=2 ) at posttreatment , the average number of completed modules was M=5.1 out of the seven modules . LIMITATIONS The study only included a waiting-list comparison and it is not possible to determine which treatment components were the most effective . CONCLUSIONS We conclude that there is initial evidence that BA with components of ACT can be effective in reducing symptoms of depression |
1,722 | 26,385,379 | Conclusion These systematic review s are the first to systematic ally gather evidence and recommendations for the reporting of specific items in pediatric protocol s and trials .
They provide useful and translatable evidence on which to build pediatric extensions to the SPIRIT and CONSORT reporting guidelines .
The result ing SPIRIT-C and CONSORT-C will provide guidance to the authors of pediatric protocol s and reports , respectively , helping to alleviate concerns of inappropriate and inconsistent reporting , and reduce research waste | Background Complete and transparent reporting of clinical trial protocol s and reports ensures that these documents are useful to all stakeholders , that bias is minimized , and that the research is not wasted .
However , current studies repeatedly conclude that pediatric trial protocol s and reports are not appropriately reported .
Guidelines like SPIRIT ( St and ard Protocol Items : Recommendations for Interventional Trials ) and CONSORT ( Consoli date d St and ards of Reporting Trials ) may improve reporting , but do not offer guidance on issues unique to pediatric trials . | INTRODUCTION Reporting of r and omized controlled trials ( RCTs ) should be of high quality to support the conclusions reached by the authors . Poor- quality reporting has been associated with an overestimation in intervention efficacy . Within the field of paediatric dentistry , no study has assessed the quality of reporting . OBJECTIVE The aim of this study was to assess published RCTs in paediatric dental journals between 1985 and 2006 for : ( i ) whether quality of reporting allows readers to assess the validity of trials ; and ( ii ) whether quality of reporting has improved since the introduction of the Consoli date d St and ards of Reporting Trials ( CONSORT ) guidelines . METHODS H and search of the main paediatric dentistry journals ; inclusion criteria were : the trial was performed on children , and RCT . CONSORT guidelines were made into an operational checklist . Trials published between 1985 and 1997 , and between 1998 and 2006 were compared to determine any improvement since the publication of the CONSORT guidelines . RESULTS One hundred and seventy-three of 5635 articles met the inclusion criteria . Reporting quality was poor overall and showed heterogeneity . It had improved slightly since the publication of CONSORT . Few trials were reported adequately . CONCLUSION The quality of reporting of clinical trials is poor , and often not adequate to allow readers to assess trial validity . Overall quality of reporting has not substantially improved since the publication of CONSORT There is consensus that children have question able decisional capacity and , therefore , in general a parent or a guardian must give permission to enroll a child in a research study . Moreover , freedom from duress and coercion , the cardinal rule in research involving adults , is even more important for children . This principle is embodied prominently in the Nuremberg Code ( 1947 ) and is embodied in various federal human research protection regulations . In a program named " SATURN " ( Student Athletic Testing Using R and om Notification ) , each school in the Oregon public-school system may implement a m and atory drug-testing program for high school student athletes . A prospect i ve study to identify drug use among student-athletes , SATURN is design ed both to evaluate the influence of r and om drug testing and to vali date the survey data through identification of individuals who do not report drug use . The enrollment of students in the drug-testing study is a requirement for playing a school sport . In addition to the coercive nature of this study design , there were ethically question able practice s in recruitment , informed consent , and confidentiality . This article concerns the question of whether research can be conducted with high school students in conjunction with a m and atory drug-testing program , while adhering to prevailing ethical st and ards regarding human-subjects research and specifically the participation of children in research Background All r and omized clinical trials ( RCTs ) require a protocol ; however , numerous studies have highlighted protocol deficiencies . Reporting guidelines may improve the content of research reports and , if developed using robust methods , may increase the utility of reports to stakeholders . The objective of this study was to systematic ally identify and review RCT protocol guidelines , to assess their characteristics and methods of development , and to compare recommendations . Methods We conducted a systematic review of indexed literature ( MEDLINE , EMBASE and the Cochrane Methodology Register from inception to September 2010 ; reference lists ; related article features ; forward citation search ing ) and a targeted search of supplementary sources , including a survey of major trial funding agencies in six countries . Records were eligible if they described a content guideline in English or French relevant to RCT protocol s. Guidelines were excluded if they specified content for protocol s for trials of specific procedures or conditions or were intended to assess trial quality . We extracted guideline characteristics and methods . Content was mapped for a subset of guidelines that described development methods or had institutional endorsement . Results Forty guidelines published in journals , books and institutional reports were included in the review ; seven were specific to RCT protocol s. Only eight ( 20 % ) described development methods which included informal consensus methods , pilot testing and formal validation ; no guideline described all of these methods . No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development . The guidelines included a median of 23 concepts per guideline ( interquartile range ( IQR ) = 14 to 34 ; range = 7 to 109 ) . Among the subset of guidelines ( n = 23 ) for which content was mapped , approximately 380 concepts were explicitly addressed ( median concepts per guideline IQR = 31 ( 24,80 ) ; range = 16 to 150 ) ; most concepts were addressed in a minority of guidelines . Conclusions Existing guidelines for RCT protocol content varied substantially in their recommendations . Few reports described the methods of guideline development , limiting comparisons of guideline validity . Given the importance of protocol s to diverse stakeholders , we believe a systematic ally developed , evidence -informed guideline for clinical trial protocol s is needed BACKGROUND Despite the high prevalence and negative physical and psychosocial consequences of overweight and obesity in adolescents , very little research has evaluated treatment in this population . Consequently , clinicians working with overweight and obese adolescents have little empirical research on which to base their practise . Cognitive behavioural therapy has demonstrated efficacy in promoting behaviour change in many treatment resistant disorders . Motivational interviewing has been used to increase motivation for change and improve treatment outcomes . In this paper we describe the rationale and design of a r and omised controlled trial testing the efficacy of motivational interviewing and cognitive behaviour therapy in the treatment of overweight and obese adolescents . METHODS Participants took part in a motivational interview or a st and ard semi-structured assessment interview and were then r and omly allocated to a cognitive behavioural intervention or a wait-list control condition . The cognitive behavioural intervention , the CHOOSE HEALTH Program , consisted of 13 individual treatment sessions ( 12 face-to-face , 1 phone call ) followed by 9 maintenance sessions ( 7 phone calls , 2 face-to-face ) . Assessment s were conducted prior to participation , after the treatment phase and after the maintenance phase of intervention . Improvement in body composition was the primary outcome ; secondary outcomes included improved cardiovascular fitness , eating and physical activity habits , family and psychosocial functioning . CONCLUSION Despite the demonstrated effectiveness of motivational interviewing and cognitive behavioural therapy in the long-term management of many treatment resistant disorders , these approaches have been under-utilised in adolescent overweight and obesity treatment . This study provides baseline data and a thorough review of the study design and treatment approach to allow for the assessment of the efficacy of motivational interviewing and cognitive behavioural therapy in the treatment of adolescent overweight and obesity . Data obtained in this study will also provide much needed information about the behavioural and psychosocial factors associated with adolescent overweight and obesity Purpose This article is aim ed at describing the methodology of “ ethical reasoning ” that finally led TEDDYNoE ( Task-force in Europe for Drug Development for the Young ) to propose the integration of international human rights law to develop coherent and exhaustive ethical recommendations on paediatric research at a European level . Methods A large number of ethical guidelines and texts of varying legal force existing in the field of clinical research and in particular related to paediatrics are analysed . Differences and non-coordinated implementation are pointed out . Results Differences , tensions or outright contradictions among the provisions of these texts can generate confusion leading to the adoption of different ethical st and ards across Europe . In this context , the real challenge is to ensure that each child involved in a clinical trial in the EU territory may rely directly on the same principles and rights . Taking international human rights law as the main starting point to develop a coherent framework for paediatric research that incorporates all the relevant ethical considerations and existing guidelines is a way of achieving this objective . Conclusions The implementation , at national and local level , of the “ European Ethical Recommendations ” ( Eudralex 2008 vol . 10 ) , based on international human rights law , seems to be the next step in facilitating a coordinated approach to the application of the Directive 2001/20/EC , as well as developing quality and ethically sound paediatric research Cortisol does not exhibit a straightforward relationship with mood states ; administration of glucocorticoids to human subjects has produced mixed effects on mood and emotional processing . In this study , participants ( N=46 ) received intravenous hydrocortisone ( synthetic cortisol ; 0.1mg/kg body weight ) and placebo in r and omized order over two sessions 48h apart . Following the infusion , participants rated neutral and unpleasant pictures . In Session 1 , participants reported elevated negative affect ( NA ) following the picture-rating task , regardless of treatment . In Session 2 , however , only participants who received cortisol ( and thus who had received placebo in Session 1 ) reported elevated NA . Arousal ratings for unpleasant pictures followed a similar pattern . These findings suggest that the effects of cortisol on emotion vary based on situational factors , such as drug administration order or familiarity with the tasks and setting . Such factors can influence cortisol 's effects on emotion in two ways : ( A ) cortisol may only potentiate NA and arousal ratings in the absence of other , overwhelming influences on affect , such as the novelty of the setting and tasks in Session 1 ; and ( B ) cortisol in Session 1 may facilitate learning processes ( e.g. , habituation to the stimuli and setting ; extinction of aversive responses ) such that emotional responses to the pictures are lessened in Session 2 . This interpretation is compatible with a body of literature on the effects of glucocorticoids on learning and memory processes CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion Objective To evaluate how often sample size calculations and methods of statistical analysis are pre-specified or changed in r and omised trials . Design Retrospective cohort study . Data source Protocol s and journal publications of published r and omised parallel group trials initially approved in 1994 - 5 by the scientific-ethics committees for Copenhagen and Frederiksberg , Denmark ( n=70 ) . Main outcome measure Proportion of protocol s and publications that did not provide key information about sample size calculations and statistical methods ; proportion of trials with discrepancies between information presented in the protocol and the publication . Results Only 11/62 trials described existing sample size calculations fully and consistently in both the protocol and the publication . The method of h and ling protocol deviations was described in 37 protocol s and 43 publications . The method of h and ling missing data was described in 16 protocol s and 49 publications . 39/49 protocol s and 42/43 publications reported the statistical test used to analyse primary outcome measures . Unacknowledged discrepancies between protocol s and publications were found for sample size calculations ( 18/34 trials ) , methods of h and ling protocol deviations ( 19/43 ) and missing data ( 39/49 ) , primary outcome analyses ( 25/42 ) , subgroup analyses ( 25/25 ) , and adjusted analyses ( 23/28 ) . Interim analyses were described in 13 protocol s but mentioned in only five corresponding publications . Conclusion When reported in publications , sample size calculations and statistical methods were often explicitly discrepant with the protocol or not pre-specified . Such amendments were rarely acknowledged in the trial publication . The reliability of trial reports can not be assessed without having access to the full protocol The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . 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 . Treating malaria before immunizing has been st and ard in malaria vaccine field trials . To assess the impact of this practice on subsequent infection and disease incidence , we conducted a r and omized cohort study in B and iagara , Mali . Subjects received a treatment dose of sulfadoxine-pyrimethamine ( SP ) or no treatment at the beginning of the transmission season . Cumulative and age-specific incidence of clinical episodes was similar between the 2 groups , but SP treatment delayed the median time to first clinical episode from 38.5 to 68 days , and after this initial period of protection , disease incidence in the SP group quickly surpassed the incidence in the untreated group . Parasite densities during disease episodes were lower in the SP group . SP was chosen as the drug for initial parasite clearance for the following reasons : 1 ) it has been used in previous vaccine trials ; 2 ) our studies have found it to have > 99 % efficacy in treating uncomplicated malaria in Mali compared to 85 - 90 % efficacy for chloroquine in this area ; 3 ) SP is the approved second-line antimalarial agent in Mali ; and 4 ) its single-dose regimen ensures compliance when treatment is directly observed Objective To evaluate the quality of reports of complementary and alternative medicine ( CAM ) r and omized controlled trials ( RCTs ) in the pediatric population . We also examined whether there was a change in the quality of reporting over time . Methods We used a systematic sample of 251 reports of RCTs that used a CAM intervention . The quality of each report was assessed using the number of CONSORT checklist items included , the frequency of unclear allocation concealment , and a 5-point quality assessment instrument . Results Nearly half ( 40 % ) of the CONSORT checklist items were included in the reports , with an increase in the number of items included . The majority ( 81.3 % ) of RCTs reported unclear allocation concealment with no significant change over time . The quality of reports achieved approximately 40 % of their maximum possible total score as assessed with the Jadad scale with no change over time . Information regarding adverse events was reported in less than one quarter of the RCTs ( 22 % ) and information regarding costs was mentioned in only a minority of reports ( 4 % ) . Conclusions RCTs are an important tool for evidence based health care decisions . If these studies are to be relevant in the evaluation of CAM interventions it is important that they are conducted and reported with the highest possible st and ards . There is a need to redouble efforts to ensure that children and their families are participating in RCTs that are conducted and reported with minimal bias . Such studies will increase their usefulness to a board spectrum of interested stakeholders Background Ghost authors hip , the failure to name , as an author , an individual who has made substantial contributions to an article , may result in lack of accountability . The prevalence and nature of ghost authors hip in industry-initiated r and omised trials is not known . Methods and Findings We conducted a cohort study comparing protocol s and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994–1995 . We defined ghost authors hip as present if individuals who wrote the trial protocol , performed the statistical analyses , or wrote the manuscript , were not listed as authors of the publication , or as members of a study group or writing committee , or in an acknowledgment . We identified 44 industry-initiated trials . We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators , and none of the protocol s stated that clinical investigators were to be involved with data analysis . We found evidence of ghost authors hip for 33 trials ( 75 % ; 95 % confidence interval 60%–87 % ) . The prevalence of ghost authors hip was increased to 91 % ( 40 of 44 articles ; 95 % confidence interval 78%–98 % ) when we included cases where a person qualifying for authors hip was acknowledged rather than appearing as an author . In 31 trials , the ghost authors we identified were statisticians . It is likely that we have overlooked some ghost authors , as we had very limited information to identify the possible omission of other individuals who would have qualified as authors . Conclusions Ghost authors hip in industry-initiated trials is very common . Its prevalence could be considerably reduced , and transparency improved , if existing guidelines were followed , and if protocol s were publicly available Objectives To evaluate the risk of bias tool , introduced by the Cochrane Collaboration for assessing the internal validity of r and omised trials , for inter-rater agreement , concurrent validity compared with the Jadad scale and Schulz approach to allocation concealment , and the relation between risk of bias and effect estimates . Design Cross sectional study . Study sample 163 trials in children . Main outcome measures Inter-rater agreement between review ers assessing trials using the risk of bias tool ( weighted κ ) , time to apply the risk of bias tool compared with other approaches to quality assessment ( paired t test ) , degree of correlation for overall risk compared with overall quality scores ( Kendall ’s τ statistic ) , and magnitude of effect estimates for studies classified as being at high , unclear , or low risk of bias ( metaregression ) . Results Inter-rater agreement on individual domains of the risk of bias tool ranged from slight ( κ=0.13 ) to substantial ( κ=0.74 ) . The mean time to complete the risk of bias tool was significantly longer than for the Jadad scale and Schulz approach , individually or combined ( 8.8 minutes ( SD 2.2 ) per study v 2.0 ( SD 0.8 ) , P<0.001 ) . There was low correlation between risk of bias overall compared with the Jadad scores ( P=0.395 ) and Schulz approach ( P=0.064 ) . Effect sizes differed between studies assessed as being at high or unclear risk of bias ( 0.52 ) compared with those at low risk ( 0.23 ) . Conclusions Inter-rater agreement varied across domains of the risk of bias tool . Generally , agreement was poorer for those items that required more judgment . There was low correlation between assessment s of overall risk of bias and two common approaches to quality assessment : the Jadad scale and Schulz approach to allocation concealment . Overall risk of bias as assessed by the risk of bias tool differentiated effect estimates , with more conservative estimates for studies at low risk Adolescent girls with body dissatisfaction ( N = 481 , SD = 1.4 ) were r and omized to a dissonance-based thin-ideal internalization reduction program , healthy weight control program , expressive writing control condition , or assessment -only control condition . Dissonance participants showed significantly greater decreases in thin-ideal internalization , body dissatisfaction , negative affect , eating disorder symptoms , and psychosocial impairment and lower risk for eating pathology onset through 2- to 3-year follow-up than did assessment -only controls . Dissonance participants showed greater decreases in thin-ideal internalization , body dissatisfaction , and psychosocial impairment than did expressive writing controls . Healthy weight participants showed greater decreases in thin-ideal internalization , body dissatisfaction , negative affect , eating disorder symptoms , and psychosocial impairment ; less increases in weight ; and lower risk for eating pathology and obesity onset through 2- to 3-year follow-up than did assessment -only controls . Healthy weight participants showed greater decreases in thin-ideal internalization and weight than did expressive writing controls . Dissonance participants showed a 60 % reduction in risk for eating pathology onset , and healthy weight participants showed a 61 % reduction in risk for eating pathology onset and a 55 % reduction in risk for obesity onset relative to assessment -only controls through 3-year follow-up , implying that the effects are clinical ly important and enduring Objectives : R and omized clinical trials are commonly overseen by a Data and Safety Monitoring Board comprised of experts in medicine , ethics , and biostatistics . Data and Safety Monitoring Board responsibilities include protocol approval , interim review of study enrollment , protocol compliance , safety , and efficacy data . Data and Safety Monitoring Board decisions can affect study design and conduct , as well as reported findings . Research ers must incorporate Data and Safety Monitoring Board oversight into the design , monitoring , and reporting of r and omized trials . Design : Case study , narrative review . Methods : The Data and Safety Monitoring Board ’s role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression ( CRISIS ) Prevention Trial is described . Findings : The National Institutes of Health-appointed CRISIS Data and Safety Monitoring Board was charged with monitoring sample size adequacy and feasibility , safety with respect to adverse events and 28-day mortality , and efficacy with respect to the primary nosocomial infection/sepsis outcome . The Federal Drug Administration also requested Data and Safety Monitoring Board interim review before opening CRISIS to children below 1 yr of age . The first interim analysis found higher 28-day mortality in one treatment arm . The Data and Safety Monitoring Board maintained trial closure to younger children and requested a second interim data review 6 months later . At this second meeting , mortality was no longer of concern , whereas a weak efficacy trend of lower infection/sepsis rates in one study arm emerged . As over 40 % of total patients had been enrolled , the Data and Safety Monitoring Board elected to examine conditional power and unmask treatment arm identities . On finding somewhat greater efficacy in the placebo arm , the Data and Safety Monitoring Board recommended stopping CRISIS due to futility . Conclusions : The design and operating procedures of a multicenter r and omized trial must consider a pivotal Data and Safety Monitoring Board role . Maximum study design flexibility must be allowed , and investigators must be prepared for protocol modifications due to interim findings . The Data and Safety Monitoring Board must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups The term urinary tract infection ( UTI ) encompasses a broad range of clinical entities that share one characteristic : a positive urine culture . Clinical manifestations and responses to therapy are diverse even when comparable numbers of a particular bacterial species are identified on urine culture . These guidelines include discussion of acute uncomplicated cystitis , acute uncomplicated pyelonephritis , and complicated infections of the urinary tract . It is proposed that the finding of > or = 10(3 ) cfu/mL of urine defines significant bacteriuria in acute uncomplicated cystitis , > or = 10(4 ) cfu/mL in acute uncomplicated pyelonephritis and UTI in men , and > or = 10(5 ) cfu/mL in complicated UTI . The preferred clinical study design is prospect i ve , r and omized , and controlled with an active agent . Ideally , treatment with antimicrobial agents should eradicate the infecting organism , bring about the resolution of clinical signs and symptoms , have few adverse effects , and prevent reinfection The recent spread of cholera to Latin America , together with the persistent burden of this disease in Asia and Africa , have stimulated efforts to evaluate new cholera vaccines in field setting s. Although the st and ard experimental paradigm for vaccine field trials is well established , the success of these trials will also depend on suitable consideration of the epidemiology of cholera and of cholera vaccination in the setting under study . Epidemiological studies done in Bangladesh emphasize the importance of appreciating the poorly predictable , multifocal occurrence of cholera in estimating a probable incidence of cholera for a field trial . They also underscore how the filtering effect of enrolling subjects into a prospect i ve trial can dramatically reduce the available population for study , and can yield a study sample whose expected risk of cholera differs markedly from that for the source population . Finally , the data highlight the subtle effects that the mode of surveillance and the choice of an outcome definition can have upon protective efficacy , and emphasize the need for subgroup analyses that address the distinctive variations in vaccine protection that may occur in subjects differing in age and in ABO blood groups , and in subjects exposed to classical versus El Tor cholera BACKGROUND : Several studies suggest that many parents and research participants have poor underst and ing of the elements of consent , particularly the risks and benefits . However , some data suggest that the format and framing of research risks and benefits may be an important determinant of subject underst and ing . We examined the effect of tabular and graphical presentation of risks and benefits on parents ' underst and ing of a research study . METHODS : Parents of children scheduled to undergo an elective surgical procedure ( n = 408 ) were r and omized to receive information about the risks and benefits of a sham study of postoperative pain control using text , tables , or pictographs and then completed a question naire to examine their gist ( essential ) and verbatim ( actual ) underst and ing of the information . Parent demographics were recorded and their literacy and numeracy skills measured . RESULTS : Parents r and omized to receive information using tables or pictographs had significantly ( P < 0.025 ) greater gist and verbatim underst and ing than did parents who received the information using st and ard text . Tables and pictographs were also superior to text in promoting underst and ing among parents with low numeracy and literacy skills . CONCLUSIONS : Many parents and patients have difficulty in assimilating and interpreting risk/benefit information for both research and treatment . This is due , in part , to the manner in which risks and benefits are communicated and to the literacy and numeracy abilities of the individual . The results of this study suggest a simple and practical method for enhancing underst and ing of risk/benefit statistics for parents with varying numeracy and literacy skills Objective : To assess the clinical safety and tolerability of the macrocyclic contrast agent gadobutrol ( Gadovist/Gadavist ) overall and in specific patient population s based on clinical trials and postmarketing experience . Material s and Methods : In total , 5545 patients enrolled in 34 prospect i ve clinical studies were evaluated in an integrated analysis of safety . Of all enrolled patients , 4549 received gadobutrol at a dose of ≤0.09 mmol/kg body weight to a maximum of 0.51 mmol/kg body weight , with most patients ( 53.5 % ) receiving the recommended dose of > 0.09 to 0.11 mmol/kg body weight . Data include comparisons with other extracellular contrast agents and subgroup analyses in pediatric patients , and patients with allergic disposition , renal impairment , hepatic impairment , or cardiovascular disease . Furthermore , worldwide postmarketing safety surveillance results , including nephrogenic systemic fibrosis reports , based on more than 5.7 million estimated applications are described . Results : One or more adverse events ( AEs ) assessed as related to the administration of gadobutrol were reported by 182 ( 4.0 % ) of the 4549 patients who participated in clinical trials . This is comparable to the incidence observed with the comparator contrast agents ( 74/1844 patients , 4.0 % ) . The most common AEs , independent of drug relationship , were headache , nausea , feeling hot , and dysgeusia . The favorable safety profile of gadobutrol was also demonstrated in the following specific sub population s in whom similar incidence rates were seen : pediatric patients aged 2 to 17 years ( 8/138 patients , 5.8 % ) , patients with severe or moderate renal impairment ( 9/366 patients , 2.5 % ) , patients with severe or moderate hepatic impairment ( 9/214 patients , 4.2 % ) , and patients with cardiovascular disorders ( 42/1506 patients , 2.8 % ) . Having been established in controlled clinical trials , this safety profile was also confirmed by postmarketing surveillance data . With more than 5.7 million estimated administrations of gadobutrol , a total of 1175 ( 0.02 % ) suspected adverse drug reactions have been reported . The most serious adverse reactions seen in postmarketing surveillance included rare reports of cardiac arrest , respiratory arrest , anaphylactoid shock , and nephrogenic systemic fibrosis . Incidence and type of AEs from postmarketing surveillance were consistent with the established safety profile . Conclusion : The comprehensive analysis of safety data obtained from 34 clinical studies demonstrates that gadobutrol has an excellent safety profile and a positive benefit risk profile when used in patients in need of contrast-enhanced magnetic resonance imaging . Gadobutrol was well tolerated by adults , by children , by patients with impaired liver or kidney function , and by patients with cardiovascular disease . The favorable safety profile is confirmed by the available postmarketing surveillance data and is compared with that of other gadolinium-based contrast agents OBJECTIVES to compare the impact of two methods of supplementary feeding of pre-term babies ( bottle vs cup ) on subsequent breast feeding and to assess the feasibility of using a r and omised controlled trial ( RCT ) to investigate the topic . DESIGN AND METHOD small scale prospect i ve RCT . Data on breast feeding , as defined as the exclusive method of feeding , were collected . A range of relevant bio- data was also collected and their impact on breast feeding assessed . SETTING a special care baby unit in a District General Hospital in the UK . PARTICIPANTS over a three-month period , all pre-term babies ( 32 - 37 weeks ' gestation ) who fulfilled the inclusion criteria and has been born to mothers who had expressed a pre-partum desire to breast feed , who had consented to take part , were included ( n=14 ) . PROCEDURE the eligible babies were r and omly allocated to supplementary feeding of breast milk , via either a cup or a bottle . Whether or not the baby was being breast fed at discharge was noted . FINDINGS the study suggested that this RCT framework is a viable method of investigating baby feeding . Because of the small-scale nature of the project , the actual data base must be treated with extreme caution . No significant differences were found between the two groups in terms of breast feeding . However , the mothers reported high levels of support and also the breast-feeding rates were above the national averages . These two findings could have contributed to the non-significant results observed in this analysis . CONCLUSIONS if the present findings could be supported by further research , then the non-significant results relating method of supplementary feeds to subsequent breast feeding could be explained by reference to three factors . Firstly , there is , in fact , no real effect of method of supplementary feeding and subsequent breast feeding ; secondly , the method adopted differed from existing research and thus may be expected to produce non-corroborative results ; and finally , the overall levels of breast feeding within the Unit generally were higher than the national average . The relevance of the RCT for investigating this subject is also discussed with reference to the present data set . Further experimental work to develop these ideas and to identify causal links is required OBJECTIVE : The goal was to assess the risk of bias among pediatric , r and omized , controlled trials ( RCTs ) reported in 8 high-impact journals . METHODS : We search ed PubMed for all pediatric RCTs reported between July 1 , 2007 , and June 30 , 2008 , in 8 journals with high impact factors . Using Cochrane Collaboration methods for risk assessment , we evaluated all reports for risk of bias according to domain ( ie , r and omized sequence generation , allocation concealment , masking , incomplete outcome data , selective outcome reporting , and other ) . We used multiple logistic regression to test for associations between the presence of a high risk of bias according to domain and funding source , intervention type , trial registration , and multicenter status . RESULTS : Industry-funded RCTs were more likely to show a high risk of bias for sequence generation , compared with government-funded RCTs ( adjusted odds ratio [ aOR ] : 6.1 [ 95 % confidence interval [ CI ] : 1.70– 21.89 ] ) , and behavioral/educational trials were more likely to show a high risk of bias for sequence generation ( aOR : 2.8 [ 95 % CI : 1.06–7.36 ] ) and allocation concealment ( aOR : 4.09 [ 95 % CI : 1.69–9.90 ] ) , compared with drug trials . Registered trials were less likely to have a high risk of bias for sequence generation , compared with nonregistered trials ( aOR : 0.33 [ 95 % CI : 0.15–0.71 ] ) . CONCLUSIONS : Overall , we found a large proportion of pediatric RCT reports with a high risk of bias for sequence generation and allocation concealment . Factors associated with a high risk of bias included industry funding and assessment of behavioral/educational interventions , whereas trial registration was associated with a lower risk of bias Aim : To evaluate whether paediatric r and omized clinical trials ( RCTs ) adopt recent guidance on Data Monitoring Committees ( DMCs ) , interim analysis and early termination Hypertensive adults demonstrate decreased performance on neurocognitive testing compared with that of normotensive controls . There is now emerging , preliminary evidence that children with hypertension also manifest neurocognitive differences when compared with normotensive controls , findings postulated to potentially represent early signs of hypertensive target organ damage to the brain . However , reports in children to date have been limited to data base and single-center studies . We have established an ongoing , prospect i ve , multicenter study of neurocognition in children with primary hypertension . This article outlines the study methods , with particular attention to the unique challenges in this area of clinical research . We highlight aspects of the study design that are specifically design ed as solutions to these challenges OBJECTIVE To examine the level of children 's underst and ing of informed consent in clinical trials and factors that may influence these processes . DESIGN Twenty nine children who were included in clinical trials for treatment of cancer or HIV , were offered the possibility to complete a semidirective interview , with parental permission . METHODS Children 's underst and ing was measured by a score of 0 - 9 including items required to obtain a valid consent according to French and European legislations . RESULTS Children were 8.5 - 18 years old ( 13.6 + /- 2.8 years ) . The higher percentage of underst and ing was obtained for the study objectives ( n = 18 , 62 % ) , the risks ( n = 17 , 58 % ) , the potential self- benefits ( n = 18 , 62 % ) and the potential benefits to other children ( n = 17 , 58 % ) . The lower percentage of underst and ing was obtained for the procedures ( n = 5 , 17 % ) , the possibility of alternative treatments ( n = 9 , 31 % ) , the duration of participation ( n = 6 , 21 % ) , their right to withdraw ( n = 6 , 21 % ) , and the voluntary participation ( n = 6 , 21 % ) . Sixteen children ( 55 % ) thought that the given information was adequate . Underst and ing was significantly correlated with child 's age ( r = 0.65 ; P = 0.0001 ) and the mean score was higher in patients over 14 years old compared to patients under the age of 14 ( 4.4 + /- 2.4 , n = 14 vs. 2.6 + /- 2.6 , n = 15 , P < 0.05 ) . The mean score was also higher in children when informed consent was sought some time after the diagnosis ( > 7 days ) rather than at the same time ( < 7 days ) ( score : 4.14 + /- 2.59 n = 21 vs. 1.87 + /- 2.03 n = 8 ; P = 0.03 ) . The clarity of information perceived by children did not influence their underst and ing ( score : 3.6 + /- 2.6 n = 14 vs. 3.5 + /- 2.7 n = 15 ; P = 0.91 ) . CONCLUSION Children have an incomplete underst and ing of the elements included in the informed consent forms . Underst and ing is related to age and timing of informed consent BACKGROUND R and omized clinical trials ( RCTs ) are uncommon in pediatric surgical specialties and the quality of reporting is unknown . Our primary purpose was to analyze published surgical RCTs involving children to measure adherence to the Consoli date d St and ards of Reporting Trials ( CONSORT ) guidelines . STUDY DESIGN Published RCTs from January 1 , 2000 through December 31 , 2009 were review ed . The trials were evaluated for the presence of 7 CONSORT guidelines and also grade d according to the Jadad scale . RESULTS Two hundred and twenty-eight trials were included . Five trials met all 7 CONSORT criteria ( 2 % ) and 53 had a Jadad score of ≥3 ( 23 % ) . Slightly more than 50 % of all trials specified primary outcomes and < 25 % described power calculations according to CONSORT . Adherence to CONSORT guidelines for allocation concealment , r and omization description , and attrition details was even lower . There were significant differences between surgical specialties with regard to CONSORT adherence to the majority of the guidelines . Pediatric general surgery had the largest number of published RCTs . Pediatric orthopaedic surgery had the highest proportion of trials with a Jadad score ≥3 ( 40 % ) . CONCLUSIONS Adherence to CONSORT guidelines is low across the spectrum of children 's surgical specialties , although significant differences do exist . Future RCTs in children 's surgical specialties should specifically focus on areas of low adherence to reporting guidelines This paper summarizes the results of screening for participation in research programs involving functional neuromuscular stimulation ( FNS ) . It examines the characteristics of a group of children and teenagers with spinal cord injuries ( SCI ) identified as potential c and i date s for FNS as defined by the rigorous inclusion criteria of the research studies . One hundred and thirteen children and teenagers under the age of 20 with cervical , thoracic or lumbar level spinal cord injuries were examined for inclusion in an experimental program of FNS to provide st and ing , walking , or prehension . Although biased towards adolescents with complete midthoracic and midcervical injuries , the age , sex , injury level , etiology , and neurological status of the sample coincided with previously published reports and consisted predominantly of teenage males injured in motor vehicle or sports related accidents . Approximately half of the individuals examined were physically appropriate for research participation without preparatory intervention . Treatment options to prepare individuals for FNS were identified in 25 % of those considered inappropriate at the initial evaluation , indicating that the potential user population of clinical systems may be larger than estimates obtained from research applications . Peripheral denervation was the single most prevalent physical impediment to the application of FNS . Although the incidence of lower motor neuron ( LMN ) involvement was similar in subjects with tetraplegia and paraplegia , those with cervical lesions more frequently exhibited other medical complications that interfered with the application of FNS . Surgical procedures involving transfer of paralyzed but excitable muscles were identified in almost one third of the c and i date s with tetraplegia who were excluded due to denervation . Of those physically appropriate , psychological factors eliminated several c and i date s from consideration . Such concerns may also be addressed with suitable intervention in preparation for the clinical application of FNS . Almost 50 % of those appropriate for FNS research elected to participate in the programs , with those declining citing the hospitalization , time and travel commitments as the primary factors influencing their decisions . Results suggest that FNS for st and ing , walking and h and grasp may be an option for a significant percentage of the pediatric SCI population AIMS To develop a population pharmacokinetic model for penciclovir ( famciclovir is a prodrug of penciclovir ) in adults and children and suggest an appropriate dose for children . Furthermore , to develop a limited sampling design based on sampling windows for three different paediatric age groups ( 1 - 2 , 2 - 5 and 5 - 12 years ) using an adequate number of subjects for future pharmacokinetic studies . METHODS Penciclovir plasma data from six different adult and paediatric studies were supplied by Novartis . Population pharmacokinetic modelling was undertaken in NONMEM version VI . Simulations in MATLAB were used to select an oral paediatric dose that gives similar exposure to 500 mg in adults . Optimal sampling times and sampling windows were obtained in MATLAB and simulations in NONMEM were used to select adequate sample sizes for three paediatric age groups . RESULTS A two-compartment , first-order absorption model with an absorption lag time , allometric weight models on V(1 ) , V(2 ) and Q , and an allometric weight model , age and creatinine clearance as covariates on CL adequately describe the pharmacokinetics of penciclovir in adults and children . Estimated CL ( l h(-1 ) 70 kg(-1 ) ) and V(ss ) ( l.70 kg(-1 ) ) were 31.2 and 83.1 , respectively . An oral dose of 10 mg kg(-1 ) body weight in children was predicted to give similar exposure as 500 mg in adults . A single sampling windows design ( 0.25 - 0.4 , 0.5 - 1 , 1.25 - 1.75 , 2.75 - 3.5 and 7.25 - 8 h ) for five sample s per subject and 10 subjects in each of the paediatric age groups is recommended for future studies . CONCLUSIONS A population pharmacokinetic model of penciclovir in adults and children has been developed . A prospect i ve study design , including dose adjustment , cohort size and blood sampling design has been recommended OBJECTIVES The purpose of this study was to investigate the quality of reporting of r and omised clinical trials ( RCTs ) published in dental specialty journals . METHODS The journals possessing the highest impact factor ( 2008 data ) in the six major dental specialties were included in the study . The contents of the 24 most recent issues of each journal were h and - search ed and research articles identified as r and omised controlled trials ( RCTs ) were selected . Quality evaluation was performed using the modified Consoli date d St and ards of Reporting Trials ( CONSORT ) statement checklist . The data were analysed using descriptive statistics followed by univariate and multivariate examination of statistical associations ( alpha=0.05 ) . RESULTS Ninety-five RCTs were identified with generally suboptimal scores on quality reporting on key CONSORT areas . Significant differences were found among journals with the Journal of Clinical Periodontology achieving the highest score , followed by the American Journal of Orthodontics and Dentofacial Orthopedics . There was a positive association between quality score and number of authors , involvement of statistician/epidemiologist , and multicentre trials . CONCLUSIONS The quality scores of RCTs in major dental journals are considered suboptimal in key CONSORT areas . This receives critical importance considering that improved quality of RCTs is a fundamental prerequisite for improved dental care BACKGROUND : Research information for children is often presented in a manner that is difficult to underst and . We design ed this study , therefore , to examine the effect of improved readability and processability of written study information on childrens ' underst and ing . METHODS : One-hundred-ninety children aged 7–17 yr who were hospitalized for a surgical procedure or medical treatment were r and omized to receive study information using either a st and ard form or a modified form with improved readability and processability . Children were interviewed to determine their underst and ing of eight study elements , including the risks , benefits , protocol , etc . , and their responses scored by two independent assessors . RESULTS : Children who were r and omized to the modified form had significantly greater overall underst and ing of the information and greater underst and ing of the protocol and benefits ( P < 0.05 ) . The modified form was particularly effective in improving younger children 's ( 7–10 yr ) underst and ing of the material . Multivariate analysis identified several predictors of underst and ing , including the modified format , age , reading ability and the degree to which the child read the information . When shown both forms , 81.3 % of children preferred the modified form stating that it was “ friendlier ” and “ easier to read . ” The use of a larger font size and pictures were particularly popular . CONCLUSIONS : Results of this study suggest that modification of study information to better fit the ages and meet the reading and cognitive abilities of children results in their improved underst and ing and acceptance of the material We are pleased to announce the development of CONSORT-SPI : a new reporting guideline for r and omised controlled trials ( RCTs ) of social and psychological interventions . We invite the readership of Journal of Child Psychology and Psychiatry ( JCPP ) to participate in this project by visiting our website ( http://tinyurl.com/CONSORT- study ) . Well- design ed and conducted r and omised trials are essential for improving services for children and young people . Not only can they help us to establish ‘ what works ’ in child and adolescent mental health ( Maughan , 2013 ) , but they can also help us to underst and how interventions work , and to identify ways in which individual characteristics affect susceptibility to intervention effects . The JCPP has led the way in promoting a high- quality evidence -base for interventions in this field . Over a decade ago , Harrington , Cartwright-Hatton , and Stein ( 2002 ) pointed to the importance of ‘ well- design ed and unambiguously reported RCTs [ .. to .. ] provide the best possible evidence about effectiveness of interventions , ’ and drew attention to the many special considerations entailed in design ing and interpreting RCTs in the field of child mental health . For example , they describe how interventions in this field are complex , involving multiple systems and professions . Moreover , interventions operate against a backdrop of developmental change , and multiple , interacting levels of social influence on the child . Measurement of outcomes often requires multi method assessment of child well-being , psychopathology , and co-morbidities , as well as family functioning . Thus , given the complexity of these interventions and their outcomes , they are difficult to evaluate . To underst and intervention effects and to keep services up to date , research ers , clinicians , commissioners , policymakers , journalists , and consumers rely on research reports of RCTs in scientific journals . Such reports should explain the methods , including the design , delivery , uptake , and context of interventions , and subsequent results . Accurate , complete , and transparent reporting is essential for readers to make best use of new evidence , to In this chapter , the design of pharmacokinetic studies and phase III trials in children is discussed . Classical approaches and relatively novel approaches , which may be more useful in the context of drug research in children , are discussed . The burden of repeated blood sampling in pediatric pharmacokinetic studies may be overcome by the population pharmacokinetics approach using nonlinear mixed effect modeling as the statistical solution to sparse data . Indications and contraindications for phase III trials are discussed : only when there is true " equipoise " in the medical scientific community , it is ethical to conduct a r and omized clinical trial . The many reasons why a pediatric trial may fail are illustrated with examples . Inadequate sample sizes lead to inconclusive results . Twelve classical strategies to minimize sample sizes are discussed followed by an introduction to group sequential design , boundaries design , and adaptive design . The evidence that these design s reduce sample sized between 35 and 70 % is review ed . The advantages and disadvantages of the different approaches are highlighted to give the reader a broad idea of the design types that can be considered . Finally , working with DMCs during the conduct of trials is introduced . The evidence regarding DMC activities , interim analysis results , and early termination of pediatric trials is presented . So far reporting is incomplete and heterogeneous , and users of trial reports may be misled by the results . A proposal for a checklist for the reporting of DMC issues , interim analyses , and early stopping is presented AIMS To assess whether an adaptive design in early clinical trials based on the paradigm of variable dosing and controlled exposure can provide better dosing recommendations compared with the st and ard fixed dose approach . METHODS In a clinical trial simulation setting , a paediatric study was simulated using a pharmacokinetic model previously developed for abacavir . Plasma concentrations following the current recommended dose ( 8 mg kg⁻¹ ) were taken at st and ard sampling times , exposures ( AUC ) were calculated and doses individually adapted to reach the target exposure ( i.e. effective exposure in adults ) . A second round of simulations followed with the adapted doses , and the result ing concentrations were fitted again with the same model . Exposure distributions in both conditions ( i.e. fixed dose and controlled exposure ) were compared with the target exposure . RESULTS The AUC distribution after the current dose result ed in a median exposure of 6.43 mg h l⁻¹ ( 90th percentile 3.13 - 10.67 mg h l⁻¹ ) . A total of 61 of 128 subjects showed AUC values either too low or to high compared with the target exposure . After dose adjustment , the median exposure was 6.94 mg h l⁻¹ ( 5.57 - 8.25 mg h l⁻¹ ) , and only 14 subjects deviated from the target range . CONCLUSIONS Adaptive r and omization can be used to optimize dosing regimens in early paediatric clinical trials . The r and omization of patients to target exposure rather than dose increases the probability of demonstrating efficacy ( i.e. study power ) compared with dose-controlled trials . Furthermore , it contributes to further underst and ing of the role of dose on the total heterogeneity in clinical response BACKGROUND / PURPOSE Reports of clinical trials often lack adequate descriptions of design and analysis ; recent attention has focused on improving this omission so readers can properly assess the strength of the findings and draw their own conclusions . Similar analysis of study design and method ologic st and ards associated with quality reporting has not been carried out for pediatric surgery journals . METHODS All studies ( n = 642 ) published in 1998 in Journal of Pediatric Surgery ( JPS ) and Pediatric Surgery International ( PSI ) , were review ed for demographic data and study design . The frequency of reporting of 11 basic elements of design and analysis was evaluated in r and omized clinical trials ( RCT ) , nonr and omized clinical trials ( N RCT ) , and retrospective cohorts ( RC ) from JPS by consensus of 2 assessors . RESULTS Of the 642 studies , 17 % of articles ( 111 of 642 ) were classified as clinical studies . Sixty-three were comparative studies and consisted of RC ( n = 48 ) , N RCT ( n = 12 ) , and RCT ( n = 3 ) . Two-thirds of articles published were either case reports or case series ( 431 of 642 ) , and 16 % were basic science articles . Demographic analysis showed a wide range of topics addressed , 4 authors per article , and multiple country of origin of authors . More than 66 % of all RCT in JPS reported on eligibility criteria , admission before allocation , r and om allocation , method of r and omization , patients ' blindness to treatment , treatment complications , statistical analyses , statistical methods , loss to follow-up , and statistical methods ; 2 elements of design and analysis , however , were poorly reported : blind assessment of outcome ( 33 % ) and power ( 17 % ) . CONCLUSIONS There were few r and omized , controlled trials in pediatric surgery journals , and further attention should be given to evaluate the causal factors . Nine elements of quality reporting were well reported ; however , 2 others were poorly reported ; this may improve if editors of pediatric surgical journals provide authors with guidelines on how to report clinical trial design and analysis Objective : Pediatric studies for new biological agents are m and ated by recent legislation , necessitating careful thought to evaluation of emerging multiple sclerosis ( MS ) therapies in children with MS . Challenges include a small patient population , the lack of prior r and omized clinical trials , and ethical concerns . The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research . Methods : The Steering Committee of the International Pediatric MS Study Group identified key focus areas for discussion . A total of 69 meeting attendees were assembled , including 35 academic experts . Regulatory and pharmaceutical representatives also attended , and provided input , which informed academic expert consensus decisions . Results : The academic experts agreed that clinical trials were necessary in pediatric MS to obtain pharmacokinetic , safety and efficacy data , and regulatory approval allowing for greater medication access . The academic experts agreed that relapse was an appropriate primary outcome measure for phase III pediatric trials . An international st and ardized cognitive battery was identified . The pros and cons of various trial design s were discussed . Guidelines surrounding MRI studies , pharmacokinetics , pharmacodynamics , and registries were developed . The academic experts agreed that given the limited subject pool , a stepwise approach to the launch of clinical trials for the most promising medications is necessary in order to ensure study completion . Alternative approaches could result in unethical exposure of patients to trial conditions without gaining knowledge . Conclusion : Consensus points for conduct of clinical trials in the rare disease pediatric MS were identified amongst a panel of academic experts , informed by regulatory and industry stakeholders School environments that provide consistent and reliable nutrition information promote the development of healthful eating in children . High-energy , nutrient-poor beverages offered for sale to children during the school day compete with healthful choices . The primary objective of this prospect i ve , quasiexperimental study was to encourage children to choose more healthful beverages during the school day without adversely affecting the profits realized from vending sales . Fifteen of 18 schools completed voluntary changes to beverage sales practice s during the school day between August 2005 and May 2006 . Twelve of 15 schools reported increased profits from the previous year ( 2004 - 2005 ) while offering more healthful beverage choices at discounted prices . Units of carbonated soft drinks sold declined when sports drinks , 100 % fruit juice , and water were made available in their place . Passive marketing in the form of vending machine fronts , attractive pricing with a nominal 10 % to 25 % discount , and changing the types and proportions of beverages offered encouraged children to make more healthful choices . Local school administrators were receptive to making changes to beverage sales when local needs were incorporated into the study design . Profit information from this study informed state legislators and the Mississippi State Board of Education in the development and adoption of statewide snack and beverage vending guidelines . Registered dietitians serve as advocates to foster these collaborative efforts , inform key decision makers , and work in their local communities to develop and promote healthful practice s in K-12 school setting BACKGROUND Due to the new European regulations for pediatric medications , future clinical trials will include an increasing number of minors . It is therefore important to reconsider and evaluate recent method ological and ethical aspects of clinical trials in minors . PROCEDURE The following questions were investigated : How are r and omized controlled clinical trials ( RCTs ) performed in practice ? Do investigators take into consideration biomedical ethical principles , explicated for example by Beauchamp and Childress , when planning and conducting a trial ? The study was conducted in a descriptive manner . A systematic , algorithm-guided search focusing on RCTs in minors with malignant diseases was carried out in PubMed . One-thous and -nine-hundred-sixty-two publications from 2001 to 2005 were r and omized in sequence . The first 1,000 publications were screened according to a priori defined inclusion criteria . One hundred seventy-five publications met the criteria and were review ed using the SIGN method ological checklist ( 2004 ) , the CONSORT Statement ( 2001 , section Methods , items 3 - 12 ) and indicators for ethical aspects . Seventeen publications were checked by two raters . RESULTS Information on r and omization and blinding was often equivocal . The publications were mainly rated positive for the criteria of the SIGN checklist , and mostly rated negative for the additional items of the CONSORT Statement . Regarding the ethical principles , only few contributions were found in the publications . Inter-rater reliability was good . CONCLUSIONS In the publications analyzed , we found only limited information concerning methods and reflections on ethical principles of the trials . Improvements are thus necessary and possible . We suggest how such trials and their respective publications can be optimized for these aspects |
1,723 | 25,646,407 | CONCLUSIONS From the presented data in the current systematic review , we conclude that : i ) exogenous insulin and amino acid administration effectively increase muscle protein synthesis , but this effect is attributed to the hyperaminoacidemia ; ii ) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis ; iii ) exogenous insulin result ing in supraphysiological insulin levels exceeding 50 , 000 pmol/l may effectively augment muscle protein synthesis ; iv ) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance ; and v ) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy , young adults | BACKGROUND Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism , there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans .
OBJECTIVE To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults . | BACKGROUND Loss of muscle mass with aging is a major public health concern . Omega-3 ( n-3 ) fatty acids stimulate protein anabolism in animals and might therefore be useful for the treatment of sarcopenia . However , the effect of omega-3 fatty acids on human protein metabolism is unknown . OBJECTIVE The objective of this study was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis in older adults . DESIGN Sixteen healthy , older adults were r and omly assigned to receive either omega-3 fatty acids or corn oil for 8 wk . The rate of muscle protein synthesis and the phosphorylation of key elements of the anabolic signaling pathway were evaluated before and after supplementation during basal , postabsorptive conditions and during a hyperaminoacidemic-hyperinsulinemic clamp . RESULTS Corn oil supplementation had no effect on the muscle protein synthesis rate and the extent of anabolic signaling element phosphorylation in muscle . Omega-3 fatty acid supplementation had no effect on the basal rate of muscle protein synthesis ( mean ± SEM : 0.051 ± 0.005%/h compared with 0.053 ± 0.008%/h before and after supplementation , respectively ; P = 0.80 ) but augmented the hyperaminoacidemia-hyperinsulinemia-induced increase in the rate of muscle protein synthesis ( from 0.009 ± 0.005%/h above basal values to 0.031 ± 0.003%/h above basal values ; P < 0.01 ) , which was accompanied by greater increases in muscle mTOR(Ser2448 ) ( P = 0.08 ) and p70s6k(Thr389 ) ( P < 0.01 ) phosphorylation . CONCLUSION Omega-3 fatty acids stimulate muscle protein synthesis in older adults and may be useful for the prevention and treatment of sarcopenia . This trial was registered at clinical trials.gov as NCT00794079 Men have more muscle than women , but most studies evaluating sex differences in muscle protein metabolism have been unable to discern sexual dimorphism in basal muscle protein turnover rates in young and middle-aged adults . We hypothesized that the anabolic response to nutritional stimuli ( i.e. , amino acids and insulin ) would be greater in young/middle-aged men than women . We therefore measured the rates of muscle protein synthesis ( MPS ) in 16 healthy individuals [ 8 men and 8 women , matched for age ( mean + /- SE : 37.7 + /- 1.5 yr ) and body mass index ( 25.2 + /- 0.7 kg/m2 ) ] after an overnight fast ( plasma insulin approximately 5 microU/ml and plasma phenylalanine approximately 60 microM ) and during a hyperinsulinemic-hyperaminoacidemic-euglycemic clamp ( plasma insulin approximately 28 microU/ml ; plasma phenylalanine approximately 110 microM ; plasma glucose approximately 5.4 mM ) . The rates of MPS were not different between men and women ( ANOVA main effect for sex ; P = 0.49 ) . During the clamp , the rate of MPS increased by approximately 50 % ( P = 0.003 ) with no difference in the increases from basal values between men and women ( + 0.019 + /- 0.004 vs. + 0.018 + /- 0.010%/h , respectively ; P = 0.93 ) . There were also no differences between men and women in the basal concentrations of muscle phosphorylated Akt(Ser473 ) , Akt(Thr308 ) , mTOR(Ser2448 ) , and p70s6k(Thr389 ) or in the hyperinsulinemia-hyperaminoacidemia-induced increases in phosphorylation of those signaling elements ( P > or = 0.25 ) . We conclude that there are no major differences in the rate of MPS and its intracellular control during basal conditions and during hyperinsulinemia-hyperaminoacidema between young and middle-aged adult men and women To determine the in vivo effect of amino acids ( AAs ) alone or in combination with insulin on splanchnic and muscle protein dynamics , we infused stable isotope tracers of AAs in 36 healthy subjects and sample d from femoral artery and vein and hepatic vein . The subjects were r and omized into six groups and were studied at baseline and during infusions of saline ( group 1 ) , insulin ( 0.5 mU. kg(-1 ) . min(-1 ) ) ( group 2 ) , insulin plus replacement of AAs ( group 3 ) insulin plus high-dose AAs ( group 4 ) , or somatostatin and baseline replacement doses of insulin , glucagon and GH plus high dose of AAs ( group 5 ) or saline ( group 6 ) . Insulin reduced muscle release of AAs mainly by inhibition of protein breakdown . Insulin also enhanced AA-induced muscle protein synthesis ( PS ) and reduced leucine transamination . The main effect of AAs on muscle was the enhancement of PS . Insulin had no effect on protein dynamics or leucine transamination in splanchnic bed . However , AAs reduced protein breakdown and increased synthesis in splanchnic bed in a dose-dependent manner . AAs also enhanced leucine transamination in both splanchnic and muscle beds . Thus insulin 's anabolic effect was mostly on muscle , whereas AAs acted on muscle as well as on splanchnic bed . Insulin achieved anabolic effect in muscle by inhibition of protein breakdown , enhancing AA-induced PS , and reducing leucine transamination . AAs largely determined protein anabolism in splanchnic bed by stimulating PS and decreasing protein breakdown OBJECTIVE Skeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy , nondiabetic older adults . This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling . We hypothesized that , in older subjects , pharmacological restoration of insulin-induced capillary recruitment would improve the response of muscle protein synthesis and anabolism to insulin . RESEARCH DESIGN AND METHODS Twelve healthy , nondiabetic older subjects ( 71 ± 2 years ) were r and omized to two groups . Subjects were studied at baseline and during local infusion in one leg of insulin alone ( Control ) or insulin plus sodium nitroprusside ( SNP ) at variable rate to double leg blood flow . We measured leg blood flow by dye dilution ; muscle microvascular perfusion with contrast enhanced ultrasound ; Akt/mTORC1 signaling by Western blotting ; and muscle protein synthesis , amino acid , and glucose kinetics using stable isotope method ologies . RESULTS There were no baseline differences between groups . Blood flow , muscle perfusion , phenylalanine delivery to the leg , and intracellular availability of phenylalanine increased significantly ( P < 0.05 ) in SNP only . Akt phosphorylation increased in both groups but increased more in SNP ( P < 0.05 ) . Muscle protein synthesis and net balance ( nmol · min−1 · 100 ml · leg−1 ) increased significantly ( P < 0.05 ) in SNP ( synthesis , 43 ± 6 to 129 ± 25 ; net balance , −16 ± 3 to 26 ± 12 ) but not in Control ( synthesis , 41 ± 10 to 53 ± 8 ; net balance , −17 ± 3 to −2 ± 3 ) . CONCLUSIONS Pharmacological enhancement of muscle perfusion and amino acid availability during hyperinsulinemia improves the muscle protein anabolic effect of insulin in older adults To define the mechanism of insulin 's anticatabolic action , the effects of three different dosages of insulin ( 0.25 , 0.5 , and 1.0 mU x kg(-1 ) x min(-1 ) ) versus saline on protein dynamics across splanchnic and skeletal muscle ( leg ) beds were determined using stable isotopes of phenylalanine , tyrosine , and leucine in 24 healthy subjects . After an overnight fast , protein breakdown in muscle exceeded protein synthesis , causing a net release of amino acids from muscle bed , while in the splanchnic bed protein synthesis exceeded protein breakdown , result ing in a net uptake of these amino acids . Insulin decreased ( P < 0.003 ) muscle protein breakdown in a dose-dependent manner with no effect on muscle protein synthesis , thus decreasing the net amino acid release from the muscle bed . In contrast , insulin decreased protein synthesis ( P < 0.03 ) in the splanchnic region with no effect on protein breakdown , thereby decreasing the net uptake of the amino acids . In addition , insulin also decreased ( P < 0.001 ) leucine nitrogen flux substantially more than leucine carbon flux , indicating increased leucine transamination ( an important biochemical process for nitrogen transfer between amino acids and across the organs ) , in a dose-dependent manner , with the magnitude of effect being greater on skeletal muscle than on the splanchnic bed . In conclusion , muscle is in a catabolic state in human subjects after an overnight fast and provides amino acids for synthesis of essential proteins in the splanchnic bed . Insulin achieves amino acid balance across splanchnic and skeletal muscle beds through its differential effects on protein dynamics in these tissue beds We have determined the individual and combined effects of insulin and prior exercise on leg muscle protein synthesis and degradation , amino acid transport , glucose uptake , and alanine metabolism . Normal volunteers were studied in the postabsorptive state at rest and about 3 h after a heavy leg resistance exercise routine . The leg arteriovenous balance technique was used in combination with stable isotopic tracers of amino acids and biopsies of the vastus lateralis muscle . Insulin was infused into a femoral artery to increase the leg insulin concentrations to high physiologic levels without substantively affecting the whole-body level . Protein synthesis and degradation were determined as rates of intramuscular phenylalanine utilization and appearance , and muscle fractional synthetic rate ( FSR ) was also determined . Leg blood flow was greater after exercise than at rest ( P<0.05 ) . Insulin accelerated blood flow at rest but not after exercise ( P<0.05 ) . The rates of protein synthesis and degradation were greater during the postexercise recovery ( 65+/-10 and 74+/-10 nmol x min(-1 ) x 100 ml(-1 ) leg volume , respectively ) than at rest ( 30+/-7 and 46+/-8 nmol x min(-1 ) x 100 ml(-1 ) leg volume , respectively ; P<0.05 ) . Insulin infusion increased protein synthesis at rest ( 51+/-4 nmol x min(-1 ) x 100 ml(-1 ) leg volume ) but not during the postexercise recovery ( 64+/-9 nmol x min(-1 ) x 100 ml(-1 ) leg volume ; P<0.05 ) . Insulin infusion at rest did not change the rate of protein degradation ( 48+/-3 nmol x min(-1 ) 100 ml(-1 ) leg volume ) . In contrast , insulin infusion after exercise significantly decreased the rate of protein degradation ( 52+/-9 nmol x min(-1 ) x 100 ml(-1 ) leg volume ) . The insulin stimulatory effects on inward alanine transport and glucose uptake were three times greater during the postexercise recovery than at rest ( P<0.05 ) . In contrast , the insulin effects on phenylalanine , leucine , and lysine transport were similar at rest and after exercise . In conclusion , the ability of insulin to stimulate glucose uptake and alanine transport and to suppress protein degradation in skeletal muscle is increased after resistance exercise . Decreased amino acid availability may limit the stimulatory effect of insulin on muscle protein synthesis after exercise We have investigated the mechanisms of the anabolic effect of insulin on muscle protein metabolism in healthy volunteers , using stable isotopic tracers of amino acids . Calculations of muscle protein synthesis , breakdown , and amino acid transport were based on data obtained with the leg arteriovenous catheterization and muscle biopsy . Insulin was infused ( 0.15 mU/min per 100 ml leg ) into the femoral artery to increase femoral venous insulin concentration ( from 10 + /- 2 to 77 + /- 9 microU/ml ) with minimal systemic perturbations . Tissue concentrations of free essential amino acids decreased ( P < 0.05 ) after insulin . The fractional synthesis rate of muscle protein ( precursor-product approach ) increased ( P < 0.01 ) after insulin from 0.0401 + /- 0.0072 to 0.0677 + /- 0.0101%/h . Consistent with this observation , rates of utilization for protein synthesis of intracellular phenylalanine and lysine ( arteriovenous balance approach ) also increased from 40 + /- 8 to 59 + /- 8 ( P < 0.05 ) and from 219 + /- 21 to 298 + /- 37 ( P < 0.08 ) nmol/min per 100 ml leg , respectively . Release from protein breakdown of phenylalanine , leucine , and lysine was not significantly modified by insulin . Local hyperinsulinemia increased ( P < 0.05 ) the rates of inward transport of leucine , lysine , and alanine , from 164 + /- 22 to 200 + /- 25 , from 126 + /- 11 to 221 + /- 30 , and from 403 + /- 64 to 595 + /- 106 nmol/min per 100 ml leg , respectively . Transport of phenylalanine did not change significantly . We conclude that insulin promoted muscle anabolism , primarily by stimulating protein synthesis independently of any effect on transmembrane transport |
1,724 | 16,441,466 | As many of these therapies have not been subjected to controlled clinical trials , some , at least , of their efficacy may reflect the high-placebo response rate that is characteristic of irritable bowel syndrome .
There is , however , evidence to support efficacy for hypnotherapy , some forms of herbal therapy and certain probiotics in irritable bowel syndrome .
All complementary and alternative medicine is not the same and some , such as hypnotherapy , forms of herbal therapy , specific diets and probiotics , may well have efficacy in irritable bowel syndrome . | BACKGROUND Complementary and alternative medical therapies and practice s are widely employed in the treatment of the irritable bowel syndrome .
AIM To review the usage of complementary and alternative medicine in the irritable bowel syndrome , and to assess critically the basis and evidence for its use .
RESULTS A wide variety of complementary and alternative medical practice s and therapies are commonly employed by irritable bowel syndrome patients both in conjunction with and in lieu of conventional therapies . | Background : Patients with irritable bowel syndrome ( IBS ) often feel they have some form of dietary intolerance and frequently try exclusion diets . Tests attempting to predict food sensitivity in IBS have been disappointing but none has utilised IgG antibodies . Aims : To assess the therapeutic potential of dietary elimination based on the presence of IgG antibodies to food . Patients : A total of 150 out patients with IBS were r and omised to receive , for three months , either a diet excluding all foods to which they had raised IgG antibodies ( enzyme linked immunosorbant assay test ) or a sham diet excluding the same number of foods but not those to which they had antibodies . Methods : Primary outcome measures were change in IBS symptom severity and global rating scores . Non-colonic symptomatology , quality of life , and anxiety/depression were secondary outcomes . Intention to treat analysis was undertaken using a generalised linear model . Results : After 12 weeks , the true diet result ed in a 10 % greater reduction in symptom score than the sham diet ( mean difference 39 ( 95 % confidence intervals ( CI ) 5–72 ) ; p = 0.024 ) with this value increasing to 26 % in fully compliant patients ( difference 98 ( 95 % CI 52–144 ) ; p<0.001 ) . Global rating also significantly improved in the true diet group as a whole ( p = 0.048 , NNT = 9 ) and even more in compliant patients ( p = 0.006 , NNT = 2.5 ) . All other outcomes showed trends favouring the true diet . Relaxing the diet led to a 24 % greater deterioration in symptoms in those on the true diet ( difference 52 ( 95 % CI 18–88 ) ; p = 0.003 ) . Conclusion : Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research BACKGROUND The cause of irritable bowel syndrome ( IBS ) is unknown . It may follow gastroenteritis and be associated with an abnormal gut flora and with food intolerance . Our study was design ed to assess whether these factors were associated with colonic malfermentation . METHODS We carried out a crossover controlled trial of a st and ard diet and an exclusion diet matched for macronutrients in six female IBS patients and six female controls . During the final 72 h on each diet , faecal excretion of fat , nitrogen , starch , and non-starch polysaccharide NSP was measured , and total excretion of hydrogen and methane collected over 24 h in a purpose -built 1.4 m3 whole-body calorimeter . Breath hydrogen and methane excretion were then measured for 3 h after 20 g oral lactulose . FINDINGS The maximum rate of gas excretion was significantly greater in patients than in controls ( 2.4 mL/min IQR 1.7 - 2.6 vs 0.6 , 0.4 - 1.1 ) . Although total gas production in patients was not greater than in controls ( median 527 mL/24 h IQR 387 - 660 vs 412 , 234 - 507 ) , hydrogen production was higher ( 332 , 318 - 478 vs 162 , 126 - 217 , p=0.009 ) . In patients , the exclusion diet reduced symptoms and produced a fall in maximum gas excretion ( 0.5 mL/min IQR 0.3 - 0.7 ) . After lactulose , breath hydrogen was greater on the st and ard than on the exclusion diet . INTERPRETATION Colonic-gas production , particularly of hydrogen , is greater in patients with IBS than in controls , and both symptoms and gas production are reduced by an exclusion diet . This reduction may be associated with alterations in the activity of hydrogen-consuming bacteria . Fermentation may be an important factor in the pathogenesis of IBS CONTEXT Irritable bowel syndrome ( IBS ) is a common functional bowel disorder for which there is no reliable medical treatment . OBJECTIVE To determine whether Chinese herbal medicine ( CHM ) is of any benefit in the treatment of IBS . DESIGN R and omized , double-blind , placebo-controlled trial conducted during 1996 through 1997 . SETTING Patients were recruited through 2 teaching hospitals and 5 private practice s of gastroenterologists , and received CHM in 3 Chinese herbal clinics . PATIENTS A total of 116 patients who fulfilled the Rome criteria , an established st and ard for diagnosis of IBS . INTERVENTION Patients were r and omly allocated to 1 of 3 treatment groups : individualized Chinese herbal formulations ( n = 38 ) , a st and ard Chinese herbal formulation ( n = 43 ) , or placebo ( n = 35 ) . Patients received 5 capsules 3 times daily for 16 weeks and were evaluated regularly by a traditional Chinese herbalist and by a gastroenterologist . Patients , gastroenterologists , and herbalists were all blinded to treatment group . MAIN OUTCOME MEASURES Change in total bowel symptom scale scores and global improvement assessed by patients and gastroenterologists and change in the degree of interference in life caused by IBS symptoms assessed by patients . RESULTS Compared with patients in the placebo group , patients in the active treatment groups ( st and ard and individualized CHM ) had significant improvement in bowel symptom scores as rated by patients ( P=.03 ) and by gastroenterologists ( P=.001 ) , and significant global improvement as rated by patients ( P=.007 ) and by gastroenterologists ( P=.002 ) . Patients reported that treatment significantly reduced the degree of interference with life caused by IBS symptoms ( P=.03 ) . Chinese herbal formulations individually tailored to the patient proved no more effective than st and ard CHM treatment . On follow-up 14 weeks after completion of treatment , only the individualized CHM treatment group maintained improvement . CONCLUSION Chinese herbal formulations appear to offer improvement in symptoms for some patients with IBS AIM Irritable bowel syndrome ( IBS ) is a common disorder and many patients fail to find adequate relief from conventional therapies for their symptoms . This study tests the cl aim that acupuncture is effective for a majority of these patients . METHODS A prospect i ve , blinded , sham acupuncture-controlled trial of traditional Chinese acupuncture was performed at a single postgraduate teaching hospital in Europe . Sixty patients with well-established IBS were recruited . The blinded comparator was sham acupuncture administered by the second of two acupuncturists who alone was aware of the r and omization , and who otherwise followed the prescription of the first . The primary end-point was a defined fall in the symptom score at 13 wk ( by intention to treat ) . The prior expectation was a 30 % placebo response , and a response rate of 70 % from acupuncture , for which the study was adequately powered . RESULTS Patients in treated and sham groups improved significantly during the study -mean improvement in scores being equal ( minus 1.9 ) and significant for both ( P<0.05 ; one-tailed t test ) . There was a small numeric but non-significant difference between the response rate in patients receiving acupuncture ( 40.7 % ) and sham treatment ( 31.2 % ) . Several secondary end-points marginally favored active treatment , but an improved symptom score of any degree of magnitude occurred more often with sham therapy ( 65.6 % vs 59.2 % ) . For no criterion was statistical significance approached . CONCLUSION Traditional Chinese acupuncture is relatively ineffective in IBS in the European hospital setting , and the magnitude of any effect appears insufficient to warrant investment in acupuncture services CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient BACKGROUND Irritable bowel syndrome ( IBS ) is a significant problem for primary care , as treatment options are limited and it can frequently develop into a chronic condition . Complementary and alternative medicine , including reflexology , is being turned to increasingly in an attempt to manage symptoms . There are currently no studies which address the effectiveness of reflexology for IBS . Despite this , it continues to be advocated and used . AIM To provide the first evidence on the effectiveness of reflexology in the management of the core defining symptoms of IBS . DESIGN OF STUDY A single-blind trial carried out in primary care setting s. SETTING Thirty-four participants diagnosed with IBS on the basis of the Rome Criteria . METHOD Participants were allocated to receive either a reflexology foot massage or a non-reflexology foot massage control group . RESULTS On none of the three symptoms monitored -- abdominal pain , constipation/diarrhoea , and abdominal distention -- was there a statistically or clinical ly significant difference between reflexology and control groups . CONCLUSION On the basis of these results there is nothing to suggest that reflexology produces any specific benefit for patients with IBS . There is currently no evidence to support its use . However this was one ( relatively ) small scale study ; further research that , for example , assesses the impact of therapist ( professional and lay ) versus therapy , is still needed OBJECTIVE To determine whether clinical trials originating in certain countries always have positive results . DATA SOURCES Abstract s of trials from Medline ( January 1966-June 1995 ) . STUDY SELECTION Two separate studies were conducted . The first included trials in which the clinical outcome of a group of subjects receiving acupuncture was compared to that of a group receiving placebo , no treatment , or a nonacupuncture intervention . In the second study , r and omized or controlled trials of interventions other than acupuncture that were published in China , Japan , Russia/USSR , or Taiwan were compared to those published in Engl and . DATA EXTRACTION Blinded review ers determined inclusion and outcome and separately classified each trial by country of origin . DATA SYNTHESIS In the study of acupuncture trials , 252 of 1085 abstract s met the inclusion criteria . Research conducted in certain countries was uniformly favorable to acupuncture ; all trials originating in China , Japan , Hong Kong , and Taiwan were positive , as were 10 out of 11 of those published in Russia/USSR . In studies that examined interventions other than acupuncture , 405 of 1100 abstract s met the inclusion criteria . Of trials published in Engl and , 75 % gave the test treatment as superior to control . The results for China , Japan , Russia/USSR , and Taiwan were 99 % , 89 % , 97 % , and 95 % , respectively . No trial published in China or Russia/USSR found a test treatment to be ineffective . CONCLUSIONS Some countries publish unusually high proportions of positive results . Publication bias is a possible explanation . Research ers undertaking systematic review s should consider carefully how to manage data from these countries In a r and omized , double-blind controlled trial , 42 children with irritable bowel syndrome ( IBS ) were given pH-dependent , enteric-coated peppermint oil capsules or placebo . After 2 weeks , 75 % of those receiving peppermint oil had reduced severity of pain associated with IBS . Peppermint oil may be used as a therapeutic agent during the symptomatic phase of IBS To determine the efficacy and tolerability of an enteric-coated peppermint-oil formulation ( Colpermin ) , we conducted a prospect i ve , r and omized , double-blind , placebo-controlled clinical study in 110 out patients ( 66 men/44 women ; 18–70 years of age ) with symptoms of irritable bowel syndrome . Patients took one capsule ( Colpermin or placebo ) three to four times daily , 15–30 min before meals , for 1 month . Fifty-two patients on Colpermin and 49 on placebo completed the study . Forty-one patients on Colpermin ( 79 % ) experienced an alleviation of the severity of abdominal pain ( 29 were pain-free ) ; 43 ( 83 % ) had less abdominal distension , 43 ( 83 % ) had reduced stool frequency , 38 ( 73 % ) had fewer borborygmi , and 41 ( 79 % ) less flatulence . Corresponding figures for the placebo group were : 21 patients ( 43 % ) with reduced pain ( 4 were pain-free ) 14 ( 29 % ) with reduced distension , 16 ( 32 % ) with reduced stool frequency , 15 ( 31 % ) with fewer borborygmi , and 11 ( 22 % ) with less flatulence . Symptom improvements after Colpermin were significantly better than after placebo ( P<0.05 ; Mann-Whitney U-test ) . One patient on Colpermin experienced heartburn ( because of chewing the capsules ) and one developed a mild transient skin rash . There were no significant changes in liver function test results . Thus , in this trial , Colpermin was effective and well tolerated To assess the efficacy and safety of enteric coated capsules containing a fixed combination of 90 mg peppermint oil and 50 mg caraway oil ( PCC ; Enteroplant ) in patients with functional dyspepsia Complementary and alternative medical ( CAM ) therapies ( also known as integrative or unconventional therapies ) have been defined as those interventions neither taught widely at U.S. medical schools nor generally available in U.S. hospitals ( 1 , 2 ) . While imperfect , this definition has been used to identify representative CAM therapies , which have been studied for prevalence of use in two national r and om-household telephone surveys ( 1 , 2 ) . Data from these surveys indicate that CAM therapy use and expenditures increased substantially in the United States between 1990 and 1997 ( 1 ) . Overall prevalence of use increased by 25 % ; total visits by an estimated 47 % , from 427 to 629 million ; and expenditures for CAM services by an estimated 45 % , which totaled $ 21 billion ( 1 ) . National surveys performed in other countries have suggested similar rates of CAM use throughout the industrialized world ( 3 - 7 ) . Less well documented , however , are the reasons that adults typically use ( and pay out of pocket for ) these therapies , most of which have not been satisfactorily evaluated for relative effectiveness , safety , or mechanisms of action . Only one U.S. national survey published in a peer- review ed journal has explored reasons for CAM use ( 8) . Astin 's survey , conducted in 1994 on a convenience sample of 1035 adults , found that reasons for CAM use included a holistic orientation to health ; having had a transformational experience that changed the person 's world view ; and classification in a cultural group identifiable by their commitment to environmentalism , commitment to feminism , and interest in spirituality and personal growth psychology ( 8) . National surveys in the United States of CAM use in 1990 and 1997 revealed that adults typically do not disclose their use of CAM therapies to their medical doctors ( 1 , 2 ) . In 1997 , as in 1990 ( 1 ) , fewer than 40 % of CAM therapies used in the previous 12 months were discussed with a medical doctor . A recent analysis of data on U.S. national medical expenditures corroborated these findings and suggested that the percentage of CAM users who disclose their CAM visits to their medical doctors may be as low as 20 % ( 9 ) . This paper summarizes 1997 national survey data on respondents ' perceptions about use and nondisclosure of CAM therapies relative to conventional medical care . Methods Sample We conducted a nationally representative telephone survey between November 1997 and February 1998 . Survey methods were approved by the Beth Israel Deaconess Committee on Clinical Investigations , Boston , Massachusetts . The survey used r and om-digit dialing techniques to select households and r and om selection of one resident per household , age 18 years or older , as the respondent . Eligibility was limited to English- language speakers for whom cognitive or physical impairment did not prevent completion of the interview . The survey sample and weighting methods have been previously described ( 1 ) . Interview The interview was presented as a survey by investigators from Harvard Medical School about the health care practice s of persons in the United States . No mention was made of alternative , integrative , unproven , or complementary therapies in the introductory comments . The first substantive questions addressed perceived health , health worries , days spent in bed , and functional impairment due to health conditions . Next , respondents were asked about their interactions with a medical doctor , defined as a medical doctor , MD , or an osteopath , DOnot a chiropractor or other nonmedical doctor . The term medical doctor was used throughout the remainder of the interview . Respondents were asked if they had experienced any of a list of specified common medical conditions in the previous 12 months . Those who reported experiencing more than three conditions were asked to identify the three most bothersome or serious medical conditions . Respondents were then asked about seeing a medical doctor for these principal medical conditions and about perceptions of confidence in the medical doctor and the helpfulness and efficacy of their interactions . Next , respondents were asked about use of CAM therapies in the past 12 months and over their lifetime and whether each of these therapies was used for each of their principal medical conditions . We distinguished between use under the supervision of a professional ( a provider of CAM therapy ) and personal use without such supervision . Persons who reported having supervised use were asked about the number of visits during the past 12 months to providers of each therapy , perceptions of helpfulness and efficacy , and confidence in their CAM therapy providers . Respondents were asked whether they typically see a CAM provider before , after , or concurrent with their visits to a medical doctor . In addition , respondents were asked whether they agreed or disagreed with a list of thoughts about the use of alternative therapies ( Figure 1 ) . Each question was intended to eluci date perceptions about CAM therapy use relative to conventional care . All users of CAM therapies who had seen their medical doctor in the past year were asked if they had discussed use of each therapy with their medical doctor and if not , why they had not . They were then provided a list of possible reasons why people might not discuss certain therapies with a medical doctor and were asked to say yes to any number of items on the list that explained their own reasons for nondisclosure and no to items that did not . Additional details of the survey instrument are described elsewhere ( 1 ) . Figure 1 . Perceptions about complementary and alternative medical ( CAM ) therapy relative to conventional therapy . white bars shaded bars darkly shaded bars n n Statistical Analysis As previously described ( 1 ) , we calculated sampling weights for each respondent to reflect the probability of selection and to parallel the aggregate distribution of demographic characteristics of the U.S. population . We used SUDAAN software ( 10 ) to compute weighted estimates of the proportion of respondents giving specific answers to study questions . We applied the McNemar test to compare respondents ' evaluations of the helpfulness of CAM therapies and conventional care among respondents who used both for the same medical condition . Role of the Funding Sources This research was funded by grants from the National Institutes of Health , the John E. Fetzer Institute , and the American Society of Actuaries . Additional support for the completion of analyses and manuscript preparation was provided by unrestricted gifts from the Friends of Beth Israel Deaconess Medical Center , the Kenneth J. Germeshausen Foundation , the J.E. and Z.B. Butler Foundation , and The American Specialties Health Plan . None of the sponsors had access to the primary data , nor did they review the manuscript before su bmi ssion . Results Characteristics of the Respondents The weighted survey response rate was 60 % ( 1 ) . The sociodemographic characteristics of the survey sample ( n = 2055 ) were similar to the population distributions published by the U.S. Bureau of the Census ( 1 ) . Among the 2055 survey participants , 1802 ( 87 % weighted ) reported seeing a medical doctor in the previous 12 months . Of these , 831 ( 45 % weighted ) reported using CAM therapy ( excluding use of self-prayer alone ) in the past 12 months , and 411 ( 23 % weighted ) reported seeing a CAM provider in the past 12 months ( 1 ) . Perceptions of CAM Relative to Conventional Therapy Use Figure 1 summarizes responses among respondents who used conventional care and CAM therapies in the past 12 months . As a preface to these questions , the interview script read , I am going to read you some thoughts people have about their use of alternative therapies , like chiropractic , massage , acupuncture and the others I mentioned earlier . For each statement , please tell me if you agree or disagree . As shown in Figure 1 , fewer than 1 in 4 ( 21 % ) CAM therapy users ( n = 831 ) agreed with the statement , Alternative therapies are superior to conventional therapies , and roughly 4 of 5 ( 79 % ) respondents agreed that Using both conventional and alternative therapies is better than using either one alone [ for your problems ] . For respondents who saw a CAM therapy provider and a medical doctor ( n = 411 ) , we asked whether they agreed or disagreed that their CAM provider did a better job of listening or explaining their medical problems than their medical doctor . Forty-one percent agreed that their CAM provider was a better listener , and 52 % disagreed ; 42 % agreed that their CAM provider did a better job of explaining their medical conditions , and 56 % disagreed . Sequence of Seeking Care from CAM Providers and Medical Doctors We asked respondents who reported seeing both a medical doctor and a CAM provider during the past 12 months ( n = 411 ) the following : The next questions are about your use of alternative therapies in general . People generally fall into one of three groups regarding their use of alternative medicine . Some people see an alternative provider before they consult a medical doctor ; some see both alternative providers and conventional doctors at the same time ; and some see an alternative provider after they have seen a medical doctor . Which of these best describes your pattern of seeing alternative providers ? As summarized in Figure 2 , 7 of 10 respondents reported typically seeking the services of a CAM provider after or concurrent with their visit to a medical doctor . Fewer than 1 in 6 ( 15 % ) said they saw a CAM therapy provider before seeing a medical doctor . Figure 2 . Sequence of seeking care from complementary and alternative medical ( CAM ) providers and medical doctors . n Overall Helpfulness of Therapies The Table summarizes perceived relative helpfulness for 10 of the most commonly reported principal medical conditions identified in the 1997 national survey among respondents who used both conventional care and CAM therapies for each condition . The CAM therapies were judged more helpful OBJECTIVE : The influence of the gastrointestinal ( GI ) microflora in patients with irritable bowel syndrome ( IBS ) has not been clearly eluci date d. This study was undertaken to see if patients with IBS have an imbalance in their normal colonic flora , as some bacterial taxa are more prone to gas production than others . We also wanted to study whether the flora could be altered by exogenous supplementation . In a previous study we have characterized the mucosa-associated lactobacilli in healthy individuals and found some strains with good colonizing ability . Upon colonization , they seemed to reduce gas formation . METHODS : The study comprised 60 patients with IBS and a normal colonoscopy or barium enema . Patients fulfilling the Rome criteria , without a history of malabsorption , and with normal blood tests underwent a sigmoidoscopy with biopsy . They were r and omized into two groups , one receiving 400 ml per day of a rose-hip drink containing 5 × 107 cfu/ml of Lactobacillus plantarum ( DSM 9843 ) and 0.009 g/ml oat flour , and the other group receiving a plain rose-hip drink , comparable in color , texture , and taste . The administration lasted for 4 wk . The patients recorded their own GI function , starting 2 wk before the study and continuing throughout the study period . Twelve months after the end of the study all patients were asked to complete the same question naire regarding their symptomatology as at the start of the study . RESULTS : All patients tolerated the products well . The patients receiving Lb . plantarum had these bacteria on rectal biopsies . There were no major changes of Enterobacteriaceae in either group , before or after the study , but the Enterococci increased in the placebo group and remained unchanged in the test group . Flatulence was rapidly and significantly reduced in the test group compared with the placebo group ( number of days with abundant gas production , test group 6.5 before , 3.1 after vs 7.4 before and 5.6 after for the placebo group ) . Abdominal pain was reduced in both groups . At the 12-month follow-up , patients in the test group maintained a better overall GI function than control patients . There was no difference between the groups regarding bloating . Fifty-nine percent of the test group patients had a continuous intake of fermented products , whereas the corresponding figure for the control patients was 73 % . CONCLUSIONS : The results of the study indicate that the administration of Lb . plantarum with known probiotic properties decreased pain and flatulence in patients with IBS . The fiber content of the test solution was minimal and it is unlikely that the fiber content could have had any effect . This type of probiotic therapy warrants further studies in IBS patients OBJECTIVE To observe the clinical efficacy of the combination of traditional Chinese medicine and western medicine in treating irritable bowel syndrome ( IBS ) and the result of intestinal flora regulation . METHODS Sixty IBS patients , 36 males and 24 females , were divided into two groups , with 30 patients in each group . Herbal formula of TongxieYaofang and clostridium butyricum ( Cb ) were used in the first group for four weeks , while only Cb was used for four weeks in the second group . We observed the changes of coliform group , enterococcus , lactobacillus , bifidobacterium after treatment . RESULTS The effective rate of the Tongxie Yaofang and Cb treated group was significantly higher than that of the Cb treated group ( P < 0.05 ) . The numbers of bifidobacterium and lactobacillus increased , while the numbers of coliform group and enterococcus decreased after the treatment , and the changes of intestinal flora in the integrative medicine treated group were significantly greater than those in the Cb treated group . CONCLUSION After treatment with the combination of traditional Chinese medicine and western medicine , the intestinal flora can be regulated to equilibrium state BACKGROUND & AIMS The aim of this study was to compare the response of symptoms and cytokine ratios in irritable bowel syndrome ( IBS ) with ingestion of probiotic preparations containing a lactobacillus or bifidobacterium strain . METHODS Seventy-seven subjects with IBS were r and omized to receive either Lactobacillus salivarius UCC4331 or Bifidobacterium infantis 35624 , each in a dose of 1 x 10 10 live bacterial cells in a malted milk drink , or the malted milk drink alone as placebo for 8 weeks . The cardinal symptoms of IBS were recorded on a daily basis and assessed each week . Quality of life assessment , stool microbiologic studies , and blood sampling for estimation of peripheral blood mononuclear cell release of the cytokines interleukin (IL)-10 and IL-12 were performed at the beginning and at the end of the treatment phase . RESULTS For all symptoms , with the exception of bowel movement frequency and consistency , those r and omized to B infantis 35624 experienced a greater reduction in symptom scores ; composite and individual scores for abdominal pain/discomfort , bloating/distention , and bowel movement difficulty were significantly lower than for placebo for those r and omized to B infantis 35624 for most weeks of the treatment phase . At baseline , patients with IBS demonstrated an abnormal IL-10/IL-12 ratio , indicative of a proinflammatory , Th-1 state . This ratio was normalized by B infantis 35624 feeding alone . CONCLUSIONS B infantis 35624 alleviates symptoms in IBS ; this symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine , suggesting an immune-modulating role for this organism , in this disorder BACKGROUND / AIMS The aim of this pilot study was to investigate the potential value of acupuncture in the treatment of irritable bowel syndrome ( IBS ) . METHODOLOGY The study was an open design study of 7 patients with established irritable bowel syndrome in which assessment was by a diary card . RESULTS The results showed a significant improvement both in general well-being and in symptoms of bloating . CONCLUSIONS Acupuncture seems to be effective in the treatment of irritable bowel syndrome and merits further study A large proportion of the American population avails itself of a variety of complementary and alternative medicine ( CAM ) interventions . Allopathic practitioners often dismiss CAM because of distrust or a belief that there is no sound scientific evidence that has established its utility . However , although not widely appreciated , there are thous and s of r and omized controlled trials ( RCTs ) that have addressed the efficacy of CAM . We review ed the RCTs of herbal and other natural products , acupuncture , and homeopathy as examples of typical CAM modalities , focusing on conditions of interest to gastroenterologists . Peppermint ( alone or in combination ) has supportive evidence for use in patients with dyspepsia , irritable bowel syndrome , and as an intraluminal spasmolytic agent during barium enemas or endoscopy . Ginger appeared to be effective in relieving nausea and vomiting due to motion sickness or pregnancy . Probiotics were useful in childhood diarrhea or in diarrhea due to antibiotics ; one particular formulation ( VSL#3 ) prevented pouchitis . Acupuncture appeared to ameliorate postoperative nausea and vomiting and might be useful elsewhere . There is even a suggestion that homeopathy has efficacy in treatment of gastrointestinal problems or symptoms . The major problem in interpreting these CAM data is the generally low quality of the RCTs , although that quality might not be different compared to RCTs in the general medical literature . Gastroenterologists should become familiar with these techniques ; it is likely that their patients already are In this study , Herbert Benson 's ( 1975 ) Relaxation Response Meditation program was tested as a possible treatment for Irritable Bowel Syndrome ( IBS ) . Participants were 16 adults who were matched into pairs based on presence of Axis I disorder , primary IBS symptoms and demographic features and r and omized to either a six week meditation condition or a six week wait list symptom monitoring condition . Thirteen participants completed treatment and follow-up . All subjects assigned to the Wait List were subsequently treated . Patients in the treatment condition were taught the meditation technique and asked to practice it twice a day for 15 minutes . Composite Primary IBS Symptom Reduction ( CPSR ) scores were calculated for each patient from end of baseline to two weeks post-treatment ( or to post wait list ) . One tailed independent sample t-tests revealed that Meditation was superior to the control ( P=0.04 ) . Significant within-subject improvements were noted for flatulence ( P=0.03 ) and belching ( P=0.02 ) by post-treatment . By three month follow-up , significant improvements in flatulence ( P<0.01 ) , belching ( P=0.02 ) , bloating ( P=0.05 ) , and diarrhea ( P=0.03 ) were shown by symptom diary . Constipation approached significance ( P=0.07 ) . Benson 's Relaxation Response Meditation appears to be a viable treatment for IBS |
1,725 | 25,735,375 | The OS and PFS with high MVD were significant poorer than with low MVD in ovarian cancer patients .
However , high MVD detected by CD34 seems to be more associated with survival for patients without pre-chemotherapy | BACKGROUND The prognostic value of microvessel density ( MVD ) , reflecting angiogenesis , detected in ovarian cancer is currently controversial .
Here we performed a meta- analysis of all relevant eligible studies . | OBJECTIVE Potential predictive/prognostic angiogenic markers were prospect ively examined in a phase II trial of bevacizumab in epithelial ovarian cancer (EOC)/ primary peritoneal cancer ( PPC ) . METHODS Recurrent/persistent EOC/PPC patients were treated with bevacizumab ( 15 mg/kg IV q21days ) until disease progression . Vali date d-immunohistochemistry ( IHC ) assays were performed on pre-cycle 1/4 tumor biopsies for CD31-microvessel density ( MVD ) , VEGF-histoscore ( HS ) , p53-HS , and TSP1 image analysis score ( IA ) . Pre-cycle 1/4 serum and plasma VEGF were quantified using a vali date d-ELISA . RESULTS CD31-MVD and serum VEGF , evaluated pre-cycle 1 in 41/61 and 51/61 eligible patients , respectively , did not appear to be correlated . High CD31-MVD , categorized at the median , appeared to be associated with tumor response , a 13-month shorter median survival , and an increased risk of death ( unadjusted hazard ratio [ HR ] = 2.2 , 95 % confidence interval [ CI ] = 1.067 - 4.467 ) . In addition , each st and ard deviation ( SD ) increase in CD31-MVD appeared to be associated with worse survival in unadjusted and adjusted analyses . IHC and plasma biomarkers did not change with bevacizumab treatment except for serum VEGF , which appeared to decrease during bevacizumab treatment . This decrease was not associated with response . High pre-cycle 1 serum VEGF , categorized at the median , was associated with 22-month shorter median survival and an increased risk of death ( unadjusted HR = 2.7 , 95 % CI = 1.369 - 5.191 ) . Categorized p53 appeared to be associated with unadjusted survival and each SD increase in TSP1-IA appeared to be associated with a decreased risk of progression in unadjusted and adjusted analyses . CONCLUSIONS Despite the limitations in sample size and exploratory nature of the study , angiogenic markers in tumor and serum may provide prognostic value in recurrent/persistent EOC/PPC , and are being prospect ively evaluated in the GOG phase III trial of carboplatin , paclitaxel and bevacizumab/placebo in previously untreated EOC/PPC BACKGROUND Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma , but it does not fully account for the varied disease outcome . More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are c and i date s for systemic adjuvant therapy . Our recent findings indicated that microvessel density ( count or grade ) in invasive breast carcinoma ( a measure of tumor angiogenesis ) is associated with metastasis and thus may be a prognostic indicator . PURPOSE This study was design ed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma . METHODS In a prospect i ve , blinded study of 165 consecutive patients , the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen . Using light microscopy , we counted microvessels per 200x field in the most active areas of neovascularization and grade d microvessel density . These findings were correlated , by univariate and multivariate analyses , with overall and relapse-free survival , axillary node status , and other prognostic indicators ( median follow-up , 51 months ) . RESULTS There was a highly significant ( P < or = .001 ) association of microvessel density with overall survival and relapse-free survival in all patients , including node-negative and node-positive subsets . All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis , compared with less than 5 % of the patients with breast carcinoma having 33 or fewer microvessels per 200x field . Moreover , microvessel density was the only statistically significant predictor of overall survival among node-negative women ( P < .001 ) . Only microvessel density ( P < .001 ) and histologic grade ( P = .04 ) showed statistically significant correlations with relapse-free survival in the node-negative subset . CONCLUSIONS Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma ( I or II by International Union Against Cancer criteria ) . IMPLICATION S Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation . These patients could then be given systemic adjuvant therapy BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias Hazard ratios ( HRs ) are used commonly to report results from r and omized clinical trials in oncology . However , they remain one of the most perplexing concepts for clinicians . A good underst and ing of HRs is needed to effectively interpret the medical literature to make important treatment decisions . This article provides clear guidelines to clinicians about how to appropriately interpret HRs . While this article focuses on the commonly used methods , the authors acknowledge that other statistical methods exist for analyzing survival data OBJECTIVES The aims of this study were to examine prognostic significance of microvessel density ( MVD ) in previously-untreated , advanced epithelial ovarian cancer ( EOC ) and explore associations between MVD and factors that affect angiogenesis . METHODS MVD was determined by immunohistochemical expression of CD31 or CD105 in tumor sections from 106 women treated on GOG r and omized phase III trials . Average MVD hotspots were quantified by light microscopy at high power ( x400 ) and categorized as low ( or = upper quartile ) . Immunoblot expression of MASPIN , THBS-1 , bFGF , VEGF , VEGFR-1 and p53 status ( mutation and overexpression ) was previously determined . RESULTS Of 106 evaluable cases , 25 % exhibited high CD31-MVD ( > 24.25 vessels/high power field [ HPF ] ) or high CD105-MVD ( > 19.25 vessels/HPF ) . After adjusting for age and stratifying by GOG performance status , stage , cell type , grade , debulking status and treatment regimen , high versus low CD105-MVD was associated with increased risk of disease progression ( hazard ratio [HR]=1.873 ; 95 % confidence interval [ CI ] : 1.102 - 3.184 ; p=0.020 ) , but not death ( HR=1.125 ; 95 % CI : 0.654 - 1.935 ; p=0.670 ) whereas CD31-MVD was not associated with risk of disease progression ( HR=1.578 ; 95 % CI=0.918 - 2.711 ; p=0.099 ) or death ( HR=1.678 ; 95 % CI=0.957 - 2.943 ; p=0.071 ) . CD31-MVD was correlated with CD105-MVD ( p=0.001 ) and MASPIN ( p=0.016 ) . Neither CD31-MVD nor CD105-MVD was associated with p53 status , THBS-1 , bFGF , VEGF or VEGFR-1 . CONCLUSIONS High MVD assessed using CD105 , a marker of proliferating endothelial cells and neoangiogenesis , but not CD31 a pan-endothelial marker , appeared to be an independent prognostic factor for worse progression-free survival in women with advanced EOC after adjusting for prognostic clinical covariates |
1,726 | 29,077,028 | The current literature indicates positive effects of dietary NO3− supplementation in older adults on physiological performance , with some evidence indicating benefits on cardiovascular and cerebrovascular health .
Effects on cognitive performance were mixed and studies on metabolic health indicated no benefit . | Supplementation with nitrate (NO3−)-rich beetroot juice has been shown to improve exercise performance and cardiovascular ( CV ) responses , due to an increased nitric oxide ( NO ) availability .
However , it is unclear whether these benefits are greater in older adults who have an age-related decrease in NO and higher risk of disease . | Abstract —Single dose administration of dietary inorganic nitrate acutely reduces blood pressure ( BP ) in normotensive healthy volunteers , via bioconversion to the vasodilator nitric oxide . We assessed whether dietary nitrate might provide sustained BP lowering in patients with hypertension . We r and omly assigned 68 patients with hypertension in a double-blind , placebo-controlled clinical trial to receive daily dietary supplementation for 4 weeks with either dietary nitrate ( 250 mL daily , as beetroot juice ) or a placebo ( 250 mL daily , as nitrate-free beetroot juice ) after a 2-week run-in period and followed by a 2-week washout . We performed stratified r and omization of drug-naive ( n=34 ) and treated ( n=34 ) patients with hypertension aged 18 to 85 years . The primary end point was change in clinic , ambulatory , and home BP compared with placebo . Daily supplementation with dietary nitrate was associated with reduction in BP measured by 3 different methods . Mean ( 95 % confidence interval ) reduction in clinic BP was 7.7/2.4 mm Hg ( 3.6–11.8/0.0–4.9 , P<0.001 and P=0.050 ) . Twenty-four-hour ambulatory BP was reduced by 7.7/5.2 mm Hg ( 4.1–11.2/2.7–7.7 , P<0.001 for both ) . Home BP was reduced by 8.1/3.8 mm Hg ( 3.8–12.4/0.7–6.9 , P<0.001 and P<0.01 ) with no evidence of tachyphylaxis over the 4-week intervention period . Endothelial function improved by ≈20 % ( P<0.001 ) , and arterial stiffness was reduced by 0.59 m/s ( 0.24–0.93 ; P<0.01 ) after dietary nitrate consumption with no change after placebo . The intervention was well tolerated . This is the first evidence of durable BP reduction with dietary nitrate supplementation in a relevant patient group . These findings suggest a role for dietary nitrate as an affordable , readily-available , adjunctive treatment in the management of patients with hypertension ( funded by The British Heart Foundation ) . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01405898 Beetroot has a high concentration of inorganic nitrate , which can serially reduced to form nitrite and nitric oxide ( NO ) after oral ingestion . Increased renal resistive index ( RRI ) measured by Doppler ultrasonography is associated with higher cardiovascular mortality in hypertensive patients with reduced renal function over time defined as chronic kidney disease ( CKD ) . Our aim was to investigate whether the supplementation of dietary nitrate by administration of beetroot juice is able to reduce blood pressure and renal resistive index ( RRI ) as prognostic markers for cardiovascular mortality in CKD patients . In a cross-over study design , 17 CKD patients were r and omized to either a dietary nitrate load ( 300 mg ) by highly concentrated beetroot juice ( BJ ) or placebo ( water ) . Hemodynamic parameters as well as plasma nitrate concentration and RRI were measured before and 4 h after treatment . In this cohort , CKD was mainly caused by hypertensive or diabetic nephropathy . The mean eGFR was 41.6 ± 12.0 ml/min/m2 . Plasma nitrate concentrations were significantly increased after ingestion of BJ compared to control . Peripheral systolic and diastolic blood pressure as well as mean arterial pressure ( MAP ) were significantly reduced secondary to the dietary nitrate load compared to control ( e.g. ΔMAPBJ = -8.2 ± 7.6 mmHg vs. ΔMAPcontrol = -2.2 ± 6.0 mmHg , p = 0.012 ) . BJ also led to significantly reduced RRI values ( ΔRRIBJ = -0.03 ± 0.04 versus ΔRRIcontrol = 0.01 ± 0.04 ; p = 0.017 ) . Serum potassium levels were not altered secondary to the treatment . In this study , administration of the nitrate donor BJ led to significantly reduced RRI values and peripheral blood pressure which might be explained by release of the vasodilatator NO after oral intake . Whether supplementation of dietary nitrate in addition to routine pharmacologic therapy is able to decelerate progression of cardiovascular and renal disease in CKD , remains to be investigated PURPOSE Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance . However , it is presently unknown whether it may enhance performance during simulated competition . The present study investigated the effects of acute dietary nitrate supplementation on power output ( PO ) , VO2 , and performance during 4- and 16.1-km cycling time trials ( TT ) . METHODS After familiarization , nine club-level competitive male cyclists were assigned in a r and omized , crossover design to consume 0.5 L of beetroot juice ( BR ; containing ∼ 6.2 mmol of nitrate ) or 0.5 L of nitrate-depleted BR ( placebo , PL ; containing ∼ 0.0047 mmol of nitrate ) , ∼ 2.5 h before the completion of a 4- and a 16.1-km TT . RESULTS BR supplementation elevated plasma [ nitrite ] ( PL = 241 ± 125 vs BR = 575 ± 199 nM , P < 0.05 ) . The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance ( P > 0.05 ) , but BR significantly increased mean PO during the 4-km ( PL = 279 ± 51 vs BR = 292 ± 44 W , P < 0.05 ) and 16.1-km TT ( PL = 233 ± 43 vs BR = 247 ± 44 W , P < 0.01 ) . Consequently , BR improved 4-km performance by 2.8 % ( PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min , P < 0.05 ) and 16.1-km performance by 2.7 % ( PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min , P < 0.01 ) . CONCLUSIONS These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy , as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance Circulating nitrate ( NO3− ) , derived from dietary sources or endogenous nitric oxide production , is extracted from blood by the salivary gl and s , accumulates in saliva , and is then reduced to nitrite ( NO2− ) by the oral microflora . This process has historically been viewed as harmful , because nitrite can promote formation of potentially carcinogenic N-nitrosamines . More recent research , however , suggests that nitrite can also serve as a precursor for systemic generation of vasodilatory nitric oxide , and exogenous administration of nitrate reduces blood pressure in humans . However , whether oral nitrate-reducing bacteria participate in “ setting ” blood pressure is unknown . We investigated whether suppression of the oral microflora affects systemic nitrite levels and hence blood pressure in healthy individuals . We measured blood pressure ( clinic , home , and 24-h ambulatory ) in 19 healthy volunteers during an initial 7-day control period followed by a 7-day treatment period with a chlorhexidine-based antiseptic mouthwash . Oral nitrate-reducing capacity and nitrite levels were measured after each study period . Antiseptic mouthwash treatment reduced oral nitrite production by 90 % ( p < 0.001 ) and plasma nitrite levels by 25 % ( p = 0.001 ) compared to the control period . Systolic and diastolic blood pressure increased by 2–3 .5 mm Hg , increases correlated to a decrease in circulating nitrite concentrations ( r2 = 0.56 , p = 0.002 ) . The blood pressure effect appeared within 1 day of disruption of the oral microflora and was sustained during the 7-day mouthwash intervention . These results suggest that the recycling of endogenous nitrate by oral bacteria plays an important role in determination of plasma nitrite levels and thereby in the physiological control of blood pressure Nitric oxide ( NO ) synthase inhibition reduces leg glucose uptake during cycling without reducing leg blood flow ( LBF ) in young , healthy individuals . This study sought to determine the role of NO in glucose uptake during exercise in individuals with type 2 diabetes . Nine men with type 2 diabetes and nine control subjects matched for age , sex , peak pulmonary oxygen uptake ( VO(2 ) peak ) , and weight completed two 25-min bouts of cycling exercise at 60 + /- 2 % VO(2 ) peak , separated by 90 min . N(G)-monomethyl-L-arginine ( L-NMMA ) ( total dose 6 mg/kg ) or placebo was administered into the femoral artery for the final 15 min of exercise in a counterbalanced , blinded , crossover design . LBF was measured by thermodilution in the femoral vein , and leg glucose uptake was calculated as the product of LBF and femoral arteriovenous glucose difference . During exercise with placebo , glucose uptake was not different between control subjects and individuals with diabetes ; however , LBF was lower and arterial plasma glucose and insulin levels were higher in individuals with diabetes . L-NMMA had no effect on LBF or arterial plasma glucose and insulin concentrations during exercise in both groups . L-NMMA significantly reduced leg glucose uptake in both groups , with a significantly greater reduction ( P = 0.04 ) in the diabetic group ( 75 + /- 13 % , 5 min after L-NMMA ) compared with the control group ( 34 + /- 14 % , 5 min after L-NMMA ) . These data suggest a greater reliance on NO for glucose uptake during exercise in individuals with type 2 diabetes compared with control subjects Diets rich in green , leafy vegetables have been shown to lower blood pressure ( BP ) and reduce the risk of cardiovascular disease . Green , leafy vegetables and beetroot are particularly rich in inorganic nitrate . Dietary nitrate supplementation , via sequential reduction to nitrite and NO , has previously been shown to lower BP and improve endothelial function in healthy humans . We sought to determine if supplementing dietary nitrate with beetroot juice , a rich source of nitrate , will lower BP and improve endothelial function and insulin sensitivity in individuals with type 2 diabetes ( T2DM ) . Twenty-seven patients , age 67.2±4.9 years ( 18 male ) , were recruited for a double-blind , r and omized , placebo-controlled crossover trial . Participants were r and omized to begin , in either order , a 2-week period of supplementation with 250ml beetroot juice daily ( active ) or 250ml nitrate-depleted beetroot juice ( placebo ) . At the conclusion of each intervention period 24-h ambulatory blood pressure monitoring , tests of macro- and microvascular endothelial function , and a hyperinsulinemic isoglycemic clamp were performed . After 2 weeks administration of beetroot juice mean ambulatory systolic BP was unchanged : 134.6±8.4mmHg versus 135.1±7.8mmHg ( mean±SD ) , placebo vs active-mean difference of -0.5mmHg ( placebo-active ) , p=0.737 ( 95 % CI -3.9 to 2.8 ) . There were no changes in macrovascular or microvascular endothelial function or insulin sensitivity . Supplementation of the diet with 7.5mmol of nitrate per day for 2 weeks caused an increase in plasma nitrite and nitrate concentration , but did not lower BP , improve endothelial function , or improve insulin sensitivity in individuals with T2DM Although dietary nitrate ( NO3- ) ingestion appears to enhance exercise capacity and performance in young individuals , inconclusive findings have been reported in older people . Therefore , we conducted a double-blind , crossover r and omized clinical trial using beetroot juice in older healthy participants , who were classified as normal weight and overweight . We tested whether consumption of beetroot juice ( a rich source of NO3- ) for 1 week would increase nitric oxide bioavailability via the nonenzymatic pathway and enhance ( 1 ) exercise capacity during an incremental exercise test , ( 2 ) physical capability , and ( 3 ) free-living physical activity . Twenty nonsmoking , healthy participants between 60 and 75 years of age and with a body mass index of 20.0 to 29.9 kg/m2 were included . Presupplementation and postsupplementation resting , submaximal , maximal , and recovery gas exchanges were measured . Physical capability was measured by h and -grip strength , time-up- and -go , repeated chair rising test , and 10-m walking speed . Free-living physical activity was assessed by triaxal accelerometry . Changes in urinary and plasmaNO3-concentrations were measured by gas chromatography-mass spectrometry . Nineteen participants ( male-to-female ratio , 9:10 ) completed the study .Beetroot juice increased significantly both plasma and urinary NO3-concentrations ( P<.001 ) when compared with placebo . Beetroot juice did not influence resting or submaximal and maximal oxygen consumption during the incremental exercise test . In addition , measures of physical capability and physical activity levels measured in free-living conditions were not modified by beetroot juice ingestion . The positive effects of beetroot juice ingestion on exercise performance seen in young individuals were not replicated in healthy , older adults . Whether aging represents a modifier of the effects of dietary NO3-on muscular performance is not known , and mechanistic studies and larger trials are needed to test this hypothesis Nitric oxide alters gastric blood flow , improves vascular function , and mediates glucose uptake within the intestines and skeletal muscle . Dietary nitrate , acting as a source of nitric oxide , appears to be a potential low-cost therapy that may help maintain glucose homeostasis . In a r and omized , double-blind , placebo-controlled crossover study , 31 young and older adult participants had a st and ardized breakfast , supplemented with either nitrate-rich beetroot juice ( 11.91 mmol nitrate ) or nitrate-depleted beetroot juice as placebo ( 0.01 mmol nitrate ) . MRI was used to assess apparent diffusion coefficient ( ADC ) , portal vein flux , and velocity . Plasma glucose , incretin , and C-peptide concentrations and blood pressure were assessed . Outcome variables were measured at baseline and hourly for 3 h. Compared with a placebo , beetroot juice result ed in a significant elevation in plasma nitrate and plasma nitrite concentration . No differences were seen for the young or older adult cohorts between placebo and beetroot juice for ADC , or portal vein flux . There was an interaction effect in the young adults between visits for portal vein velocity . Nitrate supplementation did not reduce plasma glucose , active GLP-1 , total GLP-1 , or plasma C-peptide concentrations for the young or older adult cohorts . Despite a significant elevation in plasma nitrite concentration following an acute dose of ( 11.91 mmol ) nitrate , there was no effect on hepatic blood flow , plasma glucose , C-peptide , or incretin concentration in healthy adults Little is known about the effect of dietary nitrate on the nitrate/nitrite/nitric oxide cycle in older adults . We examined the effect of a 3-day control diet vs high-nitrate diet , with and without a high-nitrate supplement ( beetroot juice ) , on plasma nitrate and nitrite kinetics and blood pressure using a r and omized 4-period crossover controlled design . We hypothesized that the high-nitrate diet would show higher levels of plasma nitrate/nitrite and lower blood pressure compared with the control diet , which would be potentiated by the supplement . Participants were 8 normotensive older men and women ( 5 female , 3 male , 72.5 ± 4.7 years old ) with no overt disease or medications that affect nitric oxide metabolism . Plasma nitrate and nitrite levels and blood pressure were measured before and hourly for 3 hours after each meal . The mean daily changes in plasma nitrate and nitrite were significantly different from baseline for both control diet + supplement ( P < .001 and P = .017 for nitrate and nitrite , respectively ) and high-nitrate diet + supplement ( P = .001 and P = .002 ) , but not for control diet ( P = .713 and P = .741 ) or high-nitrate diet ( P = .852 and P = .500 ) . Blood pressure decreased from the morning baseline measure to the three 2-hour postmeal follow-up time points for all treatments , but there was no main effect for treatment . In healthy older adults , a high-nitrate supplement consumed at breakfast elevated plasma nitrate and nitrite levels throughout the day . This observation may have practical utility for the timing of intake of a nitrate supplement with physical activity for older adults with vascular dysfunction Peripheral arterial disease ( PAD ) results in a failure to adequately supply blood and oxygen ( O(2 ) ) to working tissues and presents as claudication pain during walking . Nitric oxide ( NO ) bioavailability is essential for vascular health and function . Plasma nitrite ( NO(2)(- ) ) is a marker of vascular NO production but may also be a protected circulating " source " that can be converted to NO during hypoxic conditions , possibly aiding perfusion . We hypothesized that dietary supplementation of inorganic nitrate in the form of beetroot ( BR ) juice would increase plasma NO(2)(- ) concentration , increase exercise tolerance , and decrease gastrocnemius fractional O(2 ) extraction , compared with placebo ( PL ) . This was a r and omized , open-label , crossover study . At each visit , subjects ( n = 8) underwent resting blood draws , followed by consumption of 500 ml BR or PL and subsequent blood draws prior to , during , and following a maximal cardiopulmonary exercise ( CPX ) test . Gastrocnemius oxygenation during the CPX was measured by near-infrared spectroscopy . There were no changes from rest for [ NO(2)(- ) ] ( 152 ± 72 nM ) following PL . BR increased plasma [ NO(2)(- ) ] after 3 h ( 943 ± 826 nM ; P ≤ 0.01 ) . Subjects walked 18 % longer before the onset of claudication pain ( 183 ± 84 s vs. 215 ± 99 s ; P ≤ 0.01 ) and had a 17 % longer peak walking time ( 467 ± 223 s vs. 533 ± 233 s ; P ≤ 0.05 ) following BR vs. PL . Gastrocnemius tissue fractional O(2 ) extraction was lower during exercise following BR ( 7.3 ± 6.2 vs. 10.4 ± 6.1 arbitrary units ; P ≤ 0.01 ) . Diastolic blood pressure was lower in the BR group at rest and during CPX testing ( P ≤ 0.05 ) . These findings support the hypothesis that NO(2)(-)-related NO signaling increases peripheral tissue oxygenation in areas of hypoxia and increases exercise tolerance in PAD The purpose of this study was to eluci date the mechanistic bases for the reported reduction in the O(2 ) cost of exercise following short-term dietary nitrate ( NO(3)(- ) ) supplementation . In a r and omized , double-blind , crossover study , seven men ( aged 19 - 38 yr ) consumed 500 ml/day of either nitrate-rich beet root juice ( BR , 5.1 mmol of NO(3)(-)/day ) or placebo ( PL , with negligible nitrate content ) for 6 consecutive days , and completed a series of low-intensity and high-intensity " step " exercise tests on the last 3 days for the determination of the muscle metabolic ( using (31)P-MRS ) and pulmonary oxygen uptake ( Vo(2 ) ) responses to exercise . On days 4 - 6 , BR result ed in a significant increase in plasma [ nitrite ] ( mean + /- SE , PL 231 + /- 76 vs. BR 547 + /- 55 nM ; P < 0.05 ) . During low-intensity exercise , BR attenuated the reduction in muscle phosphocreatine concentration ( [ PCr ] ; PL 8.1 + /- 1.2 vs. BR 5.2 + /- 0.8 mM ; P < 0.05 ) and the increase in Vo(2 ) ( PL 484 + /- 41 vs. BR 362 + /- 30 ml/min ; P < 0.05 ) . During high-intensity exercise , BR reduced the amplitudes of the [ PCr ] ( PL 3.9 + /- 1.1 vs. BR 1.6 + /- 0.7 mM ; P < 0.05 ) and Vo(2 ) ( PL 209 + /- 30 vs. BR 100 + /- 26 ml/min ; P < 0.05 ) slow components and improved time to exhaustion ( PL 586 + /- 80 vs. BR 734 + /- 109 s ; P < 0.01 ) . The total ATP turnover rate was estimated to be less for both low-intensity ( PL 296 + /- 58 vs. BR 192 + /- 38 microM/s ; P < 0.05 ) and high-intensity ( PL 607 + /- 65 vs. BR 436 + /- 43 microM/s ; P < 0.05 ) exercise . Thus the reduced O(2 ) cost of exercise following dietary NO(3)(- ) supplementation appears to be due to a reduced ATP cost of muscle force production . The reduced muscle metabolic perturbation with NO(3)(- ) supplementation allowed high-intensity exercise to be tolerated for a greater period of time BACKGROUND In this sub study of the effect of dietary nitrate on blood pressure , endothelial function , and insulin sensitivity in type 2 diabetes , we report the development of a novel nitrate depleted beetroot juice for use clinical trials and determine if dietary nitrate supplementation improved cognitive function in patients with type 2 diabetes mellitus . METHODS Beetroot juice was treated with the anion exchange resin Purolite A520e . UV-vis-spectrophotometry , and a blind taste test were performed along with determination of sugar content , measurement of ascorbate and dehydroascorbate , the ionic composition of juice and Proton NMR . Subsequently , 27 patients , age 67.2±4.9 years , ( 18 male ) were recruited for a double blind , r and omised , placebo-controlled crossover trial . Participants were r and omised to begin in either order beetroot juice ( nitrate content 7.5 mmol per 250 ml ) or placebo ( nitrate depleted beetroot juice nitrate content 0.002 mmol per 250 ml ) . At the end of each 2 week supplementation period cognitive function was assessed using E-prime , E-Studio software with 5 separate tests being performed . The tests utilised in the present study have been adapted from the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) . RESULTS The differences in the UV-vis spectra were comparable to the natural variation found in differing cultivars . There were no discernable differences in taste , sugar content , or Proton NMR . Ascorbate and dehydroascorbate were undetectable in either juice . After 2 weeks of beetroot juice simple reaction time was significantly quicker in the active arm at 327±40 ms versus 341.8±52.7 ms in the placebo arm , mean difference 13.9±25.6 ms ( 95 % CI 3.8 - 24.0 ms ) , p=0.009 . No other measures of cognitive function differed between treatment arms . CONCLUSION We have developed an effective placebo beetroot juice for use in trials of supplementation of dietary nitrate . Two weeks supplementation of the diet with 7.5 mmol of nitrate per day caused a significant improvement in simple reaction time in individuals with T2DM Dietary nitrate ( NO3(- ) ) supplementation via beetroot juice has been shown to increase the exercise capacity of younger and older adults . The purpose of this study was to investigate the effects of acute NO3(- ) ingestion on the submaximal constant work rate exercise capacity of COPD patients . Fifteen patients were assigned in a r and omized , single-blind , crossover design to receive one of two treatments ( beetroot juice then placebo or placebo then beetroot juice ) . Submaximal constant work rate exercise time at 75 % of the patient 's maximal work capacity was the primary outcome . Secondary outcomes included plasma NO3(- ) and nitrite ( NO2(- ) ) levels , blood pressure , heart rate , oxygen consumption ( VO2 ) , dynamic hyperinflation , dyspnea and leg discomfort . Relative to placebo , beetroot ingestion increased plasma NO3(- ) by 938 % and NO2(- ) by 379 % . Median ( + interquartile range ) exercise time was significantly longer ( p = 0.031 ) following the ingestion of beetroot versus placebo ( 375.0 + 257.0 vs. 346.2 + 148.0 s , respectively ) . Compared with placebo , beetroot ingestion significantly reduced iso-time ( p = 0.001 ) and end exercise ( p = 0.008 ) diastolic blood pressures by 6.4 and 5.6 mmHg , respectively . Resting systolic blood pressure was significantly reduced ( p = 0.019 ) by 8.2 mmHg for the beetroot versus the placebo trial . No other variables were significantly different between the beetroot and placebo trials . These results indicate that acute dietary NO3(- ) supplementation can elevate plasma NO3(- ) and NO2(- ) concentrations , improve exercise performance , and reduce blood pressure in COPD patients Dietary nitrate ( NO(3)(- ) ) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults . We investigated whether these effects might also be evident in older adults . In a double-blind , r and omized , crossover study , 12 healthy , older ( 60 - 70 yr ) adults supplemented their diet for 3 days with either nitrate-rich concentrated beetroot juice ( BR ; 2 × 70 ml/day , ∼9.6 mmol/day NO(3)(- ) ) or a nitrate-depleted beetroot juice placebo ( PL ; 2 × 70 ml/day , ∼0.01 mmol/day NO(3)(- ) ) . Before and after the intervention periods , resting blood pressure and plasma [ nitrite ] were measured , and subjects completed a battery of physiological and cognitive tests . Nitrate supplementation significantly increased plasma [ nitrite ] and reduced resting systolic ( BR : 115 ± 9 vs. PL : 120 ± 6 mmHg ; P < 0.05 ) and diastolic ( BR : 70 ± 5 vs. PL : 73 ± 5 mmHg ; P < 0.05 ) blood pressure . Nitrate supplementation result ed in a speeding of the Vo(2 ) mean response time ( BR : 25 ± 7 vs. PL : 28 ± 7 s ; P < 0.05 ) in the transition from st and ing rest to treadmill walking , although in contrast to our hypothesis , the O(2 ) cost of exercise remained unchanged . Functional capacity ( 6-min walk test ) , the muscle metabolic response to low-intensity exercise , brain metabolite concentrations , and cognitive function were also not altered . Dietary nitrate supplementation reduced resting blood pressure and improved Vo(2 ) kinetics during treadmill walking in healthy older adults but did not improve walking or cognitive performance . These results may have implication s for the enhancement of cardiovascular health in older age |
1,727 | 27,820,035 | Types of outcome measures : Studies will be included if they have assessed the effects of a strategy on the following outcomes : 1 .
severity of agitated behaviours 2 .
frequency of agitated behaviours 3 .
use of pharmacotherapy in relation to agitated | Review Objectives : The purpose of this systematic review is to critically analyse the literature to determine which non-pharmacological strategies can be effectively implemented by nurses within a residential aged care facility to manage the symptom of agitation in person with advanced dementia .
Review Questions : 1 .
What non-pharmacological strategies have been implemented , by nurses , for the symptom management of agitation in persons with advanced dementia living in a residential aged care facility ?
2 .
Which of the identified strategies were most effective in : -Reducing the severity of agitated behaviours ?
-Reducing the frequency of agitated behaviours ?
-Reducing the frequency and dosage of pharmacotherapy for the symptom of agitation ? | AIMS AND OBJECTIVES To investigate the efficacy of acupressure in decreasing agitated behaviours associated with dementia . BACKGROUND Agitated behaviour is found in nearly half of all patients who have dementia . The presence of these behaviours increases the likelihood of injury , weakness , dehydration and lack of sleep and contributes to caregiver frustration and fatigue . DESIGN This pilot study was design ed with subjects receiving both acupressure and the control treatment . Each subject served as his or her own control . Subjects received four weeks of acupressure protocol s ; to avoid a carry-over effect there was a treatment-free period of one week . Subjects then were visited by one of the investigators for a six-week period . METHODS Participants were recruited from a nursing home caring specifically for patients with dementia . Twenty of the 31 subjects ( 64.5 % ) completed the study , while 11 were discharged or hospitalized . All the subjects were assigned to an experimental protocol and had a six-week acupressure treatment program . Baseline data were collected in the first week . Individual treatment sessions began at the second week of the study and lasted 15 minutes , twice a day , five days a week for four weeks . After a treatment-free period of one week , all the subjects served as controls undergoing a four-week control protocol consisting of companionship and conversation . RESULTS Comparison between the control and experimental phases indicated significant differences between the two groups on all outcome measures ( Cohen-Mansfield Agitation Inventory , daily agitation records about physical attack , verbal and non-verbal attack and non-physical attack ) with better results found during the acupressure phase . CONCLUSIONS Acupressure is recommended as an efficacious and non-intrusive method for decreasing the agitation behaviours in patients with dementia . RELEVANCE TO CLINICAL PRACTICE Conducting the acupressure treatment takes 15 minutes . It could provide caregivers with a viable alternative to deal with patients with dementia Alzheimer 's disease is characterized by progressive cognitive decline . However , little is known about the " typical " rate of decline , the degree of individual heterogeneity evident in decline , or the types of factors that influence such decline . This study investigated these questions in a sample of 106 patients with Alzheimer 's disease , assessed at 1 - 5 points in time , spanning up to three years . At each time point , the Mini-Mental State Exam , a measure of global cognitive function , was administered to all patients . Measures of behavioral disturbance ( including the presence/absence of hallucinations , depression , incontinence , w and ering , and agitation ) , health status ( including presence/absence of neurological , cardiovascular , and other diseases ) , and descriptive information ( such as gender , age at time of onset , and duration of deficits ) were obtained at entry into the study . A two-stage r and om effects regression model was fit to the data and then used to assess the effect of these behavioral , health , and descriptive measures on the rate of decline . Results indicate that the rate of cognitive decline in Alzheimer 's disease is quite variable . Patients with various health and behavioral problems declined at a rate between 1.4 and 5 times faster than patients without such problems . Alcohol abuse , additional neurological disease , and agitation were significantly related to rate of decline . Overall number of problems was not . The association of these problems with accelerated decline may have prognostic and treatment implication Background Disruptive behaviors are prevalent in nursing home residents with dementia and often have negative consequences for the resident , caregiver , and others in the environment . Behavioral interventions might ameliorate them and have a positive effect on residents ’ mood ( affect ) . Objectives This study tested two interventions —an activities of daily living and a psychosocial activity intervention— and a combination of the two to determine their efficacy in reducing disruptive behaviors and improving affect in nursing home residents with dementia . Methods The study had three treatment groups ( activities of daily living , psychosocial activity , and a combination ) and two control groups ( placebo and no intervention ) . Nursing assistants hired specifically for this study enacted the interventions under the direction of a master ’s prepared gerontological clinical nurse specialist . Nursing assistants employed at the nursing homes recorded the occurrence of disruptive behaviors . Raters analyzed videotapes filmed during the study to determine the interventions ’ influence on affect . Results Findings indicated significantly more positive affect but not reduced disruptive behaviors in treatment groups compared to control groups . Conclusions The treatments did not specifically address the factors that may have been triggering disruptive behaviors . Interventions much more precisely design ed than those employed in this study require development to quell disruptive behaviors . Nontargeted interventions might increase positive affect . Treatments that produce even a brief improvement in affect indicate improved quality of mental health as m and ated by federal law Background : Treatment of agitation is a crucial problem in the care of patients with AD . Although antipsychotic and antidepressant medications and behavior management techniques ( BMT ) have each been used to treat agitation , clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment design s. Objective : To compare haloperidol , trazodone , and BMT with placebo in the treatment of agitation in AD out patients . Methods : A total of 149 patients with AD and their caregivers participated in a r and omized , placebo-controlled , multicenter trial . Blind assessment was conducted at baseline and after 16 weeks of treatment . The three active treatments were haloperidol , trazodone , and BMT . The Alzheimer ’s Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure . Secondary outcomes included patient agitation , cognition , and function , and caregiver burden . Results : Thirty-four percent of subjects improved relative to baseline . No significant differences on outcome were obtained between haloperidol ( mean dose , 1.8 mg/d ) , trazodone ( mean dose , 200 mg/d ) , BMT , or placebo . Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm . No other significant difference in adverse events was seen . Symptoms did not respond differentially to the different treatments . Conclusions : Comparable modest reductions in agitation occurred in patients receiving haloperidol , trazodone , BMT , and placebo . More effective pharmacologic , nonpharmacologic , and combination treatments are needed |
1,728 | 24,130,513 | Results Based on 7,282 abstract s , 57 studies met the quality criteria and were evidence grade d. The data were too limited to draw any conclusions regarding : red and processed meat intake in relation to cardiovascular disease ( CVD ) and iron status ; potatoes and berries regarding any study outcomes ; and dairy consumption in relation to risk of breast cancer and CVD .
However , dairy consumption seemed unlikely to increase CVD risk ( moderate- grade evidence ) .
There was probable evidence ( moderate- grade ) for whole grains protecting against type 2 diabetes and CVD , and suggestive evidence ( low- grade ) for colorectal cancer and for dairy consumption being associated with decreased risk of type 2 diabetes and increased risk of prostate cancer .
The WCRF/AICR concludes that red and processed meat is a convincing cause of colorectal cancer .
Conclusions Probable ( moderate ) evidence was only observed for whole grains protecting against type 2 diabetes and CVD . | Background In preparing the fifth edition of the Nordic Nutrition Recommendations ( NNR ) , the scientific basis of specific food-based dietary guidelines ( FBDG ) was evaluated .
Objective A systematic review ( SR ) was conducted to up date the NNR evidence based on the association between the consumption of potatoes , berries , whole grains , milk and milk products , and red and processed meat , and the risk of major diet-related chronic diseases . | Many epidemiologic studies have reported a positive association between dairy products and prostate cancer . Calcium or saturated fatty acid in dairy products has been suspected as the causative agent . To investigate the association between dairy products , calcium , and saturated fatty acid and prostate cancer in Japan , where both the intake of these items and the incidence of prostate cancer are low , we conducted a population -based prospect i ve study in 43,435 Japanese men ages 45 to 74 years . Participants responded to a vali date d question naire that included 138 food items . During 7.5 years of follow-up , 329 men were newly diagnosed with prostate cancer . Dairy products were associated with a dose-dependent increase in the risk of prostate cancer . The relative risks ( 95 % confidence intervals ) comparing the highest with the lowest quartiles of total dairy products , milk , and yogurt were 1.63 ( 1.14 - 2.32 ) , 1.53 ( 1.07 - 2.19 ) , and 1.52 ( 1.10 - 2.12 ) , respectively . A statistically significant increase in risk was observed for both calcium and saturated fatty acid , but the associations for these were attenuated after controlling for potential confounding factors . Some specific saturated fatty acids increased the risk of prostate cancer in a dose-dependent manner . Relative risks ( 95 % confidence intervals ) on comparison of the highest with the lowest quartiles of myristic acid and palmitic acid were 1.62 ( 1.15 - 2.29 ) and 1.53 ( 1.07 - 2.20 ) , respectively . In conclusion , our results suggest that the intake of dairy products may be associated with an increased risk of prostate cancer . ( Cancer Epidemiol Biomarkers Prev 2008;17(4):930–7 CONTEXT Although increased intake of grain products has been recommended to prevent cardiovascular disease ( CVD ) , prospect i ve data examining the relation of whole grain intake to risk of ischemic stroke are sparse , especially among women . OBJECTIVE To examine the hypothesis that higher whole grain intake reduces the risk of ischemic stroke in women . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort of 75,521 US women aged 38 to 63 years without previous diagnosis of diabetes mellitus , coronary heart disease , stroke , or other CVDs in 1984 , who completed detailed food frequency question naires ( FFQs ) in 1984 , 1986 , 1990 , and 1994 , and were followed up for 12 years as part of the Nurses ' Health Study . MAIN OUTCOME MEASURE Incidence of ischemic stroke , confirmed by medical records , by quintile of whole grain intake according to FFQ responses . RESULTS During 861,900 person-years of follow-up , 352 confirmed incident cases of ischemic stroke occurred . We observed an inverse association between whole grain intake and ischemic stroke risk . The age-adjusted relative risks ( RRs ) from the lowest to highest quintiles of whole grain intake were 1.00 ( referent ) , 0.68 ( 95 % confidence interval [ CI ] , 0.49 - 0.94 ) , 0.69 ( 95 % CI , 0.51 - 0.95 ) , 0.49 ( 95 % CI , 0.35 - 0.69 ) , and 0.57 ( 95 % CI , 0.42 - 0.78 ; P = .003 for trend ) . Adjustment for smoking modestly attenuated this association ( RR comparing extreme quintiles , 0.64 ; 95 % CI , 0.47 - 0.89 ) . This inverse association remained essentially unchanged with further adjustment for known CVD risk factors , including saturated fat and transfatty acid intake ( multivariate-adjusted RR comparing extreme quintiles , 0.69 ; 95 % CI , 0.50 - 0.98 ) . The inverse relation between whole grain intake and risk of ischemic stroke was also consistently observed among subgroups of women who never smoked , did not drink alcohol , did not exercise regularly , or who did not use postmenopausal hormones . No significant association was observed between total grain intake and risk of ischemic stroke . CONCLUSIONS In this cohort , higher intake of whole grain foods was associated with a lower risk of ischemic stroke among women , independent of known CVD risk factors . These prospect i ve data support the notion that higher intake of whole grains may reduce the risk of ischemic stroke Background — Little is known about the role of dietary intake in the development of deep vein thrombosis or pulmonary embolus ( venous thromboembolism [ VTE ] ) . Homocysteine , factor VIII , and von Willebr and factor levels , risk factors for VTE , are influenced by dietary intake . We tested the hypothesis that foods rich in B vitamins and & ohgr;-3 fatty acids are negatively associated and meat intake is positively associated with incidence of VTE . Methods and Results — In a prospect i ve study over 12 years , 14 962 middle-aged adults participating in the Atherosclerosis Risk in Communities study were followed up for incident VTE . All hospitalizations were identified , and 196 VTEs were vali date d by chart review . A food frequency question naire assessed dietary intake at baseline and year 6 . In separate proportional hazards regression analyses , risk of developing VTE was computed across quintiles of selected nutrients , major food groups , and the Western diet pattern , with adjustment for demographic and lifestyle factors , body mass index , and diabetes . Hazard ratios and 95 % confidence intervals of VTE incidence across quintiles of fruit and vegetable intake were 1.0 ( reference ) , 0.73 ( 0.48 to 1.11 ) , 0.57 ( 0.37 to 0.90 ) , 0.47 ( 0.29 to 0.77 ) , and 0.59 ( 0.36 to 0.99 ) ( Ptrend=0.03 ) . Eating fish 1 or more times per week was associated with 30 % to 45 % lower incidence of VTE for quintiles 2 to 5 compared with quintile 1 , suggestive of a threshold effect . Hazard ratios of VTE across quintiles of red and processed meat intake were 1.0 , 1.24 ( 0.78 to 1.98 ) , 1.21 ( 0.74 to 1.98 ) , 1.09 ( 0.64 to 1.87 ) , and 2.01 ( 1.15 to 3.53 ) ( Ptrend=0.02 ) . Hazard ratios were attenuated only slightly after adjustment for factors VIIc and VIIIc and von Willebr and factor . Conclusions — A diet including more plant food and fish and less red and processed meat is associated with a lower incidence of VTE Background : Calcium , vitamin D , and dairy products are highly correlated factors , each with potential roles in breast carcinogenesis . Few prospect i ve studies have examined these relationships in postmenopausal women . Methods : Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed question naire on diet , vitamin and mineral supplement use , medical history , and lifestyle in 1992 to 1993 . After exclusion of women with a history of cancer and incomplete dietary data , 68,567 postmenopausal women remained for analysis . During follow-up through August 31 , 2001 , we identified 2,855 incident cases of breast cancer . Multivariate-adjusted rate ratios ( RR ) were calculated using Cox proportional hazards models . Results : Women with the highest intake of dietary calcium ( > 1,250 mg/d ) were at a lower risk of breast cancer than those reporting ≤500 mg/d [ RR , 0.80 ; 95 % confidence interval ( 95 % CI ) , 0.67 - 0.95 ; Ptrend = 0.02 ] ; however , neither use of supplemental calcium nor vitamin D intake was associated with risk . Consumption starting at two or more servings of dairy products per day was likewise inversely associated with risk ( RR , 0.81 ; 95 % CI , 0.69 - 0.95 ; Ptrend = 0.002 , compared with < 0.5 servings/d ) . The associations were slightly stronger in women with estrogen receptor – positive tumors comparing highest to lowest intake : dietary calcium ( RR , 0.67 ; 95 % CI , 0.51 - 0.88 ; Ptrend = 0.004 ) ; dairy products ( RR , 0.73 ; 95 % CI , 0.57 - 0.93 ; Ptrend = 0.0003 ) , and dietary vitamin D ( RR , 0.74 ; 95 % CI , 0.59 - 0.93 ; Ptrend = 0.006 ) . Conclusions : Our results support the hypothesis that dietary calcium and /or some other components in dairy products may modestly reduce risk of postmenopausal breast cancer . The stronger inverse associations among estrogen receptor – positive tumors deserve further study . ( Cancer Epidemiol Biomarkers Prev 2005;14(12):2898–904 We examined prospect ively the association between whole grain consumption and colorectal cancer risk in the population -based Swedish Mammography Cohort . A total of 61 433 women completed a food-frequency question naire at baseline ( 1987–1990 ) and , through linkage with the Swedish Cancer Registry , 805 incident cases of colorectal cancer were identified during a mean follow-up of 14.8 years . High consumption of whole grains was associated with a lower risk of colon cancer , but not of rectal cancer . The multivariate rate ratio ( RR ) of colon cancer for the top category of whole grain consumption ( ⩾4.5 servings day−1 ) compared with the bottom category ( < 1.5 servings day−1 ) was 0.67 ( 95 % confidence interval ( CI ) , 0.47–0.96 ; P-value for trend=0.06 ) . The corresponding RR after excluding cases occurring within the first 2 years of follow-up was 0.65 ( 95 % CI , 0.45–0.94 ; P-value for trend=0.04 ) . Our findings suggest that high consumption of whole grains may decrease the risk of colon cancer in women Background Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes , but the role of specific dietary factors in the etiology of type 2 diabetes is less well established . We evaluated intakes of whole grain , bran , and germ in relation to risk of type 2 diabetes in prospect i ve cohort studies . Methods and Findings We followed 161,737 US women of the Nurses ' Health Studies ( NHSs ) I and II , without history of diabetes , cardiovascular disease , or cancer at baseline . The age at baseline was 37–65 y for NHSI and 26–46 y for NHSII . Dietary intakes and potential confounders were assessed with regularly administered question naires . We documented 6,486 cases of type 2 diabetes during 12–18 y of follow-up . Other prospect i ve cohort studies on whole grain intake and risk of type 2 diabetes were identified in search es of MEDLINE and EMBASE up to January 2007 , and data were independently extracted by two review ers . The median whole grain intake in the lowest and highest quintile of intake was , respectively , 3.7 and 31.2 g/d for NHSI and 6.2 and 39.9 g/d for NHSII . After adjustment for potential confounders , the relative risks ( RRs ) for the highest as compared with the lowest quintile of whole grain intake was 0.63 ( 95 % confidence interval [ CI ] 0.57–0.69 ) for NHSI and 0.68 ( 95 % CI 0.57–0.81 ) for NHSII ( both : p-value , test for trend < 0.001 ) . After further adjustment for body mass index ( BMI ) , these RRs were 0.75 ( 95 % CI 0.68–0.83 ; p-value , test for trend < 0.001 ) and 0.86 ( 95 % CI 0.72–1.02 ; p-value , test for trend 0.03 ) respectively . Associations for bran intake were similar to those for total whole grain intake , whereas no significant association was observed for germ intake after adjustment for bran . Based on pooled data for six cohort studies including 286,125 participants and 10,944 cases of type 2 diabetes , a two-serving-per-day increment in whole grain consumption was associated with a 21 % ( 95 % CI 13%–28 % ) decrease in risk of type 2 diabetes after adjustment for potential confounders and BMI . Conclusions Whole grain intake is inversely associated with risk of type 2 diabetes , and this association is stronger for bran than for germ . Findings from prospect i ve cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes BACKGROUND Certain dietary components may play a role in the prevention of type 2 diabetes . OBJECTIVE We examined prospect ively the associations between whole- and refined-grain intake and the risk of type 2 diabetes in a large cohort of men . DESIGN Men from the Health Professionals Follow-up Study without a history of diabetes or cardiovascular disease in 1986 ( n = 42898 ) were followed for < /=12 y. Intakes of whole and refined grains , measured every 4 y by use of food-frequency question naires , were used to predict subsequent type 2 diabetes risk through multivariate analysis . RESULTS We ascertained 1197 cases of incident type 2 diabetes . After adjustment for age ; physical activity ; cigarette smoking ; alcohol consumption ; family history of diabetes ; and fruit , vegetable , and energy intakes , the relative risk of type 2 diabetes was 0.58 ( 95 % CI : 0.47 , 0.70 ; P for trend < 0.0001 ) comparing the highest with the lowest quintile of whole-grain intake . The association was moderately attenuated when additionally adjusted for body mass index ( relative risk : 0.70 ; 95 % CI : 0.57 , 0.85 ; P for trend = 0.0006 ) . Intake of refined grains was not significantly associated with risk of type 2 diabetes . After further adjustment for magnesium intake , cereal fiber intake , and glycemic load , the association between whole grains and type 2 diabetes was attenuated and the trend no longer significant . CONCLUSIONS In men , a diet high in whole grains is associated with a reduced risk of type 2 diabetes in men that may be mediated by cereal fiber . Efforts should be made to replace refined-grain with whole-grain foods Background Epidemiological studies indicate beneficial effects of flavonoids on cardiovascular disease ( CVD ) risk . Aim of the study To study the effect of flavonoid-rich sea buckthorn berry ( SBB ) on circulating lipid markers associated with CVD risk and plasma flavonol concentration . Also investigated was whether changes in the circulating flavonol concentrations correlate with the SBB induced changes in C-reactive protein ( CRP ) concentration observed previously . Subjects and methods In all 229 healthy participants completed the r and omized double-blind study and consumed daily 28 g of SBB or placebo for 3 months . Fasting blood sample s for the analysis of lipid markers and flavonols were obtained at the beginning and end of the study . Results Compared to the placebo , the consumption of SBB increased the plasma concentration of the flavonols quercetin and isorhamnetin significantly [ treatment differences 3.0 ng/ml ( P = 0.03 ) and 3.9 ng/ml ( P < 0.01 ) , respectively ] . The increase of kaempferol concentration was not significant [ treatment difference 0.7 ng/ml ( P = 0.08 ) ] . SBB did not affect the serum total , HDL , LDL cholesterol , or the serum triacylglycerol concentrations . There was no correlation between the changes in flavonol and CRP concentrations of participants . Conclusions The consumption of SBB significantly increased the fasting plasma concentration of quercetin and isorhamnetin indicating that it is a good dietary source of flavonols . However , this did not convert to affecting the circulating concentrations of lipid markers in healthy , normolipidemic adults having healthy diets We examined consumption of animal foods , protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospect i ve Investigation into Cancer and Nutrition . Associations were examined using Cox regression , stratified by recruitment centre and adjusted for height , weight , education , marital status and energy intake . After an average of 8.7 years of follow-up , there were 2727 incident cases of prostate cancer , of which 1131 were known to be localised and 541 advanced-stage disease . A high intake of dairy protein was associated with an increased risk , with a hazard ratio for the top versus the bottom fifth of intake of 1.22 ( 95 % confidence interval ( CI ) : 1.07–1.41 , Ptrend=0.02 ) . After calibration to allow for measurement error , we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32 % ( 95 % CI : 1–72 % , Ptrend=0.04 ) . Calcium from dairy products was also positively associated with risk , but not calcium from other foods . The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer BACKGROUND Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women ; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets . Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures . OBJECTIVE We assessed relations between postmenopausal hip fracture risk and calcium , vitamin D , and milk consumption . DESIGN In an 18-y prospect i ve analysis in 72 337 postmenopausal women , dietary intake and nutritional supplement use were assessed at baseline in 1980 and up date d several times during follow-up . We identified 603 incident hip fractures result ing from low or moderate trauma . Relative risks ( RRs ) from proportional hazards models were controlled for other dietary and nondietary factors . RESULTS Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37 % lower risk of hip fracture ( RR = 0.63 ; 95 % CI : 0.42 , 0.94 ) than did women consuming < 3.5 microg/d . Total calcium intake was not associated with hip fracture risk ( RR = 0.96 ; 95 % CI : 0.68 , 1.34 for > or = 1200 compared with < 600 mg/d ) . Milk consumption was also not associated with a lower risk of hip fracture ( P for trend = 0.21 ) . CONCLUSIONS An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women . Neither milk nor a high-calcium diet appears to reduce risk . Because women commonly consume less than the recommended intake of vitamin D , supplement use or dark fish consumption may be prudent BACKGROUND Dietary carbohydrates may influence the development of type 2 ( non-insulin-dependent ) diabetes , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women BACKGROUND Dairy intake may increase prostate cancer risk , but whether this is due to calcium 's suppression of circulating vitamin D remains unclear . Findings on calcium and vitamin D intake and prostate cancer are inconsistent . OBJECTIVE We examined the association of dairy , calcium , and vitamin D intake with prostate cancer . DESIGN In a prospect i ve study of 3612 men followed from 1982 - 1984 to 1992 for the first National Health and Nutrition Examination Epidemiologic Follow-up Study , 131 prostate cancer cases were identified . Dietary intake was estimated from question naires completed in 1982 - 1984 . Relative risk ( RR ) and 95 % CIs were estimated by using Cox proportional hazards models adjusted for age , race , and other covariates . RESULTS Compared with men in the lowest tertile for dairy food intake , men in the highest tertile had a relative risk ( RR ) of 2.2 ( 95 % CI : 1.2 , 3.9 ; trend P = 0.05 ) . Low-fat milk was associated with increased risk ( RR = 1.5 ; 95 % CI : 1.1 , 2.2 ; third compared with first tertile ; trend P = 0.02 ) , but whole milk was not ( RR = 0.8 ; 95 % CI : 0.5 , 1.3 ; third compared with first tertile ; trend P = 0.35 ) . Dietary calcium was also strongly associated with increased risk ( RR = 2.2 ; 95 % CI : 1.4 , 3.5 ; third compared with first tertile ; trend P = 0.001 ) . After adjustment for calcium intake , neither vitamin D nor phosphorus was clearly associated with risk . CONCLUSIONS Dairy consumption may increase prostate cancer risk through a calcium-related pathway . Calcium and low-fat milk have been promoted to reduce risk of osteoporosis and colon cancer . Therefore , the mechanisms by which dairy and calcium might increase prostate cancer risk should be clarified and confirmed BACKGROUND Whether the intake of dietary fiber can protect against colorectal cancer is a long-st and ing question of considerable public health import , but the epidemiologic evidence has been inconsistent . OBJECTIVE The objective was to investigate the relation between dietary fiber and whole-grain food intakes and invasive colorectal cancer in the prospect i ve National Institutes of Health-AARP Diet and Health Study . DESIGN The analytic cohort consisted of 291 988 men and 197 623 women aged 50 - 71 y. Diet was assessed with a self-administered food-frequency question naire at baseline in 1995 - 1996 ; 2974 incident colorectal cancer cases were identified during 5 y of follow-up . The Cox proportional hazards model was used to estimate the relative risks ( RRs ) and 95 % CIs . RESULTS Total dietary fiber intake was not associated with colorectal cancer . The multivariate RR for the highest compared with the lowest intake quintile ( RR(Q5-Q1 ) ) was 0.99 ( 95 % CI : 0.85 , 1.15 ; P for trend = 0.96 ) . In analyses of fiber from different food sources , only fiber from grains was associated with a lower risk of colorectal cancer ( multivariate RR(Q5-Q1 ) : 0.86 ; 95 % CI : 0.76 , 0.98 ; P for trend = 0.01 ) . Whole-grain intake was inversely associated with colorectal cancer risk : the multivariate RR(Q5-Q1 ) was 0.79 ( 95 % CI : 0.70 , 0.89 ) for the whole cohort ( P for trend < 0.001 ) . The association with whole grain was stronger for rectal than for colon cancer . CONCLUSIONS In this large prospect i ve cohort study , total dietary fiber intake was not associated with colorectal cancer risk , whereas whole-grain consumption was associated with a modest reduced risk BACKGROUND Prospect i ve studies suggested that substituting whole-grain products for refined-grain products lowers the risks of type 2 diabetes and cardiovascular disease ( CVD ) in women . Although breakfast cereals are a major source of whole and refined grains , little is known about their direct association with the risk of premature mortality . OBJECTIVE We prospect ively evaluated the association between whole- and refined-grain breakfast cereal intakes and total and CVD-specific mortality in a cohort of US men . DESIGN We examined 86,190 US male physicians aged 40 - 84 y in 1982 who were free of known CVD and cancer at baseline . RESULTS During 5.5 y , we documented 3114 deaths from all causes , including 1381 due to CVD ( 488 myocardial infa rct ions and 146 strokes ) . Whole-grain breakfast cereal intake was inversely associated with total and CVD-specific mortality , independent of age ; body mass index ; smoking ; alcohol intake ; physical activity ; history of diabetes , hypertension , or high cholesterol ; and use of multivitamins . Compared with men who rarely or never consumed whole-grain cereal , men in the highest category of whole-grain cereal intake ( > or = 1 serving/d ) had multivariate-estimated relative risks of total and CVD-specific mortality of 0.83 ( 95 % CI : 0.73 , 0.94 ; P for trend < 0.001 ) and 0.80 ( 0.66 , 0.97 ; P for trend < 0.001 ) , respectively . In contrast , total and refined-grain breakfast cereal intakes were not significantly associated with total and CVD-specific mortality . These findings persisted in analyses stratified by history of type 2 diabetes , hypertension , and high cholesterol . CONCLUSIONS Both total mortality and CVD-specific mortality were inversely associated with whole-grain but not refined-grain breakfast cereal intake . These prospect i ve data highlight the importance of distinguishing whole-grain from refined-grain cereals in the prevention of chronic diseases BACKGROUND Potatoes , a high glycemic form of carbohydrate , are hypothesized to increase insulin resistance and risk of type 2 diabetes . OBJECTIVE The objective was to examine prospect ively the relation between potato consumption and the risk of type 2 diabetes . DESIGN We conducted a prospect i ve study of 84,555 women in the Nurses ' Health Study . At baseline , the women were aged 34 - 59 y , had no history of chronic disease , and completed a vali date d food-frequency question naire . The participants were followed for 20 y with repeated assessment of diet . RESULTS We documented 4496 new cases of type 2 diabetes . Potato and french fry consumption were both positively associated with risk of type 2 diabetes after adjustment for age and dietary and nondietary factors . The multivariate relative risk ( RR ) in a comparison between the highest and the lowest quintile of potato intake was 1.14 ( 95 % CI : 1.02 , 1.26 ; P for trend = 0.009 ) . The multivariate RR in a comparison between the highest and the lowest quintile of french fry intake was 1.21 ( 95 % CI : 1.09 , 1.33 ; P for trend < 0.0001 ) . The RR of type 2 diabetes was 1.18 ( 95 % CI : 1.03 , 1.35 ) for 1 daily serving of potatoes and 1.16 ( 95 % CI : 1.05 , 1.29 ) for 2 weekly servings of french fries . The RR of type 2 diabetes for substituting 1 serving potatoes/d for 1 serving whole grains/d was 1.30 ( 95 % CI : 1.08 , 1.57 ) . The association between potato consumption and risk of type 2 diabetes was more pronounced in obese women . CONCLUSIONS Our findings suggest a modest positive association between the consumption of potatoes and the risk of type 2 diabetes in women . This association was more pronounced when potatoes were substituted for whole grains High intakes of whole grain foods are inversely related to the incidence of coronary heart diseases and type 2 diabetes , but the mechanisms remain unclear . Our study aim ed to evaluate the effects of a diet rich in whole grains compared with a diet containing the same amount of refined grains on insulin sensitivity and markers of lipid peroxidation and inflammation . In a r and omized crossover study , 22 women and 8 men ( BMI 28 + /- 2 ) were given either whole-grain or refined-grain products ( 3 bread slices , 2 crisp bread slices , 1 portion muesli , and 1 portion pasta ) to include in their habitual daily diet for two 6-wk periods . Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic clamp tests . 8-Iso-prostagl and in F(2alpha ) ( 8-iso PGF(2alpha ) ) , an F(2)-isoprostane , was measured in the urine as a marker of lipid peroxidation , and highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers of inflammation . Peripheral insulin sensitivity [ mg glucose . kg body wt(-1 ) . min(-1 ) per unit plasma insulin ( mU/L ) x 100 ] did not improve when subjects consumed whole-grain products ( 6.8 + /- 3.0 at baseline and 6.5 + /- 2.7 after 6 wk ) or refined products ( 6.4 + /- 2.9 and 6.9 + /- 3.2 , respectively ) and there were no differences between the 2 periods . Whole-grain consumption also did not affect 8-iso-PGF(2alpha ) in urine , IL-6 and C-reactive protein in plasma , blood pressure , or serum lipid concentrations . In conclusion , substitution of whole grains ( mainly based on milled wheat ) for refined-grain products in the habitual daily diet of healthy moderately overweight adults for 6-wk did not affect insulin sensitivity or markers of lipid peroxidation and inflammation BACKGROUND Previous studies have suggested that a daily intake of 3 servings of whole-grain foods is associated with a reduced risk of coronary heart disease ( CHD ) . However , methods for the assessment of whole-grain intake differ . Furthermore , any additional effects of added bran and germ , which are components of whole grains , have not been reported . OBJECTIVE The objective was to evaluate the association of whole-grain , bran , and germ intakes ( with the use of new quantitative measures ) with the incidence of CHD . DESIGN This was a prospect i ve cohort study of 42,850 male health professionals aged 40 - 75 y at baseline in 1986 who were free from cardiovascular disease , cancer , and diabetes . Daily whole-grain , bran , and germ intakes were derived in grams per day from a detailed semiquantitative dietary question naire . RESULTS During 14 y of follow-up , we documented 1818 incident cases of CHD . After cardiovascular disease risk factors and the intakes of bran and germ added to foods were controlled for , the hazard ratio of CHD between extreme quintiles of whole-grain intake was 0.82 ( 95 % CI : 0.70 , 0.96 ; P for trend=0.01 ) . The hazard ratio of CHD in men with the highest intake of added bran was 0.70 ( 95 % CI : 0.60 , 0.82 ) compared with men with no intake of added bran ( P for trend < or = 0.001 ) . Added germ was not associated with CHD risk . CONCLUSION This study supports the reported beneficial association of whole-grain intake with CHD and suggests that the bran component of whole grains could be a key factor in this relation BACKGROUND Fiber and whole-cereal intakes may protect against hyperinsulinemia and the risk of type 2 diabetes . OBJECTIVE The aim was to study whether the long-term use of high-fiber rye bread and white-wheat bread modifies glucose and insulin metabolism in healthy postmenopausal women . DESIGN The study was a r and omized crossover trial consisting of 8-wk test and 8-wk washout periods . The subjects were 20 postmenopausal women [ macro x + /- SD age : 59 + /- 6.0 y ; body mass index ( in kg/m(2 ) ) : 27.5 + /- 2.9 ; baseline fasting serum cholesterol : 6.5 + /- 0.8 mmol/L ] , of whom 3 had impaired glucose tolerance as determined by a 2-h oral-glucose-tolerance test . The test breads were high-fiber rye and white-wheat breads , planned to make up > or = 20 % of energy . Fasting blood sample s were collected for the measurement of plasma glucose and insulin at the beginning and at the end of both bread periods . The frequently sample d intravenous-glucose-tolerance test was performed at the run-in and at the end of both bread periods . The acute insulin response , insulin sensitivity , and glucose effectiveness were calculated . RESULTS The rye bread made up 23.4 + /- 4.3 % and wheat bread 26.7 + /- 8.2 % of total energy intake . Compared with that during the run-in period , the acute insulin response increased significantly more during the rye bread period ( 9.9 + /- 24.2 % ) than during the wheat bread period ( 2.8 + /- 36.3 % ; P = 0.047 ) . Other measured variables did not change significantly during the study . CONCLUSIONS Modification of carbohydrate intake by high-fiber rye bread did not alter insulin sensitivity in postmenopausal , hypercholesterolemic women . High-fiber rye bread appears to enhance insulin secretion , possibly indicating improvement of b cell function BACKGROUND Prospect i ve studies evaluating associations between food intake and risk of heart failure ( HF ) in diverse population s are needed . OBJECTIVES Relationships between incident HF ( death or hospitalization ) and intake of seven food categories ( whole grains , fruits/vegetables , fish , nuts , high-fat dairy , eggs , red meat ) were investigated in an observational cohort of 14,153 African-American and white adults , age 45 to 64 years , sample d from four US communities . METHODS Between baseline ( 1987 - 1989 ) and Exam 3 ( 1993 - 1995 ) , dietary intake was based on responses to a 66-item food frequency question naire administered at baseline ; thereafter , intake was based on averaged baseline and Exam 3 responses . Hazard ratios ( HR [ 95 % CI ] ) for HF were calculated per 1-daily serving difference in food group intake . RESULTS During a mean of 13 years , 1,140 HF hospitalizations were identified . After multivariable adjustment ( energy intake , demographics , lifestyle factors , prevalent cardiovascular disease , diabetes , hypertension ) , HF risk was lower with greater whole-grain intake ( 0.93 [ 0.87 , 0.99 ] ) , but HF risk was higher with greater intake of eggs ( 1.23 [ 1.08 , 1.41 ] ) and high-fat dairy ( 1.08 [ 1.01 , 1.16 ] ) . These associations remained significant independent of intakes of the five other food categories , which were not associated with HF . CONCLUSIONS In this large , population -based sample of African-American and white adults , whole-grain intake was associated with lower HF risk , whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders Intake of calcium and /or dairy products has been associated with increased risk of prostate cancer in some epidemiological studies . One potential biological mechanism is that high calcium intake down-regulates 1,25 dihydroxy vitamin D(3 ) , which may increase cell proliferation in the prostate . We examined the association between calcium , dairy intake , and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort , a prospect i ve cohort of elderly United States adults . Participants in the study completed a detailed question naire on diet , medical history , and lifestyle at enrollment in 1992 - 1993 . After excluding men with a history of cancer or incomplete dietary information , 65,321 men remained for analysis . During follow-up through August 31 , 1999 , we documented 3811 cases of incident prostate cancer . Multivariate-adjusted rate ratios ( RRs ) were calculated using Cox proportional hazards models . Total calcium intake ( from diet and supplements ) was associated with modestly increased risk of prostate cancer [ RR = 1.2 , 95 % confidence interval ( CI ) = 1.0 - 1.6 for > or=2000 versus < 700 mg/day , P trend = 0.02 ) . High dietary calcium intake ( > or=2000 versus < 700 mg/day ) was also associated with increased risk of prostate cancer ( RR = 1.6 , 95 % CI = 1.1 - 2.3 , P trend = 0.10 ) , although moderate levels of dietary calcium were not associated with increased risk . Dairy intake was not associated with prostate cancer risk . The association between prostate cancer and total calcium intake was strongest for men who reported not having prostate-specific antigen testing before 1992 ( RR = 1.5 , 95 % CI = 1.1 - 2.0 , P trend < 0.01 for > or= 2000 mg/day of total calcium ; RR = 2.1 , 95 % CI = 1.3 - 3.4 > or=2000 mg/day of dietary calcium , P trend = 0.04 ) . Our results support the hypothesis that very high calcium intake , above the recommended intake for men , may modestly increase risk of prostate cancer Background : Consumption of wholegrain ( WG ) products may protect against colon and rectal cancer . Methods : The associations between total and individual WG product consumption and colon and rectal cancer risk were prospect ively examined using data on 461 incident cases of colon cancer and 283 incident cases of rectal cancer that developed during 10.6 years ( median ) of follow-up among 26 630 men and 29 189 women taking part in the Diet , Cancer and Health cohort . Incidence rate ratios ( IRRs ) of colon and rectal cancer related to total or individual WG product intake were calculated using Cox regression . Results : Higher WG product intake was associated with lower risk of colon cancer and rectal cancer in men . The adjusted IRR ( 95 % CI ) was 0.85 ( 0.77–0.94 ) for colon cancer and 0.90 ( 0.80–1.01 ) for rectal cancer per daily 50 g increment in intake . For colon cancer the association was confined to intake of WG bread in particular . No consistent associations between total or individual WG product consumption and colon or rectal cancer risk were observed in women . Conclusion : The findings suggest that higher total WG product intake is associated with a lower risk of colon and perhaps rectal cancer in men , but not in women High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk , but available prospect i ve data regarding these associations are inconsistent . We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol , Beta-Carotene ( ATBC ) Cancer Prevention Study , a cohort of 29,133 male smokers aged 50 - 69 years at study entry . Dietary intake was assessed at baseline using a vali date d 276-item food use question naire . Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer . During 17 years of follow-up , we ascertained 1,267 incident cases of prostate cancer . High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk . The multivariate relative risk ( RR ) of prostate cancer for > or = 2,000 mg/day compared to < 1,000 mg/day of calcium intake was 1.63 ( 95 % confidence interval ( CI ) , 1.27 - 2.10 ; p trend < 0.0001 ) . Total dairy intake was also positively associated with risk of prostate cancer . The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 ( 95 % CI , 1.04 - 1.51 ; p trend = 0.03 ) . However , no association with total dairy intake remained after we adjusted for calcium ( p trend = 0.17 ) . Findings were similar by stage and grade of prostate cancer . The results from this large prospect i ve study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk CONTEXT Components of the insulin resistance syndrome ( IRS ) , including obesity , glucose intolerance , hypertension , and dyslipidemia , are major risk factors for type 2 diabetes and heart disease . Although diet has been postulated to influence IRS , the independent effects of dairy consumption on development of this syndrome have not been investigated . OBJECTIVE To examine associations between dairy intake and incidence of IRS , adjusting for confounding lifestyle and dietary factors . DESIGN The Coronary Artery Risk Development in Young Adults ( CARDIA ) study , a population -based prospect i ve study . SETTING AND PARTICIPANTS General community sample from 4 US metropolitan areas of 3157 black and white adults aged 18 to 30 years who were followed up from 1985 - 1986 to 1995 - 1996 . MAIN OUTCOME MEASURE Ten-year cumulative incidence of IRS and its association with dairy consumption , measured by diet history interview . RESULTS Dairy consumption was inversely associated with the incidence of all IRS components among individuals who were overweight ( body mass index > or = 25 kg/m(2 ) ) at baseline but not among leaner individuals ( body mass index < 25 kg/m(2 ) ) . The adjusted odds of developing IRS ( 2 or more components ) were 72 % lower ( odds ratio , 0.28 ; 95 % confidence interval , 0.14 - 0.58 ) among overweight individuals in the highest ( > or = 35 times per week , 24/102 individuals ) compared with the lowest ( < 10 times per week , 85/190 individuals ) category of dairy consumption . Each daily occasion of dairy consumption was associated with a 21 % lower odds of IRS ( odds ratio , 0.79 ; 95 % confidence interval , 0.70 - 0.88 ) . These associations were similar for blacks and whites and for men and women . Other dietary factors , including macronutrients and micronutrients , did not explain the association between dairy intake and IRS . CONCLUSIONS Dietary patterns characterized by increased dairy consumption have a strong inverse association with IRS among overweight adults and may reduce risk of type 2 diabetes and cardiovascular disease BACKGROUND Diet and lifestyle modifications can substantially reduce the risk of type 2 diabetes . While a strong inverse association has been reported between dairy consumption and the insulin resistance syndrome among young obese adults , the relation between dairy intake and type 2 diabetes is unknown . METHODS We prospect ively examined the relation between dairy intake and incident cases of type 2 diabetes in 41,254 male participants with no history of diabetes , cardiovascular disease , and cancer at baseline in the Health Professionals Follow-up Study . RESULTS During 12 years of follow-up , we documented 1243 incident cases of type 2 diabetes . Dairy intake was associated with a modestly lower risk of type 2 diabetes . After adjusting for potential confounders , including body mass index , physical activity , and dietary factors , the relative risk for type 2 diabetes in men in the top quintile of dairy intake was 0.77 ( 95 % confidence interval [ CI ] , 0.62 - 0.95 ; P for trend , .003 ) compared with those in the lowest quintile . Each serving-per-day increase in total dairy intake was associated with a 9 % lower risk for type 2 diabetes ( multivariate relative risk , 0.91 ; 95 % CI , 0.85 - 0.97 ) . The corresponding relative risk was 0.88 ( 95 % CI , 0.81 - 0.94 ) for low-fat dairy intake and 0.99 ( 95 % CI , 0.91 - 1.07 ) for high-fat dairy intake . The association did not vary significantly according to body mass index ( < 25 vs > or = 25 kg/m(2 ) ; P for interaction , .57 ) . CONCLUSION Dietary patterns characterized by higher dairy intake , especially low-fat dairy intake , may lower the risk of type 2 diabetes in men Recommendations for whole-grain ( WG ) intake are based on observational studies showing that higher WG consumption is associated with reduced CVD risk . No large-scale , r and omised , controlled dietary intervention studies have investigated the effects on CVD risk markers of substituting WG in place of refined grains in the diets of non-WG consumers . A total of 316 participants ( aged 18 - 65 years ; BMI > 25 kg/m2 ) consuming < 30 g WG/d were r and omly assigned to three groups : control ( no dietary change ) , intervention 1 ( 60 g WG/d for 16 weeks ) and intervention 2 ( 60 g WG/d for 8 weeks followed by 120 g WG/d for 8 weeks ) . Markers of CVD risk , measured at 0 ( baseline ) , 8 and 16 weeks , were : BMI , percentage body fat , waist circumference ; fasting plasma lipid profile , glucose and insulin ; and indicators of inflammatory , coagulation , and endothelial function . Differences between study groups were compared using a r and om intercepts model with time and WG intake as factors . Although reported WG intake was significantly increased among intervention groups , and demonstrated good participant compliance , there were no significant differences in any markers of CVD risk between groups . A period of 4 months may be insufficient to change the lifelong disease trajectory associated with CVD . The lack of impact of increasing WG consumption on CVD risk markers implies that public health messages may need to be clarified to consider the source of WG and /or other diet and lifestyle factors linked to the benefits of whole-grain consumption seen in observational studies Objective : To test the hypothesis that milk drinking increases the risk of ischaemic heart disease ( IHD ) and ischaemic stroke in a prospect i ve study . Design : In the Caerphilly Cohort Study dietary data , including milk consumption , were collected by a semiquantitative food frequency question naire in 1979–1983 . The cohort has been followed for 20–24 y and incident IHD and stroke events identified . Subjects : A representative population sample in South Wales , of 2512 men , aged 45–59 y at recruitment . Main outcome measures : In total , 493 men had an IHD event and 185 an ischaemic stroke during follow-up . Results : After adjustment , the hazard ratio in men with a milk consumption of one pint ( 0.57 l ) or more per day , relative to men who stated that they consumed no milk , is 0.71 ( 0.40–1.26 ) for IHD and 0.66 ( 0.24–1.81 ) for ischaemic stroke . At baseline , 606 men had had clinical or ECG evidence of vascular disease , and in these the vascular risk was even lower ( 0.37 ; 0.15–0.90 ) . The hazard ratio for IHD and ischaemic stroke combined is 0.64 ( 0.39–1.06 ) in all men and 0.37 ( 0.15–0.90 ) in those who had had a prior vascular event . Conclusion : The data provide no convincing evidence that milk consumption is associated with an increase in vascular disease risk . Evidence from an overview of all published cohort studies on this topic should be informative . Sponsorship : The Medical Research Council , the University of Wales College of Medicine and Bristol University . Current support is from the Food St and ards Agency Background / Objectives : Dairy foods contain various nutrients that may affect health . We investigated whether intake of dairy products or related nutrients is associated with mortality due to cardiovascular disease ( CVD ) , cancer and all causes . Subjects/ Methods : We carried out a 16-year prospect i ve study among a community-based sample of 1529 adult Australians aged 25–78 years at baseline . Habitual intakes of dairy products ( total , high/low-fat dairy , milk , yoghurt and full-fat cheese ) , calcium and vitamin D were estimated as mean reported intake using vali date d food frequency question naires ( FFQs ) self-administered in 1992 , 1994 and 1996 . National Death Index data were used to ascertain mortality and cause of death between 1992 and 2007 . Hazard ratios ( HRs ) were calculated using Cox regression analysis . Results : During an average follow-up time of 14.4 years , 177 participants died , including 61 deaths due to CVD and 58 deaths due to cancer . There was no consistent and significant association between total dairy intake and total or cause-specific mortality . However , compared with those with the lowest intake of full-fat dairy , participants with the highest intake ( median intake 339 g/day ) had reduced death due to CVD ( HR : 0.31 ; 95 % confidence interval ( CI ) : 0.12–0.79 ; P for trend=0.04 ) after adjustment for calcium intake and other confounders . Intakes of low-fat dairy , specific dairy foods , calcium and vitamin D showed no consistent associations . Conclusions : Overall intake of dairy products was not associated with mortality . A possible beneficial association between intake of full-fat dairy and cardiovascular mortality needs further assessment and confirmation Objective : We examined the relation between whole grains , fruit , vegetables and dietary fiber and colon cancer risk in the prospect i ve Cancer Prevention Study II Nutrition Cohort . Methods : In 1992–1993 , 62,609 men and 70,554 women completed question naires on medical history , diet and lifestyle behaviors . After exclusions , we confirmed 298 cases of incident colon cancer among men and 210 among women through August 31 , 1997 . Results : Multivariate rate ratios ( RR ) and 95 % confidence intervals ( CI ) for all dietary factors were null . However , a statistically non-significant 30 % reduction in risk was observed for men with the highest vegetable intakes ( RR = 0.69 , CI = 0.47–1.03 , top versus . bottom quintile , p trend = 0.10 ) . Men with very low ( lowest tertile within the lowest quintile ) intakes of vegetables and dietary fiber were at increased risk compared to those in the highest four quintiles of intake ( vegetables RR = 1.79 , CI = 1.22–2.61 , p trend = 0.04 , and fiber RR = 1.96 , CI = 1.24–3.10 , p trend = 0.006 ) . Women with very low intakes of fruit were also at increased risk ( RR = 1.86 , CI = 1.18–2.94 , p trend = 0.06 ) . Conclusions : Higher intakes of plant foods or fiber were not related to lower risk of colon cancer . However , our data suggest that very low intakes of plant foods may increase risk , and that certain phytochemical subgroups may decrease risk Objective To evaluate the association of meat and dairy food consumption with subsequent risk of prostate cancer . Methods In 1989 , 3,892 men 35 + years old , who participated in the CLUE II study of Washington County , MD , completed an abbreviated Block food frequency question naire . Intake of meat and dairy foods was calculated using consumption frequency and portion size . Incident prostate cancer cases ( n = 199 ) were ascertained through October 2004 . Cox proportional hazards regression was used to calculate hazard ratios ( HR ) of total and advanced ( SEER stages three and four ; n = 54 ) prostate cancer and 95 % confidence intervals ( CI ) adjusted for age , BMI at age 21 , and intake of energy , saturated fat , and tomato products . Results Intakes of total meat ( HR = 0.90 , 95 % CI 0.60–1.33 , comparing highest to lowest tertile ) and red meat ( HR = 0.87 , 95 % CI 0.59–1.32 ) were not statistically significantly associated with prostate cancer . However , processed meat consumption was associated with a non-statistically significant higher risk of total ( 5 + vs. ≤1 servings/week : HR = 1.53 , 95 % CI 0.98–2.39 ) and advanced ( HR = 2.24 ; 95 % CI 0.90–5.59 ) prostate cancer . There was no association across tertiles of dairy or calcium with total prostate cancer , although compared to ≤1 serving/week consumption of 5 + servings/week of dairy foods was associated with an increased risk of prostate cancer ( HR = 1.65 , 95 % CI 1.02–2.66 ) . Conclusion Overall , consumption of processed meat , but not total meat or red meat , was associated with a possible increased risk of total prostate cancer in this prospect i ve study . Higher intake of dairy foods but not calcium was positively associated with prostate cancer . Further investigation into the mechanisms by which processed meat and dairy consumption might increase the risk of prostate cancer is suggested Objective : To study the effect of sea buckthorn berries on the number and duration of common cold ( CC ) infections . As secondary objectives the effects on digestive and urinary tract infections ( DTI , UTI ) , and serum C-reactive protein ( CRP ) concentrations were also investigated . Subjects : A total of 254 healthy volunteers were r and omly assigned to receive sea buckthorn or placebo product during the study , which 233 of them completed . Results : There were no significant differences in the number or duration of CC or DTI between groups ( CC : relative risks ( sea buckthorn vs placebo ) for the number and duration were 1.15 ( 95 % CI 0.90–1.48 ) and 1.05 ( 95 % CI 0.87–1.27 ) , respectively ) . In the sea buckthorn group , as compared to the placebo , the serum CRP concentrations decreased significantly ( difference in median change −0.059 mg/l , P=0.039 ) . The number of UTI was too small to draw solid conclusions , but the results indicate the subject merits further investigation . Conclusion : Sea buckthorn berries did not prevent CC or DTI . However , a reductive effect on CRP , a marker of inflammation , and a risk factor for cardiovascular diseases , was detected OBJECTIVES This study examined the association between intake of whole vs refined grain and the risk of type 2 diabetes mellitus . METHODS We used a food frequency question naire for repeated dietary assessment s to prospect ively evaluate the relation between whole-grain intake and the risk of diabetes mellitus in a cohort of 75,521 women aged 38 to 63 years without a previous diagnosis of diabetes or cardiovascular disease in 1984 . RESULTS During the 10-year follow-up , we confirmed 1879 incident cases of diabetes mellitus . When the highest and the lowest quintiles of intake were compared , the age and energy-adjusted relative risks were 0.62 ( 95 % confidence interval [ CI ] = 0.53 , 0.71 , P trend < .0001 ) for whole grain , 1.31 ( 95 % CI = 1.12 , 1.53 , P trend = .0003 ) for refined grain , and 1.57 ( 95 % CI = 1.36 , 1.82 , P trend < .0001 ) for the ratio of refined- to whole-grain intake . These findings remained significant in multivariate analyses . The findings were most evident for women with a body mass index greater than 25 and were not entirely explained by dietary fiber , magnesium , and vitamin E. CONCLUSIONS These findings suggest that substituting whole- for refined-grain products may decrease the risk of diabetes mellitus Aims /hypothesisCalcium and vitamin D have been implicated in the development of type 2 diabetes , but epidemiological evidence is limited . We examined prospect ively the relation of calcium and vitamin D intake to type 2 diabetes risk in a Japanese cohort . Methods Participants were 59,796 middle-aged and older men and women , who participated in the Japan Public Health Center-based Prospect i ve Study and had no history of type 2 diabetes or other serious diseases . Dietary intake of calcium and vitamin D were estimated using a vali date d food frequency question naire . Logistic regression was used to assess the association between intake of these nutrients and self-reported newly diagnosed type 2 diabetes . Results During a 5 year follow-up , 1,114 cases of type 2 diabetes were documented . Overall , calcium intake was not associated with a significantly lower risk of type 2 diabetes ; the multivariable odds ratio for the highest vs lowest quartiles was 0.93 ( 95 % CI 0.71–1.22 ) in men and 0.76 ( 95 % CI 0.56–1.03 ) in women . However , among participants with a higher vitamin D intake , calcium intake was inversely associated with diabetes risk ; the odds ratio for the highest vs lowest intake categories was 0.62 ( 95 % CI 0.41–0.94 ) in men and 0.59 ( 95 % CI 0.38–0.91 ) in women . Dairy food intake was significantly associated with a lower risk of type 2 diabetes in women only . Conclusions /interpretationCalcium and vitamin D may not be independently associated with type 2 diabetes risk . Our finding suggesting a joint action of these nutrients against type 2 diabetes warrants further investigation Objective : There is indirect evidence suggesting that strawberries , containing several key nutrients , may be associated with the risk of cardiovascular disease ( CVD ) . In the Women ’s Health Study , we examined strawberry intake for both its prospect i ve association with CVD risk in 38,176 women and its cross-sectional association with lipids and C-reactive protein ( CRP ) in a subset of 26,966 women . Methods : Strawberry intake was assessed from a baseline semiquantitative food frequency question naire , along with other self-reported lifestyle , clinical and dietary factors . Participants returned baseline bloods which were assayed for lipids and CRP . We computed the relative risks ( RRs ) for total CVD ( 1,004 cases ) ( including confirmed myocardial infa rct ion , stroke , revascularization , and cardiovascular death ) occurring during 10.9 years of follow-up . Results : At baseline , 25.6 % , 41.9 % , 24.8 % , and 7.7 % of women reported corresponding strawberry intake of none , 1–3 servings/month , 1 serving/week , and ≥2 servings/week . For total CVD , the multivariate RRs ( 95 % confidence intervals ) for increasing categories of strawberry intake were 1.00 ( ref ) , 1.01 ( 0.85–1.19 ) , 0.95 ( 0.77–1.17 ) , and 1.27 ( 0.94–1.72 ) ( P , trend = 0.06 ) . We found a similar lack of an association for individual cardiovascular endpoints and comparing mean levels of lipids and CRP by category of strawberry intake . However , women consuming ≥2 servings/week versus none had a borderline significant , multivariate 14 % lower likelihood of an elevated CRP of ≥3 mg/L. Conclusions : Strawberry intake was unassociated with the risk of incident CVD , lipids , or CRP in middle-aged and older women , though higher strawberry intake may slightly reduce the likelihood of having elevated CRP levels . Additional epidemiologic data are needed to clarify any role of strawberries in CVD prevention Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods . The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospect i ve Investigation into Cancer and Nutrition study . A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers . Single 24-h dietary recalls ( 24-HDR ) were collected using a st and ardized computerized interview program . Food intakes were computed according to their degree of processing ( moderately/nonprocessed foods , processed staple foods , highly processed foods ) . Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels . At the population level , mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men ( P = 0.0016 ) and in women ( P = 0.0012 ) . At the individual level , these associations remained but at a much lower level in men ( r = 0.08 , P = 0.006 ) and in women ( r = 0.09 , P = 0.0001 ) . The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European population BACKGROUND A Western diet is associated with breast cancer risk . OBJECTIVE We investigated the relation of meat , egg , and dairy product consumption with breast cancer risk by using data from the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . DESIGN Between 1992 and 2003 , information on diet was collected from 319,826 women . Disease hazard ratios were estimated with multivariate Cox proportional hazard models . RESULTS Breast cancer cases ( n = 7119 ) were observed during 8.8 y ( median ) of follow-up . No consistent association was found between breast cancer risk and the consumption of any of the food groups under study , when analyzed by both categorical and continuous exposure variable models . High processed meat consumption was associated with a modest increase in breast cancer risk in the categorical model ( hazard ratio : 1.10 ; 95 % CI : 1.00 , 1.20 ; highest compared with lowest quintile : P for trend = 0.07 ) . Subgroup analyses suggested an association with butter consumption , limited to premenopausal women ( hazard ratio : 1.28 ; 95 % CI : 1.06 , 1.53 ; highest compared with lowest quintile : P for trend = 0.21 ) . Between-country heterogeneity was found for red meat ( Q statistic = 18.03 ; P = 0.05 ) and was significantly explained ( P = 0.023 ) by the proportion of meat cooked at high temperature . CONCLUSIONS We have not consistently identified intakes of meat , eggs , or dairy products as risk factors for breast cancer . Future studies should investigate the possible role of high-temperature cooking in the relation of red meat intake with breast cancer risk The effects on blood lipids and blood pressure of a diet corresponding to present Nordic Nutrition Recommendations , i.e. less than 30 % of energy from fat and with a fibre content exceeding 3 g/MJ , were studied in 18 men and 12 women ( mean age , 24 years ) under strict dietary control over 8 months . Blood sampling , blood pressure and body weight measurement were performed at four occasions on their habitual diet and once a month during the intervention period . An age-matched control group ( 17 men , 8 women ) was followed with monthly measurements parallel to the intervention group . The habitual diets , assessed by 7-day records , showed an average fat content corresponding to 36 % of energy . Initial levels of total cholesterol and HDL cholesterol ( X + /- SD ) were 4.21 + /- 0.61 and 1.23 + /- 0.23 mmol/l for the men in the intervention group ; 4.35 + /- 0.79 and 1.21 + /- 0.26 mmol/l for the male controls ; 4.61 + /- 0.59 and 1.46 + /- 0.31 mmol/l for the women in the intervention group and 4.48 + /- 0.64 and 1.48 + /- 0.29 mmol/l for the female controls . Significantly decreased levels of total cholesterol and HDL cholesterol throughout the experimental period were seen for both sexes in the intervention group . Total cholesterol fell 0.49 mmol/l ( 95 % CI : 0.41 - 0.56 ) in the male subjects and 0.49 mmol/l ( 95 % CI : 0.39 - 0.59 ) in the female subjects . The fall in HDL cholesterol was 0.16 mmol/l ( 95 % C : 0.13 - 0.18 ) and 0.18 mmol/l ( 95 % CI : 0.12 - 0.23 ) , respectively . Total cholesterol changes were independent of initial values . All subjects were normotensive at the start of the study with an average blood pressure of 122/68 mmHg for men and 112/68 mmHg for the women . Systolic blood pressure dropped gradually and significantly in the male subjects of the intervention group . A minimum of 6 mmHg below initial values was noted after six months of dietary intervention . No significant changes in dietary intake and blood lipids were observed in the control group . Thus , changes of present dietary habits of young healthy Danish subjects to an intake in accordance with the Nordic Nutrition Recommendations 1989 will favourably affect suggested risk factors for disease OBJECTIVE To assess the impact of increased consumption of milk , without other dietary advice , on older adults ' energy and nutrient intakes , weight , cardiovascular risk factors ( blood pressure , plasma lipid levels ) , and quality of life . SUBJECTS/ SETTING Two hundred four healthy men and women , aged 55 to 85 years , who consumed fewer than 1.5 dairy servings per day were chosen from six US academic health centers . DESIGN R and omized , controlled open trial . INTERVENTION Advice to increase skim or 1 % milk intake by 3 cups per day ( n = 101 ) or to maintain usual diet ( n = 103 ) for 12 weeks after a 4-week baseline period . MAIN OUTCOME MEASURES Changes in energy and nutrient intake assessed from 3-day food records , body weight , blood pressure , and plasma lipid levels . STATISTICAL ANALYSES PERFORMED Group-by-time analysis of variance with repeated- measures , chi 2 test . RESULTS Compliance with the intervention was good . Compared with controls , participants in the milk-supplemented group significantly increased energy , protein , cholesterol , vitamins A , D , and B-12 , riboflavin , pantothenate , calcium , phosphorus , magnesium , zinc , and potassium intakes . Prevalence of nutrient inadequacy , assessed for nutrients with Estimated Average Requirements , decreased among women in the milk group for magnesium ( 40 % at baseline vs 13 % at 12 weeks , P < .001 ) and vitamin B-12 ( 6 % vs 0 % , P < .05 ) and tended to decrease ( P < .10 ) for protein and thiamin ( women ) and magnesium and vitamin B-6 ( men ) . The milk group gained 0.6 kg more than control group ( P < .01 ) ; however , weight gain was less than predicted , which suggests some compensation for the added energy from milk . Blood pressure decreased similarly over time in both groups . Total and low-density lipoprotein cholesterol levels , and the ratio of total cholesterol to high-density lipoprotein cholesterol , were unchanged . Triglyceride levels increased within the normal range in the milk group ( P = .002 ) . Quality of life scores were high at baseline and remained high throughout . APPLICATIONS/ CONCLUSIONS Older adults can successfully increase milk intake , thereby meaningfully improving their nutrient intakes . Dietitians can play a key role in disseminating this advice Purpose Bilberries are abundant in polyphenols . Dietary polyphenols have been associated with strategies for prevention and treatment of chronic inflammatory diseases . We investigated the effect of bilberry juice on serum and plasma biomarkers of inflammation and antioxidant status in subjects with elevated levels of at least one risk factor for cardiovascular disease ( CVD ) . Methods In a r and omized controlled trial , participants consumed either bilberry juice ( n = 31 ) or water ( n = 31 ) for 4 weeks . Results Supplementation with bilberry juice result ed in significant decreases in plasma concentrations of C-reactive protein ( CRP ) , interleukin (IL)-6 , IL-15 , and monokine induced by INF-γ ( MIG ) . Unexpectedly , an increase in the plasma concentration of tumor nuclear factor-α ( TNF-α ) was observed in the bilberry group . CRP , IL-6 , IL15 , MIG , and TNF-α are all target genes of nuclear factor- kappa B ( NF-κB ) , —a transcription factor that is crucial in orchestrating inflammatory responses . Plasma quercetin and p-coumaric acid increased in the bilberry group , otherwise no differences were observed for clinical parameters , oxidative stress or antioxidant status . Furthermore , we studied the effect of polyphenols from bilberries on lipopolysaccharide (LPS)-induced NF-κB activation in a monocytic cell line . We observed that quercetin , epicatechin , and resveratrol inhibited NF-κB activation . Conclusions These findings suggest that supplementation with bilberry polyphenols may modulate the inflammation processes . Further testing of bilberry supplementation as a potential strategy in prevention and treatment of chronic inflammatory diseases is warranted OBJECTIVE the aim of this study was to investigate the effects of a healthy Nordic diet ( ND ) on cardiovascular risk factors . DESIGN AND SUBJECTS in a r and omized controlled trial ( NORDIET ) conducted in Sweden , 88 mildly hypercholesterolaemic subjects were r and omly assigned to an ad libitum ND or control diet ( subjects ' usual Western diet ) for 6 weeks . Participants in the ND group were provided with all meals and foods . Primary outcome measurements were low-density lipoprotein ( LDL ) cholesterol , and secondary outcomes were blood pressure ( BP ) and insulin sensitivity ( fasting insulin and homeostatic model assessment -insulin resistance ) . The ND was rich in high-fibre plant foods , fruits , berries , vegetables , whole grains , rapeseed oil , nuts , fish and low-fat milk products , but low in salt , added sugars and saturated fats . RESULTS the ND contained 27 % , 52 % , 19 % and 2 % of energy from fat , carbohydrate , protein and alcohol , respectively . In total , 86 of 88 subjects r and omly assigned to diet completed the study . Compared with controls , there was a decrease in plasma cholesterol ( -16 % , P < 0.001 ) , LDL cholesterol ( -21 % , P < 0.001 ) , high-density lipoprotein ( HDL ) cholesterol ( -5 % , P < 0.01 ) , LDL/HDL ( -14 % , P < 0.01 ) and apolipoprotein (apo)B/apoA1 ( -1 % , P < 0.05 ) in the ND group . The ND reduced insulin ( -9 % , P = 0.01 ) and systolic BP by -6.6 ± 13.2 mmHg ( -5 % , P < 0.05 ) compared with the control diet . Despite the ad libitum nature of the ND , body weight decreased after 6 weeks in the ND compared with the control group ( -4 % , P < 0.001 ) . After adjustment for weight change , the significant differences between groups remained for blood lipids , but not for insulin sensitivity or BP . There were no significant differences in diastolic BP or triglyceride or glucose concentrations . CONCLUSIONS a healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinical ly relevant levels in hypercholesterolaemic subjects BACKGROUND Nonanemic iron deficiency is common in toddlers in developed countries . Food-based strategies are safe methods to control and prevent mild micronutrient deficiencies . OBJECTIVE Our objective was to determine the efficacy of an increased intake of red meat , or the consumption of iron-fortified milk , in improvement of iron status in toddlers at a population level . DESIGN In this 20-wk r and omized placebo-controlled trial , 225 healthy nonanemic 12 - 20-mo-old children were assigned to 1 of 3 groups : red meat ( toddlers encouraged to consume approximately 2.6 mg iron from red meat dishes daily ) , fortified milk [ toddlers ' regular milk replaced with iron-fortified ( 1.5 mg iron/100 g prepared milk ) cow milk ] , or control [ toddlers ' regular milk replaced with nonfortified ( 0.01 mg iron/100 g prepared milk ) cow milk ] . Blood sample s were collected at baseline and at 20 wk for hemoglobin , serum ferritin , serum transferrin receptor , and C-reactive protein . The prevalence of suboptimal iron status ( ie , depleted iron stores , iron-deficient erythropoiesis , and iron deficiency anemia ) was determined , and body iron was calculated . RESULTS No intervention effects were shown on the prevalence of suboptimal iron status . Serum ferritin increased by 44 % ( 95 % CI : 14 % , 82 % ; P = 0.002 ) in the fortified milk group , did not change ( + 10 % ) in the red meat group ( 95 % CI : -7 % , 30 % ; P = 0.241 ) , and tended to decrease ( -14 % ) in the control group ( 95 % CI : -27 % , 1 % ; P = 0.063 ) . By 20 wk , in comparison with the control group , serum ferritin and body iron were significantly higher in the fortified milk group ( both P < 0.001 ) , and serum ferritin was significantly higher in the red meat group ( P = 0.033 ) . CONCLUSIONS Consumption of iron-fortified milk can increase iron stores in healthy nonanemic toddlers , whereas increased intakes of red meat can prevent their decline . This trial was registered at actr.org.au as ACTRN12605000487617 |
1,729 | 30,196,267 | 1 RESULTS : Effectiveness of school-based universal interventions was found to be neutral or small with more positive effects found for poorer quality studies and those based in primary schools ( pupils aged 9 - 12 years ) .
Overall , results suggested a trend whereby higher quality studies reported less positive effects .
The current evidence suggests there are neutral to small effects of universal , school-based interventions in the UK that aim to promote emotional or mental well-being or the prevention of mental health difficulties . | OBJECTIVES The present review aim ed to assess the quality , content and evidence of efficacy of universally delivered ( to all pupils aged 5 - 16 years ) , school-based , mental health interventions design ed to promote mental health/well-being and resilience , using a vali date d outcome measure and provided within the UK in order to inform UK schools-based well-being implementation . | OBJECTIVE The study aim ed to assess the effectiveness of an 18-hr cognitive behavioral group intervention in reducing depressive symptoms ( and associated outcomes ) in a universal sample of students in mainstream schools in Engl and . The intervention , the UK Resilience Programme ( UKRP ) , was based on the Penn Resiliency Program for Children and Adolescents . METHOD Students ( N = 2,844 ; 49 % female ; 67 % White ) were ages 11 - 12 at 16 schools . Classes of students were assigned arbitrarily into intervention ( UKRP ) or control ( usual school provision ) conditions based on class timetables . Outcome measures were the Children 's Depression Inventory ( Kovacs , 1992 ) ( depressive symptoms , primary outcome ) ; Revised Children 's Manifest Anxiety Scale ( C. R. Reynolds & Richmond , 1985 ) ( anxiety ) ; and child-reported Goodman ( 1997 ) Strengths and Difficulties Question naire ( behavior ) . Students were surveyed at baseline , postintervention , 1-year follow-up , and 2-year follow-up . RESULTS At postintervention , UKRP students reported lower levels of depressive symptoms than control group students , but the effect was small ( d = 0.093 , 95 % CI [ -0.178 , -0.007 ] , p = .034 ) and did not persist to 1-year or 2-year follow-ups . There was no significant impact on symptoms of anxiety or behavior at any point . CONCLUSIONS UKRP produced small , short-term impacts on depression symptoms and did not reduce anxiety or behavioral problems . These findings suggest that interventions may produce reduced impacts when rolled out and taught by regular school staff . We discuss the implication s of these findings for policy and for future dissemination efforts BACKGROUND Anxiety in children is common , impairs everyday functioning , and increases the risk of severe mental health disorders in adulthood . We investigated the effect of a classroom-based cognitive behaviour therapy prevention programme ( FRIENDS ) on anxiety symptoms in children . METHODS Preventing Anxiety in Children though Education in Schools ( PACES ) is a three-group parallel cluster r and omised controlled trial . Interventions were given between September , 2011 , and July , 2012 , with schools as the unit of allocation and individual participants as the unit of analysis . We enrolled state-funded junior schools in southwest Engl and . We sent information to all eligible schools ( state-funded junior schools in southwest Engl and ) inviting them to enrol in the study . School year groups were assigned by computer-generated r and omisation ( 1:1:1 ) to receive either school-led FRIENDS ( led by teacher or school staff member ) , health-led FRIENDS ( led by two trained health facilitators ) , or usual school provision . Children were not masked to treatment allocation . The allocated programme was given to all students ( aged 9 - 10 years ) in the school year ( ie , universal delivery ) as part of the school curriculum as nine , 60 min weekly sessions . Outcomes were collected by self-completed question naire administered by research ers masked to allocation . Primary outcome was symptoms of anxiety and low mood at 12 months assessed by the Revised Child Anxiety and Depression Scale ( RCADS 30 ) . Analyses were intention to treat and accounted for the clustered nature of the design . The study is registered , number IS RCT N23563048 . FINDINGS 45 schools were enrolled : 14 ( n=497 children ) were r and omly assigned to school-led FRIENDS , 14 ( n=509 ) to health-led FRIENDS , and 12 ( n=442 ) to usual school provision . 1257 ( 92 % ) children completed 12 month assessment s ( 449 in health-led FRIENDS , 436 in school-led FRIENDS , and 372 in usual school provision ) . We recorded a difference at 12 months in adjusted mean child-reported RCADS scores for health-led versus school-led FRIENDS ( 19·49 [ SD 14·81 ] vs 22·86 [ 15·24 ] ; adjusted difference -3·91 , 95 % CI -6·48 to -1·35 ; p=0·0004 ) and health-led FRIENDS versus usual school provision ( 19·49 [ 14·81 ] vs 22·48 [ 15·74 ] ; -2·66 , -5·22 to -0·09 ; p=0·043 ) . We noted no differences in parent or teacher ratings . Training teachers to deliver mental health programmes was not as effective as delivery by health professionals . INTERPRETATION Universally delivered anxiety prevention programmes can be effective when used in schools . However , programme effectiveness varies depending on who delivers them . FUNDING National Institute for Health Research Public Health Research Programme Objectives To investigate whether intergroup contact in addition to education is more effective than education alone in reducing stigma of mental illness in adolescents . Design A pragmatic cluster r and omised controlled trial compared education alone with education plus contact . Blocking was used to r and omly stratify classes within schools to condition . R and om allocation was concealed , generated by a computer algorithm , and undertaken after pretest . Data was collected at pretest and 2-week follow-up . Analyses use an intention-to-treat basis . Setting Secondary schools in Birmingham , UK . Participants The parents and guardians of all students in year 8 ( age 12–13 years ) were approached to take part . Interventions A 1-day educational programme in each school led by mental health professional staff . Students in the ‘ contact ’ condition received an interactive session with a young person with lived experience of mental illness . Outcomes The primary outcome was students ’ attitudinal stigma of mental illness . Secondary outcomes included knowledge-based stigma , mental health literacy , emotional well-being and resilience , and help-seeking attitudes . Results Participants were recruited between 1 May 2011 and 30 April 2012 . 769 participants completed the pretest and were r and omised to condition . 657 ( 85 % ) provided follow-up data . At 2-week follow-up , attitudinal stigma improved in both conditions with no significant effect of condition ( 95 % CI −0.40 to 0.22 , p=0.5 , d=0.01 ) . Significant improvements were found in the education-alone condition compared with the contact and education condition for the secondary outcomes of knowledge-based stigma , mental health literacy , emotional well-being and resilience , and help-seeking attitudes . Conclusions Contact was found to reduce the impact of the intervention for a number of outcomes . Caution is advised before employing intergroup contact with younger student age groups . The education intervention appeared to be successful in reducing stigma , promoting mental health knowledge , and increasing mental health literacy , as well as improving emotional well-being and resilience . A larger trial is needed to confirm these results . Trial registration number IS RCT N07406026 ; Results BACKGROUND Mindfulness-based approaches for adults are effective at enhancing mental health , but few controlled trials have evaluated their effectiveness among young people . AIMS To assess the acceptability and efficacy of a schools-based universal mindfulness intervention to enhance mental health and well-being . METHOD A total of 522 young people aged 12 - 16 in 12 secondary schools either participated in the Mindfulness in Schools Programme ( intervention ) or took part in the usual school curriculum ( control ) . RESULTS Rates of acceptability were high . Relative to the controls , and after adjusting for baseline imbalances , children who participated in the intervention reported fewer depressive symptoms post-treatment ( P = 0.004 ) and at follow-up ( P = 0.005 ) and lower stress ( P = 0.05 ) and greater well-being ( P = 0.05 ) at follow-up . The degree to which students in the intervention group practised the mindfulness skills was associated with better well-being ( P<0.001 ) and less stress ( P = 0.03 ) at 3-month follow-up . CONCLUSIONS The findings provide promising evidence of the programme 's acceptability and efficacy Background Effective methods to prevent adolescent depressive symptoms could reduce suffering and burden across the lifespan . However , psychological interventions delivered to adolescents show efficacy only in symptomatic or high-risk youth . Targeting causal risk factors and assessing mechanistic change can help devise efficacious universal or classroom based prevention programs . Methods A non-r and omized longitudinal design was used to compare three classroom-based prevention programs for adolescent depression ( Behavioral Activation with Reward Processing , “ Thinking about Reward in Young People ” ( TRY ) ; Cognitive Behavioral Therapy ( CBT ) and Mindfulness Based Cognitive Therapy ( MBCT ) ) , and determine cognitive mechanisms of change in these programs . Cognitive mechanisms examined were reward-seeking , negative self-beliefs ( assessed with behavioral tasks ) and over-general autobiographical memory . 256 healthy adolescents aged 13–14 participated with 236 ( 92 % ) and 227 ( 89 % ) completing the pre- and post- assessment s. Results TRY was the only intervention associated with a reduction in depressive symptoms at follow-up . Reward-seeking increased following TRY . In the other programs there were non-significant changes in cognitive mechanisms , with more reflective negative self-beliefs in CBT and fewer over-general autobiographical memories in MBCT In the TRY program , which focused on increasing sensitivity to rewarding activities , reward seeking increased and this was associated with decreased depressive symptoms . Limitations Due to the infeasibility of a cluster r and omized controlled trial , a non-r and omized design was used . Conclusions Increased reward-seeking was associated with decreased depressive symptoms and may be a mechanism of depressive symptom change in the intervention with a focus on enhancing sensitivity and awareness of reward . This study provides preliminary evidence to suggest that incorporating activities to enhance reward sensitivity may be fruitful in r and omized controlled trials of universal prevention programs for depression 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 Research suggests that the sequelae of childhood anxiety disorders , if left untreated , can include chronic anxiety , depression , and substance abuse . The current study evaluated the maintenance of outcomes of children who received a 16-week cognitive-behavioral treatment for primary anxiety disorders ( generalized , separation , and social anxiety disorders ) an average of 7.4 years earlier . The 86 participants ( ages 15 to 22 years ; 91 % of the original sample ) and their parents completed diagnostic interviews and self- and parent-report measures . According to the diagnostic interviews , a meaningful percentage of participants maintained significant improvements in anxiety at long-term follow-up . With regard to sequelae , positive responders to anxiety treatment , as compared with less positive responders , had a reduced amount of substance use involvement and related problems at long-term follow-up . The findings are discussed with regard to child anxiety and some of its sequelae |
1,730 | 18,254,017 | No significant change in or total or HDL cholesterol , HbA1c , fasting glucose , fasting insulin or body weight was observed .
The increase in VLDL remained significant only in trials of longer duration and in hypertriglyceridemic patients .
The elevation in LDL cholesterol was non-significant in subgroup analyses .
No adverse effects of the intervention were reported .
Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL cholesterol , but may raise LDL cholesterol ( although results were non-significant in subgroups ) and has no statistically significant effect on glycemic control or fasting insulin . | BACKGROUND People with type 2 diabetes mellitus are at increased risk from cardiovascular disease .
Dietary omega-3 polyunsaturated fatty acids ( PUFAs ) are known to reduce triglyceride levels , but their impact on cholesterol levels , glycemic control and vascular outcomes are not well known .
OBJECTIVES To determine the effects of omega-3 PUFA supplementation on cardiovascular outcomes , cholesterol levels and glycemic control in people with type 2 diabetes mellitus . | In a double-blind , placebo-controlled study we investigated the effects of dietary fish oil supplementation on arterial wall characteristics in 20 patients with non-insulin-dependent diabetes mellitus . Estimates reflecting compliance values in the large arteries and more peripheral vasculature , as measured by pulse-contour analysis , improved significantly after 6 weeks of fish oil therapy compared with values recorded at baseline and after 6 weeks ' administration of olive oil . The large-artery compliance estimate increased from 1.50 ( confidence interval [ CI ] , 1.31 to 1.69 ) mL/mm Hg at baseline to 1.68 ( CI , 1.52 to 1.84 ) mL/mm Hg after fish oil administration ( P < .01 ) . The oscillatory compliance value increased from 0.015 ( CI , 0.011 to 0.019 ) mL/mm Hg at baseline to 0.022 ( CI , 0.016 to 0.028 ) mL/mm Hg after fish oil ingestion ( P < .05 ) . No changes occurred in arterial blood pressure , cardiac output , stroke volume , or systemic vascular resistance with either intervention . The improved compliance estimates with fish oil ingestion occurred without altering fasting blood glucose and cholesterol concentrations . These results support the hypothesis that fish oils alter vascular reactivity and favorably influence arterial wall characteristics in patients with non-insulin-dependent diabetes mellitus . These direct vascular effects , expressed at the level of the vessel wall , may contribute to the cardioprotective actions of fish oil in humans Objective : Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus . However , fish oil may have deleterious effects on lipid peroxidation and glycemic control . Design : In this study , 44 type 2 diabetic patients were r and omized to vitamin E st and ardized ( 53.6 mg/day ) supplementation ( capsules ) with 4 g daily of either fish oil ( n=23 ) or corn oil ( n=21 ) for 8 weeks preceded by a 4 week run-in period of corn oil supplementation . LDL was isolated by density gradient ultracentrifugation and oxidized in vitro with Cu2 + . As a marker of in vivo oxidation malondialdehyde concentration in LDL ( LDL-MDA ) was measured . Results : Fish oil reduced both mean lag time ( before , 57.8 ; after , 48.8 min , P<0.001 ) and mean propagation rate ( before , 0.018 ΔOD/min ; after , 0.015 ΔOD/min , P<0.001 ) , whereas corn oil had no influence on lag time and propagation rate . The changes in lag time and propagation rate differed significantly between fish oil and corn oil treatment . LDL-MDA changes differed borderline significantly between groups ( FO , 110.4 pmol/mg protein ; CO , 6.7 pmol/mg protein ; P=0.057 ) . Fish oil supplementation had no influence on glycemic control as assessed from HbA1c and fasting blood glucose . Conclusion : According to our findings , fish oil supplementation leads to increased in vivo oxidation and increased in vitro oxidation susceptibility of LDL particles . More studies are needed to clarify the clinical importance of this finding . Sponsorship : Financially supported by The Danish Heart Association and Dansk Droge A/S. Dansk Droge A/S generously provided the fish oil and corn oil capsules Summary This study was conducted to examine the effect of ω3 fatty acid supplementation on plasma lipid , cholesterol and lipoprotein fatty acid content of non-insulin-dependent diabetic individuals consuming a higher ( 0.65 , n = 10 ) or lower ( 0.44 , n = 18 ) ratio of dietary polyunsaturated to saturated fatty acid ( P/S ) . The participants were initially given an olive oil supplement ( placebo ) equivalent to 35 mg of 18:1 · kg body weight–1 · day–1 for 3 months . This was followed by two ω3 supplement periods in a r and omized crossover . In these 3-month periods , participants were given a linseed oil supplement equivalent to 35 mg of 18:3ω3 · kg body weight–1 · day–1 or a fish oil supplement equivalent to 35 mg of 20:5ω3 + 22:6ω3 · kg body weight–1 · day–1 . At the end of each supplement period , a blood sample was drawn from each participant for lipid , lipoprotein , insulin , glucagon and C-peptide analyses . At the end of each 3-month period a 7-day dietary record was completed to calculate dietary fat intake and P/S ratio . Results indicate that fish oil significantly reduced plasma triacylglycerol level ( p < 0.05 ) and increased 20:5ω3 and 22:6ω3 content of all lipoprotein lipid classes . Linolenic acid supplementation had no effect on plasma triacylglycerol level , but it increased 18:3ω3 content of lipoprotein cholesterol ester fractions ( p < 0.05 ) . A slight increase in 20:5ω3 , but not 22:6ω3 , content was noted in lipoprotein lipid classes as a result of 18:3ω3 supplementation . LDL and HDL cholesterol , insulin , glucagon and C-peptide levels were not affected by either ω3 supplement . It is concluded that a modest intake of ω3 fatty acids , such as could be obtained from consuming fish regularly , will reduce plasma triglyceride level without affecting LDL or HDL cholesterol levels . [ Diabetologia ( 1997 ) 40 : 45–52 The study assessed the efficacy of fish oil supplementation in counteracting the classic dyslipidemia of the atherogenic lipoprotein phenotype ( ALP ) . In addition , the impact of the common apolipoprotein E ( apoE ) polymorphism on the fasting and postpr and ial lipid profile and on responsiveness to the dietary intervention was established . Fifty-five ALP males ( aged 34 to 69 years , body mass index 22 to 35 kg/m(2 ) , triglyceride [ TG ] levels 1.5 to 4.0 mmol/L , high density lipoprotein cholesterol [ HDL-C ] < 1.1 mmol/l , and percent low density lipoprotein [LDL]-3 > 40 % total LDL ) completed a r and omized placebo-controlled crossover trial of fish oil ( 3.0 g eicosapentaenoic acid/docosahexaenoic acid per day ) and placebo ( olive oil ) capsules with the 6-week treatment arms separated by a 12-week washout period . In addition to fasting blood sample s , at the end of each intervention arm , a postpr and ial assessment of lipid metabolism was carried out . Fish oil supplementation result ed in a reduction in fasting TG level of 35 % ( P<0.001 ) , in postpr and ial TG response of 26 % ( TG area under the curve , P<0.001 ) , and in percent LDL-3 of 26 % ( P<0.05 ) . However , no change in HDL-C levels was evident ( P=0.752 ) . ANCOVA showed that baseline HDL-C levels were significantly lower in apoE4 carriers ( P=0.035 ) . The apoE genotype also had a striking impact on lipid responses to fish oil intervention . Individuals with an apoE2 allele displayed a marked reduction in postpr and ial incremental TG response ( TG incremental area under the curve , P=0.023 ) and a trend toward an increase in lipoprotein lipase activity relative to non-E2 carriers . In apoE4 individuals , a significant increase in total cholesterol and a trend toward a reduction in HDL-C relative to the common homozygous E3/E3 profile was evident . Our data demonstrate the efficacy of fish oil fatty acids in counteracting the proatherogenic lipid profile of the ALP but also that the apoE genotype influences responsiveness to this dietary treatment BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration Eicosapentaenoic acid ( EPA ) ethyl ester ( 1.8 g/d ) was administered to 16 diabetic patients ( 5 insulin-dependent and 11 noninsulin-dependent diabetics ) for 6 mon . EPA in total plasma fatty acids increased from 4.0±2.4 mol% ( mean±SD ) to 7.5±3.1 mol% ( p<0.001 ) . Albumin excretion , measured with spot urine , was significantly reduced from 65 to 36 mg/g creatinine ( geometric means , p<0.001 ) . Fasting blood sugar levels , glycohemoglobin , body weight and blood pressure did not change significantly during the study . There were also no significant changes in serum levels of creatinine , urea nitrogen , total cholesterol and triglycerides . Although no overt hemorrhage was observed in the patients , hematocrit was reduced from 42.6±2.8 % to 41.0±3.9 % ( p<0.02 ) . Ten other similar diabetic patients ( 4 insulin-dependent and 6 non-insulin-dependent diabetics ) were followed as a reference group , not concomitantly , for 6 mon with neither EPA ethyl ester nor placebo . The parameters mentioned above were not changed significantly in this group during 6 mon . EPA administration might retard the appearance of overt diabetic nephropathy The short-term effect of high fiber intake on fish-oil treatment in 15 free-living , non-insulin-dependent diabetic patients was evaluated by using a controlled , sequential study design . During an 8-wk fish-oil-treatment period when patients received 20 g fish oil/d , the usual daily fiber intake was increased with a 15-g pectin supplement at midpoint . Fish oil alone lowered triacylglycerol and very-low-density-lipoprotein-cholesterol concentrations by 41 % and 36 % , respectively ( both P < 0.01 by the end of the treatment period ) with unchanged mean total , low-density- , and high-density-lipoprotein-cholesterol concentrations . When the fiber intake was increased , however , total and low-density-lipoprotein-cholesterol concentrations decreased significantly ( P < 0.001 and < 0.05 , respectively ) with fish-oil treatment . The cholesterol ester fraction of plasma lipids was reduced by 34 % when compared with fish oil alone ( P < 0.05 ) . The plasma triacylglycerol fraction decreased further by 44 % ( P < 0.001 ) . Other beneficial effects observed included a 30 % decline in the fatty acid fraction ( P < 0.002 ) by end of the treatment period . Diabetic control was maintained during the 12-wk study . In conclusion , a high fiber intake may be beneficial in fish oil-treated diabetic patients Fish-oil supplementation decreases serum triacylglycerols but may worsen hyperglycemia in patients with non-insulin-dependent diabetes mellitus . The reason for the possible deterioration of glycemia is unclear . We examined whether inhibition of triacylglycerol synthesis by n-3 fatty acids changes lipolysis , glycerol gluconeogenesis , or fatty acid oxidation . Nine obese patients with non-insulin-dependent diabetes mellitus participated in a r and omized double-blind crossover study in which 6 wk of n-3 fatty acid supplementation ( 12 g fish oil ) was compared with 6 wk of corn plus olive oil . Serum triacylglycerols decreased by 30 % during n-3 fatty acid supplementation . Glycerol gluconeogenesis ( [U-14C]glycerol ) increased by 32 % . However , overall glucose production ( [3 - 3H]glucose ) , glycemic control , and fatty acid oxidation remained unchanged . Thus , 6 wk of n-3 fatty acid supplementation lowers triacylglycerols in patients with non-insulin-dependent diabetes mellitus without worsening glycemic control . However , n-3 fatty acid supplementation increases glycerol gluconeogenesis , which could contribute to deterioration of glycemic control during long-term treatment with high doses of fish-oil supplements A multicenter , r and omized , double-blind , place-bo-controlled study evaluated the possible worsening of glycemic control after a moderate daily intake of n-3 fatty acid ethyl esters in patients with hypertriglyceridemia with and without glucose intolerance or diabetes . A total of 935 patients of both sexes in 63 Italian clinical centers were selected ; 55 % had either impaired glucose tolerance or non-insulin-dependent diabetes mellitus ( NIDDM ) . They received for 2 mo either 1 g n-3 ethyl esters three times a day or a corresponding placebo , followed by 4 mo of either 1 g n-3 ethyl esters twice a day or placebo . In addition to the complete lipid and lipoprotein evaluation , patients with impaired glucose tolerance also underwent an oral-glucose-tolerance test ; in patients with NIDDM , serum insulin and glycated hemoglobin ( Hb A1c ) concentrations were determined . Plasma triacylglycerol concentrations decreased significantly , up to 21.53 % at 6 mo compared with baseline ( decreased 15 % compared with placebo ) , with a tendency toward a progressive reduction with time . There was no evidence for a different response in patients with either NIDDM or impaired glucose tolerance . Among NIDDM patients , the triacylglycerol reduction was greater in those with high-density-lipoprotein cholesterol < or = 0.91 mmol/L. There was no alteration in the major glycemic indexes : fasting glucose , Hb A1c , insulinemia , and oral glucose tolerance in patients with impaired glucose tolerance or NIDDM after treatment with n-3 ethyl esters . Treatment with a moderate daily dose of n-3 ethyl esters over a prolonged period of time significantly reduced triacylglycerol concentrations without any worsening of glucose tolerance in patients with hypertriglyceridemia with and without impaired glycemic regulation BACKGROUND Regular consumption of n-3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk . OBJECTIVE This study aim ed to determine whether eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids have differential effects on serum lipids and lipoproteins , glucose , and insulin in humans . DESIGN In a double-blind , placebo-controlled trial of parallel design , 59 overweight , nonsmoking , mildly hyperlipidemic men were r and omly assigned to receive 4 g purified EPA , DHA , or olive oil ( placebo ) daily while continuing their usual diets for 6 wk . RESULTS Fifty-six men aged 48.8 + /- 1.1 y completed the study . Relative to those in the olive oil group , triacylglycerols fell by 0.45 + /- 0.15 mmol/L ( approximately 20 % ; P = 0.003 ) in the DHA group and by 0.37 + /- 0.14 mmol/L ( approximately 18 % ; P = 0.012 ) in the EPA group . Neither EPA nor DHA had any effect on total cholesterol . LDL , HDL , and HDL(2 ) cholesterol were not affected significantly by EPA , but HDL(3 ) cholesterol decreased significantly ( 6.7 % ; P = 0.032 ) . Although HDL cholesterol was not significantly increased by DHA ( 3 . 1 % ) , HDL(2 ) cholesterol increased by approximately 29 % ( P = 0.004 ) . DHA increased LDL cholesterol by 8 % ( P = 0.019 ) . Adjusted LDL particle size increased by 0.25 + /- 0.08 nm ( P = 0.002 ) with DHA but not with EPA . EPA supplementation increased plasma and platelet phospholipid EPA but reduced DHA . DHA supplementation increased DHA and EPA in plasma and platelet phospholipids . Both EPA and DHA increased fasting insulin significantly . EPA , but not DHA , tended to increase fasting glucose , but not significantly so . CONCLUSIONS EPA and DHA had differential effects on lipids , fatty acids , and glucose metabolism in overweight men with mild hyperlipidemia BACKGROUND Long-chain n-3 polyunsaturated fatty acids have variable effects on LDL cholesterol , and the effects of docosahexaenoic acid ( DHA ) are uncertain . OBJECTIVE The objective of the study was to determine the effect on blood lipids of a daily intake of 0.7 g DHA as triacylglycerol in middle-aged men and women . DESIGN Men and women aged 40 - 65 y ( n = 38 ) underwent a double-blind , r and omized , placebo-controlled , crossover trial of treatment with 0.7 g DHA/d for 3 mo . RESULTS DHA supplementation increased the DHA concentration in plasma by 76 % ( P < 0.0001 ) and the proportion in erythrocyte lipids by 58 % ( P < 0.0001 ) . Values for serum total cholesterol , LDL cholesterol , and plasma apolipoprotein B concentrations were 4.2 % ( 0.22 mmol/L ; P = 0.04 ) , 7.1 % ( 0.23 mmol/L ; P = 0.004 ) , and 3.4 % ( P = 0.03 ) higher , respectively , with DHA treatment than with placebo . In addition , the LDL cholesterol : apolipoprotein B ratio was 3.1 % higher with DHA treatment than with placebo ( P = 0.04 ) , which suggested an increase in LDL size . Plasma lathosterol and plant sterol concentrations were unaffected by treatment . CONCLUSION A daily intake of approximately 0.7 g DHA increases LDL cholesterol by 7 % in middle-aged men and women . It is suggested that DHA down-regulates the expression of the LDL receptor Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat , high complex carbohydrate diet . Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation ; plasma total and HDL cholesterol concentrations did not change . The LDL cholesterol level was significantly increased with fish oil supplementation , suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and /or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease . The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein ( LDL ) oxidation was examined in 20 treated hypertensive subjects . The r and omized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil . Fish oil significantly ( -24 % , P < 0.01 ) reduced plasma triglyceride , and increased LDL-cholesterol ( + 6 % , P < 0.01 compared to corn oil ) . LDL particles were larger ( P < 0.01 ) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride ( P < 0.001 ) both before and after fish oil supplementation , and positively correlated with high density lipoprotein cholesterol ( P < 0.01 ) . Fish oil reduced lag time before onset of copper-induced LDL oxidation ( -25 % , P < 0.001 ) and significantly increased production of thiobarbituric acid-reactive substances ( TBARS ) during oxidation , compared with corn oil . Corn oil had no significant effect on lag time and oxidation rate . Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL . Corn oil was without effect . Additionally , macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly ( P < 0.001 ) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids . We conclude that from the st and point of atherosclerosis , fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable OBJECTIVE To determine whether serum lipid intervention , in addition to conventional diabetes treatment , could alter cardiovascular outcomes in type 2 diabetes . RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects ( 117 men , 47 women ) without a history of clinical cardiovascular disease r and omized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospect ively for a minimum of 3 years . Serial biochemical and noninvasive vascular assessment s , carotid and femoral artery B-mode ultrasound measurements , and those pertaining to coronary heart disease (CHD)— clinical history , the World Health Organization ( WHO ) cardiovascular question naire , and resting and exercise electrocardiogram (ECG)—were recorded . RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride ( −32 vs. 4 % , P = 0.001 ) , total cholesterol ( −7 vs. −0.3 % , P = 0.004 ) , and total−to-HDL cholesterol ratio ( −12 vs. −0.0 % , P = 0.001 ) , and an increase in HDL cholesterol ( 6 vs. −2 % , P = 0.02 ) as compared with placebo . There was a trend toward a greater reduction of fibrinogen ( −18 vs. −6 % , P = 0.08 ) at 3 years . No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease . In those treated with bezafibrate , there was a significant reduction ( P = 0.01 , log-rank test ) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infa rct ion . CONCLUSIONS Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease , although the lower rate of “ definite CHD events ” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease The metabolic effect of 3-week dietary supplementation with a fish oil concentrate was examined in not markedly obese , not hypertriglyceridemic men with non-insulin-dependent diabetes mellitus ( NIDDM ) treated with hypoglycemic agents . Ten patients were given 15 ml/d of fish oil ( Martens Oil , Norway ) equivalent to 3.1 g of n-3 fatty acid ( FA ) per day , and compared to 10 diabetics treated with placebo ( 15 ml/d saline ) . While fish oil leads to expected increase in the ratio of n-3 to n-6 FA intake , it does not alter fasting and mixed meal stimulated blood glucose , plasma insulin and C-peptide concentrations . There were no changes in insulin action estimated by the metabolic clearance rates of glucose at plasma insulin levels of about 100 microU/ml and 1400 microU/ml during hyperinsulinemic isoglycemic clamp , and no changes were seen in insulin binding to erythrocytes . Even though our short-term study does not warrant authoritative conclusions , no adverse effects of low-dose fish oil on glucose homeostasis have been found in not markedly obese NIDDM patients treated with oral hypoglycemics OBJECTIVE The increased risk of coronary heart disease associated with type 2 diabetes may be partially explained by dyslipidemia characterized by high plasma triacylglycerol ( TAG ) , low HDL cholesterol , and a predominance of atherogenic small dense LDLs . Fish oil reduces plasma TAG and has previously been shown to improve the distribution of LDL subclasses in healthy subjects and might , therefore , be a good nonpharmacological treatment for type 2 diabetic patients . In the present study , we investigate the effect of fish oil supplementation on the fasting lipid profile , including LDL and HDL subclasses . RESEARCH DESIGN AND METHODS A total of 42 type 2 diabetic patients were r and omized to supplementation ( capsules ) with 4 g daily of either fish oil ( n = 20 ) or corn oil ( n = 22 ) for 8 weeks preceded by a 4-week run-in period of corn oil supplementation . Blood was drawn before and after the 8-week intervention period . Plasma lipoproteins , including LDL and HDL subclasses , were separated by ultracentrifugation . RESULTS Fish oil lowered TAG ( group difference : P = 0.025 ) and raised HDL-2b cholesterol ( P = 0.012 ) and HDL-2a cholesterol ( P = 0.007 ) concentrations as compared with corn oil . We observed no significant effects of fish oil on LDL cholesterol , HDL cholesterol , or the concentration of small dense LDL particles . CONCLUSIONS Fish oil supplementation may partially correct the dyslipidemia of type 2 diabetic patients . However , the putative very important aspect of diabetic dyslipidemia-the predominance of small dense LDL particles-was unaffected by fish oil OBJECTIVE Supplementation of type II diabetic diets with n-3 fatty acids ( FAs ) from fish oil ( FO ) has been associated with lowered triglyceride and VLDL levels , although reports of impaired glycemic control have limited their use . Effects of n-3FAs from nonmarine sources are less well documented . Therefore , an investigation comparing the effects of linseed oil ( LO ) with FO supplementation was undertaken in subjects with type II diabetes . RESEARCH DESIGN AND METHODS Eleven subjects with type II diabetes were given supplements with LO and FO for 3 months each in a r and omized double-blind crossover fashion after 3 months of olive oil placebo . Oils were given as 35 mg FA · kg body wt−1 · day−1 . After each 3-month period , fasting glucose and insulin levels , HbA1c , lipid profiles , insulin sensitivity ( SI ) , glucose effectiveness ( SG ) , and acute insulin response to glucose ( AIRG ) were evaluated . RESULTS HbA1c and lipid values were within the normal range at r and omization . Repeated measures analysis of variance testing found no significant differences in weight ; fasting glucose and insulin levels ; HbA1c ; total , LDL , and HDL cholesterol levels ; SI ; SG ; or AIRG with either active oil . FO was associated with significant reductions in triglycerides and a trend toward decreased SI . CONCLUSIONS In a population with well-controlled type II diabetes , 3 months of FO but not LO result ed in lowered triglyceride levels . Neither LO nor FO significantly affected glycemic control , cholesterol values , SG , or insulin secretion , while a nonsignificant trend toward decreased insulin sensitivity was found with FO Non-insulin-dependent diabetes mellitus ( NIDDM ) is associated with increased very-low-density lipoprotein ( VLDL ) and triglyceride concentrations as abnormalities of low-density lipoprotein ( LDL ) composition . Because fish oil has a strong triglyceride lowering effect in case of normolipemic subjects , we investigated the influence of supplementary fish oil diet in patients suffering from NIDDM ( n = 19 ) , who until now were not treated by drugs but only by diet . The study was started with a placebo-run-in-period for four weeks ( phase I , 6 g rape seed oil capsules/d ) , followed by a verum period for twelve weeks ( phase II , 6 g fish oil concentrate capsules/d ) , and a wash-out-period for four weeks ( phase III , 6 g rape seed oil capsules/d ) . The fish oil supplementation contained at least 3 g eicosapentenoic and docosahexenoic acid . The lipoproteins , apolipoproteins , blood glucose , and insulin level ( fasting and after load test ) were checked at the beginning and at the end of each phase . In comparison to the placebo rape seed oil supplementation , the fish oil diet effected a decrease of serum triglycerides by 29 % . LDL-cholesterol increased by 9 % , HDL-cholesterol by 9 % ( especially HDL2-cholesterol ) , and apolipoprotein B by 4 % . Apolipoprotein A-I was reduced by 9 % . The fasting blood glucose and the glucose load test as the insulin level ( fasting and after load test ) showed no significant changes at the end of the verum period in comparison to the run-in-phase . ( ABSTRACT TRUNCATED AT 250 WORDS Recently , nicotinic acid has been recommended as a first-line hypolipidemic drug . To determine the effectiveness of nicotinic acid in dyslipidemic patients with non-insulin-dependent diabetes mellitus , 13 patients were treated in a r and omized crossover trial . Patients received either nicotinic acid ( 1.5 g three times daily ) or no therapy ( control period ) for 8 weeks each . Compared with the control period , nicotinic acid therapy reduced the plasma total cholesterol level by 24 % , plasma triglyceride level by 45 % , very-low-density lipoprotein cholesterol level by 58 % , and low-density lipoprotein cholesterol level by 15 % , and it increased the high-density lipoprotein cholesterol level by 34 % . However , nicotinic acid therapy result ed in the deterioration of glycemic control , as evidence d by a 16 % increase in mean plasma glucose concentrations , a 21 % increase in glycosylated hemoglobin levels , and the induction of marked glycosuria in some patients . Furthermore , a consistent increase in plasma uric acid levels was observed . Therefore , despite improvement in lipid and lipoprotein concentrations , because of worsening hyperglycemia and the development of hyperuricemia , nicotinic acid must be used with caution in patients with non-insulin-dependent diabetes mellitus with dyslipidemia . We suggest that the drug not be used as a first-line hypolipidemic drug in patients with non-insulin-dependent diabetes mellitus Non-insulin-dependent diabetes mellitus ( NIDDM ) is associated with elevated very-low-density lipoprotein ( VLDL ) triglyceride concentrations and abnormalities of low-density lipoprotein ( LDL ) composition . Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects , we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM . Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design . Medications , including antidiabetic therapy , were continued through the study . Compared with safflower oil treatment , fish oil supplementation result ed in a significant reduction of total plasma triglycerides of 24 % at the 4-g dose and a larger reduction of 39 % at the 7.5-g dose . These decreases were due to similar reductions in VLDL triglycerides . LDL cholesterol levels were mildly elevated , but a larger 20 % increase in LDL apolipoprotein B ( apoB ) concentration was observed . During supplementation with the fish oil concentrate , the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values , but not when compared with safflower oil treatment . Highdensity lipoprotein ( HDL ) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment . At the 7.5-g dose , fasting glucose and glycohemoglobin levels increased by 20 and 12 % , respectively , but were unchanged at the lower level of supplementation . Thus , in NIDDM patients , dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels . However , the observed increase in LDL apoB levels , and the deterioration in glycemic control , indicate thatfurther study will be required to establish whether fish oil has a role in the treatment of NIDDM Dietary cod-liver oil containing eicosapentaenoic acid is effective on microvascular albumin leakage in diabetic patients with albuminuria . We determined the long-term effects of oral pure eicosapentaenoic acid ethyl ( EPA-E : 900 mg/day ) administration on diabetic nephropathy in non-insulin dependent diabetic ( NIDDM ) patients . The effects of EPA-E were determined by observing the changes of the index of urine albumin excretion level/urine creatinine ( Cr ) excretion level ( UAI ) , the ratio of beta 2-microglobulin excretion level/urine Cr excretion level ( beta 2-MG/Cr ) and the ratio of N-acetyl-D-glucosaminidase excretion level/urine Cr excretion level ( NAG/Cr ) at 3 , 6 and 12 months after the start of the treatment . Oral EPA-E administration immediately improved the increased UAI at 3 months after the start of treatment . A significant improvement of the UAI by EPA-E was sustained 12 months later . EPA E administration also tended to decrease the urine beta 2-MG/Cr ratio from 6 months , but the difference was statistically not significant . However , the urine NAG/Cr ratio was not changed by EPA-E administration . EPA-E administration did not affect blood pressure levels , glycemic control and lipid metabolism in these patients . The present data indicated that EPA-E administration improved increased albumin excretion in NIDDM patients with nephropathy and its effects on albuminuria sustained for at least 12 months after the start of treatment . However , tubular factors were not influenced by EPA-E administration Subjects with diabetes have a greatly increased risk of CHD , which is only partially related to their elevated glucose . Other factors such as insulin resistance and dyslipidemia are likely to be important . The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels , although all lipoproteins have compositional abnormalities . Surprisingly few good prospect i ve studies of lipoprotein levels in relation to CHD have been done in diabetic subjects . Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies . In studies in which total cholesterol and triglyceride were done , cholesterol and triglycerides were risk factors for CHD , although triglycerides were often a stronger predictor . However , the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables ( e.g. , hypertension , plasminogen activator inhibitor 1 [ PAI-1 ] , etc . ) . In clinical trials in diabetic subjects , LDL reduction with statins has led to significant reductions in CHD incidence . In addition , overall mortality was reduced with statin therapy , although the results were not statistically significant . Gemfibrozil has led to reductions in CHD incidence in diabetic subjects , although the results were not statistically significant perhaps because of low sample size . Regarding lipoproteins and CHD risk in diabetic patients , the very positive results of statin trials point to LDL cholesterol being more important than previous realized . Apparently , having a borderline high LDL cholesterol ( between 130 and 160 mg/dl ) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject . Therefore , the primary target of therapy in diabetic patients is lowering LDL cholesterol ( or possibly , non-HDL cholesterol ) . Statins are the preferred pharmacological agent in this situation . Once LDL cholesterol levels have been lowered , attention can be given to treatment of residual hypertriglyceridemia and low HDL . The goal here is weight reduction and increased exercise . However , for selected patients , combining a fibric acid ( or low-dose nicotinic acid ) with a statin also can be considered . Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence OBJECTIVE The triglyceride-lowering effects of ω-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM . However , fish oil may impair glycemic control in NIDDM . The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat ( 30 % total energy ) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients . RESEARCH DESIGN AND METHODS In a controlled , 8-week intervention , 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and /or HDL cholesterol < 1.0 mmol/l were r and omly assigned to a low-fat diet ( 30 % daily energy intake ) with or without one fish meal daily ( 3.6 g ω-3/day ) and further r and omized to a moderate ( 55–65 % VO2max ) or light ( heart rate < 100 bpm ) exercise program . An oral glucose tolerance test ( 75 g ) , fasting serum glucose , insulin , lipids , and GHb were measured before and after intervention . Self-monitoring of blood glucose was performed throughout . RESULTS In the 49 subjects who completed the study , moderate exercise improved aerobic fitness ( VO2max ) by 12 % ( from 1.87 to 2.07 l/min , P = 0.0001 ) . Fish consumption reduced triglycerides ( 0.80 mmol/l , P = 0.03 ) and HDL3 cholesterol ( 0.05 mmol/l , P = 0.02 ) and increased HDL2 cholesterol ( 0.06 mmol/l , P = 0.01 ) . After adjustment for age , sex , and changes in body weight , fish diets were associated with increases in GHb ( 0.50 % , P = 0.05 ) and self-monitored glucose ( 0.57 mmol/l , P = 0.0002 ) , which were prevented by moderate exercise . CONCLUSIONS A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients . Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise Summary Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease . Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations , principally by improving the release of nitric oxide from injured endothelium . Using forearm venous occlusion plethysmography we studied vascular responses to 60 , 120 , 180 and 240 nmol/min of acetylcholine ( an endothelium-dependent vasodilator ) and 3 , 6 and 9 nmol/min of glyceryl trinitrate ( an endothelium-independent vasodilator ) infused into the brachial artery in 23 patients with Type 2 ( non-insulin-dependent ) diabetes mellitus . NG monomethyl-l-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium . On completion of the baseline studies patients r and omly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase . Studies , identical to the initial baseline studies , were performed at the end of the active treatment periods at 6 and 18 weeks . Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration ( p<0.01 ) . Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies . NG monomethyl-l-arginine significantly reduced forearm blood flow from maximal stimulated values to acetylcholine when compared to the uninhibited decline in flow to acetylcholine infusions at comparable time points ( p<0.01 ) . Treatment with fish oils improved endothelium-dependent responses to acetylcholine without altering endothelium-independent responses to glyceryl trinitrate . By increasing stimulated nitric oxide release from the endothelium fish oils may afford protection against vasospasm and thrombosis in patients with diabetes mellitus OBJECTIVE To study the effects of a low dose of ω-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellus ( NIDDM ) . RESEARCH DESIGN AND METHODS We performed a r and omized , prospect i ve , double-blind , controlled study of a low dose of ω-3 fatty acids ( 2.5 g/day ) in 20 ambulatory subjects with NIDDM . Subjects ingested five 1-g fish oil capsules each containing 0.5 g ω-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period . RESULTS Nine subjects completed the study in each group . Both groups exhibited moderate control of glucose levels ; modest elevations in baseline total cholesterol , low-density lipoprotein ( LDL ) cholesterol , and triglyceride ( TG ) levels ; and normal blood pressure values . In the fish oil group , plasma ω-3 fatty acid levels increased significantly . Fish oil significantly reduced the slope of the dose-response curves for collagen-induced platelet aggregation to one-third the value observed with safflower oil . No difference was observed in collageninduced production of thromboxane A2 ( TXA2 , measured as the stable derivative TXB2 ) , or in adenosine-5'-diphosphate- ( ADP ) induced platelet aggregation or TXA2 generation . Patients with high initial collagen-induced platelet TXA2 production showed a significantly larger drop after fish oil than safflower oil . Fish oil significantly reduced TG levels by 44 mg/dl and decreased upright systolic blood pressure ( sBP ) by 8 mmHg compared with safflower oil . Fish oil caused a significant but small increase in HbA1c ( 0.56 % ) and total cholesterol ( 20 mg/dl ) but had no effect on fasting glucose , high-density lipoprotein cholesterol , or LDL-cholesterol levels . CONCLUSIONS Small doses of fish oil inhibit platelet aggregation and TXA2 production , reduce upright sBP and TG levels , and have only a small effect on glucose and cholesterol levels in patients with moderately controlled NIDDM . Small quantities of ω-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients Objective : To see whether mortality among men with angina can be reduced by dietary advice . Design : A r and omized controlled factorial trial . Setting : Male patients of general practitioners in south Wales . Subjects : A total of 3114 men under 70 y of age with angina . Interventions : Subjects were r and omly allocated to four groups : ( 1 ) advised to eat two portions of oily fish each week , or to take three fish oil capsules daily ; ( 2 ) advised to eat more fruit , vegetables and oats ; ( 3 ) given both the above types of advice ; and ( 4 ) given no specific dietary advice . Mortality was ascertained after 3–9 y. Results : Compliance was better with the fish advice than with the fruit advice . All-cause mortality was not reduced by either form of advice , and no other effects were attributable to fruit advice . Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised ; the adjusted hazard ratio was 1.26 ( 95 % confidence interval 1.00 , 1.58 ; P=0.047 ) , and even greater for sudden cardiac death ( 1.54 ; 95 % CI 1.06 , 2.23 ; P=0.025 ) . The excess risk was largely located among the subgroup given fish oil capsules . There was no evidence that it was due to interactions with medication . Conclusion : Advice to eat more fruit was poorly complied with and had no detectable effect on mortality . Men advised to eat oily fish , and particularly those supplied with fish oil capsules , had a higher risk of cardiac death . This result is unexplained ; it may arise from risk compensation or some other effect on patients ' or doctors ' behaviour . Sponsorship : British Heart Foundation , Seven Seas Limited , Novex Pharma Limited , The Fish Foundation The effects on lipoprotein and glucose metabolism of addition of n-3 fatty acids were studied in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA ( 3 g n-3 fatty acids ) or placebo ( olive oil ) per day in a r and omized double-blind cross-over study during two consecutive 8-week periods . After MaxEPA treatment , there was a marked increase in long-chain polyunsaturated fatty acids of the n-3 series in the plasma lipid esters and in the platelet phospholipids , while the n-6 fatty acid content decreased . The very low density lipoprotein ( VLDL ) triglyceride concentrations decreased significantly ( by 22 % ) on MaxEPA treatment . However , these changes were not significantly different from those observed during the placebo period . The blood glucose concentration tended to increase during MaxEPA treatment , and to decrease during the placebo period , the changes under the two regimes being significantly different ( P less than 0.01 ) . In addition , the rate constant for glucose disappearance ( k value ) for the intravenous insulin-tolerance test , which reflected the peripheral insulin sensitivity , tended to decrease during MaxEPA treatment and increase during administration of the placebo , there being a significant difference ( P less than 0.03 ) between the changes during the two treatments . The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear The effects of fish oil on lipoprotein subfractions and low density lipoprotein ( LDL ) size in non-insulin-dependent diabetes mellitus ( NIDDM ) patients with hypertriglyceridemia are unknown . To eluci date this , 16 NIDDM hypertriglyceridemic patients ( plasma triglyceride 2.25- 5.65 mmol/l , plasma cholesterol < or = 7.75 mmol/l ) were r and omly assigned to a 6-month period with either moderate amounts of fish oil ( n = 8) or placebo ( n = 8) after 4 weeks of wash-out and 3 weeks of run-in . Diet and hypoglycemic treatment were unchanged throughout the experiment . LDL size were evaluated at baseline and after 6 months . Three VLDL and LDL subfractions were measured at the end of the two periods . The total lipid concentration of all very low density lipoprotein ( VLDL ) subfractions was lower at the end of fish oil treatment compared with placebo ( large VLDL 124.3 + /- 19.7 mg/dl vs 156.7 + /- 45.5 mg/dl ; intermediate VLDL 88.5 + /- 9.5 mg/dl vs 113.9 + /- 23.2 mg/dl ; small VLDL 105.9 + /- 9.7 mg/dl vs 128.9 + /- 40.7 mg/dl ) ( mean + /- SEM ) , although the difference was not statistically significant . Moreover , at the end of the two treatments , the percentage distribution of VLDL subfractions was very similar ( large 37.5 + /- 3.3 % vs 37.6 + /- 2.6 % , intermediate 27.6 + /- 0.9 % vs 31.0 + /- 2.4 % ; small 34.9 + /- 3.7 % vs 31.4 + /- 2.1 % ) . Concerning LDL , no significant change in LDL size was observed after the two treatments ( 255.4 + /- 2.2 A vs 254.2 + /- 1.7 A , fish oil ; 253.7 + /- 2.0 A vs 253.3 + /- 1.7 A , placebo ) . LDL subfraction distribution was also very similar ( large 17 + /- 3 % vs 17 + /- 2 % ; intermediate 62 + /- 3 % vs 65 + /- 3 % ; small 21 + /- 3 % vs 18 + /- 2 % ) , at the end of the two periods , confirming the lack of effects on LDL size . In conclusion , our study indicates that in NIDDM patients with hypertriglyceridemia , fish oil does not induce any improvement in LDL distribution and LDL size despite its positive effects on plasma triglycerides OBJECTIVE To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus ( NIDDM ) . RESEARCH DESIGN AND METHODS Forty subjects ( 18 men and 22 women ; aged 53.9 ± 7.0 years ) with NIDDM and hyperlipidemia were r and omly assigned to one of four treatment groups : 9 g of fish oil , 18 g of fish oil , 9 g of corn oil , or 18 g of corn oil daily supplementation for 12 weeks . RESULTS The level of oil supplements ( 9 g compared with 18 g ) did not have a significant effect within each oil group on glycemic control and lipids . Significant differences ( P < 0.05 ) in lipids were found when the 9-g and 18-g groups were combined . In subjects consuming fish oil , plasma very-low-density lipoprotein ( VLDL ) cholesterol ( P = 0.0001 ) , plasma triglyceride ( TG ) ( P = 0.0001 ) , and plasma VLDL TGs ( P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks ) were significantly lowered compared with subjects consuming corn oil . Plasma VLDL cholesterol increased across time in the corn oil group ( P = 0.04 ) . Plasma low-density lipoprotein ( LDL ) cholesterol was temporarily increased ( P = 0.008 ) in the fish oil group at 6 weeks , but the effect was no longer present at 12 weeks . No significant differences between fish oil – or corn oil-supplemented diets were found in total plasma cholesterol , high-density lipoprotein cholesterol , fasting plasma glucose , glycosylated HbA1c , weight , and blood pressure . CONCLUSIONS In this study , fish oil supplementation improved plasma VLDL cholesterol , VLDL TGs , and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM . Furthermore , fish oil supplementation had no significant deleterious effect on glycemic control OBJECTIVE To examine the association of seal oil and salmon consumption with impaired glucose tolerance ( IGT ) and non-insulin-dependent diabetes mellitus ( NIDDM ) among Alaska Natives . RESEARCH DESIGN AND METHODS Screening was performed on 666 Yup'ik Eskimos and Athabaskan Indians ≥40 years old in 15 villages . Self-administered question naires were used to obtain partial food frequency data . A case was defined as IGT or NIDDM , either newly discovered or known . Newly discovered cases ( 11 patients with NIDDM and 17 with IGT ) were determined by r and om blood glucose testing followed by a 2-h 75-g oral glucose tolerance test ( OGTT ) for those with values ≥ 6.72 mmol/l or for subjects with unconfirmed histories of glucose intolerance . Known cases included 26 patients with NIDDM and 1 with IGT . Control subjects had r and om blood glucoses < 6.72 or normal OGTT results . RESULTS Compared with less-than-daily consumption , both daily seal oil ( odds ratio [ OR ] 0.2 , 95 % confidence interval [ CI ] 0.1–0.8 ) and daily salmon consumption ( OR 0.5 , CI 0.2–1.1 ) were associated with a lower prevalence of glucose intolerance , controlling for age , ethnicity , body mass index , and sex . The effects were similar when limited to newly discovered cases : OR 0.3 , CI 0.1–1.3 for seal oil and OR 0.4 , CI 0.1–1.3 for salmon . Consumption of seal oil at least five times per week was required to reduce risk . CONCLUSIONS Consumption of seal oil and salmon , high in ω-3 fatty acids , appears to lower the risk of glucose intolerance and is a potentially modifiable risk factor for NIDDM in Alaska Natives n-3 Fatty acids in the form of ethyl esters ( EE ) allow lower daily doses and improved compliance . Administration of n-3 fatty acids to patients with glucose intolerance has led to controversial findings , some studies indicating worsening of the disorder , others no effect , or an improvement . A total of 935 patients with hypertriglyceridemia , associated with additional cardiovascular risk factors , i.e. glucose intolerance , NIDDM and /or arterial hypertension were entered a double blind ( DB ) protocol lasting 6 months with n-3 EE versus placebo , followed by a further 6 months of open study ( n = 868 ) on 2 g a day of n-3 EE . At the end of the DB period , triglyceridemia in the total group was reduced significantly more by n-3 EE , without alterations in glycemic parameters . In the 6 months open follow up , patients on n-3 EE with type IIB hyperlipoproteinemia showed a significant reduction of total cholesterol , both in cases with ( -4.15 % vs. the 6 month levels ) and without NIDDM ( -3.8 % ) . HDL-cholesterol had an overall mean rise of 7.4 % , maximal in type IV patients with ( + 9.1 % ) and without ( + 10.1 % ) NIDDM . No alterations in glycemic parameters were detected in treated patients . Administration of n-3 EE to patients with hypertriglyceridemia associated with NIDDM or impaired glucose tolerance appears safe and effective Lipid peroxidation may be important in the development of cardiovascular disease , a common cause of mortality and morbidity in non-insulin dependent diabetes mellitus ( NIDDM ) . We assessed the degree of lipid peroxidation by measuring plasma malondialdehyde , as thiobarbituric acid reacting substances ( TBARS ) , in 23 non-insulin diabetic patients . Plasma levels of st and ardised alpha-tocopherol ( vitamin E ) , lipid content of whole plasma and lipoprotein fractions , glycosylated haemoglobin , glycosylated low density lipoprotein ( LDL ) and fasting blood glucose were also measured . On completion of the baseline studies patients r and omly received either fish oil or matching olive oil capsules in a double blind crossover fashion for 6 weeks followed by a 6 week washout period and a final 6 week treatment phase . Studies , identical to the initial baseline studies , were performed at the end of the of the active treatment periods at 6 and 18 weeks . Treatment with olive oil did not change levels of TBARS , vitamin E or indices of glycaemic control compared with baseline . Total cholesterol and triglyceride ( TG ) content of plasma and lipoprotein fractions were not significantly altered . Treatment with fish oil result ed in elevation of TBARS ( P < 0.001 ) and reduction of vitamin E ( P < 0.01 ) compared with baseline and olive oil treatment . Plasma cholesterol was unchanged . A reduction in plasma TG compared with baseline occurred but failed to reach significance ( P = 0.07 ) . Changes in apo B containing lipoproteins induced by fish oil failed to reach significance . No significant changes were observed in concentration or composition of high density lipoprotein ( HDL ) . Fish oil treatment showed no change in glycaemic control as assessed by glycosylated haemoglobin and LDL although a rise in fasting blood glucose just failed to reach significance ( P = 0.06 ) . Lipid peroxidation in NIDDM can be exacerbated by dietary fish oil . This potentially adverse reaction may limit the therapeutic use of fish oils in such patients Abstract . The effects of dietary supplementation with n‐3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non‐insulin‐dependent diabetic patients who were given 10 g of MaxEPA ( 3 g n‐3 fatty acids ) or placebo ( olive oil ) per day in a r and omized double‐blind cross‐over study during two consecutive 8‐week periods . The serum triglyceride ( TG ) concentrations decreased by 27 % ( P < 0.01 ) after addition of MaxEPA with a reduction of VLDL TG by 36 % ( P < 0.05 ) while LDL cholesterol increased by 6 % ( P= 0.05 ) . The fasting blood sugar and HbA1c . concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period . The highest glucose concentrations at fasting and after an i.v . glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged . The peripheral insulin sensitivity , as measured by a euglycaemic , hyperinsulinaemic clamp technique , did not change during the study . The mean plasminogen inhibitor‐1 ( PAI‐1 ) activity of the patients was elevated compared with healthy controls . In spite of the reduction of the triglyceride concentrations and unchanged insulin levels , there was a significant increase of the activity of PAI‐1 ( + 21 % , P < 0.01 ) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity . In many situations there seems to be a reduction of PAI‐1 when the triglycerides are lowered . In the diabetic patients given n‐3 fatty acids this was not the case OBJECTIVES The effect of a fish oil preparation , K-85 , in which the omega-3 fatty acid content was concentrated to 92 % of total fat , on serum lipid and lipoprotein concentrations was investigated in patients with primary hypertriglyceridaemia . DESIGN The study was a r and omized , double-blind , placebo-controlled study . SETTING Seven centres participated in the study , five secondary referral centres and two general practice s. SUBJECTS Men and women aged 18 - 70 years with fasting serum triglyceride concentrations between 2 and 10 mmol/l and fasting serum cholesterol concentrations > 5.2 mmol/l were studied . Patients with diabetes mellitus , hypothyroidism , serious illness in the previous 3 months or severe concurrent illness were excluded from the study , as were drug or alcohol abusers and pregnant and lactating women . Ninety-five subjects entered the study , 79 completed the study . INTERVENTIONS Patients were r and omized to receive K-85 2 g twice daily or corn oil 2 g twice daily for 14 weeks . MAIN OUTCOME MEASUREMENTS The serum concentrations of triglycerides and cholesterol , very low-density lipoprotein ( VLDL ) , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) and lipoprotein ( a ) . Fasting blood glucose and blood pressure . RESULTS Serum triglycerides and VLDL-cholesterol were significantly lower in the group treated with K-85 than in the placebo group after 6 , 10 and 14 weeks ( all P < 0.01 ) and there was a decrease in the serum triglyceride concentration from 3.99 ( 2.94 - 9.47 ) to 2.87 ( 1.2 - 9.93 ) mmol/l ( P < 0.001 ) and in VLDL-cholesterol from 1.47 ( 0.77 - 3.63 ) to 1.12 ( 0.21 - 3.67 ) mmol/l ( P < 0.01 ) in patients receiving K-85 . Serum HDL-cholesterol increased from 0.98 ( 0.95 - 1.01 ) to 1.11 ( 1.07 - 1.15 ) mmol/l ( P < 0.01 ) in the patients with type IV hyperlipoproteinaemia but did not change in those with type IIb . Serum LDL-cholesterol , lipoprotein ( a ) and fasting blood glucose were unaffected by K-85 . Diastolic blood pressure decreased from 86 + /- 11 to 80 + /- 12 mmHg ( P < 0.02 ) and was also lower than in the placebo group ( P < 0.05 ) . The corn oil placebo did not affect any of the parameters . CONCLUSION K-85 is effective in lowering serum triglycerides and VLDL in patients with primary hypertriglyceridaemia and may have utility as a triglyceride-lowering agent The authors examined the association between dietary intake of fish and omega 3 fatty acids from seafood and the risk of cardiovascular disease in a prospect i ve cohort study of 21,185 US male physicians who are participants in the Physicians ' Health Study . In 4 years of follow-up , there were 281 incident cases of total ( fatal and nonfatal ) myocardial infa rct ion , 173 cases of stroke , and 121 cardiovascular deaths . There was no evidence for association between dietary intake of fish and any cardiovascular endpoint , including myocardial infa rct ion , stroke , and cardiovascular death . The relative risks of total myocardial infa rct ion , adjusted for age and r and omized treatment assignment , for categories of fish intake were : 1.0 for < 1 meal/week ( referent ) , 1.6 ( 95 % confidence interval ( Cl ) 1.1 - 2.3 ) for 1 fish meal/week ; 1.4 ( 95 % Cl 1.0 - 2.0 ) for 2 - 4 fish meals/week ; and 1.2 ( 95 % Cl 0.6 - 2.2 ) for > or = 5 fish meals/week ; chi 2 for trend = 0.9 , p = 0.34 . The relative risks were similar for omega 3 fatty acid intake and for specific types of fish , and did not change after adjustment for history of hypertension , hypercholesterolemia , diabetes mellitus , or angina pectoris , parental history of myocardial infa rct ion before age 60 years , obesity , exercise , smoking , alcohol use , saturated fat intake , and vitamin supplement use . These data do not support the hypothesis that moderate fish consumption lowers the risk of cardiovascular disease A r and omised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infa rct ion ( MI ) . 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors : a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat , an increase in fatty fish intake , and an increase in cereal fibre intake . The advice on fat was not associated with any difference in mortality , perhaps because it produced only a small reduction ( 3 - 4 % ) in serum cholesterol . The subjects advised to eat fatty fish had a 29 % reduction in 2 year all-cause mortality compared with those not so advised . This effect , which was significant , was not altered by adjusting for ten potential confounding factors . Subjects given fibre advice had a slightly higher mortality than other subjects ( not significant ) . The 2 year incidence of reinfa rct ion plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens . A modest intake of fatty fish ( two or three portions per week ) may reduce mortality in men who have recovered from MI The use of lipid-lowering drugs is now established clinical practice . However , not all patient categories have been covered in the l and mark studies ( 4S , WOSCOPS and CARE ) , leaving the arena open for widely differing opinions . Dyslipidoemia in patients with diabetes mellitus and arteriosclerotic disease of the aorta , limb arteries or carotid arteries should be corrected . The benefit remains unproven for patients with coronary artery disease and normal lipid levels , and for the elderly . Omega-3 supplements are approved in Norway for hypertriglyceridoemia , but clinical benefit has not been established for this treatment , in contrast to treatment with gemfibrosil . Hormone replacement therapy for postmenopausal women effectively lowers LDL cholesterol levels and the results of r and omised studies with clinical endpoints are awaited . The rapid effect ( within six months ) of lowered cholesterol on coronary events suggests that starting treatment during middle age is adequate for many patients , except for those with familial hyperlipidemias Abstract Aims /hypothesisThe aim of the study was to examine the impact of statin or omega-3-acid ethyl esters 90 ( omega-3 EE90 ; omega-3-acid ethyl esters 90 refers to a mixture of ethyl esters of n-3 fatty acids ) on estimated cardiovascular disease ( CVD ) risk in community-based people with type 2 diabetes but without known CVD and not taking lipid-lowering therapy . Methods A central computer r and omised 800 patients in 59 UK general practice s to atorvastatin ( n = 401 , 20 mg/day ) or placebo ( n = 399 ) and omega-3 EE90 ( n = 397 , 2 g/day ) or placebo ( n = 403 ) in a concealed factorial manner . Participants with LDL-cholesterol < 2.6 mmol/l , triacylglycerol < 1.5 mmol/l and estimated 10-year CVD risk < 20 % were compared at 4 months . Results Mean ( SD ) age was 63.5 ( 11.7 ) years , HbA1c 6.9 ( 1.1 ) % and known diabetes duration ( median [ interquartile range ] ) was 4 ( 2–8 ) years . Fifty-seven per cent were men , 90 % white and 74 % had an estimated 10-year CVD risk ≥20 % . Of 732 patients with 4-month data , more allocated atorvastatin ( n = 371 ) compared with placebo ( n = 361 ) achieved LDL-cholesterol < 2.6 mmol/l ( 91 % vs 24 % , p < 0.001 ) and had estimated 10-year CVD risks < 20 % ( 38 % vs 26 % , p < 0.001 ) . No differences were seen between those allocated omega-3 EE90 ( n = 371 ) compared with placebo ( n = 361 ) for participants achieving triacylglycerol < 1.5 mmol/l ( 65 % vs 60 % , p = 0.18 ) or estimated 10-year CVD risks < 20 % ( 34 % vs 30 % , p = 0.18 ) . There were no side effects of note . Conclusions /interpretationMany community-based diabetic patients without known CVD remain at high CVD risk despite statin treatment and require additional risk-reduction strategies . The impact of omega-3 EE90 on CVD risk will remain uncertain until clinical endpoint trial results are available . Trial registration : IS RCT no. 76737502 Funding : The study was funded by Pfizer OBJECTIVE To assess the effects of low-dose eicosapentaenoic acid-ethyl-ester on diabetes regulation , lipid metabolism , blood rheology , and platelet reactivity . RESEARCH DESIGN AND METHODS In a double-blind , r and omized , placebo-controlled study , 24 NIDDM subjects received 1800 mg of EPA-E , 900 mg of EPA-E , or a placebo ( 1656 mg olive oil ) daily for 8 wk . RESULTS The EPA : arachidonic acid plasma ratio increased over an 8-wk period , then declined after a 4-wk wash-out period in the fish-oil groups in a dosedependent way . Platelet-activating factor-induced platelet aggregation decreased from 75 ± 7 % at wk 0 to 35 ± 21 % at wk 8 in the 900-mg group ( P = 0.016 ) and from 72 ± 11 to 40 ± 30 % in the 1800-mg group ( P = 0.039 ) , but did not change in the placebo group . No effects on A DP- or collagen-induced aggregation could be attributed to EPA-E. In the 1800-mg group low-density-lipoprotein cholesterol increased significantly , without concomitant rise in apolipoprotein B. Triglycerides , glycemic control , lipoprotein ( a ) , blood and plasma viscosity , erythrocyte deformability , and platelet adhesion to and aggregate formation on extracellular endothelial cell matrix were not significantly influenced . CONCLUSIONS Purified EPA-E in doses of 900 and 1800 mg reduces Plateletactivating factor-induced platelet aggregation without negatively affecting glycemic control . Low-density-lipoprotein cholesterol was elevated in the 1800-mg group We investigated the efficacy of fish oils in Portuguese patients with hypertriglyceridaemia and mixed hyperlipidaemia , and the influence of fish consumption on the triglyceride lowering capacity of fish oils . Forty patients participated in this double-blind study , consisting of a 4-week dietary or wash-out baseline period after which patients were r and omly assigned to receive either 12 fish oil capsules ( 3.6 g/day of omega 3 ) or similar 12 soya oil capsules per day for a period of 2 months . There were no statistically significant changes of total , HDL or LDL-cholesterol , and triglycerides . Nevertheless , triglycerides increased 19.9 % with soya oil and decreased 27.8 % with fish oils . Also , there was an inverse relationship ( rho = -0.352 ) between fish consumption and fish oils effect on triglycerides , and the triglyceride lowering with fish oils increased ( from 27.8 % to 44.4 % ) , reaching borderline significance , if we excluded patients consuming one or more meals with fish per day . Glucose increased 11 % ( P = 0.0047 ) with fish oils . These findings suggest that the triglyceride lowering effect of fish oils is affected by fish consumption , and confirm that fish oils increase blood glucose levels in diabetics and non-diabetics OBJECTIVE To assess in diabetic patients with coronary heart disease ( CHD ) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events . RESEARCH DESIGN AND METHODS A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infa rct ion or angina pectoris , serum total cholesterol 5.5–8.0 mmol/l , and serum triglycerides ≤ 2.5 mmol/l who were participating in the Sc and inavian Simvastatin Survival Study ( 4S ) . Participants in the 4S were r and omly assigned to double-blind treatment with simvastatin , 20 mg daily , with blinded dosage titration up to 40 mg daily , according to cholesterol response during the first 6–18 weeks , or placebo . Endpoints were 1 ) total mortality , 2 ) major CHD events ( CHD death or nonfatal myocardial infa rct ion ) , 3 ) other acute atherosclerotic events , 4 ) myocardial revascularization procedures . RESULTS Over the 5.4-year median follow-up period , simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients . The relative risks ( RRs ) of main endpoints in simvastatin-treated diabetic patients were as follows : total mortality 0.57 ( 95 % CI , 0.30–1.08 ; P = 0.087 ) , major CHD events 0.45 ( 95 % CI , 0.27–0.74 ; P = 0.002 ) , and any atherosclerotic event 0.63 ( 95 % CI , 0.43–0.92 ; P = 0.018 ) . The corresponding RRs in nondiabetic patients were the following : 0.71 ( 95 % CI , 0.58–0.87 ; P = 0.001 ) , 0.68 ( 95 % CI , 0.60–0.77 ; P < 0.0001 ) , and 0.74 ( 95 % CI , 0.68–0.82 ; P < 0.0001 ) . CONCLUSIONS The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD . The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events To compare the impact of dietary fish oil supplementation ( FO , 22 ml daily , containing 4.6 g of n-3 ( omega-3 ) fatty acids , equalling 14.4 mmol ) on carbohydrate and lipid metabolism with that of conventional lipostatic therapy ( Gemfibrozil ( G ) , 900 mg daily , equalling 3.6 mmol ) on hyperlipidemic non-insulin dependent diabetes mellitus ( NIDDM ) , 10 patients were selected for a r and omized , short-time , cross-over study . Each patient was treated for a duration of 2 weeks , with an individual washout period of 8 weeks . Metabolic variables and intravenous glucose tolerances ( 1.2 mmol/kg body weight , t = 30 min ) were determined on days 1 and 15 of each treatment period . Plasma lipid concentrations were identical at baseline , but were reduced more markedly following G as against FO exposure ( % change vs. baseline : total cholesterol ( chol ) , - 13**/-6 * ( G vs FO : p = 0.05 ) ; total triglycerides ( TG ) , -39**/-18 * * ( p < 0.05 ) ; APO B , -17**/- 10 * ( N.S. ) ; LDL-chol , -15**/0 ( p < 0.02 ) ; VLDL-chol , -50***/- 34 * * * ( N.S. ) ; VLDL-TG , -44***/-27 * * ( N.S. ) ; ( p vs. baseline : * < 0.05 , * * < 0.01 , * * * < 0.001 ) . Total-HDL , HDL2 , HDL3 and APO A were not influenced by either FO or G. Neither FO nor G induced a change in intravenous glucose tolerances or associated basal and incremental concentrations of insulin and C-peptide . We concluded , based on short-time applications , that ( a ) neither treatment affected the carbohydrate metabolism in patients with NIDDM , and ( b ) a greater hypolipidemic efficacy had to be assigned to Gemfibrozil than to fish oil . It would therefore appear that Gemfibrozil acts as a useful lipostatic pharmacologic compound , whilst fish oil could serve as a potential ingredient of a prudent cardio-protective diet which favours the low plasma triglyceride concentrations found in NIDDM patients OBJECTIVE The aim of this study was to evaluate the long-term ( 6-month ) effects of moderate fish oil supplementation on insulin sensitivity and plasma lipoproteins in NIDDM patients with hypertriglyceridemia . RESEARCH DESIGN AND METHODS The study has been performed according to a r and omized double-blind placebo-controlled design with a parallel group sequence . After a washout period of 4 weeks and a run-in period of 3 weeks , 16 NIDDM patients with hypertriglyceridemia ( triglyceride [ TG ] , 2.25–5.65 mmol/l ) were r and omly assigned to either fish oil ( 2.7 g/day eicosapentaenoic plus docosahexaenoic acid for 2 months , then 1.7 g/day for 4 more months ) ( n = 8) or placebo ( n = 8) . Diet and hypoglycemic drugs remained unchanged throughout the whole experiment . At baseline and after 6 months , insulin sensitivity was measured by euglycemic hyperinsulinemic clamp ( insulin infused , 2.0 mIU · kg−1 body wt · min−1 ) . At the same time , blood glucose control , fasting and postpr and ial serum insulin and nonesterified fatty acid ( NEFA ) concentrations , and fasting plasma lipoprotein concentrations were evaluated . RESULTS In the group treated with ffish oil compared with the baseline , there was : 1 ) a significant reduction in both plasma TG ( 2.92 ± 0.23 vs. 3.85 ± 0.32 [ mean ± SE ] mmol/l , P < 0.001 ) and VLDL-TG ( 2.35 ± 0.24 vs. 4.25 ± 0.66 mmol/l , P < 0.01 ) , without significant changes in blood glucose control ; 2 ) a significant reduction in fasting NEFA concentrations ( 572 ± 100 vs. 825 ± 131 μmol/l , P < 0.01 ) ; and 3 ) a significant enrichment in long-chain ω-3 fatty acids of erythrocyte membrane phospholipids . In the placebo group , there were no changes in any of the variables analyzed . The insulin-mediated glucose uptake was unchanged in both groups ( fish oil , 4.04 ± 0.82 mg · kg−1 · min−1 at baseline and 3.96 ± 0.50 mg · kg−1 · min−1 at 6 months ; placebo , 3.51 ± 0.62 mg · kg−1 · min−1 at baseline and 4.09 ± 0.49 mg · kg−1 · min−1 at 6 months ) . CONCLUSIONS In NIDDM patients with hypertriglyceridemia , moderate amounts of fish oil induce a long-term significant reduction in plasma triglycerides , VLDL triglycerides , and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain ω-3 fatty acids , without deteriorating blood glucose control . However , this amount of ω-3 fatty acids was unable to improve insulin sensitivity in this group of patients The long-term influence of n-3 polyunsaturated fatty acids ( n-3 PUFAs ) on serum lipids and glucose homeostasis was studied in a group of non-diabetic , moderately hypertriglyceridaemic patients undergoing coronary artery bypass grafting . They were investigated according to the same procedure before and 6 months after the operation . Following r and omization postoperatively , 28 patients received 3.4 g eicosapentaenoic and docosahexaenoic acid per day , whereas 29 patients comprised the control group . The decline in serum triglycerides after 6 months was significantly greater in the n-3 PUFA group than in the control group ( median decline , -33.2 % vs. -11.1 % , p = 0.002 ) , while no group difference was noted in serum total , HDL , or LDL cholesterol levels . Fasting plasma glucose levels decreased less in the n-3 PUFA group compared with the control group ( median change , -0.2 mmol l-1 vs. -0.5 mmol l-1 , p = 0.054 ) . The corresponding changes in fasting insulin levels were -2 mIU ml-1 in the n-3 PUFA group and no change in the control group ( p = 0.039 ) . In both groups combined , the recorded changes in serum triglyceride and serum insulin levels were negatively correlated with the change in serum phospholipid n-3 fatty acids ( r = -0.35 , p = 0.008 and r = -0.32 , p = 0.016 , respectively ) . An oral glucose tolerance test revealed no significant group differences after 6 months , neither in the peak levels , nor in the areas under the curves between 0 and 3h after the glucose load for glucose , insulin , and C-peptide . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Recent studies in nondiabetic kidney diseases suggest that dietary supplementation with n-3 polyunsaturated fatty acids ( fish oil ) may have beneficial effects on albuminuria , kidney function , arterial blood pressure , and dyslipidemia . Therefore , we evaluated the long-term effect of fish oil in diabetic nephropathy . RESEARCH DESIGN AND METHODS A 1-year double-blind r and omized controlled study comparing fish oil ( 4.6 g n-3 fatty acids/day ) with placebo ( olive oil ) was performed in an outpatient clinic in a tertiary referral center . Thirty-six normotensive IDDM patients with diabetic nephropathy were included ; 18 were treated with fish oil . Seven patients dropped out ( four received fish oil ) , and results for the remaining 29 are presented . Albuminuria ( enzyme immunoassay ) , glomerular filtration rate ( 51Cr-labeled EDTA plasma clearance ) , 24-h ambulatory blood pressure , and lipid profile were determined every 6 months . RESULTS Albuminuria increased by 22 % ( 1–46 % ) ( mean [ 95 % CI ] ) in the fish oil group vs. 15 % ( −11–49 % ) in the placebo group ( NS ) . Glomerular filtration rate decreased from 116 ± 7 to 105 ± 7 ml · min−1 · 1.73 m−2 ( mean ± SE ) vs. from 108 ± 6 to 103 ± 7 , fish oil and placebo , respectively ( NS ) . No significant changes occurred in 24-h ambulatory blood pressure : from 141 ± 4/82 ± 2 mmHg to 142 ± 5/83 ± 2 vs. from 140 ± 4/78 ± 2 to 144 ± 4/80 ± 3 , fish oil and placebo , respectively ( NS ) . In the fish oil group , serum triglycerides ( median [ range ] ) decreased from 0.97 ( 0.5–4.0 ) mmol/l to 0.8 ( 0.4–3.0 ) vs. from 1.01 ( 0.4–2.0 ) to 1.09 ( 0.4–2.0 ) in the placebo group ( P < 0.05 ) and VLDL cholesterol decreased from 0.45 ( 0.23–1.88 ) to 0.37 ( 0.21–1.43 ) mmol/l vs. from 0.44 ( 0.21–0.94 ) to 0.41 ( 0.17–1.94 ) ( P < 0.05 ) , but total and LDL cholesterol rose in the fish oil compared with the placebo group . CONCLUSIONS Our study does not suggest that fish oil has beneficial effects on albuminuria , kidney function , blood pressure , and dyslipidemia in normotensive IDDM patients suffering from diabetic nephropathy BACKGROUND A state of increased oxidative stress has been recognised in type 2 diabetes mellitus ( DM ) . The present study was done to assess the effects of low dose omega-3 fatty acids substitution in patients with type 2 DM with special reference to oxidative stress . METHOD Sixty-five patients with type 2 DM of body mass index ( BMI ) < 27 kg/m2 and thirty age and sex matched healthy controls were evaluated for blood glucose , blood pressure and lipid profile and oxidative stress was assessed in them by measuring lipid peroxides ( LP ) , diene conjugates ( DC ) and reduced glutathione ( RG ) in the serum . Of the 65 , 40 motivated patients were r and omly divided into two groups -- group 1 comprising of fifteen patients prescribed a diabetic diet along with a placebo and group 2 consisting of twenty-five patients on the same diet with the addition of 0.6 g omega-3 fatty acids as one capsule Maxigard ( containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid ) twice daily . All parameters were reassessed after six weeks . RESULTS The levels of lipid peroxides ( micromol/L ) , diene conjugates ( OD units ) and reduced glutathione ( mmol GSH/L ) were significantly altered indicating increased oxidative stress in the diabetics compared to the healthy controls : 4.106 + /- 0.889 , 2.751 + /- 0.424 , 1.344 + /- 0.316 and 1.91 + /- 0.541 , 1.735 + /- 0.315 , 1.919 + /- 0.310 , respectively ( p < 0.001 for all the three ) . Patients in group 1 and 2 were comparable in all respects including oxidative stress at the start of therapy . After six weeks , on comparing the mean % changes in the three parameters of oxidative stress between the two groups , it was seen that the % change was significantly higher in group 2 ( Maxigard group ) compared to group 1 ( Placebo ; 5.22 + /- 1.056 ( p = 0.05 ) , 3.28 + /- 0.608 ( p = 0.01 ) , 5.27 + /- 0.585 ( p < 0.001 ) and 0.82 + /- 0.123 , 0.18 + /- 0.017 , 0.56 + /- 0.035 ( p < 0.001 ) , respectively . The patients in group 2 also exhibited significantly greater improvement in glycemic status , blood pressure and lipid profiles . CONCLUSIONS The present study documented the existence of a state of increased oxidative stress in type 2 diabetics . Significant beneficial effects of low dose omega-3 fatty acids substitution for PUFA-6 were observed not only on oxidative stress parameters but also on blood pressure and metabolic profile n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms . Despite this , there has been concern that these fatty acids may increase lipid peroxidation . The data in vivo are inconclusive , due in part to limitations in the method ologies . In this regard , the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress . This study aim ed to assess the effects of supplementation with purified eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , the two major n-3 fatty acids , on urinary F2-isoprostanes and markers of inflammation , in type 2 diabetic patients . In a double-blind , placebo controlled trial of parallel design , 59 nonsmoking , treated-hypertensive , type 2 diabetic subjects , were r and omized to 4 g daily of purified EPA , DHA , or olive oil for 6 weeks , while maintaining their usual diet . F2-isoprostanes , measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-alpha ) , were measured before and after intervention . Thirty-nine men and 12 women aged 61.2 + /- 1.2 years , with body mass index ( BMI ) , 29.5 + /- 0.5 kg/m2 ; 24 h blood pressure , 138/73 mmHg ; HbA1c , 7.3 + /- 0.1 % and fasting glucose , 7.9 + /- 0.2 mmol/l completed the intervention . Baseline urinary F2-isoprostanes were positively associated with HbA1c ( p=.011 ) and fasting glucose ( p=.032 ) . Relative to the olive oil group , postintervention urinary F2-isoprostanes were decreased 19 % by EPA ( p=.017 ) and 20 % by DHA ( p=.014 ) . There were no significant changes in CRP , IL-6 , and TNF-alpha following EPA or DHA supplementation . In regression analysis , Delta F2-isoprostanes were positively associated with Delta HbA1c ( p=.007 ) independent of treatment group ; and with Delta TNF-alpha ( p=.034 ) independent of age , gender , BMI , and treatment group . There were no associations with Delta CRP or Delta IL-6 . This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation , in treated hypertensive , type 2 diabetic subjects The aim of this study was to evaluate the effects of a fish oil preparation ( MaxEPA ) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic ( NIDDM ) subjects . Eighty NIDDM out patients aged 55.9 yr ( mean SD 11.5 yr ) participated in a prospect i ve double-blind placebo-controlled study of MaxEPA capsules ( 10 g/day ) or olive oil ( control ) treatment over 6 wk . Patients received either MaxEPA or olive oil in addition to preexisting therapy . Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk . Platelet membrane eicosapentaenoic acid ( EPA ) content increased in the treatment group ( P < 0.001 ) . MaxEPA supplementation was associated with a significant fall in total triglycerides ( P < 0.001 ) but did not affect total cholesterol ( P = 0.7 ) compared with control treatment . Fasting plasma glucose increased after 3 wk ( P = 0.01 ) but not after 6 wk ( P = 0.17 ) treatment with MaxEPA . Spontaneous platelet aggregation in whole blood fell in the MaxEPA group ( P < 0.02 ) after 6 wk , but there were no changes in agonist-induced platelet aggregation , thromboxane generation in platelet-rich plasma , or plasma P-thromboglobulin and platelet factor IV levels . An increase in clotting factor VII ( P = 0.02 ) , without changes in fibrinogen or factor X levels , occurred in the MaxEPA group . Similar reductions in blood pressure were observed in both groups . Dietary supplementation with MaxEPA capsules ( 10 g/day ) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels . Most indices of platelet function are unaffected by this therapy |
1,731 | 22,509,755 | This meta- analysis does not show an effect of the timing of restorations on implant MBL .
The selection of restoration protocol s should be based on factors other than MBL | BACKGROUND The advancement in implant dentistry has allowed shortened treatment time by restoring the implants earlier .
Whether the timing of restoration has an impact on implant marginal bone level has not been systematic ally analyzed .
The aim of this study is to compare marginal bone loss ( MBL ) between implants that were restored with the following protocol s : 1 ) immediate restoration/loading ( IR/L ) ; 2 ) early loading ( EL ) ; and 3 ) conventional loading ( CL ) . | PURPOSE To compare the efficacy of immediate functionally loaded implants placed with a flapless procedure ( test group ) versus implants placed after flap elevation and conventional load-free healing ( control group ) in partially edentulous patients . MATERIAL S AND METHODS Forty patients were r and omized : 20 to the flapless immediately loaded group and 20 to the conventional group . To be immediately loaded , implants had to be inserted with a minimum torque > 45 Ncm . Implants in the immediately loaded group were provided with full acrylic resin temporary restorations the same day . Implants in the conventional group were submerged ( anterior region ) or left unsubmerged ( posterior region ) and were left load-free for 3 months ( m and ibles ) or 4 months ( maxillae ) . Provisional restorations were replaced with definitive single metal-ceramic crowns 1 month postloading . Outcome measures were prosthesis and implant failures , biological and prosthetic complications , postoperative edema , pain , and use of analgesics . Independent sample chi2 tests , Mann-Whitney tests , t tests , and paired t tests were used with a significance level of .05 . RESULTS Fifty-two implants were placed in the flapless group and 56 in the conventionally loaded group . In the flapless group , 1 flap had to be raised to control the direction of the bur and 1 implant did not reach the planned primary stability and was treated as belonging to the conventional group . After 3 years no dropouts or failures occurred . There was no statistically significant difference for complications ; however , patients in the conventional group had significantly more postoperative edema and pain and consumed more analgesics than those in the flapless group . Osstell values were significantly higher at baseline in the flapless group ( P = .033 ) . When comparing baseline data with years 1 , 2 , and 3 within each group , mean Osstell values of the flapless group did not increase , whereas there were statistically significant increases in the Periotest values . CONCLUSIONS Implants can be successfully placed flapless and loaded immediately without compromising success rates ; the procedure decreases treatment time and patient discomfort The aim of this study was to compare the success rates after 1 and 2 years of conventionally and early loaded pairs of unsplinted ITI implants supporting m and ibular overdentures in edentulous patients . Twenty-four participants ( age range 55 - 80 years ) were r and omly allocated with maximum concealment to two treatment groups . In the first group , the implants were allowed to heal for 12 weeks before being functionally loaded ( control ) and the second group had 6 weeks of healing with identical loading . All participants had new conventional complete maxillary and m and ibular dentures prior to the study . Two s and blasted large-grit acid-etched ( SLA ) surface ITI implants were placed in the m and ibular interforaminal area , following a st and ardized nonsubmerged surgical protocol . After 6 or 12 weeks of healing , matrices were processed into the fitting surface of the pre-existing m and ibular dentures and the implants loaded . Implant success was determined using mobility tests and radiographs taken at baseline and 52 and 104 weeks after surgery . Clinical peri-implant parameters were also documented . Results showed all implants successfully osseointegrated , according to accepted criteria , after 2 years . Mean loss of crestal bone height after 1 year was 0.35 + /- 0.22 mm ( control ) vs. 0.27 + /- 0.18 mm ( test ) . After 2 years this reduced to 0.09 + /- 0.06 mm ( control ) vs. 0.12 + /- 0.17 mm ( test ) . The mean Periotest value after 1 year was -4.9 ( control ) vs.-3.78 ( test ) . After 2 years , the mean resonance frequency value for the control implants was 6797 Hz [ mean implant stability quotient ( ISQ ) = 64.77 ] and for the test implants 6670 Hz ( mean ISQ = 62.0 ) . Shortened loading periods for these ITI implants did not cause any statistically significant differences in osseointegration or peri-implant parameters . We conclude that pairs of unsplinted SLA-surface ITI implants can be successfully loaded with m and ibular overdentures 6 weeks after surgery AIM this study compared the outcome of immediate non-occlusal loading with conventional loading for single implants in the maxillary aesthetic zone . It was hypothesized that immediate non-occlusal loading is not inferior to conventional loading . MATERIAL S AND METHODS sixty-two patients with a missing maxillary anterior tooth were r and omly assigned to be treated with an implant that was either restored with a non-occluding temporary crown within 24 h after implant placement ( the " immediate group " ) or was restored according to a two-stage procedure after 3 months ( the " conventional group " ) . All implants were installed in healed sites . Follow-up visits were conducted after 6 and 18 months post-implant placement . Outcome measures were radiographic marginal bone-level changes , survival , soft tissue aspects ( probing depth , plaque , bleeding , soft tissue level ) , aesthetics and patient satisfaction . RESULTS no significant differences were found between both study groups regarding marginal bone loss ( immediate group 0.91 ± 0.61 mm , conventional group 0.90 ± 0.57 mm ) , survival ( immediate group 96.8 % : one implant lost , conventional group 100 % ) , soft tissue aspects , aesthetic outcome and patient satisfaction . CONCLUSION within the limitations of this study ( sample size , follow-up duration ) , it was demonstrated that , for single implants in the anterior maxilla , the outcome of immediate non-occlusal loading was not less favourable than conventional loading The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . 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 . PURPOSE The aim of this study was to report a clinical comparative assessment of crestal bone level change around single implants in fresh extraction sockets in the esthetic zone of the maxilla either immediately loaded or loaded after a delay . MATERIAL S AND METHODS Forty patients were included in a prospect i ve , r and omized study . All patients required 1 tooth extraction ( ie , 1 tooth with a hopeless prognosis ) and were r and omized into either the test group or the control group . Implants were positioned immediately after tooth extraction and were loaded immediately in the test group ( 20 implants ) and after 3 months in the control group ( 20 implants ) . The implant site was prepared , with at least 4 mm of sound apical bone below the implant apex , and the coronal margin of the implant was placed at the buccal level of the bone crest . All implants were 13 mm long ; 30 implants had a diameter of 5 mm , and 10 had a diameter of 3.75 mm . Radiographic examinations were made at baseline , at 6 months , and at 24 months . To compare the mean values between test and control group , a paired t test was performed ( considered statistically significant at P < .05 ) . RESULTS After a 24-month follow-up period , a cumulative survival rate of 100 % was reported for all implants . The control group result ed in a mean mesial bone loss of 1.16 + /- 0.32 mm and a mean distal bone loss of 1.17 + /- 0.41 ( mean bone loss , 1.16 + /- 0.51 mm ) . The test group result ed in a mesial bone loss of 0.93 + /- 0.51 mm and a distal bone loss of 1.1 + /- 0.27 mm ( mean bone loss , 1.02 + /- 0.53 mm ) . No statistically significant difference between control and test groups ( P > .05 ) was found . CONCLUSION The success rate and radiographic results of immediate restorations of dental implants placed in fresh extraction sockets were comparable to those obtained in delayed loading group PURPOSE This prospect i ve r and omized controlled trial aim ed to compare single implant-supported m and ibular molar restorations using either an immediate or a delayed loading protocol . MATERIAL S AND METHODS Thirty subjects requiring single m and ibular molar replacement were consecutively treated . One implant was placed in each patient . Fifteen subjects were assigned to delayed loading protocol and 15 to immediate loading protocol according to a r and omization table . After insertion , the delayed loaded implants were connected to a healing abutment and restored after 3 to 4 months of healing without loading . The immediately loaded implants were loaded within 24 hours of surgery with a provisional restoration . The interim prosthesis was placed in centric occlusion . All contacts in lateral excursions were eliminated . At implant placement the maximum value of insertion torque was recorded . Radiographic bone level change was measured on periapical radiographs obtained at the time of implant placement and 12 months after loading . Means of the 2 groups were compared by Student t test and analysis of variance ( ANOVA ) . The level of significance was set at .05 . RESULTS No implants were lost in the delayed loading group ( 0/15 ) , whereas 1 implant failed ( 1/15 ) in the immediate loading group . No differences were observed in relation to implant length or insertion torque between the groups . The average radiographic bone level change after 1 year of function was 1.2 + /- 0.55 mm ( range , 0.5 to 2.6 mm ) and 0.77 + /- 0.38 mm ( range , 0.29 to 1.23 mm ) for the delayed loaded and the immediately loaded implants , respectively . The difference in radiographic bone level change between the delayed and immediate loading groups was statistically significant ( P = .022 ; CI = -0.79 to -0.06 ; Student t test ) . CONCLUSIONS Immediate loading of wide-diameter implants supporting single restorations in m and ibular molar sites seems to be a suitable clinical option . Moreover , the radiographic bone level change observed after 12 months of loading was significantly less for immediately loaded implants BACKGROUND Recent studies have showed that immediate/early loading of dental implants is a clinical ly feasible concept with results similar to those for st and ard two-stage procedures , especially in the m and ible . However , there are only a few studies regarding the immediate/early loading of maxillary implants supporting single-tooth crowns . PURPOSE The aim of this study was to compare the clinical and radiological outcomes of early- and delayed-loaded dental implants supporting single-tooth crowns in the maxilla . MATERIAL S AND METHODS Twenty-nine patients were consecutively treated between 2000 and 2002 with 59 Brånemark System MK III TiUnite implants ( Nobel Biocare AB , Göteborg , Sweden ) in the maxilla . Two groups were formed according to the loading protocol s. In the test group , definitive implant-supported single crowns were delivered to 19 patients 6 weeks after the implant placement . In the control group , definitive implant-supported single crowns were delivered to 10 patients 6 months after the implant placement . Clinical and radiographic parameters were recorded at baseline , 1 to 4 years . Implant stability measurements have only been performed at 4-year follow-up recall . RESULTS Overall , three implants were lost during the study period . Two implants were lost in the test group including 36 implants , which indicated a survival rate of 94.4 % . One of the lost implants was replaced and then osseointegrated successfully . One implant was lost in the control group during the healing period , which indicated a survival rate of 95.7 % . The average marginal bone loss was 1.11 mm for 56 implants after 4 years . There were no significant differences in marginal bone levels , insertion torque , and resonance frequency values between the two groups . CONCLUSION The results of this study indicate that 6 weeks of early loading period for TiUnite-surface titanium implants in the maxilla is reliable and predictable for this patient population and may offer an alternative to the st and ard loading protocol The aim of this r and omized controlled clinical trial was to compare the efficacy of implants placed with a flapless procedure and restored immediately ( test group ) or early ( 6 weeks ) ( control group ) in partially edentulous patients up to 1 year after loading . Both groups were nonocclusally loaded . Ten patients were included in each group . No patients dropped out and no failures were recorded . Two complications occurred in the early loading group , but both were resolved . It can be concluded that the use of a flapless technique for placing implants in conjunction with nonocclusal immediate loading in select patients can provide excellent clinical results . These preliminary findings should be confirmed by larger r and omized clinical trials PURPOSE Achieving primary implant stability in areas with poor bone density is often challenging to the clinician . Previous research has suggested that modified surgical protocol s might be beneficial in such situations . The objective of the present clinical study was to evaluate the survival rate of implants placed using undersized implant site preparation in areas with poor bone density . MATERIAL S AND METHODS A total of 52 implants were placed in 29 patients . Of the 52 implants , 26 were surgically placed according to the st and ard drilling protocol ( control group ) and 26 were placed in low-density bone using an adapted bone drilling method ( test group ) . The maximum insertion torque values and resonance frequency analysis measurements were also recorded . All implants were examined clinical ly and radiographically at follow-up visits during the study period . Oral hygiene status , bleeding on probing , peri-implant probing depth , and implant survival rate were assessed . RESULTS According to the survival criteria used in the present study , no failure was recorded , and the overall survival rate was 100 % for both groups after 12 months . The mean probing depth was 2.75 ± 0.75 mm in the test group and 2.87 ± 0.79 mm in the control group . The mean insertion torque value was 35.19 ± 4.79 Ncm in the test group and 34.62 ± 5.82 Ncm in the control group . The resonance frequency analysis value was 68.58 ± 4.81 implant stability quotient and 66.69 ± 5.41 implant stability quotient in the test and control groups , respectively . The observed differences were not statistically significant ( P > .05 ) . CONCLUSIONS The results of the present study suggest that placement of implants by an adapted drilling technique in sites with poor bone density is beneficial in enhancing primary implant stability and improving the implant survival rate PURPOSE The objective of this prospect i ve study was to assess the overall outcome of immediate single implant treatment in the anterior maxilla after a 3-year observation period . MATERIAL AND METHODS Thirty consecutively treated patients with a thick gingival biotype , ideal gingival level/contour and intact socket walls at the time of tooth extraction were treated for single-tooth replacement in the aesthetic zone by two experienced clinicians . Treatment included minimal mucoperiosteal flap elevation , immediate implant placement ( NobelReplace TiUnite ( ® ) ) , insertion of a grafting material between the implant and the socket wall and connection of a screw-retained provisional restoration . The latter was replaced by a cemented crown 6 months thereafter . Patients were clinical ly and radiographically re-examined after 3 years to assess implant survival , complications and hard and soft tissue conditions . The aesthetic outcome was objective ly rated using the Pink Esthetic Score ( PES ) and White Esthetic Score ( WES ) by a blinded clinician who had not been involved in the treatment . RESULTS Twenty-five patients could be re-evaluated after 3 years . One early implant failure had occurred result ing in an implant survival rate of 96 % . Radiographic examination yielded on average 1.13 mm mesial , respectively 0.86 mm distal bone loss . The clinical conditions showed fairly low peri-implant plaque ( 18 % ) and bleeding ( 24 % ) and mean probing depth was 3.17 mm . Mean mesial/distal papilla shrinkage and midfacial soft tissue recession in reference to the pre-operative status accounted for 0.05 , 0.08 and 0.34 mm , respectively . Between the 1- and 3-year re assessment mesial papillae showed significant re-growth ( 0.36 mm ; p=0.015 ) . Advanced midfacial recession ( > 1 mm ) was found in 2/25 ( 8 % ) cases . Five ( 21 % ) cases were aesthetic failures ( PES<8 and /or WES<6 ) and 5/24 ( 21 % ) showed an ( almost ) perfect outcome ( PES≥12 and WES≥9 ) . The remainder ( 14/24 or 58 % ) demonstrated acceptable aesthetics . CONCLUSIONS The proposed strategy seems a valuable and predictable treatment option for well-selected patients in the mid-long term as shown by almost full papillary re-growth and a low risk for advanced midfacial recession 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 OBJECTIVE Immediate and early loading of implants can simplify treatment and increase patient satisfaction . This 3-year r and omized-controlled trial will therefore evaluate survival rates and bone-level changes with immediately and early loaded Straumann implants with the SLActive surface . MATERIAL AND METHODS Partially edentulous patients > or=18 years of age were enrolled . Patients received a temporary restoration ( single crown or two to four unit fixed partial denture ) out of occlusal contact either immediately ( immediate loading ) or 28 - 34 days later ( early loading group ) , with permanent restorations placed 20 - 23 weeks after surgery . The primary endpoint was change in crestal bone level from baseline ( implant placement ) to 12 months ; the secondary variables were implant survival and success rates . RESULTS A total of 383 implants ( 197 immediate and 186 early ) were placed in 266 patients ; 41.8 % were placed in type III and IV bone . The mean patient age was 46.3+/-12.8 years . Four implants failed in the immediate loading group and six in the early loading group , giving implant survival rates of 98 % and 97 % , respectively ( P = NS ) . There were no implant failures in type IV bone . The overall mean bone level change from baseline to 12 months was 0.77+/-0.93 mm ( 0.90+/-0.90 and 0.63+/-0.95 mm in the immediate and early groups , respectively ; P<0.001 ) . However , a significant difference in implantation depth between the two groups ( P<0.0001 ) was found . After adjusting for this slight difference in initial surgical placement depth , time to loading no longer had a significant influence on bone-level change . Significant influence was found for : center ( P<0.0001 ) , implant length ( P<0.05 ) and implant position ( P<0.0001 ) . Bone gain was observed in approximately 16 % of implants . CONCLUSIONS The results demonstrated that Straumann implants with the SLActive surface are safe and predictable when used in immediate and early loading procedures . Even in poor- quality bone , survival rates were comparable with those from conventional or delayed loading . The mean bone-level change was not deemed to be clinical ly significant and compared well with the typical bone resorption observed in conventional implant loading PURPOSE This is a follow-up of an earlier 1-year prospect i ve study on implant success rates and the peri-implant response after immediate placement and provisionalization of single implants in the esthetic zone . The effects of gingival biotype on the peri-implant tissues were also evaluated . MATERIAL S AND METHODS Thirty-five patients were evaluated clinical ly and radiographically at presurgical examination ( T0 ) , immediately after immediate implant placement and provisionalization ( T1 ) , 1 year after implant surgery ( T2 ) , and the latest follow-up appointment ( T3 ) . Data were analyzed using t tests and repeated- measures analysis of variance at the significance level of alpha = .05 . RESULTS After a mean follow-up time of 4 years ( range , 2 to 8.2 years ) , all implants remained in function . At T3 , the mean mesial and distal marginal bone level changes were significantly greater than those observed at T2 . At T3 , the mean mesial and distal papilla level changes were significantly smaller than those observed at T2 , whereas the mean facial gingival level change was significantly greater than that observed at T2 . Sites with a thick gingival biotype exhibited significantly smaller changes in facial gingival levels than sites with a thin gingival biotype at both T2 and T3 . CONCLUSIONS Favorable implant success rates and peri-implant tissue responses can be achieved with this procedure . While the results suggest the possibility of spontaneous papilla regeneration over time following this procedure , continuing recession of the facial gingival tissue was also observed . The effect of gingival biotype on peri-implant tissue response seemed to be limited only to facial gingival recession and did not influence interproximal papilla or proximal marginal bone levels OBJECTIVES The aim of this prospect i ve clinical study was to evaluate the clinical outcomes of dental implants placed in the m and ibular molar sites and immediately functionally restored compared with conventionally loaded controls in an in-patient study . MATERIAL AND METHODS Twenty-four dental implants were placed in 12 patients who had first molar loss bilaterally in the m and ibular area . One site of the patient was determined as immediately loaded ( IL ) and the other side was conventionally loaded ( CL ) . Resonance frequency analyses for implant stability measurements , radiographic examinations for marginal bone levels and peri-implant evaluations were performed during the clinical follow-up appointments within 12 months . RESULTS During the 12-month follow-up period , only one implant was lost in the IL group . The mean implant stability quotient values were 74.18+/-5.72 and 75.18+/-3.51 for Groups IL and CL at surgery , respectively , and the corresponding values were 75.36+/-5.88 and 75.64+/-4.84 at 1-year recall , respectively . The difference was not statistically significant between the two groups during the 12-month study period ( P>0.05 ) . When peri-implant parameters were evaluated , excellent peri-implant health was demonstrated during the 1-year observation period and all implants showed less than 1 mm of marginal bone resorption during the first year . CONCLUSIONS In the present study , immediate functionally loading did not negatively affect implant stability , marginal bone levels and peri-implant health when compared with conventional loading of single-tooth implants PURPOSE The aim of this study was to compare implant-supported restorations placed and loaded immediately or with a delay in a longitudinal case control study . MATERIAL S AND METHODS Seventy-six patients with 222 implants were enrolled in this study . One hundred eleven implants ( 45 patients ) were su bmi tted to immediate functional or nonfunctional loading . These were compared to 111 implants ( 51 patients ) that received delayed loading after submerged healing . The mean observation time was 40.3 months ( 3.36 years ) . Implant success was determined , and peri-implant soft tissue parameters and esthetic outcomes for anterior restorations were evaluated . The implants were divided into four groups according to their treatment protocol : immediate ( I ) or delayed ( D ) implant placement ( P ) or function ( F ) , ie : group 1 = IF+IP , group 2 = IF+DP , group 3 = DF+IP , and group 4 = DF+DP . RESULTS Five implants were lost during healing , giving an overall success rate of 97.7 % . Implants with delayed function showed significantly better results ( 100.0 % ) than implants that were immediately loaded ( 95.5 % ) . Four of the five lost implants had been placed immediately post extraction ( success rate for delayed implant placement , 99.4 % , versus 93.1 % for immediate implant placement ) . Regarding the four treatment protocol s , group 1 showed a success rate of 91.3 % ; group 2 achieved 98.5 % ; and both delayed function groups showed 100 % success . No statistically significant difference was seen between the four groups . Esthetically significant advantages were seen for the implants placed into immediate function . Probing depths and bleeding on probing were significantly lower in the group of implants placed into immediate function . CONCLUSIONS Implants that are loaded immediately can achieve good outcomes . However , the risk of implant loss appears to be increased in cases where immediate function is combined with immediate implant placement PURPOSE The purpose s of this study are to determine if there is a difference in the papilla fill between implant and teeth comparing immediate provisionalized and delayed single tooth implant restorations , and to determine the relationships between the vertical and horizontal bone levels to papilla filling the inter-dental region with single implant restorations . PATIENTS AND METHODS Two groups of patients treated with single tooth implant restorations were prospect ively followed . One group had immediate provisionalization of their implants , and the second group a delayed approach . Serial radiographs and photographs were used to collect bone level measurements for the vertical distance between contact point to bone level on the adjacent tooth , implant , and the midcrestal region . The horizontal distances were also recorded . Papilla morphology was scored 1 through 4 . Univariate analysis was used to evaluate the relationships between bone levels and papilla morphology . RESULTS There were no differences between papilla or bone levels comparing immediate provisionalization to delayed approaches . There were significant ( P < .05 ) relationships between the vertical distance from contact point to bone levels , with the distance from the contain point to the adjacent tooth the distance most critical to papilla maintenance . There were no significant relationships between horizontal distance and papilla maintenance . CONCLUSION As the distance from the contact point to the implant increased , there was a significant chance of loss of papilla . There was no difference between delayed or immediate provisionalization and papilla scores . The horizontal distance from adjacent tooth bone level did not correlate to papilla score within the range of clinical ly relevant distances PURPOSE To compare the efficacy of immediate nonocclusal loading ( test group ) versus early loading ( control group ) in partially edentulous patients . MATERIAL S AND METHODS Fifty-two patients in 5 Italian private practice s were r and omized to 1 of the treatments : 25 to the immediately loaded group and 27 to the early loaded group . To be immediately loaded , single implants had to be inserted with a torque of > 30 Ncm , and splinted implants had to be inserted with a torque of > 20 Ncm . Implants in the immediately loaded group were provided with full acrylic resin nonoccluding temporary restorations within 48 hours after placement . After 2 months , full occluding provisional restorations were provided . Implants in the early loading group were not submerged and were loaded after 2 months . At 8 months , provisional restorations were replaced with definitive metal-ceramic prostheses . Outcome measures were prosthesis and implant failures as well as biologic and prosthetic complications recorded by nonblinded assessors . The Fisher exact test was used to compare the proportion of implant failures . RESULTS Fifty-two implants were placed in the immediately loaded group and 52 in the early loaded group . No dropouts or complications occurred up to 14 months postinsertion . One single implant failed in the immediately loaded group 2 months after placement . There was no statistically difference for the tested outcome measures between the 2 procedures ( P > .99 ) . CONCLUSIONS The results of this r and omized controlled clinical trial with 25 patients rehabilitated with immediately restored nonocclusally loaded implant-supported prostheses compared to 27 patients restored 2 months following placement suggest that there are no major clinical differences in implant survival between these 2 protocol s. No biologic or prosthetic complications occurred BACKGROUND The concept of immediate loading of root-form implants for fixed restorations has received increasing interest over the last 5 years . Several authors have commented on parameters that may influence results , including implant number , implant length , bone density , and patient habits . The trigger for bone remodeling around an implant may occur from the surgical trauma of insertion or the mechanical environment of strain at the interface . In the classic two-stage approach , these were divided episodes , separated by 3 to 6 months . Immediate loading compresses this time frame ; the two driving mechanisms for bone repair occur concurrently . A scientific approach to the interface development is to match the bone healing response of trauma ( woven bone of repair ) to the response of mechanical load ( reactive woven bone ) , so the sum of these two entities does not result in fibrous tissue formation and clinical mobility of the implant . PURPOSE It is the purpose of this article to review the scientific rationale of these statements and coordinate them to bone physiology and bone biomechanics . MATERIAL S AND METHODS Findings from previous reports in the literature were review ed and summarized to form the basis of a prospect i ve study using a bone quality -based implant system ( Biohorizons , Maestro Dental Implants , Birmingham , AL , USA ) . A transitional prosthesis was delivered either on the day of surgery or within 2 weeks for 30 patients and 31 arches . A total of 244 implants were used to support these restorations , for an average of 7.8 implants per prosthesis . After 4 to 7 months , the final restorations were fabricated . One year after the final restoration was loaded , the implant survival was 100 % ; the 31 restorations also had a survival of 100 % over this time frame . This report presents these implants and restorations over a 1- to 5-year period , with an average follow-up period of 2.6 years . RESULTS The bone loss from implant insertion to final prosthesis delivery averaged 0.7 mm . The first-year bone loss after final prosthesis delivery averaged 0.07 mm . A slight increase in bone height was observed after the first year , but generally no increase was observed over the remaining evaluation period . CONCLUSIONS In the current report , no implant failure occurred , and crestal bone loss values were similar to or less than values reported with the conditional two-stage approach . This may be related to the number and position of implants , implant design , and /or the surface condition of the implant loading A clinical and radiographical study was performed to evaluate the treatment outcome of single tooth replacements with artificial crowns retained to implants installed according to a 1-stage surgical procedure and immediate loading ( Experimental Group = EG ) in comparison to the original 2-stage concept ( Control Group = CG ) . The EG comprised 14 patients (= 14 implants ) and the CG comprised 8 patients (= 8 implants ) , all with single tooth losses anterior to the molars . Beyond the non-smoking criterion the following criteria were adopted : i ) the amount of bone had to allow for installation of a fixture with a minimum length of 13 mm and Ø = 3.75 mm , ii ) the jaw relationship had to allow for bilateral occlusal stability , iii ) the patients should be judged to be non-bruxers , and iv ) the patients had to be available for the follow-up and maintenance programme . In the EG a temporary crown was connected to the implant within 24 h following fixture installation . Six months later this crown was replaced with a permanent one . In the CG the surgical and prosthetic treatment followed the st and ard protocol . Out of the 14 fixtures in the EG 2 were lost up to 5 months in function and were subsequently removed . All remaining 12 implants were stable at every subsequent follow-up examination . No fixture losses were recorded in the CG and all implants in this group were stable at the follow-ups . At the 6-month observation interval all the participating 20 patients were radiographically examined , an examination that was repeated at the 18-month follow-up . The analysis of the radiographs from the EG as well as from the CG disclosed that during the 12-month observation period the mean change of bone support was about 0.1 mm . Further studies , design ed as controlled multicenter ones , have to be performed before the results of this pilot study can be recommended for more general use OBJECTIVE Immediate and early loading of dental implants can simplify treatment and increase overall patient satisfaction . The purpose of this 3-year prospect i ve r and omized-controlled multicenter study was to assess the differences in survival rates and bone level changes between immediately and early-loaded implants with a new chemically modified surface ( SLActive ) . This investigation shows interim results obtained after 5 months . MATERIAL AND METHODS Patients > or = 18 years of age missing at least one tooth in the posterior maxilla or m and ible were enrolled in the study . Following implant placement , patients received a temporary restoration either on the day of surgery ( immediate loading ) or 28 - 34 days after surgery ( early loading ) ; restorations consisted of single crowns or two to four unit fixed dental prostheses . Permanent restorations were placed 20 - 23 weeks following surgery . The primary efficacy variable was change in bone level ( assessed by st and ardized radiographs ) from baseline to 5 months ; secondary variables included implant survival and success rates . RESULTS A total of 266 patients were enrolled ( 118 males and 148 females ) , and a total of 383 implants were placed ( 197 and 186 in the immediate and early loading groups , respectively ) . Mean patient age was 46.3+/-12.8 years . After 5 months , implant survival rates were 98 % in the immediate group and 97 % in the early group . Mean bone level change from baseline was 0.81+/-0.89 mm in the immediate group and 0.56+/-0.73 mm in the early group ( P<0.05 ) . Statistical analysis revealed a significant center effect ( P<0.0001 ) and a significant treatment x center interaction ( P=0.008 ) . CONCLUSIONS The results suggested that Straumann implants with an SLActive can be used predictably in time-critical ( early or immediate ) loading treatment protocol s when appropriate patient selection criteria are observed . The mean bone level changes observed from baseline to 5 months ( 0.56 and 0.81 mm ) corresponded to physiological observations from other studies , i.e. , were not clinical ly significant . The presence of a significant center effect and treatment x center interaction indicated that the differences in bone level changes between the two groups were center dependent PURPOSE This clinical study aim ed to assess the dimensional stability of peri-implant soft tissues around immediately placed and restored implants in the maxillary esthetic zone . MATERIAL S AND METHODS Twelve systemically healthy patients presenting with a hopeless maxillary central incisor were selected . Provisional restorations were delivered immediately after tooth extraction and implant placement . Periimplant soft tissue dimensions were measured either by direct clinical examination or evaluation of study casts . Measurements were performed before extraction ; immediately after implant and restoration placement ; and 6 weeks , 3 months , 6 months , 12 months , and 18 months postoperatively . The distances assessed were : tip of the mesial papilla to the mesioincisal edge of the adjacent central incisor , tip of the distal papilla to the mesioincisal edge of the adjacent lateral incisor , and the length of the clinical crown of the definitive restoration . RESULTS All patients completed the study , and no implants failed within the 18-month follow-up period ( 100 % survival rate ) . No statistical differences were observed in the distances between the incisal edge of the adjacent teeth and the mesial and distal papilla tips ( P = .303 and .099 , respectively ) at any follow-up appointment . Likewise , there were no alterations in the definitive clinical crown dimensions during the follow-up period ( P = .406 ) . CONCLUSION The findings of this 18-month prospect i ve study indicate that , within the selection criteria and technique presented in this study , immediate implants with immediate restorations can be a predictable option for the replacement of teeth in the esthetic zone , providing stability to the peri-implant soft tissue Immediate loading of dental implants can reduce treatment time and management concerns , thus increasing patient acceptance . This paper reports the authors ' preliminary experience with partially edentulous patients having received non-occlusally loaded provisional restorations within 24 hours of surgery , compared to patients treated according to an early loading protocol . The present data suggest that implant supported fixed partial prostheses can be immediately non-occlusally loaded and restored with a predictability similar to early loaded implants BACKGROUND The aim of this study was to compare the bone loss pattern and soft tissue healing of immediately versus one-stage loaded 3.0-mm-diameter implants in cases involving a single missing lateral maxillary incisor . METHODS Sixty patients with a missing lateral incisor in the maxilla were r and omized to one of the treatments : 30 patients in the immediate-restoration group and 30 patients in the one-stage group . All implants were placed in healed sites and had to be inserted with a torque > 25 Ncm . The implants in the immediate-restoration group were fitted with a non-occluding temporary crown on the day of surgery . Both groups received a full occluding final crown 6 months after surgery . Mean marginal bone loss , probing depth , and bleeding on probing were assessed at 6- , 12- , 24- , and 36-month follow-up examinations by a masked examiner . RESULTS Sixty 3.0-mm-diameter implants were placed between July 2003 and February 2006 ; 27 ( 45.0 % ) were in men , and 33 ( 55.0 % ) were in women . All implants osseointegrated and were clinical ly stable at the 6-month follow-up . No statistically significant differences were observed for bleeding or plaque index . No implant fractures occurred . At the 36-month follow-up , the accumulated mean marginal bone loss and probing depth were 0.85 + /- 0.71 mm and 1.91 + /- 0.59 mm , respectively , for the immediate-loading group ( n = 30 ) and 0.75 + /- 0.63 mm and 2.27 + /- 0.81 mm , respectively , for the one-stage group ( n = 30 ) . There was no statistically significant difference ( P > 0.05 ) for the tested outcome measures between the two procedures . CONCLUSIONS In the rehabilitation of a single missing lateral maxillary incisor , no statistically significant difference was assessed between immediately and one-stage restored small-diameter implants with regard to implant survival , mean marginal bone loss , and probing depth . Three-millimeter-diameter implants proved to be a predictable treatment option in our test and control groups if a strict clinical protocol was followed PURPOSE The aim of this study was to determine the clinical effectiveness of placing dental implants with microtextured surfaces into full occlusal loading at the time of placement in partially edentulous patients . MATERIAL S AND METHODS Two demographically similar groups of 14 patients each were treated with a total of 92 Spline Twist Implants ( Centerpulse Dental , Carlsbad , CA ) . Test implants were placed into immediate full occlusal loading , and control implants were restored using a conventional delayed loading procedure . Otherwise , both groups of patients received similar therapy from the same treatment team . Radiographs , periodontal indices , and Periotest values were recorded every 6 months during routine clinical follow-up appointments . The mean loading time for all prostheses was 24 months at the time of this report . RESULTS No implants failed in the test group , and 1 implant failed before loading in the control group . Cumulative implant success was 98.9 % for all implants placed ( test group = 100 % ; control group = 92.9 % ) . Periodontal measurements indicated no significant clinical differences between implants placed into immediate full occlusal loading and those loaded via a conventional delayed protocol . DISCUSSION Immediate full occlusal loading of partial prostheses supported by microtextured implants in partially edentulous patients demonstrated excellent clinical results , with no adverse periodontal effects after 24 months of function . Additional follow-up will provide invaluable information on the long-term effects of this technique . CONCLUSION Immediate full occlusal loading of partial prostheses supported by microtextured implants can be successfully achieved for 24 months in highly motivated patients with excellent oral hygiene The aim of this investigation was to evaluate the clinical success of immediately loaded implants versus implants loaded in a delayed fashion in the posterior m and ible . Three implants were placed distal to the canines bilaterally in the edentulous distal m and ibular ridges of 12 patients . One side was r and omly selected for placement of three implants ( delayed loading ; control sites ) with a progressive thread design for submerged healing , and after 3 months the implants were exposed and loaded with provisional splinted crowns , which were replaced 6 weeks later by the definitive restorations . Three additional implants ( immediately loaded ; test sites ) , of the same size were placed in the contralateral side of the m and ible . The test implants had abutments placed and were loaded immediately using the same protocol as the control implants . After a mean loading period of 25.3 months , the patients showed normal mean clinical values without significant differences ( P < 0.05 ) for test and control implants , respectively , as follows : Plaque Index : 0.4 versus 0.8 ; Sulcus Bleeding Index : 0.5 versus 0.3 ; probing pocket depth : 1.9 mm versus 2.1 mm ; width of keratinized mucosa : 2.5 mm versus 3.3 mm ; Periotest value : -3.7 versus -3.2 . Twenty-nine of the examined sites showed no bone loss . After 2 years of loading in the posterior m and ible , test and control implants had the same prognosis 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 OBJECTIVES To compare peri-implant bone and soft-tissue levels of immediately non-occlusally loaded vs. non-submerged early loaded implants in partially edentulous patients up to 14 months after placement . MATERIAL AND METHODS Fifty-two patients were r and omized in five Italian private practice s : 25 in the immediately loaded group and 27 in the early loaded group . To be immediately loaded , single implants had to be inserted with a torque of > or = 30 N cm , and splinted implants with a torque of > or = 20 N cm . Immediately loaded implants were provided with non-occluding temporary restorations within 48 h. After 2 months , the provisional restorations were placed in full occlusion . Implants were early loaded after 2 months . Final restorations were provided 8 months after placement . Blinded assessors evaluated peri-implant bone and soft-tissue levels . RESULTS Fifty-two implants were immediately loaded and 52 were early loaded . No drop-out occurred . One single immediately loaded implant failed 2 months after placement . Both groups gradually lost peri-implant bone in a highly statistically significant manner at 2 , 8 , and 14 months . After 14 months , patients of both groups lost an average of 1.1 mm of peri-implant bone . There were no statistically significant differences between the two loading strategies for peri-implant bone and soft-tissue level changes ( P > 0.05 ) . After 14 months , the position of the soft tissues did not change significantly from baseline ( delivery of the final restorations 8 months after placement ) . CONCLUSIONS There were no statistically or clinical ly significant differences between immediate and early loading of dental implants with regard to peri-implant bone and soft-tissue levels as evaluated in the present study |
1,732 | 32,030,125 | When assessing the current body of literature , it can be inferred that performing RT through a full ROM confers beneficial effects on hypertrophy of the lower body musculature versus training with a partial ROM .
No study to date has investigated how ROM influences muscle growth of the trunk musculature . | The purpose of this study was to systematic ally review the literature as to the effects of performing exercise with a full versus partial range of motion ( ROM ) during dynamic , longitudinal resistance training ( RT ) programs on changes in muscle hypertrophy .
Based on the available literature , we aim ed to draw evidence -based recommendations for RT prescription . | We have determined whole body protein kinetics , i.e. , protein synthesis ( PS ) , breakdown ( PB ) , and net balance ( NB ) in human subjects in the fasted state and following ingestion of ~40 g [ moderate protein ( MP ) ] , which has been reported to maximize the protein synthetic response or ~70 g [ higher protein ( HP ) ] protein , more representative of the amount of protein in the dinner of an average American diet . Twenty-three healthy young adults who had performed prior resistance exercise ( X-MP or X-HP ) or time-matched resting ( R-MP or R-HP ) were studied during a primed continuous infusion of l-[(2)H5]phenylalanine and l-[(2)H2]tyrosine . Subjects were r and omly assigned into an exercise ( X , n = 12 ) or resting ( R , n = 11 ) group , and each group was studied at the two levels of dietary protein intake in r and om order . PS , PB , and NB were expressed as increases above the basal , fasting values ( mg·kg lean body mass(-1)·min(-1 ) ) . Exercise did not significantly affect protein kinetics and blood chemistry . Feeding result ed in positive NB at both levels of protein intake : NB was greater in response to the meal containing HP vs. MP ( P < 0.00001 ) . The greater NB with HP was achieved primarily through a greater reduction in PB and to a lesser extent stimulation of protein synthesis ( for all , P < 0.0001 ) . HP result ed in greater plasma essential amino acid responses ( P < 0.01 ) vs. MP , with no differences in insulin and glucose responses . In conclusion , whole body net protein balance improves with greater protein intake above that previously suggested to maximally stimulating muscle protein synthesis because of a simultaneous reduction in protein breakdown Manipulating joint range of motion during squat training may have differential effects on adaptations to strength training with implication s for sports and rehabilitation . Consequently , the purpose of this study was to compare the effects of squat training with a short vs. a long range of motion . Male students ( n = 17 ) were r and omly assigned to 12 weeks of progressive squat training ( repetition matched , repetition maximum sets ) performed as either a ) deep squat ( 0–120 ° of knee flexion ) ; n = 8 ( DS ) or ( b ) shallow squat ( 0–60 of knee flexion ) ; n = 9 ( SS ) . Strength ( 1 RM and isometric strength ) , jump performance , muscle architecture and cross-sectional area ( CSA ) of the thigh muscles , as well as CSA and collagen synthesis in the patellar tendon , were assessed before and after the intervention . The DS group increased 1 RM in both the SS and DS with ~20 ± 3 % , while the SS group achieved a 36 ± 4 % increase in the SS , and 9 ± 2 % in the DS ( P < 0.05 ) . However , the main finding was that DS training result ed in superior increases in front thigh muscle CSA ( 4–7 % ) compared to SS training , whereas no differences were observed in patellar tendon CSA . In parallel with the larger increase in front thigh muscle CSA , a superior increase in isometric knee extension strength at 75 ° ( 6 ± 2 % ) and 105 ° ( 8 ± 1 % ) knee flexion , and squat-jump performance ( 15 ± 3 % ) were observed in the DS group compared to the SS group . Training deep squats elicited favourable adaptations on knee extensor muscle size and function compared to training shallow squats Abstract The currently accepted amount of protein required to achieve maximal stimulation of myofibrillar protein synthesis ( MPS ) following resistance exercise is 20–25 g. However , the influence of lean body mass ( LBM ) on the response of MPS to protein ingestion is unclear . Our aim was to assess the influence of LBM , both total and the amount activated during exercise , on the maximal response of MPS to ingestion of 20 or 40 g of whey protein following a bout of whole‐body resistance exercise . Resistance‐trained males were assigned to a group with lower LBM ( ≤65 kg ; LLBM n = 15 ) or higher LBM ( ≥70 kg ; HLBM n = 15 ) and participated in two trials in r and om order . MPS was measured with the infusion of 13C6‐phenylalanine tracer and collection of muscle biopsies following ingestion of either 20 or 40 g protein during recovery from a single bout of whole‐body resistance exercise . A similar response of MPS during exercise recovery was observed between LBM groups following protein ingestion ( 20 g – LLBM : 0.048 ± 0.018%·h−1 ; HLBM : 0.051 ± 0.014%·h−1 ; 40 g – LLBM : 0.059 ± 0.021%·h−1 ; HLBM : 0.059 ± 0.012%·h−1 ) . Overall ( groups combined ) , MPS was stimulated to a greater extent following ingestion of 40 g ( 0.059 ± 0.020%·h−1 ) compared with 20 g ( 0.049 ± 0.020%·h−1 ; P = 0.005 ) of protein . Our data indicate that ingestion of 40 g whey protein following whole‐body resistance exercise stimulates a greater MPS response than 20 g in young resistance‐trained men . However , with the current doses , the total amount of LBM does not seem to influence the response 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 . Summary Six healthy women ( 21.8±0.4 y ) did isometric strength training of the left plantarflexors at an ankle joint angle of 90 ° . Training sessions , done 3 times per week for 6 weeks , consisted of 2 sets of ten 5 s maximal voluntary contractions . Prior to and following the training , and in r and om order , voluntary and evoked isometric contraction strength was measured at the training angle and at additional angles : 5 ° , 10 ° , 15 ° , and 20 ° intervals in the plantarflexion and dorsiflexion directions . Evoked contraction strength was measured as the peak torque of maximal twitch contractions of triceps surae . Training increased voluntary strength at the training angle and the two adjacent angles only ( p<0.05 ) . Time to peak twitch torque was not affected by training . Twitch half relaxation time increased after training ( p=0.013 ) , but the increase was not specific to the training angle . There was a small ( 1.1 % , p<0.05 ) increase in calf circumference after training . Evoked twitch torque did not increase significantly at any joint angle . It was therefore concluded that a neural mechanism is responsible for the specificity of joint angle observed in isometric training Abstract Pinto , RS , Gomes , N , Radaelli , R , Botton , CE , Brown , LE , and Bottaro , M. Effect of range of motion on muscle strength and thickness . J Strength Cond Res 26(8 ) : 2140–2145 , 2012—The purpose of this investigation was to compare partial range-of-motion vs. full range-of-motion upper-body resistance training on strength and muscle thickness ( MT ) in young men . Volunteers were r and omly assigned to 3 groups : ( a ) full range of motion ( FULL ; n = 15 ) , ( b ) partial range of motion ( PART ; n = 15 ) , or ( c ) control ( CON ; n = 10 ) . The subjects trained 2 d·wk−1 for 10 weeks in a periodized program . Primary outcome measures included elbow flexion maximal strength measured by 1 repetition maximum ( 1RM ) and elbow flexors MT measured by ultrasound . The results indicated that elbow flexion 1RM significantly increased ( p < 0.05 ) for the FULL ( 25.7 ± 9.6 % ) and PART groups ( 16.0 ± 6.7 % ) but not for the CON group ( 1.7 ± 5.5 % ) . Also , FULL 1RM strength was significantly greater than the PART 1RM after the training period . Average elbow flexor MT significantly increased for both training groups ( 9.65 ± 4.4 % for FULL and 7.83 ± 4.9 for PART ) . These data suggest that muscle strength and MT can be improved with both FULL and PART resistance training , but FULL may lead to greater strength gains Abstract Baroni , BM , Pompermayer , MG , Cini , A , Peruzzolo , AS , Radaelli , R , Brusco , CM , and Pinto , RS . Full range of motion induces greater muscle damage than partial range of motion in elbow flexion exercise with free weights . J Strength Cond Res 31(8 ) : 2223–2230 , 2017—Load and range of motion ( ROM ) applied in resistance training ( RT ) affect the muscle damage magnitude and the recovery time-course . Because exercises performed with partial ROM allow a higher load compared with those with full ROM , this study investigated the acute effect of a traditional RT exercise using full ROM or partial ROM on muscle damage markers . Fourteen healthy men performed 4 sets of 10 concentric-eccentric repetitions of unilateral elbow flexion on the Scott bench . Arms were r and omly assigned to partial-ROM ( 50–100 ° ) and full-ROM ( 0–130 ° ) conditions , and load was determined as 80 % of 1 repetition maximum ( 1RM ) in the full- and partial-ROM tests . Muscle damage markers were assessed preexercise , immediately , and 24 , 48 , and 72 hours after exercise . Primary outcomes were peak torque , muscle soreness during palpation and elbow extension , arm circumference , and joint ROM . The load lifted in the partial-ROM condition ( 1RM = 19.1 ± 3.0 kg ) was 40 ± 18 % higher compared with the full-ROM condition ( 1RM = 13.7 ± 2.2 kg ) . Seventy-two hours after exercise , the full-ROM condition led to significant higher soreness sensation during elbow extension ( 1.3–4.1 cm vs. 1.0–1.9 cm ) and smaller ROM values ( 97.5–106.1 ° vs. 103.6–115.7 ° ) . Peak torque , soreness from palpation , and arm circumference were statistically similar between conditions , although mean values in all time points of these outcomes have suggested more expressive muscle damage for the full-ROM condition . In conclusion , elbow flexion exercise with full ROM seems to induce greater muscle damage than partial-ROM exercises , even though higher absolute load was achieved with partial ROM Purpose The purpose of this study was to determine the effect of a 15-week partial range of motion ( ROM ) resistance training program on the vastus lateralis ( VL ) architecture and mechanical properties , when the time under tension ( TUT ) was equalized . Methods Nineteen untrained male subjects were r and omly assigned to a control ( Control ; n = 8) or training ( TG ; n = 11 ) group . In the TG , the dominant and nondominant legs were r and omly selected to be trained with a full ROM ( FULL ) or a partial ROM ( PART ) in an isokinetic dynamometer . Training volume was equalized based on the TUT by manipulating sets and repetitions . The VL muscle architecture was assessed by B-mode ultrasonography at rest and during maximal isometric knee extension contractions ( MVCs ) at ten knee angles . The VL fascicle force and specific tension were calculated from the MVCs with superimposed stimuli , accounting for the moment arm length , muscle architecture , and antagonist coactivation . Results The FULL training induced changes in fascicle length ( FL ) ( 4.9 ± 2.0 % , P < 0.001 ) and specific tension ( 25.8 ± 18.7 % , P < 0.001 ) . There was a moderate effect of PART training on the physiological cross-sectional area ( PCSA ) ( 7.8 ± 4.0 % , P < 0.001 , dav = 0.6 ) and torque – angle adaptations ( average increase 17.7 ± 3.9 % , P < 0.05 ) . Conclusions These results provide evidence that crucial architectural and mechanical muscle adaptations are dependent on the ROM used in strength training . It seems that muscle FL and specific tension can be increased by pure concentric training if greater ROM is used . Conversely , restricting the ROM to shorter muscle lengths promotes a greater PCSA and angle-specific strength adaptations Purpose The purpose of this study was to compare the effects of squat training with different depths on lower limb muscle volumes . Methods Seventeen males were r and omly assigned to a full squat training group ( FST , n = 8) or half squat training group ( HST , n = 9 ) . They completed 10 weeks ( 2 days per week ) of squat training . The muscle volumes ( by magnetic resonance imaging ) of the knee extensor , hamstring , adductor , and gluteus maximus muscles and the one repetition maximum ( 1RM ) of full and half squats were measured before and after training . Results The relative increase in 1RM of full squat was significantly greater in FST ( 31.8 ± 14.9 % ) than in HST ( 11.3 ± 8.6 % ) ( p = 0.003 ) , whereas there was no difference in the relative increase in 1RM of half squat between FST ( 24.2 ± 7.1 % ) and HST ( 32.0 ± 12.1 % ) ( p = 0.132 ) . The volumes of knee extensor muscles significantly increased by 4.9 ± 2.6 % in FST ( p < 0.001 ) and 4.6 ± 3.1 % in HST ( p = 0.003 ) , whereas that of rectus femoris and hamstring muscles did not change in either group . The volumes of adductor and gluteus maximus muscles significantly increased in FST ( 6.2 ± 2.6 % and 6.7 ± 3.5 % ) and HST ( 2.7 ± 3.1 % and 2.2 ± 2.6 % ) . In addition , relative increases in adductor ( p = 0.026 ) and gluteus maximus ( p = 0.008 ) muscle volumes were significantly greater in FST than in HST . Conclusion The results suggest that full squat training is more effective for developing the lower limb muscles excluding the rectus femoris and hamstring muscles |
1,733 | 27,444,188 | Store- and -forward image transmission coupled with real-time videoconferencing is a suitable alternative to overcome poor internet transmission speeds | Introduction Advances in imaging capabilities and the evolution of real-time teleophthalmology have the potential to provide increased coverage to areas with limited ophthalmology services .
However , there is limited research assessing the diagnostic accuracy of face-to-face teleophthalmology consultation .
This systematic review aims to determine if real-time teleophthalmology provides comparable accuracy to face-to-face consultation for the diagnosis of common eye health conditions . | This study evaluated the impact of telemedicine technology on the provision of neurosurgical health services . We focused on the differences between the use of real time audio-visual teleconferencing and teleradiology versus conventional telephone consultations in the referral of neurosurgical patients from a large district general hospital . All patients requiring emergency neurosurgical consultation were included for r and omization into telephone consultation only ( Mode A ) , teleradiology and telephone consultation ( Mode B ) and video-consultation ( Mode C ) . Measures of effectiveness included diagnostic accuracy and adverse events during the transfer and Glasgow Outcome Score . In a 10-month period , 327 patients were recruited and r and omized into the study : the male/female ratio was 2:1 and the number of patients required to be transferred to the neurosurgical unit was 125 ( 38 % ) . There was a trend towards a more favourable outcome in the video-consultation mode ( 44 % , Mode C ) , versus teleradiology ( 31 % , Mode B ) , versus telephone consultation ( 38 % , Mode A ) . The interim data of this prospect i ve r and omized trial suggests that video-consultation may have a favourable impact on emergency neurosurgical consultations Background Inter-hospital teleconsultation improves stroke care . To transfer this concept into the emergency medical service ( EMS ) , the feasibility and effects of prehospital teleconsultation were investigated . Methodology /Principal Findings Teleconsultation enabling audio communication , real-time video streaming , vital data and still picture transmission was conducted between an ambulance and a teleconsultation center . Pre-notification of the hospital was carried out with a 14-item stroke history checklist via e-mail-to-fax . Beside technical assessment s possible influences on prehospital and initial in-hospital time intervals , prehospital diagnostic accuracy and the transfer of stroke specific data were investigated by comparing telemedically assisted prehospital care ( telemedicine group ) with local regular EMS care ( control group ) . All prehospital stroke patients over a 5-month period were included during weekdays ( 7.30 a.m. –4.00 p.m. ) . In 3 of 18 missions partial dropouts of the system occurred ; neurological co-evaluation via video transmission was conducted in 12 cases . The stroke checklist was transmitted in 14 cases ( 78 % ) . Telemedicine group ( n = 18 ) vs. control group ( n = 47 ) : Prehospital time intervals were comparable , but in both groups the door to brain imaging times were longer than recommended ( median 59.5 vs. 57.5 min , p = 0.6447 ) . The prehospital stroke diagnosis was confirmed in 61 % vs. 67 % , p = 0.8451 . Medians of 14 ( IQR 9 ) vs. 5 ( IQR 2 ) stroke specific items were transferred in written form to the in-hospital setting , p<0.0001 . In 3 of 10 vs. 5 of 27 patients with cerebral ischemia thrombolytics were administered , p = 0.655 . Conclusions Teleconsultation was feasible but technical performance and reliability have to be improved . The approach led to better stroke specific information ; however , a superiority over regular EMS care was not found and in-hospital time intervals were unacceptably long in both groups . The feasibility of prehospital tele-stroke consultation has future potential to improve emergency care especially when no highly trained personnel are on-scene . Trial Registration International St and ard R and omised Controlled Trial Number Register ( IS RCT N ) IS RCT N83270177 83270177 OBJECTIVE To evaluate the reliability of strabismus assessment using telemedicine ( TM ) technology . DESIGN Two prospect i ve interobserver agreement studies . One study compared the agreement between a st and ard and a TM examination , whereas the other assessed agreement between two independent st and ard examinations . PARTICIPANTS Strabismus patients over 4 years of age examined at a remote community clinic and patients assessed in a strabismologist 's urban practice . METHODS Forty-two patients were examined in person by a pediatric ophthalmologist at the remote community and independently by a pediatric ophthalmology fellow by means of TM ( TM-st and ard study ) . The TM examination was performed with the help of a qualified ophthalmic assistant at the remote telecommunication center using a Power Cam 100 camera , a Picture Tel Concorde 4500 teleconferencing system , and a 224 kilobyte b and width . For comparison , independent in person examinations were performed on 43 patients by both examiners ( st and ard-st and ard study ) . Agreement was measured using unweighted kappa ( k ) for categorical data , the intraclass correlation coefficient ( ICC ) for continuous data , and percent agreement . The odds of disagreement with TM ( comparing the TM-st and ard versus st and ard-st and ard studies ) was assessed with logistic regression analysis . MAIN OUTCOME MEASURES Three parameters were assessed : ( 1 ) category of strabismus , determined by observation without cover test ; ( 2 ) angle of deviation at 0.33 and 6.0 m ; and ( 3 ) ocular muscle action . RESULTS Agreement on the category of strabismus was good ( k > 0.61 ) other than for vertical deviations . However , there was good to excellent agreement between TM and st and ard examinations on the vertical ( ICC = 0.78 ) and horizontal ( ICC = 0.79 ) angles of deviation with 6-m fixation with the cover test . Muscle ratings agreed within one point for the lateral , superior , and inferior rectus muscle actions in more than 90 % of the eyes examined . Although good agreement was observed in the TM-st and ard study , it was inferior to the agreement in the st and ard-st and ard study . Examination by TM increased the odds of disagreement compared with examination in person by twofold to threefold . CONCLUSIONS Strabismus examination can be performed with a good level of reliability with the use of medium b and width video teleconferencing equipment . However , reduced reliability has been noted in the detection of small vertical deviations by inspection and in evaluating oblique muscle actions OBJECTIVE To prospect ively measure accuracy , reliability , and image quality of telemedical retinopathy of prematurity ( ROP ) diagnosis . METHODS Two-hundred forty-eight eyes from 67 consecutive infants underwent wide-angle retinal imaging by a trained neonatal nurse at 31 to 33 weeks ' and /or 35 to 37 weeks ' postmenstrual age ( PMA ) using a st and ard protocol . Data were uploaded to a Web-based telemedicine system and interpreted by 3 expert retinal specialist grade rs who provided a diagnosis ( no ROP , mild ROP , type 2 prethreshold ROP , treatment-requiring ROP ) and an evaluation of image quality for each eye . Findings were compared with a reference st and ard of indirect ophthalmoscopy by an experienced pediatric ophthalmologist . RESULTS At 35 to 37 weeks ' PMA , sensitivity and specificity for diagnosis of mild or worse ROP were 0.908 and 1.000 for grade r A , 0.971 and 1.000 for grade r B , and 0.908 and 0.977 for grade r C. Sensitivity and specificity for diagnosis of type 2 prethreshold or worse ROP were 1.000 and 0.943 for grade r A , 1.000 and 0.930 for grade r B , and 1.000 and 0.851 for grade r C. At 35 to 37 weeks ' PMA , weighted kappa for inter grade r reliability was 0.791 to 0.889 , and kappa for intra grade r reliability for detection of type 2 prethreshold or worse ROP was 0.769 to 1.000 . Image technical quality was rated as " adequate " or " possibly adequate " for diagnosis in 93.3 % to 100 % of eyes . CONCLUSION A telemedicine system using nurse-captured retinal images has the potential to improve existing shortcomings of ROP management , particularly at later PMAs Objective : Evaluate whether telemedicine can be used to perform dysmorphology and neurologic examinations in the neonatal intensive care unit ( NICU ) by determining the examination accuracy , limitations and optimized procedures . Study Design : Prospect i ve evaluation of NICU patients referred for subspecialty consultation for dysmorphic features ( n=10 ) or encephalopathy ( n=10 ) . A physician at bedside ( bedside clinician ) performed an in-person examination that was viewed in real time by a remote physician ( remote consultant ) . St and ardized examinations were recorded and compared . Subsequently , a qualitative approach established technique adjustments and optimization procedures necessary to improve visualization . Result : Telemedicine examinations identified 81 of 87 ( 93 % ) dysmorphology examination abnormalities and 37 of 39 ( 92 % ) neurologic examination abnormalities . Optimization of remote consultant visualization required an active bedside clinician assisting in camera and patient adjustments . Conclusion : Telemedicine can be used to perform accurately many components of the dysmorphology or neurologic examinations in NICU patients , but physicians must be mindful of specific limitations Introduction . Diabetic retinopathy ( DR ) is the leading cause of preventable blindness in Australia . Up to 50 % of people with proliferative DR who do not receive timely treatment will become legally blind within five years . Innovative and accessible screening , involving a variety of primary care providers , will become increasingly important if patients with diabetes are to receive optimal eye care . Method . An open controlled trial design was used . Five intervention practice s in urban , regional , and rural Australia partnered with ophthalmologists via telehealth undertook DR screening and monitoring of type 2 diabetes patients and were compared with control practice s undertaking usual care 2011–2014 . Results . Recorded screening rates were 100 % across intervention practice s , compared with 22–53 % in control practice s. 31/577 ( 5 % ) of patients in the control practice s were diagnosed with mild-moderate DR , of whom 9 ( 29 % ) had appropriate follow-up recorded . This was compared with 39/447 ( 9 % ) of patients in the intervention group , of whom 37 ( 95 % ) had appropriate follow-up recorded . Discussion and Conclusion . General practice -based DR screening via Annual Cycle of Care arrangements is effective across differing practice locations . It offers improved recording of screening outcomes for Australians with type 2 diabetes and better follow-up of those with screen abnormalities Background / aims Digital retinal imaging using store- and -forward technology is used to screen for diabetic retinopathy ( DR ) . Its usefulness in detecting non-diabetic eye diseases is uncertain . We determined the level of agreement between teleretinal imaging supplemented with visual acuity and intraocular pressure ( IOP ) measurements ( ie , technology-assisted eye ( TAE ) exam ) and a comprehensive eye exam in evaluation for DR and non-diabetic ocular conditions . Methods We conducted a prospect i ve , observational study with two parallel evaluations . Patients with diabetes ( n=317 ) had a TAE exam and a comprehensive eye exam on the same day . A subset of participants with normal baseline exams ( n=72 ) had follow-up exams 1 year later . We measured the level of agreement for referable ocular findings . Results Agreement for referable ocular findings was moderate ( n=389 , agreement : 77 % ; κ : 0.55 ) , due in part to ungradable exams ( 22 % ) . However , about half of the ungradable exams had findings that warranted referral . There was substantial agreement for follow-up exams ( n=72 , agreement : 93 % ; κ : 0.63 ) . Among all gradable exams ( n=303 ) , the TAE exam had 86 % sensitivity and 84 % specificity for referable ocular findings , with high agreement ( ≥94 % ) for DR and other major ocular diagnoses . Conclusions There was moderate-to-substantial agreement between a TAE exam and a comprehensive eye exam for referable ocular findings in patients with diabetes . Ungradable exams were a frequent marker of ocular pathology . Teleretinal imaging may be a useful evaluation for both diabetic and non-diabetic ocular conditions OBJECTIVE To report a pilot study of telemedical direct ophthalmoscopy in the diagnosis of acquired immune deficiency syndrome (AIDS)-related retinopathy in a human immunodeficiency virus (HIV)-positive population and in the diagnosis of glaucoma , cataract , and retinopathy in a diabetic population . DESIGN Prospect i ve comparative case series . PARTICIPANTS Seventeen HIV-positive and 20 diabetic patients . METHODS A direct ophthalmoscope custom-fitted with a digital microcamera capable of transmitting images from any of 61 sites within the Georgia Statewide Telemedicine Program was used by a nonophthalmologist to examine 34 eyes of 17 HIV-positive patients and 39 eyes of 20 patients with diabetes . Fundus images were transmitted in real-time to a review ing ophthalmologist . An in-person , comprehensive examination including indirect ophthalmoscopy , was performed by a second ophthalmologist . Telemedical examination was compared to the in-person comprehensive examination . RESULTS For the HIV study , 21 eyes did not show HIV retinopathy ( noninfectious retinopathy with cotton-wool spots ) by in-person examination . Telemedical examination correctly identified 20 of these eyes as disease-free ( specificity = 95 % ) . HIV retinopathy was present in 12 of the 34 eyes by in-person evaluation with telemedical examination correctly diagnosing 10 of these eyes ( sensitivity = 83 % ) . One eye with dense cataract and retinal detachment was unable to be evaluated ophthalmoscopically by either in-person or telemedical examination . Telemedical and in-person assessment s for HIV retinopathy were identical in 100 % of eyes without cataract . Disagreement in diagnosis between telemedical and in-person examination was associated with cataract ( P < 0.0007 ) . For the diabetes study , because of an inadequate image , telemedical examination was unable to classify 46 % and 36 % of eyes for glaucoma and diabetic retinopathy , respectively . Inability to make a telemedical determination for glaucoma ( P < 0.011 ) , nonproliferative ( P < 0.064 ) and proliferative ( P < 0.064 ) diabetic retinopathy was associated with cataract . Of the eyes that were able to be assessed by telemedical examination for diabetic retinopathy ( n = 25 ) , glaucoma ( n = 21 ) , and cataract ( n = 39 ) , the accuracy was poor ( sensitivity = 29 % , 50 % , and 41 % , respectively ) . Telemedical examination for diabetic retinopathy and glaucoma was more likely to agree with in-person examination in eyes without cataract as compared to eyes with cataract ( not statistically significant ) . CONCLUSION Telemedical direct ophthalmoscopic , real-time fundus imaging may provide a valuable means for providing ophthalmic consultation to the primary care physician in younger patients without lens or media opacity , but is inadequate for eyes with any degree of lens or media opacity PURPOSE To report the accuracy of telemedical slit-lamp evaluation in examination of ocular adnexa and anterior segment . METHODS By means of contingency tables , slit-lamp findings by live examination and by real-time telemedicine were compared in 50 eyes of 25 patients . RESULTS Sensitivity percentages ( proportion with findings correctly identified by telemedicine)/specificity percentages ( proportion without the finding that was correctly identified by telemedicine ) were 100/64 for eyelid mass , 100/85 for conjunctival pigment , 100/100 for posterior synechiae , 80/0 for blepharitis , 83/93 for iridotomy , 70/93 for pinguecula , 75/93 for iris lesions , 56/98 for corneal scar , 0/100 for chamber inflammation , 57/93 for nuclear cataract , and 37/100 for intraocular lens presence . CONCLUSIONS By means of monocular slit-lamp telemedical evaluation , clinical findings with high contrast cues for color and depth have the highest sensitivity and specificity PURPOSE To determine the feasibility of remote diagnostic screening for cytomegalovirus ( CMV ) retinitis among HIV patients in northern Thail and . DESIGN Prospect i ve , observational cross-sectional study . METHODS One hundred eighty-two eyes from 94 consecutive patients with HIV seen in 2008 and 2009 at a tertiary university-based medical center were photographed using a digital retinal camera . Individual and composite images were uploaded to a secure web site . Three expert grade rs accessed the electronic images and grade d each image for signs of CMV retinitis . Results of remote expert grading were compared with on-site patient examination by local expert ophthalmologists . RESULTS On-site ophthalmologists diagnosed CMV retinitis in 89 ( 48.9 % ) of 182 eyes . Trained ophthalmic photographers obtained digital retinal images for all 182 eyes . As compared with the on-site examinations , the sensitivity for detecting CMV retinitis by remote readers using composite retinal images ranged from 89 % to 91 % . The specificity for detecting CMV retinitis by remote readers ranged from 85 % to 88 % . Intrarater reliability was high , with each grade r achieving a κ value of 0.93 . Interrater reliability among the 3 grade rs also was high , with a κ value of 0.86 . CONCLUSIONS Remote diagnostic screening for CMV retinitis among HIV-positive patients may prove to be a valuable tool in countries where the burden of HIV exceeds the capacity of the local eye care providers to screen for ocular opportunistic infections |
1,734 | 27,749,286 | mDCF chemotherapy with splitted weekly or biweekly schedules , or reduced 3-weekly doses , is a very effective and well-tolerated regimen in metastatic GC .
By providing a 50 % ORR , such regimens may be particularly indicated for younger and fit patients for cytoreductive purpose s ( conversion therapy ) or in case of symptomatic tumor burden | Combination of docetaxel , cisplatin , and 5-fluorouracil ( DCF ) is an active but not well-tolerated regimen for advanced gastric cancer ( GC ) with st and ard 3-weekly doses .
Several modified schedules ( mDCFs ) have been design ed to reduce acute toxicities and improve feasibility as first-line therapy in patients with metastatic GC .
The objective of this systematic review was to evaluate overall survival ( OS ) , progression-free survival ( PFS ) , overall response rate ( ORR ) , and grade ( G ) greater than or equal to 3 adverse event of mDCF chemotherapy in this setting . | PURPOSE For patients with advanced gastric or gastroesophageal cancer ( AGGEC ) providing clinical benefit with improved palliation is highly desirable . However , a prospect i ve evaluation of clinical benefit in AGGEC patients has never before been reported in a phase III setting . PATIENTS AND METHODS In a multinational trial ( V325 ) , 445 patients were r and omly assigned and treated with either docetaxel plus cisplatin and fluorouracil ( DCF ) or cisplatin and fluorouracil ( CF ) . Clinical benefit was prospect ively evaluated in this trial as a secondary end point . The primary measure for clinical benefit analysis was time to definitive worsening by one or more categories of Karnofsky performance status ( KPS ) . Secondary clinical benefit end points included time to 5 % definitive weight loss , time to definitive worsening of appetite by one grade , pain-free survival ( defined as time to first appearance of pain ) , and time to first cancer pain-related opioid intake . Clinical benefit assessment s were recorded at each clinic visit . RESULTS Clinical benefit assessment s were performed in more than 75 % of patients throughout V325 . DCF significantly prolonged time to definitive worsening of KPS compared with CF ( median , 6.1 v 4.8 months ; hazard ratio , 1.38 ; 95 % CI , 1.08 to 1.76 ; log-rank P = .009 ) . Although time to definitive weight loss and time to definitive worsening of appetite favored DCF , the results were not statistically significant . Pain-free survival and time to first cancer pain-related opioid intake were comparable . CONCLUSION To our knowledge , V325 is the first phase III trial to report clinical benefit in AGGEC patients . Clinical benefit was assessed beyond protocol -specific chemotherapy . The addition of D to CF not only significantly improved clinical benefit but also improved quality of life , time to progression , and overall survival compared with CF Purpose The aim of this retrospective study ( from January 2007 to December 2011 ) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy-naïve AGC patients . Patients Patients ( n = 54 ) with locally inoperable or distant metastasis and performance status of 0–2 were eligible . The triplet combination chemotherapy consisting of docetaxel 60 mg/m2 on day 1 , cisplatin 60 mg/m2 on day 1 , and 5-fluorouracil 600 mg/m2 for 5 days of continuous infusion were administered every 21 days , up to nine cycles . Prophylactic G-CSF was not allowed . Results In all , 36 ( 67 % ) patients were male and 18 ( 33 % ) were female ; median age was 59 years . The majority of patients ( n = 46 , 85 % ) had metastatic disease and 8 ( 15 % ) of them had locally advanced disease . Liver metastasis and peritonitis carcinomatosa were found in 20 ( 43 % ) and 18 ( 39 % ) of the 46 cases , respectively . The median cycle of chemotherapy was 6 . In assessing 50 patients for response evaluation , one had complete response . Partial response was achieved in 27 ( 54 % ) patients . Seventeen patients ( 34 % ) had stable disease and 5 ( 10 % ) had progressive disease , while 4 % ( n = 2 ) and 11 % ( n = 6 ) of the patients developed severe ( grade 3–4 ) neutropenia and anemia , respectively . During the median follow-up time ( 6.9 months , range 0.4–24 ) , 28 ( 52 % ) patients died . The overall and progression-free survival were 10.7 [ 95 % CI 8.9–12.4 ] and 6.8 [ 95 % CI 5.8–7.8 ] months , respectively . Conclusions Although this was not a prospect i ve comparative study , the mDCF regimen seems to be as effective as the original DCF in AGC with acceptable and manageable side effects Gastric cancer is the second most common among cancer-related deaths in the world . Systemic chemotherapy for patients with gastric cancer has limited impact on overall survival . We performed a retrospective analysis of the efficacy and side effects of Docetaxel and Cisplatin Plus Fluorouracil ( DCF ) versus Modified-Dose Docetaxel , Cisplatin , and 5-Fluorouracil ( mDCF ) in the metastatic gastric cancer with first-line chemotherapy treated patients . Retrospectively were review ed 107 locally advanced or metastatic gastric cancer patients who were treated DCF or mDCF as first-line treatment from June 2007 to August 2011 in Dicle University Hospital , Department of Medical Oncology . The DCF protocol included 75 mg/m2 docetaxel and cisplatin on day 1 and 750 mg/m2/day 5-FU infusion for 5 days , repeated every 3 weeks . The mDCF protocol included 60 mg/m² docetaxel and cisplatin on day 1 and 600 mg/m² 5-Fluorouracil continuous infusion per day on days 1 - 5 , every 3 weeks . Patients were treated using DCF arm 85 ( M : 56 , F : 29 ) , the mDCF arm 22 ( M : 13 , F : 9 ) After treatment toxicities were : Grade III-IV neutropenia ( 48.2 % vs 13.6 % p=0.003 ) , anemia ( 21.2 % vs 4.5 % p=0.06 ) , nausea ( 44.7 % vs 13.6 % p=0.008 ) and vomiting ( 31.8 % vs 4.5 % , p=0.01 ) was higher in the DCF arm . Other toxicities profile was similar in both groups ( p>0.05 ) . The rate of response was similar in both arm . Among patients with the DCF and mDCF arm rate complete response ( 10.3 % vs 6.7 % , p>0.05 ) , partial response ( 35.3 % vs 40.0 % , p>0.05 ) , stable disease ( 32.4 % vs 33.3 % , p>0.05 ) , progressive disease ( 22.1 % vs 20.0 % , p>0.05 ) and overall response ( 45.6 % vs 46.7 % , p>0.05 ) did not have a statistically difference ( p>0.05 ) . Progression-free survival ( PFS ) and overall survival ( OS ) were more favorable in the DCF arm than mDCF arm , but the difference was not significant statistically ( 9.9 vs 8.6 , 7.4 vs 6.5 p>0.05)In conclusion , the response rate , median PFS and median OS are similar in both arms , while the mDCF regimen are more favorable than the DCF for toxicity profile regimen in advanced gastric cancer patients who were undergoing first-line palliative treatment . Therefore , a prospect i ve and larger clinical trials are needed Background This study was conducted to determine the optimal dosage of the docetaxel-capecitabine-cisplatin ( DXP ) regimen and to evaluate its efficacy and safety in patients with advanced gastric cancer . Methods Patients with advanced gastric or esophagogastric junctional adenocarcinoma received capecitabine ( days 1–14 ) and intravenous docetaxel and cisplatin ( day 1 ) every 3 weeks . Results In the phase I study , 15 patients were treated with 4 different dose levels . Asthenia and neutropenic fever were the dose-limiting toxicities . For the phase II study , 1,125 mg/m2 of capecitabine was initially recommended with 60 mg/m2 docetaxel and 60 mg/m2 cisplatin . However , frequent dose modifications at this dose level result ed in a final optimal dose of 937.5 mg/m2 capecitabine . Among the 40 patients enrolled in the phase II study , 4 complete and 23 partial responses were observed , presenting objective response rate of 68 % . Ten patients achieving good response with complete disappearance of distant metastases underwent surgery , and 4 pathologic complete responses were identified . After the median follow-up of 83.7 months ( range , 20.2–86.5 ) in surviving patients , the median overall survival was 14.4 months and median progression-free survival was 7.6 months . The most frequent grade 3/4 adverse events were neutropenia ( 62.5 % ) and asthenia ( 37.5 % ) . Ten per cent of the patients experienced neutropenic fever , with one case of sepsis-induced death . Conclusion DXP displays considerable antitumor activity , and may thus present effective first-line treatment for advanced gastric cancer . Further investigation of the efficacy and safety of this regimen in both first-line and neoadjuvant setting s is warranted BACKGROUND Phase II and III trials of docetaxel , cisplatin and fluorouracil ( DCF ) have shown superior efficacy versus cisplatin and fluorouracil alone but high rates of hematologic toxicity in advanced gastric cancer . To reduce toxicity while maintaining the efficacy of DCF , we investigated split doses of docetaxel ( T ) , cisplatin ( P ) , leucovorin ( L ) and fluorouracil ( F ) . PATIENTS AND METHODS Chemotherapy-naive patients with advanced gastric-/esophageal adenocarcinomas received T 50 mg/m(2 ) and P 50 mg/m(2 ) on days 1 , 15 and 29 and L 500 mg/m(2 ) plus F 2000 mg/m(2 ) weekly , every 8 weeks . Because significant dose reductions to < 80 % became necessary in 80 % of patients , the regimen was amended after the first 15 patients to T 40 mg/m(2 ) , P 40 mg/m(2 ) , L 200 mg/m(2 ) and F 2000 mg/m(2 ) . The primary endpoint was response rate . RESULTS Sixty patients were enrolled : 24 had locally advanced ( LA ) tumors and 36 had metastatic disease . Grade 3/4 toxicities included neutropenia ( 22 % ) , febrile neutropenia ( 5 % ) , diarrhea ( 20 % ) and lethargy ( 18 % ) . The overall response rate was 47 % . Twenty-three LA patients underwent secondary surgical resection ( 96 % ) ; complete resection was achieved in 87 % . Overall , median time to progression and overall survival were 9.4 and 17.9 months , respectively ( 8.1 and 15.1 months , respectively , for patients with metastatic disease ) . CONCLUSION T-PLF regimen is highly active and has a favorable toxicity profile Background The V325 study showed that docetaxel , cisplatin , and fluorouracil ( DCF ) prolonged overall survival ( OS ) of patients with advanced gastric cancer , but with a high incidence of dose-limiting toxicities . We investigated the efficacy and safety of a modified DCF ( mDCF ) regimen for Chinese patients with advanced gastric cancer . Methods Untreated advanced gastric cancer patients r and omly received docetaxel and cisplatin at 60 mg/m2 ( day 1 ) followed by fluorouracil at 600 mg/m2/day ( days 1–5 ; mDCF regimen ) or cisplatin at 75 mg/m2 ( day 1 ) followed by fluorouracil at 600 mg/m2/day ( days 1–5 ; CF ) every 3 weeks . The primary end point was progression-free survival ( PFS ) . The secondary end points were OS , overall response rate ( ORR ) , time-to-treatment failure ( TTF ) , and safety . Results In total , 243 patients were r and omized to treatment ( mDCF regimen 121 ; CF 122 ) . Compared with CF , the mDCF regimen significantly improved PFS and OS : the median PFS was 7.2 and 4.9 months , respectively [ hazard ratio ( HR ) 0.58 , log-rank P = 0.0008 ] , and the median OS was 10.2 and 8.5 months , respectively ( HR = 0.71 , P = 0.0319 ) . Additionally , the mDCF regimen improved the parameters used as secondary objectives : the ORR was 48.7 % with the mDCF regimen versus 33.9 % with CF ( P = 0.0244 ) ; the median TTF was 3.4 months with the mDCF regimen and 2.4 months with CF ( HR = 0.67 , P = 0.0027 ) . Grade 3 and grade 4 treatment-related adverse events occurred in 77.3 % of patients who received the mDCF regimen versus 46.1 % of patients who received CF ( P < 0.001 ) . Conclusions The mDCF regimen , compared with CF , significantly prolonged PFS and OS and enhanced ORR of Chinese patients with advanced gastric cancer . The mDCF regimen achieved efficacy comparable to that of DCF but with fewer toxicities , which is appropriate for the Chinese population Purpose This phase II trial aim ed to evaluate the efficacy and safety of docetaxel , cisplatin , and fluorouracil ( DCF ) combination in neoadjuvant setting in patients with locally advanced gastric adenocarcinoma . Methods Fifty-nine patients with resectable or unresectable locally advanced gastric and gastroesophageal cancer were recruited in this multicenter , single-arm , open-label , local clinical phase II study conducted at three centers from Turkey between June 2006 and March 2012 . Patients had T3–4 or lymph node-positive disease . After staging with imaging and laparotomy or laparoscopy , they received three cycles of DCF with lenograstim . Imaging studies were repeated after the last two cycles . Patients who underwent surgery were followed up for at least 1 year after the surgery . Toxicity and response were evaluated in accordance with NCI-CTC version3.0 and RECIST 1.0 . Results At baseline , 66.1 % of patients were considered resectable . In 47 patients evaluable , partial response in 16 ( 34.0 % ) , stable disease in 27 ( 57.5 % ) , and progressive disease in four ( 8.5 % ) were observed . Forty-six patients underwent surgery . In 38 ( 64.4 % ; 95 % confidence interval ( CI ) 52.2–76.6 % ) out of 59 patients , complete resection ( R0 ) was achieved . Median overall and disease-free survival were 19.1 months ( 95 % CI 13.5–24.7 ) and 11.6 months ( 95 % CI 5.9–17.4 ) , respectively . The most frequent grade 3–4 adverse events were neutropenia ( 52.5 % ) , febrile neutropenia ( 11.9 % ) , leukopenia ( 39.0 % ) , and diarrhea ( 10.5 % ) . One patient died from an unknown cause . Conclusions Classical DCF triplet with lenograstim showed a good clinical response with acceptable safety profile in the treatment of locally advanced gastric and gastroesophageal cancer with a significant R0 rate and manageable toxicity BACKGROUND A phase III trial involving docetaxel , cisplatin , and fluorouracil ( DCF ) in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone , but with a high rate of hematologic toxicity . To reduce toxicity while maintaining the efficacy of DCF , we reduced the doses of docetaxel ( D ) and cis-platinum ( CDDP ) , and administered 5-fluorouracil ( 5-FU ) via a continuous intravenous ( CIV ) infusion . METHODS Chemotherapy-naive patients with gastric adenocarcinomas received D ( 60 mg/m(2 ) 1 hour on day 1 ) , CDDP ( 30 mg/m(2 ) on days 1 and 2 ) , and 5-FU ( 1500 mg × m(-2) × 24 h(-1 ) CIV on days 1 and 8 every 3 weeks ) . The primary endpoint was the response rate . RESULTS Fourteen patients were enrolled . Based on the efficacy evaluation following at least 2 cycles of treatment , there was 7.1 % complete remission ( CR ) , 71 % partial remission ( PR ) , 14 % stable disease ( NC/SD ) , and 7.1 % progressive disease ( PD ) . The median survival time was 13 months . Nine patients ( 64 % ) had grade III-IV neutropenia , and 4 patients ( 29 % ) had grade IV neutropenia , among whom 1 had grade IV neutropenia with grade III nausea and vomiting . CONCLUSION The modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer PURPOSE In the r and omized , multinational phase II/III trial ( V325 ) of untreated advanced gastric cancer patients , the phase II part selected docetaxel , cisplatin , and fluorouracil ( DCF ) over docetaxel and cisplatin for comparison against cisplatin and fluorouracil ( CF ; reference regimen ) in the phase III part . PATIENTS AND METHODS Advanced gastric cancer patients were r and omly assigned to docetaxel 75 mg/m2 and cisplatin 75 mg/m2 ( day 1 ) plus fluorouracil 750 mg/m2/d ( days 1 to 5 ) every 3 weeks or cisplatin 100 mg/m2 ( day 1 ) plus fluorouracil 1,000 mg/m2/d ( days 1 to 5 ) every 4 weeks . The primary end point was time-to-progression ( TTP ) . RESULTS In 445 r and omly assigned and treated patients ( DCF = 221 ; CF = 224 ) , TTP was longer with DCF versus CF ( 32 % risk reduction ; log-rank P < .001 ) . Overall survival was longer with DCF versus CF ( 23 % risk reduction ; log-rank P = .02 ) . Two-year survival rate was 18 % with DCF and 9 % with CF . Overall response rate was higher with DCF ( chi2 P = .01 ) . Grade 3 to 4 treatment-related adverse events occurred in 69 % ( DCF ) v 59 % ( CF ) of patients . Frequent grade 3 to 4 toxicities for DCF v CF were : neutropenia ( 82 % v 57 % ) , stomatitis ( 21 % v 27 % ) , diarrhea ( 19 % v 8 % ) , lethargy ( 19 % v 14 % ) . Complicated neutropenia was more frequent with DCF than CF ( 29 % v 12 % ) . CONCLUSION Adding docetaxel to CF significantly improved TTP , survival , and response rate in gastric cancer patients , but result ed in some increase in toxicity . Incorporation of docetaxel , as in DCF or with other active drug(s ) , is a new therapy option for patients with untreated advanced gastric cancer PURPOSE Therapy of patients with advanced gastric or gastroesophageal junction cancer should provide symptom relief and improve quality of life ( QOL ) because most patients are symptomatic at baseline . Using vali date d instruments , we prospect ively assessed QOL ( even after completion of protocol treatment ) as one of the secondary end points of the V325 phase III trial . PATIENTS AND METHODS Four hundred forty-five patients r and omly received either docetaxel 75 mg/m(2 ) and cisplatin 75 mg/m(2 ) each on day 1 plus fluorouracil 750 mg/m(2)/d continuous infusion on days 1 to 5 every 3 weeks ( DCF ) or cisplatin 100 mg/m(2 ) on day 1 plus fluorouracil 1,000 mg/m(2)/d continuous infusion on days 1 to 5 every 4 weeks ( CF ) . The European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) and , where available , the EuroQOL EQ-5D question naire were administered every 8 weeks from baseline until progression and then every 3 months . Time to definitive deterioration of QOL parameters was analyzed . RESULTS The proportions of patients having assessable EORTC QLQ-C30 and EQ-5D question naires at baseline were 86.0 % and 78.7 % with DCF , respectively , and 89.7 % and 92.8 % with CF , respectively . Time to 5 % deterioration of global health status ( primary end point ) significantly favored DCF over CF ( log-rank test , P = .01 ) . QOL was preserved longer for patients on DCF than those on CF for all time to deterioration analyses , demonstrating the statistical superiority of DCF compared with CF . CONCLUSION V325 represents the largest trial with the longest prospect ively controlled evaluations of QOL during protocol chemotherapy and follow-up in patients with advanced gastric or gastroesophageal junction cancer . In V325 , advanced gastric or gastroesophageal junction cancer patients receiving DCF not only had statistically improved overall survival and time to tumor-progression , but they also had better preservation of QOL compared with patients receiving CF |
1,735 | 23,832,632 | The literature provides high- grade evidence that SCIT reduces asthma symptoms , asthma medication usage , rhinitis/rhinoconjunctivitis symptoms , conjunctivitis symptoms , and rhinitis/rhinoconjunctivitis disease-specific quality of life in comparison to placebo or usual care .
There is moderate evidence that SCIT decreases rhinitis/rhinoconjunctivitis medication usage .
Respiratory reactions were the most common systemic reaction .
Generally moderate to strong evidence supports the effectiveness of SCIT for treatment of allergic rhinitis and asthma , particularly with single-allergen immunotherapy regimens .
Adverse reactions to SCIT are common , but no deaths were reported in the included studies | OBJECTIVES /HYPOTHESIS To systematic ally review the effectiveness and safety of subcutaneous immunotherapy ( SCIT ) for treatment of allergic rhinoconjunctivitis and asthma , using formulations currently approved in the United States . | A double-blind , placebo-controlled trial of immunotherapy was conducted in patients with Dermatophagoides pteronyssinus rhinitis . Thirty patients received an extract with a high content of Der p I ( Pharmalgen ) , 20 received a conventional mite extract ( Allpyral ) , and 30 patients received histamine chloride ( placebo ) . Specific IgG and subclasses were measured before and after 3 and 12 months of treatment by RIA and /or ELISA , and specific IgE by RAST . Clinical outcome was assessed by skin prick tests , nasal challenge , visual analogue , and diary-card symptom and drug scores ; from these findings , a clinical index was derived . An IgG response occurred only in the Pharmalgen-treated group : D. pter IgG and IgG1 increased by 3 months ( p less than 0.05 ) and then plateaued to 12 months ( p less than 0.05 ) . IgG4 levels increased throughout treatment ( p less than 0.05 and p less than 0.01 ) , as did the IgG/IgE ratio . A subclass switch from IgG1 to IgG4 occurred . D. pter IgE rose at 3 months ( p less than 0.05 ) . Clinical improvement occurred at 3 and 12 months in the Pharmalgen-treated group only . Pretreatment levels of IgE , IgG1 , or IgG4 did not predict clinical outcome . Our findings are compatible with the hypothesis that IgG subclasses may modulate antigen-IgE interactions , although the antibody response to this potent extract need not be causally related to improvement The present work reports the results of a double‐blind clinical trial , comparing the effects of hyposensitization treatment versus placebo in 33 patients with allergic rhinitis , sensitive to a crude extract of the pollen of four different grasses ( Dactylis glamerata , Lolium perenne , Secale cereale , and Phlewn pratense ) . The distribution of these patients in the two groups was done r and omly and gave two comparable groups , as far as clinical and biological features are concerned . The treatment course included five low doses of the aqueous extract followed by 12 injections of Al(OH)3‐adsorbed aliquots of the same extract . Evaluation of the clinical scores was based on diary cards on which symptoms and medications were recorded . A reevaluation of the significance of the symptom and medication scores is presented and the link between both scores is studied . Particular attention is given to the method ological and statistical problems raised during this study . The non‐parametric tests reveal a significant difference ( P < 0.03 ) in the total clinical score between the treated and the placebo groups for the second half of the observation period , when the pathology was most intense Background Little information is available on the effect of allergen-specific immunotherapy on airway responsiveness and markers in exhaled air . The aims of this study were to assess the safety of immunotherapy with purified natural Alt a1 and its effect on airway responsiveness to direct and indirect bronchoconstrictor agents and markers in exhaled air . Methods This was a r and omized double-blind trial . Subjects with allergic rhinitis with or without mild/moderate asthma sensitized to A alternata and who also had a positive skin prick test to Alt a1 were r and omized to treatment with placebo ( n = 18 ) or purified natural Alt a1 ( n = 22 ) subcutaneously for 12 months . Bronchial responsiveness to adenosine 5'-monophosphate ( AMP ) and methacholine , exhaled nitric oxide ( ENO ) , exhaled breath condensate ( EBC ) pH , and serum Alt a1-specific IgG4 antibodies were measured at baseline and after 6 and 12 months of treatment . Local and systemic adverse events were also registered . Results The mean ( 95 % CI ) allergen-specific IgG4 value for the active treatment group increased from 0.07 μg/mL ( 0.03 - 0.11 ) at baseline to 1.21 μg/mL ( 0.69 - 1.73 , P < 0.001 ) at 6 months and to 1.62 μg/mL ( 1.02 - 2.22 , P < 0.001 ) at 12 months of treatment . In the placebo group , IgG4 value increased nonsignificantly from 0.09 μg/mL ( 0.06 - 0.12 ) at baseline to 0.13 μg/mL ( 0.07 - 0.18 ) at 6 months and to 0.11 μg/mL ( 0.07 - 0.15 ) at 12 months of treatment . Changes in the active treatment group were significantly higher than in the placebo group both at 6 months ( P < 0.001 ) and at 12 months of treatment ( P < 0.0001 ) . However , changes in AMP and methacholine responsiveness , ENO and EBC pH levels were not significantly different between treatment groups . The overall incidence of adverse events was comparable between the treatment groups . Conclusion Although allergen-specific immunotherapy with purified natural Alt a1 is well tolerated and induces an allergen-specific IgG4 response , treatment is not associated with changes in AMP or methacholine responsiveness or with significant improvements in markers of inflammation in exhaled air . These findings suggest dissociation between the immunotherapy-induced increase in IgG4 levels and its effect on airway responsiveness and inflammation Background Calcium phosphate‐adsorbed allergen extracts are used for subcutaneous immunotherapy to avoid the use of aluminium adjuvants Inl and areas of northern California have an intense grass pollination in the spring of each year . This is accompanied by a stirking rise in the incidence of asthma . We documented this relationship and design ed a trial to test the efficacy of immunotherapy for grass-pollen asthma . Aeroallergen counts were performed on the roof of the allergy clinic of David Grant Medical Center from January 1981 to December 1984 by a gravity collector . These counts were compared to counts done on a Rotorod at a nearby hospital from July 1982 to September 1984 . Climatologic factors were also tabulated . Visits for asthma and rhinitis to our emergency room and asthma admissions to our hospital were counted for the 4-year period . A r and omized , double-blinded , placebo-controlled trial of immunotherapy with grass-pollen extract was performed from November 1984 to June 1985 . Two groups of clinical ly and immunologically well-matched subjects were started on an accelerated preseasonal trial of immunotherapy . One group received a st and ardized grass extract , and the other group did not . Both groups received other extracts of aeroallergens to which they were skin test positive that occur locally in the spring and summer . This was done because of our dissatisfaction with a histamine placebo used in a previous pilot study . Symptom medication scores ( SMS ) and immunologic parameters were followed . For the 4-year period , grass-pollen count ( GPC ) correlated strongly with asthma emergency room visits ( r = 0.90 ; p less than 0.001 ) and for rhinitis ( r = 0.92 ; p less than 0.001 ) . Asthma admissions also correlated strongly with GPC ( r = 0.72 ; p less than 0.001 ) . Other aeroallergens either did not correlate significantly or occurred in such small numbers that they could not be seriously considered . Rotorod counts supported these conclusions with the exceptions of some Basidiomycetes . Climatologic factors demonstrated no relationship to the incidence of asthma . Asthma SMS were lower in the grass-treated group , p less than 0.05 . Rhinitis SMS were also lower but did not reach significance , p = 0.11 . RGGI sIgE did not rise significantly in the grass-treated group but did in the placebo-treated group . RGGI sIgE rose in both groups , although to significantly higher levels in the grass-treated group , p less than 0.001 . The asthma SMS were inversely related to increasing RGGI cumulative dose , p less than 0.10 . Linear regression analysis of the dose-response scattergram suggests that a cumulative dose of approximately 90 micrograms of RGGI may be desirable . ( ABSTRACT TRUNCATED AT 400 WORDS We have performed a comparative study to evaluate seasonal and perennial schedules after 3 years of immunotherapy . Sixty patients suffering from rhinitis and /or asthma due to grass pollen sensitization were r and omly allocated to receive a semi-depot extract of Phleum pratense according to a perennial or seasonal schedule . The last year of the study , 14 patients were recruited as a control group without immunotherapy . The cumulative dose was 602 BU in the perennial group and 372 BU in the seasonal group . The frequency and severity of side-effects were similar and very low in both treated groups . The IgE level was significantly lower after perennial immunotherapy at the end of the first 2 years . A seasonal decrease in specific IgG levels was observed in patients who interrupted immunotherapy , while this was not observed in patients under the perennial schedule . Symptoms and medication scores did not show differences between groups . Nevertheless , we found a significant difference between treated patients and the control group OBJECTIVE --To evaluate the efficacy and safety of immunotherapy ( hyposensitisation ) in patients with severe summer hay fever . DESIGN --A r and omised , double blind , placebo controlled study of a biologically st and ardised depot grass pollen extract . SETTING --Allergy clinic , Royal Brompton and National Heart Hospital , London . PATIENTS --40 adults ( mean age 35 years ) with a history of severe grass pollen allergy uncontrolled by st and ard antiallergic drugs . Patients with perennial asthma were specifically excluded . INTERVENTION-- Patients were r and omised to receive either an active preparation ( Alutard SQ , a grass pollen ( Phleum pratense ) extract ) or placebo at a rate of two subcutaneous injections a week in increasing doses until a maintenance dose was reached . This maintenance dose was given once a month . MAIN OUTCOME MEASURES -- Clinical efficacy was evaluated by symptom and drug diary cards , visual analogue scores during the grass pollen season , and a postseasonal assessment by the patients and a doctor . Conjunctival and skin sensitivity to local allergen provocation was measured before and after eight months of treatment . RESULTS --There was a highly significant decrease ( median Alutard SQ v median placebo ( 95 % confidence interval for difference between medians ] in total symptom scores ( p=0.001 ) in the Alutard SQ treated group ( 360 v 928 ( 238 to 825 ] . Significant differences were also found in total drug use ( p=0.002 , 129 v 627 ( 178 to 574 ] . Visual analogue symptom scores were also reduced in the active group ( p=0.02 , 2.2 v 5.5 ( -4.8 to -0.5 ] . The postseasonal assessment , by either the doctor or the patients , showed a large improvement ( p less than 0.001 ) in favour of Alutard SQ . Provocation tests showed a greater than 10-fold reduction for the active group in immediate conjunctival allergen sensitivity ( p=0.001 ) , a 40 % decrease in early phase response ( p=0.02 ) , and a 57 % decrease in the late phase ( p=0.001 ) cutaneous response after intradermal allergen . A total of 523 active injections were given . There was one systemic reaction at 10 minutes after injection , which was rapidly reversed with intramuscular adrenaline . There was one mild delayed urticarial reaction at 2 1/2 hours . CONCLUSION --Immunotherapy is effective in patients with severe summer hay fever , but immediate anaphylactic reactions limit its use to specialised centres . Patient selection is extremely important , and chronic perennial asthma should be specifically excluded . As serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary BACKGROUND Grass pollen immunotherapy for allergic rhinitis is a disease-modifying treatment that results in long-term clinical tolerance lasting years after treatment discontinuation . Active treatment is associated with generation of inhibitory grass pollen-specific IgG antibodies capable of blocking allergen-IgE interactions . OBJECTIVES We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy . METHODS We conducted a 4-year study in which patients who had moderate-to-severe allergic rhinitis underwent a r and omized , double-blind , placebo-controlled discontinuation of subcutaneous grass pollen immunotherapy . All subjects received grass pollen immunotherapy injections for 2 years ( n = 13 ) , followed by a further 2 years of either active ( n = 7 ) or placebo ( n = 6 ) injections . Clinical outcomes included seasonal symptoms and use of rescue medication . Serum specimens were collected at baseline and after 2 and 4 years for quantification of allergen-specific IgG antibodies . Sera were also tested for IgG-dependent inhibitory bioactivity against IgE-allergen binding in cellular assays by using flow cytometry and confocal microscopy to detect binding of IgE-grass pollen allergen complexes to B cells . RESULTS Clinical improvement was maintained after 2 years of discontinuation . Although immunotherapy-induced grass pollen-specific IgG1 and IgG4 levels decreased to near-preimmunotherapy levels during discontinuation , inhibitory bioactivity of allergen-specific IgG antibodies was maintained unchanged . CONCLUSION Grass pollen immunotherapy induces a sub population of allergen-specific IgG antibodies with potent inhibitory activity against IgE that persists after treatment discontinuation and that could account for long-term clinical tolerance Most extracts used in hyposensitization are complex and ill‐defined mixtures of a large number of antigenic components . A highly refined ( purified ) and well‐characterized allergen preparation from Timothy pollen ( Phleum pratense ) is now available BACKGROUND Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis , although it is question able whether there is long-term benefit after the discontinuation of treatment . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective . During the three years of this trial , primary outcome measures were scores for seasonal symptoms and the use of rescue medication . Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge . Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells ( TH2 cells ) ( as evidence d by the presence of interleukin-4 messenger RNA ) . A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease . RESULTS Scores for seasonal symptoms and the use of rescue antiallergic medication , which included short courses of prednisolone , remained low after the discontinuation of immunotherapy , and there was no significant difference between patients who continued immunotherapy and those who discontinued it . Symptom scores in both treatment groups ( median areas under the curve in 1995 , 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy ; P=0.60 ) were markedly lower than those in the group that had not received immunotherapy ( median value in 1995 , 2863 ) . Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation , there was a sustained reduction in the late skin response and associated CD3 + T-cell infiltration and interleukin-4 messenger RNA expression . CONCLUSIONS Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity BACKGROUND Although several studies support the efficacy of specific immunotherapy in allergic asthma , its benefit compared with that of st and ardized pharmacologic intervention remains unknown . OBJECTIVE A double-blind , placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite ( HDM ; Dermatophagoides species ) was conducted to assess the effects of specific immunotherapy added to guideline -adjusted pharmacologic treatment and allergen avoidance . METHODS After 1 observational year of pharmacologic treatment and st and ard measures of HDM avoidance , 2 groups of asthmatic subjects were r and omly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine ( n=41 ) or placebo ( n=31 ) for 3 years . Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines . RESULTS The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects . The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators , an increase in morning and evening peak expiratory flow , and a reduced skin sensitivity to HDM extracts . The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids , asthma symptoms , lung volumes , or bronchial responsiveness to methacholine . CONCLUSION These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits , possibly by reducing the allergic response of asthmatic patients sensitized to HDM Fraction A , a concentrate derived from short ragweed extract by (NH4)2SO4 precipitation , contains all major allergens including antigen E. Therapeutic efficacy and safety of this alum-adsorbed product was evaluated in a multicenter double-blind clinical trial by comparing it to placebo in 131 r and omly matched ragweed hay fever patients who were not treated for at least 1 year . Therapeutic response to fraction A injections was more significant than placebo ( p less than 0.05 ) by investigators ' evaluation , by average daily symptom score ( 1.097 vs. 1.378 , p less than 0.05 ) during the peak ragweed season , or by average proportion of days in which medication was required ( 0.411 vs. 0.584 , p = 0.01 ) . Fraction A patients exhibited a significantly higher ( p less than 0.0005 ) increase in hemagglutinating titer after treatment than placebo controls . Radioallergosorbent binding , evaluated in a subgroup of 31 patients before and after the ragweed season , was unchanged or decreased in 12 of 15 patients treated with fraction A. In contrast , 9 of 16 placebo-treated patients showed an increase in this index . Systemic effects were noted after 42 ( 1.5 % ) of 2.641 injections , while local reactions occurred at the rate of 2.3 % . It is concluded that a single course of preseasonal immunotherapy wih alum-adsorbed fraction A is effective and relatively safe In this study , the effect of a single preseasonal course of injection therapy on the symptoms of patients with allergic rhinitis or asthma due to pollen from the conifer , mountain cedar , was evaluated in a double-blind controlled manner . Patients treated with specific injection therapy were found to have significantly fewer symptoms than those who received placebo injections . Specific serum IgE antimountain cedar antibody decreased during the pollen season in the treated group and increased in the placebo group Objectives To evaluate the effectiveness of specific immunotherapy ( SIT ) in patients with severe house dust mite (HDM)‐induced perennial allergic rhinitis using diary cards and objective endpoints Background The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America A placebo‐controlled , double‐blind study of immunotherapy with the mould species Cladosporium was performed in 22 adult asthmatics . The diagnosis of Cladosporium allergy was based on a combination of bronchial provocation test and daily symptom score in the Cladosporium season . An aqueous preparation of a potent , biologically st and ardized and purified extract was used in a clustered dose‐increase regimen . The clinical efficacy was evaluated by a combination of symptoms ( asthma score + peak flow ) and consumption of antiasthmatic medication . The mean changes in symptoms and medication consumption over a 10–week registration period ( peak Cladosporium season ) in 1982 after 5–7 months of immunotherapy were compared with the corresponding 1981 pretreatment 10‐week period A significant ( P= 0.03 ) difference in terms of “ improved ” , “ unchanged ” and “ deteriorated ” patients in favour of Cladosporium treatment was found . Approximately 80 % in the Cladosporium group showed improved/unchanged symptoms contrary to 30 % of the placebo treated . Side effects were observed frequently but only in the Cladosporium‐treated . About 70 % experienced a large local reaction and 100 % had episodes of asthma during dose‐increase phase . Only a few severe systemic reactions occurred . Based on the clinical efficacy of the treatment we consider immunotherapy with Cladosporium feasible for highly specialized clinics Dermatophagoides pteronyssinus ( Dp ) is the major allergen in allergic asthma in France . St and ardized and lyophilized Dp extracts are available , and their effectiveness after a short course of rush immunotherapy was examined in a placebo-controlled , double-blind study . Twenty patients received the Dp st and ardized extract , and 10 other patients received a placebo extract . Before and 7 weeks after rush immunotherapy , in vivo and in vitro parameters were examined . Bronchial provocation tests performed in a st and ardized manner demonstrated that a provocative dose causing a 20 % fall in FEV1 , a 25 % fall in maximum mild expiratory flow rate , a 25 % fall in maximum flow when 50 % of the forced vital capacity has been expired , and a 35 % fall in specific airway conductance were significantly ( p less than 0.005 to p less than 0.01 , Wilcoxon W test ) improved in the treated group and remained unchanged in the placebo group . Skin test titration demonstrated that patients placed in the treated group had a significant ( p less than 0.001 , Wilcoxon W test ) decrease of both end point titer and size of the largest wheal . No significant difference was observed in the placebo group . Serum Dp-IgE did not vary significantly in either group . Serum Dp antigen P1-IgG was significantly ( p less than 0.001 , Wilcoxon W test ) increased in the treated group and slightly increased in the placebo-treated group . This study demonstrated that a Dp st and ardized extract administered by a rush protocol elicits a rapid and significant immune response and leads to a significant protection of the patients BACKGROUND Although the efficacy of allergen immunotherapy has been demonstrated in seasonal pollen allergy , there is no report of a double-blind placebo-controlled trial with st and ardized pollen extract in seasonal respiratory allergy from India . In the agricultural area of eastern India , Phoenix sylvestris Roxb or date sugar palm is grown or cultivated and seasonal allergic rhinitis is common during the pollen season . OBJECTIVE The objective of the present study was to observe the clinical and immunological changes during a 2-year double-blind placebo-controlled trial of immunotherapy with st and ardized P sylvestris pollen extract in respiratory patients sensitive to pollen from this wild date palm . Thirty-five subjects with typical seasonal allergic rhinitis with or without bronchial asthma were selected . A symptom-medication score ( based on a question naire and diary ) was correlated with pollen counts as recorded in a Burkard sample r. Eighteen subjects were r and omized to a specific immunotherapy ( SIT ) group receiving regular injections containing st and ardized allergen extract and 17 to a placebo control group . Changes in the level of specific immunoglobulin ( Ig ) E , IgG1 , and IgG4 were recorded at 3-month intervals . Measurement of wheal diameter , total IgE level and forced expiratory volume in 1 second ( FEV1 ) were performed before starting and a month after finishing therapy . RESULTS The SIT group showed decreases of 33.5 % and 57 % from the baseline symptom-medication scores during the first and second treatment season , respectively . This group showed significant decreases in skin-reactivity to P sylvestris pollen extract and in specific IgE levels , and significant increases in FEV , , specific IgGI ( 1.95 - 3.2 times higher ) and IgG4 ( 21.24 - 30.83 times higher ) . There were no significant changes in total IgE levels . The control group showed no significant changes for any parameter except the development of new sensitization in 2 cases ( to Saccharum officinarum pollen grain and Alternaria species spores ) . The rate of local adverse reactions was 0.024 % . CONCLUSION After a 2-year study , allergen immunotherapy with st and ardized P sylvestris pollen extract was found to be effective in seasonal respiratory allergic subjects susceptible to P sylvestris pollen with a narrow range of sensitization Perennial hyposensitization with a partially purified timothy extract result ed in a statistically significantly higher degree of clinical protection than treatment with the two timothy major allergens ( Nos. 19 and 25 ) and protected better from the second -- than during the first grass pollen season . The extracts were st and ardized biologically and adsorbed to aluminium hydroxide for administration . The therapy had a more beneficial influence on sneezing than on rhinorrhoea and blockage of nasal airways , and an excellent effect on grass pollen asthma was obtained with the partially purified timothy extract . Associated birch pollen allergy was not influenced by hyposensitization with grass pollen BACKGROUND Short-term immunotherapy ( STI ) can be beneficial for patients who are noncompliant with long-term specific immunotherapy . OBJECTIVE The efficacy and tolerance of STI with seven preseasonal injections of molecular st and ardized allergens from grass and rye pollen has been investigated in a double-blind , placebo-controlled multicenter study with 87 patients at 12 German University hospitals . METHODS Symptoms of the eyes , nose , and bronchi and use of symptomatic drugs were documented daily in diaries by patients with allergic rhinitis to grass and /or rye pollen and without bronchial asthma . Patients were monitored by skin prick test titration and measurement of levels of specific IgE and IgG4 . RESULTS The median nasal score for the 10 weeks with the strongest symptoms during the grass pollen season was significantly lower ( p = 0.014 ) with 35.0 for STI ( n = 41 ) versus 69.0 for placebo ( n = 40 ) ; the overall symptom score was 54.0 for STI versus 97.5 for placebo ( p = 0.020 ) . Only STI-treated patients exposed to less than 40 pollen grains per cubic meter per week showed a significantly lower nasal symptom score of 39.0 versus 75.0 for placebo ( p = 0.006 ) ; these patients also had fewer nasal symptoms and less use of topical nasal drugs ( p < 0.001 ) . The threshold dose in skin prick tests was significantly higher , being 9.06 histamine equivalent for skin prick test ( HEP ) for STI-treated patients who received the maximum dose ( n = 22 ) versus 4.33 HEP for placebo ( p = 0.005 ) . Specific IgE levels were significantly higher , being 55.9 SU/ml for STI versus 39.2 SU/ml for placebo after seven injections ( p = 0.006 ) and level of specific IgG4 was 5.36 % for STI versus 1.28 % for placebo ( p < 0.001 ) . No severe systemic reactions were observed . CONCLUSION STI with seven preseasonal injections with molecular st and ardized allergens is effective and well tolerated OBJECTIVE This study aim ed to evaluate the clinical efficacy and antibody response changes after specific immunotherapy ( SIT ) using Dermatophagoides pteronyssinus ( Dpt ) allergens with or without bacterial extracts in Brazilian mite-atopic patients . METHODS One-hundred patients with allergic rhinitis were selected for a r and omized double-blind , placebo-controlled trial and distributed into 4 groups : Dpt ( Dpt allergen extract ) , Dpt+MRB ( Dpt allergen plus mixed respiratory bacterial extracts ) , MRB ( MRB extract only ) and placebo . Rhinitis symptom and medication scores ; skin prick test ( SPT ) to Dpt extract ; and serum immunoglobulin ( Ig ) E , IgG4 , and IgG1 levels to Dpt , Der p 1 , and Der p 2 allergens were evaluated before and after a year of treatment . RESULTS After 1 year , the SPT response was reduced in the Dpt group ( P=.03 ) , whereas IgE levels to Der p 2 decreased only in the Dpt ( P = .048 ) and Dpt+MRB ( P = .005 ) groups . IgG4 and IgG1 levels to Dpt and Der p 1 increased in the Dpt group ( P < .05 ) , whereas in the Dpt + MRB group the IgG1 level only increased to Dpt ( P=.001 ) and the IgG4 only increased to Der p 1 ( P=.049 ) . IgE levels to Dpt decreased only in the MRB ( P= .005 ) and Dpt + MRB ( P= .001 ) groups . Rhinitis symptom and medication scores fell in all groups , including the placebo group ( P<.001 ) . CONCLUSIONS SIT using Dpt extract alone was effective in reducing SPT response and IgE levels to Der p 2 allergen , while bacterial extracts induced decreases in IgE levels to whole Dpt extract . However , only groups receiving Dpt allergen had higher levels of IgG1 and IgG4 to Dpt and Der p 1 after a year of treatment To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts , we performed a double‐blind , placebo‐controlled immunotherapy study in 30 patients with proven allergy to mite allergens . The specific immunotherapy with st and ardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated . After 1 year of treatment , the actively treated group showed a significant improvement compared to their starting value as well as to the placebo‐treated patients with regard to skin prick test , conjunctival provocation test , and subjective rhinitis score . The subjective asthma score and bronchial hyperreactivity , measured by the methacholine provocation test , was improved in comparison to the starting value , but not to the placebo group , after 12 months . However , a further , open comparison of the placebo‐ and verum‐treated groups at 18 months revealed a significant reduction . The drug intake was not increased in the verum‐treated group . Exposure to mite levels was constant throughout this time period , as revealed by antigen measurement . We conclude that specific immunotherapy in perennial , mite‐allergen‐induced asthma may reduce not only immediate , IgE‐mediated symptoms but , after a rather long time period of 12–18 months , also the inflammatory component of bronchial asthma , thus leading to a reduction of unspecific hyperreactivity The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol . Nine active-treatment subjects who received a mean cumulative dose of cat allergen , 1 of 10.9 units , and eight placebo-treatment subjects completed the study . Active treatment result ed in significant reductions in bronchial sensitivity ( p less than 0.05 ) and prick test titer ( p less than 0.01 ) . In addition , active treatment result ed in a significant delay in the onset of ocular ( p less than 0.05 ) and pulmonary ( p less than 0.02 ) symptoms on exposure to living cats . Significant increases in IgG antibody to cat allergen 1 ( p less than 0.001 ) and cat albumin ( p less than 0.01 ) also occurred with active treatment . There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils . These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations In 44 patients highly sensitive to ragweed , we compared weekly injections of single doses of ragweed extract ( RW-Wk , 15 patients ) with clustered doses of ragweed extract at 3-wk intervals ( RW-Cl , 18 patients ) for effects on ragweed hay fever symptom-medication scores and immunologic variates . Patients were matched and r and omly assigned to treatment groups . Ragweed doses were advanced to the highest tolerated dose . Doses and number of visits were lower in the RW-Cl group than in the RW-Wk group . Despite lower doses , systemic reactions were not reduced and antiragweed IgE levels increased significantly more in the RW-Cl group than those in the RW-Wk group . Both the RW-Cl and RW-Wk groups had significant increases in antiragweed IgG levels , decreases in seasonal rise in antiragweed IgE levels , and lower symptom-medication scores ( p less than 0.01 ) in comparison with the placebo group . We conclude that the RW-Cl regimen offered no important advantage over RW-Wk . Seventeen patients had previously received Rinkel- method immunotherapy with 0.5 ml of end-point dilution of ragweed extract for 1 to 2 yr without significant clinical improvement or immunologic changes . After adequate treatment with either RW-Wk or RW-Cl , these patients had significantly lower symptom-medication scores than those of the placebo groups and immunologic changes similar to those of the entire active-treatment group . Therefore , treatment failures on Rinkel immunotherapy respond well to adequate dose immunotherapy by either schedule T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings . We studied the role of IL-10 in the induction of clinical , cellular , and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis . Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen ( Phleum pratense , Phl P ) immunotherapy . We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy , but only during the pollen season . IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA+ cells . These changes were not observed in placebo-treated subjects or in healthy controls . Fifteen and 35 % of IL-10 mRNA signals were colocalized to CD3 + T cells and CD68 + macrophages , respectively , whereas only 1–2 % of total CD3 + cells and 4 % of macrophages expressed IL-10 . Following immunotherapy , peripheral T cells cultured in the presence of grass pollen extract also produced IL-10 . Immunotherapy result ed in blunting of seasonal increases in serum allergen Phl p 5-specific IgE , 60- to 80-fold increases in Phl p 5-specific IgG , and 100-fold increases in Phl p 5-specific IgG4 . Post-immunotherapy serum exhibited inhibitory activity , which coeluted with IgG4 , and blocked IgE-facilitated binding of allergen-IgE complexes to B cells . Both the increases in IgG and the IgG “ blocking ” activity correlated with the patients ’ overall assessment of improvement . Thus , grass pollen immunotherapy may induce allergen-specific , IL-10-dependent “ protective ” IgG4 responses BACKGROUND Specific immunotherapy is widely used to treat allergic rhinitis , but few large-scale clinical trials have been performed . OBJECTIVE We sought to assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with st and ard drug therapy . METHODS We performed a double-blind , r and omized , placebo-controlled study of 410 subjects ( 203 r and omized to 100,000 st and ardized quality units [ SQ-U ] maintenance , 104 to 10,000 SQ-U , and 103 to placebo ) . Three hundred forty-seven ( 85 % ) completed treatment . Groups were well matched for demographics and symptoms . RESULTS Across the whole pollen season , mean symptom and medication scores were 29 % and 32 % lower , respectively , in the 100,000-SQ-U group compared with those in the placebo group ( both P < .001 ) . Over the peak pollen season , mean symptom and medication scores were 32 % and 41 % lower , respectively , than those in the placebo group . The 10,000-SQ-U group had 22 % less symptoms than the placebo group over the whole season ( P < .01 ) , but medication scores reduced by only 16 % ( P = .16 ) . Quality -of-life measures confirmed the superiority of both doses to placebo . Local and delayed side effects were common but generally mild . Clinical ly significant early and delayed systemic side effects were confined to the 100,000-SQ-U group , but no life-threatening reactions occurred . CONCLUSIONS One season of immunotherapy with Alutard grass pollen reduced symptoms and medication use and improved the quality of life of subjects with moderately severe hay fever . The 100,000-SQ-U regimen was more effective , but the 10,000-SQ-U regimen caused fewer side effects The IgE response of patients only allergic to grass pollens differs from response of patients allergic to multiple-pollen species . The IgE immunoblots to orchard-grass pollens confirmed that polysensitized patients had more proteins revealed than patients only allergic to grass pollens . To determine if both groups of patients present a different response toward specific immunotherapy ( IT ) , a double-blind , placebo-controlled study was performed in 70 patients . Patients receiving the active treatment had a rush IT with either a st and ardized orchard grass-pollen extract or with a st and ardized mixed-pollen extract prepared , depending on the sensitivity of the patients . The maintenance dose was defined as that dose effective in grass-pollen IT in previous experiments . The same equipotent maintenance dose was administered for all pollen species . Symptom-medication scores during the pollen season and nasal challenge with orchard grass-pollen grains demonstrated that grass pollen-allergic patients had a significantly improved efficacy by comparison to placebo treatment , whereas polysensitized patients had a nonsignificant improvement . Serum grass-pollen IgG was significantly increased after IT in both treated groups . This study demonstrate that the response toward specific IT differs in patients only allergic to grass pollens by comparison to polysensitized patients Objectives To assess the efficacy of specific immunotherapy with st and ardized cat d and er extract , using objective endpoints and simulated ‘ natural ’ exposure to cats A double-blind controlled trial of house dust mite hyposensitization was carried out in 14 patients with asthma , who were hypersensitive on skin testing to the house dust mite alone . Measurements were made , using a Wright 's peak flowmeter , during the 15-month trial period . Pre caution s were taken in the home to reduce the mite population . At the end of the trial , no clinical improvement was noted subjectively or objective ly , despite a reduced bronchial sensitivity to allergen in the treated group . The role of the house dust mite as a cause of asthma is discussed BACKGROUND Specific immunotherapy ( SIT ) duration for respiratory allergy is currently based on individual decisions . OBJECTIVE To evaluate the differences in clinical efficacy of SIT as a result of the duration between the current recommended limits ( 3 - 5 years ) . METHODS A 5-year prospect i ve , controlled clinical trial of SIT blind until the first year and r and omization to a 3-year ( IT3 ) or 5-year ( IT5 ) course was conducted . Of the 239 patients with respiratory allergy caused by D pteronyssinus initially included , 142 completed 3 years of SIT with good compliance . Twenty-seven controls were included at the third year . Efficacy of SIT after 3 ( T3 ) and 5 ( T5 ) years was assessed by using clinical scores , visual analog scales ( VASs ) , rhinitis ( RQLQ ) and asthma ( AQLQ ) quality of life question naires , skin tests , and serum immunoglobulins . RESULTS At T3 , significant reductions were observed in rhinitis ( 44 % in IT3 and 50 % in IT5 ; P < .001 ) , asthma ( 80.9 % in IT3 and 70.9 % in IT5 ; P < .001 ) scores , VAS ( P < .001 in both ) , RQLQ ( P < .001 in both ) and AQLQ ( P < .001 in both ) . At T5 , the clinical benefit was maintained in both groups , and IT5 patients presented additional decreases ( 19 % ; P = .019 ) in rhinitis scores . At Tf , specific IgG(4 ) measurements were lower in IT3 ( P = .03 ) without detecting differences in IT5 . An increase in asthma score of 133 % was the only difference observed in controls . CONCLUSION Clinical improvement is obtained with 3 years of D pteronyssinus SIT . Two additional years of SIT add clinical benefit in rhinitis only In 22 patients with cat asthma who were highly sensitive to cat , we compared , double-blind , the effects of immunotherapy with cat-hair and d and er extract ( 11 patients ) with effects of placebo ( 11 patients ) . Patients were matched by the dose of the cat extract expressed in Food and Drug Administration ( FDA ) units of Fel d I ( previously called cat allergen 1 ) required for end point reaction in intradermal skin test end point titration ( STEPT ) , for in vitro leukocyte histamine release ( LHR ) , and for the dose of cat extract producing a 20 % fall in FEV1 ( cat-extract PD20 ) in bronchoprovocation test . Patients were matched also for bronchoprovocation dose of methacholine producing a 20 % fall in FEV1 ( methacholine PD20 ) . Patients were r and omly assigned to one of two treatment groups . During immunotherapy , doses were increased to maintenance dose of 4.56 FDA units of Fel d I , or , if this were less , to the highest tolerated dose . Systemic reactions to cat-extract immunotherapy were mild and infrequent . Before and during immunotherapy , we measured ( in FDA units of Fel d I ) cat-extract PD20 , cat-extract intradermal STEPT , cat-extract in vitro LHR , serum levels of cat IgG and cat IgE , and methacholine PD20 . After they had received 1 year of immunotherapy , patients receiving cat extract , in comparison to patients receiving placebo , had decreased cat-extract PD20 ( p less than 0.01 ) , diminished responses to cat-extract intradermal STEPT ( p less than 0.025 ) , increased IgE antibodies toward cat extract ( p less than 0.01 ) , increased IgG antibodies toward cat extract , Fel d I , and cat albumin ( p less than 0.001 ) , but no significant change in cat-extract in vitro LHR or in methacholine PD20 . We conclude that cat-extract immunotherapy was well tolerated , significantly decreased skin and bronchial responses to cat extract , and significantly increased IgE antibodies to cat extract and IgG antibodies to cat extract , Fel d I , and cat albumin BACKGROUND Immunotherapy effectively treats the symptoms of allergic rhinitis and improves its pathophysiology . We studied whether the effects of immunotherapy on the early response to nasal challenge with antigen and seasonal symptoms persist after discontinuation . METHODS Twenty subjects with ragweed allergy who were receiving immunotherapy and who had nasal challenges performed before initiation of treatment were selected . The patients had been receiving maintenance therapy with aqueous ragweed extract at a dose of 12 microg of Amb a 1 equivalent for a minimum of 3 years , at which point they were r and omized to receive either placebo injections or to continue with the maintenance dose . Nasal challenges were performed before and 1 year after r and omization . Nasal challenges were monitored by counting the number of sneezes and measuring histamine , N-alpha-tosyl-L-arginine methyl ester-esterase activity , and kinins in recovered nasal lavages . In the same year symptom diaries were collected during the ragweed season . RESULTS The initial immunotherapy significantly reduced responses to nasal challenge in both groups . The group continuing to receive active treatment showed no significant changes from the response before r and omization . In contrast , the group r and omized to placebo treatment showed a partial return of histamine , kinins , and N-alpha-tosyl-L-arginine methyl ester-esterase in nasal secretions and the numbers of sneezes . IgG antibodies to ragweed declined only in the group switched to placebo treatment . Seasonal rises of IgE antibodies to ragweed did not return during the first season after treatment was stopped . Symptoms reported during the ragweed season were not different between the groups . CONCLUSIONS One year after discontinuation of ragweed immunotherapy , nasal challenges showed partial recrudescence of mediator responses even though reports during the season appeared to indicate continued suppression of symptoms BACKGROUND The immunologic response to allergen immunotherapy with 3 serial 5-fold doses of cat extract has been studied after approximately 5 weeks of immunotherapy . The highest dose containing 15 mug of Fel d 1 produced the most consistent and favorable response . It is unknown whether the comparative response on reaching a maintenance dose is maintained with long-term maintenance therapy . OBJECTIVE The purpose of this investigation was to evaluate the immunologic responses with these 3 serial doses of cat hair and d and er extract at baseline , after reaching the maintenance dose ( approximately 5 weeks ) , and after 1 year of maintenance immunotherapy . METHODS Twenty-eight patients with cat allergy r and omized in a double-blind study were assigned to one of 4 treatment groups : placebo or cat hair and d and er extract containing 0.6 mug of Fel d 1 , 3 mug of Fel d 1 , and 15 mug of Fel d 1 at maintenance . Studies included skin prick tests and late cutaneous reactions with cat hair and d and er extract , titrated nasal challenges with the extract , serum cat allergen-specific IgG4 and IgE measurement , and flow cytometric and ELISA analysis of whole blood and intranasal cytokines ( TGF-beta , IL-10 , IFN-gamma , IL-4 , and IL-5 ) . RESULTS Twenty-six subjects completed the study . After both 5 weeks and 1 year , significant and dose-dependent differences were seen with total symptom scores on nasal challenge ( P < .0001 ) , with titrated skin prick testing with cat d and er extract at 5 weeks ( P = .014 ) and 1 year ( P < .0001 ) , and with cat-specific IgG4 measurement at 5 weeks ( P = .004 ) and 1 year ( P = .003 ) . At 1 year , neither flow cytometry of whole blood nor ELISA evaluation of nasal cytokines demonstrated any significant differences among the treatment groups . CONCLUSION The response to titrated nasal allergen challenge , titrated skin prick testing , and allergen-specific IgG4 measurement to cat immunotherapy at 5 weeks is predictive of the response at 1 year BACKGROUND Both specific immunotherapy ( SIT ) and nasal steroid ( NS ) have been shown to effectively reduce symptoms of allergic rhinitis . Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies , few comparative studies have been performed . OBJECTIVE The purpose of this study was to compare the effects of preseason SIT with a st and ardized allergen extract and NS in seasonal allergic disease ( rhinoconjunctivitis and asthma ) . METHODS We examined 41 patients allergic to birch pollen , 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma ; they were treated in a r and omized , double-blinded comparative study with birch SIT and NS ( budesonide 400 microg daily ) . Bronchial hyperresponsiveness was measured before and during the season . Changes in eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity ( ECA ) in peripheral blood were investigated . RESULTS Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season ( P = .03 and P = .04 , respectively ) . Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients ( P = .01 ) . In the NS-treated patients , bronchial hyperresponsiveness increased significantly during the season ( P = .0001 ) ; however , SIT treatment prevented seasonal PC(20 ) increase in the asthmatic patients . Measurement of blood eosinophils , eosinophil cationic protein , and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients . CONCLUSION Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis ; however , the 2 therapies were equivalent in terms of the need for rescue medication . SIT prevented seasonal increase in bronchial hyperresponsiveness , eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity only in asthmatic patients . The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma BACKGROUND Grass pollen immunotherapy significantly reduces hay fever symptoms and medication requirements . Effects on seasonal asthma are less clear , and concerns over safety persist . OBJECTIVE The goal of this study was to assess the effects of grass pollen immunotherapy on symptoms , bronchial hyperresponsiveness , and quality of life in seasonal rhinitis and asthma . METHODS Forty-four patients with severe summer hay fever ( of whom 36 reported seasonal chest symptoms and 28 had seasonal bronchial hyperresponsiveness ) participated in a r and omized , double-blind , placebo-controlled , parallel group study . After symptom monitoring for one summer , participants received injections of a depot grass pollen vaccine ( n = 22 ) or matched placebo injections ( n = 22 ) in a rapid updosing cluster regimen for 4 weeks , followed by monthly injections for 2 years . Outcome measures included hay fever symptoms and medication use , health-related quality of life , and measurements of nonspecific bronchial responsiveness . RESULTS Significant reductions were observed in the immunotherapy group compared with the placebo group in hay fever symptoms ( 49 % , 15 % ; P = .01 ) , medication scores ( 80 % , 18 % ; P = .007 ) , and seasonal chest symptoms ( 90 % , 11 % ; P < .05 ) . Impairment of overall quality of life ( mean score of 7 domains ) during the pollen season was less in the immunotherapy group than in the placebo group ( median difference [ 95 % CI ] , 0.8 [ 0.18 - 1.5 ] ; P = .02 ) . During the pollen season there was no change in airway methacholine PC(20 ) ( provocation concentration producing a 20 % fall in FEV(1 ) ) in the immunotherapy-treated group ( P = .5 ) , compared with an almost 3 doubling-dose decrease in the placebo-treated group ( P = .01 , between-group difference ) . There were no significant local or systemic side effects during the study . CONCLUSION Grass pollen immunotherapy improves quality of life in seasonal allergic rhinitis and reduces seasonal asthma symptoms and bronchial hyperresponsiveness Allergen-specific immunotherapy ( ASIT ) with fungal extracts has been beset by safety and efficacy problems , which result mainly from qualitative and quantitative variations . Little has been published on the safety and efficacy of these extracts . The objective was to analyze the safety and efficacy of ASIT with an Alternaria alternata extract . A total of 28 patients were selected with rhinitis and /or bronchial asthma because of Alternaria allergy and monosensitization to molds . The patients were r and omized to an active ASIT or placebo group , both groups on a conventional immunotherapy schedule ( increasing weekly doses until maintenance dose and then monthly doses ) . Adverse reactions were classified with the European Academy of Allergology and Clinical Immunology system . Clinical efficacy was analyzed for a year with symptom/medication diary cards , peak expiratory flow ( PEF ) measures , clinical severity score , severity of symptoms ( visual analog scale ) , subjective evaluation of treatment by the patient and the physician , and a quality of life question naire . Twenty-three patients completed the study ; all reached the established maintenance dose with only two mild adverse reactions in the whole sample . Significant improvements were found after 6 months in respiratory symptoms in the active treatment group , and in all symptoms in both groups . PEF increased significantly in the active treatment group but not in the placebo group . The severity of asthma decreased in the active treatment group , and the severity of rhinitis decreased in both groups . Visual analog scale scores for severity of symptoms improved in all phases in the active treatment group , but only after 12 months in the placebo group . Physicians judged the disease course as significantly better in the active treatment group . ASIT with the A. alternata extract was safe , with clinical improvements after one year of treatment The effect of hyposensitization ( HS ) upon the allergen evoked immediate asthmatic reaction ( IAR ) , late asthmatic reaction ( LAR ) and upon bronchial reactivity towards histamine was examined . Eighteen young asthmatic patients were studied using a double-blind , placebo-controlled design . All were allergic to house dust mite ( HDM ) and demonstrated an IAR and a LAR after bronchial provocation with HDM . Furthermore , all , except one child , demonstrated bronchial hyperreactivity towards histamine ( median provocative dose producing a 20 % fall in forced expiratory volume in one second ( PD20 ) histamine = 0.19 mg.ml-1 , range : 0.02 - 8 mg.ml-1 ) . The subjects were r and omly divided into two groups to receive HDM or placebo injections during one year . After the one year period , the IAR was less severe in the subjects who received HDM injections ( p = 0.02 ) , while this reduction was not observed in the subjects who received placebo injections . Also , in the HDM group a small but significant increase of the median PD20 HDM was observed ( p = 0.04 ) . Furthermore , the LAR was less severe in the subjects who received HDM injections ( p = 0.02 ) , while the subjects who received placebo injections showed the same severity of LAR after one year ( p = 0.44 ) . Histamine reactivity did not change after HDM injections or after placebo injections . Thus , HS reduces the severity of the IAR and LAR without any change in histamine reactivity BACKGROUND Activation of mast cells and eosinophils under pollen exposure can be inhibited by specific immunotherapy . OBJECTIVE The effect of short-term immunotherapy with 7 preseasonal injections of molecular st and ardized allergens from grass and rye pollen on eosinophil cationic protein ( ECP ) and tryptase levels in nasal secretions has been compared with symptomatic drug treatment in an open , r and omized study with 48 patients . METHODS Nasal reactivity and mediator levels in nasal secretions were measured at baseline , before season , in season , and after season . RESULTS Symptom scores in the immunotherapy group were 134.5 ( 95 % CI , 65 to 336 ) versus 386 . 0 ( 95 % CI , 185 to 563 ) , significantly lower as in the drug-treated group . ECP and tryptase levels increased significantly during natural allergen exposition . The seasonal levels in the immunotherapy group were significantly lower than in the drug-treated group with 272.1 ng/mL ( 252.0 to 293.9 ng/mL ; immunotherapy ) versus 470.4 ng/mL ( SEM , 435.6 to 508.0 ng/mL ; drugs ) for ECP and with 8.73 ng/mL ( SEM , 8.20 to 9.29 ng/mL ) versus 17.47 ng/mL ( 16.42 to 18.60 ng/mL ) for tryptase ( all , P < .001 ) . The ECP level induced by nasal provocation was 105.6 ng/mL ( 99.0 to 112.6 ng/mL ) versus 180.4 ng/mL ( 169.2 to 192.4 ng/mL ) , significantly lower ( P < .001 ) in the immunotherapy group , as was the tryptase level with 12.12 ng/mL ( 11.53 to 12.75 ng/mL ) versus 8.19 ng/mL ( 7 . 79 to 8.62 ng/mL ; P < .001 ) at the after-season visit . CONCLUSION Short-term immunotherapy is able to reduce tryptase and ECP in nasal secretions more effectively than drug treatment in patients with allergic rhinitis Background : Bronchial hyperresponsiveness ( BHR ) and airway inflammation are frequently associated with allergic rhinitis , and may be important risk factors for the development of asthma . Specific immunotherapy ( SIT ) reduces symptom in subjects with allergic rhinitis , but the mechanisms are not clear Twenty adult patients presenting a respiratory allergy to the pollen of Cupressus sempervirens were r and omly divided into two groups ; one received a placebo the other one an equal mixture of Cupresssus sempervirens and Cryptomeria japonica pollen during a period of 3 years ( 1993 - 1996 ) . According to the following criteria : symptoms score , drug consumption , skin test and RAST , nasal provocation test , the results for the treated group were statistically better than those for the placebo group . No side effects were observed Allergic rhinitis is often associated with bronchial hyperresponsiveness ( BHR ) and airway inflammation , and it seems to be an important risk factor for the development of asthma . Specific immunotherapy ( SIT ) reduces symptoms and medication requirements in subjects with allergic rhinitis , but the mechanisms by which SIT promotes these beneficial effects are less clear . We have investigated the effects of Parietaria-SIT on rhinitis symptoms , BHR to inhaled methacholine , eosinophilic inflammation and cytokine production ( interferon gamma and interleukin-4 ) in the sputum . The effect on asthma progression was also examined . Thirty non-asthmatic subjects with seasonal rhinitis and monosensitized to Parietaria judaica participated in a r and omized , double-blind , placebo-controlled , parallel group study . Participants were r and omly assigned to receive injections of a Parietaria pollen vaccine ( n = 15 ) or matched placebo injections ( n = 15 ) in a rapid updosing cluster regimen for 7 weeks , followed by monthly injections for 34 months . Throughout the 3-year study we collected data on symptoms and medication score , airway responsiveness to methacholine , eosinophilia and soluble cytokines in sputum , followed by a complete evaluation of the clinical course of atopy . Hay fever symptom and medication scores were well controlled by SIT . By the end of the study , in the placebo group , symptom and medication scores significantly increased by a median ( interquartile range ) of 121 % ( 15 - 280 % ) and 263 % ( 0 - 4400 % ) respectively ( p < 0.01 ) , whereas no significant difference was observed in the SIT group . We found no significant changes in the sputum parameters and methacholine PC15 values in both groups throughout the study . By the end of the investigation , a total of 9 out of 29 participants developed asthma symptoms ; of these , seven ( 47 % ) belonged to the placebo group , whereas only 2 ( 14 % ) to the SIT-treated group ( p = 0.056 ) . In conclusion , Parietaria-SIT is effective in controlling hay fever symptoms and rescue medications , but no changes in the BHR to methacholine or sputum eosinophilia were observed . Moreover , Parietaria-SIT appears to prevent the natural progression of allergic rhinitis to asthma , suggesting that SIT should be considered earlier in the management of this condition Thirty‐one adult patients with asthma caused by house‐dust mites ( HDM ) were included in this placebo‐controlled , double‐blind study to evaluate the efficacy and safety of specific immunotherapy ( SIT ) with biologically st and ardized extracts of HDM . The specific diagnosis was confirmed by skin prick tests , specific IgE , and bronchial provocation tests with HDM allergens . The patients were r and omized to receive active treatment with extracts of either Dermatophagoides pteronyssinus ( Dpt ) or D. farinae ( Dfa ) ( Alutard ® SQ , ALK , Denmark ) or placebo injections . Twenty‐three patients completed the study . After 1 year of treatment , we found a clinical ly important and significant reduction in both asthma medicine consumption ( inhaled steroids 38 % and p2–agonists 46 % ) and symptom score ( 57 % ) in the actively treated group , but not the placebo group . These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group . Additionally , there was a significant difference in the patients ' scores for effect in favor of the actively treated group . Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group . Spirometric lung‐function measurements showed a significant increase in forced expiratory volume in 1 s ( FEV1 ) from 85 % before to 89 % of predicted values after treatment for the actively treated group . Peak‐flow measurements at home showed no significant changes during the study . It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM A double-blind study was carried out to determine the effect of dosage in the treatment of ragweed hay fever with injections of aqueous ragweed pollen extract . Two concentrations of extract were used , one 20-fold smaller than the other . The volumes administered were such that the dose at the higher concentration was close to the maximum that it is practical to administer . During the ragweed season , the group of patients receiving the higher concentration fared significantly better than the group receiving the lower concentration . It is concluded that large dosages of pollen extract are more effective than small dosages in the treatment of hay fever . The findings indicate that the very low dosages recommended by some would have little influence on the course of pollenosis This study investigated the specificity and efficacy of immunotherapy with Artemisia vulgaris ( Artemisia ) extract . We studied 25 patients with a more than two year lasting history of seasonal rhinoconjunctivitis and who had only two clinical ly important allergies , either to Artemisia and Betula verrucosa ( Betula ) or to Artemisia and Phleum pratense ( Phleum ) . Patient selection was r and omized and evaluation of results was conducted in double blind fashion . Twenty patients completed two years of specific immunotherapy . Nine patients were treated with extracts of Artemisia and 11 with extracts of either Betula ( n = 3 ) or Phleum ( n = 8) . Treatment with Artemisia was followed by a significant decrease in skin sensitivity ( p < 0.05 ) and eye sensitivity ( p < 0.01 ) to Artemisia but not to Betula/phleum . No significant decrease was observed in medicine consumption or symptom scores . Patients treated with Betula or Phleum experienced a significant decrease in skin sensitivity to Betula or Phleum ( p < 0.001 ) , and eye sensitivity to Betula or Phleum ( p < 0.05 ) , but not to Artemisia and had significant decreases in medicine and symptom scores ( p < 0.05 ) in Betula/phleum seasons but not in the Artemisia season . The treatment was both effective and specific with the one unexplained exception that both patient groups ( Artemisia and Betula/Phleum ) decreased their skin sensitivity to Artemisia We design ed a cluster schedule of immunotherapy for patients allergic to Dermatophagoides pteronyssinus which showed good safety and clinical efficacy . Here we compare the in vivo and in vitro changes with those of a conventional schedule in a controlled trial . Sixty-three patients were r and omized as follows : 29 were treated with the cluster schedule , 15 with a conventional schedule and 19 received no immunotherapy . A st and ardized extract was used . Changes in in vivo parameters ( skin prick test and conjunctival provocation test ) and in in vitro parameters ( IgE , IgG , IgG1 and IgG4 for the complete extract , Der p 1 and Der p 2 ) were measured before immunotherapy ( T0 ) , on reaching maintenance phase ( T1 ) , and after 6 ( T2 ) , 12 ( T3 ) and 18 months of maintenance ( T4 ) . Cutaneous reactivity showed a significant decrease from T1 in both the cluster and conventional schedules , and conjunctival reactivity was also significantly lowered from T1 in these groups . Specific IgE decreased and specific IgG , IgG1 and IgG4 increased significantly from T1 in the cluster and conventional schedules . Neither of these parameters showed any changes in the group without immunotherapy . In conclusion , our cluster schedule induced changes in cutaneous and conjunctival reactivity and in immunological parameters that were similar to those achieved with the conventional schedule ; these changes did not appear in patients who did not undergo immunotherapy Thirty patients with asthma and /or monosensitized allergic rhinitis caused by grass pollen whose ages ranged from 15 to 35 years were selected . Two groups were established at r and om : an active group and a placebo group , and a double‐blind study was done on treatment with immunotherapy for a period of 3 continuous years , with initiation doses administered according to the rush immunotherapy technique . Grass‐pollen allergen extract Alutard SQ and histamine as a placebo were used . The objective parameters of efficacy evaluated were end‐point cutaneous tests , conjunctival provocation , bronchial provocation , and symptom/medication scores , as well as specific immunoglobulin determinations . The statistical evaluation of the results was significant for the differences existing between the initial and final time of the active group , and there were significant differences between the two groups for all of the parameters considered . We found no relationship between clinical improvement and the range of specific immunoglobulin E values . Regarding the safety of the treatment , systemic adverse effects were manifested only in the initial phase ( rush immunotherapy ) . and were easily controlled by treatment . We conclude that the efficacy and safety of immunotherapy with grass pollen make it possible to consider this treatment fundamental in these patients Background : Few placebo‐controlled studies have examined the effect of allergen specific immunotherapy ( SIT ) on early and late phase asthmatic reactions . In this placebo‐controlled study we have investigated the effect of 1 year of SIT with st and ardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients BACKGROUND The conventional schedule for subcutaneous immunotherapy with allergen extracts , although efficacious and safe , is slow during the dose-increase phase . OBJECTIVE We sought to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus st and ardized extract given in a 6-week cluster period and a conventional 12-week schedule during the incremental-dose phase . METHODS Of 239 patients with rhinitis , allergic bronchial asthma , or both caused by D pteronyssinus , 120 were r and omly assigned to the cluster schedule , and 119 were r and omly assigned to the conventional schedule . A biologically st and ardized D pteronyssinus depot extract ( ALK-Abelló S.A. , Madrid , Spain ) was administered in a placebo-controlled , double-blind fashion during the initial phase of cluster or conventional treatment . We recorded adverse reactions , clinical efficacy , cutaneous reactivity , and serum specific immunoglobulins to D pteronyssinus before immunotherapy , when the maximum dose was reached in the cluster and conventional schedules , and after 1 year of treatment . RESULTS The cluster schedule reduced the time to maintenance dose by 46 % and caused systemic adverse reactions ( all mild ) after only 0.15 % of injections , with no differences in comparison with the conventional schedule . Cluster immunotherapy led to decreases in asthma and rhinitis symptoms , reduced the cutaneous reactivity , and produced the increase in specific IgE and IgG 4 levels on reaching the maintenance dose in the sixth week , 6 weeks earlier than with the conventional schedule . CONCLUSION The cluster schedule for the initial phase of immunotherapy with incremental doses of D pteronyssinus is a safe alternative to conventional immunotherapy and offers the further advantage of achieving clinical and immunologic improvements sooner Twenty-eight patients ( 14 in an active treatment group and 14 in a placebo group ) with rhinoconjunctivitis and asthma caused by cat hypersensitivity took part in a placebo-controlled , r and omized , double-blind study to evaluate the risk-benefit quotient of the maintenance dose corresponding to 13.2 micrograms Fel d I antigen . The cat extract was biologically st and ardized and quantified with monoclonal antibodies ( 100 biological units : 33 microgram of Fel d I antigen , 650 micrograms of albumin , and 99 micrograms of Fel d Bd/K30 antigen ) . After 1 year of treatment , the systemic reactions to cat extract immunotherapy were mild and infrequent . Improvement was observed in the active treatment group in comparison with the placebo group in the medication-symptoms score ( p < 0.001 ) ; in skin prick test ( p < 0.001 ) , conjunctival provocation test ( p < 0.001 ) , and allergen bronchoprovocation test ( p < 0.05 ) results , and in nonspecific bronchial hyperreactivity measured with methacholine , which was not statistically significant . This study demonstrates the favorable risk-benefit quotient of the dose of 13.2 micrograms of Fel d I antigen , which may serve as a future reference in defining the optimum dose and appropriate proportion of antigens that should be administered in cat extract immunotherapy Abstract In a double-blind study , we compared the effects of the Rinkel and the current st and ard methods of immunotherapy with ragweed pollen extract and those of placebo on symptoms of ragweed hay fever and immunologic parameters in 43 patients highly sensitive to ragweed . Each had a skin-test end point by Rinkel serial titration at 1:312,500 w/v or greater dilution , a 2 + skin test to ragweed AgE 0.01 μg/ml , and in vitro histamine release by ragweed pollen extract . None had had immunotherapy for at least 7 yr . Patients were matched on the basis of leukocyte histamine release to ragweed pollen extract and assigned to treatment groups . Fourteen received ragweed pollen extract by the Rinkel method , 14 received placebo , and 15 received ragweed pollen extract by the current st and ard method weekly between February and October , 1979 . Rinkel method doses were derived from skin-test end points and were advanced to 0.5 ml of the end-point dilution ; current st and ard method doses were advanced to the highest tolerated dose . The median maintenance dose for Rinkel method patients was 0.5 ml of 1:1,562,500 w/v ( 0.001 μg AgE ) , and for current st and ard method patients was 0.3 ml of 1:100 w/v ( 11 μg AgE ) . An additional unmatched group of nine similar patients received Rinkel method immunotherapy in both 1978 and 1979 . Under the conditions of this study , the current st and ard method of immunotherapy produced a significant decrease in ragweed hay fever symptom-medication scores , increase in antiragweed IgG levels , and decrease in seasonal rise in antiragweed IgE levels in comparison with the effects of either Rinkel method or placebo . The effect of the Rinkel method on these variates was not significantly different from the effects of placebo BACKGROUND Although allergen immunotherapy is effective for allergic rhinitis , its role in treating asthma is unclear . METHODS We examined the efficacy of immunotherapy for asthma exacerbated by seasonal ragweed exposure . During an observation phase , adults with asthma who were sensitive to ragweed kept daily diaries and recorded peak expiratory flow rates between July and October . Those who reported seasonal asthma symptoms and medication use as well as decreased peak expiratory flow were r and omly assigned to receive placebo or ragweed-extract immunotherapy in doses that increased weekly for an additional two years . RESULTS During the observation phase , the mean ( + /- SE ) peak expiratory flow rate measured in the morning during the three weeks representing the height of the pollination season was 454 + /- 20 liters per minute in the immunotherapy group and 444 + /- 16 liters per minute in the placebo group . Of the 77 patients who began the treatment phase , 64 completed one year of the study treatment and 53 completed two years . During the two treatment years , the mean peak expiratory flow rate was higher in the immunotherapy group ( 489 + /- 16 liters per minute , vs. 453 + /- 17 in the placebo group [ P = 0.06 ] during the first year , and 480 + /- 12 liters per minute , vs. 461 + /- 13 in the placebo group [ P = 0.03 ] during the second ) . Medication use was higher in the immunotherapy group than in the placebo group during observation and lower during the first treatment year ( P = 0.01 ) but did not differ in the two groups during the second year ( P = 0.7 ) . Asthma-symptom scores were similar in the two groups ( P = 0.08 in year 1 and P = 0.3 in year 2 ) . The immunotherapy group had reduced hay-fever symptoms , skin-test sensitivity to ragweed , and sensitivity to bronchial challenges and increased IgG antibodies to ragweed as compared with the placebo group ; there was no longer a seasonal increase in IgE antibodies to ragweed allergen in the immunotherapy group after two years of treatment . Reduced medication costs were counterbalanced by the costs of immunotherapy . CONCLUSIONS Although immunotherapy for adults with asthma exacerbated by seasonal ragweed exposure had positive effects on objective measures of asthma and allergy , the clinical effects were limited and many were not sustained for two years |
1,736 | 23,369,256 | The introduction of simple hypothermia prevention messages and interventions into evidence -based , cost-effective packages for maternal and newborn care has promising potential to decrease the heavy global burden of newborn deaths attributable to severe infections , prematurity , and asphyxia .
Because preventing and treating newborn hypothermia in health institutions and communities is relatively easy , addressing this widespread challenge might play a substantial role in reaching Millennium Development Goal 4 , a reduction of child mortality | Background To provide evidence on the global epidemiological situation of neonatal hypothermia and to provide recommendations for future policy and research directions .
Results Hypothermia is common in infants born at hospitals ( prevalence range , 32 % to 85 % ) and homes ( prevalence range , 11 % to 92 % ) , even in tropical environments .
The lack of thermal protection is still an underappreciated major challenge for newborn survival in developing countries .
Although hypothermia is rarely a direct cause of death , it contributes to a substantial proportion of neonatal mortality globally , mostly as a comorbidity of severe neonatal infections , preterm birth , and asphyxia .
Thresholds for the definition of hypothermia vary , and data on its prevalence in neonates is scarce , particularly on a community level in Africa .
Thermoprotective behavior changes such as skin-to-skin care or the use of appropriate devices have not yet been scaled up globally . | BACKGROUND Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years . 90 % of deliveries in the poorest quintile of households happen at home . We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates . METHODS We pair-matched 42 geopolitical clusters in Makwanpur district , Nepal , selected 12 pairs r and omly , and r and omly assigned one of each pair to intervention or control . In each intervention cluster ( average population 7000 ) , a female facilitator convened nine women 's group meetings every month . The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them . We monitored birth outcomes in a cohort of 28?931 women , of whom 8 % joined the groups . The primary outcome was neonatal mortality rate . Other outcomes included stillbirths and maternal deaths , uptake of antenatal and delivery services , home care practice s , infant morbidity , and health-care seeking . Analysis was by intention to treat . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N31137309 . FINDINGS From 2001 to 2003 , the neonatal mortality rate was 26.2 per 1000 ( 76 deaths per 2899 livebirths ) in intervention clusters compared with 36.9 per 1000 ( 119 deaths per 3226 livebirths ) in controls ( adjusted odds ratio 0.70 [ 95 % CI 0.53 - 0.94 ] ) . Stillbirth rates were similar in both groups . The maternal mortality ratio was 69 per 100000 ( two deaths per 2899 livebirths ) in intervention clusters compared with 341 per 100000 ( 11 deaths per 3226 livebirths ) in control clusters ( 0.22 [ 0.05 - 0.90 ] ) . Women in intervention clusters were more likely to have antenatal care , institutional delivery , trained birth attendance , and hygienic care than were controls . INTERPRETATION Birth outcomes in a poor rural population improved greatly through a low cost , potentially sustainable and scalable , participatory intervention with women 's groups OBJECTIVE : Preterm infants are prone to hypothermia immediately following birth . Among other factors , excessive evaporative heat loss and the relatively cool ambient temperature of the delivery room may be important contributors . Most infants < 29 weeks gestation had temperatures < 36.4 ° C on admission to our neonatal unit ( NICU ) . Therefore we conducted a r and omized , controlled trial to evaluate the effect of placing these infants in polyurethane bags in the delivery room to prevent heat loss and reduce the occurrence of hypothermia on admission to the NICU . METHODS : After parental consent was obtained , infants expected to be < 29 weeks gestation were r and omized to intervention or control groups just prior to their birth . Infants r and omized to the intervention group were placed in polyurethane bags up to their necks immediately after delivery before being dried . They were then resuscitated per NRP guidelines , covered with warm blankets , and transported to the NICU , where the bags were removed and rectal temperatures were recorded . Control infants were resuscitated , covered with warm blankets , and transported without being placed in polyurethane bags . Delivery room temperatures were recorded so this potentially confounding variable could be assessed . RESULTS : Intervention patients were less likely than control patients to have temperature < 36.4 ° C on admission , 44 vs 70 % ( p<0.01 ) and the intervention group had a higher mean admission temperature , 36.5 ° C vs 36.0 ° C ( p<0.003 ) . This effect remained significant ( p<0.0001 ) when delivery room temperature was controlled in analysis . Warmer delivery room temperatures ( ≥26 ° C ) were associated with higher admission temperatures in both intervention and control infants , but only the subgroup of intervention patients born in warmer delivery rooms had a mean admission temperature > 36.4 ° C . CONCLUSIONS : Placing infants < 29 weeks gestation in polyurethane bags in the delivery room reduced the occurrence of hypothermia and increased their NICU admission temperatures . Maintaining warmer delivery rooms helped but was insufficient in preventing hypothermia in most of these vulnerable patients without the adjunctive use of the polyurethane bags Objective : To describe the effects of out-of-hospital birth on early neonatal morbidity and outcome among referred newborns . Methods : Using a structured case record form , we prospect ively collected data on place of birth , morbidity , and outcome of all neonates admitted to the Emergency Ward , University College Hospital , Ibadan , in the first week of life . Results : Of the 541 admitted in the early neonatal period , 61.8 % and 38.2 % were delivered outside and inside the hospital setting , respectively . Babies were delivered at religious or " mission " house ( 46.7 % ) , house of residence ( 38.0 % ) , traditional birth attendants ' homes ( 8.4 % ) , and on the way to the hospital ( 6.9 % ) . Births outside the hospital significantly increased as the birth order increased ( χ = 34.04 ; P = 0.000 ) . Over half of the out-of-hospital deliveries took place under personnel whose primary responsibilities did not include labor care . Women who had less than secondary level of education and those from the lower social class were more likely to deliver outside the hospital ( P < 0.05 ) . Out-of-hospital births were significantly associated with many complications , namely , hypothermia ( 53.6 % ) , perinatal asphyxia ( 48.5 % ) , hemorrhage ( 26.5 % ) , cephalhematoma ( 12.9 % ) , prematurity ( 9.9 % ) , and neonatal tetanus ( 4.2 % ) . Neonatal mortality rate of 12.6 % in the out-of-hospital group was significantly higher than 6.3 % obtained in the hospital birth group ( P = 0.019 ) . Conclusions : Out-of-hospital births had greater risk of morbidity than hospital births . There is need to retrain and monitor the activities of birth attendants and midwives involved in births outside the hospitals closer than it is presently done The objective of this study is to correlate the severity of hypothermia in sick extramural neonates with fatality and physiological derangements . This is a prospect i ve observational study carried out at the referral neonatal unit of a teaching hospital admitting extramural neonates . The subjects comprised of 100 extramural hypothermic neonates transported to the Referral neonatal unit . Neonates weighing more than 1000 g , with abdominal skin temperature less than 36.5 degrees C at admission were included in the study . Hypothermia was classified as per WHO recommendations . Clinical features including age , weight , gestational age , clinical diagnosis , vitals , place of delivery , details of transportation and capillary filling time were recorded at the time of admission . Oxygen saturation was recorded by a pulse oximeter . Sample s for sepsis screen , blood culture and blood glucose were taken at admission . During the study it was observed that fatality was 39.3 % in mildly hypothermic babies , 51.6 % in moderately hypothermic babies and 80 % in severely hypothermic babies . However , the presence of associated illness ( birth asphyxia , neonatal sepsis and respiratory distress ) , physiological derangements ( hypoxia , hypoglycemia and shock ) and weight less than 2000 g were associated with more than 50 % fatality even in mildly hypothermic babies . When moderate hypothermia was associated with hypoxia or shock , the fatality was 83.3 % and 90.9 % respectively . Similarly , mild hypothermia with hypoglycemia was associated with 71.4 % fatality . The conclusion drawn from this study is that the WHO classification of severity of hypothermia correlates with the risk of fatality . However , it considers only body temperature to classify severity of hypothermia . The presence of associated illness ( birth asphyxia , neonatal sepsis and respiratory distress ) , physiological derangements ( hypoxia , hypoglycemia and shock ) and weight less than 2000 g should be considered adverse factors in hypothermic neonates . Their presence should classify hypothermia in the next higher category of severity in WHO classification A prospect i ve cohort study was carried out at the University Teaching Hospital , Lusaka , Zambia , to investigate the prevalence of neonatal hypothermia , type of infant care and incidence of mortality . Two-hundred- and -sixty-one infants , aged 0 - 7 days , admitted to the pediatric unit during the ' warm ' season were recruited to the study . Forty-four per cent of the infants were hypothermic ( < 36 degrees C ) on admission , and admission hypothermia correlated to admission weight and home delivery in the youngest age group ( 0 - 24 hours ) . Exclusively breastfed infants ( age group 1 - 7 days ) were less likely to be hypothermic at admission . ' Hypothermia ' was not recorded as an admission diagnosis and no special attention was given to those infants in terms of clinical management . Mean time to reach a body temperature above 35.9 degrees C did not differ between infants kept in a cot and in an incubator . Total numbers of death was 82 ( 31 per cent ) and the mortality was higher in infants who were hypothermic at admission compared to those who were not . This study demonstrates that a change of existing care routines is needed OBJECTIVE To determine the incidence rate and factors associated with hypothermia in Iranian newborns and to discover the effect of hypothermia on neonatal morbidity and mortality . METHODS We selected a r and om sample of 1952 neonates using a multistage sampling technique from February 2004 to February 2005 in University Teaching Hospitals in Iran . We measured repeatedly at different time points the rectal temperature of these newborns . At each time of measurement , those with rectal temperature < 36 degrees C were considered as hypothermic . RESULTS The obtained results showed that approximately one third of newborns became hypothermic immediately after birth . In addition , the regression analysis revealed that low birth weights , prematures , low apgar scores , infants of multiple pregnancies and those who received cardiopulmonary resuscitation had higher risk for being hypothermic . It was also found that hypothermia increases the risk of metabolic acidosis , jaundice , respiratory distress , hypoglycemia , pulmonary hemorrhage and death , regardless of the newborn 's weight and gestational age . CONCLUSION There is an urgent need to train mothers and all levels of neonatal care staff to control this health problem in our country Aim : To eluci date the impact of bathing on the prevalence of hypothermia among newborn babies exposed to the skin‐to‐skin ( STS ) care technique before and after bathing . Methods : Non‐asphyxiated newborns after vaginal delivery ( n=249 ) in a Ug and an referral hospital were consecutively enrolled and r and omized either to bathing at 60 min postpartum ( n=126 ) or no bathing ( n=123 ) . All mothers practised skin‐to‐skin care of their newborns . Four rectal and tympanic registration s of newborn temperatures were carried out in both groups directly after drying at birth , and at 60 , 70 and 90 min postpartum . Results : Bathing of newborns in the first hour after delivery result ed in a significantly increased prevalence of hypothermia , defined as temperature < 36.5 ° C , at 70 and at 90 min postpartum despite the use of warmed water and the application of the STS method . There was no neonatal mortality . Aside from the bathing procedure , no background factor potentially predisposing the newborns to hypothermia was identified An assessment of the incubators in use at the Kathm and u Maternity Hospital neonatal unit was undertaken ; this was followed by a prospect i ve survey of neonatal temperatures on the unit . In the incubator assessment 11 studies were carried out in five incubators . Three of the thermostats in the five incubators did not work at all and those in the other two incubators were more than 3 degrees C inaccurate . All the incubator thermometers gave recordings less than the actual temperature ( with a range of error : 1.3 - 4.4 degrees C ) . Six out of the 11 babies studied were hypothermic ( defined as rectal temperature < 36 degrees C ) . In the prospect i ve survey of temperatures a high incidence of hypothermia was found on the neonatal unit at the time of first temperature measurement ( 64 per cent had a rectal temperature of < 36 degrees C ) . A significant association between admission hypothermia and mortality was noted . Sixteen per cent ( 10/64 ) of babies admitted with temperatures < 36 degrees C died within the first week , compared to 0 ( 0/36 ) of those admitted with temperatures > or = 36 degrees Objective To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a re source poor country with limited access to healthcare . Design Prospect i ve , cluster r and omised and controlled effectiveness study . Setting Lufwanyama , an agrarian , poorly developed district located in the Copperbelt province , Zambia . All births carried out by study birth attendants occurred at mothers ’ homes , in rural village setting s. Participants 127 traditional birth attendants and mothers and their newborns ( 3559 infants delivered regardless of vital status ) from Lufwanyama district . Interventions Using an unblinded design , birth attendants were cluster r and omised to intervention or control groups . The intervention had two components : training in a modified version of the neonatal resuscitation protocol , and single dose amoxicillin coupled with facilitated referral of infants to a health centre . Control birth attendants continued their existing st and ard of care ( basic obstetric skills and use of clean delivery kits ) . Main outcome measures The primary outcome was the proportion of liveborn infants who died by day 28 after birth , with rate ratios statistically adjusted for clustering . Secondary outcomes were mortality at different time points ; and comparison of causes of death based on verbal autopsy data . Results Among 3497 deliveries with reliable information , mortality at day 28 after birth was 45 % lower among liveborn infants delivered by intervention birth attendants than control birth attendants ( rate ratio 0.55 , 95 % confidence interval 0.33 to 0.90 ) . The greatest reductions in mortality were in the first 24 hours after birth : 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants ( 0.40 , 0.19 to 0.83 ) . Deaths due to birth asphyxia were reduced by 63 % among infants delivered by intervention birth attendants ( 0.37 , 0.17 to 0.81 ) and by 81 % within the first two days after birth ( 0.19 , 0.07 to 0.52 ) . Stillbirths and deaths from serious infection occurred at similar rates in both groups . Conclusions Training traditional birth attendants to manage common perinatal conditions significantly reduced neonatal mortality in a rural African setting . This approach has high potential to be applied to similar setting s with dispersed rural population s. Trial registration Clinical trials.gov NCT00518856 OBJECTIVE To compare the effect of Kangaroo mother care ( KMC ) and conventional methods of care ( CMC ) on growth in LBW babies ( > 2000 g ) . STUDY DESIGN R and omized controlled trial . SETTING Level III NICU of a teaching institution in western India . SUBJECTS 206 neonates with birth weight < 2000 g. INTERVENTION The subjects were r and omized into two groups : the intervention group ( KMC-103 ) received Kangaroo mother care . The control group ( CMC : 103 ) received conventional care . OUTCOME MEASURES Growth , as measured by average daily weight gain and by other anthropometrical parameters at 40 weeks postmenstrual age in preterm babies and at 2500 g in term SGA infants was assessed . RESULTS The KMC babies had better average weight gain per day ( KMC : 23.99 g vs CMC : 15.58 g , P < 0.0001 ) . The weekly increments in head circumference ( KMC : 0.75 cm vs CMC : 0.49 cm , P = 0.02 ) and length ( KMC : 0.99 cm vs CMC : 0.7 cm , P = 0.008 ) were higher in the KMC group . A significantly higher number of babies in the CMC group suffered from hypothermia , hypoglycemia , and sepsis . There was no effect on time to discharge . More KMC babies were exclusively breastfed at the end of the study ( 98 % vs 76 % ) . KMC was acceptable to most mothers and families at home . CONCLUSION Kangaroo mother care improves growth and reduces morbidities in low birth weight infants . It is simple , acceptable to mothers and can be continued at home BACKGROUND Infections and complications of prematurity are main causes of neonatal mortality . Very low birthweight premature infants have compromised skin barrier function , and are at especially high risk for serious infections and mortality . Our aim was to ascertain whether topical application of emollients to enhance skin barrier function would prevent nosocomial infections in this population . METHODS We r and omly assigned infants born before week 33 of gestation after admission to Dhaka Shishu Hospital , Bangladesh , to daily massage with sunflower seed oil ( n=159 ) or Aquaphor ( petrolatum , mineral oil , mineral wax , lanolin alcohol ; n=157 ) . We then compared incidence of nosocomial infections among infants in these two groups with an untreated control group ( n=181 ) by an intention-to-treat analysis . FINDINGS 20 patients in the control group , and 22 in each of the treatment groups left the hospital early , but were included in the final analysis . Overall , infants treated with sunflower seed oil were 41 % less likely to develop nosocomial infections than controls ( adjusted incidence rate ratio [ IRR ] 0.59 , 95 % CI 0.37 - 0.96 , p=0.032 ) . Aquaphor did not significantly reduce the risk of infection ( 0.60 , 0.35 - 1.03 , p=0.065 ) . No adverse events were seen . INTERPRETATION Our findings confirm that skin application of sunflower seed oil provides protection against nosocomial infections in preterm very low birthweight infants . The low cost , availability , simplicity , and effect of treatment make it an important intervention for very low birthweight infants admitted to hospital in developing countries BACKGROUND : The incidence of morbidities among home-cared neonates in rural areas has not been studied . OBJECTIVES : To estimate the incidence of various neonatal morbidities and the associated risk of death in home-cared neonates in rural setting .To estimate the variation in the incidence of neonatal morbidities by season and by day of life . To identify the scope for prevention of morbidities and suggest a hypothesis . STUDY DESIGN : A prospect i ve observational study nested in the first year of the field trial in rural Gadchiroli , India . Trained village health workers in 39 villages observed neonates at the time of birth and in subsequent eight home visits up to 28 days . We diagnosed 20 neonatal morbidities by using clinical definitions . The data were analyzed for the incidence , case fatality , and relative risk of death and for the seasonal and day-wise variation in the incidence of morbidities . RESULTS : We observed total 763 neonates in 1 year . The incidence of morbidities was a mean of 2.2 morbidities per neonate . The case fatality in 13 morbidities was > 10 % . Only 2.6 % neonates were seen or treated by a physician , and 0.4 % were hospitalized . Hypothermia , fever , upper respiratory symptoms , umbilical and skin infections , and conjunctivitis showed statistically significant seasonal variation . Although the morbidities were concentrated in the first week of life , new cases continued to appear throughout the neonatal period . Various morbidities showed different distribution of incidence during 1 to 28 days . CONCLUSIONS : A large burden of disease occurs in rural home-cared neonates , and many morbidities are associated with high case fatality . Some morbidities show strong seasonal and day-wise variation in incidence , indicating poor care at home . We hypothesize that changes in practice s and better home-based care will prevent the seasonal and temporal increase in morbidities . Some morbidities may not be preventable and will need early detection and treatment . Therefore , frequent home visits by a health worker are necessary to identify sick neonates In this prospect i ve study , the axillary temperature of newborns delivered at home were recorded by a field worker once within a period of 24 h after the birth in 10 villages of Haryana , India , during 1992–1993 . Room air temperature was measured at the same time . Family members were interviewed to record newborn care practice s. Of the 189 babies , 11.1 % were found to be hypothermic ( temperature < 35.6 ° C ) and 22.8 % were hyperthermic ( temperature > 37.3 ° C ) . During winter months 19.1 % were hypothermic as compared to only 3.1 % in summer whereas 8.5 % were hyperthermic in winter compared to 36.8 % in summer . Room air temperature of < 24 ° C was recorded in 41 % . A strong correlation was observed between room air temperature and neonatal temperature . At the time of birth , 13.2 % of the delivery rooms in summer and 73.6 % in winter were reported to have heat source : 58.2 % babies were reported to be wiped soon after birth ; 97.3 % were wrapped in cloth ; the head was covered in 59.1 % cases in winter and 10.5 % in summer ; 97.3 % babies were kept with mother in same bed but not in skin-to-skin contact ; and 65 % were bathed within 24 h after delivery . Neonatal hypothermia is a common problem in developing countries . It is important that information , education and communication strategy about appropriate technologies for prevention and management of neonatal hypothermia is provided at domiciliary level . A significant proportion of babies are likely to suffer from hyperthermia in warm countries , specially in summer . Therefore , guidelines for thermal control in home births should be tailored to the specific environmental situation To identify the incidence rate and risk factors of neonatal hypothermia at referral hospitals in Tehran , Islamic Republic of Iran , 900 neonates were r and omly selected . Body temperature was measured repeatedly at different time points after birth . More than 50 % became hypothermic soon after birth . Multiple regression analysis showed that low birth weight , low gestational age environmental temperature , low Apgar score , multiple pregnancy and receiving cardiopulmonary resuscitation were significantly associated with hypothermia . These findings suggested that there is an urgent need to sensitize and educate all levels of staff dealing with neonates in our country Cleaning newborn infants with coconut oil shortly after birth is a common practice in Malaysian labour rooms . This study aim ed : ( 1 ) to determine whether this practice was associated with a significant decrease in the core temperature of infants ; and ( 2 ) to identify significant risk factors associated with neonatal hypothermia . The core temperature of 227 r and omly selected normal-term infants immediately before and after cleaning in labour rooms was measured with an infrared tympanic thermometer inserted into their left ears . Their mean post-cleaning body temperature ( 36.6 degrees C , SD = 1.0 ) was significantly lower than their mean pre-cleaning temperature ( 37.1 degrees C , SD = 1.0 ; p < 0.001 ) . Logistic regression analysis showed that the risk factors significantly associated with pre-cleaning hypothermia ( < 36.5 degrees C ) were : ( 1 ) not being placed under radiant warmer before cleaning p = 0.03 ) ; and ( 2 ) lower labour room temperature ( p < 0.001 ) . Logistic regression analysis also showed that the risk factors significantly associated with post-cleaning hypothermia were : ( 1 ) lower labour room temperature ( p < 0.001 ) ; ( 2 ) lower pre-cleaning body temperature ( p < 0.001 ) ; and ( 3 ) longer duration of cleaning ( p = 0.002 ) . In conclusion , to prevent neonatal hypothermia , labour room temperature should be set at a higher level and cleaning infants in the labour room should be discouraged BACKGROUND Majority of the neonates in developing countries are born and cared for in rural homes but the available information is mostly hospital based . OBJECTIVES To estimate : ( i ) the incidence of various neonatal morbidities and associated case fatality in home-cared rural neonates , ( ii ) proportion of neonates with indications for health care , and ( iii ) the proportion who actually receive it . DESIGN Prospect i ve observational study . SETTING Rural homes . METHODS Neonates in 39 study villages in the Gadchiroli district ( Maharashtra , India ) were observed during one year ( 1995 - 96 ) by 39 trained female village health workers at birth and during neonatal period ( 0 - 28 days ) by making eight home visits . A physician checked the data and the morbidities were diagnosed by a computer program . Vital statistics in these villages was independently collected . RESULTS Out of 1016 live births , 95 % occurred at home and 763 ( 75&% ) neonates were observed . The agreement between observations by health workers and physician was 92 % . Total 48.2 & neonates suffered high risk morbidities ( associated case fatality > 10 % ) , 72.2 % suffered low risk morbidities , and 17.9 % gained inadequate weight ( less than 300 g ) . Seventeen percent neonates developed clinical picture suggestive of sepsis . Though 54.4 % neonates had indications for health care and 38 out of total 40 neonatal deaths occurred in these , only 2.6 % received medical attention . The neonatal mortality rate was 52.4/1000 live births . CONCLUSION Nearly half of the neonates in rural homes developed high risk morbidities ten times the neonatal morbidity rate and needed health care but practically none received it . The magnitude of care gap suggests an urgent need for developing home-based neonatal care to reduce neonatal morbidities and BACKGROUND Hypothermia at birth has been associated with increased morbidity and mortality in preterm infants . OBJECTIVE To evaluate the effect of wrap with polyethylene bag at birth on admission temperatures and the incidences of hypothermia on admission in preterm infants gestational age < or = 32 weeks . MATERIAL AND METHOD A r and omized controlled trial was conducted in thirty-eight preterm infants with gestational age < or = 32 weeks . The infants were assigned and placed in polyethylene bag immediately after birth without drying under a radiant warmer or received st and ard thermal care including being dried and placed under a radiant warmer . Rectal temperatures were recorded on admission to neonatal unit and incidences o hypothermia were compared between the two groups . RESULTS The body temperatures of preterm infants with polyethylene bag were significantly higher than those of the control group { median 36.5 degrees C ( range 35.5 degrees C-37.2 degrees C ) vs. 35.9 degrees C ( range 34.9 degrees C-36.5 degrees C ) , p < 0.001}. On admission , the incidence of hypothermia in preterm infants wrap with polyethylene bag was significantly lower than in the control group ( 26 % vs. 89 % , p < 0.001 ) with a risk reduction of 0.63 ( 95 % CI 0.39 - 0.87 ) and a number needed to treat of 1.58 . CONCLUSION Polyethylene bag prevents heat loss at delivery in preterm infant less than 32 weeks gestation . Incidence of hypothermia was significantly reduced by use of polyethylene bag , a simple and inexpensive intervention The objective of this study was to determine the mortality risk related to hypothermia at the moment of admission and other factors such as clinical and geographical related to the transportation of the newborns admitted to the Instituto Materno Infantil de Pernambuco IMIP from 8 March to 11 June 2000 . A prospect i ve study involving 320 newborns arriving from home or health centres was carried out . Babies that were dead on arrival or subsequently transferred to other units were excluded . The risk of death was determined according to exposure to hypothermia and other types of exposure , using logistical regression . The risk of death was higher ( RR = 3.09 ; CI = 2.15 - 4.43 ) in the group exposed to moderate hypothermia ( temperature between 32.5 degrees C and 35.99 degrees C ) than in the non-exposed group ( temperature equal to or greater than 36.00 degrees C ) . The relative risk of death was also higher for newborns with a weight of less than 2500 g , that were less than 1 day old , respiratory distress syndrome , premature babies or with congenital malformations , that had used oxygen and /or intravenous infusion during transit , that came from the interior and that had travelled more than 150 km . In the final result of the multivariate analysis , sepsis ( ' adjusted ' RO = 6.23 ; 95 % CI = 5.66 - 6.80 ) , respiratory distress syndrome ( ' adjusted ' RO = 5.28 ; 95 % CI = 5.03 - 5.59 ) , moderate hypothermia ( ' adjusted ' RO = 3.49 , 95 % CI = 3.18 - 3.81 ) , and distance undertaken greater than 50 km ( ' adjusted ' RO = 2.39 ; 95 % CI = 2.14 - 2.63 ) remained . Hypothermia on admission showed itself to be an important and independent risk factor for neonatal death A prospect i ve observational study of post‐delivery care and neonatal body temperature , carried out at Kathm and u Maternity Hospital , was followed by a r and omized controlled intervention study using three simple methods for maintaining body temperature . There were 500 infants in the initial observation study and 300 in the intervention study . In the observation study , 85 % ( 420/495 ) of infants had temperatures < 36 ° C at 2 h and nearly 50 % ( 198/405 ) had temperatures < 36 ° C at 24 h ( 14 % were < 35 ° C ) . Most of the infants who were cold at 24 h had initially become cold at the time of delivery ( only seven infants had been both well dried and wrapped ) . In the intervention study , all infants were dried and wrapped before r and om assignment to one of the three methods : the “ kangaroo ” method , the traditional “ oil massage ” or a “ plastic swaddler ” . All three were found to be equally effective . Overall , 38 % ( 114/298 ) of the infants had temperatures < 36 ° C at 2 h and 18 % ( 41/231 ) at 24 h ( when none was < 35 ° C ) The present study was planned to evaluate the safety and efficacy of vinyl bags in prevention of hypothermia during resuscitation at birth in very low birth weight neonates . Sixty neonates of gestational age ≤32 weeks and birth weight ≤ 1500gm were r and omised to either study group , or control group . Study group neonates were put in vinyl bags up to neck and the head was covered with a cap after drying immediately following delivery and resuscitated under radiant warmer . Control group neonates were resuscitated by conventional drying under radiant warmer . Mean axillary and rectal temperature recorded immediately after admission to NICU were significantly higher in the study group compared to control group . Temperature recorded after 1 hour of admission to NICU were however comparable between the two groups . As temperature maintenance in these VLBW neonates is of tremendous importance , it would make sense to recommend the use of vinyl bags during their resuscitation |
1,737 | 20,447,543 | CONCLUSIONS People with smaller apo(a ) isoforms have an approximately 2-fold higher risk of CHD or ischemic stroke than those with larger proteins . | OBJECTIVES The purpose of this study was to assess the association of apolipoprotein(a ) ( apo[a ] ) isoforms with cardiovascular disease risk .
BACKGROUND Although circulating lipoprotein(a ) ( Lp[a ] ) is likely to be a causal risk factor in coronary heart disease ( CHD ) , the magnitude of this association is modest .
Lipoprotein(a ) particles with smaller , rather than larger , apo(a ) isoforms may be stronger risk factors . | CONTEXT High levels of lipoprotein(a ) are associated with increased risk of myocardial infa rct ion ( MI ) . OBJECTIVE To assess whether genetic data are consistent with this association being causal . DESIGN , SETTING , AND PARTICIPANTS Three studies of white individuals from Copenhagen , Denmark , were used : the Copenhagen City Heart Study ( CCHS ) , a prospect i ve general population study with 16 years of follow-up ( 1991 - 2007 , n = 8637 , 599 MI events ) ; the Copenhagen General Population Study ( CGPS ) , a cross-sectional general population study ( 2003 - 2006 , n = 29 388 , 994 MI events ) ; and the Copenhagen Ischemic Heart Disease Study ( CIHDS ) , a case-control study ( 1991 - 2004 , n = 2461 , 1231 MI events ) . MAIN OUTCOME MEASURES Plasma lipoprotein(a ) levels , lipoprotein(a ) kringle IV type 2 ( KIV-2 ) size polymorphism genotype , and MIs recorded from 1976 through July 2007 for all participants . RESULTS In the CCHS , multivariable-adjusted hazard ratios ( HRs ) for MI for elevated lipoprotein(a ) levels were 1.2 ( 95 % confidence interval [ CI ] , 0.9 - 1.6 ; events/10,000 person-years , 59 ) for levels between the 22nd and 66th percentile , 1.6 ( 95 % CI , 1.1 - 2.2 ; events/10,000 person-years , 75 ) for the 67th to 89th percentile , 1.9 ( 95 % CI , 1.2 - 3.0 ; events/10,000 person-years , 84 ) for the 90th to 95th percentile , and 2.6 ( 95 % CI , 1.6 - 4.1 ; events/10,000 person-years , 108 ) for levels greater than the 95th percentile , respectively , vs levels less than the 22nd percentile ( events/10,000 person-years , 55 ) ( trend P < .001 ) . Numbers of KIV-2 repeats ( sum of repeats on both alleles ) ranged from 6 to 99 and on analysis of variance explained 21 % and 27 % of all variation in plasma lipoprotein(a ) levels in the CCHS and CGPS , respectively . Mean lipoprotein(a ) levels were 56 , 31 , 20 , and 15 mg/dL for the first , second , third , and fourth quartiles of KIV-2 repeats in the CCHS , respectively ( trend P < .001 ) ; corresponding values in the CGPS were 60 , 34 , 22 , and 19 mg/dL ( trend P < .001 ) . In the CCHS , multivariable-adjusted HRs for MI were 1.5 ( 95 % CI , 1.2 - 1.9 ; events/10,000 person-years , 75 ) , 1.3 ( 95 % CI , 1.0 - 1.6 ; events/10,000 person-years , 66 ) , and 1.1 ( 95 % CI , 0.9 - 1.4 ; events/10,000 person-years , 57 ) for individuals in the first , second , and third quartiles , respectively , as compared with individuals in the fourth quartile of KIV-2 repeats ( events/10,000 person-years , 51 ) ( trend P < .001 ) . Corresponding odds ratios were 1.3 ( 95 % CI , 1.1 - 1.5 ) , 1.1 ( 95 % CI , 0.9 - 1.3 ) , and 0.9 ( 95 % CI , 0.8 - 1.1 ) in the CGPS ( trend P = .005 ) , and 1.4 ( 95 % CI , 1.1 - 1.7 ) , 1.2 ( 95 % CI , 1.0 - 1.6 ) , and 1.3 ( 95 % CI , 1.0 - 1.6 ) in the CIHDS ( trend P = .01 ) . Genetically elevated lipoprotein(a ) was associated with an HR of 1.22 ( 95 % CI , 1.09 - 1.37 ) per doubling of lipoprotein(a ) level on instrumental variable analysis , while the corresponding value for plasma lipoprotein(a ) levels on Cox regression was 1.08 ( 95 % CI , 1.03 - 1.12 ) . CONCLUSION These data are consistent with a causal association between elevated lipoprotein(a ) levels and increased risk of MI A size polymorphism ( K IV VNTR ) and largely unknown sequence variation in the apolipoprotein(a ) [ apo(a ) ] gene on chromosome 6q26–q27 together determine most of the extreme variation in apo(a ) glycoprotein expression and lipoprotein(a ) [ Lp(a ) ] plasma concentration in Caucasians . We have determined Lp(a ) plasma concentrations , the number of kringle IV ( K IV ) repeats in the apo(a ) gene and the expression of the apo(a ) glycoprotein in four ethnic groups ( Khoi San , South African Blacks , Hong Kong Chinese and Caucasians from the Tyrol , total n = 788 ) . The distributions of Lp(a ) concentrations , the frequencies of expressed and non-expressed apo(a ) K IV alleles , and the impact of the size polymorphism on Lp(a ) concentrations were all heterogeneous across population s. In contrast , the effect of the K IV repeat alleles appeared homogeneous . Lp(a ) concentrations were higher in Africans and Chinese than in Caucasians , but this was not explained by differences in K IV repeat allele frequencies among population s. Lp(a ) concentrations were highest in Khoi San , suggesting that high Lp(a ) is an old African trait . When expressed as Spearman rank correlations the impact of the size polymorphism was smallest in African Blacks ( R = −0.386 ) and largest in the Chinese ( R = −0.692 ) . In all four population s , the distribution of non-expressed apo(a ) alleles was non-r and om . Rather they were significantly associated with distinct size alleles and overall positively with high K IV repeat numbers . The negative correlation of K IV repeat length with Lp(a ) concentration was nonlinear in Khoi San and the average apo(a)-size-allele-associated Lp(a ) concentrations were markedly different between all population s. We conclude that besides the apo(a ) size variation , other factors affect Lp(a ) concentrations to different degrees in the study population s. Most likely , this is sequence variation in apo(a ) which is not the same in the different ethnic groups BACKGROUND Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a ) [ Lp(a ) ] , depending on Lp(a ) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a ) [ apo(a ) ] isoforms . Epidemiological studies may contribute to assessment of the relevance of these findings in the general population . METHODS AND RESULTS This study prospect ively investigated the association between Lp(a ) plasma concentrations , apo(a ) phenotypes , and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a r and om sample population of 826 individuals . We differentiated early atherogenesis ( incident nonstenotic atherosclerosis ) from advanced ( stenotic ) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms . Lp(a ) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion , with this association being confined to subjects with LDL cholesterol levels above the population median ( 3.3 mmol/L ) . Apo(a ) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis . In contrast , apo(a ) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis , especially when associated with high Lp(a ) plasma concentrations ( odds ratio , 6.4 ; 95 % CI , 2.8 to 14 . 9 ) . CONCLUSIONS Lp(a ) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis . Lp(a ) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol . Low-molecular-weight apo(a ) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol ( HDL-C ) and elevated triglycerides for patients at moderately high to high coronary heart disease ( CHD ) risk . Combination therapy is often required to achieve multiple lipid treatment goals , and > or = 50 % reduction in low-density lipoprotein cholesterol ( LDL-C ) is needed in some patients to achieve aggressive LDL-C targets . In this context , we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin ( niacin ER ) , a statin plus ezetimibe , and a highly potent statin alone . This was an open-label , multicenter , 12-week study in 292 patients ( 50 % women ) who qualified for drug therapy based on number of CHD risk factors . Patients were r and omized to four parallel arms , titrated from low to moderate or high doses : atorvastatin/niacin ER , rosuvastatin/niacin ER , simvastatin/ezetimibe , or rosuvastatin alone . Baseline mean values were , for LDL-C 197 mg/dL ( 5.1 mmol/L ) , HDL-C 49 mg/dL ( 1.3 mmol/L ) , triglycerides 168 mg/dL ( 1.9 mmol/L ) . There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment . All groups lowered LDL-C by approximately 50 % or more ( range -49 to -57 % ) , achieving mean levels of 82 - 98 mg/dL ( 2.1 - 2.5 mmol/L ) . Changes in non-HDL-C ( range -46 to -55 % ) mirrored those for LDL-C and did not differ among treatment groups . Statin/niacin ER combination regimens also increased HDL-C and large HDL ( HDL2 ) and lowered triglycerides and lipoprotein ( a ) significantly more than other regimens . No drug-related myopathy or hepatotoxicity was observed . In this study , low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD The objective of the present study was to examine the possible associations between low molecular weight ( LMW ) apolipoprotein(a ) ( apo(a ) ) isoforms ( F , B , S1,S2 ) and coronary heart disease ( CHD ) . We conducted a nested case-control ( prospect i ve ) study of five cohorts of white men : The 1936 cohort ( baseline 1976 , n = 548 ) and four cohorts from MONICA I born in 1923 ( n = 463 ) , 1933 ( n = 491 ) , 1943 ( n = 504 ) and 1953 ( n = 448 ) studied at baseline in 1983 . At follow up in 1991 , 52 subjects had developed a first myocardial infa rct ion and 22 had been hospitalized with angina pectoris . Plasma sample s obtained at baseline were stored frozen until 1993 - 94 , when case sample s ( n = 74 ) were analyzed together with sample s from matched ( disease free ) controls ( n = 190 ) . In a statistical model ( conditional logistic regression ) including all age groups , cholesterol ( or apo B ) level ( P < 0.01 ) , systolic blood pressure ( P = 0.05 ) and smoking ( P = 0.02 ) predicted CHD . In the statistical model Lp(a ) interacted significantly with age ( OR = 5.7 ; 95 % CI : 1.4 - 23.6 ; P = 0.016 ) , and high Lp(a ) ( over 45 mg/dl ) was associated with significantly increased risk in subjects under 60 years ( OR = 3.82 ; 95 % CI : 1.47 - 9.96 ) , but not in older men ( OR = 0.67 ; 95 % CI : 0.235 - 1.89 ) . Therefore , we studied the impact of Lp(a)/apo(a ) and other variables in subjects who had been under 60 years when they became cases . Among the younger subjects the presence of LMW apo(a ) isoforms significantly predicted the development of CHD ( OR = 3.83 ; 95 % CI : 1.18 - 12.4 ) . The increased risk pertained to high Lp(a ) ( above versus below 45 mg/dl : OR = 3.68 ; 95 % CI : 1.03 - 13.10 ) , and to Lp(a ) concentrations when entered into the model as a continuous variable ( P = 0.04 ) . Cholesterol or apo B ( P < 0.01 ) , smoking ( P = 0.02 ) , systolic blood pressure ( P = 0.05 ) and low alcohol consumption ( under nine drinks/week ) ( P = 0.04 ) were also significant predictors of CHD . We conclude that LMW apo(a ) isoforms are significantly associated with increased risk of CHD in men under 60 years Objective The aim of this study was to investigate the possible associations between lipoprotein(a ) [ Lp(a ) ] concentrations or apolipoprotein(a ) isoforms and the mode of clinical presentation of coronary heart disease ( CHD ) ( acute thrombotic event or not ) . Methods A total of 131 CHD patients and 71 age- and gender-matched individuals without known CAD ( free of symptoms of heart disease ) were enrolled in the study . CHD patients were classified into patients with a history of an acute coronary syndrome ( ACS , n=94 ) and patients with stable angina ( SA , n=37 ) . Lp(a ) levels were measured with an ELISA method , whereas apolipoprotein(a ) isoform analysis was performed ( in all patients and 33 controls ) by electrophoresis in 1.5 % SDS-agarose gels followed by immunoblotting . Isoform size was expressed as the number of kringle 4 ( K4 ) repeats . Results ACS patients had higher Lp(a ) plasma levels [ 21.9 ( 0.8–84.1 ) mg/dl ] and a greater proportion of elevated ( ≥ 30 mg/dl ) Lp(a ) concentrations ( 25.5 % ) compared with SA patients [ 9.2 ( 0.8–50.5 ) mg/dl , P < 0.01 and 10.8 % , P < 0.05 ] and controls [ 8.0 ( 0.8–55.0 ) mg/dl , P < 0.01 and 11.2 % , P < 0.05 ] , while there were no differences between SA patients and controls . The median apolipoprotein(a)-isoform size was 26 K4 . In 17 ( 10 % ) patients we could not detect any apolipoprotein(a ) isoform b and s by immunoblotting . ACS patients had a higher proportion of isoforms < 26 K4 ( low molecular weight ) than SA patients ( 56/85 vs. 12/33 , P < 0.005 ) and controls ( 10/29 , P < 0.005 ) . Conclusions CAD patients with a history of ACS have higher Lp(a ) plasma levels and a significantly higher proportion of low molecular weight apolipoprotein(a ) isoforms compared with patients with SA or to controls Objective : To determine the distribution of apolipoprotein ( a ) ( apo[a ] ) isoforms and their relation to the clinical severity of different ischemic stroke subtypes . Methods : Ninety-four hospital cases with a first-ever ischemic stroke and 188 r and omly selected control subjects matched for age , gender , and ethnicity were enrolled . Stroke etiology was defined according to Trial of Org 10172 in Acute Stroke Treatment criteria . NIH Stroke Scale ( NIHSS ) was used to assess the severity of stroke on admission Results : In univariate analysis , the presence of at least one small apo(a ) isoform was associated with ischemic stroke in men ( p = 0.02 ) but not in women ( p = 0.33 ) . After allowance for age , gender and traditional vascular risk factors , subjects carrying at least one small apo(a ) isoform were at increased risk of atherothrombotic stroke ( odds ratio [ OR ] 7.1 , 95 % CI 2.8 to 17.5 , p = 0.00001 ) but not of lacunar infa rct ion ( OR 1.1 , 95 % CI 0.5 to 2.7 , p = 0.78 ) . Multivariate logistic regression analysis revealed that in the atherothrombotic stroke group , the presence of at least one small-sized apo(a ) phenotype was associated with an NIHSS score ≥6 ( OR 13.6 , 95 % CI 1.6 to 111.9 , p = 0.015 ) . Conclusion : Small apolipoprotein ( a ) isoforms distinguish atherothrombotic stroke from lacunar infa rct ion and are associated with the severity of atherothrombotic stroke A high plasma concentration of lipoprotein(a ) [ Lp(a ) ] has been suggested as a risk factor for coronary heart disease ( CHD ) , but some recent prospect i ve studies have question ed the significance of Lp(a ) . Lp(a ) concentrations are determined to a large extent by the hypervariable apo(a ) gene locus on chromosome 6q2.7 , which contains a variable number of identical t and emly arranged transcribed kringle IV type 2 repeats . The number of these repeats correlates inversely with plasma Lp(a ) concentration . We analyzed whether apo(a ) gene variation ( kringle IV repeat number ) is associated with CHD . Apo(a ) genotypes were determined by pulsed-field gel electrophoresis/genomic blotting in CHD patients who had undergone angiography ( n = 69 ) and control subjects matched for age , sex , and ethnicity ( n = 69 ) and were related to Lp(a ) concentration , apo(a ) isoform in plasma , and disease status . Apo(a ) alleles with a low kringle IV copy number ( < 22 ) and high Lp(a ) concentration were significantly more frequent in the CHD group ( P < .001 ) , whereas large nonexpressed alleles were more frequent in control subjects . The odds ratio for CHD increased continuously with a decreasing number of kringle IV repeats and ranged from 0.3 in individuals with > 25 kringle IV repeats on both alleles to 4.6 in those with < 20 repeats on at least one allele . This provides direct genetic evidence that variation at the apo(a ) gene locus , which determines Lp(a ) levels , is also a determinant of CHD risk BACKGROUND The association between lipoprotein(a ) levels , apolipoprotein(a ) size and the (TTTTA)(n ) polymorphism which is located in the 5 ' non-coding region of the apo(a ) gene was studied in 263 patients with severe coronary heart disease and 97 healthy subjects . METHODS Lp(a ) levels were measured by ELISA , apo(a ) isoform size was determined by SDS-agarose gel electrophoresis , and analysis of the (TTTTA)(n ) was carried out by PCR . For statistical calculation , both groups were divided into low ( at least one apo(a ) isoform with < or = 22 Kringle IV ) and high ( both isoforms with > 22 KIV ) apo(a ) isoform sizes , and into low number ( < 10 in both alleles ) and high number of ( > or = 10 at least one allele ) TTTTA repeats . RESULTS Lp(a ) levels were higher ( P=0.007 ) , apo(a ) isoforms size < or = 22 KIV and TTTTA repeats > or = 10 were more frequent ( P=0.007 and 0.01 ) in cases than in controls . Lp(a ) levels were found to be increased with low apo(a ) weight in both groups ( both P<0.0001 ) . In multivariate logistic regression analysis , only the Lp(a ) levels ( P=0.005 ) and (TTTTA)(n ) polymorphism ( P=0.002 ) were found to be significantly associated with CHD . CONCLUSION Nevertheless , these results indicate that in CHD patients the (TTTTA)(n ) polymorphism has an effect on Lp(a ) levels which is independent of the apo(a ) size Cardiovascular disease rates vary greatly between ethnic groups in Canada . To establish whether this variation can be explained by differences in disease risk factors and sub clinical atherosclerosis , we undertook a population -based study of three ethnic groups in Canada : South Asians , Chinese and Europeans . A total of 985 participants were recruited from three cities ( Hamilton , Toronto and Edmonton ) by stratified r and om sampling . Clinical cardiovascular disease was defined by history or electrocardiographic findings . Carotid atherosclerosis was measured with B-mode ultrasonography . Conventional ( smoking , hypertension , diabetes , raised cholesterol ) and novel risk factors ( markers of a prothrombotic state ) were measured . Within each ethnic group and overall , the degree of carotid atherosclerosis was associated with a higher prevalence of cardiovascular disease . South Asians had the highest prevalence of this condition compared with Europeans and Chinese ( 11 % , 5 % and 2 % , respectively ; p=0.0004 ) . Despite this finding , Europeans had more atherosclerosis ( mean of the maximum intimal medial thickness 0.75 [ 0.16 ] mm ) than South Asians ( 0.72 [ 0.15 ] mm ) and Chinese ( 0.69 [ 0.16 ] mm ) . South Asians had an increased prevalence of glucose intolerance , higher total and low-density lipoprotein cholesterol , higher triglycerides and lower high-density lipoprotein cholesterol , and much greater abnormalities in novel risk factors including higher concentrations of fibrinogen , homocysteine , lipoprotein(a ) , and plasminogen activator inhibitor-1 . Although there are differences in conventional and novel risk factors between ethnic groups , this variation and the degree of atherosclerosis only partly explains the higher rates of cardiovascular disease among South Asians compared with Europeans and Chinese . The increased risk of cardiovascular events could be due to factors affecting plaque rupture , the interaction between prothrombotic factors and atherosclerosis , or as yet undiscovered risk factors |
1,738 | 15,802,417 | For women with bacterial vaginosis , antibiotics reduced the risk of persistent infection but did not reduce the risk of preterm birth or the incidence of associated adverse outcomes for the general population or for any subgroup analyzed .
For women with Trichomonas vaginalis , metronidazole reduced the risk of persistent infection but increased the incidence of preterm birth .
CONCLUSION : Contrary to the conclusions of 3 recent systematic review s , we found no evidence to support the use of antibiotic treatment for bacterial vaginosis or Trichomonas vaginalis in pregnancy to reduce the risk of preterm birth or its associated morbidities in low- or high-risk women | OBJECTIVE : To determine whether antibiotic treatment for bacterial vaginosis or Trichomonas vaginalis during pregnancy decreases the risk of preterm birth and associated adverse outcomes . | OBJECTIVES : To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora grade d as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora . METHODS : A prospect i ve cohort study of pregnant women in an antenatal clinic of a district general hospital . The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora . Two hundred and thirty-seven women were evaluable . Women with abnormal Gram-stained smears ( grade d as II or III ) on clinic recall were r and omised to receive treatment ( intravaginal clindamycin cream ) or placebo and followed to assess outcome of pregnancy , vaginal flora , and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment . RESULTS : Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square ( P = 0.2 ) . However , women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes ( P = 0.03 ) and return to normal vaginal flora ( P = 0.01 ) ( logistic regression analysis model ) . This may be due to differences in vaginal bacterial species in these grade s. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated ( revertants ) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy . CONCLUSIONS : Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora . Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome , possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen Available information suggests that some instances of preterm birth or premature rupture of membranes are associated with clinical ly unrecognized infection and inflammation of the lower uterine segment , decidua , and fetal membranes . Various cervicovaginal microorganisms have been recovered from these sites . Many of these microorganisms produce factors that may lead to weakening of the fetal membranes , release of prostagl and ins , or both . This study evaluated the presence of various lower genital tract microflora and bacterial conditions in 229 women enrolled in a double-blind , placebo-controlled trial of short-course erythromycin treatment at 26 to 30 weeks ' gestation to prevent preterm birth . Demographic , obstetric , and microbiologic parameters were prospect ively evaluated . Premature rupture of membranes occurred less frequently ( p less than 0.01 ) among women who received erythromycin ( 6 % ) versus placebo ( 16 % ) . Preterm premature rupture of membranes also occurred less frequently , although not significantly ( p = 0.3 ) in patients who received erythromycin ( 2 % ) versus placebo ( 5 % ) . Erythromycin treatment significantly decreased the occurrence of premature rupture of membranes among women who were initially positive for Chlamydia trachomatis infection . Logistic regression analysis demonstrated that C. trachomatis ( p = 0.05 ; odds ratio , 9 ) , vaginal wash phospholipase C ( p = 0.08 ; odds ratio , 6 ) and prior preterm birth ( p = 0.007 ; odds ratio 17 ) were associated with increased risk of preterm birth . Bacterial vaginosis , Mycoplasma hominis , Ureaplasma urealyticum were not significantly associated with increased risk of preterm birth or preterm rupture of membranes . These findings support a role for selected lower genital tract microflora in preterm birth and premature rupture . Large controlled treatment trials of specific infections or conditions associated with preterm birth and premature rupture of membranes are required to confirm the value of antimicrobial treatments in prevention of microbial-associated preterm birth In a prospect i ve study of 202 women ( gestational age 24 + /- 4 weeks ) , we evaluated possible influences of lower genital tract infection or bacterial conditions on obstetric outcomes , including preterm labor , preterm premature rupture of membranes , and preterm birth . The presence of bacterial vaginosis ( 18.7 % ) was associated with an increased risk of preterm labor ( relative risk , 2.6 ; 95 % confidence interval , 1.08 to 6.46 ) . For women with bacterial vaginosis who also had Mobiluncus species morphotypes identified on Gram stain , the relative risk of preterm labor was 3.8 ( 95 % confidence interval , 1.32 to 11.5 ) . Presence of vaginal Mycoplasma hominis ( 10.8 % of patients ) was associated with both preterm labor ( relative risk , 1.8 ; 95 % confidence interval , 0.77 to 4.4 ) and preterm birth ( relative risk , 5.1 ; 95 % confidence interval , 1.45 to 17.9 ) . Recovery of Staphylococcus aureus ( 3.0 % ) was associated with preterm labor ( relative risk , 3.1 ; 95 % confidence interval 1.12 to 8.7 ) . Identification of two or more bacterial-linked abnormalities was also associated with preterm labor ( relative risk , 3.3 ; 95 % confidence interval , 1.44 to 7.58 ) . An increased level of vaginal wash protease ( greater than or equal to 10 trypsin units ) ( 16 % ) was associated with preterm labor and was noted in 50 % of women with preterm premature rupture of membranes . A history of prior preterm birth was the single best historical predictor of both preterm labor ( relative risk , 3.6 ; 95 % confidence interval , 1.92 to 6.83 ) and preterm birth ( relative risk , 6.7 ; 95 % confidence interval , 2.2 to 20.4 ) . History of three or more abortions , antenatal urinary tract infection , and occurrence of medical complications during pregnancy also correlated with increased risk of preterm labor . These findings affirm and refine associations of various maternal reproductive tract infections with preterm labor , premature rupture of membranes , and birth , allowing for controlled treatment trials aim ed at prevention of preterm birth OBJECTIVE To assess the ability of clindamycin vaginal cream to reduce the incidence of preterm birth in women with abnormal genital tract flora in the second trimester of pregnancy . METHODS This was a r and omized , double-blind , placebo-controlled , tricenter study . A total of 409 women with abnormal genital tract flora on Gram stain of vaginal secretions at 13–20 weeks ' gestation were r and omized to receive a 3-day course of clindamycin vaginal cream or placebo . Those women who still had abnormal vaginal flora 3 weeks later received a 7-day course of the original study drug ( ie , either clindamycin vaginal cream or placebo as per original r and omization ) . The primary outcome measure was the incidence of preterm birth . RESULTS There was a statistically significant reduction in the incidence of preterm birth in the clindamycin vaginal cream group ( 4 % ) compared with placebo ( 10 % ) ( P < .03 ) . Significantly more babies born preterm ( 63 % ) required admission to the neonatal intensive care unit compared with term infants ( 4 % ) ( P < .001 ) . CONCLUSION A 2 % clindamycin vaginal cream , when compared with placebo administered to women with abnormal genital tract flora before 20 weeks ' gestation , can reduce the incidence of preterm birth by 60 % and hence the need for neonatal intensive care OBJECTIVE The purpose of this study was to assess the association of presumptive Trichomonas vaginalis treatment during pregnancy and birth outcomes . STUDY DESIGN A community-r and omized trial of presumptive sexually transmitted disease treatment during pregnancy was conducted between 1994 and 1999 in Rakai district , Ug and a. A sub analysis of a trial of presumptive therapy with azithromycin , cefixime , and metronidazole assessed Trichomonas vaginalis treatment in pregnant women . RESULTS Children of 94 women with Trichomonas who were treated had increased low birth weight ( relative risk , 2.49 ; 95 % CI , 1.12 - 5.50 ) , preterm birth rate ( relative risk , 1.28 ; 95 % CI , 0.81 - 2.02 ) , and 2-year mortality rate ( relative risk , 1.58 ; 95 % CI , 0.99 - 2.52 ) , compared with children of 112 women with Trichomonas who were not treated . CONCLUSION Treatment of Trichomonas vaginalis during pregnancy may be deleterious , and we infer that this may be due to metronidazole . This is consistent with a National Institute for Child Health and Human Development trial that found an excess of preterm births in children of women with Trichomonas vaginalis infection who were treated with metronidazole OBJECTIVE Our purpose was to analyze ( 1 ) the effects of prevalent lower reproductive tract infections and ( 2 ) the effect of systematic diagnosis and treatment to reduce risks of early pregnancy loss ( < 22 weeks ) , preterm premature rupture of membrances , and overall preterm birth . STUDY DESIGN A prospect i ve , controlled treatment trial was conducted on 1260 women . During the first 7 months of the program ( observation , phase I ) , women were examined at initiation of prenatal care for a panel of lower genital tract microorganisms and bacterial vaginosis . Women were followed up with reexaminations at 22 to 29 weeks and after 32 weeks ' gestation . The recommended treatments of the Centers for Disease Control ( i.e. , 300 mg of clindamycin orally twice daily for 7 days for bacterial vaginosis ) were used for infected women during the second 8 months of the study ( treatment , phase II ) . Data were analyzed according to intent to treat by means of univariate and multivariate methods . RESULTS Overall , presence of bacterial vaginosis ( 32.5 % ) at enrollment was associated with pregnancy loss at < 22 weeks ' gestation ( relative risk 3.1 , 95 % confidence interval 1.4 to 6.9 ) . Among women in the observation phase bacterial vaginosis was associated with increased risk of both preterm birth ( relative risk 1.9 , 95 % confidence interval 1.2 to 3.0 ) and preterm premature rupture of membranes ( relative risk 3.5 , 95 % confidence interval 1.4 to 8.9 ) . Within this population ( phase I ) 21.9 % of preterm birth overall ( 43.8 % premature rupture of membranes ) is estimated as attributable to bacterial vaginosis . Among women with bacterial vaginosis phase II ( treatment ) was associated with reduced preterm birth ( relative risk 0.5 , 95 % confidence interval 0.3 to 0.9 ) ; there was a similar reduction for women with preterm premature rupture of membranes ( relative risk 0.5 , 95 % confidence interval 0.2 to 1.4 ) . Women with both bacterial vaginosis and trichomoniasis were at highest risk of preterm birth ( 28 % ) ; treatment of both conditions ( phase II ) reduced preterm birth ( 17 % ) but did not eliminate this risk . Earlier patient enrollment and oral antibiotic treatment were associated with reduced preterm birth . CONCLUSIONS This prospect i ve , controlled trial confirms that the presence of bacterial vaginosis is associated with increased risks of pregnancy loss at < 22 weeks , preterm premature rupture of membranes , and preterm birth . Orally administered clindamycin treatment is associated with a 50 % reduction of bacterial vaginosis-linked preterm birth and preterm premature rupture of membranes . Women at risk for preterm birth or preterm premature rupture of membranes because of bacterial vaginosis or common genital tract infections should be screened , treated , reevaluated for cure , and re-treated if necessary BACKGROUND Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery . We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks ' gestation . METHODS In 624 pregnant women at risk for delivering prematurely , vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks ' gestation . We then performed a 2:1 double-blind r and omization to treatment with metronidazole and erythromycin ( 433 women ) or placebo ( 191 women ) . After treatment , the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time ( a mean of 27.6 weeks ' gestation ) . RESULTS A total of 178 women ( 29 percent ) delivered infants at less than 37 weeks ' gestation . Eight women were lost to follow-up . In the remaining population , 110 of the 426 women assigned to metronidazole and erythromycin ( 26 percent ) delivered prematurely , as compared with 68 of the 190 assigned to placebo ( 36 percent , P = 0.01 ) . However , the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis ( rate of preterm delivery , 31 percent with treatment vs. 49 percent with placebo ; P = 0.006 ) . Of the 358 women who did not have bacterial vaginosis when initially examined , 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely ( P = 0.55 ) . The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery ( preterm delivery in the treatment group , 39 percent ; and in the placebo group , 57 percent ; P = 0.02 ) and in women who weighed less than 50 kg before pregnancy ( preterm delivery in the treatment group , 14 percent ; and in the placebo group , 33 percent ; P = 0.04 ) . CONCLUSIONS Treatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery We tested topical intravaginal clindamycin phosphate at concentrations of 0.1 , 1.0 , and 2.0 % in the treatment of 62 women with symptomatic bacterial vaginosis in a prospect i ve , r and omized , double-blind , placebo-controlled trial , and offered open-label treatment with 1.0 % clindamycin to patients with persistent disease after blinded treatment . Blinded intravaginal clindamycin phosphate treatment cured bacterial vaginosis in 93.5 % ( 43 of 46 ) of patients 4 - 7 days after therapy , compared with 25.0 % ( four of 16 ) of patients receiving placebo ( P<.001 ) . One month later , 89.7 % ( 35 of 39 ) of those who initially responded to clindamycin treatment showed persistent cure . There were no significant side OBJECTIVE The pathogenesis of preterm birth and other adverse pregnancy outcomes linked with reproductive tract infection remains poorly understood . Mucolytic enzymes , including mucinases and sialidases ( neuraminidase ) , are recognized virulence factors among enteropathogens and bacteria that cause periodontal infection . Perturbation of maternal cervicovaginal mucosa membrane host defenses by such enzyme-producing microorganisms may increase the risk of sub clinical intrauterine infection during pregnancy and thus increase risks of preterm birth . STUDY DESIGN We prospect ively evaluated vaginal fluid mucinase and sialidase and selected cervicovaginal bacteria along with pregnancy outcomes in 271 women . Within this study , women with bacterial vaginosis ( 16 to 27 week ' gestation ) were treated with 2 % clinadmycin vaginal cream or placebo . Enzyme , microbial findings , treatment effects , and pregnancy outcomes were compared among drug- and placebo-treated women and control women without bacterial vaginosis . RESULTS Presence of bacterial vaginosis at intake was associated with increased risk of preterm birth ( relative risk 3.3 , 95 % confidence interval 1.2 to 9.1 , p = 0.02 ) , premature rupture of membranes ( relative risk 3.8 , 95 % confidence interval 1.6 to 9.0 , p = 0.002 ) , and preterm premature rupture of membranes . Mucinase and sialidase activities were more commonly identified , and they occurred in higher concentrations , if present , in women with bacterial vaginosis ( mucinase : 44.3 % with bacterial vaginosis vs 27.4 % without , p = 0.007 ; sialidase : 45 % with bacterial vaginosis vs 12 % without p < 0.001 ) . Sialidase activity was associated with bacterial vaginosis-linked organisms ( Gardnerella vaginalis , Mobiluncus spp , and Mycoplasma hominis ) and Chlamydia trachomatis and yeast species ; mucinase activity was associated only with bacterial vaginosis-linked microorganisms . Clindamycin , 2 % cream , was effective treatment for bacterial vaginosis and temporarily reduced mucinase and sialidase activities . Topical treatment of bacterial vaginosis did not reduce risks of perinatal morbidity . Women with persistent or recurrent sialidase 8 weeks after treatment were at increased risk of preterm birth ( 15.6 % vs 7.4 % ) premature rupture of membranes ( 30 % vs 15 % ) , and low birth weight ( 20 % vs 3 % , relative risk 6.8 , 95 % confidence interval 1.6 to 28.1 ) . CONCLUSIONS Persistence of sialidase-producing vaginal microorganisms in numbers sufficient to increase vaginal fluid sialidase activity may be a risk factor for possibly preventable sub clinical intrauterine infection and preterm birth . This study confirms and further informs our underst and ing of the association of bacterial vaginosis and preterm birth ; studies to evaluate whether systemic treatment for bacterial vaginosis can effectively reduce vaginal mucolytic enzymes and risks of prematurity and other morbid outcomes are continuing Background : Several studies have suggested that pregnant women infected with Trichomonas vaginalis may be at increased risk of an adverse outcome . Goal : To evaluate prospect ively the association between T. vaginalis and risk of adverse pregnancy outcome in a large cohort of ethnically diverse women . Study Design : At University‐affiliated hospitals and antepartum clinics in five United States cities , 13,816 women ( 5,241 black , 4,226 Hispanic , and 4,349 white women ) were enrolled at mid‐gestation , tested for T. vaginalis by culture , and followed up until delivery . Results : The prevalence of T. vaginalis infection at enrollment was 12.6 % . Race‐specific prevalence rates were 22.8 % for black , 6.6 % for Hispanic , and 6.1 % for white women . After multivariate analysis , vaginal infection with T. vaginalis at mid‐gestation was significantly associated with low birth weight ( odds ratio 1.3 ; 95 % confidence interval 1.1 to 1.5 ) , preterm delivery ( odds ratio 1.3 ; 95 % confidence interval 1.1 to 1.4 ) , and preterm delivery of a low birth weight infant ( odds ratio 1.4 ; 95 % confidence interval 1.1 to 1.6 ) . The attributable risk of T. vaginalis infection associated with low birth weight in blacks was 11 % compared with 1.6 % in Hispanics and 1.5 % in whites . Conclusions : After considering other recognized risk factors including co‐infections , pregnant women infected with T. vaginalis at mid‐gestation were statistically significantly more likely to have a low birth weight infant , to deliver preterm , and to have a preterm low birth weight infant . Compared with whites and Hispanics , T. vaginalis infection accounts for a disproportionately larger share of the low birth weight rate in blacks BACKGROUND The study tested the hypothesis that community-level control of sexually transmitted disease ( STD ) would result in lower incidence of HIV-1 infection in comparison with control communities . METHODS This r and omised , controlled , single-masked , community-based trial of intensive STD control , via home-based mass antibiotic treatment , took place in Rakai District , Ug and a. Ten community clusters were r and omly assigned to intervention or control groups . All consenting residents aged 15 - 59 years were enrolled ; visited in the home every 10 months ; interviewed ; asked to provide biological sample s for assessment of HIV-1 infection and STDs ; and were provided with mass treatment ( azithromycin , ciprofloxacin , metronidazole in the intervention group , vitamins/anthelmintic drug in the control ) . Intention-to-treat analyses used multivariate , paired , cluster-adjusted rate ratios . FINDINGS The baseline prevalence of HIV-1 infection was 15.9 % . 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group . 75.0 % of intervention-group and 72.6 % of control-group participants provided at least one follow-up sample for HIV-1 testing . At enrolment , the two treatment groups were similar in STD prevalence rates . At 20-month follow-up , the prevalences of syphilis ( 352/6238 [ 5.6 % ] ) vs 359/5284 [ 6.8 % ] ; rate ratio 0.80 [ 95 % CI 0.71 - 0.89 ] ) and trichomoniasis ( 182/1968 [ 9.3 % ] vs 261/1815 [ 14.4 % ] ; rate ratio 0.59 [ 0.38 - 0.91 ] ) were significantly lower in the intervention group than in the control group . The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups ( rate ratio 0.97 [ 0.81 - 1.16 ] ) . In pregnant women , the follow-up prevalences of trichomoniasis , bacterial vaginosis , gonorrhoea , and chlamydia infection were significantly lower in the intervention group than in the control group . No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses . INTERPRETATION We observed no effect of the STD intervention on the incidence of HIV-1 infection . In the Rakai population , a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors Objective To determine whether treatment of bacterial vaginosis ( BV ) with vaginal clindamycin affects pregnancy outcome OBJECTIVE Our purpose was to determine whether treatment of bacterial vaginosis with metronidazole in patients with preterm delivery in the penultimate pregnancy from preterm labor or premature rupture of membranes reduces the risk of subsequent preterm birth . STUDY DESIGN From January 1989 to June 1992 patients with a singleton gestation between 13 and 20 weeks and a history of preterm birth in the preceding pregnancy from either idiopathic preterm labor or premature rupture of membranes were screened for bacterial vaginosis . Those with a positive screen were r and omized to receive 250 mg of metronidazole three times a day for 7 days or placebo in a double-blind design . Data were analyzed with Student t and chi 2 tests , and differences considered significant at p < 0.05 . RESULTS Of 94 eligible patients , 80 were enrolled and completed the study , of which 44 received metronidazole . Both groups were comparable in number of entry variables . Compared with the placebo group , patients in the metronidazole group had significantly fewer hospital admissions for preterm labor , 12 ( 27 % ) versus 28 ( 78 % ) ; preterm births , eight ( 18 % ) versus 16 ( 39 % ) ; births of infants weighing < 2500 gm , six ( 14 % ) versus 12 ( 33 % ) ; and premature rupture of membranes , two ( 5 % ) versus 12 ( 33 % ) . CONCLUSION Treatment of bacterial vaginosis with metronidazole was effective in reducing preterm births in patients with a history of prematurity in the preceding pregnancy BACKGROUND Bacterial vaginosis has recently been associated with preterm labor and delivery . The purpose of our study was to determine whether regular prenatal vaginal pH testing result ed in more frequent diagnoses of bacterial vaginosis and other vaginal infections , more frequent treatment with antibiotics , and fewer preterm deliveries . We also sought to determine the sensitivity and specificity of pH testing and vaginal symptom reporting in identifying vaginal infections . METHODS Our study was a prospect i ve clinical trial involving 121 pregnant women r and omized to receive either st and ard prenatal care , including routine inquiry about vaginal symptoms , or st and ard care supplemented by vaginal pH testing . Women with symptoms or a vaginal pH level > 4.5 received a wet mount examination . Confirmed infections were treated according to study protocol s. RESULTS Women who received regular pH testing showed significantly higher detection rates for bacterial vaginosis than controls ( 48.4 % vs 27.1 % , P = .015 ) and more frequent detection of Trichomonas vaginalis ( 7.8 % vs 1.7 % , P = .116 ) . A higher percentage of women in the experimental group were treated for bacterial vaginosis and trichomoniasis ( 46.9 % vs 27.1 % , P = .024 ) , and the preterm birth rate was one half that of the control group ( 4.7 % vs 10.2 % , P = .243 ) . The presence of vaginal symptoms or a vaginal pH level > 4.5 identified bacterial vaginosis or trichomoniasis with 84.4 % sensitivity . CONCLUSIONS In our study , frequent vaginal pH testing during pregnancy result ed in more frequent diagnosis and treatment of bacterial vaginosis . Since vaginal symptoms and elevated pH levels appear to be useful in screening for bacterial vaginosis and trichomoniasis , frequent pH testing should be evaluated in larger studies OBJECTIVE Our purpose was to determine whether erythromycin treatment of pregnant women colonized with group B streptococci would reduce the occurrence of low birth weight ( < 2500 gm ) and preterm ( < 37 completed weeks ) birth . STUDY DESIGN In a double-blind clinical trial , 938 carriers of group B streptococci were r and omized to receive erythromycin base ( 333 mg three times a day ) or matching placebo beginning during the third trimester and before 30 weeks and continuing for 10 weeks or until 35 weeks 6 days of pregnancy . RESULTS Pregnancy outcomes were available for 97 % of r and omized women ; 14 % of subjects withdrew from the trial . Birth weight < 2500 gm occurred in 8.6 % of the erythromycin and 6.1 % of the placebo recipients ( relative risk 1.4 , 0.9 to 2.2 , p = 0.16 ) . Preterm delivery occurred in 11.4 % of women r and omized to erythromycin and in 12.3 % r and omized to placebo ( relative risk 0.9 , 95 % confidence limits 0.6 to 1.3 , p = 0.65 ) . Greater benefit of erythromycin in reducing these outcomes was not observed among women reporting the best compliance . CONCLUSIONS In this study of pregnant women colonized with group B streptococci treatment with erythromycin was not shown to be effective at prolonging gestation or reducing low birth weight . Greater than anticipated complicating factors , including spontaneous clearance of the organism , use of nontrial antibiotics , and density of colonization , may have result ed in population sizes too small to detect a benefit of treatment . Future studies should take these factors into account in determining sample sizes Objective To ascertain whether metronidazole treatment of women with a heavy growth of Gardnerella vaginalis during mid‐pregnancy would reduce the risk of spontaneous preterm birth OBJECTIVE To assess the efficacy of treatment of bacterial vaginosis ( BV ) using metronidazole to reduce preterm labour in primigravidae and multigravidae with previous midtrimester abortion or preterm labour . DESIGN R and omised controlled trial . SETTING Tertiary academic hospital . METHOD Two different groups of patients were screened for BV at the first antenatal visit , namely primigravidae and high-risk multigravidae who had had a previous midtrimester abortion or preterm delivery . Patients where BV was diagnosed clinical ly or on Gram 's stain of a smear taken from the posterior vaginal fornix , received either 400 mg metronidazole , or 100 mg vitamin C orally twice daily for 2 days . The Gram 's stain was repeated after 4 weeks . If BV was found again , treatment with the same drug was repeated . OUTCOME MEASURES Preterm delivery , birth weight and perinatal deaths . RESULTS One thous and and five patients entered the study , but 40 were excluded for various reasons and 10 were lost to follow-up . There were 464 primigravidae , of whom 150 ( 32 % ) had BV . Except for the 5-minute Apgar score , no significant differences were found between primigravidae negative for BV and those who received either metronidazole or vitamin C. There were 491 high-risk multigravidae , of whom 127 ( 26 % ) had BV . The mean gestational age in the BV-negative group was 37 weeks , in contrast to 37.4 weeks in the vitamin C group and 35.6 weeks in the metronidazole group . Birth weights in these three groups were 2,752 g , 2,759 g and 2,475 g respectively , significantly less ( P = 0.0109 ) in the metronidazole group in comparison with the BV-negative group . Delivery before 37 weeks occurred in 29 % of high-risk multigravidae with no BV but in 24 % of those who took vitamin C and in 43 % who took metronidazole . Differences were significant between the BV-negative and metronidazole groups ( P = 0.0231 ) and also between the metronidazole and vitamin C groups ( P = 0.0274 ) . Delivery before 28 weeks occurred in 4 % of the high-risk multigravidae with no BV but in 10 % of those with BV who took metronidazole . The difference was significant ( P = 0.0430 ) . Analysis for maximum likelihood estimates for preterm labour identified only previous preterm labour or midtrimester abortion as risk factors . CONCLUSION Metronidazole does not seem to reduce the prevalence of preterm labour when given for BV before 26 weeks ' gestation Objective To characterize the natural history of bacterial vaginosis in pregnancy and to assess the efficacy of short courses of oral metronidazole therapy for long-term suppression of bacterial vaginosis flora BACKGROUND Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery . We aim ed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population . METHODS We screened 6120 pregnant women attending hospital for their first antenatal visit -- who were at 12 - 22 weeks ' gestation ( mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora . We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis , in accordance with Nugent 's criteria . We r and omly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days . Primary endpoints were spontaneous preterm delivery ( birth > or = 24 but < 37 weeks ) and late miscarriage ( pregnancy loss > or = 13 but < 24 weeks ) . Analysis was intention to treat . FINDINGS Nine women were lost to follow-up or had elective termination . Thus , we analysed 485 women with complete outcome data . Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries ( 13/244 ) than did those in the placebo group ( 38/241 ; percentage difference 10.4 % , 95 % CI 5.0 - 15.8 , p=0.0003 ) . Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores , with maximum effect in women with the highest Nugent score of 10 . INTERPRETATION Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population A double-blind , placebo-controlled , r and omized trial was conducted to evaluate the efficacy , safety , and tolerance of a course of clindamycin ( administered for 3 days intravenously and 4 days orally ) among hospitalized women with preterm labor at less than or equal to 34 weeks ' gestation who were treated with tocolytics . One hundred three woman-perinate pairs were analyzed . Univariate analysis demonstrated that pregnancies were continued longer in women treated with clindamycin than in women who received placebo ( clindamycin-treated group , 35 days ; placebo-treated group , 25 days ; p = 0.02 ) . Survival analysis showed that pregnancy continued at least 35.5 days in 50 % of clindamycin-treated women versus 20 days for control women ( p = 0.03 ) . Obstetric and microbiologic parameters associated with treatment outcomes were also sought . Women with bacterial vaginosis more often delivered preterm ( p = 0.03 ; relative risk , 1.4 ; 95 % confidence interval , 1.04 to 2.0 ) . Among women with bacterial vaginosis , trends for increased duration of pregnancy ( clindamycin-treated group , 36 days ; placebo-treated group , 19 days ) , increased birth weight ( clindamycin-treated group , 2634 gm ; placebo-treated group , 2256 gm ) , and increased mean gestational age at delivery ( clindamycin-treated group , 35 weeks ; placebo-treated group , 34 weeks ) were associated with clindamycin treatment . Women with either group B streptococcus , Chlamydia trachomatis , Trichomonas vaginalis , or Staphylococcus aureus were more likely to have preterm premature rupture of membranes ( p = 0.01 ) . Clindamycin treatment of these women reduced the incidence of preterm premature rupture of membranes to that of uninfected subjects . Stratification by gestational age at enrollment showed clindamycin treatment to be associated with an increased interval to delivery only among mothers enrolled before 33 weeks ' gestation ( clindamycin-treated group , 40 days ; placebo-treated group , 28 days ; p less than 0.05 ) . Treatment with clindamycin appeared safe and well tolerated , with benefits limited to women who were less than or equal to 32 weeks ' gestation OBJECTIVE The purpose of this study was to determine if azithromycin is effective in reducing lower genital colonization of Ureaplasma urealyticum in women with preterm labor or preterm premature rupture of membranes ( PROM ) . METHODS A r and omized , double-blinded , placebo-controlled prospect i ve study of 60 pregnancies was carried out between 22 and 34 weeks . Genital mycoplasma cultures were performed at the time of admission . Patients were r and omized to receive either a single dose of azithromycin ( four 250 mg capsules ) or a placebo in addition to prophylactic intravenous ampicillin . Repeat cultures were done on undelivered patients 7 days after enrollment . The study had power to detect a 50 % decrease in colonization . RESULTS Overall , lower genital colonization was 47/59 ( 79.7 % ) for U. urealyticum . Seven days after enrollment , U. urealyticum was isolated in 14/15 ( 93.3 % ) of the azithromycin-treated cases and in 11/14 ( 78.6 % ) of the controls ( RR = 1.19 , 95 % CI = 0.88 - 1.61 ) . Vertical transmission of U. urealyticum was 3/15 ( 20 % ) in the azithromycin-treated cases and 5/10 ( 50 % ) for the controls ( RR = 0.40 , 95 % , CI = 0.12 - 1.31 ) . CONCLUSION These data suggests that a single 1 g dose of azithromycin is ineffective in reducing lower genital colonization with U. urealyticum OBJECTIVE To examine associations between bacterial vaginosis and other prevalent lower genital tract infections and clinical ly recognized first-trimester bleeding ; possible independent and joint effects of gestational bleeding and bacterial vaginosis or other prevalent infections on preterm birth and premature rupture of membranes ; and effects of antimicrobial treatment on reducing risks of preterm birth among these women . METHODS A secondary analysis was conducted of 1100 pregnant women enrolled in a prospect i ve observational study that examined the effects of st and ardized diagnosis and treatment of lower genital tract infections to prevent preterm birth . RESULTS Sixty percent of women with first-trimester bleeding had one or more study infections detected at the initial examination . First-trimester bleeding was associated independently with the presence of bacterial vaginosis ( odds ratio [ OR ] 1.5 , 95 % confidence interval [ CI ] 1.0 , 2.3 ) , Trichomonas vaginalis ( OR 2.3 , 95 % CI 1.3 , 4.2 ) , and Chlamydia trachomatis ( OR 2.7 , 95 % CI 1.4 , 5.1 ) . Preterm birth was increased among women with first-trimester bleeding and bacterial vaginosis ( relative risk [ RR ] 4.4 , 95 % CI 2.0 , 9.5 ) and bacterial vaginosis and T vaginalis ( RR 3.0 , 95 % CI 1.0 , 8.8 ) . Systemic antimicrobial treatment reduced the rate of preterm birth among women with bacterial vaginosis without first-trimester bleeding ( RR 0.37 , 95 % CI 0.16 , 0.88 ) . Treatment of women with both first-trimester bleeding and bacterial vaginosis reduced preterm birth ( RR 0.52 , 95 % CI 0.18 , 1.55 ) , but not significantly . CONCLUSION First-trimester bleeding was increased among women with bacterial vaginosis , T vaginalis , C trachomatis , and combinations of these infections . Women with bacterial vaginosis who also experienced first-trimester bleeding were at heightened risk for preterm birth . Treatment of studied infections reduced significantly the risks of preterm birth among women without first-trimester bleeding OBJECTIVE Our goal was to evaluate whether treatment of bacterial vaginosis during pregnancy with 2 % clindamycin vaginal cream reduces the incidence of either preterm delivery or low birth weight or of both . STUDY DESIGN A multicenter , double-blind , r and omized , placebo-controlled trial in Indonesia compared a 2 % clindamycin vaginal cream with a placebo cream . Women seeking prenatal care at 14 to 26 weeks of gestational age who had bacterial vaginosis ( Gram stain score > 6 and pH of vaginal fluid > 4.5 ) were invited to participate . Of the 745 women enrolled , 681 ( 91.4 % ) women were followed up through delivery . RESULTS Clindamycin vaginal cream was an effective treatment for bacterial vaginosis . Two weeks after completion of the treatment , 85.5 % of the women were cured . The rate of preterm delivery ( < 37 weeks ) was 15.0 % for clindamycin patients and 13.5 % for placebo patients ( odds ratio 1.1 , 95 % confidence interval 0.7 to 1.7 ) . The rate of low birth weight was 9.0 % for clindamycin patients and 6.8 % for placebo patients ( odds ratio 1.3 , 95 % confidence interval 0.8 to 2.4 ) . CONCLUSIONS Treatment of bacterial vaginosis with clindamycin vaginal cream did not reduce preterm delivery or low birth weight . Although clindamycin vaginal cream is an effective treatment for bacterial vaginosis , intravaginal treatment would not be effective against bacterial vaginosis-associated microorganisms harbored in the upper genital tract . Systemic treatment may be required to eradicate upper tract infection to reduce preterm delivery Objective To test the hypothesis that prophylactic administration of clindamycin 2 % vaginal cream can reduce the incidence of preterm birth in a high risk population Objective To determine whether treatment of bacterial vaginosis ( BV ) in early pregnancy decreases the risk of preterm delivery and peripartum infectious morbidity . Methods In this multicenter , r and omized , double-masked , placebo-controlled intervention trial , screening for BV was performed by vaginal Gram stain obtained from 5432 healthy women with singleton pregnancies during the first antenatal clinic visit at 10–17 weeks ' gestation . Bacterial vaginosis-positive women with no past history of preterm delivery were r and omized to a single course of treatment with either 2 % vaginal clindamycin cream or identical placebo cream for 7 days . Repeat Gram stains were taken 1 week after treatment and at 30–36 weeks ' gestation . Preterm delivery was defined as spontaneous delivery before 37 gestational weeks . Peripartum infectious morbidity was defined as postpartum endometritis , postpartum sepsis , postcesarean wound infection , or episiotomy wound infection , necessitating antimicrobial therapy . According to the power analysis , 180 patients were needed for both treatment arms to show a three-fold difference in the rates of preterm births . Results The overall prevalence of BV was 10.4 % . Of all BV-positive women , 375 ( 66 % ) were r and omized to the treatment arms . The primary cure rate was 66 % in the clindamycin group ; in the placebo group , 34 % spontaneously cleared BV ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 , 2.8 ) . The rate of preterm deliveries was 5 % in the clindamycin group and 4 % in the placebo group ( OR 1.3 , 95 % CI 0.5 , 3.5 ) . The rate of peripartum infectious morbidity was 11 % in the clindamycin group and 18 % in the placebo group ( OR 1.6 , 95 % CI 0.9 , 2.8 ) . Bacterial vaginosis recurred in 7 % of women . The rate of preterm deliveries was 15 % in this subgroup compared with 2 % among women who remained BV negative ( OR 9.3 , 95 % CI 1.6 , 53.5 ) . Conclusion Vaginal clindamycin did not decrease the rate of preterm deliveries or peripartum infections , but recurrent or persistent BV increased the risk for these complications OBJECTIVE Bacterial vaginosis causes symptomatic vaginal discharge and has been associated with preterm birth and with the acquisition of human immunodeficiency virus . Half of all women with bacterial vaginosis are free of symptoms , and treatment of these women is controversial . The objective of this study was to determine the extent of poor symptom recognition in this group of women . STUDY DESIGN Seventy-five women attending a sexually transmitted disease clinic who had asymptomatic bacterial vaginosis were entered into a r and omized , double-blind , placebo-controlled trial comparing metronidazole gel with placebo . Subjects ' perceptions about changes in vaginal discharge and odor were determined , and treatment and placebo groups were compared by means of st and ard statistical analysis . RESULTS When subjects were stratified by treatment group , there were no differences in their retrospective assessment s of vaginal discharge and odor . A subset of women who had normalization of clinical parameters or of Gram stain scores did admit retrospectively to improvement ; however , the difference between this group and the group without normalization was not statistically significant . Twenty-one percent of treated women subsequently had vaginal c and idiasis . CONCLUSIONS A greater percentage of women with resolution of bacterial vaginosis did retrospectively notice improvement in vaginal discharge and odor in comparison with those women without resolution ; however , this was not statistically significant . These findings do not support routine treatment of women with asymptomatic bacterial vaginosis A r and omized clinical trial was conducted to test the postulate that erythromycin treatment of pregnant mothers may prevent preterm deliveries and low birth weight ( LBW ) in India . Vaginal swabs ( for Ureaplasma urealyticum and Mycoplasma hominis cultures ) and endocervical specimens ( for Chlamydia trachomatis antigen testing ) were obtained from 437 pregnant women : 219 for the erythromycin group and 218 for the placebo group . Findings of the study showed that mean birth weight and the incidence of LBW and preterm deliveries in both groups were similar . This result is in opposition with the existing body of evidence that reports that infections in the genital tract caused by U. urealyticum and C. trachomatis may be associated with LBW and prematurity . The study therefore concludes that erythromycin treatment of pregnant women neither decreases the incidence of LBW or preterm deliveries nor will it improve birth weight of infants BACKGROUND Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery . It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery . METHODS We screened pregnant women for trichomoniasis by culture of vaginal secretions . We r and omly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole ( 320 women ) or placebo ( 297 women ) 48 hours apart . We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation . The primary outcome was delivery before 37 weeks of gestation . RESULTS Between r and omization and follow-up , trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group ( 92.6 percent ) and 92 of 260 women with follow-up cultures in the placebo group ( 35.4 percent ) . Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group . Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group ( 19.0 percent ) and 31 women in the placebo group ( 10.7 percent ) ( relative risk , 1.8 ; 95 percent confidence interval , 1.2 to 2.7 ; P=0.004 ) . The difference was attributable primarily to an increase in preterm delivery result ing from spontaneous preterm labor ( 10.2 percent vs. 3.5 percent ; relative risk , 3.0 ; 95 percent confidence interval , 1.5 to 5.9 ) . CONCLUSIONS Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery . Routine screening and treatment of asymptomatic pregnant women for this condition can not be recommended The purpose of this investigation was to evaluate the efficacy of amoxicillin for treatment of bacterial vaginosis during pregnancy . The diagnosis of bacterial vaginosis was established by clinical examination and microscopic examination of a Gram stain and saline preparation of vaginal secretions . In a double-blind , r and omized manner , 108 patients at 15 - 25 weeks ' gestation were assigned to treatment with oral amoxicillin , 500 mg three times daily for 14 days , or placebo . Patients were evaluated 2 weeks after treatment , at 34 - 36 weeks ' gestation , and at delivery . There were no significant differences between the two groups with respect to any clinical or microbiologic measure of treatment outcome . There were also no significant differences in the frequency of obstetric complications . We conclude that amoxicillin is not effective therapy for bacterial vaginosis in pregnant We prospect ively studied the relationship of pregnancy outcome to bacterial vaginosis , an anaerobic vaginal condition , and to other selected genital pathogens among 534 gravid women . Bacterial vaginosis was presumptively diagnosed by gas-liquid chromatographic identification of microbial organic acid metabolites in 102 women ( 19 % ) , and cervical infection with Chlamydia trachomatis was found in 47 ( 9 % ) of the women . Although women with and without bacterial vaginosis had similar demographic and obstetric factors , neonates born to women with bacterial vaginosis had lower mean birth weight than did neonates born to women without bacterial vaginosis ( 2960 + /- 847 g vs 3184 + /- 758 g ) . Bacterial vaginosis was significantly associated with preterm premature rupture of the membranes ( odds ratio [ OR ] , 2.0 ; 95 % confidence interval [ Cl ] , 1.1 to 3.7 ) , preterm labor ( OR , 2.0 ; Cl , 1.1 to 3.5 ) , and amniotic fluid infection ( OR , 2.7 ; Cl , 1.1 to 6.1 ) , but not with birth weight below 2500 g ( OR , 1.5 ; Cl , 0.8 to 2.0 ) . Cervical infection with C trachomatis was independently associated with preterm premature rupture of the membranes , preterm labor , and low birth weight ( OR , 1.5 ; Cl , 0.8 to 2.0 ) Eighty-nine women with either bacterial vaginosis , Trichomonas vaginalis , or both , who also had a positive fetal fibronectin test result were r and omized to two courses of metronidazole treatment as part of a Maternal-Fetal Medicine Network Units study of the National Institute of Child Health and Human Development . In this subgroup analysis , compared with the placebo group , women who were treated with metronidazole had a nonsignificant reduction in spontaneous preterm birth from 14.6 % to 8.3 % Objective To analyse alterations in the vaginal flora after 2 % clindamycin vaginal cream or placebo administered for the prevention of preterm delivery in high risk women Antenatal patients free of Trichomonas vaginalis vaginal infection were compared with infected patients , half of whom were treated and half left untreated . The treated group was given benzoylmetronidazole 50 ml ( 2 g metronidazole equivalent ) as a single dose . The mode of treatment was found to be very palatable and highly effective . The birth weights and gestational age at delivery were similar in all three groups Among 640 r and omly selected women who were attending a sexually transmitted disease clinic and did not have trichomoniasis , 33 % had bacterial vaginosis as defined by a composite of four clinical criteria : ( 1 ) Vaginal discharge was homogeneous ; ( 2 ) vaginal discharge had a pH greater than or equal to 4.7 ; ( 3 ) vaginal discharge had an amine-like odor when mixed with 10 % potassium hydroxide ; ( 4 ) vaginal discharge contained clue cells representing greater than or equal to 20 % of vaginal epithelial cells . Previously published Gram stain criteria for bacterial vaginosis correlated better than results of semiquantitative cultures for Gardnerella vaginalis with presence or absence of clue cells and with composite clinical criteria . Of 293 women with bacterial vaginosis by Gram stain criteria , 65 % had symptoms of increased vaginal discharge and /or vaginal malodor , while 74 % had signs of characteristic homogeneous vaginal discharge or amine-like odor . Elevated vaginal pH was the least specific and amine-like odor the least sensitive sign of bacterial vaginosis . Gram stain criteria for bacterial vaginosis were not associated with the concentrations of endocervical or vaginal inflammatory cells but were significantly associated with a clinical diagnosis of pelvic inflammatory disease . After adjusting for coinfection , sexual behavior , and other variables , bacterial vaginosis remained associated with adnexal tenderness ( odds ratio = 9.2 , p = 0.04 ) . Bacterial vaginosis , previously implicated as a risk factor for obstetric infections , may be a risk factor for pelvic inflammatory disease Background Women with cervicitis frequently have bacterial vaginosis ( BV ) . Prior studies have suggested that BV is involved in the pathogenesis of cervicitis . Goals To delineate the association of BV and cervicitis and to determine whether treatment of BV results in increased resolution of cervicitis . Study Design Women with clinical ly diagnosed cervicitis and BV received doxycycline and ofloxacin and were r and omized to treatment with metronidazole gel or placebo . Resolution of BV and cervicitis was assessed . Results Metronidazole gel was associated with resolution of BV . Resolution of cervicitis was associated with use of metronidazole gel versus placebo ( 24/27 [ 88.9 % ] versus 15/24 [62.5%];P = 0.03 ) . When further stratified by resolution of BV , those whose BV resolved were more likely to have resolution of cervicitis than those with persistent BV . Although these trends persisted in multivariate analyses , they did not achieve statistical significance . Conclusion Univariate analyses suggest an association between BV and cervicitis . An association between the use of metronidazole gel and resolution of cervicitis was demonstrated . Hypotheses regarding the latter include nonspecific antiinflammatory effects of metronidazole , its effect on BV flora , and its effect on a specific unrecognized pathogen |
1,739 | 26,881,842 | In particular , younger , healthier patients may benefit from higher hemoglobin targets , and the harm may be concentrated in older individuals with preexisting cardiovascular risk factors . | Chronic kidney disease ( CKD ) is a global health epidemic ( 1 ) that is increasing in incidence and prevalence ( 2 , 3 ) .
Anemia is common in CKD ( 4 ) ; its treatment with erythropoietin-stimulating agents ( ESAs ) reduces the need for blood transfusions and has varying effects on morbidity and mortality ( 57 ) .
The optimal hemoglobin targets for treating anemia with ESAs are controversial , with safety concerns around the normalization of hemoglobin levels due to the increased risk for cardiovascular events ( 812 ) .
Clinical practice guidelines recommend hemoglobin targets of 10 to 11 g/L ( 13 , 14 ) , but individualization of hemoglobin targets remains relatively common among clinicians .
In 2007 , the U.S. Food and Drug Administration placed black box warnings on ESAs ( 15 ) .
Publication of the trial by Pfeffer and colleagues ( 16 ) , combined with changes in Medicare reimbursement in 20102011 , has led to decreased ESA use .
Nonetheless , higher hemoglobin targets for some patients ( that is , individualization of treatment ) continues to be discussed and practice d. Most clinicians believe that treatment of anemia in CKD influences health-related quality of life ( HRQOL ) and its various domains ( 17 , 18 ) . | A disease-specific question naire was developed for patients receiving chronic hemodialysis by interviewing patients to determine which aspects of their quality of life were adversely affected by their disease . The final question naire contained 26 questions in five dimensions ( physical symptoms , fatigue , depression , relationships with others , frustration ) . The question naire demonstrated construct validity when compared with the Sickness Impact Profile , time trade-off technique and an exercise stress test . It was reproducible in stable , placebo-treated patients ( correlation coefficient 0.85 - 0.98 for the 5 dimensions ) . It was more responsive than other measures in detecting an improvement with erythropoietin therapy in a r and omized , placebo-controlled trial . This question naire should be useful for the assessment of the effect of various interventions upon the quality of life of hemodialysis patients In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials The Normal Hematocrit Trial ( NHT ) was the largest trial of epoetin r and omizing 1265 hemodialysis patients with cardiac disease to lower ( 9–11 g/dl ) or higher ( 13–15 g/dl ) hemoglobin ( Hgb ) , hypothesizing that higher Hgb would reduce mortality , and improve survival and quality of life . The trial was terminated early , and a 1998 publication reported that targeting higher hematocrit levels led to an insignificant increase in the primary end points ( death or myocardial infa rct ) , or risk ratio 1.3 , 95 % confidence interval ( CI ) , 0.9–1.90 , but the P-value was not given , and all-cause death risk was not reported . A higher target reportedly did not increase hospitalization rates , but did significantly improve the ‘ physical function ' domain of quality of life . Comparing the 1996 Food and Drug Administration ( FDA ) -filed clinical trial report to the 1998 publication , however , found several discrepancies . Among these , the 1998 article reported interim trial results with only the adjusted CI but did not state that the unadjusted CIs were 99.912th percentile , and despite being a secondary end point , reported only the association of achieved Hgb with higher quality of life score . R and omization to the higher target had actually increased the risk for the primary end point ( risk ratio 1.28 , 95 % CI=1.06–1.56 ; P=0.0112 ; 99.92 % CI=0.92–1.78 ) , the risk of death ( risk ratio 1.27 , 95 % CI=1.04–1.54 ) , non-access thrombotic events ( P=0.041 ) , and hospitalization rate ( P=0.04 ) , while ‘ physical function ' did not improve ( P=0.88 ) . Hence , disclosure of these results in the 1998 publication or access to the FDA -filed report on the NHT in the late 1990s would likely have led to earlier concerns about epoetin safety and greater doubts about its benefits BACKGROUND The Dialysis Outcomes and Practice Patterns Study ( DOPPS ) is a prospect i ve , observational study based on data collected from nationally representative sample s of haemodialysis facilities . The burden of anaemia in haemodialysis patients is substantial , leading to considerable morbidity , mortality and reduced quality of life . This study examines anaemia management and outcomes based on data from five European countries participating in the DOPPS : France , Germany , Italy , Spain and the UK . METHODS Baseline data on demographics , co-morbidities and anaemia management in 4591 haemodialysis patients from 101 nephrology facilities were collected in 1998 - 2000 . Using multivariate Cox survival analyses to adjust for patient characteristics , relationships between haemoglobin concentration at study entry and rates of mortality and hospitalization were evaluated . RESULTS For a year 2000 sample of prevalent patients on haemodialysis > 180 days , mean haemoglobin concentration was 11.0 g/dl ; 53 % had a haemoglobin concentration > or = 11 g/dl [ 1998 - 1999 = 44 % ( P < 0.05 ) ] . In 2000 , 84 % of prevalent patients were prescribed recombinant human erythropoietin ( rHuEpo ) . Higher haemoglobin concentrations were associated with decreased relative risk ( RR ) for mortality ( RR = 0.95 for every 1 g/dl higher haemoglobin , P = 0.03 ) and hospitalization ( RR = 0.96 , P = 0.02 ) . Patients with haemoglobin < 10 g/dl were 29 % more likely to be hospitalized than patients with haemoglobin 11 - 12 g/dl ( P < 0.001 ) . CONCLUSION Even after adjustment , lower haemoglobin concentrations were associated with higher morbidity and mortality in European haemodialysis patients . A trend to increased haemoglobin concentrations was observed following publication of the European Best Practice Guidelines ( EBPG ) on anaemia management for chronic kidney disease patients , but efforts must continue to achieve EBPG goals BACKGROUND AND OBJECTIVES The effects of different hemoglobin targets when using erythropoiesis-stimulating agents on quality of life are somewhat controversial , and predictors of change in quality of life in endstage renal disease have not been well characterized . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were r and omly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 weeks , using epoetin_alfa as primary therapy . Patients and attending physicians were masked to treatment assignment . Quality of life , a secondary outcome , was prospect ively recorded using the Kidney Disease Quality of Life ( KDQoL ) question naire at weeks 0 , 24 , 36 , 48 , 60 , 72 , 84 , and 96 , with prespecified outcomes being fatigue and quality of social interaction . RESULTS The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr . Mortality was low , reflecting the relatively healthy group enrolled . Of 20 domains within the KDQoL only the prespecified domain of fatigue showed significant change over time between the two groups . Improvement in fatigue scores in the high-target group ranged from 3.2 to 7.9 over time ( P = 0.007 ) compared with change in the low-target group . Higher body mass index and lower erythropoietin dose at baseline were independent predictors of improvement in multiple KDQoL domains . CONCLUSIONS In relatively healthy hemodialysis patients , normal hemoglobin targets may have beneficial effects on fatigue . Improvement in multiple domains of quality of life is associated with higher body mass index and lower erythropoietin requirements BACKGROUND Patients with diabetes and anemia are at high risk of cardiovascular disease . The Anemia CORrection in Diabetes ( ACORD ) Study aim ed to investigate the effect of anemia correction on cardiac structure , function , and outcomes in patients with diabetes with anemia and early diabetic nephropathy . METHODS One hundred seventy-two patients with type 1 or 2 diabetes mellitus , mild to moderate anemia , and stage 1 to 3 chronic kidney disease were r and omly assigned to attain a target hemoglobin ( Hb ) level of either 13 to 15 g/dL ( 130 to 150 g/L ; group 1 ) or 10.5 to 11.5 g/dL ( 105 to 115 g/L ; group 2 ) . The primary end point was change in left ventricular mass index ( LVMI ) . Secondary end points included echocardiographic variables , renal function , quality of life , and safety . RESULTS Median Hb level and LVMI were similar in groups 1 and 2 ( Hb , 11.9 and 11.7 g/dL [ 119 and 117 g/L ] ; LVMI , 113.5 and 112.3 g/m(2 ) , respectively ) . At study end , Hb levels were 13.5 g/dL ( 135 g/L ) in group 1 and 12.1 g/dL ( 121 g/L ) in group 2 ( P < 0.001 ) . No significant differences were observed in median LVMI at month 15 between study groups ( group 1 , 112.3 g/m(2 ) ; group 2 , 116.5 g/m(2 ) ) . Multivariate analysis showed a nonsignificant decrease in LVMI ( P = 0.15 ) in group 1 versus group 2 . Anemia correction had no effect on the rate of decrease in creatinine clearance , but result ed in significantly improved quality of life in group 1 ( P = 0.04 ) . There were no clinical ly relevant differences in adverse events between study groups . CONCLUSION In patients with diabetes with mild to moderate anemia and moderate left ventricular hypertrophy , correction to an Hb target level of 13 to 15 g/dL ( 130 to 150 g/L ) does not decrease LVMI . However , normalization of Hb level prevented an additional increase in left ventricular hypertrophy , was safe , and improved quality of life BACKGROUND This r and omized clinical trial is design ed to assess whether the prevention and /or correction of anemia , by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease , would delay left ventricular ( LV ) growth . Study design and sample size calculations were based on previously published Canadian data . METHODS One hundred seventy-two patients were r and omly assigned . The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin ( Hgb ) level targets of 12.0 to 14.0 g/dL ( 120 to 140 g/L ) . The control/delayed treatment group had Hgb levels of 9.0 + /- 0.5 g/dL ( 90 + /- 5 g/L ) before therapy was started : target level was 9.0 to 10.5 g/dL ( 90 to 105 g/L ) . Optimal blood pressure and parathyroid hormone , calcium , and phosphate level targets were prescribed ; all patients were iron replete . The primary end point is LV growth at 24 months . RESULTS One hundred fifty-two patients were eligible for the intention-to-treat analysis : mean age was 57 years , 30 % were women , 38 % had diabetes , and median glomerular filtration rate was 29 mL/min ( 0.48 mL/s ; range , 12 to 55 mL/min [ 0.20 to 0.92 mL/s ] ) . Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline . Erythropoietin therapy was administered to 77 of 78 patients in the treatment group , with a median final dose of 2,000 IU/wk . Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk . There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index ( LVMI ) from baseline to 24 months , which was 5.21 + /- 30.3 g/m2 in the control/delayed treatment group versus 0.37 + /- 25.0 g/m2 in the treatment group . Absolute mean difference between groups was 4.85 g/m2 ( 95 % confidence interval , -4.0 to 13.7 ; P = 0.28 ) . Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL ( 127.5 g/L in treatment group versus 11.46 g/dL [ 114.6 g/L ] in control/delayed treatment group ; P = 0.0001 ) . LV growth occurred in 20.1 % in the treatment group versus 31 % in the control/delayed treatment group ( P = 0.136 ) . In patients with a stable Hgb level , mean LVMI did not change ( -0.25 + /- 26.7 g/m2 ) , but it increased in those with decreasing Hgb levels ( 19.3 + /- 28.2 g/m2 ; P = 0.002 ) . CONCLUSION This trial describes disparity between observational and r and omized controlled trial data : observed and r and omly assigned Hgb level and LVMI are not linked ; thus , there is strong evidence that the association between Hgb level and LVMI likely is not causal . Large r and omized controlled trials with unselected patients , using morbidity and mortality as outcomes , are needed 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 The risks/ benefits of anemia treatment in dialysis patients have been redefined in the US Epoetin α label . This analysis was carried out to determine if increasing hemoglobin ( Hb ) levels improve exercise tolerance and physical function in anemic dialysis patients . This is a new analysis of the Canadian Erythropoietin Study Group trial , a double-blind , r and omized , placebo-controlled trial in dialysis patients . Subjects were 18 to 75 years old , on hemodialysis for > 3 months , and had a baseline Hb < 9.0 g/dL. Patients with a history of diabetes mellitus , ischemic heart disease , or severe/uncontrolled hypertension were excluded . Patients were r and omized to receive Epoetin α to a target Hb of 9.5 to 11.0 g/dL ( n=40 ) or a target of 11.5 to 13.0 g/dL ( n=38 ) , or receive placebo ( n=40 ) . Results from patients in the Epoetin-α-treated arms were combined for this analysis . Hb level , exercise tolerance ( Treadmill Stress Test and 6-Minute Walk Test ) and patient-reported physical function measures ( Physical Summary domain from the Kidney Disease Question naire , and 4 domains from the Sickness Impact Profile ) were reported at baseline and months 2 , 4 , and 6 . Differences in measures were statistically significant for exercise tolerance ( Treadmill Stress , P=0.0001 ) and patient-reported physical function ( Kidney Disease Question naire Physical , P=0.0001 ; Sickness Impact Profile Physical , P=0.0015 ) across all time points for Epoetin-α-treated patients compared with placebo . Improvements were seen at 2 months and were maintained through months 4 and 6 . Dialysis patients receiving Epoetin α showed improved exercise tolerance and physical function . These findings should be considered as physicians weigh the risks and benefits of treatment The investigators evaluated the impact of recombinant human erythropoietin ( r-HuEPO ) therapy on health-related quality of life ( HRQL ) in predialysis chronic renal disease patients with anemia . Eighty-three patients were entered into a r and omized , parallel-group , open-label clinical trial with follow-up evaluations over 48 weeks . Forty-three patients were assigned to r-HuEPO treatment , and 40 patients were assigned to an untreated control group . Hematocrit levels were measured at baseline and monthly . HRQL was assessed at baseline and at weeks 16 , 32 , and 48 . The HRQL assessment included measures of physical function , energy , role function , health distress , cognitive function , social function , home management , sexual dysfunction , depression , and life satisfaction . Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group ( P < 0.0001 ) , and no changes were seen in the untreated group . Correction of anemia ( hematocrit > or = 36 ) occurred in 79 % of r-HuEPO-treated patients and 0 % of control patients . Significant improvements in assessment s of energy ( P < 0.05 ) , physical function ( P < 0.05 ) , home management ( P < 0.05 ) , social activity ( P < 0.05 ) , and cognitive function ( P < 0.05 ) were found for the r-HuEPO-treated group . No changes were observed in the control group , except for a decrease in physical function ( P < 0.05 ) . Between-group differences favoring the r-HuEPO-treated group were found for energy ( P < 0.05 ) and physical functioning ( P < 0.05 ) . In patients receiving r-HuEPO , significant improvements were seen in hemotocrit levels , and these increases result ed in improvements in HRQL BACKGROUND This study is design ed to assess the effect of early and complete correction of anemia by using recombinant human erythropoietin ( epoetin ) alfa on the progression of chronic kidney disease ( CKD ) . METHODS Patients were r and omly assigned to achieve high ( 13 to 15 g/dL [ 130 to 150 g/L ] ) or low ( 11 to 12 g/dL [ 110 to 120 g/L ] ) hemoglobin-level targets during 4 months of stabilization , followed by 36 months of maintenance . Glomerular filtration rate ( GFR ) decrease was measured by using iohexol clearance . Quality of life , nutrition , and safety also were monitored . RESULTS Because of labeling changes for subcutaneous administration of epoetin alfa ( Eprex ; Johnson and Johnson , Schaffhausen , Switzerl and ) , the study was terminated prematurely . There were 195 patients enrolled in each group ; 108 high-hemoglobin and 133 low-hemoglobin patients entered the maintenance phase . Mean maintenance duration was 7.4 months for the high-hemoglobin group and 8.3 months for the low-hemoglobin group . GFR decrease was numerically , but not statistically significantly , lower with the high-hemoglobin group ( 0.058 versus 0.081 mL/min/1.73 m2/mo [ < 0.01 mL/s/1.73 m2/mo ] ) . Physical quality -of-life measures showed trends ( Role-Physical , P = 0.055 ; Physical Function , P = 0.083 ) or statistically significant improvement ( Vitality , P = 0.042 ) with high hemoglobin levels at the end of the stabilization phase . Adverse events were similar between groups . Cardiovascular adverse events occurred in 25 % of the high-hemoglobin and 18 % of the low-hemoglobin patients ( P = 0.137 ) . Neither epoetin dosage nor hemoglobin level was associated with cardiovascular adverse events or death . CONCLUSION These data suggest that normalization of hemoglobin levels in patients with CKD is safe . Longer duration studies are needed to clarify efficacy benefits with high hemoglobin levels BACKGROUND AND OBJECTIVES Quality of life ( QOL ) is markedly impaired in patients with anemia , diabetes mellitus , and chronic kidney disease . Limited data exist regarding the effect of anemia treatment on patient perceptions . The objectives were to determine the longitudinal impact of anemia treatment on quality of life in patients with diabetes and chronic kidney disease and to determine the predictors of baseline and change in QOL . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In a large , double blind study , patients with type 2 diabetes mellitus , nondialysis chronic kidney disease ( estimated GFR , 20 to 60 ml/min per 1.73 m(2 ) ) , and anemia ( hemoglobin 10.4 g/dl ) were r and omized to darbepoetin alfa or placebo . QOL was measured with Functional Assessment of Cancer Therapy-Fatigue , Short Form-36 , and EuroQol scores over 97 weeks . RESULTS Patients r and omized to darbepoetin alfa reported significant improvements compared with placebo patients in Functional Assessment of Cancer Therapy-Fatigue , and EuroQol scores visual analog scores , persisting through 97 weeks . No consistent differences in Short Form-36 were noted . Consistent predictors of worse change scores include lower activity level , older age , pulmonary disease , and duration of diabetes . Interim stroke had a substantial negative impact on fatigue and physical function . CONCLUSION Darbepoetin alfa confers a consistent , but small , improvement in fatigue and overall quality of life but not in other domains . These modest QOL benefits must be considered in the context of neutral overall effect and increased risk of stroke in a small proportion of patients . Patient 's QOL and potential treatment risk should be considered in any treatment decision BACKGROUND Partial correction of renal anaemia with erythropoietin improves quality of life ( QoL ) . We aim ed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe . METHODS 416 Sc and inavian patients with renal anaemia [ pre-dialysis , haemodialysis ( HD ) and peritoneal dialysis patients ] were r and omized to reach a normal haemoglobin of 135 - 160 g/l ( n=216 ) or a subnormal haemoglobin of 90 - 120 g/l ( n=200 ) with or without epoetin alfa . Study duration was 48 - 76 weeks . QoL was measured using Kidney Disease Question naires in 253 Swedish dialysis patients . Safety was examined in all patients . RESULTS QoL improved , measured as a decrease in physical symptoms ( P=0.02 ) , fatigue ( P=0.05 ) , depression ( P=0.01 ) and frustration ( P=0.05 ) in the Swedish dialysis patients when haemoglobin was normalized . In pre-dialysis patients , diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks . However , the progression rate of chronic renal failure was comparable . In the normal haemoglobin group ( N-Hb ) , 51 % had at least one serious adverse event compared with 49 % in the subnormal haemoglobin group ( S-Hb ) ( P=0.32 ) . The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ . The mortality rate was 13.4 % in the N-Hb group and 13.5 % in the S-Hb group ( P=0.98 ) . Mortality decreased with increasing mean haemoglobin in both groups . CONCLUSIONS Normalization of haemoglobin improved QoL in the subgroup of dialysis patients , appears to be safe and can be considered in many patients with end-stage renal disease BACKGROUND In patients with end-stage renal disease , anemia develops as a result of erythropoietin deficiency , and recombinant human erythropoietin ( epoetin ) is prescribed to correct the anemia partially . We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis . METHODS We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis : 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent , and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study . The median duration of treatment was 14 months . The primary end point was the length of time to death or a first nonfatal myocardial infa rct ion . RESULTS After 29 months , there were 183 deaths and 19 first nonfatal myocardial infa rct ions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infa rct ions among those in the low-hematocrit group ( risk ratio for the normal-hematocrit group as compared with the low-hematocrit group , 1.3 ; 95 percent confidence interval , 0.9 to 1.9 ) . Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary , the study was halted . The causes of death in the two groups were similar . The mortality rates decreased with increasing hematocrit values in both groups . The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group . CONCLUSIONS In patients with clinical ly evident congestive heart failure or ischemic heart disease who are receiving hemodialysis , administration of epoetin to raise their hematocrit to 42 percent is not recommended It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular ( LV ) hypertrophy . A r and omized controlled trial was performed with 155 patients with chronic kidney disease ( creatinine clearance , 15 to 50 ml/min ) , with entry hemoglobin concentrations ( [ Hb ] ) of 110 to 120 g/L ( female patients ) or 110 to 130 g/L ( male patients ) . Patients were monitored for 2 yr or until they required dialysis ; the patients were r and omized to receive epoetin alpha as necessary to maintain [ Hb ] between 120 and 130 g/L ( group A ) or between 90 and 100 g/L ( group B ) . [ Hb ] increased for group A ( from 112 + /- 9 to 121 + /- 14 g/L , mean + /- SD ) and decreased for group B ( from 112 + /- 8 to 108 + /- 13 g/L ) ( P < 0.001 , group A versus group B ) . On an intent-to-treat analysis , the changes in LV mass index for the groups during the 2-yr period were not significantly different ( 2.5 + /- 20 g/m(2 ) for group A versus 4.5 + /- 20 g/m(2 ) for group B , P = NS ) . There was no significant difference between the groups in 2-yr mean unadjusted systolic BP ( 141 + /- 14 versus 138 + /- 13 mmHg ) or diastolic BP ( 80 + /- 6 versus 79 + /- 7 mmHg ) . The decline in renal function in 2 yr , as assessed with nuclear estimations of GFR , also did not differ significantly between the groups ( 8 + /- 9 versus 6 + /- 8 ml/min per 1.73 m(2 ) ) . In conclusion , maintenance of [ Hb ] above 120 g/L , compared with 90 to 100 g/L , had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy . The maintenance of [ Hb ] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function Background The prevalence of chronic kidney disease ( CKD ) increases with age , and the risk of significant anaemia increases as renal function declines . The objectives of this study were to assess the effect of darbepoetin alfa administration on health-related quality of life ( HRQOL ) through treatment for anaemia in older patients with CKD . Methods In this multicentre , r and omised , placebo-controlled trial , older patients ( aged ≥70 years ) with CKD ( Stages 3–5 , predialysis ) and haemoglobin ( Hb ) < 11.0 g/dL were r and omised to darbepoetin alfa ( n = 28 ) or placebo ( n = 23 ) . HRQOL was measured using a number of instruments including Short Form-36 ( SF-36 ) and Functional Assessment of Cancer Therapy-Anaemia ( FACT-An ) . Results The primary endpoint , mean SF-36 Vitality Score at Week 24 , was comparable between the darbepoetin alfa ( 51.4 [ 95 % CI 48.0 , 54.9 ] ) and placebo ( 46.7 [ 40.9 , 52.5 ] ) groups . Darbepoetin alfa-treated patients experienced statistically significant improvements in some SF-36 and FACT-An Subscale Scores . Mean Hb was higher with darbepoetin alfa ( 12.5 [ 12.1 , 12.9 ] g/dL ) than with placebo ( 10.5 [ 10.1 , 11.0 ] g/dL ) . The safety profiles were comparable between the treatment groups . The study was limited by only 20 % of the planned patient recruitment being achieved . Conclusions Darbepoetin alfa increased Hb and , within study limitations , suggested that improvements in some HRQOL domains in older CKD patients with anaemia may be achieved with more physiological haemoglobin BACKGROUND Hemoglobin levels below 10 g/dL lead to left ventricular ( LV ) hypertrophy , LV dilation , a lower quality of life , higher cardiac morbidity , and a higher mortality rate in end-stage renal disease . The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown . METHODS One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were r and omly assigned to receive doses of epoetin alpha design ed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks . The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation . RESULTS In patients with concentric LV hypertrophy , the changes in LV mass index were similar in the normal and low target hemoglobin groups . The changes in cavity volume index were similar in both targets in the LV dilation group . Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved ( 8 mL/m2 per 1 g/dL hemoglobin decrement , P = 0.009 ) . Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation . Normalization of hemoglobin led to improvements in fatigue ( P = 0.009 ) , depression ( P = 0.02 ) , and relationships ( P = 0.004 ) . CONCLUSIONS Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation . It may , however , prevent the development of LV dilation , and it leads to improved quality of life It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation . In this r and omized , double-blind study , lower ( 9.5 to 11.5 g/dl ) and higher ( 13.5 to 14.5 g/dl ) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk . Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation . The primary outcome measure was left ventricular volume index ( LVVI ) . The study enrolled 596 patients . Mean age , duration of dialysis therapy , baseline predialysis hemoglobin , and LVVI were 50.8 yr , 0.8 yr , 11.0 g/dl , and 69 ml/m2 , respectively ; 18 % had diabetic nephropathy . Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl , respectively , at 24 wk . Percentage changes in LVVI between baseline and last value were similar ( 7.6 % in the higher and 8.3 % in the lower target group ) as were the changes in left ventricular mass index ( 16.8 versus 14.2 % ) . For the secondary outcomes , the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group ( 1.21 versus -2.31 ; P = 0.036 ) . Overall adverse event rates were similar in both target groups ; higher ( P < 0.05 ) rates of skeletal pain , surgery , and dizziness were seen in the lower target group , and headache and cerebrovascular events were seen in the higher target group . Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure , compared with partial correction Fourteen nondialyzed patients with chronic renal insufficiency ( serum creatinine 265 to 972 mumol/L [ 3.0 to 11.0 mg/dL ] ) and severe anemia ( hematocrit less than 30 % ) were r and omized to receive either recombinant human erythropoietin ( r-HuEPO ) or a placebo subcutaneously thrice weekly for 12 weeks or until reaching a hematocrit of 38 % to 40 % . Anemia was significantly ameliorated in the treated patients . No acceleration in the progression of renal failure ( 1/serum creatinine v time ) or change in serum potassium was noted for either the placebo or treated group over the 12-week period . Six of seven treated patients had a significant decrease in serum ferritin and percent transferrin saturation ( plasma iron/total iron-binding capacity ) . This result ed in functional iron deficiency and the requirement for iron supplementation . The average systolic and diastolic blood pressure did not differ significantly between the two groups of patients during the study . Quality of life was improved in all r-HuEPO-treated patients but not in those in the placebo group . This study demonstrates the safety and efficacy of r-HuEPO in the correction of anemia in predialysis patients without adverse effects on renal function over a 12-week period . Improved patient well-being as a result of the correction of anemia result ed in one patient refusing appropriate initiation of dialysis therapy BACKGROUND Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established . METHODS We r and omly assigned 603 patients with an estimated glomerular filtration rate ( GFR ) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia ( hemoglobin level , 11.0 to 12.5 g per deciliter ) to a target hemoglobin value in the normal range ( 13.0 to 15.0 g per deciliter , group 1 ) or the subnormal range ( 10.5 to 11.5 g per deciliter , group 2 ) . Subcutaneous erythropoietin ( epoetin beta ) was initiated at r and omization ( group 1 ) or only after the hemoglobin level fell below 10.5 g per deciliter ( group 2 ) . The primary end point was a composite of eight cardiovascular events ; secondary end points included left ventricular mass index , quality -of-life scores , and the progression of chronic kidney disease . RESULTS During the 3-year study , complete correction of anemia did not affect the likelihood of a first cardiovascular event ( 58 events in group 1 vs. 47 events in group 2 ; hazard ratio , 0.78 ; 95 % confidence interval , 0.53 to 1.14 ; P=0.20 ) . Left ventricular mass index remained stable in both groups . The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year , respectively ( P=0.40 ) . Dialysis was required in more patients in group 1 than in group 2 ( 127 vs. 111 , P=0.03 ) . General health and physical function improved significantly ( P=0.003 and P<0.001 , respectively , in group 1 , as compared with group 2 ) . There was no significant difference in the combined incidence of adverse events between the two groups , but hypertensive episodes and headaches were more prevalent in group 1 . CONCLUSIONS In patients with chronic kidney disease , early complete correction of anemia does not reduce the risk of cardiovascular events . ( Clinical Trials.gov number , NCT00321919 [ Clinical Trials.gov ] . ) BACKGROUND Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease . Although darbepoetin alfa can effectively increase hemoglobin levels , its effect on clinical outcomes in these patients has not been adequately tested . METHODS In this study involving 4038 patients with diabetes , chronic kidney disease , and anemia , we r and omly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo , with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter . The primary end points were the composite outcomes of death or a cardiovascular event ( nonfatal myocardial infa rct ion , congestive heart failure , stroke , or hospitalization for myocardial ischemia ) and of death or end-stage renal disease . RESULTS Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo ( hazard ratio for darbepoetin alfa vs. placebo , 1.05 ; 95 % confidence interval [ CI ] , 0.94 to 1.17 ; P=0.41 ) . Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo ( hazard ratio , 1.06 ; 95 % CI , 0.95 to 1.19 ; P=0.29 ) . Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo ( hazard ratio , 1.92 ; 95 % CI , 1.38 to 2.68 ; P<0.001 ) . Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo ( P<0.001 ) . There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group . CONCLUSIONS The use of darbepoetin alfa in patients with diabetes , chronic kidney disease , and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes ( either death or a cardiovascular event or death or a renal event ) and was associated with an increased risk of stroke . For many persons involved in clinical decision making , this risk will outweigh the potential benefits . ( Clinical Trials.gov number , NCT00093015 . The health-related quality of life ( HRQOL ) cl aims in the current Epoetin alfa label are based on the reanalyses of the exercise and physical function data from the Canadian Erythropoietin Study Group trial . The re analysis was done to comply with the Food and Drug Administration 's requirement of using statistical methods that are currently st and ard in evaluating clinical trial data . Presented here are HRQOL results associated with anemia . The Canadian Erythropoietin Study Group trial was a multicenter , double blind , r and omized , placebo-controlled trial evaluating the effects of Epoetin alfa on HRQOL in anemic hemodialysis patients . A total of 118 patients who were 18 - 75 years old , on hemodialysis for > 3 months , who had a hemoglobin < 9.0 g/dL , and did not have coronary artery disease or diabetes mellitus , were r and omized to either receive placebo ( n=40 ) , or receive intravenous Epoetin alfa to achieve a target hemoglobin of 9.5 - 11.0 g/dL ( n=40 ) or a target of 11.5 - 13.0 g/dL ( n=38 ) . Patients were followed for 6 months . The two Epoetin alfa-treatment groups were combined for all analyses performed . This post hoc analysis was conducted using an intent-to-treat repeated measures mixed model analysis of variance using Bonferroni 's multiplicity correction . The Epoetin alfa-treated group showed a statistically significant improvement in the Kidney Disease Question naire symptom of fatigue in comparison with placebo . Additionally , the change in hemoglobin at 2 months was correlated with change in fatigue , energy , shortness of breath , and weakness , but had minimal effect on depression . These analyses confirm previously reported results , which indicate that treating hemodialysis patients with an erythropoiesis-stimulating agent improves HRQOL |
1,740 | 29,948,453 | Based on the RCTs available , LLLT is better to be used at initial phase of RME , because it has some benefits in increasing the rate of bone remodeling | Rapid maxillary expansion ( RME ) is one of the common treatments of transverse maxillary deficiency , and low-level laser therapy ( LLLT ) is one of the recommended solutions to enhance biological wound or bone healing .
This review article aims to answer the following question : “ What are the effects of LLLT , on patients who underwent surgical or non-surgical RME , in improving clinical success , wound healing , and bone regeneration ? ” | The aim of this study was to evaluate the behavior of the transverse dimension of the maxilla after surgically assisted rapid expansion with and without using a transpalatal arch fixed retention . Sixty cast models of the maxilla and 60 posteroanterior radiographs from 30 adult subjects , 16 male subjects and 14 female subjects , were evaluated . The subjects were 18.1 to 53.2 years old ( mean age , 27.3 years ) , had been su bmi tted to surgically assisted rapid maxillary expansion , and were using the expansion appliance for four months . The subjects were r and omly assigned into two groups of 15 subjects . One group , called the group with retention , received a transpalatal arch fixed retention and another group , which received no retention , was called the group without retention . The assessment s were performed at two time points : at the removal of the expansion appliance ( T1 ) and 6 months after the removal of the expansion appliance ( T2 ) . In the cast models , interpremolar distances ( A-A1 ) and intermolar distances ( B-B1 ) were measured and in the posteroanterior radiographs , maxillom and ibular discrepancy was used . A reduction in the distances A-A1 ( −0.76 mm ) and B-B1 ( −1.54 mm ) was observed among the time points studied in the group without retention and this difference was statistically significant . In the group with retention , the difference between the time points T1 and T2 was not statistically significant . The assessment of the maxillom and ibular difference showed an increase between the time points T1 and T2 in the group with retention ( 1.54 mm ) and the group without retention ( 0.84 mm ) , which means a reduction in the maxillary width in the posteroanterior radiograph . In the comparison between the groups , the assessment of the cast models and the assessment of the posteroanterior radiograph showed no statistically significant difference in any of the variables studied OBJECTIVE : To investigate , by digital radiology , the bone regeneration process in rats su bmi tted to femoral osteotomy and treated with low power laser therapy . METHODS : Forty-five Wistar rats were subjected to transverse osteotomy of the right femur and divided r and omly into three experimental groups ( n = 15 ) : animals not treated with laser therapy G ( C ) , animals that received laser therapy with λ : 660 nm G ( 660 nm ) and animals that received laser therapy with λ : 830 nm G ( 830 nm ) . Animals were sacrificed after 7 , 14 and 21 days . The bone calluses were evaluated by digital X-ray at 65 kVp , 7mA and 0.032 s exposures . RESULTS : The values obtained were su bmi tted to variance analysis ( ANOVA ) followed by the Tukey-Kramer test . The significance level adopted was 5 % . The groups G ( C ) , G ( 660 nm ) , and G ( 830 nm ) at the 7th day showed a significant bone development , with p < 0.0116 ; the groups G ( C ) , G ( 660 nm ) , and G ( 830 nm ) at the 14th day showed values of p < 0.0001 ; at the 21st day , a higher degree of bone repair were observed in group G ( 830 nm ) , and G ( 660 nm ) , with p < 0.0169 . CONCLUSION : Based on the radiographic findings , G ( 830 nm ) showed more complete bone regeneration , as shown in the gray shades of the images . Level of Evidence II , Individual Study With Experimental Design This study evaluated the effect of low-level laser therapy ( LLLT ) on bone regeneration at the midpalatal suture ( MPS ) after rapid maxillary expansion ( RME ) , using cone beam computed tomography . Fourteen 8–14-year-old patients with transverse maxillary deficiency underwent RME with a Hyrax-type exp and er activated with one full turn after installation and two half turn daily activations until achieving overcorrection . Patients were r and omly assigned to either a control group ( RME alone , n = 4 ) or an experimental group ( n = 10 ) in which RME was followed by 12 LLLT sessions ( GaAlAs , p = 70 mW , λ = 780 nm , Ø = 0.04 cm2 ) . Two tomographic images of the MPS were obtained — T0 , after disjunction and T1 , after 4 months . Bone regeneration was evaluated by measuring the optical density ( OD ) on the tomographic images using InVivo Dental 5.0 software . Data were analyzed by the paired Student ’s t test ( α = 0.05 % ) . A statistically significant difference between T0 and T1 OD values was observed in the laser-treated group ( p = 0.00 ) , but this difference was not significant in the control group ( p = 0.20 ) . Intergroup comparison of OD values at T1 revealed higher OD in the laser-treated group ( p = 0.05 ) . In conclusion , LLLT had a positive influence on bone regeneration of the midpalatal suture by accelerating the repair process To evaluate the effectiveness low-level laser therapy ( LLLT ) on the repair of the mid palatal suture , after rapid maxillary expansion ( RME ) . A single-operator , r and omized single-blind placebo-controlled study was performed at the Orthodontic Department at the Dental Hospital of Bellvitge . Barcelona University , Hospitalet de Llobregat , Spain . Thirty-nine children ( range 6–12 years old ) , completed RME and were r and omized to receive active LLLT ( n = 20 ) or placebo ( n = 19 ) . The laser parameters and dose were 660 nm , 100 mW , CW , InGaAlP laser , illuminated area 0.26 cm2 , 332 mW/cm2 , 60 s to four points along midpalatal suture , and 30 s to a point each side of the suture . A total of seven applications were made on days 1 , 7 , 14 , 28 , 42 , 56 , and 70 of the retention phase RME . A cone beam computed tomography ( CBCT ) scan was carried out on the day of the first laser treatment , and at day 75 , a second CBCT scan was performed . Two radiologists synchronized the slices of two scans to be assessed . P = 0.05 was considered to be statistically significant . At day 75 of the suture , the irradiated patients presented a greater percentage of approximate zones in the anterior ( p = 0.008 ) and posterior ( p = 0.001 ) superior suture— and less approximation in the posterior superior suture ( p = 0.040)—than the placebo group . LLLT appears to stimulate the repair process during retention phase after RME OBJECTIVE The aim of this study was to evaluate the effects of laser therapy on bone regeneration in the midpalatal anterior suture ( MPAS ) after surgically assisted rapid maxillary expansion ( SARME ) . METHODS Thirteen patients aged between 18 and 33 years old with maxillary transverse deficiency ( > or = 7.0 mm ) were evaluated . All patients underwent subtotal Le Fort I osteotomy with separation of the pterygomaxillary suture with the use of Hyrax exp and er , and were divided into 2 groups : control group ( n = 6 ) and laser group ( n = 7 ) . A GaAlAs laser ( P = 100 mW , lambda = 830 nm , Ø = 0.06 cm(2 ) ) was used . The laser was applied in 8 treatment sessions with intervals of 48 hours . Each treatment session consisted of laser applications , per point ( E = 8.4J , ED = 140J/cm(2 ) ) , at 3 points on the MPAS , and total dose of E = 25.2 J , ED = 420 J/cm(2 ) . Digital radiographs were taken before the surgical procedure and at 1- , 2- , 3- , 4- , and 7-month follow-up visits . Optical density analysis of the regenerated bone was performed using Adobe Photoshop 8.0 software . RESULTS Bone regeneration associated with the use of laser after SARME showed a statistically significant difference . A higher mineralization rate was found in the laser group ( 26.3 % , P < .001 ) than the control group . CONCLUSION Low-level laser irradiation ( GaAlAs ) accelerates bone regeneration in MPAS after SARME . However , the optical density measurements after 7 months of follow-up were lower in comparison with the preoperative measurements ABSTRACT Objective : To assess the volumetric changes that occur in the nasomaxillary complex of mouth-breathing patients with transverse maxillary deficiency subjected to rapid maxillary expansion ( RME ) . Methods : This was a controlled , prospect i ve intervention study involving 38 mouth-breathing patients presenting with transverse maxillary deficiency , regardless of malocclusion type or race . Twenty-three of them comprised the experimental group , which was composed of 11 ( 47.8 % ) boys , and 12 ( 52.2 % ) girls , with a mean age of 9.6 years , ranging from 6.4 to 14.2 years and st and ard deviation of 2.3 years ; and 15 of them comprised the control group , composed of 9 ( 60 % ) boys and 6 ( 40 % ) girls with an mean age of 10.5 years , ranging from 8.0 to 13.6 years , and st and ard deviation of 1.9 years . All patients were scanned ( CT ) according to a st and ard protocol : Initial CT ( T1 ) , and CT three months thereafter ( T2 ) , and the patients in the experimental group were treated with RME using a Hyrax exp and er for the correction of maxillary deficiency during the T1-T2 interval . The CT scans were manipulated using Dolphin ® Imaging version 11.7 software for total and partial volumetric assessment of the nasomaxillary complex . Results : The results revealed that in the experimental group there was a significant increase in the size of the structures of interest compared to the control group , both in general aspect and in specific regions . Conclusions : Rapid maxillary expansion ( RME ) provided a significant expansion in all the structures of the nasomaxillary complex ( nasal cavity , oropharynx , right and left maxillary sinuses ) This study evaluated rapid maxillary expansion ( RME ) dentoskeletal effects by means of computed tomography ( CT ) , comparing tooth tissue-borne and tooth-borne exp and ers . The sample comprised eight girls aged 11 to 14 years presenting Class I or II malocclusions with posterior unilateral or bilateral crossbite that were r and omly divided into two treatment groups , palatal acrylic ( Haas-type ) and hygienic ( Hyrax ) exp and ers . All appliances were activated up to the full seven mm capacity of the expansion screw . The patients were subjected to a spiral CT scan before expansion and after a three-month retention period when the exp and er was removed . One-millimeter-thick axial sections were scanned parallel to the palatal plane , comprising the dentoalveolar area and the base of the maxilla up to the inferior third of the nasal cavity . Multiplanar reconstruction was used to measure maxillary transverse dimensions and posterior teeth inclination by means of a computerized method . The results showed that RME produced a significant increase in all measured transverse linear dimensions , decreasing in magnitude from dental arch to basal bone . The transverse increase at the level of the nasal floor corresponded to one-third of the amount of screw activation . Tooth-borne ( Hyrax ) and tooth tissue-borne ( Haas-type ) exp and ers tended to produce similar orthopedic effects . In both methods , RME led to buccal movement of the maxillary posterior teeth , by tipping and bodily translation . The second premolars displayed more buccal tipping than the appliance-supporting teeth . The tooth tissue-borne exp and er produced a greater change in the axial inclination of appliance-supporting teeth , especially first premolars , compared with the tooth-borne exp and er Immediate dental implant placement in the molar region is critical , because of the high amount of bone loss and the discrepancy between alveolar crest thickness and the implant platform . Laser phototherapy ( LPT ) improves bone repair . The aim of this study was to evaluate the human alveolar bone repair 40 days after molar extraction in patients su bmi tted to LPT . Twenty patients were selected for this r and omized controlled clinical trial ; 10 underwent LPT ( laser group ) with a GaAlAs diode laser ( 808 nm , 100 mW , 0.04 cm(2 ) , 75 J/cm(2 ) , 30s per point , 3 J per point , at five points ) . The control group patients ( n=10 ) were not irradiated . Forty days later , the tissue formed inside the sockets was analyzed by micro-computed tomography and histomorphometry . Data from the two groups were compared with Student 's t-test and Pearson 's correlation test . The relative bone volume was significantly higher in the laser group ( P<0.0001 ) . The control group showed negative correlations ( P<0.01 ) between number and thickness , and between number and separation of trabeculae , and a positive correlation between thickness and separation of trabeculae . The laser group showed a significant negative correlation between the number and thickness of trabeculae ( P<0.01 ) . The results suggest that LPT is able to accelerate alveolar bone repair after molar extraction , leading to a more homogeneous trabecular configuration represented by thin and close trabeculae |
1,741 | 30,186,838 | Conclusion : AVC and myocardial fibrosis imaging biomarkers predict the outcomes in AS , and help underst and ing AS pathophysiology and setting therapeutic targets | Background : Detecting among patients with aortic stenosis ( AS ) those who are likely to rapidly progress , yet potentially benefiting from prophylactic aortic valve replacement , is needed for improved patient care .
The objective of this study was to evaluate the role of imaging biomarkers in predicting the progression to clinical symptoms and death in patients with AS . | Background — Diffuse myocardial fibrosis is a final end point in most cardiac diseases . It is missed by the cardiovascular magnetic resonance ( CMR ) late gadolinium enhancement technique . Currently , quantifying diffuse myocardial fibrosis requires invasive biopsy , with inherent risk and sampling error . We have developed a robust and noninvasive technique , equilibrium contrast CMR ( EQ – CMR ) to quantify diffuse fibrosis and have vali date d it against the current gold st and ard of surgical myocardial biopsy . Methods and Results — The 3 principles of EQ – CMR are a bolus of extracellular gadolinium contrast followed by continuous infusion to achieve equilibrium ; a blood sample to measure blood volume of distribution ( 1−hematocrit ) ; and CMR to measure pre- and postequilibrium T1 ( with heart rate correction ) . The myocardial volume of distribution is calculated , reflecting diffuse myocardial fibrosis . Clinical validation occurred in patients undergoing aortic valve replacement for aortic stenosis or myectomy in hypertrophic cardiomyopathy ( n=18 and n=8 , respectively ) . Surgical biopsies were analyzed for picrosirius red fibrosis quantification on histology . The mean histological fibrosis was 20.5±11 % in aortic stenosis and 17.1±7.4 % in hypertrophic cardiomyopathy . EQ – CMR correlated strongly with biopsy histological fibrosis : aortic stenosis , r2=0.86 , Kendall Tau coefficient (T)=0.71 , P<0.001 ; hypertrophic cardiomyopathy , r2=0.62 , T=0.52 , P=0.08 ; combined r2=0.80 , T=0.67 , P<0.001 . Conclusions — We have developed and vali date d a new technique , EQ – CMR , to measure diffuse myocardial fibrosis as an add-on to a st and ard CMR scan , which allows for the noninvasive quantification of the diffuse fibrosis burden in myocardial diseases Background — The pathophysiology of aortic stenosis is incompletely understood , and the relative contributions of valvular calcification and inflammation to disease progression are unknown . Methods and Results — Patients with aortic sclerosis and mild , moderate , and severe stenosis were compared prospect ively with age- and sex-matched control subjects . Aortic valve severity was determined by echocardiography . Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride ( 18F-NaF ) and 18F-fluorodeoxyglucose ( 18F-FDG ) uptake with the use of positron emission tomography . One hundred twenty-one subjects ( 20 controls ; 20 aortic sclerosis ; 25 mild , 33 moderate , and 23 severe aortic stenosis ) were administered both 18F-NaF and 18F-FDG . Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 ( 18F-NaF ) and ±0.13 ( 18F-FDG ) for maximum tissue-to- background ratios . Activity of both tracers was higher in patients with aortic stenosis than in control subjects ( 18F-NaF : 2.87±0.82 versus 1.55±0.17 ; 18F-FDG : 1.58±0.21 versus 1.30±0.13 ; both P<0.001 ) . 18F-NaF uptake displayed a progressive rise with valve severity ( r2=0.540 , P<0.001 ) , with a more modest increase observed for 18F-FDG ( r2=0.218 , P<0.001 ) . Among patients with aortic stenosis , 91 % had increased 18F-NaF uptake ( > 1.97 ) , and 35 % had increased 18F-FDG uptake ( > 1.63 ) . A weak correlation between the activities of these tracers was observed ( r2=0.174 , P<0.001 ) . Conclusions — Positron emission tomography is a novel , feasible , and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis . The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF. Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT01358513 Background —Aortic valve calcification ( AVC ) is the intrinsic mechanism of valvular obstruction leading to aortic stenosis ( AS ) and is measurable by multidetector computed tomography . The link between sex and AS is controversial and that with AVC is unknown . Methods and Results —We prospect ively performed multidetector computed tomography in 665 patients with AS ( aortic valve area , 1.05±0.35 cm2 ; mean gradient , 39±19 mm Hg ) to measure AVC and to assess the impact of sex on the AVC – AS severity link in men and women . AS severity was comparable between women and men ( peak aortic jet velocity : 4.05±0.99 versus 3.93±0.91 m/s , P=0.11 ; aortic valve area index : 0.55±0.20 versus 0.56±0.18 cm2/m2 ; P=0.46 ) . Conversely , AVC load was lower in women versus men ( 1703±1321 versus 2694±1628 arbitrary units ; P<0.0001 ) even after adjustment for their smaller body surface area or aortic annular area ( both P<0.0001 ) . Thus , odds of high-AVC load were much greater in men than in women ( odds ratio , 5.07 ; P<0.0001 ) . Although AVC showed good associations with hemodynamic AS severity in men and women ( all r>0.67 ; P<0.0001 ) , for any level of AS severity measured by peak aortic jet velocity or aortic valve area index , AVC load , absolute or indexed , was higher in men versus women ( all P⩽0.01 ) . Conclusions —In this large AS population , women incurred similar AS severity than men for lower AVC loads , even after indexing for their smaller body size . Hence , the relationship between valvular calcification process and AS severity differs in women and men , warranting further pathophysiological inquiry . For AS severity diagnostic purpose s , interpretation of AVC load should be different in men and in women 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 Background Aortic valve stenosis ( AS ) is a progressive disease , but the impact of baseline AS haemodynamic or anatomic severity on AS progression remains unclear . Methods In 149 patients ( 104 mild AS , 36 moderate AS and 9 severe AS ) enrolled in 2 ongoing prospect i ve cohorts ( COFRASA/GENERAC ) , we evaluated AS haemodynamic severity at baseline and yearly , thereafter , using echocardiography ( mean pressure gradient ( MPG ) ) and AS anatomic severity using CT ( degree of aortic valve calcification ( AVC ) ) . Results After a mean follow-up of 2.9±1.0 years , mean MGP increased from 22±11 to 30±16 mm Hg ( + 3±3 mm Hg/year ) , and mean AVC from 1108±891 to 1640±1251 AU ( arbitrary units ) ( + 188±176 AU/year ) . Progression of AS was strongly related to baseline haemodynamic severity ( + 2±3 mm Hg/year in mild AS , + 4±3 mm Hg/year in moderate AS and + 5±5 mm Hg/year in severe AS ( p=0.01 ) ) , and baseline haemodynamic severity was an independent predictor of haemodynamic progression ( p=0.0003 ) . Annualised haemodynamic and anatomic progression rates were significantly correlated ( r=0.55 , p<0.0001 ) , but AVC progression rate was also significantly associated with baseline haemodynamic severity ( + 141±133 AU/year in mild AS , + 279±189 AU/year in moderate AS and + 361±293 AU/year in severe AS , p<0.0001 ) , and both baseline MPG and baseline AVC were independent determinants of AVC progression ( p<0.0001 ) . Conclusions AS progressed faster with increasing haemodynamic or anatomic severity . Our results suggest that a medical strategy aim ed at preventing AVC progression may be useful in all subsets of patients with AS including those with severe AS and support the recommended closer follow-up of patients with AS as AS severity increases . Clinical trial registration COFRASA ( clinical Trial.gov number NCT 00338676 ) and GENERAC ( clinical Trial.gov number NCT00647088 ) Background — In this prospect i ve follow-up study , the effect of myocardial fibrosis on myocardial performance in symptomatic severe aortic stenosis was investigated , and the impact of fibrosis on clinical outcome after aortic valve replacement ( AVR ) was estimated . Methods and Results — Fifty-eight consecutive patients with isolated symptomatic severe aortic stenosis underwent extensive baseline characterization before AVR . St and ard and tissue Doppler echocardiography and cardiac magnetic resonance imaging ( late-enhancement imaging for replacement fibrosis ) were performed at baseline and 9 months after AVR . Endomyocardial biopsies were obtained intraoperatively to determine the degree of myocardial fibrosis . Patients were analyzed according to the severity of interstitial fibrosis in cardiac biopsies ( severe , n=21 ; mild , n=15 ; none , n=22 ) . The extent of histologically determined cardiac fibrosis at baseline correlated closely with New York Heart Association functional class and markers of longitudinal systolic function ( all P<0.001 ) but not global ejection fraction or aortic valve area . Nine months after AVR , the degree of late enhancement remained unchanged , implying that AVR failed to reduce the degree of replacement fibrosis . Patients with no fibrosis experienced a marked improvement in New York Heart Association class from 2.8±0.4 to 1.4±0.5 ( P<0.001 ) . Only parameters of longitudinal systolic function predicted this functional improvement . Four patients with severe fibrosis died during follow-up , but no patient from the other groups died . Conclusions — Myocardial fibrosis is an important morphological substrate of postoperative clinical outcome in patients with severe aortic stenosis and was not reversible after AVR over the 9 months of follow-up examined in this study . Because markers of longitudinal systolic function appear to indicate sensitively both the severity of myocardial fibrosis and the clinical outcome , they may prove valuable for preoperative risk assessment in patients with aortic stenosis Objectives Cardiac magnetic resonance ( CMR ) was used to investigate the extracellular compartment and myocardial fibrosis in patients with aortic stenosis , as well as their association with other measures of left ventricular decompensation and mortality . Background Progressive myocardial fibrosis drives the transition from hypertrophy to heart failure in aortic stenosis . Diffuse fibrosis is associated with extracellular volume expansion that is detectable by T1 mapping , whereas late gadolinium enhancement ( LGE ) detects replacement fibrosis . Methods In a prospect i ve observational cohort study , 203 subjects ( 166 with aortic stenosis [ 69 years ; 69 % male ] ; 37 healthy volunteers [ 68 years ; 65 % male ] ) underwent comprehensive phenotypic characterization with clinical imaging and biomarker evaluation . On CMR , we quantified the total extracellular volume of the myocardium indexed to body surface area ( iECV ) . The iECV upper limit of normal from the control group ( 22.5 ml/m2 ) was used to define extracellular compartment expansion . Areas of replacement mid-wall LGE were also identified . All-cause mortality was determined during 2.9 ± 0.8 years of follow up . Results iECV demonstrated a good correlation with diffuse histological fibrosis on myocardial biopsies ( r = 0.87 ; p < 0.001 ; n = 11 ) and was increased in patients with aortic stenosis ( 23.6 ± 7.2 ml/m2 vs. 16.1 ± 3.2 ml/m2 in control subjects ; p < 0.001 ) . iECV was used together with LGE to categorize patients with normal myocardium ( iECV < 22.5 ml/m2 ; 51 % of patients ) , extracellular expansion ( iECV ≥22.5 ml/m2 ; 22 % ) , and replacement fibrosis ( presence of mid-wall LGE , 27 % ) . There was evidence of increasing hypertrophy , myocardial injury , diastolic dysfunction , and longitudinal systolic dysfunction consistent with progressive left ventricular decompensation ( all p < 0.05 ) across these groups . Moreover , this categorization was of prognostic value with stepwise increases in unadjusted all-cause mortality ( 8 deaths/1,000 patient-years vs. 36 deaths/1,000 patient-years vs. 71 deaths/1,000 patient-years , respectively ; p = 0.009 ) . Conclusions CMR detects ventricular decompensation in aortic stenosis through the identification of myocardial extracellular expansion and replacement fibrosis . This holds major promise in tracking myocardial health in valve disease and for optimizing the timing of valve replacement . ( The Role of Myocardial Fibrosis in Patients With Aortic Stenosis ; NCT01755936 Introduction The impact of coronary artery disease ( CAD ) on outcomes after transcatheter aortic valve implantation ( TAVI ) has not been clarified . Furthermore , less is known about the indication and strategy of revascularization in these high risk patients . Aims This study sought to determine the prevalence and prognostic impact of CAD in patients undergoing TAVI , and to assess the safety and feasibility of percutaneous coronary intervention ( PCI ) before TAVI . Methods Patients with severe aortic stenosis ( AS ) undergoing TAVI were included into a prospect i ve single center registry from 2007 to 2012 . Clinical outcomes were compared between patients with and without CAD . In some patients with CAD , it was decided to perform elective PCI before TAVI after decision by the Heart team . The primary endpoints were 30-day and 2-year all-cause mortality . Results A total of 91 consecutive patients with mean age of 79 ± 9 years ( 52 % men ) underwent TAVI with a median follow-up duration of 16 months ( interquartile range of 27.6 months ) . CAD was present on 46 patients ( 51 % ) . At 30-day , the incidences of death were similar between CAD and non-CAD patients ( 9 and 5 % , p = 0.44 ) , but at 2 years were 50 % in CAD patients and 24 % in non-CAD patients [ crude hazard ratio with CAD , 2.2 ; 95 % confidence interval ( CI ) , 1.1–4.6 ; p = 0.04 ] . Adjusting for age , gender , left ventricular ejection fraction , and glomerular filtration rate , the hazard of death was 2.6-fold higher in patients with CAD ( 95 % CI , 1.1–6.0 ; p = 0.03 ) . Elective PCI before TAVI was performed in 13 patients ( 28 % of CAD patients ) . There were no more adverse events in patients who underwent TAVI + PCI when compared with those who underwent isolated TAVI . Conclusion In severe symptomatic AS who underwent TAVI , CAD is frequent and adversely impacts long-term outcomes , but not procedure outcomes . In selected patients , PCI before TAVI appears to be feasible and safe BACKGROUND Valvular heart diseases are not usually regarded as a major public-health problem . Our aim was to assess their prevalence and effect on overall survival in the general population . METHODS We pooled population -based studies to obtain data for 11 911 r and omly selected adults from the general population who had been assessed prospect ively with echocardiography . We also analysed data from a community study of 16 501 adults who had been assessed by clinical ly indicated echocardiography . FINDINGS In the general population group , moderate or severe valve disease was identified in 615 adults . There was no difference in the frequency of such diseases between men and women ( p=0.90 ) . Prevalence increased with age , from 0.7 % ( 95 % CI 0.5 - 1.0 ) in 18 - 44 year olds to 13.3 % ( 11.7 - 15.0 ) in the 75 years and older group ( p<0.0001 ) . The national prevalence of valve disease , corrected for age and sex distribution from the US 2000 population , is 2.5 % ( 2.2 - 2.7 ) . In the community group , valve disease was diagnosed in 1505 ( 1.8 % adjusted ) adults and frequency increased considerably with age , from 0.3 % ( 0.2 - 0.3 ) of the 18 - 44 year olds to 11.7 % ( 11.0 - 12.5 ) of those aged 75 years and older , but was diagnosed less often in women than in men ( odds ratio 0.90 , 0.81 - 1.01 ; p=0.07 ) . The adjusted mortality risk ratio associated with valve disease was 1.36 ( 1.15 - 1.62 ; p=0.0005 ) in the population and 1.75 ( 1.61 - 1.90 ; p<0.0001 ) in the community . INTERPRETATION Moderate or severe valvular diseases are notably common in this population and increase with age . In the community , women are less often diagnosed than are men , which could indicate an important imbalance in view of the associated lower survival . Valve diseases thus represent an important public-health problem Background Measurement of the degree of aortic valve calcification ( AVC ) using electron beam computed tomography ( EBCT ) is an accurate and complementary method to transthoracic echocardiography ( TTE ) for assessment of the severity of aortic stenosis ( AS ) . Whether threshold values of AVC obtained with EBCT could be extrapolated to multislice computed tomography ( MSCT ) was unclear and AVC diagnostic value in patients with low ejection fraction ( EF ) has never been specifically evaluated . Methods Patients with mild to severe AS underwent prospect ively within 1 week MSCT and TTE . Severe AS was defined as an aortic valve area ( AVA ) of less than 1 cm2 . In 179 patients with EF greater than 40 % ( validation set ) , the relationship between AVC and AVA was evaluated . The best threshold of AVC for the diagnosis of severe AS was then evaluated in a second subset ( testing set ) of 49 patients with low EF ( ≤40 % ) . In this subgroup , AS severity was defined based on mean gradient , natural history or dobutamine stress echocardiography . Results Correlation between AVC and AVA was good ( r=−0.63 , p<0.0001 ) . A threshold of 1651 arbitrary units ( AU ) provided 82 % sensitivity , 80 % specificity , 88 % negative-predictive value and 70 % positive-predictive value . In the testing set ( patients with low EF ) , this threshold correctly differentiated patients with severe AS from non-severe AS in all but three cases . These three patients had an AVC score close to the threshold ( 1206 , 1436 and 1797 AU ) . Conclusions In this large series of patients with a wide range of AS , AVC was shown to be well correlated to AVA and may be a useful adjunct for the evaluation of AS severity especially in difficult cases such as patients with low EF BACKGROUND AND AIM OF THE STUDY Aortic valve calcification may be an independent risk factor for adverse clinical outcome . The study aim was to assess the predictive value of possible risk factors , including the severity of aortic valve calcification as quantified with 16-multislice computed tomography ( MSCT ) for adverse short-term clinical outcome in patients with asymptomatic , degenerative aortic stenosis ( AS ) . METHODS Possible risk factors for adverse short-term clinical outcome were prospect ively tested in 34 consecutive patients with asymptomatic AS as follows : ( i ) aortic valve calcium ( AVC ) score as quantified with MSCT ; ( ii ) echocardiographic parameters -- aortic valve area ( AVA ) calculated with continuity equation , mean and maximal transvalvular pressure gradients , end-diastolic septal wall diameter ; and ( iii ) laboratory tests ( brain natriuretic peptide ( BNP ) , C-reactive protein ( CRP ) ) . RESULTS Within 18 - 24 months of follow up , 11 of 34 patients developed a major adverse clinical outcome . Ten patients suffered from onset of symptoms accompanied by hemodynamic progression , and one patient died from sudden cardiac death . Six of these 10 patients underwent aortic valve replacement , one patient declined surgery , and three patients were not accepted for surgery ( one of these died suddenly shortly afterwards ) . The aortic valve calcium score was the strongest predictor of a major adverse clinical event ( p < 0.001 ) among all parameters assessed ( 1,928 + /- 789 versus 5,111 + /- 2,409 Agatston units ) . The plasma level of BNP ( p = 0.003 ) , mean transvalvular pressure gradient ( p = 0.002 ) and AVA ( p = 0.003 ) were also risk factors for adverse clinical outcome . CONCLUSION The AVC score as quantified with MSCT predicted adverse short-term clinical outcome in patients with asymptomatic AS . In patients with severe aortic valve calcification , close follow up examinations are m and atory , and early elective surgery may be considered even in the absence of symptoms . MSCT provides a comprehensive non-invasive imaging approach for risk stratification in patients with asymptomatic AS OBJECTIVES The aim of this study was to evaluate whether native T1 value of the myocardium on cardiac magnetic resonance ( CMR ) could predict clinical events in patients with significant aortic stenosis ( AS ) . BACKGROUND Although previous studies have demonstrated the prognostic value of focal fibrosis using late gadolinium enhancement ( LGE ) by CMR in AS patients , the prognostic implication of diffuse myocardial fibrosis by noninvasive imaging remains unknown . METHODS A prospect i ve observational longitudinal study was performed in 127 consecutive patients with moderate or severe AS ( 68.8 ± 9.2 years of age , 49.6 % male ) and 33 age- and sex-matched controls who underwent 3-T CMR . The degree of diffuse myocardial fibrosis was assessed by noncontrast mapping of T1 relaxation time using modified Look-Locker inversion-recovery sequence , and the presence and extent of LGE were also evaluated . The AS patients were divided into 3 groups by the native T1 value . Primary endpoint was a composite of all-cause death and hospitalization for heart failure . RESULTS Native T1 value was higher in AS patients , compared with control subjects ( 1,232 ± 53 ms vs. 1,185 ± 37 ms ; p = 0.008 ) . During follow-up ( median 27.9 months ) , there were 24 clinical events including 9 deaths ( 6 pre-operative and 3 post-operative ) , the majority of which occurred in the patients in the highest T1 tertile group ( 2.4 % vs. 11.6 % vs. 42.9 % for lowest , mid- , and highest tertile groups ; p < 0.001 by log-rank test ) . The total number of events for both pre- and post-operative events also occurred more frequently in patients in the highest T1 tertile group . EuroSCORE II , the presence and /or extent of LGE , and the native T1 value were predictors of poor prognosis ( adjusted hazard ratio for every 20-ms increase of native T1 : 1.28 ; p = 0.003 ) . In particular , the highest native T1 value provided further risk stratification regardless of the presence of LGE . CONCLUSIONS High native T1 value on noncontrast T1 mapping CMR is a novel , independent predictor of adverse outcome in patients with significant AS BACKGROUND Cardiac computed tomography angiography ( CCTA ) provides the simultaneous evaluation of the aortic valve , myocardium , and coronary arteries . In particular , aortic valve calcium score ( AVCS ) can be accurately measured on the same scanning sequence used to measure coronary artery calcification , with no additional cost or radiation exposure . We sought to evaluate the prognostic value of CCTA measures , including AVCS , in asymptomatic aortic stenosis ( AS ) . METHODS AND RESULTS Sixty-four initially asymptomatic patients with AS with a normal ejection fraction were prospect ively enrolled and followed for median 29 ( IQR=18 - 50 ) months . During follow-up , 27 ( 42 % ) patients experienced cardiac events , including five cardiac deaths , eleven aortic valve replacements . Multivariate Cox proportional hazards analysis identified three CCTA measures as significant predictors of cardiac events : aortic valve area ( per 0.1cm(2 ) decrease ; hazard ratio [ HR ] : 1.19 , 95 % confidence interval [ CI ] : 1.05 - 1.34 ) ; multi-vessel obstructive coronary artery disease ( HR : 2.84 , 95 % CI : 1.10 - 7.32 ) ; and AVCS ( per 100 ; HR : 1.09 , 95 % CI : 1.04 - 1.15 ) . Kaplan-Meier analysis showed that patients with AVCS greater than or equal to the median value of 723 had significantly worse outcomes than those with AVCS less than 723 ( p<0.0001 ) . The C-statistic value for cardiac events substantially increased when these CCTA measures were added to clinical characteristics plus echocardiographic peak transaortic velocity ( 0.913 vs. 0.702 , p<0.001 ) . CONCLUSIONS In patients with asymptomatic AS , CCTA measures of valve area , coronary stenosis , and calcification severity provide independent and incremental prognostic value after accounting for the echocardiographic severity of stenosis BACKGROUND Prior studies have shown that late gadolinium enhancement ( LGE ) by cardiac magnetic resonance ( CMR ) can detect focal fibrosis in aortic stenosis ( AS ) , suggesting that it might predict higher mortality risk . OBJECTIVES This study was conducted to evaluate whether LGE-CMR can predict post-operative survival in patients with severe AS undergoing aortic valve replacement ( AVR ) . METHODS We prospect ively evaluated survival ( all-cause and cardiovascular disease related ) according to LGE-CMR status in 154 consecutive AS patients ( 96 men ; mean age : 74 ± 6 years ) without a history of myocardial infa rct ion undergoing surgical AVR and in 40 AS patients undergoing transcatheter aortic valve replacement ( TAVR ) . RESULTS LGE was present in 29 % of patients undergoing surgical AVR and in 50 % undergoing TAVR . During a median follow-up of 2.9 years , 21 patients undergoing surgical AVR and 20 undergoing TAVR died . In surgical AVR , the presence of LGE predicted higher post-operative mortality ( odds ratio : 10.9 ; 95 % confidence interval [ CI ] : 1.2 to 100.0 ; p = 0.02 ) and worse all-cause survival ( 73 % vs. 88 % ; p = 0.02 by log-rank test ) and cardiovascular disease related survival ( 85 % vs. 95 % ; p = 0.03 by log-rank test ) on 5-year Kaplan-Meier estimates of survival after surgical AVR . Multivariate Cox analysis identified the presence of LGE ( hazard ratio : 2.8 ; 95 % CI : 1.3 to 6.9 ; p = 0.025 ) and New York Heart Association functional class III/IV ( hazard ratio : 3.2 ; 95 % CI : 1.1 to 8.1 ; p < 0.01 ) as the sole independent predictors of all-cause mortality after surgical AVR . The presence of LGE also predicted higher all-cause mortality ( p = 0.05 ) and cardiovascular disease related mortality ( p = 0.03 ) in the subgroup of patients without angiographic coronary artery disease ( n = 110 ) and higher cardiovascular disease related mortality in 25 patients undergoing transfemoral TAVR . CONCLUSIONS The presence of LGE indicating focal fibrosis or unrecognized infa rct by CMR is an independent predictor of mortality in patients with AS undergoing AVR and could provide additional information in the pre-operative evaluation of risk in these patients Aims To assess cardiovascular magnetic resonance ( CMR ) measured myocardial perfusion reserve ( MPR ) and exercise testing in asymptomatic patients with moderate-severe AS . Methods and results Multi-centre , prospect i ve , observational study , with blinded analysis of CMR data . Patients underwent adenosine stress CMR , symptom-limited exercise testing ( ETT ) and echocardiography and were followed up for 12–30 months . The primary outcome was a composite of : typical AS symptoms necessitating referral for AVR , cardiovascular death and major adverse cardiovascular events . 174 patients were recruited : mean age 66.2 ± 13.34 years , 76 % male , peak velocity 3.86 ± 0.56 m/s and aortic valve area index 0.57 ± 0.14 cm2/m2 . A primary outcome occurred in 47 ( 27 % ) patients over a median follow-up of 374 ( IQR 351–498 ) days . The mean MPR in those with and without a primary outcome was 2.06 ± 0.65 and 2.34 ± 0.70 ( P = 0.022 ) , while the incidence of a symptom-limited ETT was 45.7 % and 27.0 % ( P = 0.020 ) , respectively . MPR showed moderate association with outcome area under curve ( AUC ) = 0.61 ( 0.52–0.71 , P = 0.020 ) , as did exercise testing ( AUC = 0.59 ( 0.51–0.68 , P = 0.027 ) , with no significant difference between the two . Conclusions MPR was associated with symptom-onset in initially asymptomatic patients with AS , but with moderate accuracy and was not superior to symptom-limited exercise testing . Clinical Trials.gov ( NCT01658345 ) |
1,742 | 10,641,588 | Offspring of obese parent(s ) were consistently seen to be at increased risk of fatness , although few studies have looked at this relationship over longer periods of childhood and into adulthood .
No clear relationship is reported between socio-economic status ( SES ) in early life and childhood fatness .
However , a strong consistent relationship is observed between low SES in early life and increased fatness in adulthood .
Studies investigating SES were generally large but very few considered confounding by parental fatness .
Women who change social class ( social mobility ) show the prevalence of obesity of the class they join , an association which is not present in men .
There is good evidence from large and reasonably long-term studies for an apparently clear relationship for increased fatness with higher birth weight , but in studies which attempted to address potential confounding by gestational age , parental fatness , or social group , the relationship was less consistent .
There was almost no evidence for an influence of activity in infancy on later fatness , and inconsistent but suggestive evidence for a protective effect of activity in childhood on later fatness . | OBJECTIVE To identify factors in childhood which might influence the development of obesity in adulthood .
BACKGROUND The prevalence of obesity is increasing in the UK and other developed countries , in adults and children .
The adverse health consequences of adult obesity are well documented , but are less certain for childhood obesity .
An association between fatness in adolescence and undesirable socio-economic consequences , such as lower educational attainment and income , has been observed , particularly for women .
Childhood factors implicated in the development of adult obesity therefore have far-reaching implication s for costs to the health-services and economy .
The influence of other social factors such as family size , number of parents at home and childcare have been little research ed . | OBJECTIVE To compare nutrient intakes between vegetarians and nonvegetarians with similar health practice s , and to assess relationships with eating behavior scores from the Three-Factor Eating Question naire . DESIGN Survey . SETTING Metropolitan area in western Canada . SUBJECTS Subjects ( n = 45 ) were participants in a study comparing sub clinical menstrual disturbances between vegetarians and nonvegetarians . To be included , women had to be 20 to 40 years old , be weight stable with a body mass index ( BMI ; kg/m2 ) of 18 to 25 , be a nonsmoker , exercise 7 hours a week or less , consume one alcoholic drink or less a day , and not be using oral contraceptives . Nonvegetarians ( n = 22 ) ate red meat three times a week or more , and vegetarians ( n = 23 , 8 vegans and 15 lactovegetarians ) had excluded all meat , fish , and poultry for 2 years or more . MAIN OUTCOME MEASURES Nutrient intake assessed by three 3-day diet records ; supplement use ; body composition ; and dietary restraint ( conscious limitation of food intake ) , disinhibition , and hunger assessed by the Three-Factor Eating Question naire . STATISTICAL ANALYSES PERFORMED Anthropometric variables , nutrient intakes , and eating behavior scores were compared between vegetarians and nonvegetarians using unpaired t tests , and among vegans , lactovegetarians , and nonvegetarians using one-way analysis of variance and Duncan 's test . Supplement use was compared using chi 2 analysis . The Pearson correlation coefficient was used to evaluate relationships between variables . RESULTS Diets of all women adhered closely to current nutrition recommendations . Vegetarians had lower protein and cholesterol intakes and higher percentage of energy as carbohydrate , ratio of polyunsaturated fat to saturated fat ( P : S ratio ) , and fiber intake than nonvegetarians . Vegetarians had lower riboflavin , niacin , vitamin B-12 , zinc , and sodium intakes and higher folate , vitamin C , and copper intakes . However , many differences were not apparent between the subgroup of lactovegetarians and nonvegetarians ( their P : S ratios and carbohydrate , fiber , riboflavin , folate , vitamin C , and copper intakes were similar ) . In contrast , differences existed between the lactovegetarian and the vegan subgroups . Supplement use was similar between groups , except for greater vitamin C use by vegetarians . Vegetarians were leaner than nonvegetarians , had lower restraint scores , and had significant associations between restraint and BMI ( r = .49 ; P < .05 ) and energy per kilogram body weight ( r = -.60 ; P < .01 ) . APPLICATIONS/ CONCLUSIONS Current nutrition recommendations can be attained by vegetarians and nonvegetarians alike , but nutrient intakes can not be inferred from dietary pattern . In this study , the intakes of health-conscious nonvegetarians and lactovegetarians were more similar than the intakes of lactovegetarians and vegans . Vegans ' calcium and vitamin B-12 intakes may need attention . Vegetarians ' lower restraint scores suggest that they are not at increased risk for eating disorders Exercise has been found to be effective for prevention of weight gain and maintenance of a stable weight in adults . The objective of this study was to evaluate the effect of a school-based aerobic exercise program on the obesity indexes of preschool children . Subjects were 292 second-year elementary school pupils from 2 kindergartens in Hat Yai municipality , Songkhla province , southern Thail and . A specially design ed exercise program , including a 15-min walk before beginning the morning class and a 20-min aerobic dance session after the afternoon nap , 3 times a week , was conducted for 29.6 wk . Weight , height , and triceps skinfold thickness were measured 4 times . At the end of the study , the prevalence of obesity , using 95th percentile National Center for Health Statistics triceps-skinfold-thickness cutoffs , of both the exercise and control groups decreased . That of the exercise group decreased from 12.2 % at baseline to 8.8 % ( Wilcoxon signed-rank test , P = 0.058 ) , whereas that of the control group decreased from 11.7 % to 9.7 % ( Wilcoxon signed-rank test , P = 0.179 ) . A sex difference in the response of body mass index ( BMI ) to exercise was observed . Girls in the exercise group had a lower likelihood of having an increasing BMI slope than the control girls did ( odds ratio : 0.32 ; 95 % CI : 0.18 , 0.56 ) . In conclusion , our study suggests that a 29.6-wk school-based exercise program can prevent BMI gain in girls and may induce a remission of obesity in preschool-age children We report 10-year treatment outcomes for obese children in 4 r and omized treatment studies . At 10 years , 34 % decreased percentage overweight by 20 % or more , and 30 % were not obese . Significant effects were observed when parents and children were targeted and reinforced for weight loss in comparison with nontargeted controls and for children given lifestyle or aerobic exercise in comparison with a calisthenics control . Thirty-four percent of the variance in change in percentage overweight was predicted from sex , baseline percentage overweight , self-monitoring weight , meals eaten at home , and family and friends ' support for eating and exercise . Results show long-term changes in children depend on the treatment , and evidence converges on the importance of the family and other sources of support for eating and activity change This study examined whether preschool children differed on measures of psychosocial functioning both cross-sectionally and longitudinally . One hundred and thirty-two children who varied in levels of body fat participated in the study along with their natural parents . Results indicated that the children did not differ in levels of self-esteem and family functioning as a function of their body fat . Prospect ively , physical self-esteem weakly ( but significantly ) correlated with body fat at 1 and 2 years , and father 's perception of family functioning predicted body fat at 1 year only . Results suggested that childhood obesity may not develop as a result of psychosocial factors OBJECTIVE --To examine the patterns of physical activity among British schoolchildren aged 11 to 16 and to assess whether the children experience the intensity and duration of physical activity that are believed to stress the cardiopulmonary system appropriately . DESIGN --Cross sectional study of a sample of children drawn from a larger survey of coronary risk factors in children . Continuous monitoring of heart rate for 12 hour periods on three school days and one Saturday . SETTING --Two communities in Devon . SUBJECTS--266 Children ( 163 girls , 103 boys ) aged 11 to 16 r and omly selected from a sample of 707 children . MAIN OUTCOME MEASURES --Percentage of time and number of sustained periods in which heart rate was greater than 139 beats/min . Anthropometric measures and external assessment of sexual maturity with Tanner 's indices . RESULTS --The boys had heart rates greater than 139 beats/min for a significantly higher percentage of time than the girls ( p less than 0.01 ) during the weekday ( 6.2 % v 4.3 % ) and the Saturday ( 5.6 % v 2.6 % ) . The boys had significantly more five and 10 minute periods with heart rates greater than 139 beats/min than the girls during the Saturday and weekdays and more 20 minute periods during the weekdays . 84 Girls and 37 boys had no 10 minute period with a heart rate greater than 139 beats/min during the three weekdays and 112 girls and 65 boys had no such 10 minute period during the Saturday . No significant relation was detected in either sex between the amount or habitual physical activity ( heart rate ) and skinfold thickness or maturity group . CONCLUSIONS --British children have surprisingly low levels of habitual physical activity , and many children seldom undertake the volume of physical activity believed to benefit the cardiopulmonary system . Boys are more active than girls . The pubertal stage of development or body fatness , or both , do not seem to be sensitive indicators of physical activity in either girls or boys Using the Princeton School Family Study cohort , our specific aim was to determine whether , and to what degree , parent-offspring and sibling associations for measures of body habitus outlast the period of shared common household environment in a single well characterized community . Familial associations of measures in body habitus were assessed in two and three generation kindreds , in parents and their pediatric offspring ( less than 20-yr-old ) , parents and their adult offspring ( less than or equal to 20-yr-old ) , and in pediatric and adult siblings . The cohort included 177 r and omly recalled prob and s and 202 prob and s from a hyperlipidemic recall group ( top decile plasma cholesterol and /or triglyceride ) . In r and omly recalled whites , significant associations of body mass indices in parents and pediatric offspring and in pediatric siblings , and the absence of significant correlations in parents and adult offspring and in adult siblings , emphasize the potency of common household environmental effects relative to within-family similarities for shared body habitus . In whites from the hyperlipidemic recall group , only the mother-pediatric and adult offspring correlations for body mass indices were significant . We speculate that mothers and their offspring from kindreds selected by hyperlipidemic prob and s are more likely than fathers and their offspring to share eating habits and relative ponderosity , with these communal behaviors outlasting the period of common household environment . Alternatively , and speculatively , in the hyperlipidemic recall group , determinants for ponderosity may be shared more by mothers and their offspring than by fathers and their offspring . Particularly in the r and om recall group , within-family associations of body mass indices primarily reflect shared common household environments , and probably secondarily , the outcome of genes held in common Recent research has shown weight maintenance for obese preadolescent children over 60 and 120 month intervals , while studies on adults consistently show they fail to maintain weight loss . This paper is design ed to examine differences in percent overweight changes at 6 , 60 and 120 months in obese parents and children from 113 families who participated in r and omized controlled outcome studies evaluating family-based behavioral treatment . Analyses showed children had significantly greater changes in percent overweight than their parents at each time point . Chi-Square and Logistic Regression analyses showed children were more likely than their parents at each time point to have percent overweight decreases greater than 20 % , with over 20 % of the children and less than 1 % of the parents showing changes this large . The implication s of these results for weight control are discussed . These results suggest there may be differences in the efficacy of treating obesity in children versus adults The possible effect of maternal attitude to sweet eating habits on their offspring 's risk of overweight is a common concern . This study addresses the influence of mothers ' reports on and attitude to sweet eating habits on the subsequent risk of overweight of their offspring in young adulthood . A study of a r and omly selected cohort of 9 - 10 year old children from schools in the Copenhagen municipality was performed in 1974 . A decade later a follow-up was carried out , and 86 % of the target population participated . Overweight was defined as the 90th percentile of body mass index distribution ( weight/height2 ( kg/m2 ) ) . The odds ratio of overweight in young adulthood was assessed by logistic regression analysis taking into account body mass index in childhood , gender and social background ( both parents ' school education , householder 's occupational status , and quality of dwellings in childhood rearing areas ) . The results showed that the risk of overweight was significantly increased if the mother reported lacking knowledge about her offspring 's sweet eating habits ( OR = 4.5 ; 95 % confidence limits : 1.7 - 12.1 ; P = 0.003 ) . The risk was insignificantly increased if the mothers expressed acceptance of sweet eating habits ( OR = 1.9 ; 0.8 - 4.2 ; P = 0.1 ) , and if more than an average amount of money was given for sweets ( OR = 2.0 ; 1.0 - 3.8 ; P = 0.06 ) . On the other h and , how often the child was actually allowed to eat sweets , and the mother 's acceptance of sugary food did not significantly influence the risk . ( ABSTRACT TRUNCATED AT 250 WORDS Objectives : To examine the effect of measurement error in dietary data on the relationship between diet and body mass index ( BMI ) . To correct for the effect of measurement error on diet– BMI association by using replicate measurements of diet . The effect of measurement error on diet– BMI relationship was simulated , and its implication s are discussed . Design : Prospect i ve study design . Setting : The first and second China Health and Nutrition Survey conducted in 1989 and 1991 , respectively . Subjects : Three thous and , four hundred and seventy-nine adults age 20–45 y at the 1989 survey . Methods : Statistical methods were used to demonstrate the effect of measurement error in dietary data on the diet- BMI association . Results : By using the average of three replicate 24 h dietary recalls , the attenuation of diet- BMI association was reduced substantially . The regression coefficients of fat and energy intakes differed markedly from those computed by using only single measurement of diet . Conclusions : Measurement error in dietary data may significantly attenuate the diet-disease association . Where appropriate , specific emphasis may be needed to address the problem of measurement error in the study of diet-disease relationship . Spnosorship : This research was supported by the National Institute of Health , the Carolina Population Center and the Nutrition Institute , University of North Carolina at Chapel Hill This laboratory study examined whether making sedentary activities contingent upon being physically active would increase obese children 's physical activity . Fourteen obese children aged 8–12 y participated in a baseline session in which they had free choice among a variety of sedentary activities and riding a stationary bicycle . Children were then r and omized to either a contingent group in which watching video cassette recorder ( VCR ) movies and playing video games were contingent upon riding the bicycle or a control group in which all physical and sedentary activities remained freely available . Contingent group children increased physical activity and decreased television activities in comparison to the control , even though other sedentary activities remained freely available . Findings suggest that highly valued sedentary activities can reinforce physical activities and that sedentary activities do not completely substitute amongst themselves . The automated system used to make television activities contingent upon physical activity has potential for modifying activity in the treatment of obesity Humans show considerable interindividual variation in susceptibility to weight gain in response to overeating . The physiological basis of this variation was investigated by measuring changes in energy storage and expenditure in 16 nonobese volunteers who were fed 1000 kilocalories per day in excess of weight-maintenance requirements for 8 weeks . Two-thirds of the increases in total daily energy expenditure was due to increased nonexercise activity thermogenesis ( NEAT ) , which is associated with fidgeting , maintenance of posture , and other physical activities of daily life . Changes in NEAT accounted for the 10-fold differences in fat storage that occurred and directly predicted resistance to fat gain with overfeeding ( correlation coefficient = 0.77 , probability < 0.001 ) . These results suggest that as humans overeat , activation of NEAT dissipates excess energy to preserve leanness and that failure to activate NEAT may result in ready fat gain Individual patterns of food intake development have been investigated on the basis of a longitudinal study of nutrition and growth carried out in 112 children at the ages of 10 months , and 2 , 4 , 6 , and 8 years . On the average , energy intake increased steadily with age . However , individual subjects sometimes followed a different pattern . Approximately 1 out of 5 subjects decreased their intake between two examinations . Besides , less than half the children ( 43 % ) were in the same category of energy intake ( defined as tertiles ) at 10 months and 8 years of age . Similarly , 47 % of the children were in the same weight/height ( BMI ) category at 10 months and 8 years . Correlations computed between early intakes ( 10 months , and 2 , 4 , and 6 years ) and intakes at 8 years were better for energy and protein intake than for fat and carbohydrates ( CHO ) , showing that intake of energy or protein early in life has a better predictive value of intake at later ages . Energy intake development has been examined in those children who were found to be lean , medium , and fat at the age of 8 years ; it increased more between the ages of 4 and 6 years , in children who were fat at 8 years . Individual variations of anthropometric measurements during growth are well documented . The present study points out that similar individual variations of intake also exists . These variations could reflect regulatory processes acting during growth and should be taken into account in investigating the child 's appetite The association of various features of family life with obesity in childhood is well established , but less is known about the effect of these influences on the risk of later obesity . In this prospect i ve , population -based study , we examined the influence of parental care in childhood on the risk of obesity in the offspring in young adulthood . In 1974 , 1258 pupils aged 9 - 10 years were r and omly selected from the third grade of Copenhagen schools . Information on 987 pupils was obtained from the form teachers on family structure and the perceived support from the parents ; school medical services reported on the child 's general hygiene . 756 ( 86 % ) of the 881 eligible participants were followed up 10 years later . The influence of family factors in childhood on the risk of obesity ( body-mass index > 95th centile ) in young adulthood was estimated by odds ratios with control for age and body-mass index in 1974 , sex , and social background . Family structure ( biological or other parents and number of siblings ) did not significantly affect the risk of adult obesity . Parental neglect greatly increased the risk in comparison with harmonious support ( odds ratio 7.1 [ 95 % CI 2.6 - 19.3 ] ) . Dirty and neglected children had a much greater risk of adult obesity than averagely groomed children ( 9.8 [ 3.5 - 28.2 ] ) . However , being an only child , receiving overprotective parental support , or being well-groomed had no effect . Parental neglect during childhood predicts a great risk of obesity in young adulthood , independent of age and body-mass index in childhood , sex , and social background Abstract Objective : To investigate the relation of infant feeding practice to childhood respiratory illness , growth , body composition , and blood pressure . Design : Follow up study of a cohort of children ( mean age 7.3 years ) who had detailed infant feeding and demographic data collected prospect ively during the first two years of life . Setting : Dundee . Subjects : 674 infants , of whom 545 ( 81 % ) were available for study . Data on respiratory illness were available for 545 children ( mean age 7.3 ( range 6.1- 9.9 ) years ) ; height for 410 children ; weight and body mass index for 412 children ; body composition for 405 children ; blood pressure for 301 children ( mean age 7.2 ( range 6.9 - 10.0 ) years ) . Main outcome measures : Respiratory illness , weight , height , body mass index , percentage body fat , and blood pressure in relation to duration of breast feeding and timing of introduction of solids . Results : After adjustment for the significant confounding variables the estimated probability of ever having respiratory illness in children who received breast milk exclusively for at least 15 weeks was consistently lower ( 17.0 % ( 95 % confidence interval 15.9 % to 18.1 % ) for exclusive breast feeding , 31.0 % ( 26.8 % to 35.2 % ) for partial breast feeding , and 32.2 % ( 30.7 % to 33.7 % ) for bottle feeding . Solid feeding before 15 weeks was associated with an increased probability of wheeze during childhood ( 21.0 % ( 19.9 % to 22.1 % ) v 9.7 % ( 8.6 % to 10.8 % ) ) . It was also associated with increased percentage body fat and weight in childhood ( mean body fat 18.5 % ( 18.2 % to 18.8 % ) v 16.5 % ( 16.0 % to 17.0 % ) ; weight st and ard deviation score 0.02 ( −0.02 to 0.06 ) v −0.09 ( −0.16 to 0.02 ) . Systolic blood pressure was raised significantly in children who were exclusively bottle fed compared with children who received breast milk ( mean 94.2 ( 93.5 to 94.9 ) mm Hg v 90.7 ( 89.9 to 91.7 ) mm Hg ) . Conclusions : The probability of respiratory illness occurring at any time during childhood is significantly reduced if the child is fed exclusively breast milk for 15 weeks and no solid foods are introduced during this time . Breast feeding and the late introduction of solids may have a beneficial effect on childhood health and subsequent adult disease . Key messages Current guidelines in the United Kingdom recommend that babies are exclusively breast fed for the first 4 months of life , with solids being introduced thereafter This study found that exclusive breast feeding is associated with a significant reduction in childhood respiratory illness The early introduction of solids is associated with increased body fat and weight in childhood Exclusive bottle feeding is associated with higher systolic blood pressure in childhood Breast feeding and delaying the introduction of solids until after 15 weeks may have a beneficial effect on childhood health and subsequent adult The association between obesity and perinatal , constitutional and social factors was studied in 1363 children ( 676 males , 687 females ) living in six areas of north-east Italy . The children were r and omly selected from four age categories ( 4,8,10 and 12 years of age ) . After adjustment for age , significant associations between the risk of obesity in the child and their body weight at birth ( P < 0.01 ) and the father 's or mother 's body mass index ( P < 0.001 ) were found in both genders . When these parental and perinatal variables were included as independent variables in a multiple logistic regression model controlling for the effect of age , parental body mass index and children 's birth-weight remained independently associated with childhood obesity . In females , an interaction between birthweight and the mother 's body mass index on the prevalence of obesity in childhood was found . In conclusion , parental obesity and birthweight represent major risk factors for obesity among children in north-east Italy Longitudinal correlations were obtained between amniotic fluid insulin concentration at 32 to 38 weeks ' gestation and anthropometric characteristics at the age of 6 years in 56 children of diabetic mothers . The prospect i ve studies indicated that at the age of 6 years , as at birth , the greatest increase in weight in relation to height ( relative obesity ) was seen in children who experienced the greatest exposures to insulin in the uterus ( as judged by amniotic fluid insulin concentration ) . Significant correlations between amniotic fluid insulin and relative obesity at the age of 6 years were found after adjustment for maternal obesity and macrosomia at birth . The highest amniotic fluid insulin values are clustered in the subgroup of 14 children who were obviously obese by the age of 6 years . These findings are consistent with the hypothesis that there is an association between anthropometric development and intrauterine metabolism , and suggest that premature and excessive exposure to insulin during gestation may predispose to obesity in childhood . The amniotic fluid insulin concentration may predict this eventuality A prospect i ve study ( 1985 - 1991 ) was conducted to evaluate the role of nutrition , physical activity , and other life-style factors for the age at menarche , a known breast cancer risk factor . In 1988 - 1989 , a total of 261 girls , aged 8 - 15 years , from a nationwide representative nutrition and activity survey ( 1985 - 1988 ) responded additionally to a mailed question naire on personal maturation and anthropometric data , physical activity , and information about nutritional habits , measured by a short food-frequency question naire . All girls without menarche at the time of question naire mailing were observed for 2 years or until the event of menarche . At the end of the follow-up period , 79 % of the girls had experienced menarche . The survey and question naire data were analyzed for their relation to age at menarche using Cox 's proportional hazards method . After excluding participants with largely deviating measurements between survey and question naire , the increased energy-adjusted fat intake was associated with accelerated menarche ( relative risk = 2.1 ; 95 % confidence interval 1.1 - 4.0 ; lowest vs. highest quartile ) , while increased sports activity was associated with a delay in menarche ( relative risk = 0.3 ; 95 % confidence interval 0.1 - 0.5 ; lowest vs. highest quartile ) . Parameters of physical development such as body weight or body fatness were found to be predictors of menarche . The study provides evidence that dietary effects on breast cancer risk might be indirect by influencing hormonal events like the age at menarche The association of television viewing and obesity in data collected during cycles II and III of the National Health Examination Survey was examined . Cycle II examined 6,965 children aged 6 to 11 years and cycle III examined 6,671 children aged 12 to 17 years . Included in the cycle III sample were 2,153 subjects previously studied during cycle II . These surveys , therefore , provided two cross-sectional sample s and one prospect i ve sample . In all three sample s , significant associations of the time spent watching television and the prevalence of obesity were observed . In 12- to 17-year-old adolescents , the prevalence of obesity increased by 2 % for each additional hour of television viewed . The associations persisted when controlled for prior obesity , region , season , population density , race , socioeconomic class , and a variety of other family variables . The consistency , temporal sequence , strength , and specificity of the associations suggest that television viewing may cause obesity in at least some children and adolescents . The potential effects of obesity on activity and the consumption of calorically dense foods are consistent with this hypothesis Objective : To analyse the association between nutritional and familial factors and obesity in boys and girls . Design : R and omized , cross-sectional population study . Setting : Province de Luxembourg , Belgium . Subjects : One thous and and twenty-eight boys and girls in age strata 6–8 , 8–10 and 10–12 y , comprising 70.3 % of primary cohort . Methods : Examinations included anthropometric measurements and question naires covering familial , socioeconomic and psychosocial factors . A three day dietary record was obtained in 955 children . This was analysed in relation to the anthropometric data . Results : In comparison with similar studies from other regions and recommended allowances , the intakes of total energy , fat , particularly saturated fat and cholesterol , were high , while consumption of carbohydrate and fiber was low , as well as the polyunsaturated/saturated ratio of fat . Total energy intake showed no or weakly significant correlations with anthropometric factors . However , total fat ( P=0.045 ) and saturated fat ( P=0.0005 ) intake showed consistent positive correlations with body mass index ( BMI , kg/m2 ) and skinfold thickness , with corresponding negative relationships to carbohydrate intake ( P=0.034 ) in boys . Such relationships were also found when calculated as energy density . These associations were not statistically significant in girls . The high fat , low carbohydrate pattern of the nutritional status seemed to be more pronounced in families where the father had a low level of education ( lipids , boys , P=0.0007 ) , and where both parents were obese ( saturated fat , boys , P=0.023 ) , suggesting involvement of socioeconomic and familial factors . Conclusion : The lack of correlation between factors indicating obesity and total energy intake suggests that the positive energy balance causing obesity is due mainly to a low energy output . However , since energy intake measurements are imprecise , overeating can not be excluded , particularly since elevated consumption of food with high contents of fat , found in these children seems to be poorly regulated A prospect i ve study of a cohort of healthy infants observed from birth to 2 years of age was carried out to investigate factors influencing the development of early adiposity . Infant suckling was measured in the laboratory twice during the first month of life . Multiple regression analyses revealed that parental educational level and a measure of feeding behavior , the interval between bursts of suckling , accounted for 18 % of the variance in triceps skinfold measures at 1 year of age . A lower level of education and shorter interburst interval were associated with increased adiposity . Two feeding variables , pressure of suckling and the number of reported feeds per day , accounted for 21 % of the variance in skinfold thickness at 2 years of age . Fewer , but larger , feeds and a higher sucking pressure were associated with a greater degree of adiposity . It seems that a vigorous infant feeding style , consisting of sucking more rapidly , at higher pressure , with a longer suck and burst duration , and a shorter interval between bursts of sucking , is associated with higher caloric intake and greater adiposity . The early development of this feeding style suggests that it may be a genetically endowed behavior . Breast-feeding protected against early adiposity only to the age of 6 months in this cohort of infants A family study was conducted in Muscatine , Iowa in 1984 - 1985 to evaluate the relation between ponderosity in children and coronary risk factor levels in these children and in their family members , and the genetic contribution to familial clustering of levels of ponderosity ( body weight relative to height ) . Four groups of prob and s were selected from the 1,783 students who participated in three consecutive biennial school surveys . A r and om group ( n = 70 ) , a r and om sample of students from the entire pool ; a lean group ( n = 72 ) , students in the lowest quintile of relative weight on all three surveys ; a gain group ( n = 70 ) , students who gained at least two quintiles of relative weight over the four-year period ; and a heavy group ( n = 72 ) , students in the highest quintile of relative weight on all three surveys . The parents , siblings , a related aunt or uncle , and a first cousin of these prob and s were also examined . The data show that levels of high density lipoprotein ( HDL ) cholesterol , apolipoproteins A-1 and B , and systolic blood pressure in heavy group prob and s are consistent with increased coronary risk . This same association exists among the relatives with excess ponderosity . Levels of body mass index in the mothers , fathers , and siblings cluster with the levels in the prob and s , and genetic differences among persons explain 36 - 52 per cent of the variability in body mass index across the range of ponderosity represented by the prob and s and their relatives . While the contribution from genes is strong , these data suggest that the contribution from environmental factors is equally as important The effectiveness of the adolescent obesity intervention SHAPEDOWN was evaluated for 15 months through a r and omized experimental design study . Test groups ( no. = 37 ) participating in the intervention were compared with a no-treatment control group ( no. = 29 ) at four sites in northern California . The program employs a variety of cognitive , behavioral , and affective techniques adapted to make successive small modifications in diet , exercise , communication , and affect that are sustainable . Very-low-calorie or restrictive diets are avoided in the program . Parents are instructed on strategies for supporting their adolescents ' weight-loss efforts . Participation in the group application of the program was associated with significant improvement in relative weight , weight-related behavior , depression , and knowledge of weight management concepts at post-treatment and at 1-year follow-up . Self-esteem increased significantly regardless of condition . Change in relative weight for the test group was -9.9 + /- 14.9 % ( mean + /- st and ard deviation ) and for the control group was -0.10 + /- 13.2 % . At month 15 of the study period , weight change in the test group compared with the controls was -5.15 kg . For all subject variables examined in the test group , mean change in relative weight at 1-year follow-up was negative , suggesting that none of the characteristics examined contraindicate program participation among obese adolescents seeking care . Drop-out rate was 16 % . The study suggests that the program produces significant long-term outcomes in obese adolescents and is transferable to a variety of setting Early menarche and late menopause are risk factors for the development of breast cancer . An adequate hormonal mechanism for those observations has not been described . Because obesity has also been associated with increased breast cancer risk , we examined the relationship among height , weight , adiposity , and menstrual cycle characteristics in women who prospect ively recorded menstrual cycle intervals and reproductive events as part of the Menstrual and Reproductive History Research Program . Within this study cohort , adult height , weight , and a derived index of adiposity were related to both earlier age at menarche and later age at menopause . The association of early age at menarche with adiposity persisted from age 18 yr through middle age and into the menopausal years . There was no relationship between body mass and age at first pregnancy , another breast cancer risk factor . Women who were heavier at 18 yr of age and thereafter gained 5 lb or more had significantly greater mean menstrual cycle length and variability during the 7-yr period after menarche than the other members of the cohort . There was no obvious relationship between weight indices and menstrual cycle pattern during mature reproductive life or during the 7 yr before menopause . Our data suggest that menarcheal and menopausal age may have a common relationship to nutritional status and to constitutional features that pre date the onset of menarche and persist into later life To overcome method ologic defects ( failure to control for confounding factors , univariate statistical analyses ) in previous studies of etiologic determinants of childhood adiposity , we carried out a prospect i ve cohort study of 462 healthy , full-term infants observed from birth to 12 months . Postpartum , we obtained sociodemographic data and administered two recently vali date d scales of maternal attitudes toward feeding and infant body habitus . Parental heights and weights and infant feeding variables were determined by interview , and at 6 and 12 months we measured height and weight and triceps , subscapular , and suprailiac skinfolds . Multiple regression analysis was used to determine independently predictive factors for weight , body mass index ( BMI = weight/height ) , and the sum of the three skinfold measurements . Birth weight , sex , age at introduction of solid , and duration of breast-feeding were all significant predictors of weight at 12 months ( r2 = 0.296 , P less than 0.0001 ) . Significant determinants for BMI included birth weight , duration of breast-feeding , sex , and IBH ( r2 = 0.125 , P less than 0.0001 ) ; those for total skinfold were age at introduction of solid foods and birth weight ( r2 = 0.038 , P = 0.002 ) . Similar results were obtained at 6 months , although slightly less of the variance was explained . We conclude that the ability to predict which babies will be heavy or obese during the first year is limited . Breast-feeding and delayed introduction of solid foods do offer some protective effect , however , and thus efforts to encourage these practice s may be reaping some benefit Weight and blood pressure changes were evaluated in a 16-month controlled trial comparing three methods of involving mothers in the treatment of their obese adolescents ( aged 12 to 16 years ) . The treatments were : ( 1 ) Mother-Child Separately -- children and mothers attended separate groups ; ( 2 ) Mother-Child Together -- the children and mothers met together in the same group ; and ( 3 ) Child Alone -- the children met in groups and mothers were not involved . The program consisted of behavior modification , social support , nutrition , and exercise . The Mother-Child Separately group lost more weight ( 8.4 kg ) during treatment than did the other two groups ( 5.3 and 3.3 kg ) . Differences between the groups increased at the 1-year follow-up : compared to pretreatment weight , the Mother-Child Separately group lost 7.7 kg compared with gains of approximately 3 kg in the other two groups . Blood pressures of children with the highest initial pressures decreased by 16/9 mm Hg at the end of treatment and by 16/5 mm Hg at the 1-year follow-up . These results suggest that a program of behavior modification and parent involvement can lead to significant weight losses in obese children , and that the nature of parent involvement may be important This study reports the follow-up in 1993 of 209 adults , aged 27 to 29 years , who as children had been enrolled in a controlled trial of the prevention of children 's behavior disorders . One hundred four control subjects and 105 study subjects , representing 90 % of the original cohort , responded to a question naire detailing their present social situation and habits , educational achievements , and emotional well-being . The study subjects overall reported significantly fewer neurotic symptoms ( p < 0.001 ) than the control subjects ; the study women also reported significantly fewer depressive symptoms ( p < 0.001 ) . A greater proportion of the study subjects , compared with control subjects , had undertaken a university degree or diploma ( p < 0.013 ) , whereas fewer of the men had attended a school of technology ( p < 0.049 ) . The study women were less likely to be obese , as defined by a body mass index of 25 or more ( p < 0.030 ) . The study men and women tended to smoke less than their control subjects , though significant differences were not attained . These results in the experimental group reflected the behavior patterns recorded at 6 years of age , after initial preschool interventional therapy . It appears that the initial benefit obtained from active counseling of mothers about their preschool children 's behavior may be long lasting , favorably affecting the individuals ' psychologic well-being , educational achievements , and social habits as adults OBJECTIVES : To examine patterns of change in total body fat ( TBF ) , percent body fat ( % BF ) , and fat-free mass ( FFM ) , from 8 - -20 y of age and the effect of rate of skeletal maturation . To determine the degree of tracking of body composition for individuals from childhood into adulthood . RESEARCH DESIGN : Annual serial data for TBF , % BF and FFM from underwater weighing using a multicomponent body composition model were collected from 130 CAUcasian males and 114 CAUcasian females between 1976 and 1996 . Rate of maturation was defined as FELS skeletal age ( SA ) less chronological age ( CA ) . R and om effects models were used to evaluate general patterns of change and tracking of individual serial data over the 12 y age range . RESULTS : Changes in TBF followed a quadratic model for males and for females with declining rates of change . Changes for % BF followed a cubic model for males and females . General patterns of change for FFM followed a cubic model for males and a quadratic model for females . TBF for males and females increased with age , but the rates of change declined with age . % BF for females increased from age 8–20 y. For males , % BF increased with age , but the positive rates of change declined and became a negative when aged about 13 y and reached a minimum at about the age of 15 y. The rate of change for % BF increased thereafter . FFM for males and females increased with age , but the rates of change decreased with age . The extent of tracking is inversely related to the length of the time interval . At the same age , rapidly-maturing children have significantly larger amounts of TBF , % BF and FFM than slow-maturing children . Tracking in body composition for individuals persisted from childhood to adulthood . CONCLUSIONS : ( 1 ) There are gender-associated differences in these patterns of change for % BF and FFM but not for TBF ; ( 2 ) TBF , % BF and FFM increased with increased rates of maturation ; ( 3 ) significant tracking in body composition for individuals persists from childhood to adulthood Self-esteem has been hypothesized to be lower in obese adolescents relative to their normal weight peers and to be an important factor in preventing or reversing obesity . The present study examined the relationship between obesity and self-esteem cross-sectionally and prospect ively over three years in a cohort of 1278 adolescents in grade s 7 to 9 at baseline . Cross-sectional analyses revealed an inverse association between physical appearance self-esteem and body mass index in both males and females . In females , body mass index was inversely associated with global self-esteem , close friendship , and behavioral conduct self-esteem . In males , body mass index was inversely associated with athletic and romantic appeal self-esteem . Prospect ively , in females , physical appearance and social acceptance self-esteem at baseline were inversely related to body mass index three years later . Baseline self-esteem was unrelated prospect ively to change in body mass index in males . All associations were modest in magnitude . These results suggest that in a middle class white sample of adolescents , self-esteem specific to physical appearance is modestly associated with body mass index . Low self-esteem does not appear to predict the development of obesity over time A prospect i ve follow-up study , from birth to age 5 , of height , weight , and weight/height indices in 582 white children was carried out in a suburban private pediatric practice . The purpose of the study was to examine trends in height and weight over time , to evaluate any differences in measures of ponderosity between breast-fed and bottle-fed infants , and to locate the heaviest children at age 5 . There were significant correlations between height , weight , the ratio of height to weight , the ponderal index ( height/weight 1/3 ) , and the Quetelet index ( weight/height2 ) achieved during the first year of life , and that attained at age 5 years . However , approximately 70 % of the variance in weight and ponderosity indices at age 5 could not be accounted for by measurement of weight and ponderosity during the first year of life . Breast-fed and bottle-fed infants did not differ in weight and weight/height indices . There was a modest , but consistent , " tracking " pattern among children in the upper decile for weight and ponderosity at age 5 years in that 30 % of them were also in the top decile for weight and ponderosity at age 6 months , and 30 % to 40 % were in the top decile at age 1 year . More than half of the variance in weight or indices of body proportion at age 5 is not accounted for by these variables in the first year of life , indicating limitations to the generalizability of the concept , that obese infants become obese children Obese children 8 - 12 years old from 61 families were r and omized to treatment groups that targeted increased exercise , decreased sedentary behaviors , or both ( combined group ) to test the influence of reinforcing children to be more active or less sedentary on child weight change . Significant decreases in percentage overweight were observed after 4 months between the sedentary and the exercise groups ( -19.9 vs. -13.2 ) . At 1 year , the sedentary group had a greater decrease in percentage overweight than did the combined and the exercise groups ( -18.7 vs. -10.3 and -8.7 ) and greater decrease in percentage of body fat ( -4.7 vs. -1.3 ) . All groups improved fitness during treatment and follow-up . Children in the sedentary group increased their liking for high-intensity activity and reported lower caloric intake than did children in the exercise group . These results support the goal of reducing time spent in sedentary activities to improve weight loss The purpose of the study was to assess prospect ively the influence of social factors in childhood on risk of overweight in young adulthood , while taking into account degree of fatness in childhood . A r and om selection of children 9 - 10 years of age attending the third school grade in Copenhagen schools in 1974 was performed . Parental school education , householder 's occupational status , and quality of dwellings in the rearing area were recorded . Ten years later a follow-up was carried out , and 756 ( 86 % ) of the 881 eligible individuals participated . The effect of the social factors on the risk of overweight in adulthood was analysed by logistic regression analysis , including gender and degree of fatness in childhood as covariates . The relationship between the traditional socio-demographic factors ( parental education and occupational ) and risk of overweight in young adulthood was insignificant , when controlling for degree of fatness in childhood and gender . However , the risk of overweight was highly increased for individuals reared in an area with poor quality of dwellings compared to those from a good area ( P less than 0.001 ) , even when controlling for the effect of parental education and occupation ( P less than 0.001 ) . In conclusion , rearing area had a much stronger influence on risk of overweight in young adulthood than parental education and occupation Northern Irel and has the highest incidence of coronary heart disease ( CHD ) in the world . The physical fitness , activity patterns , health knowledge , attitudes , and dietary habits of a r and om , stratified sample of 3211 Northern Irish children , comprising 1540 boys and 1671 girls , age range 11 - 18 years were examined . At all ages boys were significantly more active than girls . The most important finding was an appreciable decline in physical activity levels after the age of 14 years reaching extremely low levels in older girls . While 75 % of exercise taken was not related to school , physical education classes constituted the only exercise taken by one third of pupils . Girls had healthier nutritional habits and were more inclined to employ weight control measures than boys . There was a preponderance of children with a higher body mass index indicating a tendency to obesity in the child population . Over 20 % of school leavers of both sexes regularly smoked cigarettes and 20 % regularly drank alcohol . The postulated relationship between childhood inactivity , adult sedentary lifestyle , and increased risk of CHD raises serious cause for concern regarding the future cardiovascular health of many children BACKGROUND AND METHODS Overweight in adolescents may have deleterious effects on their subsequent self-esteem , social and economic characteristics , and physical health . We studied the relation between overweight and subsequent educational attainment , marital status , household income , and self-esteem in a nationally representative sample of 10,039 r and omly selected young people who were 16 to 24 years old in 1981 . Follow-up data were obtained in 1988 for 65 to 79 percent of the original cohort , depending on the variable studied . The characteristics of the subjects who had been overweight in 1981 were compared with those for young people with asthma , musculoskeletal abnormalities , and other chronic health conditions . Overweight was defined as a body-mass index above the 95th percentile for age and sex . RESULTS In 1981 , 370 of the subjects were overweight . Seven years later , women who had been overweight had completed fewer years of school ( 0.3 year less ; 95 percent confidence interval , 0.1 to 0.6 ; P = 0.009 ) , were less likely to be married ( 20 percent less likely ; 95 percent confidence interval , 13 to 27 percent ; P < 0.001 ) , had lower household incomes ( $ 6,710 less per year ; 95 percent confidence interval , $ 3,942 to $ 9,478 ; P < 0.001 ) , and had higher rates of household poverty ( 10 percent higher ; 95 percent confidence interval , 4 to 16 percent ; P < 0.001 ) than the women who had not been overweight , independent of their base-line socioeconomic status and aptitude-test scores . Men who had been overweight were less likely to be married ( 11 percent less likely ; 95 percent confidence interval , 3 to 18 percent ; P = 0.005 ) . In contrast , people with the other chronic conditions we studied did not differ in these ways from the nonoverweight subjects . We found no evidence of an effect of overweight on self-esteem . CONCLUSIONS Overweight during adolescence has important social and economic consequences , which are greater than those of many other chronic physical conditions . Discrimination against overweight persons may account for these results OBJECTIVE Recent retrospective studies of older adults have demonstrated a correlation between lower birth weight and hypertension and insulin resistance . We tested this finding in our sample of urban African Americans with prospect i ve data on growth and blood pressure and also tested other variables ( in addition to birth weight ) for their relationship to adult cardiovascular risk . STUDY DESIGN A prospect i ve study of birth weight , growth , and blood pressure ( Philadelphia Perinatal Collaborative Project ) followed a sample of 137 African Americans , with nine examinations from birth through 28.0 + /- 2.7 years . Metabolic measurements ( oral glucose tolerance testing , euglycemic hyperinsulinemic clamp , and plasma lipid concentration ) were performed on the subjects as adults . Bivariate correlations among parameters were computed using the Pearson r. The chi-squared statistic was used to determine associations of outcomes with birth weight . Stepwise multiple linear regressions were computed using newborn , early childhood , adolescent , and young adult parameters to predict adult outcomes . RESULTS Birth weight and blood pressure at age 28 years are not correlated ( Pearson r = 0.06 ) . Birth weight is also unrelated to adult obesity . However , weight at 0.3 years and after and body mass index at 7 years and after are correlated with adult weight . Furthermore , weight at age 14 years is significantly negatively correlated with measures of insulin-stimulated glucose use , indicating that obese adolescents may be at greater risk than nonobese adolescents for development of non-insulin dependent diabetes in adulthood . CONCLUSIONS We found no relationship between birth weight and adult outcomes pertaining to cardiovascular risk in this sample of adult African Americans . However , we did find evidence that somatic growth ( body weight and body mass index ) is significantly related to obesity and attenuated insulin-stimulated glucose utilization in adulthood . These findings indicate that the origins of adult cardiovascular disease are related to somatic growth , but not intrauterine growth , and are evident during childhood As shown in more than 8000 prob and -parent pairs derived from a total-community sample and followed in longitudinal fashion , the 5-year incidence of obesity ( new cases per 5-year period ) approximates 8 percent for the juvenile-onset , adolescent-onset and adult-onset obese alike . Parents of juvenile-onset ( ages 5 - 9 ) , adolescent-onset ( 10 - 19 ) and adult-onset obese ( 20 - 39 ) tend to be of above-average fatness level , + 0.25Z scores , overall , regardless of the age at onset of obesity in their progeny . Except for the parents of the juvenile-onset obese , educational level of the parents tends to be below average for the sample as a whole . These new data acquired in longitudinal context and explored in retrospective- prospect i ve fashion do not substantiate the notion that different onset ages of obesity indicate separate etiologies and different family constellations We examined changes in the nutritional status of elderly patients with chest infection for a period of 3 months after discharge from hospital , including the effects of nutritional supplementation on well-being and functional status as well as on nutritional indices . Eighty-one subjects admitted to an acute medical ward aged 65 years and over with chest infection were recruited consecutively , and r and omized to receive supplement ( 500 ml of Ensure liquid daily ) for 1 month , or no supplement , on discharge . Assessment at baseline , 1 , 2 and 3 months included a question naire to determine health , mental and functional status , and anthropometric measurements . Biochemical nutritional status was assessed at baseline , 1 and 3 months , and dietary intake ( 24 h recall method ) at 1 and 3 months . During recovery , both supplement and non-supplement groups showed improvement in various measures of well-being and biochemical status . In addition , the former group showed improvement in more anthropometric measurements , in thiamine and pyridoxine status , while the non-supplement group showed a lower level of functional ability after 3 months . Various measures of well-being and biochemical status of the water-soluble vitamins were better in the supplement groups . We conclude that nutritional supplementation may have a role in helping elderly patients to recover from chest infections The effects of adding exercise to diet for weight control in obese children were evaluated by r and omizing obese girls to one of two groups : diet and diet plus exercise . During the first 6 weeks of the treatment , children exercised in a supervised three times a week exercise program , in which they walked or ran 3 miles . Significant decreases from baseline weight and in percent overweight were observed for both groups during the year of treatment . Significant decreases in percent overweight were observed at 0 to 2 months and then at 2 to 6 months for the children who were exercising , whereas percent overweight in children in the diet-alone group decreased only from 0 to 2 months . In addition , a significant improvement in fitness was observed only for children in the diet plus exercise group Summary In 1969–1970 , a r and om sample of 1002 girls aged 10·5 to 15·0 from different socio-economic strata were interviewed in Montreal schools . The mean age at menarche of these urban girls was 13·08±0·04 years ( S.D. 1·10 ) from probit analysis . French Canadian girls today commence menarche at about the same age as British girls and about 8 months earlier than Montreal girls three decades ago . Contrary to findings in most other population s ( with a different level and way of life ) , French Canadian girls from upper socio-economic groups mature later than girls from lower socio-economic groups . Girls from large families or with more linear physique were older at menarche than others . Family size and the type of physique were independent factors . There was a close relation between social class and family size , and we consider family size to be one of the most important factors contributing to the different onset of sexual maturation of girls in different socio-economic strata OBJECTIVE To compare spinal bone mineral density ( BMD ) and 1-year BMD change between premenopausal vegetarian and nonvegetarian women . DESIGN Cross-sectional comparison of spinal BMD at baseline and prospect i ve comparison of a sub sample . SETTING A western Canadian metropolitan area . SUBJECTS/ SAMPLE S Healthy vegetarian ( n = 15 lacto-ovo-vegetarian , n = 8 vegan ) and nonvegetarian ( n = 22 ) women aged 20 to 40 years , with regular menstrual cycles and stable body weight completed baseline measurements . Twenty of these women ( 6 lacto-ovo-vegetarian , 5 vegan , 9 nonvegetarian ) participated in repeat measurements at approximately 13 months . STATISTICAL ANALYSES PERFORMED Descriptive statistics , independent sample and paired t tests , 1-way analysis of variance , correlation analysis , and stepwise multiple regression were used to compare groups and to assess associations with BMD . RESULTS At baseline , subjects were 27.2 + /- 5.1 years old . Vegetarians had lower body mass index ( 21.1 + /- 2.3 vs 22.7 + /- 1.9 , P < .05 ) and percent body fat ( 24.0 + /- 5.5 % vs 27.4 + /- 5.1 % , P < .05 ) ; they also tended to have lower BMD ( 1.148 + /- 0.111 g/cm2 vs 1.216 + /- 0.132 g/cm2 , P = .06 ) , although this was not apparent with weight as a covariate ( P = .14 ) . Baseline BMD was predicted by vitamin B-12 intake and total body fat ( R2 = .24 , P = .001 ) . Participants in the follow-up differed only in their being older than non participants . Over 1 year , mean BMD increased significantly ( 1.1 % ) : by diet group , nonvegetarians ' BMD increased but vegetarians ' BMD was unchanged . No other monitored variables were associated with BMD change . APPLICATIONS/ CONCLUSIONS Vegetarian women should be aware of links between low BMD and low body weight/body fat , and should maintain adequate intakes of nutrients believed to affect BMD ABSTRACT . 226 of 243 infants who took part in a prospect i ve study of nutrition and weight during the first year of life were review ed at age 4 years . 23 of 243 infants ( 9 % ) were obese on one or more controls the first year , and 4 of 226 ( 2 % ) at age 4 years . Only 3 of 23 infants remained obese . The weight and length of the children obsese at 0–1 year of age were significantly increased at age 4 years . Overnutrition occurred during the first year in 26 infants and the number of obese infants in this group was significantly increased at age 7–12 months and of overweight children during the first two years of life . At age 4 , however , none of them were either obese or overweight In Czechoslovakia , overweight and nutrition-associated pathologies are frequent . The body mass index ( BMI ) is often used in the clinical assessment of adiposity in children and adults . Its variations during growth are well documented . A cohort of 300 newborns were selected at r and om in Prague between 1956 and 1960 . Weight and height were collected in these subjects at the ages of 3 , 6 , 9 , and 12 months and twice a year from 1 to 20 years . Charts of longitudinal variations of the BMI were drawn for males and females . The three expected phases of BMI development were observed : initial rise until 12 months , subsequent decrease , and second augmentation ( the ' adiposity rebound ' , ' AR ' ) between 4 and 8 years of age . The inverse relationship between age at AR and the BMI in adulthood was confirmed : in the leanest adults , AR had happened by age 7.6 years , in the heaviest adults , age at AR was around 5 years . Many lean ( 44 % ) and fat ( 58 % ) infants developed into average-size adults . The risk of becoming a heavy adult was increased in fat infants ( 31 % ) as opposed to non-fat ( 22 % ) ones . The relative risk of fat infants to become obese adults as compared to non-fat infants is 31/22 = 1.8 . Individual growth curves of children with very high or very low adult BMI values illustrate the relationships between BMI at 12 months , age at AR and adult BMI . The Czech BMI distribution was higher than a comparable French one at all percentiles after age 7 years . ( ABSTRACT TRUNCATED AT 250 WORDS The development of body fatness and leanness is examined in an ongoing prospect i ve nutrition and growth study . Individual skinfold thicknesses , relative weights , weight gains , activity levels , and caloric intakes were examined at seven ages between 6 months and 9 years . Changes in body fatness in this group of children provide evidence that the obese infant usually does not become the obese child . Weight gain in infancy is also a poor predictor of 9-year old obesity . Changes from obese to non-obese or lean are often not linear . There is evidence that impending or actual obesity begins at ages 6 to 9 years with some predictability provided as early as age 2 years for girls , age 3 years for boys OBJECTIVE To examine determinants of moderate and severe obesity in children at 5 years of age . METHODOLOGY A prospect i ve cohort of mothers were enrolled at first antenatal visit , and interviewed shortly after delivery , at 6 months and 5 years . Detailed health , psychological and social question naires were completed at each phase by mothers , and child health question naires at 6 months and 5 years . At 5 years 4062 children were assessed physically , the Peabody Picture Vocabulary Test administered and mothers completed a modified Child Behaviour Checklist . Moderate obesity was defined as BMI between 85th and 94th percentiles inclusively , and severe obesity as a BMI greater than the 94th percentile . RESULTS Independent predictors of severe obesity at 5 years were birthweight , female gender , maternal BMI and paternal BMI . Moderate obesity at 5 years was predicted by birthweight , paternal BMI and sleeplessness at 6 months , while small for gestational age ( SGA ) status and feeding problems at 6 months were protective factors for moderate obesity . Obesity was not associated with problems of language comprehension or behaviour . CONCLUSIONS Findings of this study suggest that biological rather than psychosocial factors are the major determinants of obesity at 5 years Project SPARK evaluates multiple effects of a health-related physical education ( PE ) program for elementary school students . Seven schools were r and omly assigned to one of three conditions : usual PE or control , trained classroom teachers , or PE specialists . The intervention was implemented throughout the fourth and fifth grade s. Data are available from one cohort of 550 children who were measured in the fall and spring of both grade s. Adiposity was assessed by triceps and calf skinfolds , and body mass index ( BMI ) was also measured . Data at each measurement point were analyzed by ANOVAs , covarying for baseline values . At no measurement point were there significant group differences in total skinfold . At both fifth grade measurement points for boys and girls , however , there was a trend for the control group to have higher skinfold values than the two intervention groups . At the final measure , the difference between the highest and lowest groups was about 3 mm for girls and 2 mm for boys . BMI s were significantly lower at some measurement points for boys and girls , but this could be due to increased lean body mass in intervention students . After two years , there was a trend for the children exposed to the PE intervention to have lower levels of body fat , but the differences were not significant |
1,743 | 18,559,804 | INTERPRETATION Short-term use of existing medical cannabinoids appeared to increase the risk of nonserious adverse events . | BACKGROUND The therapeutic use of cannabis and cannabis-based medicines raises safety concerns for patients , clinicians , policy-makers , insurers , research ers and regulators .
Although the efficacy of cannabinoids is being increasingly demonstrated in r and omized controlled trials , most safety information comes from studies of recreational use .
METHODS We performed a systematic review of safety studies of medical cannabinoids published over the past 40 years to create an evidence base for cannabis-related adverse events and to facilitate future cannabis research initiatives . | A preliminary trial of oral delta-9-tetrahydrocannabinol ( THC ) demonstrated an analgesic effect of the drug in patients experiencing cancer pain . Placebo and 5 , 10 , 15 , and 20 mg THC were administered double blind to ten patients . Pain relief significantly superior to placebo was demonstrated at high dose levels ( 15 and 20 mg ) . At these levels , substantial sedation and mental clouding were reported Context Because the same systems metabolize cannabinoids and protease inhibitors , cannabinoids might alter viral loads in HIV-infected patients taking protease inhibitors . Contribution In this r and omized trial , 62 HIV-infected patients taking indinavir or nelfinavir received a marijuana cigarette , dronabinol capsule , or placebo capsule three times daily for 21 days . Half of the patients in all three groups had undetectable viral loads during the study , and average changes in viral load with marijuana and dronabinol , relative to placebo , were small . Caution s The findings of no large harmful effects on viral loads with either smoked or oral cannabinoids need to be confirmed in larger and longer trials . The Editors Marijuana has been smoked for medicinal purpose s for centuries ( 1 ) . Introduced into western medicine in 1842 , marijuana was used to treat various illnesses on the basis of its purported analgesic , anticonvulsant , sedative , hypnotic , and antispasmodic properties . With the passage of the Marihuana Tax Act in 1937 , use of marijuana as a therapeutic agent in the United States waned until the substance was removed from the U.S. Pharmacopoeia in 1942 . The Controlled Substances Act of 1970 placed marijuana in the Schedule I category along with other substances deemed to have no medicinal value and high potential for abuse . In 1986 , the U.S. Food and Drug Administration approved a synthetic , oral form of marijuana 's main psychoactive component , delta-9-tetrahydrocannabinol ( dronabinol , Marinol , Roxane Laboratories , Columbus , Ohio ) , for treating chemotherapy-induced nausea and vomiting ( 2 - 5 ) . A r and omized , controlled trial demonstrated that dronabinol increased self-reported appetite but not weight in patients with AIDS-related wasting syndrome ; these findings led to an expansion of the labeling indication for this use in 1992 ( 6 , 7 ) . Before the advent of highly active antiretroviral therapy in the 1990s , many patients infected with HIV-1 experienced wasting as a preterminal manifestation of the disease ( 8) . Patients with AIDS-related wasting syndrome often reported that they preferred smoked marijuana to dronabinol because it was easier to titrate the dose to achieve the desired effect ; smoked marijuana delivers cannabinoids to the bloodstream much more rapidly than dronabinol ( 9 ) . By the mid-1990s , cannabis buyers ' clubs in the San Francisco Bay area were reportedly selling marijuana to 11 000 patients with HIV infection ( 10 - 12 ) . With the increased availability of protease inhibitorcontaining antiretroviral regimens in the mid-1990s , the incidence of AIDS-related wasting syndrome decreased markedly , as did most of the other late-stage opportunistic manifestations of advanced HIV disease ( 13 - 15 ) . Protease inhibitors , which can inhibit or stimulate the hepatic cytochrome P-450 enzyme system , are subject to many significant drugdrug interactions with other agents used in treating HIV infection and its complications ( 16 , 17 ) . The potential for a drugdrug interaction between protease inhibitors and marijuana is worrisome since many HIV-infected patients continue to smoke marijuana as an appetite stimulant or to decrease nausea associated with their antiretroviral therapy ( 18 , 19 ) . The likelihood of such an interaction is supported by the facts that cannabinoids are metabolized by some of the same cytochrome P-450 enzyme isoforms that metabolize the more widely prescribed protease inhibitors and that tetrahydrocannabinol has been shown to inhibit the metabolism of other drugs ( 20 - 23 ) . Although few recent clinical trials have evaluated the potential therapeutic effects of smoked marijuana , significant progress has been made in underst and ing the pharmacology of cannabinoids in humans . Of the two cannabinoid receptors identified , CB1 ( found mainly in cells of the central nervous system ) is thought to be responsible for the neurologic and behavioral effects of marijuana ( 24 , 25 ) . The identification of a CB2 receptor , found predominantly on B lymphocytes and natural killer cells , suggests that cannabinoids may also affect the immune response . Some studies suggest that marijuana can impair the immune system through B-lymphocyte modulation , tumor necrosis factor inhibition , or changes in the phenotype and function of circulating lymphocytes ( 26 - 29 ) . The hallmark of successful antiretroviral therapy is sustained suppression of HIV RNA levels associated with increasing CD4 + cell counts ( 30 - 32 ) . Considering the potential for both a protease inhibitorcannabinoid interaction and an effect of smoked marijuana on the immune system , we design ed a study to determine the safety or toxicity profile of cannabinoids ( smoked and oral ) in persons with HIV infection . We chose HIV RNA levels as our primary outcome because an intervention that interacted unfavorably with either the antiretroviral agent pharmacokinetics or the immune system directly could cause a perturbation of viral suppression . We report the overall safety results of this r and omized , controlled inpatient clinical trial . Methods Study Group Study participants were recruited by referrals from local physicians and advertisements in newspapers . Volunteers from across the country telephoned to determine whether they might be eligible to participate . Participants were required to be at least 18 years of age , have documented HIV infection , and be receiving a stable antiretroviral treatment regimen of either indinavir ( Crixivan , Merck & Co. , Inc. , North Wales , Pennsylvania ) or nelfinavir ( Viracept , Agouron Pharmaceuticals , Inc. , La Jolla , California ) for at least 8 weeks before enrollment . When enrolled , participants who had been taking the recently recommended dose of nelfinavir , 1250 mg twice daily , were switched to 750 mg three times daily for consistency of our pharmacokinetic evaluations ( 33 ) . No additional protease inhibitors were allowed for the duration of the study . Participants were also required to have a stable viral load , defined as less than a threefold ( 0.5 log10 ) change in HIV RNA level for the 16 weeks before enrollment . All participants were required to have previous experience smoking marijuana ( defined as six or more times ) to ensure that they knew how to inhale and what neuropsychiatric effects to expect . The institutional review board of the University of California , San Francisco , approved the study , and signed , informed consent was obtained from each participant before enrollment . Exclusion criteria included any active opportunistic infection or malignant condition requiring acute treatment , unintentional loss of 10 % or more of body weight during the previous 6 months , current substance dependence ascertained by completion of a confidential drug screening form and an alcohol screening form , methadone maintenance , use of tobacco or cannabinoids ( smoked or oral ) within 30 days of enrollment , history of serious pulmonary disease , pregnancy , or stage II or higher AIDS dementia complex . Laboratory exclusion criteria were hematocrit less than 0.25 and elevation of hepatic aminotransferase levels to greater than five times the upper limit of normal . Therapeutic exclusions were concurrent use within the past 8 weeks of anabolic hormones , prednisone , interleukin-2 , or other agents known to alter immune system function . Study Medications The National Institute on Drug Abuse provided prerolled marijuana cigarettes , weighing on average 0.9 g and containing 3.95 % delta-9-tetrahydrocannabinol . These cigarettes were kept in a locked and alarmed freezer until they were dispensed to a locked freezer in the General Clinical Research Center at the San Francisco General Hospital , where the inpatient study was conducted . The frozen marijuana cigarettes required rehydration overnight in a humidifier . Participants r and omly assigned to the smoked marijuana group were housed in a room with a fan ventilating to the outside . To maximize st and ardization of inhaled doses , research staff monitored participants while they followed the uniform puff procedure outlined by Foltin and colleagues ( 34 ) . Research staff weighed the marijuana cigarettes immediately before and after they were administered to participants and returned all leftover material to the pharmacy . Study participants smoked up to three complete marijuana cigarettes daily , as tolerated , 1 hour before meals . Study participants were r and omly assigned in a double-blind fashion to the oral regimens , which were given on the same schedule as the smoked marijuana . Research staff observed participants taking all treatments . Research Design and Procedures Study clinicians admitted study participants to the General Clinical Research Center for a 4-day lead-in period to obtain baseline variables . A urine sample obtained on the day of admission ( day 4 ) had to be negative for tetrahydrocannabinol . The second phase of the trial was a 21-day intervention period beginning with r and om assignment of treatments on day 0 . Patients were stratified by protease inhibitor ( indinavir or nelfinavir ) and then allocated with equal probability in blocks of 12 to the study agents ( marijuana , dronabinol , and placebo ) . The statistician generated the r and om allocation sequences , and the pharmacists maintained the sequences in a secure location and distributed the assignments to the study coordinator on day 0 . Study participants were not permitted to have visitors or to leave the General Clinical Research Center unless accompanied by research personnel during the 25-day study . All clinical laboratory tests and study procedures were obtained or performed in the center . Patients were weighed on the same calibrated scale each morning while wearing a hospital gown . Baseline blood specimens were collected on days 4 and 0 to examine within-participant variation in HIV RNA level in the absence of experimental therapies . Follow-up specimens were obtained on days 2 , 5 , 8 , 11 , 14 , 17 , 19 , and 21 . Sample s were stored at 70 C and batch-tested for HIV RNA at the end Abstract Objective To evaluate the effect of the oral synthetic δ-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis . Design R and omised double blind placebo controlled crossovertrial . Setting Outpatient clinic , University Hospital of Aarhus , Denmark . Participants 24 patients aged between 23 and 55 years with multiple sclerosis and central pain . Intervention Orally administered dronabinol at a maximum doseof 10 mg daily or corresponding placebo for three weeks ( 15 - 21days ) , separated by a three week washout period . Main outcome measure Median spontaneous pain intensity ( numericalrating scale ) in the last week of treatment . Results Median spontaneous pain intensity was significantlylower during dronabinol treatment than during placebo treatment(4.0 ( 25th to 75th centiles 2.3 to 6.0 ) v 5.0 ( 4.0 to 6.4),P = 0.02 ) , and median pain relief score ( numerical rating scale)was higher ( 3.0 ( 0 to 6.7 ) v > 0 ( 0 to 2.3 ) , P = 0.035 ) . Thenumber needed to treat for 50 % pain relief was 3.5 ( 95 % confidenceinterval 1.9 to 24.8 ) . On the SF-36 quality of life scale , thetwo items bodily pain and mental health indicated benefits fromactive treatment compared with placebo . The number of patients with adverse events was higher during active treatment , especiallyin the first week of treatment . The functional ability of themultiple sclerosis patients did not change . Conclusions Dronabinol has a modest but clinical ly relevantanalgesic effect on central pain in patients with multiple sclerosis . Adverse events , including dizziness , were more frequent withdronabinol than with placebo during the first week of treatment The objective was to determine whether a cannabis-based medicinal extract ( CBME ) benefits a range of symptoms due to multiple sclerosis ( MS ) . A parallel group , double-blind , r and omized , placebo-controlled study was undertaken in three centres , recruiting 160 out patients with MS experiencing significant problems from at least one of the following : spasticity , spasms , bladder problems , tremor or pain . The interventions were oromucosal sprays of matched placebo , or whole plant CBME containing equal amounts of delta-9- tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) at a dose of 2.5- 120 mg of each daily , in divided doses . The primary outcome measure was a Visual Analogue Scale ( VAS ) score for each patient ’s most troublesome symptom . Additional measures included VAS scores of other symptoms , and measures of disability , cognition , mood , sleep and fatigue . Following CBME the primary symptom score reduced from mean ( SE ) 74.36 ( 11.1 ) to 48.89 ( 22.0 ) following CBME and from 74.31 ( 12.5 ) to 54.79 ( 26.3 ) following placebo [ ns ] . Spasticity VAS scores were significantly reduced by CBME ( Sativex ) in comparison with placebo ( P- 0.001 ) . There were no significant adverse effects on cognition or mood and intoxication was generally mild Objectives : To determine whether plant-derived cannabis medicinal extracts ( CME ) can alleviate neurogenic symptoms unresponsive to st and ard treatment , and to quantify adverse effects . Design : A consecutive series of double-blind , r and omized , placebo-controlled single-patient cross-over trials with two-week treatment periods . Setting : Patients attended as out patients , but took the CME at home . Subjects : Twenty-four patients with multiple sclerosis ( 18 ) , spinal cord injury ( 4 ) , brachial plexus damage ( 1 ) , and limb amputation due to neurofibromatosis ( 1 ) . Intervention : Whole-plant extracts of delta-9-tetrahydrocannabinol ( THC ) , cannabidiol ( CBD ) , 1:1 CBD : THC , or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5–120 mg/24 hours . Measures used : Patients recorded symptom , well-being and intoxication scores on a daily basis using visual analogue scales . At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales , administered st and ard measures of disability ( Barthel Index ) , mood and cognition , and recorded adverse events . Results : Pain relief associated with both THC and CBD was significantly superior to placebo . Impaired bladder control , muscle spasms and spasticity were improved by CME in some patients with these symptoms . Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME . Conclusions : Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to st and ard treatments . Unwanted effects are predictable and generally well tolerated . Larger scale studies are warranted to confirm these findings Objective : To test the effectiveness and long term safety of cannabinoids in multiple sclerosis ( MS ) , in a follow up to the main Cannabinoids in Multiple Sclerosis ( CAMS ) study . Methods : In total , 630 patients with stable MS with muscle spasticity from 33 UK centres were r and omised to receive oral Δ9-tetrahydrocannabinol ( Δ9-THC ) , cannabis extract , or placebo in the main 15 week CAMS study . The primary outcome was change in the Ashworth spasticity scale . Secondary outcomes were the Rivermead Mobility Index , timed 10 metre walk , UK Neurological Disability Score , postal Barthel Index , General Health Question naire-30 , and a series of nine category rating scales . Following the main study , patients were invited to continue medication , double blinded , for up to12 months in the follow up study reported here . Results : Intention to treat analysis of data from the 80 % of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months ( Δ9-THC mean reduction 1·82 ( n = 154 , 95 % confidence interval ( CI ) 0.53 to 3.12 ) , cannabis extract 0.10 ( n = 172 , 95 % CI −0.99 to 1.19 ) , placebo −0.23 ( n = 176 , 95 % CI −1.41 to 0.94 ) ; p = 0.04 unadjusted for ambulatory status and centre , p = 0.01 adjusted ) . There was suggestive evidence for treatment effects of Δ9-THC on some aspects of disability . There were no major safety concerns . Overall , patients felt that these drugs were helpful in treating their disease . Conclusions : These data provide limited evidence for a longer term treatment effect of cannabinoids . A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS Background : Central pain in multiple sclerosis ( MS ) is common and often refractory to treatment . Methods : We conducted a single-center , 5-week ( 1-week run-in , 4-week treatment ) , r and omized , double-blind , placebo-controlled , parallel-group trial in 66 patients with MS and central pain states ( 59 dysesthetic , seven painful spasms ) of a whole-plant cannabis-based medicine ( CBM ) , containing delta-9-tetrahydrocannabinol : cannabidiol ( THC : CBD ) delivered via an oromucosal spray , as adjunctive analgesic treatment . Each spray delivered 2.7 mg of THC and 2.5 of CBD , and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours . Results : Sixty-four patients ( 97 % ) completed the trial , 34 received CBM . In week 4 , the mean number of daily sprays taken of CBM ( n = 32 ) was 9.6 ( range 2 to 25 , SD = 6.0 ) and of placebo ( n = 31 ) was 19.1 ( range 1 to 47 , SD = 12.9 ) . Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale . CBM was superior to placebo in reducing the mean intensity of pain ( CBM mean change −2.7 , 95 % CI : −3.4 to −2.0 , placebo –1.4 95 % CI : −2.0 to −0.8 , comparison between groups , p = 0.005 ) and sleep disturbance ( CBM mean change –2.5 , 95 % CI : −3.4 to −1.7 , placebo –0.8 , 95 % CI : −1.5 to −0.1 , comparison between groups , p = 0.003 ) . CBM was generally well tolerated , although more patients on CBM than placebo reported dizziness , dry mouth , and somnolence . Cognitive side effects were limited to long-term memory storage . Conclusions : Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated Objective : Cannabis may alleviate some symptoms associated with multiple sclerosis ( MS ) . This study investigated the effect of an orally administered st and ardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity . Methods : During their inpatient rehabilitation programme , 57 patients were enrolled in a prospect i ve , r and omized , double-blind , placebo-controlled crossover study of cannabis-extract capsules st and ardized to 2.5 mg tetrahydrocannabinol ( THC ) and 0.9 mg cannabidiol ( CBD ) each . Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated , being on active medication for 14 days before starting placebo . Patients in group B started with placebo for seven days , crossed to the active period ( 14 days ) and closed with a three-day placebo period ( active drug dose escalation and placebo sham escalation as in group A ) . Measures used included daily self-report of spasm frequency and symptoms , Ashworth Scale , Rivermead Mobility Index , 10-m timed walk , nine-hole peg test , paced auditory serial addition test ( PASAT ) , and the digit span test . Results : In the 50 patients included into the intention-to-treat analysis set , there were no statistically significant differences associated with active treatment compared to placebo , but trends in favour of active treatment were seen for spasm frequency , mobility and getting to sleep . In the 37 patients ( per- protocol set ) who received at least 90 % of their prescribed dose , improvements in spasm frequency ( P- 0.013 ) and mobility after excluding a patient who fell and stopped walking were seen ( P- 0.01 ) . Minor adverse events were slightly more frequent and severe during active treatment , and toxicity symptoms , which were generally mild , were more pronounced in the active phase . Conclusion : A st and ardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs Objective : To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model . Methods : Prospect i ve r and omized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy . Patients were r and omly assigned to smoke either cannabis ( 3.56 % tetrahydrocannabinol ) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days . Primary outcome measures included ratings of chronic pain and the percentage achieving > 30 % reduction in pain intensity . Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model . Results : Fifty patients completed the entire trial . Smoked cannabis reduced daily pain by 34 % ( median reduction ; IQR = −71 , −16 ) vs 17 % ( IQR = −29 , 8) with placebo ( p = 0.03 ) . Greater than 30 % reduction in pain was reported by 52 % in the cannabis group and by 24 % in the placebo group ( p = 0.04 ) . The first cannabis cigarette reduced chronic pain by a median of 72 % vs 15 % with placebo ( p < 0.001 ) . Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli ( p ≤ 0.05 ) but appeared to have little effect on the painfulness of noxious heat stimulation . No serious adverse events were reported . Conclusion : Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy . The findings are comparable to oral drugs used for chronic neuropathic pain BACKGROUND Multiple sclerosis is associated with muscle stiffness , spasms , pain , and tremor . Much anecdotal evidence suggests that cannabinoids could help these symptoms . Our aim was to test the notion that cannabinoids have a beneficial effect on spasticity and other symptoms related to multiple sclerosis . METHODS We did a r and omised , placebo-controlled trial , to which we enrolled 667 patients with stable multiple sclerosis and muscle spasticity . 630 participants were treated at 33 UK centres with oral cannabis extract ( n=211 ) , Delta9-tetrahydrocannabinol ( Delta9-THC ; n=206 ) , or placebo ( n=213 ) . Trial duration was 15 weeks . Our primary outcome measure was change in overall spasticity scores , using the Ashworth scale . Analysis was by intention to treat . FINDINGS 611 of 630 patients were followed up for the primary endpoint . We noted no treatment effect of cannabinoids on the primary outcome ( p=0.40 ) . The estimated difference in mean reduction in total Ashworth score for participants taking cannabis extract compared with placebo was 0.32 ( 95 % CI -1.04 to 1.67 ) , and for those taking Delta9-THC versus placebo it was 0.94 ( -0.44 to 2.31 ) . There was evidence of a treatment effect on patient-reported spasticity and pain ( p=0.003 ) , with improvement in spasticity reported in 61 % ( n=121 , 95 % CI 54.6 - 68.2 ) , 60 % ( n=108 , 52.5 - 66.8 ) , and 46 % ( n=91 , 39.0 - 52.9 ) of participants on cannabis extract , Delta9-THC , and placebo , respectively . INTERPRETATION Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale . However , though there was a degree of unmasking among the patients in the active treatment groups , objective improvement in mobility and patients ' opinion of an improvement in pain suggest cannabinoids might be clinical ly useful & NA ; The objective was to investigate the effectiveness of cannabis‐based medicines for treatment of chronic pain associated with brachial plexus root avulsion . This condition is an excellent human model of central neuropathic pain as it represents an unusually homogenous group in terms of anatomical location of injury , pain descriptions and patient demographics . Forty‐eight patients with at least one avulsed root and baseline pain score of four or more on an 11‐point ordinate scale participated in a r and omised , double‐blind , placebo‐controlled , three period crossover study . All patients had intractable symptoms regardless of current analgesic therapy . Patients entered a baseline period of 2 weeks , followed by three , 2‐week treatment periods during each of which they received one of three oromucosal spray preparations . These were placebo and two whole plant extracts of Cannabis sativa L. : GW‐1000‐02 ( Sativex ® ) , containing Δ9tetrahydrocannabinol (THC):cannabidiol ( CBD ) in an approximate 1:1 ratio and GW‐2000‐02 , containing primarily THC . The primary outcome measure was the mean pain severity score during the last 7 days of treatment . Secondary outcome measures included pain related quality of life assessment s. The primary outcome measure failed to fall by the two points defined in our hypothesis . However , both this measure and measures of sleep showed statistically significant improvements . The study medications were generally well tolerated with the majority of adverse events , including intoxication type reactions , being mild to moderate in severity and resolving spontaneously . Studies of longer duration in neuropathic pain are required to confirm a clinical ly relevant , improvement in the treatment of this condition The administration of single oral doses of delta‐9‐tetrahydrocannabinol ( THC ) to patients with cancer pain demonstrated a mild analgesic effect . At a dose of 20 mg , however , THC induced side effects that would prohibit its therapeutic use including somnolence , dizziness , ataxia , and blurred vision . Alarming adverse reactions were also observed at this dose . THC , 10 mg , was well tolerated and , despite its sedative effect , may have analgesic potential OBJECTIVES To assess the efficacy of a cannabis-based medicine ( CBM ) in the treatment of pain due to rheumatoid arthritis ( RA ) . METHODS We compared a CBM ( Sativex ) with placebo in a r and omized , double-blind , parallel group study in 58 patients over 5 weeks of treatment . The CBM was administered by oromucosal spray in the evening and assessment s were made the following morning . Efficacy outcomes assessed were pain on movement , pain at rest , morning stiffness and sleep quality measured by a numerical rating scale , the Short-Form McGill Pain Question naire ( SF-MPQ ) and the DAS28 measure of disease activity . RESULTS Seventy-five patients were screened and 58 met the eligibility criteria . Thirty-one were r and omized to the CBM and 27 to placebo . Mean ( S.D. ) daily dose achieved in the final treatment week was 5.4 ( 0.84 ) actuations for the CBM and 5.3 ( 1.18 ) for placebo . In comparison with placebo , the CBM produced statistically significant improvements in pain on movement , pain at rest , quality of sleep , DAS28 and the SF-MPQ pain at present component . There was no effect on morning stiffness but baseline scores were low . The large majority of adverse effects were mild or moderate , and there were no adverse effect-related withdrawals or serious adverse effects in the active treatment group . CONCLUSIONS In the first ever controlled trial of a CBM in RA , a significant analgesic effect was observed and disease activity was significantly suppressed following Sativex treatment . Whilst the differences are small and variable across the population , they represent benefits of clinical relevance and show the need for more detailed investigation in this indication Abstract Cannabinoids are known to have analgesic properties . We evaluated the effect of oro‐mucosal sativex , ( THC : CBD ) , an endocannabinoid system modulator , on pain and allodynia , in 125 patients with neuropathic pain of peripheral origin in a five‐week , r and omised , double‐blind , placebo‐controlled , parallel design trial . Patients remained on their existing stable analgesia . A self‐titrating regimen was used to optimise drug administration . Sixty‐three patients were r and omised to receive sativex and 62 placebo . The mean reduction in pain intensity scores ( primary outcome measure ) was greater in patients receiving sativex than placebo ( mean adjusted scores −1.48 points vs. −0.52 points on a 0–10 Numerical Rating Scale ( p = 0.004 ; 95 % CI : −1.59 , −0.32 ) . Improvements in Neuropathic Pain Scale composite score ( p = 0.007 ) , sleep NRS ( p = 0.001 ) , dynamic allodynia ( p = 0.042 ) , punctate allodynia ( p = 0.021 ) , Pain Disability Index ( p = 0.003 ) and Patient ’s Global Impression of Change ( p < 0.001 ) were similarly greater on sativex vs. placebo . Sedative and gastrointestinal side effects were reported more commonly by patients on active medication . Of all participants , 18 % on sativex and 3 % on placebo withdrew during the study . An open‐label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks 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 Symptoms relating to spasticity are common in multiple sclerosis ( MS ) and can be difficult to treat . We have investigated the efficacy , safety and tolerability of a st and ardized oromucosal whole plant cannabis-based medicine ( CBM ) containing delta-9 tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) , upon spasticity in MS . A total of 189 subjects with definite MS and spasticity were r and omized to receive daily doses of active preparation ( n = 124 ) or placebo ( n = 65 ) in a double blind study over 6 weeks . The primary endpoint was the change in a daily subject-recorded Numerical Rating Scale of spasticity . Secondary endpoints included a measure of spasticity ( Ashworth Score ) and a subjective measure of spasm . The primary efficacy analysis on the intention to treat ( ITT ) population ( n = 184 ) showed the active preparation to be significantly superior ( P = 0.048 ) . Secondary efficacy measures were all in favour of active preparation but did not achieve statistical significance . The responder analysis favoured active preparation , 40 % of subjects achieved > 30 % benefit ( P = 0.014 ) . Eight withdrawals were attributed to adverse events ( AEs ) ; six were on active preparation and two on placebo . We conclude that this CBM may represent a useful new agent for treatment of the symptomatic relief of spasticity in MS Spasticity is a common neurologic condition in patients with multiple sclerosis , stroke , cerebral palsy or an injured spinal cord . Animal studies suggest that THC has an inhibitory effect on polysynaptic reflexes . Some spastic patients cl aim improvement after inhaling cannabis . We tested muscle tone , reflexes , strength and performed EMGs before and after double-blinded oral administration of either 10 or 5 mg THC or placebo . The blinded examiner correctly identified the trials in which the patients received THC in seven of nine cases . For the group , 10 mg THC significantly reduced spasticity by clinical measurement ( P less than 0.01 ) . Quadriceps EMG interference pattern was reduced in those four patients with primarily extensor spasticity . THC was administered to eight other patients with spasticity and other CNS lesions . Responses varied , but benefit was seen in three of three patients with " tonic spasms . " No benefit was noted in patients with cerebellar disease UNLABELLED A r and omized , double-blind , placebo-controlled trial was conducted to determine the benefit of nabilone in pain management and quality of life improvement in 40 patients with fibromyalgia . After a baseline assessment , subjects were titrated up on nabilone , from 0.5 mg PO at bedtime to 1 mg BID over 4 weeks or received a corresponding placebo . At the 2- and 4-week visits , the primary outcome measure , visual analog scale ( VAS ) for pain , and the secondary outcome measures , number of tender points , the average tender point pain threshold , and the Fibromyalgia Impact Question naire ( FIQ ) , were evaluated . After a 4-week washout period , subjects returned for re assessment of the outcome measures . There were no significant differences in population demographics between groups at baseline . There were significant decreases in the VAS ( -2.04 , P < .02 ) , FIQ ( -12.07 , P < .02 ) , and anxiety ( -1.67 , P < .02 ) in the nabilone treated group at 4 weeks . There were no significant improvements in the placebo group . The treatment group experienced more side effects per person at 2 and 4 weeks ( 1.58 , P < .02 and 1.54 , P < .05 ) , respectively . Nabilone appears to be a beneficial , well-tolerated treatment option for fibromyalgia patients , with significant benefits in pain relief and functional improvement . PERSPECTIVE To our knowledge , this is the first r and omized , controlled trial to assess the benefit of nabilone , a synthetic cannabinoid , on pain reduction and quality of life improvement in patients with fibromyalgia . As nabilone improved symptoms and was well-tolerated , it may be a useful adjunct for pain management in fibromyalgia From folk medicine and anecdotal reports it is known that Cannabis may reduce pain . In animal studies it has been shown that delta‐9‐tetrahydrocannabinol ( THC ) has antinociceptive effects or potentiates the antinociceptive effect of morphine . The aim of this study was to measure the analgesic effect of THC , morphine , and a THC‐morphine combination ( THC‐morphine ) in humans using experimental pain models . THC ( 20 mg ) , morphine ( 30 mg ) , THC‐morphine ( 20 mg THC+30 mg morphine ) , or placebo were given orally and as single doses . Twelve healthy volunteers were included in the r and omized , placebo‐controlled , double‐blinded , crossover study . The experimental pain tests ( order r and omized ) were heat , cold , pressure , single and repeated transcutaneous electrical stimulation . Additionally , reaction time , side‐effects ( visual analog scales ) , and vital functions were monitored . For the pharmacokinetic profiling , blood sample s were collected . THC did not significantly reduce pain . In the cold and heat tests it even produced hyperalgesia , which was completely neutralized by THC‐morphine . A slight additive analgesic effect could be observed for THC‐morphine in the electrical stimulation test . No analgesic effect result ed in the pressure and heat test , neither with THC nor THC‐morphine . Psychotropic and somatic side‐effects ( sleepiness , euphoria , anxiety , confusion , nausea , dizziness , etc . ) were common , but usually mild The antiemetic activity and side-effects of delta-9-tetrahydrocannabinol ( THC ) were evaluated in 116 patients ( median age 61 years ) receiving combined 5-fluorouracil and semustine ( methyl CCNU ) therapy for gastrointestinal carcinoma . In a double-blind study , patients were r and omized to receive THC , 15 mg orally three times a day , prochlorperazine , 10 mg orally three times a day , or placebo . The THC had superior antiemetic activity in comparison to placebo , but it showed no advantage over prochlorperazine . Central nervous system side-effects , however , were significantly more frequent and more severe with THC . With the dosage and schedule we used , and in our patient population of largely elderly adults , THC therapy result ed in an overall more unpleasant treatment experience than that noted with prochlorperazine or placebo . Although THC may have a role in preventing nausea and vomiting associated with cancer chemotherapy , this role must be more clearly defined before THC can be recommended for general use BACKGROUND Central neuropathic pain ( CNP ) , pain initiated or caused by a primary lesion or dysfunction of the central nervous system , occurs in ~28 % of patients with multiple sclerosis ( MS ) . Delta(9)-Tetrahydrocannabinol/cannabidiol ( THC/CBD ) , an endocannabinoid system modulator , has demonstrated efficacy for up to 4 weeks in r and omized controlled trials in the treatment of CNP in patients with MS . OBJECTIVE The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD ( Sativex ( R ) , GW Pharmaceuticals plc , Salisbury , United Kingdom ) oromucosal spray in CNP associated with MS . METHODS This uncontrolled , open-label trial was an indefinite- duration extension of a previously reported 5-week r and omized study in patients with MS and CNP . In the initial trial , patients were r and omized to placebo or THC/CBD . Patients were only required to maintain their existing analgesia in the r and omized study . In the open-label trial they could vary their other analgesia as required . All patients ( placebo and THC/CBD ) who completed the r and omized trial commenced the open-label follow-up on THC/CBD ( 27 mg/mL : 25 mg/mL ) . Patients titrated their dosage , maintaining their existing analgesia . The primary end point of the trial was the number , frequency , and type of adverse events ( AEs ) reported by patients . Secondary end points included changes from baseline in 11-point numerical rating scale ( NRS-11 ) neuropathic pain score , hematology and clinical chemistry test results , vital signs , trial drug usage , and intoxication visual analogue scale scores . RESULTS Sixty-six patients were enrolled in the r and omized trial ; 64 ( 97 % ) completed the r and omized trial and 63 ( 95 % ) entered the open-label extension ( race , white , 100 % ; sex , male , 14 [ 22 % ] ; mean [ SD ] age , 49 [ 8.4 ] years [ range , 27 - 71 years [ ) . The mean ( SD ) duration of open-label treatment was 463 ( 378 ) days ( median , 638 days ; range , 3 - 917 days ) , with 34 ( 54 % ) patients completing > 1 year of treatment with THC/CBD and 28 ( 44 % ) patients completing the open-label trial with a mean ( SD ) duration of treatment of 839 ( 42 ) days ( median , 845 days ; range , 701 - 917 days ) . Mean NRS-11 pain scores in the final week of the r and omized trial were 3.8 in the treatment group and 5.0 in the placebo group . In the 28 ( 44 % ) patients who completed the 2-year follow up , the mean ( SD ) NRS-11 pain score in the final week of treatment was 2.9 ( 2.0 ) ( range , 0 - 8.0 ) . Fifty-eight ( 92 % ) patients experienced > or = 1 treatment-related AE . These AEs were rated by the investigator as mild in 47 ( 75 % ) patients , moderate in 49 ( 78 % ) , and severe in 32 ( 51 % ) . The most commonly reported AEs were dizziness ( 27 % ) , nausea ( 18 % ) , and feeling intoxicated ( 11 % ) . Two treatment-related serious AEs ( ventricular bigeminy and circulatory collapse ) were judged to be treatment-related . Both serious AEs occurred in the same patient and resolved completely following a period of discontinuation . Eleven ( 17 % ) patients experienced oral discomfort , 4 persistently . Regular oral examinations revealed that 7 ( 11 % ) patients developed white buccal mucosal patches and 2 ( 3 % ) developed red buccal mucosal patches ; all cases were deemed mild and resolved . Seventeen ( 25 % ) patients withdrew due to AEs . The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial . CONCLUSIONS THC/CBD was effective , with no evidence of tolerance , in these select patients with CNP and MS who completed approximately 2 years of treatment ( n = 28 ) . Ninety-two percent of patients experienced an AE , the most common of which were dizziness and nausea . The majority of AEs were deemed to be of mild to moderate severity by the investigators A prospect i ve , r and omized and double-blinded trial of the comparative effects of delta-9-tetrahydrocannabinol ( THC ) and haloperidol ( H ) was begun in February 1980 . Patients were r and omized to initially receive either THC or haloperidol with cross-over to the other agent after two courses . All patients evaluated efficacy and toxicity of each agent and those patients completing the study expressed a preference for either THC or haloperidol . All patients are receiving chemotherapeutic agents known to induce severe vomiting ( cis-platinum , nitrogen mustard , or doxorubicin ) or have a history or retching with chemotherapy . Fifty-two patients are evaluable as of October , 1980 . THC and haloperidol were equally effective in controlling nausea and vomiting as judged by number of vomiting episodes , patient evaluation of efficacy , and patient preference . About 10 % of patients had complete control of vomiting and a third had less than five episodes . Patients failing one of the antiemetics had good control with the other about half the time . Toxicities from THC were less well tolerated than those from haloperidol , but most patients had no serious side effects . Nonoverlapping toxicities and efficacy raise the possibility that a combination of the agents might be worthwhile Abstract —The authors conducted a r and omized , double-blind , placebo-controlled , twofold crossover study in 16 patients with MS who presented with severe spasticity to investigate safety , tolerability , and efficacy of oral & Dgr;9-Tetrahydrocannabinol ( THC ) and Cannabis sativa plant extract . Both drugs were safe , but adverse events were more common with plant-extract treatment . Compared with placebo , neither THC nor plant-extract treatment reduced spasticity . Both THC and plant-extract treatment worsened the participant ’s global impression Although cannabinoids have anti‐hyperalgesic effects in animal models of nerve injury , there are currently very few prospect i ve trials of the efficacy of cannabinoids in neuropathic pain in humans . This open label prospect i ve study investigated the safety , tolerability and analgesic benefit of oral Δ‐9‐tetrahydrocannabinol ( THC ) titrated to a maximal dosage of 25 mg/day in 8 consecutive patients with chronic refractory neuropathic pain . Spontaneous ongoing and paroxysmal pain , allodynia and paresthesias were assessed . The sensory and affective components of pain using the McGill pain question naire , quality of life , mood , anxiety and functionality were also evaluated . Seven patients suffered from side effects necessitating premature arrest of the drug in 5 of them . THC ( mean dosage : 16.6 ± 6.5 mg/day ) did not induce any significant effects on ongoing and paroxysmal pain , allodynia , quality of life , anxiety/depression scores and functional impact of pain . These results do not support an overall benefit of THC in pain and quality of life in patients with refractory neuropathic pain Background : The long-term treatment of Parkinson disease ( PD ) may be complicated by the development of levodopa-induced dyskinesia . Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect . The authors conducted a r and omized , double-blind , placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD . Methods : A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia . Then a r and omized placebo-controlled crossover study ( RCT ) was performed , in which 19 PD patients were r and omized to receive oral cannabis extract followed by placebo or vice versa . Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase . The primary outcome measure was a change in Unified Parkinson ’s Disease Rating Scale ( UPDRS ) ( items 32 to 34 ) dyskinesia score . Secondary outcome measures included the Rush scale , Bain scale , tablet arm drawing task , and total UPDRS score following a levodopa challenge , as well as patient-completed measures of a dyskinesia activities of daily living ( ADL ) scale , the PDQ-39 , on-off diaries , and a range of category rating scales . Results : Seventeen patients completed the RCT . Cannabis was well tolerated , and had no pro- or antiparkinsonian action . There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS , or any of the secondary outcome measures . Conclusions : Orally administered cannabis extract result ed in no objective or subjective improvement in dyskinesias or parkinsonism Fifty-five patients harboring a variety of neoplasms and previously found to have severe nausea or emesis from antitumor drugs were given antiemetic prophylaxis in a double-blind , r and omized crossover fashion . delta 9-Tetrahydrocannabinol ( THC ) , prochlorperazine , and placebo were compared . Nausea was absent in 40 of 55 patients receiving THC , in 8 of 55 patients receiving prochlorperazine , and in 5 of 55 in the placebo group . THC appeared to be more efficacious in controlling the emesis associated with cyclophosphamide , 5-fluorouracil , and doxorubicin and less so for nitrogen mustard and the nitrosourea . THC appears to offer significant control of nausea in most patients and exceeds by far that provided by prochlorperazine ( P less than 0.005 ) STUDY DESIGN Open label study to determine drug dose for a r and omized double-blind placebo-controlled parallel study . OBJECTIVES To assess the efficacy and side effects of oral Delta(9)-tetrahydrocannabinol ( THC ) and rectal THC-hemisuccinate ( THC-HS ) in SCI patients . SETTING REHAB Basel , Switzerl and . METHOD Twenty-five patients with SCI were included in this three-phase study with individual dose adjustment , each consisting of 6 weeks . Twenty-two participants received oral THC open label starting with a single dose of 10 mg ( Phase 1 , completed by 15 patients ) . Eight subjects received rectal THC-HS ( Phase 2 , completed by seven patients ) . In Phase 3 , six patients were treated with oral THC and seven with placebo . Major outcome parameters were the spasticity sum score ( SSS ) using the Modified Ashworth Scale ( MAS ) and self-ratings of spasticity . RESULTS Mean daily doses were 31 mg with THC and 43 mg with THC-HS . Mean SSS for THC decreased significantly from 16.72 ( + /-7.60 ) at baseline to 8.92 ( + /-7.14 ) on day 43 . Similar improvement was seen with THC-HS . We observed a significant improvement of SSS with active drug ( P=0.001 ) in the seven subjects who received oral THC in Phase 1 and placebo in Phase 3 . Major reasons for drop out were increase of pain and psychological side effects . CONCLUSION THC is an effective and safe drug in the treatment of spasticity . At least 15 - 20 mg per day were needed to achieve a therapeutic effect |
1,744 | 29,643,479 | In conclusion , our meta- analysis suggests that the use of statins may reduce the risk of all-type dementia , AD , and MCI , but not of incident | We conducted a systematic review and meta- analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia , Alzheimer ’s disease ( AD ) , vascular dementia ( VaD ) , and mild cognitive impairment ( MCI ) . | Background Early-onset dementia is common in Down syndrome adults , who have trisomy 21 . The amyloid precursor protein gene is on chromosome 21 , and so is over-expressed in Down syndrome , leading to amyloid β ( Aβ ) over-production , a major upstream pathway leading to Alzheimer disease ( AD ) . Statins ( microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ) , have pleiotropic effects including potentially increasing brain amyloid clearance , making them plausible agents to reduce AD risk . Animal models , human observational studies , and small scale trials support this rationale , however , there are no AD primary prevention trials in Down syndrome adults . In this study we study aim to inform the design of a full-scale primary prevention trial . Methods / Design TOP-COG is a feasibility and pilot double-blind r and omized controlled trial ( RCT ) , with a nested qualitative study , conducted in the general community . About 60 Down syndrome adults , aged ≥50 will be included . The intervention is oral simvastatin 40 mg at night for 12 months , versus placebo . The primary endpoint is recruitment and retention rates . Secondary endpoints are ( 1 ) tolerability and safety ; ( 2 ) detection of the most sensitive neurocognitive instruments ; ( 3 ) perceptions of Down syndrome adults and caregivers on whether to participate , and assessment experiences ; ( 4 ) distributions of cognitive decline , adaptive behavior , general health/ quality of life , service use , caregiver strain , and sample size implication s ; ( 5 ) whether Aβ42/Aβ40 is a cognitive decline biomarker . We will describe percentages recruited from each source , the number of contacts to achieve this , plus recruitment rate by general population size . We will calculate summary statistics with 90 % confidence limits where appropriate , for each study outcome as a whole , by treatment group and in relation to baseline age , cognitive function , cholesterol and other characteristics . Changes over time will be summarized graphically . The sample size for a definitive RCT will be estimated under alternative assumptions . Discussion This study is important , as AD is a major problem for Down syndrome adults , for whom there are currently no effective preventions or treatments . It will also delineate the most suitable assessment instruments for this population . Recruitment of intellectually disabled adults is notoriously difficult , and we shall provide valuable information on this , informing future studies .Trial registration Current Controlled Trials IS RCT N Register ID : IS RCT N67338640 ( 17 November 2011 Summary Background The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . Methods Of 19 342 hypertensive patients ( aged 40–79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10 305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo . These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . Findings Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50–0.83 ] , p = 0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56–0.96 ] , p = 0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69–0.90 ] , p = 0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59–0.86 ] , p = 0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71–1.06 ] , p = 0.16 ) . Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . Interpretation The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines BACKGROUND Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals , their efficacy and safety in elderly people is not fully established . Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with , or at high risk of developing , cardiovascular disease and stroke . METHODS We did a r and omised controlled trial in which we assigned 5804 men ( n=2804 ) and women ( n=3000 ) aged 70 - 82 years with a history of , or risk factors for , vascular disease to pravastatin ( 40 mg per day ; n=2891 ) or placebo ( n=2913 ) . Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke . Analysis was by intention-to-treat . FINDINGS Pravastatin lowered LDL cholesterol concentrations by 34 % and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo ( hazard ratio 0.85 , 95 % CI 0.74 - 0.97 , p=0.014 ) . Coronary heart disease death and non-fatal myocardial infa rct ion risk was also reduced ( 0.81 , 0.69 - 0.94 , p=0.006 ) . Stroke risk was unaffected ( 1.03 , 0.81 - 1.31 , p=0.8 ) , but the hazard ratio for transient ischaemic attack was 0.75 ( 0.55 - 1.00 , p=0.051 ) . New cancer diagnoses were more frequent on pravastatin than on placebo ( 1.25 , 1.04 - 1.51 , p=0.020 ) . However , incorporation of this finding in a meta- analysis of all pravastatin and all statin trials showed no overall increase in risk . Mortality from coronary disease fell by 24 % ( p=0.043 ) in the pravastatin group . Pravastatin had no significant effect on cognitive function or disability . INTERPRETATION Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals . PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people Sleep disturbances and decrements of daytime performance have been attributed to HMG-CoA reductase inhibitors . As a rule , lipophilic compounds more readily cross the blood-brain barrier and are more likely to affect central nervous system function . The authors compared the effects of lovastatin ( 40 mg ) , a lipophilic compound , to pravastatin ( 40 mg ) , a hydrophilic compound , in a 6-week , double-blind , r and omized , placebo-controlled , three-way Latin square design , cross-over study on 22 men with hypercholesterolemia . Patients had LDL cholesterol of more than 165 mg/dL and triglyceride of less than 350 mg/dL after 6 weeks of a low-fat ( < 30 % ) , low-cholesterol ( < 300 mg/day ) diet . Compared with placebo , there were no significant effects of lovastatin or pravastatin on the following subjective and polysomnographic sleep measures : changes in total sleep time , time in each sleep stage , sleep efficiency , sleep latency , REM density , REM activity , and number of arousals . Similarly , there were no effects of the two drugs on measures of cognitive performance . A significant increase in the duration of nocturnal tumescence ( NPT ) was observed after 2 weeks of treatment with both study drugs . This effect was not significant after 6 weeks of treatment . Both lovastatin and pravastatin caused significant ( P < .05 compared with placebo ) decreases in total cholesterol ( by 20.9 and 20.6 % , respectively ) , LDL cholesterol ( by 27.8 and 29.9 % ) , and triglycerides ( by 13.6 and 3.7 % ) . Subjects ' HDL increased by 2.3 % with lovastatin ( NS ) and by 3.1 % with pravastatin ( P < .05 ) . Lipoprotein(a ) increased by 20.5 % with lovastatin and by 1.1 % with pravastatin ; these changes were not significantly different from placebo . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Few strategies are available for the prevention of cognitive impairment in elderly persons . Serum lipoprotein levels may be important predictors of cognitive function , and drugs that lower cholesterol may be effective for the prevention of cognitive impairment . OBJECTIVE To determine whether serum lipoprotein levels , the 4-year change in serum lipoprotein levels , and the use of statin drugs are associated with cognition in older women without dementia . DESIGN , SETTING , AND PARTICIPANTS An observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/progestin Replacement Study ( participants at 10 of 20 centers ) . MAIN OUTCOME MEASURE The Modified Mini-Mental State Examination was administered at the end of the study after 4 years of follow-up . Women whose score was less than 84 points ( > 1.5 SDs below the mean ) were classified as having cognitive impairment . Lipoprotein levels ( total , high-density lipoprotein , and low-density lipoprotein [ LDL ] cholesterol and triglycerides ) were measured at baseline and at the end of the study ; statin use was documented at each visit . RESULTS Compared with women in the lower quartiles , women in the highest LDL cholesterol quartile at cognitive testing had worse mean plus minus SD Modified Mini-Mental State Examination scores ( 93.7 plus minus 6.0 vs 91.9 plus minus 7.6 ; P = .002 ) and an increased likelihood of cognitive impairment ( adjusted odds ratio , 1.76 ; 95 % confidence interval , 1.04 - 2.97 ) . A reduction in the LDL cholesterol level during the 4 years tended to be associated with a lower odds of impairment ( adjusted odds ratio , 0.61 ; 95 % confidence interval , 0.36 - 1.03 ) compared with women whose levels increased . Higher total and LDL cholesterol levels , corrected for lipoprotein(a ) levels , were also associated with a worse Modified Mini-Mental State Examination score and a higher likelihood of impairment , whereas high-density lipoprotein cholesterol and triglyceride levels were not associated with cognition . Compared with nonusers , statin users had higher mean plus minus SD Modified Mini-Mental State Examination scores ( 92.7 plus minus 7.1 vs 93.7 plus minus 6.1 ; P = .02 ) and a trend for a lower likelihood of cognitive impairment ( odds ratio , 0.67 ; 95 % confidence interval , 0.42 - 1.05 ) , findings that seemed to be independent of lipid levels . CONCLUSIONS High LDL and total cholesterol levels are associated with cognitive impairment , and lowering these lipoprotein levels may be a strategy for preventing impairment . The association between statin use and better cognitive function in women without dementia requires further study The aim of this prospect i ve cohort study was to evaluate the effects of lipid lowering agent ( LLA ) intake on cognitive function in 6,830 community-dwelling elderly persons . Cognitive performance ( global cognitive functioning , visual memory , verbal fluency , psychomotor speed , and executive function ) , clinical diagnosis of dementia , and fibrate and statin use , were evaluated at baseline , and 2 , 4 , and 7 year follow-up . Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics , mental and physical health including vascular risk factors , and genetic vulnerability ( apolipoprotein E and cholesteryl ester transfer protein ) . For women but not men , fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only ( HR = 1.29 , 95 % CI = 1.09 - 1.54 , p = 0.004 ) , and did not increase risk for incident dementia . This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate ( HR = 1.39 , 95 % CI = 1.08 - 1.79 , p = 0.01 ) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment . For both genders , no significant associations were found between statins ( irrespective of their lipophilicity ) and either cognitive decline or dementia incidence . This prospect i ve study , adjusting for multiple confounders , found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia , but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory Background : Previously reported associations between statin use and incident dementia or cognitive decline have been inconsistent . We report the results from a 3-year prospect i ve study on the association of statin use on cognitive decline and incident dementia in elderly African Americans . Methods : A community-based cohort of 1,146 African Americans aged 70 and older living in Indianapolis , Indiana , was evaluated in 2001 and 2004 . The instrument used for cognitive assessment was the Community Screening Interview for Dementia ( CSI-D ) . Cognitive decline was defined as CSI-D scores measured at 2001 minus scores at 2004 . Measurements of low-density lipoprotein cholesterol ( LDL-C ) and C-reactive protein ( CRP ) were obtained from baseline blood sample s. Results : Adjusting for age at baseline , gender , education , and the possession of ApoE ε4 allele , baseline statin use was associated with less cognitive decline ( p = 0.0177 ) . There were no significant interactions of statin use when LDL-C and CRP were included . Logistic regression with the four independent variables showed that statin use may be associated with a reduction in incident dementia ( OR = 0.32 ; p = 0.0673 ) . Association with cognitive decline was less clear when investigating statin use over time . Significance remained only for those who discontinued prior to follow-up compared to continuous users or users who started after baseline . Conclusions : The relationship between statin use and cognitive decline is complex and subjected to unknown confounders . This effect may not be associated with the cholesterol lowering or anti-inflammatory action of statins . GLOSSARY : AD = Alzheimer disease ; ANCOVA = analysis of covariance ; BMI = body mass index ; CAMDEX = Cambridge Examination for Mental Disorders of the Elderly informant interview ; CERAD = Consortium to Establish a Registry for Alzheimer ’s Disease ; CHIF = Clinician Home-based Interview to assess Function ; CRP = C-reactive protein ; CSI-D = Community Screening Instrument for Dementia ; HDL = high-density lipoprotein ; HMG-CoA = 3-hydroxy-3-methylglutaryl-coenzyme A ; LDL-C = low-density lipoprotein cholesterol ; LLAs = lipid-lowering agents ; NSAIDs = nonsteroidal anti-inflammatory drugs BACKGROUND Prior reports suggest reduced occurrence of dementia and Alzheimer disease ( AD ) in statin users , but , to our knowledge , no prospect i ve studies relate statin use and dementia incidence . OBJECTIVE To examine the association of statin use with both prevalence and incidence of dementia and AD . DESIGN Cross-sectional studies of prevalence and incidence and a prospect i ve study of incidence of dementia and AD among 5092 elderly residents ( aged 65 years or older ) of a single county . Participants were assessed at home in 1995 - 1997 and again in 1998 - 2000 . A detailed visual inventory of medicines , including statins and other lipid-lowering agents , was collected at both assessment s. MAIN OUTCOME MEASURES Diagnosis of dementia and of AD . RESULTS From 4895 participants with data sufficient to determine cognitive status , we identified 355 cases of prevalent dementia ( 200 with AD ) at initial assessment . Statin use was inversely associated with prevalence of dementia ( adjusted odds ratio , 0.44 ; 95 % confidence interval , 0.17 - 0.94 ) . Three years later , we identified 185 cases of incident dementia ( 104 with AD ) among 3308 survivors at risk . Statin use at baseline did not predict incidence of dementia or AD ( adjusted hazard ratio for dementia , 1.19 ; 95 % confidence interval , 0.53 - 2.34 ; adjusted hazard ratio for AD , 1.19 ; 95 % confidence interval , 0.35 - 2.96 ) , nor did statin use at follow-up ( adjusted odds ratio for dementia , 1.04 ; 95 % confidence interval , 0.56 - 1.81 ; adjusted odds ratio for AD , 0.85 ; 95 % confidence interval , 0.32 - 1.88 ) . CONCLUSIONS Although statin use might be less frequent in those with prevalent dementia , we found no association between statin use and subsequent onset of dementia or AD . Further research is warranted before costly dementia prevention trials with statins are undertaken Background Existing information on breastfeeding in low income countries such as Nepal has been largely derived from cross-sectional demographic health surveys . This study investigated exclusive breastfeeding rates , and compared the duration of exclusive breastfeeding between rural and urban mothers in central Nepal using an alternate cohort methodology . Methods A community-based prospect i ve cohort study was conducted among 639 recently delivered mothers representative of the Kaski district of Nepal . Breastfeeding information was obtained at birth ( n = 639 ) , 4 weeks ( n = 639 ) , 12 weeks ( n = 615 ; 96.2 % ) and 22 weeks ( n = 515 ; 80.6 % ) through repeated interviews using vali date d question naires . Risk of cessation of exclusive breastfeeding was assessed by Cox regression analysis . Results The great majority of women received breastfeeding information ( 74 % ) and were encouraged to breastfeed by health personnel or family members ( 81 % ) . Although nearly all mothers ( 98 % ) breastfed up to six months , the reported exclusive breastfeeding rate declined rapidly from 90.9 % at birth to 29.7 % at 22 weeks . Urban women experienced significantly shorter ( p = 0.02 ) exclusive breastfeeding duration ( mean 104.5 , 95 % CI 95.8 to 113.1 days ) and were more likely to cease exclusive breastfeeding ( hazard ratio ( HR ) 1.28 , 95 % CI 1.03 to 1.60 ) than their rural counterparts ( mean 144.7 , 95 % CI 132.3 to 157.1 days ) . Breastfeeding problem ( HR 2.07 , 95 % CI 1.66 to 2.57 ) and caesarean delivery ( HR 1.88 , 95 % CI 1.36 to 2.62 ) were also significantly associated with exclusive breastfeeding cessation . Conclusions Despite the almost universal practice of breastfeeding , the reported exclusive breastfeeding rates declined substantially over time . Exclusive breastfeeding up to six months was more common in rural than urban areas of central Nepal . Urban mothers also exclusively breastfed shorter than rural mothers Background / Aims : Phospholipid transfer protein ( PLTP ) and apolipoprotein E ( apoE ) are key proteins involved in lipoprotein metabolism in the peripheral circulation and in the brain . Several epidemiological studies suggested that use of 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitors ( statins ) reduces risk of Alzheimer ’s disease ( AD ) . However , the effects of statins of differing blood-brain barrier ( BBB ) penetrability on brain-derived molecules in cognitively normal individuals are largely unknown . Methods : To assess the effect of statins on these indices as a function of BBB penetration , cerebrospinal fluid ( CSF ) and plasma PLTP activity and apoE concentration were measured in cognitively intact , modestly hypercholesterolemic adults r and omly allocated to treatment with either pravastatin , which does not penetrate BBB ( 80 mg/day , n = 13 ) , or simvastatin , which penetrates BBB ( 40 mg/day , n = 10 ) . Results : Simvastatin significantly increased CSF PLTP activity ( p = 0.005 ) . In contrast , pravastatin had no such effect . In the pravastatin-treated group , CSF apoE concentration decreased significantly ( p = 0.026 ) , while the simvastatin-treated group showed a tendency towards lower CSF apoE levels , with CSF apoE concentration lowered in 8 of 10 subjects . Conclusion : Our data indicate that statins differentially affect two key lipid transfer proteins in the brain , and that effect on PLTP activity depends on statin BBB penetrability Background : Cross-sectional reports suggest that statin users are less likely to have Alzheimer disease ( AD ) . Prospect i ve studies have provided inconsistent evidence . Moreover , it is unclear whether the association differs for lipohilic statins , those that could more easily pass the blood – brain barrier and hydrophilic statins . Objectives : To prospect ively evaluate whether use of statins is associated with the risk of AD , and to determine whether associations differ for lipophilic and hydrophilic statins . Method : 6992 participants of the prospect i ve , population -based Rotterdam Study were followed , from baseline ( 1990–1993 ) until January 2005 for incident AD . Data on all filled prescriptions came from pharmacy records . For each date on which each event occurred , cholesterol-lowering drug use for the person who experienced the event and all remaining persons in the cohort was categorised as “ any ” or “ never ” use . A distinction was made between statin , lipophilic and hydrophilic statins , and non-statin cholesterol-lowering drugs . Data were analysed with the Cox regression analysis , adjusting for sex , age and potential confounders . Results : During follow-up ( mean 9 years ) , 582 persons developed AD . Compared with never use of cholesterol-lowering drugs , statin use was associated with a decreased risk of AD ( HR 0.57 ; 95 % CI 0.37 to 0.90 ) , but non-statin cholesterol-lowering drug use was not ( HR 1.05 ; 95 % CI 0.45 to 2.44 ) . HRs were equal for lipophilic ( HR 0.54 ; 95 % CI 0.32 to 0.89 ) and hydrophilic statins ( HR 0.54 ; 95 % CI 0.26 to 1.11 ) . Conclusion : In the general population , the use of statins , but not of non-statin cholesterol-lowering drugs , was associated with a lower risk of AD compared with never use of cholesterol-lowering drugs . The protective effect was independent of the lipophilicity of statins AIMS To assess the effect of statins on a range of health outcomes . METHODS We undertook a population -based cohort study to assess the effect of statins on a range of health outcomes using a propensity score-based method to control for differences between people prescribed and not prescribed statins . We vali date d our design by comparing our results for vascular outcomes with the effects established in large r and omized trials . The study was based on the United Kingdom Health Improvement Network data base that includes the computerized medical records of over four and a half million patients . RESULTS People who initiated treatment with a statin ( n = 129,288 ) were compared with a matched sample of 600,241 people who did not initiate treatment , with a median follow-up period of 4.4 years . Statin use was not associated with an effect on a wide range of outcomes , including infections , fractures , venous thromboembolism , gastrointestinal haemorrhage , or on specific eye , neurological or autoimmune diseases . A protective effect against dementia was observed ( hazard ratio 0.80 , 99 % confidence interval 0.68 , 0.95 ) . There was no effect on the risk of cancer even after > or = 8 years of follow-up . The effect sizes for statins on vascular end-points and mortality were comparable to those observed in large r and omized trials , suggesting bias and confounding had been well controlled for . CONCLUSIONS We found little evidence to support wide-ranging effects of statins on health outcomes beyond their established beneficial effect on vascular disease Objective To quantify the unintended effects of statins according to type , dose , and duration of use . Design Prospect i ve open cohort study using routinely collected data . Setting 368 general practice s in Engl and and Wales supplying data to the Q Research data base . Participants 2 004 692 patients aged 30 - 84 years of whom 225 922 ( 10.7 % ) were new users of statins : 159 790 ( 70.7 % ) were prescribed simvastatin , 50 328 ( 22.3 % ) atorvastatin , 8103 ( 3.6 % ) pravastatin , 4497 ( 1.9 % ) rosuvastatin , and 3204 ( 1.4 % ) fluvastatin . Methods Cox proportional hazards models were used to estimate effects of statin type , dose , and duration of use . The number needed to treat ( NNT ) or number needed to harm ( NNH ) was calculated and numbers of additional or fewer cases estimated for 10 000 treated patients . Main outcome measure First recorded occurrence of cardiovascular disease , moderate or serious myopathic events , moderate or serious liver dysfunction , acute renal failure , venous thromboembolism , Parkinson ’s disease , dementia , rheumatoid arthritis , cataract , osteoporotic fracture , gastric cancer , oesophageal cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Results Individual statins were not significantly associated with risk of Parkinson ’s disease , rheumatoid arthritis , venous thromboembolism , dementia , osteoporotic fracture , gastric cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction , acute renal failure , moderate or serious myopathy , and cataract . Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin . A dose-response effect was apparent for acute renal failure and liver dysfunction . All increased risks persisted during treatment and were highest in the first year . After stopping treatment the risk of cataract returned to normal within a year in men and women . Risk of oesophageal cancer returned to normal within a year in women and within 1 - 3 years in men . Risk of acute renal failure returned to normal within 1 - 3 years in men and women , and liver dysfunction within 1 - 3 years in women and from three years in men . Based on the 20 % threshold for cardiovascular risk , for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 ( 95 % confidence interval 27 to 64 ) and for oesophageal cancer was 1266 ( 850 to 3460 ) and for men the respective values were 33 ( 24 to 57 ) and 1082 ( 711 to 2807 ) . In women the NNH for an additional case of acute renal failure over five years was 434 ( 284 to 783 ) , of moderate or severe myopathy was 259 ( 186 to 375 ) , of moderate or severe liver dysfunction was 136 ( 109 to 175 ) , and of cataract was 33 ( 28 to 38 ) . Overall , the NNHs and NNTs for men were similar to those for women , except for myopathy where the NNH was 91 ( 74 to 112 ) . Conclusions Cl aims of unintended benefits of statins , except for oesophageal cancer , remain unsubstantiated , although potential adverse effects at population level were confirmed and quantified . Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely Purpose Systemic exposure to rosuvastatin in Asian subjects living in Japan or Singapore is approximately twice that observed in Caucasian subjects in Western countries or in Singapore . This study was conducted to determine whether pharmacokinetic differences exist among the most populous Asian subgroups and Caucasian subjects in the USA . Method Rosuvastatin pharmacokinetics was studied in Chinese , Filipino , Asian-Indian , Korean , Vietnamese , Japanese and Caucasian subjects residing in California . Plasma concentrations of rosuvastatin and metabolites after a single 20-mg dose were determined by mass spectrometric detection . The influence of polymorphisms in SLCO1B1 ( T521>C [ Val174Ala ] and A388>G [ Asn130Asp ] ) and in ABCG2 ( C421>A [ Gln141Lys ] ) on exposure to rosuvastatin was also assessed . Results The average rosuvastatin area under the curve from time zero to time of last quantifiable concentration was between 64 and 84 % higher , and maximum drug concentration was between 70 and 98 % higher in East Asian subgroups compared with Caucasians . Data for Asian-Indians was intermediate to these two ethnic groups at 26 and 29 % , respectively . Similar increases in exposure to N-desmethyl rosuvastatin and rosuvastatin lactone were observed . Rosuvastatin exposure was higher in subjects carrying the SLCO1B1 521C allele compared with that in non-carriers of this allele . Similarly , exposure was higher in subjects carrying the ABCG2 421A allele compared with that in non-carriers . Conclusion Plasma exposure to rosuvastatin and its metabolites was significantly higher in Asian population s residing in the USA compared with Caucasian subjects living in the same environment . This study suggests that polymorphisms in the SLCO1B1 and ABCG2 genes contribute to the variability in rosuvastatin exposure BACKGROUND Lipid-lowering medications ( LLMs ) and especially statin drugs can delay cognitive decline and dementia onset in individuals with and without mild cognitive impairment ( MCI ) at baseline . METHODS A longitudinal , observational study was conducted of 3069 cognitively healthy elderly patients ( ≥75 years of age ) who were enrolled in the Ginkgo Evaluation of Memory Study . The primary outcome measure was the time to adjudicated all-cause dementia and Alzheimer dementia ( AD ) . The secondary outcome measure was the change in global cognitive function over time measured by scores from the Modified Mini-Mental State Exam ( 3MSE ) and the cognitive subscale of the AD Assessment Scale ( ADAS-Cog ) . RESULTS Among participants without MCI at baseline , the current use of statins was consistently associated with a reduced risk of all-cause dementia ( hazard ratio [ HR ] , 0.79 ; 95 % confidence interval [ 95 % CI ] , 0.65 - 0.96 ; P = .021 ) and AD ( HR , 0.57 ; 95 % CI , 0.39 - 0.85 ; P = .005 ) . In participants who initiated statin therapy , lipophilic statins tended to reduce dementia risk more than nonlipophilic agents . In contrast , there was no significant association between LLM use ( including statins ) , dementia onset , or cognitive decline in individuals with baseline MCI . However , in individuals without MCI at baseline , there was a trend for a neuroprotective effect of statins on cognitive decline . CONCLUSIONS Statins may slow the rate of cognitive decline and delay the onset of AD and all-cause dementia in cognitively healthy elderly individuals , whereas individuals with MCI may not have comparable cognitive protection from these agents . However , the results from this observational study need to be interpreted with caution and will require confirmation by r and omized clinical trials stratifying treatment groups based on MCI status at baseline The HMG‐CoA reductase inhibitors lovastatin and pravastatin have both proven to be effective and well tolerated in the treatment of hypercholesterolemia . To evaluate whether lovastatin or pravastatin might affect daytime cognitive function , a double‐blind , placebo‐controlled , two‐period , incomplete block , crossover study was performed in 36 patients ( 24 per treatment ) with primary hypercholesterolemia . Patients received placebo , Iovastatin ( 40 mg ) , or pravastatin ( 40 mg ) for 4 weeks . Following a 1‐week washout period , patients were crossed over to either lovastatin , pravastatin , or placebo for an additional 4 weeks . Mental performance tests ( digit symbol substitution , choice reaction time , auditory vigilance , selective reminding word recall , finger tapping ) , visual analogue rating scales , and the Profile of Mood States were administered before test drug administration and after 2 and 4 weeks of each treatment . After 4 weeks , no statistically significant differences between treatments in changes from baseline were observed on any parameter with the exception of digit symbol substitution , for which lovastatin and pravastatin were both significantly better than placebo but did not differ from each other . Low‐density lipoprotein cholesterol was reduced 38 % by lovastatin and 30 % by pravastatin . In summary , neither of these chemically distinct HMG‐CoA reductase inhibitors impaired daytime cognitive performance after 4 weeks of treatment in patients with primary hypercholesterolemia 1 . The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind , placebo-controlled , r and omised crossover study . 2 . Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin , 40 mg day-1 pravastatin or placebo for 4 weeks , separated by a 4 - 6 week washout phase . 3 . CNS measures included EEG evoked potentials , power spectral analysis , Leeds Sleep Question naire , Hospital Anxiety Depression ( HAD ) Scale , and Digit Symbol Substitution Test ( DSST ) ; biochemical measures included plasma cholesterol , liver enzymes ( gamma-GT , AST , ALT ) and creatine kinase . 4 . Mean cholesterol concentrations with both drugs were significantly lower than with placebo , and the cholesterol-lowering effect was greater with simvastatin . There were no significant differences between treatment in EEG evoked potentials , HAD Scale , or DSST scores . On the sleep measure , subjects reported significantly greater difficulty in getting to sleep while on simvastatin than on pravastatin , but neither score differed from placebo . No significant correlations were observed between sleep ratings and either plasma cholesterol concentrations or EEG evoked potentials . 5 . The study showed that , while both drugs reduced plasma cholesterol concentrations , neither exerted significant effects , compared with placebo , on EEG evoked potentials , mood , sleep , or cognitive performance after 4 weeks of chronic administration in healthy volunteers BACKGROUND AND OBJECTIVE Confounding bias is a most pervasive threat to validity of observational epidemiologic research . We assessed whether authors of observational epidemiologic studies consider confounding bias when interpreting the findings . STUDY DESIGN AND SETTING We r and omly selected 120 cohort or case-control studies published in 2011 and 2012 by the general medical , epidemiologic , and specialty journals with the highest impact factors . We used Web of Science to assess citation metrics through January 2017 . RESULTS Sixty-eight studies ( 56.7 % , 95 % confidence interval : 47.8 - 65.5 % ) mentioned " confounding " in the Abstract or Discussion sections , another 20 ( 16.7 % ; 10.0 - 23.3 % ) alluded to it , and there was no mention or allusion at all in 32 studies ( 26.7 % ; 18.8 - 34.6 % ) . Authors often acknowledged that for specific confounders , there was no adjustment ( 34 studies ; 28.3 % ) or deem it possible or likely that confounding affected their main findings ( 29 studies ; 24.2 % ) . However , only two studies ( 1.7 % ; 0 - 4.0 % ) specifically used the words " caution " or " cautious " for the interpretation because of confounding-related reasons and eventually only four studies ( 3.3 % ; 0.1 - 6.5 % ) had limitations related to confounding or any other bias in their Conclusions . Studies mentioning that the findings were possibly or likely affected by confounding were more frequently cited than studies with a statement that findings were unlikely affected ( median 6.3 vs. 4.0 citations per year , P = 0.04 ) . CONCLUSIONS Many observational studies lack satisfactory discussion of confounding bias . Even when confounding bias is mentioned , authors are typically confident that it is rather irrelevant to their findings and they rarely call for cautious interpretation . More careful acknowledgment of possible impact of confounding is not associated with lower citation impact OBJECTIVE To investigate the association between statin use , incident dementia , and Alzheimer disease ( AD ) in a prospect i ve elderly African American cohort . DESIGN Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period . Diagnoses of incident AD and dementia were made by consensus . Statin use was collected at each evaluation . Measurements of low-density lipoprotein cholesterol ( LDL ) , C-reactive protein ( CRP ) and APOE genotype were obtained from baseline blood sample s. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels . SETTING Indianapolis , Indiana . PARTICIPANTS From an original cohort of 2629 participants , a sub sample of 974 African Americans aged > 70 years with normal cognition , at least one follow up evaluation , complete statin information , and biomarker availability were included . MAIN OUTCOME MEASURES Incident dementia and incident AD . RESULTS After controlling for age at diagnosis , sex , education level , presence of the APOE ε4 allele and history of stroke for the incident dementia model , baseline use of statins was associated with a significantly decreased risk of incident dementia ( OR=.44 , P=.029 ) and incident AD ( OR=.40 , P=.029 ) . The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period ( incident AD : P=.034 ; incident dementia : P=.061 ) . Additional models found no significant interaction between baseline statin use , baseline LDL , or CRP level and incident dementia/AD . CONCLUSIONS Consistent use of statin medications during eight years of follow-up result ed in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia The effects of equi-efficacious doses of the cholesterol-lowering drugs simvastatin ( 20 mg day-1 ) and pravastatin ( 40 mg day-1 ) on tests of cognitive function were investigated in a double-blind , placebo-controlled , 2-period ( 4 weeks per period ) , incomplete block , crossover study of 36 patients ( 24 per treatment ) with hypercholesterolaemia . After 4 weeks neither of the active treatments differed significantly from placebo on any cognitive measure STUDY OBJECTIVE To examine the effect of atorvastatin on cognitive function by testing two hypotheses : that atorvastatin 10 mg/day would impair cognitive function , and that other biochemical and demographic measures would better predict cognitive performance than atorvastatin alone . DESIGN R and omized , double-blind , placebo-controlled study . SETTING Two primary acute care setting s in the north and northwest of Tasmania , Australia . PATIENTS Fifty-seven patients from the Lipid Lowering and Onset of Renal Disease ( LORD ) trial . INTERVENTION Participants were r and omly assigned to receive either atorvastatin 10 mg/day or matching placebo . Cognitive testing was performed in two sessions occurring 12 weeks apart and involved three repeated measures of attention and concentration . MEASUREMENTS AND MAIN RESULTS Performance was measured using three st and ard neuropsychological tests : Digit Symbol Coding subtest , Trail Making Test , and Stroop Color-Word Reading Test . Patients received atorvastatin for a mean of 72.93 weeks and placebo for a mean of 68.85 weeks . Repeated- measures multivariate analysis of variance failed to identify any significant differences between the two groups on any of the three cognitive measures . Multiple regression analyses identified no single factor or combination of plasma cholesterol levels , renal function , liver function , or age that predicted cognitive performance in either the atorvastatin or placebo group on the three measures at either testing session . CONCLUSION Atorvastatin 10 mg/day did not produce decrements to cognitive performance . In addition , biochemical and demographic measures and the receipt of atorvastatin versus placebo did not individually or in combination predict cognitive performance on measures of attention and concentration OBJECTIVES Evidence suggests inflammation is associated with cognitive impairment , but previous epidemiological studies have reported conflicting results . DESIGN Prospect i ve population -based cohort . SETTING Epidemiology of Hearing Loss Study participants . PARTICIPANTS Individuals without cognitive impairment in 1998 - 2000 ( N = 2,422 ; 1,947 with necessary data ) . MEASUREMENTS Cognitive impairment ( Mini-Mental State Examination score < 24 or diagnosis of dementia ) was ascertained in 1998 - 2000 , 2003 - 2005 , and 2009 - 2010 . Serum C-reactive protein ( CRP ) and interleukin-6 ( IL-6 ) were measured in 1988 - 1990 , 1998 - 2000 , and 2009 - 2010 ; tumor necrosis factor-alpha was measured from 1998 - 2000 . RESULTS Participants with high CRP in 1988 - 1990 and 1998 - 2000 had lower risk of cognitive impairment than those with low CRP at both time points ( hazard ratio ( HR ) = 0.46 , 95 % confidence interval ( CI ) = 0.26 - 0.80 ) . Risk did not differ according to 10-year IL-6 profile or baseline inflammation category in the whole cohort . In sensitivity analyses restricted to statin nonusers , those with high IL-6 at both times had greater risk of cognitive impairment than those with low IL-6 at both times ( HR = 3.35 , 95 % CI = 1.09 - 10.30 ) . In secondary analyses , each doubling of IL-6 change over 20 years was associated with greater odds of cognitive impairment in 2009 - 2010 in the whole cohort ( odds ratio ( OR ) = 1.40 , 95 % CI = 1.04 - 1.89 ) , whereas a doubling of CRP change over 20 years was associated with cognitive impairment only in statin nonusers ( OR = 1.32 , 95 % CI = 1.06 - 1.65 ) . CONCLUSION With data collected over 20 years , this study demonstrated greater likelihood of cognitive impairment in individuals with repeated high or increasing IL-6 . The inconsistent CRP findings may reflect effects of statin medications , survival effects , or adverse effects associated with chronically low CRP . Further studies of long-term inflammation and cognitive impairment are needed Abstract Introduction : Concerns about the effects of HMG-CoA reductase inhibitors ( ‘ statins ’ ) on health-related quality of life may contribute to their underuse in older adults with and at risk for cardiovascular disease . These concerns also may prevent clinicians from enrolling older patients in clinical trials assessing the efficacy of statins as a preventive therapy for Alzheimer ’s disease . Objective : To determine the effects of pravastatin and tocopherol ( vitamin E ) , alone and in combination , on health-related quality of life in older adults . Study design : Double-blind , r and omised , placebo-controlled , crossover study . Participants : Forty-one community-dwelling men and women aged ≥70 years with low-density lipoprotein-cholesterol ( LDL-C ) ≥3.62 mmol/L ( 140 mg/dl ) participated . Methods : Subjects received pravastatin for 6 months then pravastatin plus tocopherol for an additional 6 months ( group 1 ) , or tocopherol for 6 months then pravastatin plus tocopherol for an additional 6 months ( group 2 ) . Dosages were pravastatin 20 mg daily and tocopherol 400IU daily . Main outcome measures : The following health-related quality -of-life measures were assessed at baseline , after 6 months and after 1 year : health perception , depression , physical function , cognitive function and sleep behaviour . In addition , data on adverse effects and laboratory abnormalities were obtained . Results : Pravastatin reduced levels of total cholesterol ( −21 % , p < 0.001 ) and LDL-C ( −29 % , p < 0.001 ) . Health-related quality -of-life scores , physical adverse effects , muscle enzyme levels and liver function tests did not change after 12 months of therapy with pravastatin , tocopherol or their combination . Conclusion : Both pravastatin and tocopherol have a good safety profile , are well tolerated and do not adversely affect health-related quality of life in older patients with hypercholesterolaemia . Given the significant beneficial cardiovascular effects of statin therapy in older adults and the potential role of statins in prevention of Alzheimer ’s disease , concerns about adverse effects on quality of life should not deter use of these medications in this population Statins have been reported to reduce the risk and be of benefit in the treatment of Alzheimer 's disease ( AD ) . Individuals enrolling in the r and omized controlled trial testing two anti-inflammatory agents for primary prevention of AD ( Alzheimer 's Disease Anti-inflammatory Prevention Trial ; ADAPT ) were allowed the elective use of statins . Our objective was to assess whether statin use is associated with reduced risk of incident AD among ADAPT participants . In primary ADAPT study , participants were assessed annually for cholesterol levels and cognitive status . If impairment in cognition was noted , a dementia evaluation was performed . Onset of mild cognitive impairment ( MCI ) or AD was taken as the date of this evaluation . Time-to-onset was analyzed in six-month intervals following enrollment . Without knowledge of primary treatment assignment in ADAPT , participants were grouped by their self-reported use of lipid-lowering agents ( LLA ) . In the current ancillary ADAPT study we found that elective statin use was associated with significantly reduced risk of incident AD after adjustment for age , gender , education and Apolipoprotein E ( ApoE ) genotype . The findings were similar when comparing all LLA use ( statin and non-statin LLA ) to non-LLA use . Cholesterol levels were lower among statin users compared with non-LLA users , but the MMSE scores were equivalent . The data suggest that statin therapy may be of benefit in reducing the risk of AD BACKGROUND The relation between plasma lipid levels and Alzheimer disease ( AD ) and vascular dementia ( VaD ) , and the impact of drugs to lower lipid levels remains unclear . OBJECTIVE To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship . DESIGN AND SETTING Cross-sectional and prospect i ve community-based cohort studies . PARTICIPANTS R and om sample of 4316 Medicare recipients , 65 years and older , residing in northern Manhattan , NY . MAIN OUTCOME MEASURES Vascular dementia and AD according to st and ard criteria . RESULTS Elevated levels of non-high-density lipoprotein ( HDL-C ) and low-density lipoprotein cholesterol ( LDL-C ) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospect i ve analyses . Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics , apolipoprotein E genotype , and cardiovascular risk factors . Treatment with drugs to lower lipid levels did not change the disease risk of either disorder . CONCLUSIONS We found a weak relation between non-HDL-C , LDL-C , and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD Objective : To assess the association between statin therapy and risk of Alzheimer disease ( AD ) in a prospect i ve cohort study with documented statin exposure and incident dementia . Methods : This is a prospect i ve , cohort study of statin use and incident dementia and probable AD . A cohort of 2,356 cognitively intact persons , aged 65 and older , were r and omly selected from a health maintenance organization ( HMO ) , and were assessed biennially for dementia . Statin use was identified using the HMO pharmacy data base . A proportional hazards model with statin use as a time-dependent covariate was used to assess the statin – dementia/AD association . Results : Among 312 participants with incident dementia , 168 had probable AD . The unadjusted hazard ratios ( HRs ) with statin use were 1.33 ( 95 % CI 0.95 to 1.85 ) for all-cause dementia and 0.90 ( CI 0.54 to 1.51 ) for probable AD . Adjusted corresponding HRs were 1.19 ( CI 0.82 to 1.75 ) and 0.82 ( CI 0.46 to 1.46 ) . A subgroup analysis of participants with at least one APOE-ε4 allele who entered the study before age 80 produced an adjusted HR of 0.33 ( CI 0.10 to 1.04 ) . Conclusion : Employing time-dependent proportional hazards modeling , the authors found no significant association between statin use and incident dementia or probable AD . In contrast , when the data were analyzed , inappropriately , as a case-control study , the authors found an OR of 0.55 for probable AD , falsely indicating a protective effect of statins . Study design and analytic methods may explain the discrepancy between the current null findings and earlier findings |
1,745 | 22,762,301 | Overall , each drug lowered blood pressure in hypertensive patients in association with only small changes in heart rate ( i.e. < 1 beat/min ) .
Plasma norepinephrine concentrations , as the most widely reported marker of sympathetic nervous system activity , showed greater increases in patients treated with amlodipine than with nifedipine GITS .
The evidence indicates that both these once-daily dihydropyridine CCBs lower blood pressure effectively with minimal effects on heart rate .
There are small differences between the drugs in the extent to which each activates the sympathetic nervous system with an overall non-significant trend in favour of nifedipine GITS | Calcium-channel blockers ( CCBs ) constitute a diverse group of compounds but are often referred to as a single homogeneous class of drug and the clinical responses indiscriminately summarized .
Even within the dihydropyridine subgroup , there are significant differences in formulations , pharmacokinetics , duration s of action and their effects on blood pressure , heart rate , end organs and the sympathetic nervous system .
Amlodipine and nifedipine in the gastrointestinal therapeutic system ( GITS ) formulation are the most studied of the once-daily CCBs .
Amlodipine has an inherently long pharmacokinetic half-life , whereas , in contrast , nifedipine has an inherently short half-life but in the GITS formulation the sophisticated delivery system allows for once-daily dosing . | BACKGROUND Recent meta-analyses suggest that once-daily dihydropyridines and angiotensin-converting enzyme inhibitors cause similar decreases in left ventricular ( LV ) mass for comparable decreases in blood pressure ( BP ) . However , some dihydropyridines , such as felodipine-extended release ( ER ) , still increase sympathetic activity and may , therefore , be less effective in decreasing LV mass . OBJECTIVES To evaluate the effects of long term antihypertensive treatment with nifedipine-gastrointestinal therapeutic system ( GITS ) and felodipine-ER compared with enalapril on LV mass relative to the extent of BP control ( assessed by 24 h ambulatory BP monitoring ) and sympathetic activity ( assessed by plasma catecholamine concentrations ) . PATIENTS AND METHODS Enalapril was started at 10 mg/day , felodipine-ER at 5 mg/day and nifedipine-GITS at 30 mg/day , all once daily . Doses were increased to 20 mg/day , 10 mg/day or 60 mg/day , respectively , if the office BP remained 160/90 mmHg or greater at the end of the dosing interval . Evaluable echocardiograms were obtained for 116 patients at the end of the study ( 30 weeks of treatment ) . RESULTS On 24 h ambulatory BP monitoring , nifedipine-GITS caused a consistent decrease in BP throughout the 24 h dosing interval , whereas felodipine-ER caused a more marked fall in BP during the day , and enalapril 's effects diminished during the night and had disappeared by the morning . Only felodipine-ER significantly increased supine and st and ing plasma noradrenaline by more than 50 % similarly after six , 18 , and 30 weeks of treatment . In BP responders ( decrease in systolic BP 10 mmHg or greater ) , enalapril and nifedipine-GITS caused clear decreases in LV mass by 12 to 16 g/m2 , whereas felodipine-ER was less effective ( decrease by only 6 g/m2 , P<0.01 versus enalapril ) . CONCLUSIONS Once-daily dihydropyridines should not be regarded as one homogeneous class and , compared with felodipine-ER , nifedipine-GITS exhibits a better profile regarding 24 h BP control , sympathetic activation and regression of LV mass Objective To compare the effects of amlodipine and nifedipine on heart rate and parameters of sympathetic nerve activity during the acute and chronic treatment periods in order to eluci date their influence on cardiovascular outcome . Design A r and omized and single-blind study . Methods We performed 24 h ambulatory electrocardiography and blood pressure monitoring of 45 essential hypertensive in patients . Plasma and urinary catecholamine levels were measured during the control ( pretreatment ) period , on the first day ( acute period ) and after 4 weeks ( chronic period ) of administration of amlodipine and of short-acting nifedipine or its slow-releasing formulation . The low-frequency and high-frequency power spectral densities and low-frequency : high-frequency ratio were obtained by heart rate power spectral analysis . Results Blood pressure was significantly and similarly reduced by administrations of amlodipine , short-acting nifedipine and slow-releasing nifedipine during the chronic period . The total QRS count per 24 h , which remained constant during the chronic period of administration of slow-releasing nifedipine and was increased by administration of nifedipine , was decreased by 2.8 % by administration of amlodipine . Administration of amlodipine decreased the plasma and urinary norepinephrine levels during the chronic period , whereas the levels were significantly increased by administration of short-acting nifedipine and not changed by administration of slow-release nifedipine . Although low-frequency : high-frequency ratio was increased significantly by administration of short-acting nifedipine and slightly by administration of slow-releasing nifedipine , administration of amlodipine reduced it during the acute and chronic periods . Conclusions Administration of amlodipine did not induce an increase in sympathetic nerve activity in essential hypertensive patients during the chronic period , suggesting that beneficial effects on essential hypertension can be expected after its long-term administration . Administration of slow-releasing nifedipine induces milder reflex sympathetic activation than does that of short-acting nifedipine The sympathetic nervous system ( SNS ) is an important regulator of the circulation . Its activity is increased in hypertension and heart failure and adversely affects prognosis . Although certain drugs inhibit SNS , dihydropyridine calcium antagonists may stimulate the system . Phenylalkylamine calcium antagonists such as verapamil have a different pharmacological profile . We therefore tested the hypothesis of whether amlodipine , nifedipine , or verapamil differs in the effects on muscle sympathetic nerve activity ( MSA ) . Forty-three patients ( 31 men , 12 women ) with mild to moderate hypertension were r and omly assigned to 1 drug for 8 weeks . Blood pressure , heart rate , and MSA ( by microneurography ) were measured at baseline and after 8 weeks of treatment . All calcium antagonists led to a similar decrease in blood pressure of 5.0±1.5 to 6.4±1.4 mm Hg at 8 weeks ( P < 0.001 versus baseline ) . There were no significant differences in MSA between groups . With amlodipine , MSA averaged 49±3 bursts/min ( 3 versus baseline ) ; with nifedipine , 48±3 bursts/min ( 2 versus baseline ) ; and with verapamil , 49±2 bursts/min ( all , P = NS ) . With verapamil , norepinephrine decreased by 4 % but tended to increase by about one third with amlodipine or nifedipine ( P = NS ) . Thus , in hypertension slow release forms of verapamil , nifedipine , and amlodipine exert comparable antihypertensive effects and do not change MSA , although there was a trend toward decreased MSA and plasma norepinephrine with verapamil This study aim ed to compare the effects of two long-acting dihydropyridine calcium channel blockers ( CCBs ) with different pharmacologic properties , lercanidipine and nifedipine Gastro-Intestinal Therapeutic System ( GITS ) , in the chronic treatment of essential hypertension . After a 4-week placebo run-in period , 60 patients of both sexes were r and omly treated with lercanidipine 10 to 20 mg or nifedipine GITS 30 to 60 mg taken orally for 48 weeks , according to a double-blind , parallel group design . For the first 4 weeks of treatment , the lowest dose of each drug was used , followed by higher doses if diastolic blood pressure ( BP ) was > 90 mm Hg . At the end of the placebo period and after 4 , 8 , 12 , 24 , and 48 weeks of active treatment BP , heart rate ( HR ) , and plasma norepinephrine ( NE ) levels were assessed . Lercanidipine and nifedipine GITS similarly reduced BP values after 48 weeks ( -21.7/15.9 mm Hg and -20.7/14.6 mm Hg , respectively , both P < .001 v placebo ) , with no change in HR . Despite the similar lack of effect on HR , the two drugs displayed different influences on plasma NE , which was significantly increased by nifedipine GITS ( + 56 pg/mL , P < .05 v placebo ) but not by lercanidipine . These findings suggest that 1 ) sympathetic activation occurs during chronic therapy with nifedipine GITS but not with lercanidipine , which might be related to the different pharmacologic characteristics of the two CCBs at the doses evaluated ; and 2 ) nifedipine GITS seems to activate peripheral but not cardiac sympathetic nerves , consistent with differing regulation of cardiac and peripheral sympathetic activity Intravenous , sublingual , or aerosolized nitroglycerin was administered to 19 patients with coronary artery disease during clinical ly indicated cardiac catheterization . Eight blood sample s were collected over 15 min from each patient , and analyzed for content of nitroglycerin , 1,2‐glycerol dinitrate , and 1,3‐glycerol dinitrate . Simultaneously , heart rate ( HR ) , systolic blood pressure ( SBP ) , and left ventricular end‐diastolic pressure ( LVEDP ) were recorded . Plasma concentrations of nitroglycerin were highest after intravenous injection and lowest after sublingual tablets . Metabolite concentrations were highest after intravenous injection at early time‐points ; at later time‐points , no betweengroup differences could be detected . SBP was minimally affected by intravenous nitroglycerin but was significantly reduced by sublingual and aerosolized formulations . Minor fluctuations in HR were observed in association with all three formulations . LVEDP was reduced by all three formulations of nitroglycerin but most rapidly by the intravenous form . Overall , no differences were detected in hemodynamic responses caused by sublingual and aerosolized nitroglycerin . Efficacy of sublingual and aerosolized nitroglycerin in patients undergoing cardiac catheterization is equivalent Objective To compare the acute and chronic effects of nifedipine retard ( NPA ) , nifedipine gastrointestinal therapeutic system ( NGITS ) and amlodipine at trough and peak plasma concentrations of drug on blood pressure and heart rate , and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension ( diastolic blood pressure 95–115 mmHg ) . Design and methods After 3 - 4 weeks ' placebo treatment , patients of both sexes were r and omly allocated to be administered 10 or 20 mg NPA twice a day , 30 or 60 mg NGITS once a day , and 5 or 10 mg amlodipine once a day for 6 weeks . Initially , for the first 2 weeks , the lowest dose of each drug was used , but higher doses were administered after 2 weeks if sitting diastolic blood pressure was > 90 mmHg . Patients were evaluated after administration of the first dose and after 6 weeks ' therapy in a hospital setting . Blood sample s were taken for high-performance liquid chromatography measurement of catecholamine and drug levels at various intervals for a period covering trough to peak drug level ranges . Results Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks ' therapy , but heart rate was increased slightly only with amlodipine ( P < 0.05 ) . Administration of NPA reduced blood pressure more abruptly whereas administrations of NGITS and amlodipine induced smoother falls after acute and chronic treatments : a significant increase in heart rate was observed with amlodipine after chronic treatment . Both acute and chronic treatments with NPA ( n = 19 ) increased norepinephrine levels ( P < 0.01 ) transiently ( 2 - 4 h ) . In contrast , administration of NGITS ( n = 22 ) did not increase norepinephrine levels and even induced a slight but significant decrease in norepinephrine levels 5 - 6 h after chronic treatments . Although administration of amlodipine ( n = 22 ) did not increase norepinephrine levels transiently either after acute or after chronic administration , it did induce a sustained rise in basal norepinephrine levels by more than 50 % after chronic therapy ( P < 0.01 ) . Plasma epinephrine levels were not increased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine ( P < 0.05 ) . Conclusions The transient increase in norepinephrine levels observed with NPA and the sustained increases in norepinephrine levels observed after chronic treatment with amlodipine suggest that sympathetic activation occurs with those two drugs . The lack of increase in norepinephrine levels after administration of NGITS suggests that this formulation does not activate the sympathetic system . The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulations N-Type calcium channel antagonists may suppress sympathetic activity . The purpose of this study was to assess the effects of amlodipine and cilnidipine on the cardiac sympathetic nervous system and the neurohormonal status of essential hypertension . 123I-metaiodobenzylguanidine ( MIBG ) cardiac imaging was performed and blood sample s were taken to determine plasma renin activity and plasma norepinephrine concentration before and 3 months after drug administration in 47 patients with mild essential hypertension . Twenty-four of the patients were treated with 5 to 10 mg/d of amlodipine ; the other 23 were treated with 10 to 20 mg/d of cilnidipine . For comparison , 12 normotensive subjects were also studied . No significant differences were found in the basal characteristics between the 2 hypertensive groups . In both hypertensive groups , both the systolic and diastolic blood pressures were significantly reduced to similar levels 3 months after drug treatment . Before the drug treatment , the 2 hypertensive groups had a significantly higher washout rate and lower heart-to-mediastinum ( H/M ) ratio compared with the normotensive subjects . The H/M ratio significantly increased ( P<0.05 ) in combination with a decreased washout rate ( P<0.02 ) after drug treatment in the cilnidipine group . In the amlodipine group , a significant decrease in washout rate ( P<0 . 04 ) was noted , without an increase in the H/M ratio . However , no significant changes were found in plasma renin activity and plasma norepinephrine concentration in either group . Thus , in patients with essential hypertension , cilnidipine suppressed cardiac sympathetic overactivity and amlodipine had a little suppressive effect . Cilnidipine may provide a new strategy for treatment of cardiovascular diseases with sympathetic overactivity Dihydropyridine and nondihydropyridine calcium channel blockers ( CCB ) differ in pharmacologic characteristics . Few clinical studies distinguish effects of CCB as monotherapy . We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension . Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were r and omly assigned to either nifedipine-GITS or verapamil-SR . Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks . Clinic blood pressure ( BP ) , 24-h ambulatory BP , exercise BP , left ventricular mass , systolic and diastolic function by echocardiography , and coronary flow reserve by split-dose thallium-201 imaging with adenosine were assessed at baseline , end of titration , 3 months and 6 months of treatment . Plasma renin activity , atrial natriuretic peptide , norepinephrine , and epinephrine were assayed . Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index . Compared to nifedipine-GITS , verapamil-SR produced a significantly lower resting and peak exercise heart rate . Nifedipine-GITS elicited a lower peak exercise systolic BP . At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels , no longer apparent by 6 months . Plasma norepinephrine was lower with verapamil-SR , also at end titration and at 3 months , but not at 6 months . Plasma epinephrine and plasma renin activity were unchanged by either drug . There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments . Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension . Differences in their hemodynamic profiles and neurohormonal responses are consistent with pre clinical pharmacologic characteristics . The clinical implication s of their similarities and differences remain to be fully evaluated in outcome studies WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Pharmacokinetic and pharmacodynamics studies are usually carried out separately with theoretical linking or interpretations . The pharmacokinetics of short- vs. long-acting formulations of nifedipine is well known , but the pharmacokinetics of different once-a-day formulations of nifedipine is generally not well known by the practising physician . WHAT THIS STUDY ADDS This study provides practical patient-based information linking pharmacokinetics to pharmacodynamics in one of the target population s of patients , those with hypertension , who might receive the two different drugs . AIMS The haemodynamic responses to nifedipine vary between short- and long-acting formulations . However , the latter have not been compared despite marked differences in their constitution . Our 1-month r and omized , crossover study was design ed to compare the 30-mg osmotic , constant-release nifedipine gastrointestinal therapeutic system ( N-GITS ) with an encapsulated mini-tablet Coracten XL . METHODS Forty-four hypertensive patients aged 63 + /- 7 years were studied . The formulation was changed on day 15 and ( for a single dose ) day 30 . At days 0 , 14 , 15 , 29 and 30 , patients were monitored for 6 h after dosing , during which blood pressure ( BP ) , heart rate ( HR ) and plasma levels of norepinephrine ( NE ) and nifedipine were measured . The primary outcome was the difference in plasma NE between formulations at the time of peak nifedipine level . RESULTS Systolic BP decreased rapidly after the first dose of Coracten , achieving nadir at 5 h. HR rose by 1.2 + /- 8.8 beats min(-1 ) . After N-GITS HR fell by 2.4 + /- 7.7 beats min(-1 ) ( P = 0.159 ) . Plasma NE was higher in the Coracten- ( 480 + /- 38.3 pg ml(-1 ) ) than N-GITS-treated patients ( 343 + /- 75.0 pg ml(-1 ) ) at the time of peak nifedipine concentrations ( 4 and 5 h , respectively ) and their change from baseline was significantly ( P = 0.0046 ) different . A similar difference between the drugs was seen again at days 15 and 30 , at 5 h after switching formulations . CONCLUSIONS This study suggests that two different formulations of once-daily nifedipine result in different BP and plasma NE responses , and that switching between formulations causes opposite effects upon the sympathetic nervous response to falling BP 1 . The effects of 1,4‐dihydropyridine calcium antagonists with different biological half‐lives , amlodipine and nifedipine retard on 24 h blood pressure ( BP ) , heart rate ( HR ) and autonomic nerve activity in patients with essential hypertension were compared Objective To determine the effects of 8 weeks of therapy with amlodipine , ramipril or telmisartan on the autonomic system over 24 h in hypertensives . Methods After a placebo run-in , 57 patients were included in a prospect i ve r and omized open-label design protocol for therapy with amlodipine ( 5 mg for 4 weeks followed by 10 mg for 4 weeks , n = 22 ) , or ramipril ( 2.5 mg for 1 week , 5.0 mg for 3 weeks and 10 mg for 4 weeks , n = 17 ) or telmisartan ( 80 mg for 8 weeks , n = 18 ) . Autonomic functions were assessed by norepinephrine ( NE ) and epinephrine ( E ) , as well as by the spectral analysis of heart rate variability ( HRV ) . Results The 24-h ambulatory blood pressure , plasma NE and HRV demonstrated the characteristic day – night circadian rhythm in hypertensives . Higher values for SBP and DBP and for NE levels , as well as for spectral analysis components – low frequency b and ( LF ) and low frequency/high frequency ( LF/HF ) ratio – were found during the day , whereas the HF was higher during the night . In patients treated with amlodipine , the HF decreased significantly during the night , while the LF and the LF/HF ratio increased during the day in association with the rise in NE . The therapy with telmisartan did increase the HF during the night and the day , while ramipril did not influence all HRV components during the night but significantly increased the HF , and decreased the LF/HF ratio during the day . No changes were observed in plasma NE with telmisartan or ramipril , but a 50 % increase in NE levels throughout the 24-h period was found in amlodipine-treated patients . Conclusion These data suggest a sympathetic activation during the day and a decrease in parasympathetic activity during the night after therapy with amlodipine , correlated with increases in plasma NE . In contrast , the therapy with telmisartan significantly increased parasympathetic activity without changes in NE during the night and day . The therapy with ramipril increased the parasympathetic activity only during the day The differences between long-acting dihydropyridines and angiotensin-converting enzyme inhibitors with regard to their long-term effects on 24-h heart rate variability ( HRV ) and left ventricular ( LV ) mass are less clear in mild-to-moderate essential hypertension . We studied the long-term effects of amlodipine and fosinopril on 24-h HRV and LV mass in mild-to-moderate essential hypertension . In this study , 27 patients with never treated mild-to-moderate essential hypertension were r and omised to receive either amlodipine or fosinopril once daily as monotherapy . At baseline and at the end of the third and sixth months , each of the patients underwent 24-h HRV and ambulatory systolic ( SBP ) and diastolic ( DBP ) blood pressure analysis . LV mass index was calculated from echocardiographic examination at baseline and at the end of the sixth month . In amlodipine group ( n = 14 ) , 24-h SBP/DBP ( mmHg ) decreased from 144 + /- 8/94 + /- 4 to 128 + /- 6/83 + /- 3 at the end of the third month and to 125 + /- 5/81 + /- 2 at the end of the sixth month ( p < 0.0001 ) . In fosinopril group ( n = 13 ) , the respective changes were 143 + /- 9/97 + /- 7 , 132 + /- 6/87 + /- 5 and 127 + /- 6/82 + /- 3 ( p < 0.0001 ) . At the end of the sixth month , LV mass index ( g/m(2 ) ) decreased from 122 + /- 26 to 105 + /- 21 in amlodipine group ( p < 0.0001 ) and from 118 + /- 23 to 101 + /- 14 in fosinopril group ( p < 0.0001 ) . There were no significant changes in HRV parameters in both the groups . It was concluded that both drugs caused significant decrease in SBP and DBP , and LV mass in patients with mild-to-moderate essential hypertension did not have significant long-term effects of either amlodipine or fosinopril on 24-h HRV parameters reflecting sympathetic or parasympathetic activity in these patients We studied differences in the effects of a long-acting angiotensin-converting enzyme ( ACE ) inhibitor ( temocapril ) and a long-acting calcium channel blocker ( amlodipine ) on ventricular ectopic beats ( VEB ) in relation to sympathetic nerve activity in 46 patients with essential hypertension . We performed 24-h Holter electrocardiography and ambulatory blood pressure ( BP ) monitoring simultaneously , and examined blood sample s during the baseline , temocapril and amlodipine treatment periods . The ambulatory BP was lower in the amlodipine period than in the temocapril period . However , the number of VEB was significantly increased in the amlodipine period compared to that in the baseline period ( 11.9 vs. 7.4/day , p<0.05 ) . In the temocapril period , the number of VEB was not significantly increased compared to that in the baseline period ( 8.6 vs. 7.4/day , p=0.30 ) . Ambulatory heart rate ( HR ) was significantly increased in the amlodipine period compared to that in the baseline period ( 24-h HR : 70 vs. 66 bpm , p<0.001 ; daytime HR : 75 vs. 71 bpm , p<0.001 ; nocturnal HR : 60 vs. 58 bpm , p<0.05 ) . Plasma norepinephrine ( NE ) also was significantly increased in the amlodipine period compared to that in the baseline period ( 457 vs. 369 pg/ml , p<0.001 ) . However , when patients receiving amlodipine were divided into a high dose group ( 8.6 + /- 1.2 mg/day ) and a low dose group ( 4.6 + /- 1.2 mg/day ) , increases in HR and plasma NE levels were found only in the high dose group . These results indicate that amlodipine is effective at lowering BP in older hypertensives , although it may increase VEB , especially when given at a high dose AIMS To compare the effects of two long-acting calcium antagonists of different types on cardiovascular stress responses in hypertension . METHODS One-hundred and forty-five patients with mild to moderate hypertension and a mean ( + /- s.e.mean ) age of 51 + /- 0.9 years received for 8 weeks the phenylalkylamine verapamil sustained release ( 240 mg ) and the dihydropyridine amlodipine ( 5 mg ) in a double-blind cross-over design , both after 4 weeks of placebo . Blood pressure , heart rate and plasma noradrenaline were monitored during 3 min of sustained isometric h and grip and 2 min of cold pressor . RESULTS Blood pressure was equally reduced by both drugs . After 3 min h and grip , systolic blood pressure , heart rate and rate-pressure product were lower with verapamil compared with amlodipine . Verapamil attenuated the increases in systolic blood pressure ( 25 + /- 2 vs 30 + /- 2 mmHg , difference 4.6 , 95 % CI ( 1.0 , 8.1 ) , P < 0.01 ) and rate-pressure product ( 3.1 + /- 0.2 vs 3.6 + /- 0.3 x 10(3 ) mmHg x beats min(-1 ) , difference 0.5 , 95 % CI ( 0.1 , 0.9 ) , P < 0.01 ) during h and grip compared with amlodipine . Similar results were observed during cold pressor . Plasma noradrenaline levels were lower with verapamil compared with amlodipine at rest and after both tests , but the increases in plasma noradrenaline were not significantly different . CONCLUSIONS Verapamil is more effective in reducing blood pressure and rate-pressure product responses to stress compared with amlodipine . Although plasma noradrenaline is lower with verapamil at rest and after stress , the increase during stress is not different Twenty-four patients completed a double-blind , r and omized clinical trial comparing the effects of nifedipine GITS ( N ) and verapamil SR ( V ) on blood pressure ( BP ) control and exercise performance . After a 2-week placebo phase , all subjects had measurements of VO2max , maximal workload , and endurance time . They were then r and omized to either N ( 30 to 90 mg/day ) or V ( 240 to 480 mg/day ) and retested when BPs had stabilized . At rest , N lowered systolic ( S ) BP by 12 mm Hg ( P = .02 compared to baseline ) and diastolic ( D ) BP by 11 mm Hg ( P = .001 ) . V lowered SBP by 8 mm Hg ( P = .013 ) and DBP by 11 mm Hg ( P = .002 ) . Neither drug affected resting heart rate . V significantly decreased resting epinephrine ( P = .05 ) and there was a tendency for V to reduce norepinephrine ( P = .07 ) and dopamine ( P = .08 ) . N tended to increase plasma renin activity ( P = .07 ) . During grade d cycle ergometry N , compared with placebo , significantly lowered DBP at all exercise levels ( P = .011 ) , but had no significant effect on heart rate ( HR ) , SBP , or heart rate pressure product ( HRPP ) . Pulse pressure ( PP ) was significantly increased ( P = .045 ) , which was most noticeable at high exercise levels . Compared with placebo , V caused a marked reduction of exercise HR ( P < .001 ) , which was more pronounced at high levels , SBP ( P = .004 ) , DBP ( P = .004 ) , mean arterial pressure ( MAP ) ( P = .001 ) , and HRPP ( P < .001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Objective The aim of this study was to compare the chronic effects of four dihydropyridine calcium antagonists with different pharmacologic characteristics , amlodipine , felodipine , lacidipine and manidipine , on blood pressure ( BP ) , heart rate ( HR ) and plasma norepinephrine ( NE ) levels in patients with mild to moderate essential hypertension . Method After a 4-week placebo period , 60 patients of both sexes were r and omly administered amlodipine 5–10 mg once daily ( o.d . ) ( n = 15 ) ; felodipine 5–10 mg o.d . ( n = 15 ) ; lacidipine 4–6 mg o.d . ( n = 15 ) ; manidipine 10–20 mg o.d . ( n = 15 ) , for 24 weeks , according to a double blind , parallel group design . Initially , for the first 2 weeks , the lowest dose of each drug was used , then higher doses were administered if sitting diastolic blood pressure ( DBP ) was > 90 mmHg . BP , HR and plasma NE were evaluated at the end of the placebo and active treatment periods . NE was assessed at trough , at peak and after 12 h from drug ingestion . Results Administration of all four drugs reduced clinic BP to the same level after 24 weeks , whereas HR increased only with felodipine ( + 3.1 bpm ; P < 0.05 ) . Significant increases in plasma NE levels were observed after chronic therapy with amlodipine and felodipine ( + 34.9 and + 39.4 % respectively ; P < 0.01 versus placebo ) but not with lacidipine ( + 7.1 % , NS ) and manidipine ( + 2.9 % , NS ) . Conclusions These findings suggest that sympathetic activation occurred during chronic treatment with amlodipine and felodipine , whereas manidipine and lacidipine did not increase plasma noradrenaline at the times measured . The reasons for this difference are unclear ; they could be related to the different pharmacological characteristic of the two drugs , lacidipine and manidipine BACKGROUND The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established . We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension . METHODS We did a prospect i ve , r and omised , double-blind trial in Europe and Israel in 6321 patients aged 55 - 80 years with hypertension ( blood pressure > or = 150/95 mm Hg , or > or = 160 mm Hg systolic ) . Patients had at least one additional cardiovascular risk factor . We r and omly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system ( GITS ) formulation ( n=3157 ) , or co-amilozide ( hydrochlorothiazide 25 mg [ corrected ] plus amiloride 2.5 mg ; n=3164 ) . Dose titration was by dose doubling , and addition of atenolol 25 - 50 mg or enalapril 5 - 10 mg . The primary outcome was cardiovascular death , myocardial infa rct ion , heart failure , or stroke . Analysis was done by intention to treat . FINDINGS Primary outcomes occurred in 200 ( 6.3 % ) patients in the nifedipine group and in 182 ( 5.8 % ) in the co-amilozide group ( 18.2 vs 16.5 events per 1000 patient-years ; relative risk 1.10 [ 95 % CI 0.91 - 1.34 ] , p=0.35 ) . Overall mean blood pressure fell from 173/99 mm Hg ( SD 14/8 ) to 138/82 mm Hg ( 12/7 ) . There was an 8 % excess of withdrawals from the nifedipine group because of peripheral oedema ( 725 vs 518 , p<0.0001 ) , but serious adverse events were more frequent in the co-amilozide group ( 880 vs 796 , p=0.02 ) . Deaths were mainly non-vascular ( nifedipine 176 vs co-amilozide 172 ; p=0.81 ) . 80 % of the primary events occurred in patients receiving r and omised treatment ( 157 nifedipine , 147 co-amilozide , difference 0.33 % [ -0.7 to 1.4 ] ) . INTERPRETATION Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications . The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy To compare the effects of valsartan and amlodipine alone or in combination on plasma norepinephrine ( NE ) at rest and st and ing for 10 minutes in patients with hypertension , 47 patients with a sitting diastolic blood pressure ( BP ) (DBP)>95 mm Hg and < 110 mm Hg were r and omized in a double-blind fashion to either valsartan or amlodipine . During the first 4 weeks of treatment , patients received a low dose of either valsartan ( 80 mg ) or amlodipine ( 5 mg ) . The patients were force-titrated to the high dose of either drug ( 160 or 10 mg ) for 4 weeks . After 8 weeks of therapy , those who still had a DBP>90 mm Hg ( nonresponders ) received combination therapy with the other drug , whereas patients with a DBP<90 mm Hg ( responders ) continued on monotherapy . Decreases in ambulatory BP and clinic systolic BP and DBP were significant ( P<.05 ) after 8 weeks ' therapy with no difference between the 2 groups . Amlodipine but not valsartan as monotherapy consistently increased NE levels at rest and enhanced NE levels during st and ing . Valsartan decreased basal NE in responders . Combination therapy with valsartan and amlodipine did not attenuate the rise in NE levels induced by amlodipine . This study indicates that therapy with amlodipine increases peripheral sympathetic basal tone and reactivity to st and ing in patients with hypertension , whereas valsartan does not . Combined therapy with amlodipine/valsartan did not attenuate the sympathetic activation induced by amlodipine . The hypotensive action of valsartan may be mediated in part by an inhibition of the sympathetic baroreflex in patients with hypertension CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P<.001 ) groups compared with chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P<.001 ) . For amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy Summary : This study compared the effects of amlodipine and valsartan on the sympathetic nervous system , the renin‐angiotensin‐ aldosterone system , and brain natriuretic peptide , which are considered important parameters of the long‐term prognosis . Seventythree elderly patients , who had received antihypertensive treatment for more than 6 months with amlodipine , participated in this study . They were r and omized to the V group ( n = 36 ) and switched to valsartan from amlodipine , or to the A group ( n = 37 ) , which continued treatment with amlodipine . The dose of valsartan was set as that which controlled the blood pressure to the same extent as before switching . Blood sample s were measured before and after 6 months of therapy . Data were analyzed by two‐way analysis of variance with the Newman‐Keuls test . In the V group , norepinephrine ( from 597.0 ± 52.9 to 475 ± 43.8 pg/ml , p < 0.05 ) and aldosterone ( from 74.5 ± 7.0 to 53.9 ± 5.3 pg/ml , p < 0.001 ) were decreased significantly after 6 months , although norepinephrine and aldosterone levels were unchanged in the A group . However , brain natriuretic peptide did not show a difference between the two groups . These findings suggested that valsartan is probably superior to amlodipine with respect to less activation of the sympathetic nervous system and preventing upregulation of the renin‐angiotensin‐aldosterone system Background Dihydropyridines have both sympathoexcitatory and sympathoinhibitory effects . To date , the latter have been characterized only in animals . During chronic treatment with long-acting dihydropyridines , sympathoexcitatory effects mediated via the arterial baroreflex are unlikely . However , increases in plasma angiotensin II in response to dihydropyridines could contribute to increases in sympathetic activity during chronic treatment . Such increases may be less in older than in young patients . Methods We evaluated the effects of 4 weeks of treatment with low-dose nifedipine gastrointestinal therapeutic system ( GITS ; 20 mg/day ) compared with placebo on muscle sympathetic nerve activity and plasma noradrenaline , in relation to changes in plasma renin activity and plasma angiotensin II and blood pressure in young and older patients with mild hypertension . Results Nifedipine GITS decreased systolic and diastolic blood pressures significantly , by 10 ± 3 mmHg and 7 ± 2 mmHg respectively , in older patients ( age 67 ± 2 years ) , but not in younger patients ( age 45 ± 2 years ) ( decreases of 1 ± 3 mmHg and 1 ± 2 mmHg , respectively ) . Nifedipine GITS caused only minor changes in plasma renin activity and plasma angiotensin II in young and older patients . Compared with changes in response to placebo ( −5.7 ± 2.4 bursts/min ) , sympathetic activity was increased significantly by nifedipine GITS in the young patients ( 2.0 ± 1.7 bursts/min ; P < 0.05 ) , but not in older patients ( 5.4 ± 1.3 bursts/min by placebo compared with 4.1 ± 3.5 bursts/min by nifedipine GITS ) . Conclusion We conclude that age-related differences in the response of muscle sympathetic nerve activity ( and plasma noradrenaline ) to low-dose nifedipine GITS in patients with mild hypertension are unlikely to be mediated by plasma angiotensin II . An increase in sympathetic activity may contribute to the absent blood pressure response in young patients with hypertension Background : Many studies have shown that autonomic activation is one of the major factors in the etiology of hypertension . Furthermore , sympathovagal imbalance may be responsible for arrhythmias and sudden cardiac death . The aim of the present study was to compare and to evaluate the effects of short-term therapy with amlodipine and verapamil on heart rate variability ( HRV ) in patients with essential hypertension . Methods : Forty patients with essential hypertension ( 11 men and 29 women , mean age 50.5+/-10.4 years ) were included in the study . Patients with cardiac , metabolic , or any other systemic disease were excluded . Patients were r and omized to receive either amlodipine ( 10 mg ; n=20 ) or verapamil ( 240 mg ; n=20 ) . Patients underwent 24-h Holter monitoring assessment before treatment and after the 4-week treatment period . St and ard deviation of normal RR intervals ( SDNN ) , st and ard deviation of all 5-min mean normal RR intervals ( SDANN ) , square root of the mean of the sum of the squares of differences between adjacent RR intervals ( r-MSSD ) , and pNN50 ( time domain variables ) and TF , high-frequency power ( HF ) , low-frequency power ( LF ) , and sympathovagal balance ( LF/HF ; frequency domain variables ) were analyzed before and after treatment . Results : Blood pressure ( BP ) was reduced to a similar degree , from 182/104 to 128/85 mmHg with verapamil and from 174/100 to 124/86 mmHg with amlodipine ( verapamil p<0.001 ; amlodipine p<0.001 ) . This study revealed that amlodipine had no significant effect on any of the time or frequency domain parameters . In contrast , in patients on verapamil , there were significant increases in all time domain parameters , and the LF/HF ratio was significantly decreased ( p<0.05 ) . Conclusions : These results suggest that verapamil may have additional positive effects on sympathico-parasympathetic control beyond lowering blood pressure compared with amlodipine , even after short-term treatment in hypertensive patients Background L-type dihydropyridine calcium channel blockers ( CCBs ) have been implicated in increased cardiovascular events in patients with hypertension , perhaps due to adverse effects on autonomic nervous system ( ANS ) function . Blockade of T-type calcium channels may limit ANS dysfunction by inhibition of T channel-mediated neuroendocrine effects . Objective and design This double-blind , parallel group study compared the effect of nifedipine gastrointestinal transport system ( GITS ) ( L-type CCB ) versus mibefradil ( T-type CCB ) on ANS function in patients with mild – moderate essential hypertension . Methods Sixteen patients ( 10 male , 6 female ; age 57.2 ± 2.3 years ) , diastolic blood pressure ( DBP ) < 95 mmHg were r and omized to nifedipine 30 mg daily or mibefradil 50 mg daily ( 2 weeks ) , then nifedipine 60 mg daily or mibefradil 100 mg daily ( 4 weeks ) . Sympathetic nervous system activity ( SNSA ) was assessed using norepinephrine kinetics . Parasympathetic nervous system activity ( PSNA ) was assessed from 24 h Holter recordings of heart rate variability ( HRV ) . Non-invasive baroreflex sensitivity ( BRS ) provided integrated assessment of ANS . Results Patient groups were well matched at baseline . Achieved DBP was lower in patients treated with mibefradil compared with nifedipine , ( 83.4 ± 1.7 versus 95.25 ± 3.3 mmHg ) . There were no significant differences in SNSA and BRS between groups , however the root mean square of successive differences and high frequency power ( HFP ) were increased in mibefradil compared with nifedipine-treated patients [ ( + 1.07 ± 1.6 versus −3.36 ± 1.2 ms , P < 0.05 ) and ( + 0.28 ± 0.1 versus −0.23 ± 0.1 ms2 , P < 0.01 ) , respectively ] . Furthermore , Ln HFP/Ln total power was increased from week 0 to week 6 in the mibefradil-treated group , ( 0.71 ± 0.02 versus 0.74 ± 0.03 , P = 0.046 ) . Conclusion No differences existed between effect of L- and T-type CCBs on SNSA and BRS . However , T-type CCBs increased PSNA , independent of achieved changes in heart rate Abstract Management of systemic hypertension with calcium antagonists is gaining increasing acceptance . 1 Anti-hypertensive therapy with these agents , however , is limited by frequent adverse effects and need for frequent daily doses . Amlodipine is a new dihydropyridine derivative currently undergoing evaluation for therapy of hypertension . Although qualitatively similar to nifedipine , amlodipine has a longer duration of action and may be useful as a single daily dose . 2 This study evaluated effects of different doses of amlodipine given once daily to patients with mild to moderate hypertension . Its effects on adrenergic response to isometric exercise 3 and plasma levels of catecholamines and lipids were also evaluated SUMMARY The pharmacokinetics and antihypertensive effects of the nifedipine tablet and capsule have been examined in six male patients with diastolic pressure > 95 mm Hg despite metoprolol therapy . On two separate mornings , a 20 mg nifedipine tablet or 2 ± 10 mg nifedipine capsules were administered with metoprolol 100 mg following a 12-h fast . Both capsule and tablet significantly reduced blood pressure ( BP ) , with the maximum fall occurring at 45 min for the capsule and 4 h for the tablet . Two patients developed postural hypotension after the capsule and a third experienced flushing and palpitations . The maximum nifedipine plasma concentration after the capsule was 257 ng/ml compared with 50 ng/ml for the tablet , and the time of maximum concentration was significantly earlier for the capsule . Although the nifedipine capsule results in a fivefold higher maximum plasma concentration and is associated with a more rapid reduction in blood pressure than the tablet , its use may be limited by postural hypotension and other untoward symptoms BACKGROUND Angiotensin II-mediated increases in sympathetic activity may contribute to smaller blood-pressure decreases in response to dihydropyridines in young versus older hypertensive patients . We evaluated whether quinapril unmasks angiotensin II-dependent sympathetic activity on amlodipine . METHODS In this double-blind , r and omized , clinical trial , young mild hypertensives were r and omized to quinapril for 1 week ( study 1 ) , followed by quinapril + amlodipine for 6 weeks ( study 2 ) , followed by amlodipine + placebo for 6 weeks ( study 3 ) , or else were r and omized to placebo for 1 week ( study 1 ) , followed by placebo + amlodipine for 6 weeks ( study 2 ) , followed by amlodipine + quinapril for 6 weeks ( study 3 ) . Muscle sympathetic nerve activity ( MSNA ) and plasma hormones were analyzed at the end of each treatment period . Twenty-one subjects completed this study . RESULTS Quinapril alone decreased BP by 8 + /- 3/6 + /- 3 ( mean + /- SD ) mm Hg , and amlodipine alone decreased BP by 6 + /- 3/4 + /- 2 ( mean + /- SD ) . Quinapril combined with amlodipine caused a drop of 13 + /- 3/13 + /- 3 ( mean + /- SD ) mm Hg in one group , and 14 + /- 3/14 + /- 2 ( mean + /- SD ) mm Hg in the second group . Six weeks after discontinuation of quinapril , amlodipine alone caused no change ( 0 + /- 3/-2 + /- 3 ) ( mean + /- SD ) . The MSNA decreased by 3 bursts/100 heartbeats at visits 2 v 1 and 3 v 2 ( P = .02 for time effect ) , regardless of treatment . Angiotensin II showed small increases with each visit in the first group , and small decreases in the second group ( P = .02 for treatment effect ) . CONCLUSIONS It appears that amlodipine does not activate the renin-angiotensin system to counteract its BP-lowering effect in young hypertensives . Similarly , no angiotensin II-dependent component in MSNA appears to be present at baseline or to be induced by amlodipine Objective The role of the renin – angiotensin system in the regulation of sympathetic nervous activity in human hypertension was evaluated in patients with moderate primary hypertension . For that purpose , the effects of selective angiotensin II ( ANG II ) receptor blockade by valsartan on sympathetic outflow to the muscle vascular bed and hemodynamic parameters were examined . Results were compared with the effects of the peripherally acting calcium antagonist amlodipine . Design Eighteen hypertensive but otherwise healthy subjects were examined in a double-blind , placebo-controlled , cross-over protocol receiving either valsartan or amlodipine or placebo for 7 days in a r and omized sequence . Treatment periods were separated by washout periods of 2 weeks . Methods At the seventh day of treatment , blood pressure , heart rate , muscle sympathetic nerve activity ( MSNA ) , norepinephrine , renin and angiotensin were measured during resting conditions . Additionally , parameters were measured after administration of negative pressure of −15 mmHg to the lower part of the body and after a cold pressor test . Results Both antihypertensive drugs significantly decreased oscillometrically measured systolic blood pressure and diastolic blood pressure without any difference in effect . While valsartan did not affect the heart rate at rest , amlodipine increased it significantly . Likewise , MSNA was significantly enhanced by amlodipine but not by valsartan . Only ANG II receptor blockade increased renin and angiotensin levels . Conclusions Selective ANG II receptor blockade not only decreases blood pressure , but also shifts the baroreflex set-point for the initiation of counter-regulatory reflex responses of heart rate and blood pressure towards normal blood pressure levels . Thus , data suggest that ANG II plays a pathogenetic role in the elevation of the baroreflex set point in primary hypertensive subjects Nifedipine steady‐state kinetics and dynamics were investigated in a placebo‐controlled study of six healthy subjects . Nifedipine was given rectally through an osmotic system at a zero‐order rate for 24 hr . Steady‐state plasma concentrations of approximately 20 ng/ml were achieved within 6 to 8 hr . Nifedipine lowered diastolic blood pressure ( DBP ) and increased forearm blood flow ( FBF ) and plasma norepinephrine concentration . On the other h and , heart rate ( HR ) and systolic blood pressure were not affected . Changes in DBP and FBF were closely related to nifedipine plasma concentrations during and immediately after the infusion period . Our data indicate that nifedipine lowers blood pressure in subjects with normotension and that it is possible by infusing the drug at a relatively low rate to dissociate its effect on blood pressure from that on HR BACKGROUND This study compares the effects of telmisartan hydrochlorothiazide ( HCTZ ) combination versus nifedipine GITS on ambulatory blood pressure ( BP ) and sympathetic activity , in patients with mild-to-moderate hypertension . METHODS One hundred twenty-four out patients with sitting diastolic BP > or = 95 mmHg and < 110 mm Hg were r and omized to telmisartan 80 mg/HCTZ 12.5 mg daily ( n = 62 ) or nifedipine GITS 60 mg daily ( n = 62 ) for 12 weeks , according to a prospect i ve , open-label , blind end point , parallel-group design . At the end of a 2-week washout period and after 12 weeks of active treatment , 24-h noninvasive ambulatory BP monitoring ( ABPM ) was performed , clinic BP and heart rate were measured , and plasma norepinephrine and cardiovascular responses to mental stress induced by the color word test were assessed . RESULTS Both treatments reduced ambulatory and clinic BP . However , the drug combination had an antihypertensive efficacy significantly greater than nifedipine GITS , as shown by the 24-h ( P < .001 ) , daytime ( P < .001 ) , and night-time ( P < .01 ) ambulatory BP monitoring values , as well as by the clinic BP at trough ( P < .05 ) . The trough-to-peak ratio was similar , but the smoothness index was significantly higher with the combination for both systolic and diastolic BP ( P < .05 ) . A significant increase in plasma norepinephrine levels in resting conditions was observed with nifedipine GITS ( + 20 % ) but not with telmisartan/HCTZ combination . The color word test produced a greater increase in plasma norepinephrine and heart rate values in the patients treated with nifedipine GITS than in those treated with the combination . CONCLUSIONS These results suggest that the telmisartan 80 mg/HCTZ 12.5 mg combination provided a more sustained and homogeneous BP control than nifedipine GITS 60 mg , without producing sympathetic activation Little is known about the effects of antihypertensive drugs on hemodynamic responses to mental stress . We studied 24 patients with mild-to-moderate hypertension in a double-blind r and om-sequence crossover study comparing placebo with amlodipine titrated up from 5 to 10 mg daily . After 1 month of treatment , the subjects performed 20 min of a frustrating cognitive task . At baseline before task , amlodipine significantly reduced systolic pressure ( 128.9+/-8.2 mm Hg v 140.3+/-10.7 mm Hg , P < .001 ) , diastolic pressure ( 81.7+/-7.7 mm Hg v 90+/-7.5 mm Hg , P < .001 ) , and total peripheral resistance ( 37.5+/-15 v 45.6+/-23.7 mm Hg/L/min , P < .05 ) , while elevating baseline norepinephrine levels ( 2286+/-731 pmol/L v 1788+/-546 pmol/L , P < .001 ) . Blood pressure during the stress task was significantly less with amlodipine than with placebo ( systolic 142.3+/-12.3 mm Hg v 150.9+/-14.6 mm Hg , P < .001 ; diastolic 87.9+/-8.4 mm Hg v 97.7+/-9.3 mm Hg , P < .001 ) , whereas norepinephrine was significantly higher ( 2754+/-1007 pmol/L v 1970+/-740 pmol/L , P < .001 ) . There were no significant differences in cardiac output , plasma lipids or lipoproteins , or markers of platelet activation . Heart rate increased significantly during stress , but there was no significant difference between amlodipine and placebo either at baseline or during stress . Our conclusion is that amlodipine reduces blood pressure at baseline and during mental stress , but raises basal and stress-related plasma catecholamines . This finding may have implication s for the recent controversy over the safety of calcium channel antagonists , and suggests the potential relevance of combining amlodipine with adrenergic blockers OBJECTIVE We compared the efficacy of two classes of antihypertensive therapy on ambulatory blood pressure control and proteinuria in patients with hypertension . Furthermore , we determined the effects of the interaction of these therapies on neurohormonal activation and of the patients ' ambient sodium intake on the outcomes . METHODS Sustained-release nifedipine ( nifedipine gastrointestinal therapeutic system , GITS ) 30 - 120 mg/day was compared in a double-blind sequential r and omized placebo-controlled trial with enalapril 5 - 30 mg/day regarding office and 24-hour blood pressure control , plasma renin activity , noradrenaline and adrenaline levels and 24-hour urinary protein and sodium in 46 elderly nondiabetic hypertensive patients in a 16- to 18-week trial . RESULTS Both nifedipine GITS and enalapril controlled ambulatory blood pressure during the day and at peak effect . Nifedipine GITS controlled ambulatory blood pressure during the early morning surge and at night time as well . Nifedipine GITS increased plasma renin activity and noradrenaline by 50 and 20 % , respectively , compared to the 150 and 0 % change produced by enalapril . Both nifedipine GITS and enalapril reduced proteinuria by 37 % . Patients had increasing levels or proteinuria proportional to higher ambient sodium intake ( r = 0.48 ; p < 0.01 ) . This effect was accentuated during nifedipine GITS therapy as compared to enalapril . CONCLUSION Nifedipine GITS was superior to enalapril in controlling ambulatory blood pressure , but they were equivalent in reducing proteinuria ( 37 % ) . They had disparate effects on neural activation and the duration of action . Raised protein excretion appears to be associated with raised sodium intake . This was apparent especially during nifedipine XL therapy |
1,746 | 10,796,768 | There was not enough evidence to show whether drug therapy was better than bladder training or useful as a supplement to it | BACKGROUND Bladder training is widely used for the treatment of urinary incontinence .
It is generally used for the treatment of people with urge incontinence or detrusor instability , although it is also thought that it might be of use for people with mixed incontinence or stress incontinence .
OBJECTIVES To assess the effects of bladder training for the treatment of urinary incontinence . | Compromised urinary bladder syndrome ( CUBS ) , a combination of frequency and incontinence , causes multiple discomforts for community-dwelling adults . A holistic intervention -- audiotaped cognitive strategies -- was design ed to augment the effects of an educational program design ed to treat CUBS . CUBS was operationalized with a voiding diary , and comfort related to bladder health was operationalized in a question naire . In this quasi-experimental design the outcomes were measured at four time points . Repeated measures multivariate analyses of variance and nonparametric analyses were conducted to assess differences between the two groups . Results indicated that the treatment group had more comfort and improved CUBS compared with the control group OBJECTIVE To evaluate the effect of a low‐intensity behavioral therapy program on urinary incontinence in older women . METHODS A r and omized clinical trial for community‐dwelling women at least 55 years reporting at least one urinary incontinent episode per week was conducted . Women were r and omly assigned to a behavioral therapy group ( n = 77 ) or a control group ( n = 75 ) . The treatment group had six weekly instructional sessions on bladder training and followed individualized voiding schedules . The control group received no instruction but kept urinary diaries for 6 weeks . After this period , the control group underwent the behavioral therapy protocol . Using per‐ protocol analyses , t and χ2 tests were used to compare the treatment and control groups , and paired t tests were used to evaluate the efficacy of behavioral therapy for all women ( treatment and control groups before and after behavioral therapy ) . RESULTS Women in the treatment group experienced a 50 % reduction in mean number of incontinent episodes recorded on a 7‐day urinary diary compared with a 15 % reduction for controls ( P = .001 ) . After behavioral therapy , all women had a 40 % decrease in mean weekly incontinent episodes ( P = .001 ) , which was maintained over 6 months ( P < .004 ) . Thirty ( 31 % ) women were 100 % improved ( dry ) , 40 ( 41 % ) were at least 75 % improved , and 50 ( 52 % ) at least 50 % improved . There were no differences in treatment efficacy by type of incontinence ( stress , urge , mixed ) or group assignment ( treatment , control ) . CONCLUSION A low‐intensity behavioral therapy intervention for urinary incontinence was effective and should be considered as a first‐line treatment for urinary incontinence in older women The efficacy of bladder training was evaluated in a r and omized clinical trial involving 123 noninstitutionalized women 55 years and older with urinary incontinence . Subjects were urodynamically categorized as those with urethral sphincteric incompetence ( N = 88 ) and those with detrusor instability with or without concomitant sphincteric incompetence ( N = 35 ) . Bladder training reduced the number of incontinent episodes by 57 % ; the effect was similar for both urodynamic diagnostic groups . The quantity of fluid loss was reduced by 54 % . This was greater for patients with detrusor instability than for those without it . Diurnal and nocturnal voluntary micturitions were also reduced . The effect on nocturnal micturition , however , was not observed in subjects with unstable detrusor function . It is recommended that bladder training be considered as an initial step in treatment of women with urinary incontinence . Provided prior comprehensive clinical evaluation is done , it can be prescribed without the need for urodynamic characterization Objectives To compare , in a r and omized trial , the effects of individual and group physiotherapy for urinary incontinence in women referred by their general practitioner ( GP ) The purpose of this study was to explore changes in psychological distress associated with behavioral treatment and drug treatment for urge incontinence in community-dwelling older women . Participants were 197 ambulatory , nondemented women ( aged 55 years or older ) with persistent urge urinary incontinence . Participants were patients in a r and omized clinical trial comparing biofeedback-assisted behavioral treatment , drug treatment with oxybutynin chloride , and a placebo-control condition . Psychological distress was measured before and after treatment using the Hopkins Symptom Checklist ( SCL-90-R ) . Multivariate and univariate analyses of variance showed that the two treatment groups and the control group had similar significant improvements on the nine subscales and the global severity index . Analysis of individual SCL-90-R subscale scores revealed trends suggesting that behavioral treatment tended to produce the largest improvements . The reductions of distress were not correlated consistently with reduction of incontinence . The results of this study showed that psychological distress was significantly reduced after treatment , regardless of the type of treatment Summary — Fifty women with urinary incontinence due to derisory instability entered a controlled clinical trial to compare in-patient bladder drill with out-patient drug therapy . Following bladder drill , 84 % of patients were continent , whereas following treatment with flavoxate hydrochloride and imipramine , 56 % 01 patients were continent . Side effects due to drug therapy were significant Abstract The current emphasis on community-based health care makes necessary the implementation and evaluation of nursing practice models that address specific health problems , such as urinary incontinence , of older women living at home in rural communities BACKGROUND The short-term efficacy of combined lifestyle and behavioural interventions led by nurses in the management of urinary incontinence has not been rigorously evaluated by r and omized controlled trial . We conducted a 6-month r and omized controlled trial to determine whether a model of service delivery that included lifestyle and behavioural interventions led by " nurse continence advisers " in collaboration with a physician with expertise in continence management could reduce urinary incontinence and pad use in an outpatient population . We also aim ed to evaluate the impact of this approach on subjects ' knowledge about incontinence and their quality of life . METHODS We used advertising in the mainstream media , newsletters to family physicians and community information sessions in 1991 to invite volunteers who were 26 years of age or older and suffered from incontinence to participate in a r and omized controlled trial . Men and women who met the eligibility criteria were r and omly allocated to receive either counselling from specialized nurses to manage incontinence using behavioural and lifestyle modification sessions every 4 weeks for 25 weeks or usual care . Symptoms of incontinence and the use of incontinence pads were the primary outcome measures . RESULTS Using sealed envelopes , 421 patients were r and omly allocated to the treatment or control groups . On average , patients in the treatment group experienced 2.1 " incontinent events " per 24 hours before treatment and 1.0 incontinent event per 24 hours at the end of the study . Control patients had an average of 2.4 incontinent events per 24 hours before the study and 2.2 incontinent events per 24 hours at the end of the study . The mean decrease in events in the treatment group was 1.2 and in the control group 0.2 ( p = 0.001 ) . Pad use declined from a mean of 2.2 per 24 hours before r and omization in the treatment group to 1.2 per 24 hours at the end of the study , compared with 2.6 pads per 24 hours in the control group at the start of the study and 2.4 per 24 hours at the end . Pad use per 24 hours decreased on average by 0.9 pads in the treatment group and 0.1 in the control group ( p = 0.021 ) . INTERPRETATION Behavioural and lifestyle counselling provided by specialized nurses with training in managing incontinence reduces incontinent events and incontinence pad use The aim of this study was to assess the usefulness of pelvic floor exercises in the treatment of urinary incontinence in women and to analyse the factors which determine a successful outcome . The study involved 66 women who had reported ' genuine stress incontinence ' to their general practitioner . They were assigned at r and om to the treatment or control group . The treatment group received instructions in pelvic floor exercises from a general practitioner . The control group received no therapy . At the start of the trial the severity of the patients ' incontinence was assessed objective ly . This assessment was repeated after three months and patients were also asked for their own perception of whether their incontinence had improved . After the three months ' evaluation the patients in the control group were also given instructions in pelvic floor exercises . After another three months they were assessed in the same way . About 60 % of the patients in the treatment group were dry or mildly incontinent after three months compared with only one patient in the control group ; the mean weekly frequency of incontinence episodes fell from 17 to five in the treatment group but remained virtually unchanged in the control group ; and about 85 % of the women in the treatment group felt that their incontinence had improved or was cured compared with no one in the control group . These results were later corroborated by those for the control group . The most important factor in the success of the treatment was the patients ' motivation , as demonstrated by their adherence to the daily exercises . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objectives : To assess the effect of nurse assessment with reinforcement of pelvic floor muscle training exercises and bladder training compared with st and ard management among women with persistent incontinence three months postnatally . Design : R and omised controlled trial with nine months ' follow up . Setting : Community intervention in three centres ( Dunedin , New Zeal and ; Birmingham ; Aberdeen ) . Participants : 747 women with urinary incontinence three months postnatally , allocated at r and om to intervention ( 371 ) or control ( 376 ) groups . Intervention : Assessment by nurses of urinary incontinence with conservative advice on pelvic floor exercises at five , seven , and nine months after delivery supplemented with bladder training if appropriate at seven and nine months . Main outcome measures : Primary : persistence and severity of urinary incontinence 12 months after delivery . Secondary : performance of pelvic floor exercises , change in coexisting faecal incontinence , wellbeing , anxiety , and depression . Results : Women in the intervention group had significantly less urinary incontinence : 167/279 ( 59.9 % ) v 169/245 ( 69.0 % ) , difference 9.1 % ( 95 % confidence interval 1.0 % to 17.3 % , P=0.037 ) for any incontinence and 55/279 ( 19.7 % ) v 78/245 ( 31.8 % ) , difference 12.1 % ( 4.7 % to 19.6 % , P=0.002 ) for severe incontinence . Faecal incontinence was also less common : 12/273 ( 4.4 % ) v 25/237 ( 10.5 % ) , difference 6.1 % ( 1.6 % to 10.8 % , P=0.012 ) . At 12 months women in the intervention group were more likely to be performing pelvic floor exercises ( 218/278 ( 79 % ) v 118/244 ( 48 % ) , P<0.001 ) . Conclusions : A third of women may have some urinary incontinence three months after childbirth . Conservative management provided by nurses seems to reduce the likelihood of urinary and coexisting faecal incontinence persisting 12 months postpartum . Further trials for faecal incontinence are needed . What is already known on this topic Vaginal delivery is a risk factor for urinary incontinence Three months after childbirth 20 - 30 % of women still experience urinary incontinence Most women do not seek treatment What this study adds Women will use conservative treatments such as pelvic floor exercises or bladder training Conservative management prevents persistent urinary incontinence in about one in 10 women who have postnatal incontinence Coexisting persistent faecal incontinence is also CONTEXT Previous research on urge urinary incontinence has demonstrated that multicomponent behavioral training with biofeedback is safe and effective , yet it has not been established whether biofeedback is an essential component that heightens therapeutic efficacy . OBJECTIVE To examine the role of biofeedback in a multicomponent behavioral training program for urge incontinence in community-dwelling older women . DESIGN Prospect i ve , r and omized controlled trial conducted from April 1 , 1995 , to March 30 , 2001 . SETTING University-based outpatient continence clinic in the United States . PATIENTS A volunteer sample of 222 ambulatory , nondemented , community-dwelling women aged 55 to 92 years with urge incontinence or mixed incontinence with urge as the predominant pattern . Patients were stratified by race , type of incontinence ( urge only vs mixed ) , and severity ( frequency of accidents ) . INTERVENTIONS Patients were r and omly assigned to receive 8 weeks ( 4 visits ) of biofeedback-assisted behavioral training ( n = 73 ) , 8 weeks ( 4 visits ) of behavioral training without biofeedback ( verbal feedback based on vaginal palpation ; n = 74 ) , or 8 weeks of self-administered behavioral treatment using a self-help booklet ( control condition ; n = 75 ) . MAIN OUTCOME MEASURES Reduction in the number of incontinence episodes as documented in bladder diaries , patients ' perceptions and satisfaction , and changes in quality of life . RESULTS Intention-to-treat analysis showed that behavioral training with biofeedback yielded a mean 63.1 % reduction ( SD , 42.7 % ) in incontinence , verbal feedback a mean 69.4 % reduction ( SD , 32.7 % ) , and the self-help booklet a mean 58.6 % reduction ( SD , 38.8 % ) . The 3 groups were not significantly different from each other ( P = .23 ) . The groups differed significantly regarding patient satisfaction : 75.0 % of the biofeedback group , 85.5 % of the verbal feedback group , and 55.7 % of the self-help booklet group reported being completely satisfied with treatment ( P = .001 ) . Significant improvements were seen across all 3 groups on 3 quality -of-life instruments , with no significant between-group differences . CONCLUSIONS Biofeedback to teach pelvic floor muscle control , verbal feedback based on vaginal palpation , and a self-help booklet in a first-line behavioral training program all achieved comparable improvements in urge incontinence in community-dwelling older women . Patients ' perceptions of treatment were significantly better for the 2 behavioral training interventions OBJECTIVE --To measure the unmet need of patients with regular urinary incontinence ( incontinence twice or more a month ) treatable by a nurse . DESIGN --Self completed postal question naire and r and omised controlled trial of assessment and intervention by a nurse . SETTING --One urban and one rural general practice in Somerset . SUBJECTS--7300 adults r and omly selected from 10,300 aged 35 and over on the combined practice lists . 515 women and 185 men with regular incontinence were offered assessment and treatment , of whom 134 women and 49 men had no intervention for three months ( historical controls ) . They then joined the assessment and treatment programme . INTERVENTION -- Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence . MAIN OUTCOME MEASURES --Number of patients desiring treatment ; self reported cure , improvement , or deterioration in continence after three months . RESULTS --The question naire achieved a 79 % response . Vali date d responses showed a prevalence of 4.4 % in men and 16.4 % in women aged 35 - 64 . 315 ( 45 % ) of the 700 patients offered assessment refused it and seven had moved away or died , 64 men and 41 women were referred to their general practitioner . 197 of 292 treated women ( 68 % ) reported cure or improvement compared with seven ( 5 % ) of controls . 22 of the 86 men desiring treatment were suitable for intervention by the nurse . Seventeen were cured or improved compared with none of the men in the control group . CONCLUSIONS --About half the people with regular urinary incontinence took up the offer of treatment ( 9.2 % of women and 3.4 % of men in the study population ) . This condition can be effectively managed by a nurse with limited training AIMS The objectives of this study were ( 1 ) to determine the effect of training on pelvic floor muscle strength ; ( 2 ) to determine whether changes in pelvic floor muscle strength correlate with changes in continence ; and ( 3 ) to determine whether demographic characteristics , clinical incontinence severity indices , or urodynamic measures predict response to pelvic floor muscle training . METHODS One hundred thirty-four women with urinary incontinence ( 95=genuine stress incontinence [ GSI ] ; 19=detrusor instability [ DI ] ; 20=mixed incontinence [ GSI+DI ] ) were r and omized to pelvic floor muscle training ( n=67 ) or bladder training ( n=67 ) . Urinary diaries , urodynamic evaluation , and vaginal pressure measurements by using balloon manometry were performed at baseline and after 12 weeks of therapy . Primary outcome measures consisted of incontinent episodes per week and vaginal pressure measurements . RESULTS Both treatment groups had a reduction in incontinent episodes ( P</=0.004 ) . Vaginal pressures increased more with pelvic floor muscle training than with bladder training ( P=0.0003 ) . Other than a weak correlation between a reduction in incontinent episodes/week and an increase in maximum sustained vaginal pressure in women with GSI ( r=0.32 , P=0.04 ) , there were no significant correlations between increases in pelvic floor muscle strength and improvement in continence status . There were no significant correlations between baseline demographic characteristics , clinical incontinence severity , or urodynamic measures and increases in vaginal pressure or improvement in clinical severity after pelvic floor muscle training . CONCLUSIONS Pelvic floor muscle training improves continence and increases vaginal pressure measurements , but the direct correlations between these alterations are weak . A woman 's response to behavioral treatment does not depend on her demographic characteristics , clinical incontinence severity , urodynamic measures , or initial pelvic floor muscle strength Regular urinary incontinence affects one in six adult women . However , for the majority , good continence services are difficult to access and few primary care-based assessment and treatment facilities are available . A large r and omised trial of assessment and treatment in primary care using a trained nurse was conducted in Somerset in 1990 . This report summarises the methods and results of the initial study and reports the four-year follow-up results . The results show that 70 per cent of women will gain long lasting benefit . This model of service provision will also benefit secondary care specialist services by ensuring that patients are appropriately managed in primary care before any possible referral The mental state of 211 women attending a urodynamic clinic was assessed using question naires . Patients with genuine stress incontinence had scores comparable with other patients with longst and ing physical complaints . Patients with sensory urgency were more anxious than those with genuine stress incontinence . Patients with detrusor instability were as anxious as patients with sensory urgency and in addition had higher scores on the hysteria scale . A subset of patients ( roughly a quarter of the total ) was identified , comprising members of all three diagnostic groups , for whom urinary symptoms rendered life intolerable . These patients were as anxious , depressed , and phobic as psychiatric in patients , emphasising the serious psychological morbidity experienced by patients with urinary symptoms . Fifty patients with detrusor instability or sensory urgency entered a r and omised trial comparing psychotherapy , bladder drill , and propantheline . The psychotherapy group significantly improved on measures of urgency , incontinence , and nocturia , though not on frequency . Bladder training was an effective treatment for frequency and patients became less anxious and depressed . There was a modest improvement in frequency of micturition in patients given propantheline . Frequency may be a learnt disorder which responds to the direct symptom oriented approach of bladder training . Patients with urgency and nocturia predominating might derive more benefit from psychotherapy OBJECTIVE --To compare terodiline with bladder retraining against placebo with bladder retraining in the treatment of detrusor instability in frail elderly patients . DESIGN --R and omised , double blind , parallel group study . Treatment lasted for six weeks . Frequency of micturition and episodes of incontinence recorded on diary chart by patients . SETTING --Incontinence clinic and a geriatric day hospital at two teaching hospitals . PATIENTS --37 frail but ambulant patients , mean ( range ) age 80.4 ( 70 - 89 ) years with urinary frequency and urge incontinence , due to detrusor instability . Two patients withdrew before the first assessment ( one in each group ) and one could not complete the diary chart ( placebo group ) . INTERVENTIONS --19 patients received bladder retraining and terodiline 25 mg daily and 18 bladder retraining and placebo . MAIN OUTCOME MEASURES --Change in urinary frequency and number of episodes of incontinence after six weeks ' treatment . Patient 's subjective evaluation of symptoms . RESULTS --Little difference was found in the results of treatment with terodiline and placebo . The change in episodes of incontinence per 24 hours was no different in the two groups ( 95 % confidence interval -0.6 to 1.2 ; p = 0.75 ) and the difference between treatments in the change in frequency of micturition per 24 hours ( -0.2 ) was not significant ( -1.1 to 1.2 ; p = 0.76 ) . Ten patients taking terodiline thought they had improved compared with seven receiving placebo ; this difference was not significant . CONCLUSION --Although the number of patients in each group was small and may have been insufficient to detect a drug effect , the possible benefit of terodiline is likely to be small The purpose of this study was to compare the effect of three conservative interventions : pelvic floor muscle training , bladder training , or both , on urodynamic parameters in women with urinary incontinence . Two hundred four women with genuine stress incontinence ( GSI ) or detrusor instability with or without GSI ( DI + /- GSI ) participated in a two-site trial comparing pelvic floor muscle training , bladder training , or both . Patients were stratified based on severity of urinary incontinence , urodynamic diagnosis , and treatment site , then r and omized to a treatment group . All women underwent a comprehensive st and ardized evaluation including multi-channel urodynamics at the initial assessment and at the end of 12 weeks of therapy . Analysis of covariance was used to detect differences among treatment groups on urodynamic parameters . Post-treatment evaluations were available for 181 women . No differences were found among treatments on the following measurements : maximum urethral closure pressure , mean urethral closure pressure , maximum Kegel urethral closure pressure , mean Kegel urethral closure pressure , functional urethral length , pressure transmission ratios , straining urethral axis , first sensation to void , maximum cystometric capacity , and the MCC minus FSV . The effect of treatment did not differ by urodynamic diagnosis . Behavioral therapy had no effect on commonly measured urodynamic parameters . The mechanism by which clinical improvement occurs remains unknown . Neurourol . Urodynam . 18:427 - 436 , 1999 OBJECTIVE To compare sexual function in women with urinary incontinence and pelvic organ prolapse and to determine the effects of therapy on sexual function . METHODS 343 community‐dwelling women older than 45 years with urinary incontinence or advanced prolapse were recruited into a multi‐armed clinical trial . Women with incontinence were stratified to receive estrogen therapy , behavioral therapy , or surgical therapy . Women with prolapse were enrolled in a r and omized surgical trial . All women completed a st and ardized urogynecologic evaluation and a sexual function question naire at baseline and after therapy . RESULTS Women with prolapse or detrusor instability were more likely to cite pelvic floor symptoms as a reason for sexual inactivity than were women with other conditions . One third of patients with prolapse reported that their pelvic floor condition affected their ability to have sexual relations “ moderately ” or “ greatly ” significantly more than did other groups . Patients with genuine stress incontinence who underwent surgical or behavioral therapy were less likely to report being worried about urine leakage during intercourse after therapy than at baseline . After surgery , women with prolapse were less likely to report that their symptoms affected their ability to have sexual relations compared with baseline . Overall sexual satisfaction was the same at baseline and remained unchanged in all therapeutic groups at 6 months . CONCLUSION Prolapse is more likely than urinary incontinence to result in sexual inactivity and to be perceived as affecting sexual relations . However , overall sexual satisfaction appears to be independent of diagnosis of or therapy for urinary incontinence or prolapse The aim of this study was to examine the efficacy of oxybutynin plus bladder training in the treatment of detrusor instability in frail elderly patients living independently in the community . It was a r and omized , double-blind , placebo-controlled parallel-group trial of oxybutynin in 57 elderly patients ( mean age 82.2 , SD 6.06 ) , with frequency and incontinence due to detrusor instability . After a 2-week run-in period patients received a bladder training and drug or placebo for the next 6 weeks . Outcome measures were changes in frequency and incontinence , recorded throughout on diary charts , and subjective evaluation of symptoms ( ' better'/'not better ' , and using a four-point scale ' cure ' to ' no change ' ) . Oxybutynin was superior to placebo in reducing daytime frequency [ 95 % confidence interval ( CI ) of difference in change in frequencies totalled over 14 days was -27.0 , -6.0 ; p = 0.003 ] and in producing subjective benefit ( at day 29 only ) , when 24/28 ( 86 % ) patients on oxybutynin described benefit compared with 16/29 ( 55 % ) on placebo ( p = 0.02 ) . There was no difference between the groups in reduction of incontinent episodes . The median dose of oxybutynin titrated for therapeutic effect was 5 mg/day , and for placebo 10 mg/day ( CI of difference 0.001 , 5.001 ; p = 0.05 ) . Side-effects reported were of similar frequency ( 50 % ) in the two groups . We conclude that oxybutynin with bladder training is superior to bladder training alone in reducing frequency due to detrusor instability in very elderly people living at home OBJECTIVE We compared the efficacy of bladder training , pelvic muscle exercise with biofeedback-assisted instruction , and combination therapy , on urinary incontinence in women . The primary hypothesis was that combination therapy would be the most effective in reducing incontinent episodes . STUDY DESIGN A r and omized clinical trial with three treatment groups was conducted in gynecologic practice s at two university medical centers . Two hundred and four women diagnosed with genuine stress incontinence ( n = 145 ) and /or detrusor instability ( n = 59 ) received a 12-week intervention program ( 6 weekly office visits and 6 weeks of mail/telephone contact ) with immediate and 3-month follow-up . Outcome variables included number of incontinent episodes , quality of life , perceived improvement , and satisfaction . Data analyses consisted of analysis of covariance using baseline values as covariates and chi2 tests . RESULTS The combination therapy group had significantly fewer incontinent episodes , better quality of life , and greater treatment satisfaction immediately after treatment . No differences among groups were observed 3 months later . Women with genuine stress incontinence had greater improvement in life impact , and those with detrusor instability had less symptom distress at the immediate follow-up ; otherwise , no differences were noted by diagnosis , incontinence severity , or treatment site . CONCLUSIONS Combination therapy had the greatest immediate efficacy in the management of female urinary incontinence regardless of urodynamic diagnosis . However , each of the 3 interventions had similar effects 3 months after treatment . Results suggest that the specific treatment may not be as important as having a structured intervention program with education , counseling , and frequent patient contact The purpose of this nursing informatics and outcomes research study was to determine the effectiveness of an expert system for disseminating knowledge to ambulatory women health care consumers with urinary incontinence . Clinical knowledge from the Agency for Health Care Policy and Research ( AHCPR ) patient guideline for urinary incontinence and research literature for behavioral treatments provided the knowledge base for the expert system . Two experimental groups ( booklet and expert system ) and one control group were utilized . Study results suggest the use of an expert system as one effective communication means for disseminating clinical information in an advisory capacity to ambulatory women with urinary incontinence OBJECTIVE The purpose of this study was to examine the effects of combining behavioral treatment and drug treatment for urge incontinence in community-dwelling older women . DESIGN Modified crossover design ( extension of a r and omized clinical trial ) . Eligible subjects were stratified according to type and severity of incontinence and r and omized to behavioral treatment , drug treatment , or a control condition ( placebo ) . Subjects not totally continent or not satisfied after 8 weeks of a single treatment were offered the opportunity to cross over into combined therapy . SETTING A university-based outpatient geriatric medicine clinic . PARTICIPANTS Subjects in the clinical trial were 197 ambulatory , nondemented , community-dwelling women ( age 55 years or older ) with persistent urge urinary incontinence . Thirty-five subjects participated in combined treatment . INTERVENTION One group of subjects received four sessions ( over 8 weeks ) of biofeedback-assisted behavioral training followed by 8 weeks of behavioral training combined with drug therapy ( oxybutynin chloride individually titrated from 2.5 mg to 15 mg daily ) . The second group received drug therapy first , followed by 8 weeks of drug therapy combined with behavioral training . MEASUREMENTS Bladder diaries completed by subjects before and after each treatment phase were used to calculate change in the frequency of incontinent episodes . RESULTS Eight subjects ( 12.7 % ) crossed from behavioral treatment alone to combined behavioral and drug therapy . Additional benefit was seen in improvement from a mean 57.5 % reduction of incontinence with single therapy to a mean 88.5 % reduction of incontinence with combined therapy ( P = .034 ) . Twenty-seven subjects ( 41.5 % ) crossed from drug therapy alone to combined drug and behavioral treatment . They also showed additional improvement , from a mean 72.7 % reduction of incontinence with single therapy to a mean 84.3 % reduction of incontinence with combined therapy ( P = .001 ) . CONCLUSIONS This study shows that combining drug and behavioral therapy in a stepped program can produce added benefit for patients with urge incontinence The aims of this study were to compare " subjective " measures of severity of urinary incontinence to similar " objective " measures , establish their statistical correlation , and determine the effect of specific urodynamic diagnosis on such correlations . Baseline data was available from 265 women entered into a clinical trial study ing pharmacologic and behavioral interventions for urinary incontinence . The " subjective " measures of incontinence were obtained by patient recall during history taking and included : the number of incontinent episodes in 1 week , the number of perineal pads used during 1 week , and the number of clothing changes required due to wetness . The " objective " measures of severity included : the number of incontinent episodes per week as recorded on a 7-day diary , the number of perineal pads used per week , also recorded on a diary , and the amount of fluid lost during a st and ardized pad test . Analysis consisted of Pearson correlations and linear regressions to determine equations for the prediction of objective measurement on the basis of the corresponding subjective measure . Significant positive correlations were seen between " subjective " and " objective " measurements for the comparisons of number of weekly incontinent episodes ( R = 0.63 ) , and for the weekly number of pads used ( R = 0.81 ) . The comparison between the number of clothing changes and the amount of fluid lost during pad testing was also significantly but less strongly correlated ( R = 0.24 ) . For the correlations between subjective and objective determinations of urinary incontinent episodes and for those between clothing changes and pad testing , the urodynamic diagnosis had no effect on the correlation coefficients , but did have a statistically significant effect on the intercept . ( ABSTRACT TRUNCATED AT 250 WORDS Objectives : This article examines change in general and condition-specific measures of health-related quality of life ( HRQL ) among participants in a r and omized trial of a community-based intervention for urinary incontinence ( UI ) . Methods : Participants were r and omized into intervention or wait control conditions . Participants were women aged 65 or older with urinary incontinence residing in Oklahoma . General HRQL measures included the Physical Function , Mental Health , Vitality , and Health Perceptions subscales of the Medical Outcomes Study Short Form–36 . Condition-specific measures included the Impact of UI and self-management strategies . Results : There were no significant group effects for the general HRQL measures . Intervention participants reported decreased Impact of UI and greater change in self-management strategies than control participants . Discussion : The intervention affected condition-specific quality of life and self-management but not general HRQL . The intervention ’s impact on quality of life involves change in howthe condition is seen as impacting on life and on selection of self-management behaviors We compared imipramine with placebo in a double-blind study in Leicester , in elderly incontinent patients . The results revealed that 14 out of 19 patients became dry after imipramine and six out of 14 after placebo treatment . Patients on imipramine also tended to become drier sooner . However , these results must only be taken as preliminary evidence of drug effect since statistical analysis between drug and placebo did not reach significance . The results do , however , confirm the great benefit of habit-retraining which all patients received . It is now our practice to try this alone first , and to reserve drugs for slow or nonresponders , because of their possible adverse effects A total of 110 women who had reported urinary incontinence to their general practitioners were r and omly assigned to a treatment or control group . Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence . The results were measured after 3 and 12 months by a research assistant on the basis of a constructed severity scale , an incontinence diary , and a comparison by the patients themselves of their previous and current conditions . After 3 months the control group were given the same treatment . After a further 3 and 12 months , they were assessed in exactly the same way as the treatment group . After 3 months about 60 % of the patients were either dry or only mildly incontinent ; the mean number of wet episodes had gone down from 20 to 7 , and 74 % of the women felt improved or cured . These results were later corroborated by the control group . After 12 months this successful outcome was improved slightly further . It may be concluded that the majority of women with incontinence can be successfully treated by the general practitioner . The effect of this treatment continues after one year PURPOSE The purpose of this study was to assess the effects of age and patients ' attribution of incontinence to aging on health-related behaviors associated with incontinence . DESIGN AND METHODS Participants in this study were 74 women who either sought treatment for urinary incontinence at a multidisciplinary continence program or volunteered for a r and omized clinical trial of behavioral and drug therapy for incontinence . As part of their clinical evaluation , women were interviewed about how they managed their incontinence and their perceptions of what had caused the condition . Self-management of incontinence was defined as behaviors used to cope with incontinence , rather than treat or cure incontinence . Self-treatment was defined as self-implementation of Kegel exercises , and formal treatment was defined as interaction with a health care provider . RESULTS Over half of the respondents attributed their incontinence to aging . In multivariate analyses , age was associated with self-management of incontinence , but not self-treatment or formal treatment . In contrast , attribution of incontinence to aging was associated with self-management and self-treatment of incontinence . There was also a trend for attribution of incontinence to aging to be associated with formal treatment for incontinence . Women who attributed their incontinence to aging were less likely to have engaged in self-management strategies and to have received a previous evaluation or treatment ; but , they were more likely to have engaged in self-treatment for incontinence . When other relevant variables were added to the regression models , perception that incontinence restricted one 's activities became the most significant predictor of performing self-management strategies and performing Kegel exercises . IMPLICATION S Attribution to aging may be an impediment to seeking treatment . Education to promote underst and ing of the actual causes and treatment of urinary incontinence may encourage people to seek appropriate intervention . Additionally , whereas attribution to aging is an important factor contributing to health-related behaviors , other factors , such as perception that one 's activities are restricted , may play an important role The purpose of this study was to clarify the mechanism by which bladder training affects urinary incontinence . Urodynamic data and specific urodynamic diagnoses of 108 women with urinary incontinence were compared before and 6 months after treatment with bladder training . Before treatment , 76 women had sphincteric incompetence , 11 had detrusor instability , and 16 had both . After treatment , 33 women no longer fulfilled the urodynamic diagnostic criteria for either sphincter or detrusor dysfunction . Controlling for severity before treatment , the number of incontinent episodes post-treatment was not associated with change in urodynamic diagnosis . Only the first sensation to void , voided volume , compliance , functional urethral length , and flow time showed any significant changes between pre- and post-treatment evaluations ; however , none were correlated with change in the number of incontinent episodes . Bladder training does not appear to affect lower tract urodynamic variables or specific urodynamic diagnosis , and it is likely that its mechanism of action reflects adaptive behavioral changes . Physiologic changes not detected with techniques and /or criteria used in this study may still occur Caffeine reduction is an internationally accepted treatment strategy for patients with urinary symptoms . However , there is little trial evidence in support of a caffeine/urinary symptom effect . A prospect i ve r and omized trial was conducted among 95 consecutive adult patients with urinary symptoms presenting to two nurse continence advisers . Frequency , urgency and leakage outcomes were tested 1 month postenrolment . Trial findings indicate that caffeine intake was reduced ( P<0.0001 ) in the experimental group and that urgency ( P=0.002 ) and frequency ( P=0.037 ) outcomes were significantly improved . Caffeine practice s and habits were surveyed and self-reports of caffeine effects indicate that urinary symptoms figured prominently as a reported effects but less so as a driver of caffeine reduction OBJECTIVES To describe changes in bladder function and voiding frequency associated with behavioral and drug treatment for urge incontinence and to examine whether these variables mediate the positive effects of treatment on the frequency of incontinence . DESIGN R and omized , double-blinded , placebo-controlled , clinical trial . Eligible patients were stratified according to type of incontinence ( urge only vs mixed urge and stress ) and severity of incontinence ( frequency of accidents as documented in bladder diary ) . SETTING University-based outpatient geriatric medicine clinic . PARTICIPANTS One hundred five ambulatory , nondemented , community-dwelling women ; mean age 67.0 ( range 55 - 91 ) ; 98 % white , 2 % African American . INTERVENTION Four sessions ( over 8 weeks ) of biofeedback-assisted behavioral training , drug treatment with individually-titrated oxybutynin chloride , or a placebo control condition . MEASUREMENTS Two-channel cystometry was performed to determine threshold volumes for first desire to void ( FDV ) , strong desire to void ( SDV ) , bladder capacity , and the volume at which detrusor instability ( DI ) or leakage occurred , before r and omization and after completion of treatment . Two-week bladder diaries were used before and after treatment to document episodes of incontinence and voiding frequency . RESULTS Bladder capacity increased by 68.9 mL in the oxybutynin group ( P < .001 ) and 17.3 mL in the behavior group and decreased 6.0 mL in the control group . SDV increased 69.9 mL in the oxybutynin group ( P < .001 ) , 40.5 in the behavior group ( P < .05 ) , and 7.8 mL in the control group . FDV increased by 44.4 mL in the oxybutynin group ( P < .001 ) , 18.8 mL in the behavior group , and 8.9 mL in the control group . One of seven patients who presented with DI ( 12.0 % ) resolved in the behavior group , seven of eight ( 87.5 % ) resolved in the oxybutynin group , and seven of 12 ( 58.3 % ) resolved in the control group . These differences were not statistically significant . Voiding frequency was significantly reduced after treatment in both the behavior and the oxybutynin group . Behavioral training result ed in a mean 82.3 % reduction in frequency of accidents , oxybutynin ( final doses 2.5 mg daily to 5 mg three times a day ) result ed in a mean 78.3 % reduction , and the control condition result ed in a mean 51.5 % reduction ( P = .002 ) . Although oxybutynin and behavioral treatment were both effective , and oxybutynin increased SDV and bladder capacity , the structural equation modeling did not demonstrate that the clinical improvement was mediated through the effects of these treatments on urodynamic or voiding frequency measures . CONCLUSIONS Studies using more-complex urodynamics and studies with larger sample sizes are needed to better characterize changes in bladder function and explore other urodynamic changes that may accompany treatment . In addition , other factors , both physiological and behavioral , need to be explored as mechanisms by which conservative therapies improve urge incontinence OBJECTIVE To assess the efficacy of physiotherapeutic treatment modalities in women with proven bladder overactivity . METHODS One hundred and twelve women received ambulatory urodynamics . Based on both urodynamic variables of ambulatory cystometry ( ACM ) and the micturition diary , the Detrusor Activity Index ( DAI ) for each patient was calculated . After r and omization , 68 women with a DAI > or = 0.50 were defined as having proven bladder overactivity . In a single blinded RCT patients were r and omized over four treatment groups , i.e. lower urinary tract exercises ( LUTE ) ; office- and home-based functional electrostimulation ( FES ) ; office-based FES and LUTE ; no treatment . Patients treated received nine treatment sessions , once weekly . The primary outcome variable was the DAI , measured before r and omization and , as soon as possible within a maximum of 14 days after the end of the study period . RESULTS Intention to treat analysis in the group of 68 patients showed a statistically significant decrease of DAI-scores in the FES group ( p=0.032 ) in comparison with no treatment , while this decrease was not statistically significant in the LUTE group ( p=0.105 ) and the LUTE+FES group ( p=0.672 ) . CONCLUSIONS Our conclusion is that , based on the DAI , in the homogeneous set of 68 patients , only FES seemed to be effective Objectives : This community-based intervention to reduce urinary incontinence ( UI ) in elderly women used a small group educational approach . This article reports on change in episodes of incontinence and other urinary symptoms . Methods : Participants were r and omly assigned to intervention orwait control condition . This article is restricted to 49 intervention and 59 control participants with acceptable diaries . Results : There was a significant treatment effect for a number of incontinent episodes . In the intervention group , 61 % had a 50 % or greater reduction in episodes , with more than one third having 100 % reduction ; 38 % of the control group had a reduction of 50 % or greater . One year postprogram , 75 % of treated women reported subjective improvement . Therewas a reduction in frequency of daily , but not nocturnal , micturition . Discussion : This community-based intervention is an encouraging option for behavioral treatment of UI . Public health models may be particularly appropriate with moderate levels of urinary incontinence Urinary incontinence ( UI ) is a commonly underreported and underdiagnosed condition . The purpose of this trial was to implement and evaluate behavioral management for continence ( BMC ) , an intervention to manage symptoms of UI with older rural women in their homes . Participants were r and omized into BMC or a control group , and 178 were followed for between 6 and 24 months . The intervention involved self-monitoring , bladder training , and pelvic muscle exercise with biofeedback . The primary outcome variable-severity of urine loss-was evaluated by pad test . Secondary variables were episodes of urine loss , micturition frequency , voiding interval , quality of life , and subjective report of severity . Urine loss severity at baseline evaluation was not significantly different in the two groups . But using the generalized linear mixed model analysis , at the four follow-ups , severity of urine loss , episodes of urine loss , quality of life , and subjective report of severity were significantly different . At 2 years the BMC group UI severity decreased by 61 % ; the control group severity increased by 184 % . Self-monitoring and bladder training accounted for most of the improvement . The results support the use of simple strategies based on bladder diaries before implementing more complex treatments We aim ed to study the impact of conservative non-pharmacological , non-surgical management on quality of life in elderly incontinent patients . Community-dwelling patients age 60 years or older were r and omized to receive immediate or delayed conservative management . A number of questions relating to quality of life were administered at admission and then at 2 , 4 , 8 and 12 months . By 4 months , incontinence was cured in 25 % and improved in 63 % of patients . The frequency and severity of incontinence was reduced ( p < 0.001 ) , and deferment time was improved ( p < 0.01 ) . There were statistically significant improvements in subjective quality of life measures at 4 and 12 months involving depression ( p < 0.001 ) , isolation ( p < 0.03 ) , embarrassment ( p < 0.001 ) , laundry ( p < 0.001 ) and smell ( p < 0.02 ) when comparing these variables with initial assessment . This effect did not appear to be a placebo effect as evidence d by comparison with the delayed intervention group , and was sustained over 12 months . There are significant short- and long-term benefits to the quality of life of older patients with incontinence when treated by conservative measures . Intervention studies should measure and report quality of life as an outcome variable |
1,747 | 23,823,038 | The results indicate that temporary clamping could significantly reduce the drainage volume , including total drainage volume , drainage volume within 24 hours postoperatively , and drainage volume within 48 hours postoperatively .
Furthermore , patients treated with temporary drainage clamping for 4 hours or more had a higher hemoglobin level 24 hours postoperatively than the patients treated with no clamping , and the number of blood transfusions per patient decreased significantly .
No significant difference was identified between the 2 practice s regarding postoperative range of motion , wound-related complications , and deep vein thrombosis . | Use of closed drainage systems after total knee arthroplasty ( TKA ) is a routine practice .
Currently , a debate exists regarding whether temporary or no clamping is optimal . | 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 The purpose of this prospect i ve study was to analyze the biochemical markers of muscle damage and inflammation in patients treated with the mini-midvastus approach or the medial parapatellar approach for total knee arthroplasty . Of 60 patients who underwent unilateral total knee arthroplasty , 30 were treated with the mini-midvastus approach ( MMV group ) and 30 were treated with the medial parapatellar approach ( MPP group ) . Serum creatine kinase , myoglobin , lactate dehydrogenase , glutamic oxaloacetic transaminase , C-reactive protein , interleukin-6 , and interleukin-1β levels were measured preoperatively , immediately postoperatively ( except for C-reactive protein level ) , and on postoperative days 1 , 2 , and 3 . Student 's t test , Pearson 's chi-square test , and Fisher 's exact test were used to compare the outcomes between the 2 groups . Compared with the MPP group , a significant increase in serum creatine kinase level existed in the MMV group on postoperative days 2 ( P=.08 ) and 3 ( P=.09 ) and cumulatively ( P=.02 ) . However , significantly elevated C-reactive protein and interleukin-6 levels existed in the MPP group . According to the serum creatine kinase levels , the mini-midvastus approach has no superiority over the medial parapatellar approach in terms of sparing muscle and may cause more muscle damage . Further study is warranted to determine the correlation between biochemical markers and functional deficits Closed suction drains reduce postoperative hematoma formation , but create an entry portal for bacteria and thus increase the risk of infection . This study attempts to establish when the risks of wound drainage outweigh the benefits . In a prospect i ve clinical trial , wound drains were used in all patients having a total knee or total hip arthroplasty . Timing of drain removal and amount drained were recorded . Drain-site swabs were sent with drain tips for bacteriology . Results suggest that the likelihood of bacterial colonization increases while wound drainage decreases with time . The authors conclude that the optimal time to remove drains is 24 hours after total joint arthroplasty Background : The purpose of this study was to determine whether repeated clamping of a suction drainage system will result in less external blood loss , blood transfusion and no increase in complications compared to a routine continuous suction drainage system . This was a r and omized prospect i ve study on patients undergoing total knee arthroplasty Total knee arthroplasty is sometimes associated with major post-operative bleeding , often requiring transfusion . A prospect i ve , r and omised study was undertaken to assess the effect on post-operative bleeding of delaying release of the clamp on the suction drains . One hundred patients were allocated into two groups : Group A- immediate release of drain following release of tourniquet , and Group B- delayed release of the drain clamp by one hour . There was a statistically significant reduction ( p = < 0.001 ) in postoperative bleeding between group A ( 1050 ml ; 95%CI 728 - 1172 ml ) compared to group B ( 732 ml ; 95 % CI 620- 845 ml ) . Average drop in corrected haemoglobin and postoperative transfusion requirement were also less in the delayed group . The results show that delaying release of the drains by one hour reduces postoperative blood loss and transfusion requirement following total knee arthroplasty Total knee replacement in severe osteoarthritis usually requires extensive soft tissue releases often associated with considerable bleeding . In a prospect i ve , r and omised trial we compared postoperative conventional suction drainage versus four hour clamping drainage in 60 patients undergoing total knee arthroplasty for severe osteoarthritis . We compared blood loss , number of transfusions , postoperative complications and knee function and found significantly less postoperative blood loss through the drains ( p < 0.001 ) , and fewer blood transfusions ( p = 0.09 ) were needed in the clamped group . We conclude that clamping drainage after total knee arthroplasty in severe osteoarthritis reduces blood loss through the drains and the need for blood transfusions . RésuméLa prothèse totale du genou dans les gonarthroses sévères nécessite souvent une résection tissulaire importante , celle-ci étant souvent associée à un saignement important . Nous avons réalisé une étude prospect i ve r and omisée comparant le drainage conventionnel post-opératoire versus clampage du drain durant 4 heures chez 60 patients ayant bénéficié d’une prothèse totale du genou pour une gonarthrose importante . Nous avons comparé les pertes sanguines , le nombre de transfusion , les complications post-opératoires , la fonction du genou . Nous avons observé qu’il y avait beaucoup moins de pertes sanguines dans les drains ( p < 0.001 ) et beaucoup moins de transfusions ( p = 0.009 ) dans le groupe des patients do nt le drain avait été clampé pendant 4 heures . Nous pouvons conclure que le clampage du drain après prothèse totale du genou dans les gonarthroses sévères permet de réduire les pertes sanguines et le nombre de transfusions Background Total knee arthroplasty ( TKA ) is a common procedure that has a risk of significant blood loss and blood transfusion , and carries a substantial risk for immunologic reactions and disease transmission . Drain clamping is a popular method that is applied to reduce blood loss after TKA . However , the clamping protocol remains controversial . Therefore , we established a new protocol , 3-h interval clamping , and compared the bleeding control efficacy of this protocol following TKA with the non-clamping technique . Methods Between March and July 2008 , we enrolled 100 patients ( 100 knees ) who underwent uncomplicated TKA using a minimally invasive surgical technique . The patients were r and omly assigned into two groups based on the draining protocol : non-clamping ( group A ) and 3-h interval clamping ( group B ) . For group A , a vacuum drain was connected to a container and was run continuously during the first postoperative day , whereas the vacuum was stopped twice ( for ~3 h each time ) for group B. Demographic characteristics and clinical data were collected , including the levels of hemoglobin and hematocrit , the total blood loss volume , the number of patients who required a blood transfusion , and any complications that developed . The perioperative data were compared between the two groups . Results The drainage blood volume in the interval-clamping group ( group B ) was significantly lower than that in the non-clamping group ( group A ) during the first 48 h following the procedure ( p < 0.001 and p = 0.005 for first and second postoperative days , respectively ) . The mean fall in hemoglobin levels at 12 h in the interval-clamping group ( 2.8 ± 0.9 g/dL ) was also lower than in the non-clamping group ( 3.2 ± 0.8 g/dL ) . In the 3-h interval clamping protocol , the number of patients requiring a transfusion was 2.2 times less than the number in the non-clamping protocol , but was not significantly different ( odds ratio = 2.20 , p = 0.24 ) , and the significant predictor of blood transfusion was the preoperative hemoglobin level ( odds ratio = 7.73 , p < 0.001 ) . No wound infection or clinical venous thromboembolisms were detected in our study . Conclusion The 3-h interval clamping is a newly developed protocol for reducing blood loss after TKA . The protocol lessens the decrease in postoperative hemoglobin levels . This protocol can be applied easily without increasing clinical thromboembolic events and wound complications 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 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 prospect ively studied the cases of 121 patients who were being operated on for insertion of a unilateral total knee prosthesis with cement , and we placed them r and omly in four groups . In Group I , the tourniquet was inflated throughout the operative procedure , and we released it postoperatively after a compressive dressing had been applied ; a splint was used postoperatively for three days . In Group II , the tourniquet remained inflated throughout the operation , but no splint was applied postoperatively , and continuous passive motion was started immediately in the recovery room . In Group III , the tourniquet was released intraoperatively , and hemostasis was achieved by cauterization ; postoperatively , a compressive dressing was applied , and a splint was used for three days . In Group IV , the tourniquet was released intraoperatively , hemostasis was established , and then the tourniquet was reinflated ; a compressive dressing was applied , and continuous passive motion was started immediately in the recovery room . Hemoglobin and hematocrit values were monitored in all patients . Blood loss in suction drainage was recorded , and the total blood loss was calculated . The results show that total knee arthroplasty is associated with major loss of blood ( mean , 1518 milliliters ) . The calculated blood loss for Groups I , II , and III averaged 1443 milliliters , while that for Group IV averaged 1793 milliliters . Loss in suction drainage correlated with total estimated blood loss and averaged 511 milliliters . The magnitude of blood loss after total knee arthroplasty should be appreciated , and special attention should be paid to the availability of adequate fluid and blood products , preferably blood donated by the patient preoperatively 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 r and omized trial of postoperative drainage-clamping practice was performed in 89 knees undergoing total knee arthroplasty . In group 1 ( 43 knees ) , drainage was clamped for the first 4 postoperative hours . In group 2 ( 46 knees ) , drainage was not clamped . The average bloody drainage was significantly less in group 1 than group 2 ( 514.85 + /- 378.0 vs 843.4 + /- 366.4 mL ) . The decrease of hemoglobin and hematocrit after surgery was also significantly less in group 1 . Group differences between postoperative range of motion and narcotics requirements , length of stay , immediate wound problems , and deep vein thrombosis were nonsignificant . These results suggested that clamping the drainage in the first 4 postoperative hours reduces postoperative blood loss without causing excess morbidity after total knee arthroplasty In a r and omised , blinded study 76 patients undergoing primary total knee arthroplasty were assigned to either immediate drain opening ( n = 45 ) or drains opened at 2 h ( n = 31 ) . No significant differences were found between the groups for the volume of drained blood , transfusion requirements , knee motion or wound status . The authors conclude that the practice of clamping drains has no benefit in routine knee arthroplasty . However , when faced with immediate brisk blood loss , the results suggest that drains can be clamped without any excess morbidity A prospect i ve study of 69 patients ( 138 knees ) who had a primary simultaneous bilateral total knee replacement 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 side for the drained versus nondrained side . The same operative technique was used in all wounds of total knee arthroplasty . The knees that had no drains had a higher incidence of drainage from the wound , had soaked dressings requiring dressing reinforcements , and had more ecchymosis and erythema around the wound . However , the final results regarding quadriceps strength , range of motion , and wound complications were not affected significantly by nonuse of closed suction drainage . Although the incidence of infection in the two groups is not statistically different , the development of infection in two knees in which drains were not used suggests that suction drainage may reduce deep infection |
1,748 | 26,256,890 | Published estimates of fatality are high among certain population s of chronic HCV patients , with liver-specific causes being an important contributor . | Despite reports that mortality is increasing , overall case fatality due to hepatitis C virus ( HCV ) is thought to be low .
Given the variability in published rates , we aim ed to synthesize estimates of liver-specific case fatality and all-cause mortality in chronic HCV according to follow-up duration , sustained viral response ( SVR ) to treatment , and liver disease severity . | BACKGROUND A total of 738 volunteer blood donors who were positive for anti-hepatitis C virus ( HCV ) were assessed for risk factors and outcomes for up to 15 years within the study and up to 54 years from the estimated onset of infection . METHODS A third-generation recombinant immunoblot assay ( RIBA ) was performed to distinguish true from false anti-HCV reactivity . Findings of HCV polymerase chain reaction classified subjects as having chronic HCV infection or as having recovered . Liver biopsy specimens were staged by Ishak fibrosis score and grade d by histologic activity index . RESULTS Of 738 anti-HCV-positive subjects , 469 ( 64 % ) had positive RIBA results , 217 ( 29 % ) had negative results , and 52 ( 7 % ) had indeterminate results . Primary independent risk factors were injection drug use ( odds ratio [ OR ] , 35.0 ; P < .0001 ) , blood transfusion ( OR , 9.9 ; P < .0001 ) , and intranasal cocaine use , including 79 " snorters " who repeatedly denied injection drug use or blood transfusion ( OR , 8.5 ; P < .0001 ) . Classification and regression tree and r and om forest analyses confirmed these risk factors . A total of 384 RIBA-positive donors ( 82 % ) were HCV RNA positive ; of these , liver biopsy specimens from 185 ( 48 % ) showed no fibrosis in 33 % , mild fibrosis in 52 % , bridging fibrosis in 12 % , and cirrhosis in 2 % a mean duration of 25 years after infection . Analysis of 63 repeat biopsy specimens showed that 8 % progressed ≥2 Ishak stages over 5 years ( mean progression , 0.06 Ishak stages/year ) . CONCLUSIONS Injection drug use and blood transfusion before 1990 are dominant risk factors for HCV acquisition ; intranasal cocaine use may be a surreptitious route of parenteral spread . After a mean of 25 years of HCV infection , histologic outcomes were relatively mild : 85 % had no or mild fibrosis , and only 2 % had cirrhosis . Nearly one-fifth spontaneously recovered BACKGROUND Liver-related mortality among those infected with hepatitis C virus ( HCV ) has been described , but little is known about non-liver-related mortality . Our objective was to determine HCV-associated all-cause , liver- , and non-liver-related mortality in the general US population . METHODS A prospect i ve cohort study of 9378 nationally representative adults aged 17 - 59 years was performed utilizing the Third National Health and Nutrition Examination Survey ( NHANES III ) Linked Mortality File that was made publicly available in 2010 . HCV status was assessed from 1988 to 1994 , with mortality follow-up of the same individuals through 2006 . RESULTS There were 614 deaths over a median follow-up of 14.8 years . After adjusting for all covariate risk factors , HCV chronic infection had a 2.37 times higher all-cause mortality rate ratio [ MRR ] ( 95 % CI : 1.28 - 4.38 ; P = .008 ) , a 26.46 times higher liver-related MRR ( 95 % CI : 8.00 - 87.48 ; P < .001 ) , and 1.79 times higher non-liver-related MRR ( 95 % CI : .77 - 4.19 ; P = .18 ) , compared with being HCV-negative . This represents an estimated 2.46 million US adults aged 17 - 59 years with chronic HCV infection who had an estimated 31,163 deaths from all causes per year , of which 57.8 % ( 95 % CI : 21.9%-77.2 % ) were attributable to HCV . Among those , there was an estimated 9569 liver-related deaths per year , of which 96.2 % ( 95 % CI : 87.5 - 98.9 % ) were attributable to HCV . Non-liver-related deaths were not significantly associated with HCV status . CONCLUSIONS Chronic HCV all-cause mortality is more than twice that of HCV-negative individuals . This suggests that those with chronic HCV infection are at a higher risk of death even after accounting for liver-related morbidity and should be closely monitored Objective : The purpose of this study was to eluci date the long-term outcome after interferon ( IFN ) therapy in chronic hepatitis C elderly patients . Methods : We studied the incidence of hepatocellular carcinoma ( HCC ) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients > 60 years . The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years . Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy . Sustained virological response ( SVR ) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy . Non-response ( NR ) was applied to patients who did not show SVR . Hepatic fibrosis was defined as the fibrosis score ( score 0–4 ) according to Knodell et al. Results : 140 patients ( 28 % ) had an SVR and 360 patients ( 72 % ) had an NR . 71 of 500 patients developed HCC during follow-up . The cumulative incidence of HCC was 9.6 % at the 5th year , 17.4 % at the 10th year , and 31.3 % at the 15th year . HCC developed with significance when : ( 1 ) HCV was not cleared after IFN therapy ( p < 0.0001 ) , ( 2 ) sex was male ( p < 0.0001 ) , and ( 3 ) staging of liver fibrosis was > 2 ( p = 0.008 ) . 53 of the patients died . The cumulative survival probability was 95.7 % at the 5th year , 86.4 % at the 10th year , and 78 % at the 15th year . Patients achieved a long survival with significance when : ( 1 ) staging of liver fibrosis was 1 ( p < 0.0001 ) , ( 2 ) HCV was cleared after IFN therapy ( p = 0.034 ) , and ( 3 ) sex was female ( p = 0.015 ) . Conclusion : Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are ≧60 years Background No study has compared the long-term prognoses of hepatitis C patients with hepatitis C virus ( HCV ) antibody-negative individuals and investigated the effects of interferon ( IFN ) treatment . To clarify the long-term prognosis of HCV-positive residents of an isolated Japanese isl and and prospect ively investigate the effects of IFN treatment in comparison with the HCV-negative general population . Methods HCV antibody was positive in 1,343 ( 7.6 % ) of the 17,712 individuals screened . 792 HCV RNA-positive , HBsAg-negative subjects were enrolled . 1,584 HCV antibody-negative , HBsAg-negative general residents were sex- and age-matched to the 792 subjects . A total of 154 < 70-year-old patients without liver cirrhosis ( LC ) or hepatocellular carcinoma ( HCC ) underwent IFN treatment . The survival rate with all-cause death as the endpoint was determined and causes of death were compared . Results The 10- and 20-year survival rates of the hepatitis C and general resident groups were 65.4 % and 87.8 % , and 40.8 % and 62.5 % , respectively ( p < 0.001 ; hazard risk ratio , 0.444 ; 95 % confidence interval ( CI ) : 0.389–0.507 ) . There were 167 liver disease-related deaths and 223 deaths from other causes in the hepatitis C group , and 7 and 451 , respectively , in the general resident group . Liver disease-related death accounted for 43.8 % and 1.5 % of deaths in the hepatitis C and general resident groups ( p < 0.0001 ) . The cumulative survival rate of the hepatitis C patients without IFN ( n = 328 ) was significantly lower than the gender- and age-matched general resident group ( n = 656 ) ( p < 0.0001 ) but there was no significant difference between the IFN-treated ( n = 154 ) and general resident groups ( n = 308 ) . Conclusions In the hepatitis C group , the proportion of liver disease-related death was markedly higher , and the survival rate lower , than the general resident group . Introduction of IFN treatment in < 70-year-old patients with hepatitis C without LC or HCC improved the survival rate to a level comparable to that of the general residents BACKGROUND / AIMS HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis . Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting . METHODS Pegylated-interferon alpha-2b and ribavirin were administered at a dose of 1 microg/kg of bwt weekly and 600 - 800 mg/day . Planned duration of treatment was 24 or 48 weeks according to HCV genotype . Patients who failed to respond at week 24 were considered as non-responders . RESULTS 61 patients were enrolled . According to intention-to-treat analysis , 44 ( 72 % ) patients were considered as treatment failure ( 31 non-responders , 4 relapsers , 9 dropout ) . Sustained virological response was achieved in 17 cases ( 28 % ) . Genotype 2 , higher doses of antivirals and absence of histological cirrhosis were predictors of sustained virological response . In the follow up , patients with sustained virological response had a significantly lower mortality compared to patients with treatment failure ( chi2=6.9 ; P<0.01 ) . CONCLUSIONS Response rate to antiviral therapy in HCV reinfection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed . Sustained virological response improves patient survival BACKGROUND & AIMS The natural history of HCV-related compensated cirrhosis has been poorly investigated in Latin-American countries . Our study evaluated mortality and clinical outcomes in compensated cirrhotic patients followed for 6 years . METHODS Four hundred and two patients with compensated HCV-related cirrhosis were prospect ively recruited in a tertiary care academic center . At the time of admission , patients were stratified as compensated ( absence [ stage 1 ] or presence [ stage 2 ] of esophageal varices ) as defined by D'Amico et al. Subjects were followed to identify overall mortality or liver transplantation and clinical complication rates . RESULTS Among 402 subjects , 294 were categorized as stage 1 and 108 as stage 2 . Over a median of 176 weeks , 42 deaths occurred ( 10 % ) , of which 30 were considered liver-related ( 7 % ) and 12 non-liver-related ( 3 % ) ; eight individuals ( 2 % ) underwent liver transplantation ; 30 patients ( 7 % ) developed HCC , 67 individuals in stage 1 ( 22 % ) developed varices and any event of clinical decompensation occurred in 80 patients ( 20 % ) . The 6-year cumulative overall mortality or liver transplantation was 15 % and 45 % , for stages 1 and 2 , respectively ( p<0.001 ) . The cumulative 6-year HCC incidence was significantly higher among patients with varices ( 29 % ) than those without varices ( 9 % ) , p<0.001 . Similarly , the cumulative 6-year incidence of any clinical liver-related complication was higher in patients with stage 2 ( 66 % ) as compared to 26 % in those with stage 1 , respectively ( p<0.001 ) . CONCLUSIONS Our results indicate significant morbidity and mortality and clinical outcome rates in compensated cirrhotic patients with varices ( stage 2 ) OBJECTIVES : The identification of prognostic factors associated with mortality is crucial in any clinical setting . METHODS : We enrolled in a prospect i ve study 352 patients with compensated hepatitis C virus (HCV)-induced cirrhosis , consecutively observed between 1989 and 1992 . At entry , patients underwent upper endoscopy to detect esophageal varices , and were then surveilled by serial clinical and ultrasonographic examination . The model for end-stage liver disease ( MELD ) score was calculated with information collected at enrollment . Baseline predictors and intercurrent events associated with mortality were assessed using the Cox regression model . RESULTS : During a median follow-up of 14.4 years , 194 subjects received a single course of interferon monotherapy , 131 patients developed decompensation ( ascites , bleeding , hepatic encephalopathy ) , 109 patients had hepatocellular carcinoma ( HCC ) , 9 had liver transplant , and 158 died . Esophageal varices were associated with development of decompensation ( hazard ratio ( HR ) , 2.09 ; 95 % confidence interval ( CI ) , 1.33–3.30 ) and liver-related death ( HR , 2.27 ; 95 % CI , 1.41–3.66 ) . A MELD score of 10 predicted overall mortality ( HR , 2.15 ; 95 % CI , 1.50–3.09 ) . Overall survival of patients with MELD ≤10 was 80 % at 10 years . HCC occurrence increased the risk of decompensation fivefold ( HR , 5.52 ; 95 % CI , 3.77–8.09 ) . Hepatic and overall mortality hazard ratios were 8.62 ( 95 % CI , 5.57–13.3 ) and 3.80 ( 95 % CI , 2.67–5.42 ) , respectively , for patients who developed HCC , and 16.9 ( 95 % CI , 9.97–28.6 ) and 7.08 ( 95 % CI , 4.88–10.2 ) for those who experienced decompensation . CONCLUSIONS : In patients with compensated HCV-induced cirrhosis , the presence of esophageal varices at baseline predicted decompensation and mortality . The development of HCC during follow-up strongly hastens the occurrence of decompensation , which is the main determinant of death . Patients with a MELD score ≤10 at study entry had a prolonged life expectancy UNLABELLED The overall mortality of patients infected with hepatitis C virus ( HCV ) has not been fully eluci date d. This study analyzed mortality in subjects positive for antibody to HCV ( anti-HCV ) in a community-based , prospect i ve cohort study conducted in an HCV hyperendemic area of Japan . During a 10-year period beginning in 1995 , 1125 anti-HCV-seropositive residents of Town C were enrolled into the study and were followed for mortality through 2005 . Cause of death was assessed by death certificates . Subjects with detectable HCV core antigen ( HCVcAg ) or HCV RNA were considered as having hepatitis C viremia and were classified as HCV carriers ; subjects who were negative for both HCVcAg and HCV RNA ( i.e. , viremia-negative ) were considered as having had a prior HCV infection and were classified as HCV noncarriers . Among the anti-HCV-positive subjects included in the analysis , 758 ( 67.4 % ) were HCV carriers , and 367 were noncarriers . A total of 231 deaths occurred in these subjects over a mean follow-up of 8.2 years : 176 deaths in the HCV carrier group and 55 in the noncarrier group . The overall mortality rate was higher in HCV carriers than in noncarriers , adjusted for age and sex ( hazard ratio , 1.53 ; 95 % confidence interval , 1.13 - 2.07 ) . Although liver-related deaths occurred more frequently among the HCV carriers ( hazard ratio , 5.94 ; 95 % confidence interval , 2.58 - 13.7 ) , the rates of other causes of death did not differ between HCV carriers and noncarriers . Among HCV carriers , a higher level of HCVcAg ( > or=100 pg/mL ) and persistently elevated alanine aminotransferase levels were important predictors of liver-related mortality . CONCLUSION The presence of viremia increases the rate of mortality , primarily due to liver-related death , among anti-HCV-seropositive persons in Japan UNLABELLED Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response ( SVR ) have a lower risk of hepatic decompensation and hepatocellular carcinoma ( HCC ) . In this prospect i ve analysis , we compared the rate of death from any cause or liver transplantation , and of liver-related morbidity and mortality , after antiviral therapy among patients who achieved SVR , virologic nonresponders ( NR ) , and those with initial viral clearance but subsequent breakthrough or relapse ( BT/R ) in the HALT-C ( Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis ) Trial . Laboratory and /or clinical outcome data were available for 140 of the 180 patients who achieved SVR . Patients with nonresponse ( NR ; n = 309 ) or who experienced breakthrough or relapse ( BT/R ; n = 77 ) were evaluated every 3 months for 3.5 years and then every 6 months thereafter . Outcomes included death , liver-related death , liver transplantation , decompensated liver disease , and HCC . Median follow-up for the SVR , BT/R , and NR groups of patients was 86 , 85 , and 79 months , respectively . At 7.5 years , the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group ( 2.2 % and 2.7 % , respectively ) was significantly lower than that of the NR group ( 21.3 % and 27.2 % , P < 0.001 for both ) but not the BT/R group ( 4.4 % and 8.7 % ) . The adjusted hazard ratio ( HR ) for time to death/liver transplantation ( HR = 0.17 , 95 % confidence interval [ CI ] = 0.06 - 0.46 ) or development of liver-related morbidity/mortality ( HR = 0.15 , 95 % CI = 0.06 - 0.38 ) or HCC ( HR = 0.19 , 95 % CI = 0.04 - 0.80 ) was significant for SVR compared to NR . Laboratory tests related to liver disease severity improved following SVR . CONCLUSION Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation , and in liver-related morbidity/mortality , although they remain at risk for HCC Context Few studies have documented histologic regression of cirrhosis . Contribution This study describes 96 patients with chronic hepatitis C and biopsy-proven cirrhosis who were treated with an interferon-based regimen and who had at least 1 post-treatment liver biopsy . Eighteen patients had biopsy-proven regression of cirrhosis . Patients with regression had better 10-year survival rates than did patients without regression ( 100 % vs. 74 % ) . Implication Cirrhosis may be reversible in some patients with chronic hepatitis C. The Editors Single or multifactorial damage to the liver ultimately leads to cirrhosis and its complications , especially hepatocellular carcinoma ( 13 ) . Different types of evidence histologic ; morphologic ( as assessed by abdominal ultrasonography or digestive endoscopy ) ; and biochemical ( as assessed by measurement of hyaluronate , procollagen III peptide , prothrombin time , and platelets ) , including analyses of native liverssupport the idea that cirrhosis can be reversed , provided that the underlying disease is controlled ( 58 ) . Nevertheless , whether cirrhosis regresses is still debated ( 9 , 10 ) . To provide definitive support for this concept , we evaluated the relation between histologic regression of cirrhosis and clinical outcome in patients treated for chronic hepatitis C. Methods Study Design We established a cohort of 143 patients with biopsy-proven cirrhosis ( METAVIR F4 ) who received specific treatment between 1988 and 2001 at a single hepatology unit in a tertiary care center in France and who underwent a second liver biopsy to assess the effect of treatment on cirrhosis ( Appendix Figure ) ( 6 , 8 , 11 ) . All patients in this cohort currently undergo prospect i ve follow-up and are seen by a senior hepatologist at least every 6 months . The institutional review board of our hospital approved the past and present studies , and all patients gave informed consent . Appendix Figure . Study flow diagram . We included patients who met the following criteria : ChildPugh class A cirrhosis related to chronic hepatitis C ; absence of hepatitis B co-infection ; absence of immunosuppression ( HIV-associated infection , long-term hemodialysis , organ transplantation , immunosuppressive therapy ) ; and treatment with conventional -interferon or pegylated interferon , with or without ribavirin . The exclusion criteria were age older than 70 years at the time of diagnosis of cirrhosis and previous liver-related complications . Sustained virologic response was defined as undetectable hepatitis C virus RNA on the latest available assaying technique and normal alanine aminotransferase level 24 weeks after the end of treatment and during follow-up . Patients who did not fulfill these criteria were classified as nonresponders and did not receive long-term treatment . Liver disease was staged and grade d according to the METAVIR score ( 12 ) , which combines an activity stage from 0 to 3 and a fibrosis grade from 0 to 4 ( 4 corresponds to cirrhosis ) . Regression of cirrhosis was defined as a decrease in the score from 4 to 2 or fewer METAVIR fibrosis units to avoid the 15 % rate of false-negative results in patients with F3 disease ( 13 , 14 ) . Patients underwent clinical and biological evaluation , including measurement of aminotransferase , bilirubin , albumin , prothrombin time , platelet , and hepatitis C viral load at each visit . All patients were screened for hepatocellular carcinoma with ultrasonography and had -fetoprotein measured every 6 months . The diagnosis of hepatocellular carcinoma followed the guidelines of the European Association for the Study of the Liver ( 15 ) . Hepatic encephalopathy was defined clinical ly ( 16 ) . Ascites was diagnosed by clinical examination and ultrasonography . The source of gastroesophageal bleeding was confirmed by endoscopy . Outcome Measures Our main goal was to evaluate the effect of regression of cirrhosis on a composite end point of liver-related complications ( ascites , hepatic encephalopathy , variceal bleeding , spontaneous bacterial peritonitis , hepatocellular carcinoma , liver transplantation ) and death from liver-related causes . For patients with more than 1 event , only the first event was analyzed . The incidence of liver-related deaths or transplantation was analyzed as a secondary end point . Statistical Analysis Total duration of follow-up was calculated from the date of the first liver biopsy until death , last consultation , or liver transplantation until November 2006 . Eight patients ( 8 % ) were not followed in our unit as of this date after a median follow-up of 96 months ( range , 36 to 127 months ) . These patients were censored at the time of the last visit . The time from diagnosis of cirrhosis ( time of the index biopsy ) to liver-related complications or to the date when the data were censored was plotted according to groups by using KaplanMeier estimates , and P values were computed with the log-rank test . All P values are 2-sided , and the type I error was set at 5 % . Continuous values are presented as medians and interquartile ranges and categorical variables as counts and proportions . The differences between groups were assessed with the Fisher exact test and the MannWhitney U test . All statistical analyses were performed by using SPSS software , version 16 ( SPSS , Chicago , Illinois ) . Role of the Funding Source This study was funded by the French Agence Nationale de la Recherche ( ANR ) . The funding source had no role in the design , analysis , or interpretation of the study or in the decision to su bmi t the manuscript for publication . Results Sample Ninety-six patients fulfilled the inclusion criteria ( Table 1 ) . All had ChildPugh class A biopsy-proven cirrhosis at enrollment and thereafter received specific therapy . The median interval between the first liver biopsy and treatment was 2 months ( interquartile range , 0 to 6 months ) . Sixty-one patients ( 64 % ) received interferon monotherapy , 34 ( 35 % ) received interferon and ribavirin , and 1 ( 1 % ) received pegylated interferon and ribavirin . Eighty-two patients ( 85 % ) did not respond to the first treatment course ; of these , 47 ( 49 % ) received at least 1 more treatment course . Thirty-nine patients ( 41 % ) achieved a sustained virologic response , and 57 ( 59 % ) did not . Table 1 . Patient Characteristics at Baseline Histologic Outcome The median interval between the end of treatment and the second liver biopsy was 17 months . The median length of the liver biopsy sample s was 15 mm ( interquartile range , 10 to 20 mm ) both before and after treatment ( P= 0.86 , Wilcoxon signed-rank test ) . In terms of fibrosis scores , 69 liver biopsies ( 71.9 % ) showed persistent cirrhosis ( METAVIR fibrosis stage 4 ) , 9 ( 9.4 % ) showed extensive fibrosis ( stage 3 ) , 10 ( 10.4 % ) showed intermediate fibrosis ( stage 2 ) , 7 ( 7.3 % ) showed moderate fibrosis ( stage 1 ) , and 1 ( 1 % ) showed no fibrosis ( stage 0 ) . Of the 18 patients with regression of cirrhosis on the second liver biopsy ( METAVIR fibrosis stage 0 , 1 , or 2 ) , 17 ( 94.4 % ) had long-term response to therapy and 1 had biochemical response ( normal liver function tests and no detectable activity on liver biopsy but persistent viremia ) to antihepatitis C therapy . Clinical Outcome The median follow-up was 118 months ( interquartile range , 86 to 138 months ) , and total follow-up was 900 patient-years . The time from achievement of sustained virologic response to the end of follow-up was similar between patients with and those without regression of cirrhosis ( P= 0.38 ) . During follow-up , 27 ( 35 % ) patients with persistent cirrhosis developed at least 1 cirrhosis-related complication ( Table 2 ) . The incidence of liver-related complications , including hepatocellular carcinoma , was lower in patients with a sustained virologic response ( Figure , top ) . Nevertheless , 4 patients with hepatitis Crelated cirrhosis developed a liver-related event , including variceal bleeding ( 1 patient ) and hepatocellular carcinoma ( 3 patients ) ; all had antihepatitis B core antigen antibodies . In contrast , patients with regression of cirrhosis had no complications ( Figure , bottom ) . The incidence of cirrhosis-related complications per 100 patient-years was 1.14 in patients with sustained virologic response and 4.63 in those without sustained virologic response ( P= 0.009 ) ; respective values in patients with and those without regression of cirrhosis were 0 and 4 ( P= 0.002 ) . Table 2 . Clinical Outcomes , by Virologic and Histologic Response Figure . KaplanMeier estimates of time to a liver-related event and death in patients with or without a sustained virologic response ( top ) and in patients with or without regression of cirrhosis ( bottom ) . Liver-related events were hepatocellular carcinoma , hepatic encephalopathy , variceal bleeding , ascites , spontaneous bacterial peritonitis , and liver transplantation . During follow-up , 22 patients ( 23 % ) without regression died ( n= 16 [ 17 % ] ) or underwent a liver transplantation ( n= 6 [ 6 % ] ) , whereas neither of these events occurred in the 18 patients with regression ( P= 0.010 ) . The incidence of liver-related death or liver transplantation per 100 patient-years was 0.85 in patients with sustained virologic response and 3.43 in those without sustained virologic response ( P= 0.004 , log-rank test ) ; respective values in patients with and those without cirrhosis were 0 and 2.96 ( P= 0.025 , log-rank test ) . Among the 6 patients who had liver transplantation , 5 survived and 1 died during the perioperative period . Four patients died of nonliver-related causes . One patient with regression of cirrhosis died of myocardial infa rct ion . Discussion During more than 10 years of follow-up in 96 patients with treated hepatitis Crelated cirrhosis , 18 patients achieved histologically proven regression . The absence of liver-related morbidity and mortality in these patients supports the concept of cirrhosis reversal . Persistence of cirrhosis carries a risk for hepatocellular carcinoma , which warrants regular screening . Regression of hepatitis Crelated cirrhosis after treatment ranges from 10 % Knowledge of the natural course and especially the total and cause-specific mortality of community-acquired chronic HCV infection is limited . The aims of our study were to determine the total and cause-specific mortality in patients infected with chronic hepatitis C in a community-based setting in northern Norway . This prospect i ve cohort study included 1010 HCV-positive patients diagnosed with recombinant immunoblot assay between 1 January 1990 and 1 January 2000 , with a median observation time from diagnosis to follow-up of 7 years . Data were collected from medical records in the period between 1 January 2004 and 30 June 2006 . Time and cause of death were ascertained from the Norwegian Causes of Death Register . Age-adjusted death rates and st and ardised mortality ratios ( SMRs ) were compared with those of the general Norwegian population . In total , 122 deaths were recorded . The Kaplan-Meier estimate of survival was 88 % at 14 years . The SMR in the cohort relative to the general population was 6.66 . Most of the excess deaths in both genders were because of liver-related causes , those associated with a drug-using lifestyle and suicide . The statistically significant increase in SMRs ranged from 4.2 for death by cancer in women to 64.6 for liver disease in women . There was no statistically significant increase in SMRs from cardiovascular disease in either gender or from cancer in men . In conclusion , our study shows that the death rate in patients infected with hepatitis C is 6.66 times higher than in the general Norwegian population |
1,749 | 16,194,185 | Studies report positive results , including improvements in mood , sleep quality and reductions in stress .
A dose-response effect has been observed between practice of Mindfulness-Based Stress Reduction and improved outcome .
Mindfulness-Based Stress Reduction has potential as a clinical ly valuable self-administered intervention for cancer patients . | AIM This paper reports a systematic review and critical appraisal of the evidence on the effectiveness of Mindfulness-Based Stress Reduction for cancer supportive care .
BACKGROUND The experience of cancer can have a negative impact on both psychological and physical health and on quality of life .
Mindfulness-Based Stress Reduction is a therapy package that has been used with patients with a variety of conditions .
In order to draw conclusions on its effectiveness for cancer patients , the evidence requires systematic assessment . | OBJECTIVE The diagnosis of breast cancer , the most common type of cancer among American women , elicits greater distress than any other diagnosis regardless of prognosis . Therefore , the present study examined the efficacy of a stress reduction intervention for women with breast cancer . METHODS As part of a larger , r and omized , controlled study of the effects on measures of stress of a mindfulness-based stress reduction ( MBSR ) intervention for women with breast cancer , the current analyses examined the effects on sleep complaints . RESULTS Analyses of the data indicated that both MBSR and a free choice ( FC ) control condition produced significant improvement on daily diary sleep quality measures though neither showed significant improvement on sleep-efficiency . Participants in the MBSR who reported greater mindfulness practice improved significantly more on the sleep quality measure most strongly associated with distress . CONCLUSION MBSR appears to be a promising intervention to improve the quality of sleep in woman with breast cancer whose sleep complaints are due to stress Objective The objective of this study was to assess the effects of participation in a mindfulness meditation – based stress reduction program on mood disturbance and symptoms of stress in cancer out patients . Methods A r and omized , wait-list controlled design was used . A convenience sample of eligible cancer patients enrolled after giving informed consent and were r and omly assigned to either an immediate treatment condition or a wait-list control condition . Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention . The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice . Results Ninety patients ( mean age , 51 years ) completed the study . The group was heterogeneous in type and stage of cancer . Patients ’ mean preintervention scores on dependent measures were equivalent between groups . After the intervention , patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression , Anxiety , Anger , and Confusion and more Vigor than control subjects . The treatment group also had fewer overall Symptoms of Stress ; fewer Cardiopulmonary and Gastrointestinal symptoms ; less Emotional Irritability , Depression , and Cognitive Disorganization ; and fewer Habitual Patterns of stress . Overall reduction in Total Mood Disturbance was 65 % , with a 31 % reduction in Symptoms of Stress . Conclusions This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and ages OBJECTIVES The purpose of this study was to examine the effects of a structured , 8-week , Mindfulness-Based Stress Reduction ( MBSR ) program on perceived stress , mood , endocrine function , immunity , and functional health outcomes in individuals infected with the human immunodeficiency virus ( HIV ) . DESIGN This study used a quasiexperimental , nonr and omized design . METHODS Subjects were specifically recruited ( nonr and om ) for intervention ( MBSR ) or comparison group . Data were collected at pretest and post-test in the MBSR group and at matched times in the comparison group . t Tests where performed to determine within-group changes and between-group differences . RESULTS Natural killer cell activity and number increased significantly in the MBSR group compared to the comparison group . No significant changes or differences were found for psychological , endocrine , or functional health variables . CONCLUSIONS These results provide tentative evidence that MBSR may assist in improving immunity in individuals infected with HIV PURPOSE Epidemiological and laboratory evidence indicates that a Western diet is associated with an increased incidence of prostate cancer . Specific components of the diet , such as high saturated fat , low fiber and high meat content , may have greatest clinical significance in the later stages of tumor promotion and progression . However , departure from the conventional diet is difficult to initiate and maintain . Therefore , we combined the well-known Mindfulness-Based Stress Reduction ( MBSR ) program with a low saturated fat , high-fiber , plant-based diet to determine the effect on the rate of change in prostate specific antigen ( PSA ) in patients with biochemical recurrence after prostatectomy . MATERIAL S AND METHODS We enrolled 10 men and their partners in a 4-month group-based diet and MBSR intervention . A pre- study post- study design in which each subject served as his own control was used to compare the rate of increase in and doubling time of PSA before and after intervention . RESULTS The rate of PSA increase decreased in 8 of 10 men , while 3 had a decrease in absolute PSA . Results of the signed rank test indicated a significant decrease in the rate of increase in the intervention period ( p = 0.01 ) . Estimated median doubling time increased from 6.5 months ( 95 % confidence interval 3.7 to 10.1 ) before to 17.7 months ( 95 % confidence interval 7.8 to infinity ) after the intervention . CONCLUSIONS Our small study provides evidence that a plant-based diet delivered in the context of MBSR decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer . Larger-scale r and omized studies are warranted to explore further the preventive and therapeutic potential of diet and lifestyle modification in men with prostate cancer OBJECTIVES This study investigated the relationships between a mindfulness-based stress reduction meditation program for early stage breast and prostate cancer patients and quality of life , mood states , stress symptoms , and levels of cortisol , dehydroepi and rosterone-sulfate ( DHEAS ) and melatonin . METHODS Fifty-nine patients with breast cancer and 10 with prostate cancer enrolled in an eight-week Mindfulness-Based Stress Reduction ( MBSR ) program that incorporated relaxation , meditation , gentle yoga , and daily home practice . Demographic and health behavior variables , quality of life , mood , stress , and the hormone measures of salivary cortisol ( assessed three times/day ) , plasma DHEAS , and salivary melatonin were assessed pre- and post-intervention . RESULTS Fifty-eight and 42 patients were assessed pre- and post-intervention , respectively . Significant improvements were seen in overall quality of life , symptoms of stress , and sleep quality , but these improvements were not significantly correlated with the degree of program attendance or minutes of home practice . No significant improvements were seen in mood disturbance . Improvements in quality of life were associated with decreases in afternoon cortisol levels , but not with morning or evening levels . Changes in stress symptoms or mood were not related to changes in hormone levels . Approximately 40 % of the sample demonstrated abnormal cortisol secretion patterns both pre- and post-intervention , but within that group patterns shifted from " inverted-V-shaped " patterns towards more " V-shaped " patterns of secretion . No overall changes in DHEAS or melatonin were found , but nonsignificant shifts in DHEAS patterns were consistent with healthier profiles for both men and women . CONCLUSIONS MBSR program enrollment was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients , and result ed in possibly beneficial changes in hypothalamic-pituitary-adrenal ( HPA ) axis functioning . These pilot data represent a preliminary investigation of the relationships between MBSR program participation and hormone levels , highlighting the need for better-controlled studies in this area Two hundred fifteen r and omly accessed cancer patients who were new admissions to three collaborating cancer centers were examined for the presence of formal psychiatric disorder . Each patient was assessed in a common protocol via a psychiatric interview and st and ardized psychological tests . The American Psychiatric Association 's DSM-III diagnostic system was used in making the diagnoses . Results indicated that 47 % of the patients received a DSM-III diagnosis , with 44 % being diagnosed as manifesting a clinical syndrome and 3 % with personality disorders . Approximately 68 % of the psychiatric diagnoses consisted of adjustment disorders , with 13 % representing major affective disorders ( depression ) . The remaining diagnoses were split among organic mental disorders ( 8 % ) , personality disorders ( 7 % ) , and anxiety disorders ( 4 % ) . Approximately 85 % of those patients with a positive psychiatric condition were experiencing a disorder with depression or anxiety as the central symptom . The large majority of conditions were judged to represent highly treatable disorders Abstract The goals of this work were to assess the effects of participation in a mindfulness meditation-based stress reduction program on mood disturbance and symptoms of stress in cancer out patients immediately after and 6 months after program completion . A convenience sample of eligible cancer patients were enrolled after they had given informed consent . All patients completed the Profile of Mood States ( POMS ) and Symptoms of Stress Inventory ( SOSI ) both before and after the intervention and 6 months later . The intervention consisted of a mindfulness meditation group lasting 1.5 h each week for 7 weeks , plus daily home meditation practice . A total of 89 patients , average age 51 , provided pre-intervention data . Eighty patients provided post-intervention data , and 54 completed the 6-month follow-up The participants were heterogeneous with respect to type and stage of cancer . Patients ' scores decreased significantly from before to after the intervention on the POMS and SOSI total scores and most subscales , indicating less mood disturbance and fewer symptoms of stress , and these improvements were maintained at the 6-month follow-up . More advanced stages of cancer were associated with less initial mood disturbance , while more home practice and higher initial POMS scores predicted improvements on the POMS between the pre- and post-intervention scores . Female gender and more education were associated with higher initial SOSI scores , and improvements on the SOSI were predicted by more education and greater initial mood disturbance . This program was effective in decreasing mood disturbance and stress symptoms for up to 6 months in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and educational background , and with disparate ages |
1,750 | 25,587,249 | The human and animal studies of Satureja Khuzestanica showed a significant antioxidative potential of the plant and its effectiveness for infertility improvement .
The use of oral antioxidants in infertility could improve sperm quality and pregnancy rates .
Improved fertility observed by SKEO in rats might be due to its antioxidative effect . | BACKGROUND The use of antioxidants in the treatment of infertility has been suggested and recent studies have indicated that oral administration of Satureja Khuzestanica essential oil ( SKEO ) to rats induces significant antioxidative effects .
OBJECTIVE This systematic review was conducted to evaluate the effectiveness of antioxidants in infertility and also to assess the effectiveness of Satureja Khuzestanica in infertility management . | We investigated the relationship between oxidative stress and poor oocyte quality and whether the antioxidant melatonin improves oocyte quality . Follicular fluid was sample d at oocyte retrieval during in vitro fertilization and embryo transfer ( IVF-ET ) . Intrafollicular concentrations of 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) in women with high rates of degenerate oocytes were significantly higher than those with low rates of degenerate oocytes . As there was a negative correlation between intrafollicular concentrations of 8-OHdG and melatonin , 18 patients undergoing IVF-ET were given melatonin ( 3 mg/day ) , vitamin E ( 600 mg/day ) or both melatonin and vitamin E. Intrafollicular concentrations of 8-OHdG and hexanoyl-lysine adduct were significantly reduced by these antioxidant treatments . One hundred and fifteen patients who failed to become pregnant with a low fertilization rate ( < or = 50 % ) in the previous IVF-ET cycle were divided into two groups during the next IVF-ET procedure ; 56 patients with melatonin treatment ( 3 mg/day ) and 59 patients without melatonin treatment . The fertilization rate was improved by melatonin treatment compared to the previous IVF-ET cycle . However , the fertilization rate was not significantly changed without melatonin treatment . Oocytes recovered from preovulatory follicles in mice were incubated with H2O2 for 12 hr . The percentage of mature oocytes with a first polar body was significantly reduced by addition of H2O2 ( 300 microm ) . The inhibitory effect of H2O2 was significantly blocked by simultaneous addition of melatonin . In conclusion , oxidative stress causes toxic effects on oocyte maturation and melatonin protects oocytes from oxidative stress . Melatonin is likely to improve oocyte quality and fertilization rates Satureja khuzestanica is an endemic plant of Iran that is widely distributed in the Southern part of the country . It has antioxidant properties and thus it seems to be useful in diseases related to oxidative stress such as diabetes and hyperlipidemia . The present study investigates the effect of S. khuzestanica supplement in metabolic parameters of hyperlipidemic patients with type 2 diabetes mellitus . Twenty-one hyperlipidemic patients with type 2 diabetes mellitus were r and omized in a double blind , placebo controlled clinical trial to receive either S. khuzestanica ( tablets contain 250 mg dried leaves ) or placebo once a day for 60 days . Blood sample s were obtained at baseline and at the end of the study . Sample s were analyzed for levels of glucose , total cholesterol , LDL-cholesterol , HDL-cholesterol , triglyceride , creatinine , thiobarbituric acid reactive substances ( TBARS ) as marker of lipid peroxidation and ferric reducing ability ( total antioxidant power , TAP ) . Treatment of patients by S. khuzestanica for 60 days induced significant decrease in total cholesterol ( P = 0.008 ) and LDL-cholesterol ( P = 0.03 ) while increased HDL-cholesterol ( P = 0.02 ) and TAP ( P = 0.007 ) in comparison with the baseline values . S. khuzestanica did not alter blood glucose , triglyceride , creatinin and TBARS levels . In comparison with baseline values , no significant change was observed in blood glucose , total cholesterol , LDL-cholesterol , HDL-cholesterol , triglyceride , creatinine , TBARS and TAP in placebo-treated group . Usage of S. khuzestanica as a supplement to drug regimen of diabetic type 2 patients with hyperlipidemia is recommended OBJECTIVE To assess the effect of treatment with a combination of clomiphene citrate as an antiestrogen and vitamin E as an antioxidant on the incidence of pregnancy and sperm variables in men with idiopathic oligozoospermia and infertility . DESIGN Prospect i ve , r and omized , placebo-controlled trial . SETTING The outpatient and rology clinic at a university hospital . PATIENT(S ) Sixty infertile men with idiopathic oligoasthenozoospermia . INTERVENTION(S ) Patients were r and omly assigned to two treatment groups : a group receiving the combination of clomiphene citrate ( 25 mg/day ) and vitamin E ( 400 mg/day ; n = 30 ) against a placebo group ( n = 30 ) . Treatment was maintained for 6 months . MAIN OUTCOME MEASURE(S ) Pregnancy incidence and variations in semen parameters . RESULT ( S ) A significantly higher pregnancy rate was found among the combination treatment group in comparison to the control group . The odds ratio was 3.76 and the 95 % confidence interval was 1.03 - 13.64 , with a 36.7 % pregnancy rate ( 11/30 ) in the combination treatment group compared with 13.3 % pregnancy rate ( 4/30 ) in the control group . The trial showed a significantly higher increase in sperm count and progressive sperm motility with nonsignificant changes in total sperm motility , percentage of abnormal forms and semen volume in the combination treatment group as compared to the control group . CONCLUSION ( S ) The combination of clomiphene citrate as an antiestrogen and vitamin E as an antioxidant can significantly increase the pregnancy rate and improve sperm count and progressive sperm motility in cases of idiopathic oligoasthenozoospermia Sperm DNA fragmentation is known to compromise male fertility . Previous findings have suggested the implication of oxidative stress in the etiology of this pathological condition . The present study was conducted to find out if the pathologically increased incidence of DNA fragmentation in ejaculated spermatozoa can be reduced by oral treatment with two antioxidants , vitamins C and E. Sixty-four men with unexplained infertility and an elevated ( > or = 15 % ) percentage of DNA-fragmented spermatozoa in the ejaculate were r and omized between an antioxidant treatment ( 1 g vitamin C and 1 g vitamin E daily for 2 months ) group and a placebo group . Sperm DNA fragmentation was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assay before and after treatment . No differences in basic sperm parameters were found between the antioxidant treatment and the placebo group before or after treatment . However , the percentage of DNA-fragmented spermatozoa was markedly reduced ( P < .001 ) in the antioxidant treatment group after the treatment ( 9.1 + /- 7.2 ) as compared with the pretreatment values ( 22.1 + /- 7.7 ) . No difference in the pretreatment and posttreatment incidence of sperm DNA fragmentation was observed in the placebo group . These data show that sperm DNA damage can be efficiently treated with oral antioxidants administered during a relatively short time period Peroxidative damage induced by reactive oxygen species ( ROS ) has been proposed as one of the major causes of defective sperm function . The ROS detected in semen reflect an imbalance between ROS generation and degradation . The objective of the present study was to investigate the relationship between the oxidative and anti-oxidative potential in semen of infertile patients and healthy donors . Specimens were obtained from 28 patients and 18 healthy donors ( controls ) . A conventional spermiogram , measurement of luminol-chemiluminescence ( CL ) in washed semen , and high performance liquid chromatography determination of ascorbic acid and urate concentrations in seminal plasma were performed . Oligozoospermic patients exhibited higher CL signals than controls ( P < 0.001 ) . Normozoospermic patients showed lower ascorbic acid ( mean + /- SE : 491 + /- 46 microM , P < 0.04 ) and urate concentrations ( 320 + /- 22 microM , P < 0.009 ) than controls ( 612 + /- 35 and 426 + /- 26 microM respectively ) . Seminal plasma ascorbic acid was negatively correlated with the CL signals ( P < 0.0006 ) and positively correlated with the percentage of spermatozoa with normal morphology ( P < 0.006 ) . This is the first report of a correlation between the anti-oxidant ascorbic acid in seminal plasma and ROS generation in human semen . Furthermore , the reduced ascorbic acid/urate concentrations found in semen of normozoospermic patients might be indicative of a reduced anti-oxidative protection OBJECTIVE To evaluate whether the association of antioxidants and anti-inflammatory compounds may be beneficial in treatment of patients with abacterial prostatovesiculoepididymitis ( PVE ) and elevated seminal leukocyte concentrations . DESIGN Open , prospect i ve , r and om study . SETTING Academic research environment . PATIENT(S ) Ninety-eight patients with PVE who had increased seminal leukocyte concentrations ( > 1 x 10(6 ) cells/mL ) . Carnitines ( group A ; n = 30 ) or nonsteroidal anti-inflammatory drugs ( group B ; n = 16 ) for 4 months ; nonsteroidal anti-inflammatory drugs for 2 months , followed by treatment with carnitines for 2 months ( group C ; n = 26 ) ; or nonsteroidal anti-inflammatory treatment given concomitantly with carnitines ( group D ; n = 26 ) for 4 months . MAIN OUTCOME MEASURE(S ) Semen variables , production of reactive oxygen species , and pregnancy outcome were evaluated before and after treatment and following a 3-month washout period . RESULT ( S ) Patients in group C had the highest reduction in production of reactive oxygen species associated with increased sperm motility and viability . Groups B and D experienced intermediate effects , and group A experienced the least effect . CONCLUSION ( S ) Antioxidant treatment with carnitines is effective in patients with abacterial PVE and increased seminal leukocyte concentrations if these patients have been pretreated with nonsteroidal anti-inflammatory drugs Numerous studies have reported beneficial effects of antioxidant drugs on semen quality , but there is no well-defined therapeutical protocol in male infertility . This study aim ed to test the effects of vitamin E and selenium supplementation on lipid peroxidation and on sperm parameters . The study included 54 voluntary and infertile men who produced semen sample s for spermiogram and for spectrophotometric measurement of a lipid peroxidatio n marker , the malondialdehyde ( MDA ) , and produced blood sample s for high-perf ormance liquid chromatography assessment of serum vitamin E level . The trial was r and omized and open . Twenty-eight men were supplemented daily by vitamin E ( 400 mg ) and selenium ( 225 µg ) , during 3 months . The remaining 26 patients received vitamin B ( 4,5 g/day ) for the same duration . Only 20 patients achieved their treatment and returned for control analysis . MDA concentrations in sperm were much less than in seminal plasma and motility and viability were inversely correlated with semen MDA levels . In contrast to vitamin B supplementation , vitamin E and selenium supplementation produced a significant decrease in MDA concentrations and an improvement of sperm motility . The results confirm the protective and beneficial effects of vitamin E and selenium on semen quality and advocate their use in male infertility treatment Asthenospermia is the main factor of male infertility among patients consulting the Asir Infertility Center in Abha , Saudi Arabia . Lipid peroxidation occurring in both the seminal plasma and spermatozoa was estimated by malondialdehyde ( MDA ) concentration . Spermatozoal MDA concentration was higher in men with decreased sperm motility . The MDA concentration in the seminal plasma exhibited no relationship with sperm concentration , sperm motility , the number of immotile spermatozoa , or even the absence of spermatozoa . The MDA concentration in sperm pellet suspensions of asthenospermic and oligoasthenospermic patients was almost twice that of the normospermic males . The MDA concentration in the sperm pellet suspension from normospermic or oligospermic patients was about 10 % that in the seminal plasma . However , the MDA concentration in the sperm pellet suspension of asthenospermic or oligoasthenospermic patients was about 15 % that in the seminal plasma . Treatment of asthenospermic patients with oral Vitamin E significantly decreased the MDA concentration in spermatozoa and improved sperm motility . Eleven out of the 52 treated patients ( 21 % ) impregnated their spouses ; nine of the spouses successfully ended with normal term deliveries , whereas the other two aborted in the first trimester . No pregnancies were reported in the spouses of the placebo-treated patients The present study aim ed to evaluate whether ascorbate , a reactive oxygen species ( ROS ) scavenger , can improve fertilization and development of human embryos in vitro when added to the simple salt solution human tubal fluid ( HTF ) or the complex tissue culture medium Ham 's F-10 , which contains iron and copper in its formulation . Human oocytes , spermatozoa and embryos from 83 infertile IVF couples were r and omly allocated and cultured in the presence or absence of 62.5 microM ascorbate in HTF medium ( 39 couples ) or Ham 's F-10 medium ( 44 couples ) . No significant effect of ascorbate on fertilization , number of cells and embryo grade per embryo on days 2 and 3 after insemination , or percentage of embryos showing developmental block on day 3 ( those embryos that were still at the 2-cell stage ) was observed when data were analysed together or divided into several groups according to the cause of infertility , quality of semen sample used for insemination and women 's age in either of the two media tested . Despite these results , a positive effect of ascorbate on fertilization and embryo development in vitro can not be totally ruled out until the effects of other , non-physiological concentrations of ascorbate and longer-term embryo cultures ( to the blastocyst stage ) have been tested In a r and omized , placebo-controlled , double-blind study we investigated whether high-dose oral treatment with vitamins C and E for 56 days was able to improve semen parameters of infertile men . Ejaculate parameters included semen volume , sperm concentration and motility , and sperm count and viability . Thirty-one patients without genital infection but with asthenozoospermia ( < 50 % motile spermatozoa ) and normal or only moderately reduced sperm concentration ( > 7 x 10(6 ) spermatozoa/ml ) ( according to WHO criteria ) were examined . To investigate the influence of the epididymal storage period on semen parameters , the patients were asked to deliver two semen sample s with abstinence times of 2 and 7 days both before and at the end of vitamin treatment . After r and omization , the patients received either 1000 mg vitamin C and 800 mg vitamin E ( n = 15 ) or identical placebo capsules ( n = 16 ) . No changes in semen parameters were observed during treatment , and no pregnancies were initiated during the treatment period . Combined high-dose antioxidative treatment with vitamins C and E did not improve conventional semen parameters or the 24-h sperm survival rate . Prolonged abstinence time increased ejaculate volume ( P < 0.05 ) , sperm count ( P < 0.05 ) , sperm concentration ( P < 0.05 ) and the total number of motile spermatozoa ( P < 0.05 ) AIM To evaluate the treatment of male infertility with a strong natural antioxidant , in addition to conventional treatment . METHODS Using a double blind , r and omized trial design , 30 men with infertility of > or = 2 months and female partners with no demonstrable cause of infertility received conventional treatment according to the guidelines of the World Health Organization ( WHO ) , and either a strong antioxidant Astaxanthin 16 mg/day ( AstaCarox , AstaReal AB , Gustavsberg , Sweden ) or placebo for 3 months . The effects of treatment on semen parameters , reactive oxygen species ( ROS ) , zona-free hamster oocyte test , serum hormones including testosterone , luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) and Inhibin B , and spontaneous or intrauterine insemination (IUI)-induced pregnancies were evaluated . RESULTS ROS and Inhibin B decreased significantly and sperm linear velocity increased in the Astaxanthin group ( n = 11 ) , but not in the placebo group ( n = 19 ) . The results of the zona-free hamster oocyte test tended to improve in the Astaxanthin group in contrast with the placebo group , though not reaching statistical significance . The total and per cycle pregnancy rates among the placebo cases ( 10.5 % and 3.6 % ) were lower compared with 54.5 % and 23.1 % respectively in the Astaxanthin group ( P = 0.028 ; P = 0.036 ) . CONCLUSION Although the present study suggests a positive effect of Astaxanthin on sperm parameters and fertility , the results need to be confirmed in a larger trial before recommending Astaxanthin for the complementary treatment of infertile men We performed a r and omized , prospect i ve , controlled , intention to treat study in order to determine the effectiveness of an antioxidant therapy in improve the quality of seminal fluid parameters and the natural pregnancies in men with persistent oligospermia ( 5–20 million/ml ) 6 months after retro grade embolization . Forty-two subjects were enrolled and r and omized in the study . Treated group ( 20 subjects ) was assigned to receive antioxidant therapy ( NAC 600 mg and vitamins – minerals ) . Untreated group ( 22 subjects ) received no adjunctive medical therapy and was used as controls . Our data were analyzed with an intention to treat strategy . A statistically significant increase in sperm count after antioxidant therapy was recorded ( P = 0.009 ) . After this therapy , no statistical differences in percentage of WHO class A motile sperm ( P = 0.752 ) and typical forms ( P = 0.926 ) were found . The univariate logistic regression analysis showed that a man treated with antioxidant therapy presented a probability to have a normal sperm count 20-fold ( OR = 20.1 ; CI 95 % = 1.05–43.2 ; P = 0.014 ) higher than a man who was untreated . No significant impact on spontaneous pregnancies was found after antioxidant therapy . Despite this preliminary data , we show that antioxidant therapy based on a combination of NAC and micronutrient supplementation can be helpful in improve the sperm count at least in a subset of oligospermic males . However , this improving in sperm count is not associated with a significant increase in spontaneous pregnancies after 12 months |
1,751 | 25,323,965 | Interpretation : Compensation is substantial even in high-compliance conditions , result ing in far less weight change than would be expected .
The simple algorithm we report allows for more realistic predictions of intervention effects in free-living population s by accounting for the significant compensation that occurs | Background : Public health and clinical interventions for obesity in free-living adults may be diminished by individual compensation for the intervention .
Approaches to predict weight outcomes do not account for all mechanisms of compensation , so they are not well suited to predict outcomes in free-living adults .
Our objective was to quantify the range of compensation in energy intake or expenditure observed in human r and omized controlled trials ( RCTs ) . | An increased consumption of fruits and vegetables ( F&V ) has been suggested as a way to limit , or even lower , energy and fat intakes . The present study examined the effects of incorporating F&V supplements into the diets of adults who reported consuming < 240 g ( three portions ) of F&V per d on energy and fat intakes , and change in body weight , over 8 weeks using a r and omised parallel design . Thirty-four males and twenty-eight females ( age 42.6 ( sd 11.1 ) years , BMI 23.7 ( sd 2.7 ) kg/m(2 ) ) were each provided with supplements of 0 , 300 or 600 g F&V per d. Food , nutrient and energy intakes were measured before , during and at the end of the supplementation period using 7 d weighed records . Mean daily energy intakes were not different among the three groups before ( P = 0.151 ) or during the supplementation periods ( P = 0.407 ) , although changes in energy intakes over the study period tended to be more positive with increasing amounts of F&V supplements ( P = 0.078 ) . There was no difference in changes of body weights during the study ( P = 0.242 ) . Carbohydrate ( P < 0.001 ) , sugar ( P < 0.001 ) , fibre ( P < 0.001 ) and weight of food consumed ( P = 0.022 ) increased in the treatment groups . There were no significant differences , or changes , in fat intakes among the three groups . Consumption of m and atory F&V supplements for 8 weeks produced beneficial changes in diet composition , but did not result in lower reported energy or fat intakes , and did not result in loss of body weight Definitive solutions wo n’t come from another million observational papers or small r and omized trials BACKGROUND Altering the macronutrient composition of the diet influences hunger and satiety . Studies have compared high- and low-protein diets , but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake . OBJECTIVE We aim ed to compare the hunger , appetite , and weight-loss responses to a high-protein , low-carbohydrate [ ( LC ) ketogenic ] and those to a high-protein , medium-carbohydrate [ ( MC ) nonketogenic ] diet in obese men feeding ad libitum . DESIGN Seventeen obese men were studied in a residential trial ; food was provided daily . Subjects were offered 2 high-protein ( 30 % of energy ) ad libitum diets , each for a 4-wk period-an LC ( 4 % carbohydrate ) ketogenic diet and an MC ( 35 % carbohydrate ) diet-r and omized in a crossover design . Body weight was measured daily , and ketosis was monitored by analysis of plasma and urine sample s. Hunger was assessed by using a computerized visual analogue system . RESULTS Ad libitum energy intakes were lower with the LC diet than with the MC diet [ P=0.02 ; SE of the difference ( SED ) : 0.27 ] at 7.25 and 7.95 MJ/d , respectively . Over the 4-wk period , hunger was significantly lower ( P=0.014 ; SED : 1.76 ) and weight loss was significantly greater ( P=0.006 ; SED : 0.62 ) with the LC diet ( 6.34 kg ) than with the MC diet ( 4.35 kg ) . The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma ( P=0.036 from baseline ; SED : 0.62 ) and 2.99 mmol/L in urine ( P<0.001 from baseline ; SED : 0.36 ) . CONCLUSION In the short term , high-protein , low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein , medium-carbohydrate nonketogenic diets OBJECTIVES We examined the viability and efficacy of a known quantity of exercise in facilitating weight loss among previously sedentary or irregularly active overweight and obese adult women residing in a slum ( favela ) in Brazil . METHODS In this r and omized controlled trial , 156 women were r and omized to a control or intervention group ( 78 in each group ) . Exercise was supervised , consisting of three 50-minute aerobic sessions each week for 6 months . RESULTS Ninety-one percent ( 71 ) of the participants in the intervention group completed 6 months of the exercise program . At 6 months , women in the treatment group showed significant reduction in weight ( mean=-1.69 kg ; 95 % confidence interval [CI]=-2.36,-1.03 ) and body mass index ( mean=-0.63 kg/m2 ; 95 % CI=-0.97 , -0.30 ) compared with controls ( P for both<.001 ) . CONCLUSIONS A moderately intense , structured exercise program result ed in modest weight loss in women when sustained for 6 months BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P < 0.01 ) , skeletal muscle fat ( 117 - 221 % ; P < 0.05 ) , visceral fat ( 24 - 31 % ; P < 0.05 ) , blood triglycerides ( 32 % ; P < 0.01 ) , and total cholesterol ( 11 % ; P < 0.01 ) . Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P < 0.05 ) . Otherwise , diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647 Coronary artery disease ( CAD ) is a substantial cause of death and disability in South Africa and Western society , with research showing obesity to be one of the most common CAD risk factors . Furthermore , obesity is speculated to be the fastest-growing CAD risk factor and to become the most prevalent CAD risk factor . Research on obesity is therefore essential , and we propose some preventative measures that will hopefully limit the expansion of this risk factor for CAD . Most of the literature has focused primarily on aerobic modes of exercise . The aim of this study , therefore , was to investigate whether resistance training would improve body composition . Twenty-eight males were matched by age , percentage of body fat and waist-to-hip ratio and r and omly assigned either to a resistance-training group ( n = 13 ) or a control group ( n = 15 ) . Each subject 's body mass , percentage body fat , lean mass , fat mass , waist-to-hip ratio and body mass index were assessed both pre- and post-experimentally following the eight-week experimental period . The resistance-training group trained three times weekly at 60 % of their one-repetition maximum using nine resistance exercises . Each exercise was performed for three sets of 15 repetitions each , whereas the control group did not exercise over this period . The dependent t-test indicated that resistance training significantly changed body mass , percentage of body fat , lean mass and fat mass ( all had a p-value of 0.00 ; p < or= 0.01 ) . Furthermore , the independent t-test demonstrated that lean mass , fat mass and percentage of body fat were statistically significantly different between the control and resistance-training groups . In conclusion , resistance training improved four of the six measured body composition variables , therefore implying that resistance training does in fact improve the majority of body composition variables and therefore CAD risk Objective : Clinical and epidemiological studies have reported the beneficial effects of tree nuts and peanuts on serum lipid levels . We studied the effects of consuming 15 % of the daily caloric intake in the form of pistachio nuts on the lipid profiles of free-living human subjects with primary , moderate hypercholesterolemia ( serum cholesterol greater than 210 mg/dL ) . Methods : Design : R and omized crossover trial . Setting : Outpatient dietary counseling and blood analysis . Subjects : 15 subjects with moderate hypercholesterolemia . Intervention : Fours weeks of dietary modification with 15 % caloric intake from pistachio nuts . Measures of Outcome : Endpoints were serum lipid levels of total cholesterol , HDL-C , LDL-C , VLDL-C , triglycerides and apolipoproteins A-1 and B-100 . BMI , blood pressure , and nutrient intake ( total energy , fat , protein , and fiber ) were also measured at baseline , during , and after dietary intervention . Results : No statistically significant differences were observed for total energy or percent of energy from protein , carbohydrate or fat . On the pistachio nut diet , a statistically significant decrease was seen for percent energy from saturated fat ( mean difference , −2.7 % ; 95 % CI , −5.4 % to −0.08 % ; p = 0.04 ) . On the pistachio nut diet , statistically significant increases were seen for percent energy from polyunsaturated fat ( mean difference , 6.5 % ; 95 % CI , 4.2 % to 8.9 % ; p<.0001 ) and fiber intake ( mean difference , 15 g ; 95 % CI , 8.4 g to 22 g ; p = 0.0003 ) . On the pistachio diet , statistically significant reductions were seen in TC/HDL-C ( mean difference , −0.38 ; 95 % CI , −0.57 to −0.19 ; p = 0.001 ) , LDL-C/HDL-C ( mean difference , −0.40 ; 95 % CI , −0.66 to −0.15 ; p = 0.004 ) , B-100/A-1 ( mean difference , −0.11 ; 95 % CI , −0.19 to −0.03 ; p = 0.009 ) and a statistically significant increase was seen in HDL-C ( mean difference , 2.3 ; 95 % CI , 0.48 to 4.0 ; p = 0.02 ) . No statistically significant differences were seen for total cholesterol , triglycerides , LDL-C , VLDL-C , apolipoprotein A-1 or apolipoprotein B-100 . No changes were observed in BMI or blood pressure . Conclusion : A diet consisting of 15 % of calories as pistachio nuts ( about 2–3 ounces per day ) over a four week period can favorably improve some lipid profiles in subjects with moderate hypercholesterolemia and may reduce risk of coronary disease To determine the effect of a 12-week high intensity intermittent exercise ( HIIE ) intervention on total body , abdominal , trunk , visceral fat mass , and fat free mass of young overweight males . Participants were r and omly assigned to either exercise or control group . The intervention group received HIIE three times per week , 20 min per session , for 12 weeks . Aerobic power improved significantly ( P < 0.001 ) by 15 % for the exercising group . Exercisers compared to controls experienced significant weight loss of 1.5 kg ( P < 0.005 ) and a significant reduction in total fat mass of 2 kg ( P < 0.001 ) . Abdominal and trunk adiposity was also significantly reduced in the exercising group by 0.1 kg ( P < 0.05 ) and 1.5 kg ( P < 0.001 ) . Also the exercise group had a significant ( P < 0.01 ) 17 % reduction in visceral fat after 12 weeks of HIIE , whereas waist circumference was significantly decreased by week six ( P < 0.001 ) . Fat free mass was significantly increased ( P < 0.05 ) in the exercising group by 0.4 kg for the leg and 0.7 kg for the trunk . No significant change ( P > 0.05 ) occurred in levels of insulin , HOMA-IR , and blood lipids . Twelve weeks of HIIE result ed in significant reductions in total , abdominal , trunk , and visceral fat and significant increases in fat free mass and aerobic power PURPOSE The INFLAME study is design ed to determine the effect of exercise training on elevated high-sensitivity C-Reactive Protein ( CRP ) concentrations in initially sedentary women and men . METHODS INFLAME will recruit 170 healthy , sedentary women and men with elevated CRP ( > or=2.0 mg/L ) to be r and omized to either an exercise group or non-exercise control group . Exercising individuals will participate in four months of supervised aerobic exercise with a total energy expenditure of 16 kcal kg(-1 ) week(-1 ) ( KKW ) . Exercise intensity will be 60 - 80 % of maximal oxygen consumption ( VO(2 ) max ) . OUTCOME The primary outcome will be changed in plasma CRP concentration . Secondary outcomes include visceral adiposity , the cytokines IL-6 and TNF-alpha , and heart rate variability ( HRV ) in order to examine potential biological mechanisms whereby exercise might affect CRP concentrations . SUMMARY INFLAME will help us underst and the effects of moderate-to-vigorous exercise on CRP concentrations in sedentary individuals . To our knowledge this will be the largest training study specifically design ed to examine the effect of exercise on CRP concentrations . This study has the potential to influence therapeutic applications since CRP measurement is becoming an important clinical measurement in Coronary Heart Disease risk assessment . This study will also contribute to the limited body of literature examining the effect of exercise on the variables of visceral adiposity , cytokines , and heart rate variability PURPOSE The study 's purpose was to evaluate the effects of walking ( W ) and walking plus resistance training ( WRT ) on cardiovascular disease risk factors in inactive middle-aged ( 49.0 ± 5.5 yr ) African-American women ( body mass index = 34.7 ± 6.4 kg·m(-2 ) ) . METHODS Body composition , blood pressure , HDL cholesterol , triglycerides , glycosylated hemoglobin ( HbA1c ) , C-reactive protein , and fibrinogen were measured before and after a 12-wk exercise intervention . Subjects were r and omly assigned to one of two training groups . The W group ( n = 25 ) was instructed to increase daily pedometer-measured walking to ≥10,000 steps per day , whereas the WRT group ( n = 19 ) was given the same walking prescription plus supervised resistance training 2 d·wk(-1 ) . A two-way repeated- measures ANOVA with an intention-to-treat analysis was performed to examine changes between groups . Significance was accepted at P ≤ 0.05 . RESULTS Both groups significantly ( P < 0.001 ) increased walking ( W = 5453 ± 2119 to 6845 ± 2279 steps per day , WRT = 4823 ± 1758 to 6859 ± 2012 steps per day ) . WRT significantly ( P < 0.001 ) increased both upper ( 100 ± 15 to 113 ± 18 kg ) and lower ( 102 ± 20 to 116 ± 25 kg ) body strength compared with W. WRT significantly decreased waist circumference ( 94.8 ± 12.3 to 92.9 ± 12.0 cm , P = 0.021 ) and total fat mass ( 42.6 ± 11.1 to 41.8 ± 10.8 kg , P = 0.036 ) compared with W. WRT also significantly decreased pre- to postintervention body fat ( 45.8 % ± 6.2 % to 45.3 % ± 6.2 % , P = 0.018 ) , HbA1c ( 5.9 % ± 1.2 % to 5.6 % ± 1.0 % , P = 0.028 ) , and mean glucose calculated from HbA1c ( 122 ± 39 to 114 ± 32 mg·dL(-1 ) , P = 0.028 ) , whereas W showed no changes . Blood pressure , HDL cholesterol , triglycerides , and C-reactive protein were not affected by either intervention . CONCLUSIONS Although both interventions increased steps per day , WRT was more effective in improving several body composition measures and glucose control in 12 wk . WRT may be an important addition to a lifestyle intervention aim ing to facilitate reductions in cardiovascular disease risk factors in overweight and obese African-American women Studies consistently show the beneficial effects of eating nuts , but as high-energy foods , their regular consumption may lead to weight gain . We tested if daily consumption of walnuts ( approximately 12 % energy intake ) for 6 months would modify body weight and body composition in free-living subjects . Ninety participants in a 12-month r and omized cross-over trial were instructed to eat an allotted amount of walnuts ( 28 - 56 g ) during the walnut-supplemented diet and not to eat them during the control diet , with no further instruction . Subjects were unaware that body weight was the main outcome . Dietary compliance was about 95 % and mean daily walnut consumption was 35 g during the walnut-supplemented diet . The walnut-supplemented diet result ed in greater daily energy intake ( 557 kJ ( 133 kcal ) ) , which should theoretically have led to a weight gain of 3.1 kg over the 6-month period . For all participants , walnut supplementation increased weight ( 0.4 ( se 0.1 ) kg ) , BMI ( 0.2 ( se 0.1 ) kg/m(2 ) ) , fat mass ( 0.2 ( se 0.1 ) kg ) and lean mass ( 0.2 ( se 0.1 ) kg ) . But , after adjusting for energy differences between the control and walnut-supplemented diets , no significant differences were observed in body weight or body composition parameters , except for BMI ( 0.1 ( se 0.1 ) kg/m(2 ) ) . The weight gain from incorporating walnuts into the diet ( control-->walnut sequence ) was less than the weight loss from withdrawing walnuts from the diet ( walnut-->control sequence ) . Our findings show that regular walnut intake result ed in weight gain much lower than expected and which became non-significant after controlling for differences in energy intake We studied the effect of moderate , short-term energy restriction on physical performance in physically fit men ( n = 13 ) and women ( n = 11 ) in a controlled clinical research setting with a metabolic kitchen , exercise testing laboratory and training facility . The experiment consisted of a 10 d baseline period followed by either 2 wk of dietary energy restriction ( 750 kcal/d ; n = 16 ) or energy balance ( control ; n = 8) . During this 24 day study , exercise energy expenditure averaged 465 + /- 5.7 kcal/d in all subjects and was accomplished through treadmill running at a self-selected pace . Body weight was maintained in the control group ( -0.36 + /- 0.24 kg ) , but energy restriction result ed in weight loss of -1.29 + /- 0.16 kg ( p < 0.001 ) . There was a trend for lean body mass to decline more in the energy restriction group ( p = 0.093 ) , accounting for 61 % of the weight loss , and urinary nitrogen excretion also tended to be higher in the energy restriction vs. control group ( i.e. , 13.2 + /- 1.1 vs. 11.2 + /- 1.0g/d ; p = 0.089 ) . Muscle strength ( leg & shoulder press ; 1 repetition maximum ) was maintained or increased during the energy restriction period . Muscle endurance , assessed by leg squats to fatigue , and 5 mile run time improved following two weeks of energy restriction or balance . Anaerobic capacity ( Wingate Test ) increased slightly in the restriction ( + 368 + /- 219 joules ) but declined in the control group 649 + /- 288 joules ; p<0.05 ) . We conclude that short-term ( 2 weeks ) moderate energy restriction ( approximately 750 kcal/d ) results in weight loss but does not impair performance in physically fit young men and women BACKGROUND Epidemiologic evidence suggests that 8,368 kJ or 2000 kcal per week of moderate physical activity , including walking and stair climbing , can reduce risk of coronary heart disease ( CHD ) . The goal of this study was to assess the effects of this amount of these two activities on physical fitness and risk factors for CHD . METHODS Twenty-two healthy , slightly overweight , sedentary , normotensive , normolipemic men , age 22 to 44 years , were r and omly assigned to an exercise or control group for 12 weeks followed by a 4-week washout period . The subjects then were crossed-over to the alternate group for an additional 12-week period . Exercise consisted of 5 days per week of supervised treadmill exercise plus stair climbing . Treadmill exercise consisted of walking for 45 minutes at 5.15 km per hour at 2 % grade for a total of 19.3 km per week . Subjects also climbed 10 floors of stairs at a time at their own pace without prescribed target heart rates for a total of 50 floors per week . The estimated total weekly energy cost of the treadmill walking plus stair climbing was 8,368 kJ or 2,000 kcal . Mean observed heart rates were 55 % and 82 % of maximal heart rate during treadmill walking and stair climbing , respectively . Data from the two exercise periods and two control periods were pooled and compared by analysis of variance . RESULTS Sixteen subjects completed all phases of the study . Maximal oxygen uptake ( VO2max ) by the Bruce treadmill exercise protocol with metabolic gas measurements was below average for age at baseline , and was not significantly affected by 12 weeks of training . No significant changes were noted between groups in body weight or percent body fat ( hydrostatic weighing ) , although there was a trend for loss of weight and fat with exercise training . Mean systolic blood pressure ( 119 mm Hg ) was unchanged in both groups . However , diastolic blood pressure ( 72 mm Hg and 78 mm Hg for the treatment and control groups , respectively ) showed an unexpected 6 mm Hg increase during the exercise period and a 5 mm Hg decline during the control period . Mean plasma lipid and lipoprotein levels were unaffected by training , except for a 16 % reduction in triglycerides ( P < .05 ) . However , a 28 % increase in plasma high density lipoprotein (HDL)-cholesterol ( P < .01 ) was noted during the initial 12-week training period , which regressed during the washout period , and was not replicated during the second 12-week exercise period . CONCLUSIONS Twelve weeks of walking and stair climbing at a moderate pace and intensity at an energy cost of about 2,000 kcal per week failed to improve physical fitness or risk factors for CHD . A reduction in physical activities other than the prescribed exercise program , as reported by a physical activity recall question naire , probably contributed to an absence of an exercise response . A longer and /or a more intense activity program is apparently required to improve these modalities BACKGROUND Fitness and health variables were measured in 128 sedentary men and women r and omly assigned to 6 months of fitness training ( F ) , a walking program ( W ) , or a control ( C ) group . METHODS The F program gradually increased volume and intensity until 4 d/wk of training , at 70 % of peak VO2 for 43 min/session was prescribed while the W group performed daily walking monitored with pedometers and increased until 10,000 steps x d-1 were prescribed . Total weekly energy expenditure was matched between the activity groups . The control group was asked to maintain their usual activity . RESULTS Body mass , waist circumference , waist/hip ratio , resting HR were reduced in all groups after 6 months ( P < .05 ) . Fasting glucose , glucose tolerance , and total cholesterol were similarly improved in all groups ( P < .05 ) . Blood pressure and HR decreased during submaximal exercise in all groups ( P < .05 ) but rating of perceived exertion ( RPE ) was decreased only in the F group ( P < .05 ) . Only the F participants showed a significant increase in ventilatory threshold ( VT ; ~15 % ) and peak VO2 ( ~9 % ) after 6 months . CONCLUSIONS Supervised fitness training in previously sedentary adults produced greater improvements in submaximal RPE , BP(sys ) , VT , and peak VO2 but not other fitness and health-related variables compared with a pedometer-based walking program matched for total energy cost BACKGROUND The success of clinical dietary interventions depends on the motivation and willingness of study participants to adhere to the prescribed or provided diet . The aim of this study was to assess participants ' adherence to their provided diet over the 6-month duration of the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy ( CALERIE ) . METHODS Investigators assessed the dietary adherence of 46 men and women who completed the first phase of the CALERIE trial . Volunteers were r and omized to 1 of 4 dietary intervention groups : control , calorie restriction , calorie restriction with exercise , and low-calorie diet . Participants were provided with foods during 2 weeks of baseline and during the first 12 weeks and the last 2 weeks of the intervention as out patients , and they completed a daily self-report form to assess diet adherence . The data are expressed as mean ± st and ard deviation or st and ard error of the mean . Pearson 's correlation coefficient was determined to examine the relationship between assigned energy levels and total energy intake . RESULTS Deviations reported were for eating non study foods as well as not eating study foods . There were few deviations , and when converted to mean calories per day these did not affect total energy ( weeks -3 to 2 = 10.25 ± 4.82 , weeks 1 - 4 = 9.93 ± 12.52 , weeks 5 - 11 = 8.38 ± 7.42 , weeks 22 - 23 = 0.53 ± 3.97 kcal/d ) . The associations between assigned energy level and actual intake were high for all groups ( P = .001 ) , weeks -3 to -2 ( r = 0.999 ) , weeks 1 - 4 ( r = 0.998 ) , weeks 5 - 11 ( r = 0.999 ) , and weeks 22 - 23 ( r = 0.998 ) . CONCLUSIONS The data provide evidence that dietary adherence is good when all foods are provided and when participants are highly motivated To determine the effects of a 6-month supervised low-volume resistance training ( RT ) program ( 1 set , 85–90 % , one repetition maximum , 1RM , 3 d·wk−1 ) on muscular strength ( 1RM ) and skeletal muscle mass ( SMM ) in previously sedentary , overweight men on an ad libitum diet . Nineteen men were r and omly assigned to a control ( CON , n = 8) or RT ( n = 11 ) group . The exercise protocol consisted of 5 upper- and 4 lower-body exercises using weight machines . CON maintained their sedentary lifestyle . One RM for upper body ( chest press [ CP ] + lat pull-down [ LPD ] ) and lower body ( leg press [ LP ] ) and SMM were assessed at baseline , and at 3 and 6 months . Adherence was 96 ± 2 % with an average time to complete each exercise session of 15 ± 2 minutes . Volume completed per exercise session significantly increased from baseline ( 2,812 ± 670 kg ) to 6 months ( 6,411 ± 2,128 kg ) . There was a group by time interaction in 1RM for CP , LPD , and LP . Upper-body strength increased significantly ( p < 0.001 ) ( 31.3 ± 9.3 % ) from baseline to 3 months and from 3 to 6 months ( 17.9 ± 8.7 % ) . Lower-body strength also increased significantly from baseline to 3 months ( 17.8 ± 16.6 % ) and from 3 to 6 months ( 32.0 ± 33.7 % ) . No changes in upper- or lower-body strength occurred in the CON group . There was no group by time interaction for SMM ( CON , 34.5 ± 2.9 kg vs. RT , 34.2 ± 2.9 kg ; p > 0.05 ) or for energy intake ( p > 0.05 ) . In conclusion , a single set resistance training program at 85 % of 1RM , 3 d·wk−1 result ed in continued increases in muscular strength and a very high adherence rate over a 6-month period in sedentary , overweight men independent of significant changes in SMM . This training protocol may increase adherence and produce long-term increases in muscular fitness as part of an adult fitness program This study compared the effects of short and long bouts of brisk walking in sedentary women . Forty seven women aged 44.4 + /- 6.2 yr ( mean + /- SD ) were r and omly assigned to either three 10-min walks per day ( short bouts ) , one 30-min walk per day ( long bouts ) or no training ( control ) . Brisk walking was done on 5 d x wk(-1 ) , at 70 to 80 % of maximal heart rate , typically at speeds between 1.6 and 1.8 m x s(-1 ) ( 3.5 and 4.0 mph ) , for 10 wk . Subjects agreed not to make changes to their diet . Twelve short-bout walkers , 12 long-bout walkers , and 10 controls completed the study . Relative to controls , VO2max ( short-bout , + 2.3 + /- 0.1 mL x kg(-1 ) x min(-1 ) ; long-bout , + 2.4 + /- 0.1 mL x kg(-1 ) x min(-1 ) ; controls , -0.5 + /- 0.1 mL x kg(-1 ) x min[-1 ] ) and the VO2 at a blood lactate concentration of 2 mmol x L(-1 ) increased in walkers ( both P < 0.05 ) , with no difference in response between walking groups . Neither heart rate during st and ard , submaximal exercise nor resting systolic blood pressure changed in a different way in walkers and controls . The sum of four skinfold thicknesses decreased in both walking groups ( P < 0.05 ) but body mass ( short-bout , -1.7 + /- 1.7 kg ; long-bout , -0.9 + /- 2.0 kg ; controls , + 0.6 + /- 0.7 kg ) and waist circumference decreased significantly only in short-bout walkers . Changes in anthropometric variables did not differ between short- and long-bout walkers . Thus short bouts of brisk walking result ed in similar improvements in fitness and were at least as effective in decreasing body fatness as long bouts of the same total duration Theoretical calculations suggest that small daily reductions in energy intake can cumulatively lead to substantial weight loss , but experimental data to support these calculations are lacking . We conducted a 1-year r and omized controlled pilot study of low ( 10 % ) or moderate ( 30 % ) energy restriction ( ER ) with diets differing in glycemic load in 38 overweight adults ( mean + /- s.d . , age 35 + /- 6 years ; BMI 27.6 + /- 1.4 kg/m(2 ) ) . Food was provided for 6 months and self-selected for 6 additional months . Measurements included body weight , resting metabolic rate ( RMR ) , adherence to the ER prescription assessed using (2)H(2)(18)O , satiety , and eating behavior variables . The 10%ER group consumed significantly less energy ( by (2)H(2)(18)O ) than prescribed over 12 months ( 18.1 + /- 9.8%ER , P = 0.04 ) , while the 30%ER group consumed significantly more ( 23.1 + /- 8.7%ER , P < 0.001 ) . Changes in body weight , satiety , and other variables were not significantly different between groups . However , during self-selected eating ( 6 - 12 months ) variability in % weight change was significantly greater in the 10%ER group ( P < 0.001 ) and poorer weight outcome on 10%ER was predicted by higher baseline BMI and greater disinhibition ( P < 0.0001 ; adj R(2 ) = 0.71 ) . Weight loss at 12 months was not significantly different between groups prescribed 10 or 30%ER , supporting the efficacy of low ER recommendations . However , long-term weight change was more variable on 10%ER and weight change in this group was predicted by body size and eating behavior . These preliminary results indicate beneficial effects of low-level ER for some but not all individuals in a weight control program , and suggest testable approaches for optimizing dieting success based on individualizing prescribed level of ER Vispute , SS , Smith , JD , LeCheminant , JD , and Hurley , KS . The effect of abdominal exercise on abdominal fat . J Strength Cond Res 25(9 ) : 2559 - 2564 , 2011—The purpose of this study was to investigate the effect of abdominal exercises on abdominal fat . Twenty-four healthy , sedentary participants ( 14 men and 10 women ) , between 18 and 40 years , were r and omly assigned to 1 of the following 2 groups : control group ( CG ) or abdominal exercise group ( AG ) . Anthropometrics , body composition , and abdominal muscular endurance were tested before and after training . The AG performed 7 abdominal exercises , for 2 sets of 10 repetitions , on 5 d·wk−1 for 6 weeks . The CG received no intervention , and all participants maintained an isocaloric diet throughout the study . Significance was set at p = 0.05 for all tests . There was no significant effect of abdominal exercises on body weight , body fat percentage , and roid fat percentage , and roid fat , abdominal circumference , abdominal skinfold and suprailiac skinfold measurements . The AG performed significantly greater amount of curl-up repetitions ( 47 ± 13 ) compared to the CG ( 32 ± 9 ) on the posttest . Six weeks of abdominal exercise training alone was not sufficient to reduce abdominal subcutaneous fat and other measures of body composition . Nevertheless , abdominal exercise training significantly improved muscular endurance to a greater extent than the CG BACKGROUND Exercise interventions elicit only modest weight loss , which might reflect a compensatory reduction in nonprescribed physical activity energy expenditure ( PAEE ) . OBJECTIVE The objective was to investigate whether there is a reduction in nonprescribed PAEE as a result of participation in a 6-mo structured exercise intervention in middle-aged men . DESIGN Sedentary male participants [ age : 54 ± 5 y ; body mass index ( in kg/m² ) : 28 ± 3 ] were r and omly assigned to a 6-mo progressive exercise ( EX ) or control ( CON ) group . Energy expenditure during structured exercise ( prescribed PAEE ) and nonprescribed PAEE were determined with the use of synchronized accelerometry and heart rate before the intervention , during the intervention ( 2 , 9 , and 18 wk ) , and within a 2-wk period of detraining after the intervention . RESULTS Structured prescribed exercise increased total PAEE and had no detrimental effect on nonprescribed PAEE . Indeed , there was a trend for greater nonprescribed PAEE in the EX group ( P = 0.09 ) . Weight loss in the EX group ( -1.8 ± 2.2 kg compared with + 0.2 ± 2.2 kg in the CON group , P < 0.02 ) reflected only ≈40 % of the 300 - 373 kcal/kg body mass potential energy deficit from prescribed exercise . Serum leptin concentration decreased by 24 % in the EX group ( compared with 3 % in the CON group , P < 0.03 ) , and we estimate that this was accompanied by a compensatory increase in energy intake of ≈100 kcal/d . CONCLUSIONS The adoption of regular structured exercise in previously sedentary , middle-aged , and overweight men does not result in a negative compensatory reduction in nonprescribed physical activity . The less-than-predicted weight loss is likely to reflect a compensatory increase in energy intake in response to a perceived state of relative energy insufficiency |
1,752 | 27,500,135 | These revealed that higher adherence to a MedDiet is associated with slower rates of cognitive decline , reduced conversion to Alzheimer 's disease , and improvements in cognitive function .
The specific cognitive domains that were found to benefit with improved Mediterranean Diet Score were memory ( delayed recognition , long-term , and working memory ) , executive function , and visual constructs . | The Mediterranean-style diet ( MedDiet ) involves substantial intake of fruits , vegetables , and fish , and a lower consumption of dairy , red meat , and sugars .
Over the past 15 years , much empirical evidence supports the suggestion that a MedDiet may be beneficial with respect to reducing the incidence of cardiovascular disease , cancer , metabolic syndrome , and dementia .
A number of cross-sectional studies that have examined the impact of MedDiet on cognition have yielded largely positive results .
The objective of this review is to evaluate longitudinal and prospect i ve trials to gain an underst and ing of how a MedDiet may impact cognitive processes over time .
The included studies were aim ed at improving cognition or minimizing of cognitive decline . | Objective Our aim was to evaluate the association between adherence to the Mediterranean Diet ( MedDiet ) and cognitive function in 823 participants ( 62 ± 6 years at baseline ) from a Spanish prospect i ve cohort ( SUN project ) . Method A vali date d 136-item food frequency question naire was used to assess the adherence to the MedDiet at baseline . The 10-point ( 0 to 9 ) MedDiet Score was used to categorize adherence to MedDiet . Cognitive function was assessed twice at follow-up with a mean follow-up time between exposure and outcome assessment of 6 and 8y using the Telephone Interview of Cognitive Status-modified ( TICS-m , range 0 to 54 points ) . ANCOVA models were used to assess the association between adherence to the MedDiet and cognitive decline . Results In the multivariable-adjusted analysis of 2-year changes , a higher cognitive decline was observed among participants with low or moderate baseline adherence to the MedDiet than among those with better adherence ( adjusted difference = −0.56 points in TICS-m , 95 % CI = −0.99 to −0.13 ) . Conclusion A higher adherence to the MedDiet might be associated with better cognitive function . However , observed differences were of small magnitude and further studies are needed to confirm this finding 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 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 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 The aim of the present study was to assess reproducibility and relative validity of a self-administered FFQ used in the PREDIMED Study , a clinical trial for primary prevention of CVD by Mediterranean diet in a population at high cardiovascular risk . The FFQ was administered twice ( FFQ1 and FFQ2 ) to explore reproducibility at 1 year . Four 3 d dietary records ( DR ) were used as reference to explore validity ; participants therefore recorded their food intake over 12 d in the course of 1 year . The degree of misclassification in the FFQ was also evaluated by a contingency table of quintiles comparing the information from the FFQ2 and the DR . A total of 158 men and women ( aged 55 - 80 years ) were asked not to modify their dietary habits during the study period . Reproducibility for food groups , energy and nutrient intake , explored by the Pearson correlation coefficient ( r ) ranged 0.50 - 0.82 , and the intraclass correlation coefficient ( ICC ) ranged from 0.63 to 0.90 . The FFQ2 tended to report higher energy and nutrient intake than the DR . The validity indices of the FFQ in relation to the DR for food groups and energy and nutrient intake ranged ( r ) from 0.24 to 0.72 , while the range of the ICC was between 0.40 and 0.84 . With regard to food groups , 68 - 83 % of individuals were in the same or adjacent quintile in both methods , a figure which decreased to 55 - 75 % for energy and nutrient intake . We concluded that FFQ measurements had good reproducibility and a relative validity similar to those of FFQ used in other prospect i ve studies OBJECTIVE To explore the associations of low serum levels of vitamin B(12 ) and folate with AD occurrence . METHODS A population -based longitudinal study in Sweden , the Kungsholmen PROJECT A r and om sample of 370 nondemented persons , aged 75 years and older and not treated with B(12 ) and folate , was followed for 3 years to detect incident AD cases . Two cut-off points were used to define low levels of vitamin B(12 ) ( < or = 150 and < or = 250 pmol/L ) and folate ( < or = 10 and < or = 12 nmol/L ) , and all analyses were performed using both definitions . AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria . RESULTS When using B(12 ) < or = 150 pmol/L and folate < or = 10 nmol/L to define low levels , compared with people with normal levels of both vitamins , subjects with low levels of B(12 ) or folate had twice higher risks of developing AD ( relative risk [ RR ] = 2.1 , 95 % CI = 1.2 to 3.5 ) . These associations were even stronger in subjects with good baseline cognition ( RR = 3.1 , 95 % CI = 1.1 to 8.4 ) . Similar relative risks of AD were found in subjects with low levels of B(12 ) or folate and among those with both vitamins at low levels . A comparable pattern was detected when low vitamin levels were defined as B(12 ) < or = 250 pmol/L and folate < or = 12 nmol/L. CONCLUSIONS This study suggests that vitamin B(12 ) and folate may be involved in the development of AD . A clear association was detected only when both vitamins were taken into account , especially among the cognitively intact subjects . No interaction was found between the two vitamins . Monitoring serum B(12 ) and folate concentration in the elderly may be relevant for prevention of AD 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 Previous studies have reported an association between a more pro-inflammatory diet profile and various chronic metabolic diseases . The Dietary Inflammatory Index ( DII ) was used to assess the inflammatory potential of nutrients and foods in the context of a dietary pattern . We prospect ively examined the association between the DII and the incidence of cardiovascular disease ( CVD : myocardial infa rct ion , stroke or cardiovascular death ) in the PREDIMED ( Prevención con Dieta Mediterránea ) study including 7216 high-risk participants . The DII was computed based on a vali date d 137-item food frequency question naire . Multivariate-adjusted hazard ratios ( HR ) and 95 % confidence intervals of CVD risk were computed across quartiles of the DII where the lowest ( most anti-inflammatory ) quartile is the referent . Risk increased across the quartiles ( i.e. , with increasing inflammatory potential ) : HRquartile2 = 1.42 ( 95%CI = 0.97–2.09 ) ; HRquartile3 = 1.85 ( 1.27–2.71 ) ; and HRquartile4 = 1.73 ( 1.15–2.60 ) . When fit as continuous the multiple-adjusted hazard ratio for each additional st and ard deviation of the DII was 1.22 ( 1.06–1.40 ) . Our results provide direct prospect i ve evidence that a pro-inflammatory diet is associated with a higher risk of cardiovascular clinical events Plasma total homocysteine ( tHcy ) concentrations are associated with deficits in cognitive performance in persons free from dementia . The extent to which age modifies these associations is in need of further investigation in large , community-based , prospect i ve studies combining the following elements : 1 ) multiple cognitive tests ; 2 ) statistical adjustment for the role of the vitamin cofactors folate , vitamin B6 , and vitamin B12 ; and 3 ) adjustment for the presence of risk factors for cardiovascular disease and stroke . Using data collected between 1991 and 2002 , the authors investigated the associations between tHcy and multiple measures of cognitive performance in 2,096 dementia- and stroke-free participants of the Framingham Offspring Study , who were stratified into three age groups ( 40 - 49 years , 50 - 59 years , 60 - 82 years ) , after findings of statistically significant tHcy-by-age interactions for multiple cognitive measures . Regardless of statistical adjustment for age , sex , gender , the vitamin cofactors , and cardiovascular risk factors , statistically significant inverse associations between tHcy and multiple cognitive domains were observed for individuals aged 60 or more years ; no such associations were observed for participants aged less than 60 years . Early preventive interventions may be important , because the inverse association between tHcy and cognitive performance is observed beyond middle age 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 OBJECTIVES Even short-term adherence to a Mediterranean-style diet may benefit aspects of psychological functioning . The aim of the present study was to assess the effects of switching to a 10-d Mediterranean-style diet on mood , cognition , and cardiovascular measures . METHODS Using a crossover design , 24 women were r and omly assigned to either the diet change ( where they switched to a Mediterranean-style diet ) or no diet change ( normal diet ) condition for 10 days before switching to the other condition for the same duration . Mood , cognition , and cardiovascular measures of blood pressure , blood flow velocity , and arterial stiffness were assessed at baseline and at the completion of the two diets ( days 11 and 22 ) . RESULTS Independent of whether the Mediterranean-style diet was undertaken before or after the crossover , it was associated with significantly elevated contentment and alertness , and significantly reduced confusion . Additionally , aspects of cognition , such as memory recall , improved significantly as a result of switching to the Mediterranean-style diet . Regarding cardiovascular measures , there was a significant reduction in augmentation pressure associated with the Mediterranean-style diet intervention , but blood flow velocity through the common carotid artery did not change . CONCLUSIONS This Mediterranean-style diet has the potential to enhance aspects of mood , cognition , and cardiovascular function in a young , healthy adult sample Objective . To design a brief cognitive screener with acceptable sensitivity and specificity for identifying subjects with cognitive impairment Design . Cohort one is assembled from a community-based survey coupled with a second-stage diagnostic evaluation using formal diagnostic criteria for dementia . Cohort two is assembled from referrals to a specialty clinic for dementing disorders that completed the same diagnostic evaluation . Setting . Urban neighborhoods in Indianapolis , Indiana and the Indiana Alzheimer Disease Center . Patients . Cohort one consists of 344 community-dwelling black persons identified from a r and om sample of 2212 black persons aged 65 and older residing in Indianapolis ; cohort two consists of 651 subject referrals to the Alzheimer Disease Center . Measurements . Formal diagnostic clinical assessment s for dementia including scores on the Mini-mental state examination ( MMSE ) , a six-item screener derived from the MMSE , the Blessed Dementia Rating Scale ( BDRS ) , and the Word List Recall . Based on clinical evaluations , subjects were categorized as no cognitive impairment , cognitive impairment-not demented , or demented . Results . The mean age of the community-based sample was 74.4 years , 59.4 % of the sample were women , and the mean years of education was 10.1 . The prevalence of dementia in this sample was 4.3 % and the prevalence of cognitive impairment was 24.6 % . Using a cut-off of three or more errors , the sensitivity and specificity of the six-item screener for a diagnosis of dementia was 88.7 and 88.0 , respectively . In the same sample , the corresponding sensitivity and specificity for the MMSE using a cut-off score of 23 was 95.2 and 86.7 . The performance of the two scales was comparable across the two population s studied and using either cognitive impairment or dementia as the gold st and ard . An increasing number of errors on the six-item screener is highly correlated with poorer scores on longer measures of cognitive impairment . Conclusions . The six-item screener is a brief and reliable instrument for identifying subjects with cognitive impairment and its diagnostic properties are comparable to the full MMSE . It can be administered by telephone or face-to-face interview and is easily scored by a simple summation of errors BACKGROUND There is evidence that offenders consume diets lacking in essential nutrients and this could adversely affect their behaviour . AIMS To test empirically if physiologically adequate intakes of vitamins , minerals and essential fatty acids cause a reduction in antisocial behaviour . METHOD Experimental , double-blind , placebo-controlled , r and omised trial of nutritional supplements on 231 young adult prisoners , comparing disciplinary offences before and during supplementation . RESULTS Compared with placebos , those receiving the active capsules committed an average of 26.3 % ( 95 % CI 8.3 - 44.33 % ) fewer offences ( P=0.03 , two-tailed ) . Compared to baseline , the effect on those taking active supplements for a minimum of 2 weeks ( n=172 ) was an average 35.1 % ( 95 % CI 16.3 - 53.9 % ) reduction of offences ( P<0.001 , two-tailed ) , whereas placebos remained within st and ard error . CONCLUSIONS Antisocial behaviour in prisons , including violence , are reduced by vitamins , minerals and essential fatty acids with similar implication s for those eating poor diets in the community Bias in self-reported dietary intake is important when evaluating the effect of dietary interventions , particularly for intervention foods . However , few have investigated this in children , and none have investigated the reporting accuracy of fish intake in children using biomarkers . In a Danish school meal study , 8- to 11-year-old children ( n 834 ) were served the New Nordic Diet ( NND ) for lunch . The present study examined the accuracy of self-reported intake of signature foods ( berries , cabbage , root vegetables , legumes , herbs , potatoes , wild plants , mushrooms , nuts and fish ) characterising the NND . Children , assisted by parents , self-reported their diet in a Web-based Dietary Assessment Software for Children during the intervention and control ( packed lunch ) periods . The reported fish intake by children was compared with their ranking according to fasting whole-blood EPA and DHA concentration and weight percentage using the Spearman correlations and cross-classification . Direct observation of school lunch intake ( n 193 ) was used to score the accuracy of food-reporting as matches , intrusions , omissions and faults . The reporting of all lunch foods had higher percentage of matches compared with the reporting of signature foods in both periods , and the accuracy was higher during the control period compared with the intervention period . Both Spearman 's rank correlations and linear mixed models demonstrated positive associations between EPA+DHA and reported fish intake . The direct observations showed that both reported and real intake of signature foods did increase during the intervention period . In conclusion , the self-reported data represented a true increase in the intake of signature foods and can be used to examine dietary intervention effects 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 The authors assessed the reproducibility and validity of an exp and ed 131-item semiquantitative food frequency question naire used in a prospect i ve study among 51,529 men . The form was administered by mail twice to a sample of 127 participants at a one-year interval . During this interval , men completed two one-week diet records spaced approximately 6 months apart . Mean values for intake of most nutrients assessed by the two methods were similar . Intraclass correlation coefficients for nutrient intakes assessed by question naires one year apart ranged from 0.47 for vitamin E without supplements to 0.80 for vitamin C with supplements . Correlation coefficients between the energy-adjusted nutrient intakes measured by diet records and the second question naire ( which asked about diet during the year encompassing the diet records ) ranged from 0.28 for iron without supplements to 0.86 for vitamin C with supplements ( mean r = 0.59 ) . These correlations were higher after adjusting for week-to-week variation in diet record intakes ( mean r = 0.65 ) . These data indicate that the exp and ed semiquantitative food frequency question naire is reproducible and provides a useful measure of intake for many nutrients over a one-year period 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 Most studies of association between diet and cognition among the elderly focus on the role of single nutrients or foods and ignore the complexity of dietary patterns and total diet quality . We prospect ively examined associations between an index of diet quality and cognitive function and decline among elderly men and women of the Cache County Study on Memory and Aging in Utah . In 1995 , 3634 resident men and women > or = 65 y of age completed a baseline survey that included a 142-item FFQ . Cognition was assessed using an adapted version of the Modified Mini-Mental State Examination ( 3MS ) at baseline and 3 subsequent interviews spanning approximately 11 y. A recommended food score ( RFS ) and non-RFS were computed by summing the number of recommended foods ( n = 57 ) and nonrecommended foods ( n = 23 ) regularly consumed . Multivariable-mixed models were used to estimate associations between the RFS and non-RFS and average 3MS score over time . Those in the highest quartile of RFS scored 1.80 points higher on the baseline 3MS test than did those in the lowest quartile of RFS ( P < 0.001 ) . This effect was strengthened over 11 y of follow-up . Those with the highest RFS declined by 3.41 points over 11 y compared with the 5.2-point decline experienced by those with the lowest RFS ( P = 0.0013 ) . The non-RFS was not associated with cognitive scores . Consuming a diverse diet that includes a variety of recommended foods may help to attenuate age-related cognitive decline among the elderly 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 CONTEXT Alcohol consumption has been associated with complex changes in cerebral vasculature and structure in older adults . How alcohol consumption affects the incidence of dementia is less clear . OBJECTIVE To determine the prospect i ve relationship of alcohol consumption and risk of dementia among older adults . DESIGN , SETTING , AND PARTICIPANTS Nested case-control study of 373 cases with incident dementia and 373 controls who were among 5888 adults aged 65 years and older who participated in the Cardiovascular Health Study , a prospect i ve , population -based cohort study in 4 US communities . The controls were frequency-matched on age , death before 1999 , and their attendance of a 1998 - 1999 clinic . Participants in this study underwent magnetic resonance imaging ( MRI ) of the brain and cognitive testing between 1992 and 1994 and were followed up until 1999 . MAIN OUTCOME MEASURES Odds of incident dementia , ascertained by detailed neurological and neuropsychological examinations according to average alcohol consumption , assessed by self-reported intake of beer , wine , and liquor at 2 visits prior to the date of the MRI . RESULTS Compared with abstention , the adjusted odds for dementia among those whose weekly alcohol consumption was less than 1 drink were 0.65 ( 95 % confidence interval [ CI ] , 0.41 - 1.02 ) ; 1 to 6 drinks , 0.46 ( 95 % CI , 0.27 - 0.77 ) ; 7 to 13 drinks , 0.69 ( 95 % CI , 0.37 - 1.31 ) ; and 14 or more drinks , 1.22 ( 95 % CI , 0.60 - 2.49 ; P for quadratic term = .001 ) . A trend toward greater odds of dementia associated with heavier alcohol consumption was most apparent among men and participants with an apolipoprotein E epsilon4 allele . We found generally similar relationships of alcohol use with Alzheimer disease and vascular dementia . CONCLUSIONS Compared with abstention , consumption of 1 to 6 drinks weekly is associated with a lower risk of incident dementia among older adults 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 Abstract Purpose Evidence suggests that dietary patterns compatible with the traditional Mediterranean diet ( MD ) may protect against cognitive decline . We prospect ively assessed whether adherence to MD in the Mediterranean country of Greece is inversely associated with cognitive decline in the elderly and whether any particular MD component may play a key role . Methods Elderly men and women ( N = 401 ) residing in the greater Athens area had dietary variables ascertained in 1994–1999 . Adherence to MD was represented by the MD score [ MDS , 0–3 ( low ) , 4–5 ( intermediate ) , 6–9 ( high ) ] . The mini-mental state examination ( MMSE ) was administered by trained professionals to individuals aged 65 years or older in 2004–2006 ( first assessment ) and re-administered in 2011–2012 ( second assessment ) . MMSE change ( cMMSE ) was categorized as : improved/unchanged ( cMMSE ≥ 0 ) , mildly lower ( cMMSE −1 to −4 ) or substantially lower ( cMMSE ≤ −5 ) . Associations were evaluated through multinomial logistic regression . Results Decline in MMSE performance was inversely associated with adherence to MD . For mild versus no decline , odds ratio ( OR ) comparing high to low MD adherence was 0.46 [ 95 % confidence interval ( CI ) 0.25–0.87 , p = 0.012 ] . For substantial versus no decline , OR comparing high to low MD adherence was 0.34 ( 95 % CI 0.13–0.89 , p = 0.025 ) . Among the nine MDS components , only vegetable consumption exhibited a significant inverse association with cognitive decline . Conclusions Closer adherence to the traditional MD is highly likely to protect against cognitive decline in this elderly Mediterranean population . Higher vegetable consumption appears to play a key role , possibly in synergy with additional components of the diet The Italian Longitudinal Study on Aging ( ILSA ) is a population -based , longitudinal study of the health status of Italians aged 65–84 years . The main objectives of ILSA are the study of the prevalence and incidence rates of common chronic conditions in the older population , and the identification of their risk and protective factors . ILSA is also design ed to assess age-associated physical and mental functional changes . A r and om sample of 5632 individuals , stratified by age and gender using the equal allocation strategy , was identified on the demographic lists of the registry office of eight municipalities : Genova , Segrate ( Milano ) , Selvazzano-Rubano ( Padova ) , Impruneta ( Firenze ) , Fermo ( Ascoli Piceno ) , Napoli , Casamassima ( Bari ) , and Catania . An extensive investigation , including interviews , physical exams , and laboratory tests , was conducted at baseline to identify the presence of cardiovascular disease ( ischemic heart disease , hypertension , congestive heart failure , arrhythmia , intermittent claudication ) , diabetes , impaired glucose tolerance , thyroid dysfunction , dementia , parkinsonism , stroke , and peripheral neuropathy , as well as assess physical and mental functional status . The baseline examination was carried out between March 1992 and June 1993 ; a second comprehensive examination will begin in March 1995 . An interim hospital discharge data survey and a mortality survey are currently ongoing to assess the hospitalization rate and the cause-specific mortality rate in this study cohort . ( Aging Clin . Exp . Res . 6 : 464 - 473 , 1994 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 |
1,753 | 25,899,057 | Our analysis also highlights specific treatments that are not cost-effective , thereby indicating areas of re source savings . | Background Complex wounds present a substantial economic burden on healthcare systems , costing billions of dollars annually in North America alone .
The prevalence of complex wounds is a significant patient and societal healthcare concern and cost-effective wound care management remains unclear .
This article summarizes the cost-effectiveness of interventions for complex wound care through a systematic review of the evidence base . | OBJECTIVES To determine the comparative effectiveness and cost-effectiveness of three dressing products , N-A , Inadine and Aquacel , for patients with diabetic foot ulcers , as well as the feasibility and consequences of less frequent dressing changes by health-care professionals . DESIGN A multicentre , prospect i ve , observer-blinded , parallel group , r and omised controlled trial , with three arms . SETTING Established expert multidisciplinary clinics for the management of diabetic foot ulcers across the UK . PARTICIPANTS Patients over age 18 with type 1 or type 2 diabetes with a chronic ( present for at least 6 weeks ) full-thickness foot ulcer ( on or below the malleoli ) not penetrating to tendon , periosteum or bone , and with a cross-sectional area between 25 and 2500 mm(2 ) . INTERVENTIONS Participants were r and omised 1:1:1 to treatment with one of N-A ( a non-adherent , knitted , viscose filament gauze ) , Inadine ( an iodine-impregnated dressing ) , both traditional dressings , or Aquacel , a newer product . MAIN OUTCOME MEASURES The primary outcome measure was the number of ulcers healed in each group at week 24 . Secondary measures included time to healing , new ulcerations , major and minor amputations , and episodes of secondary infection . RESULTS A total of 317 patients were r and omised . After 88 withdrawals , 229 remained evaluable . A greater proportion of smaller ( 25 - 100 mm(2 ) ulcers healed within the specified time ( 48.3 % versus 37.3 % ; p = 0.048 ) . There was , however , no difference between the three dressings in terms of percentage healed by 24 weeks , or in the mean time to healing , whether analysed on the basis of intention to treat ( Inadine 44.4 % , N-A 38.7 % , Aquacel 44.7 % ; not significant ) or per protocol ( Inadine 55.2 % , N-A 59.4 % , Aquacel 63.0 % ; not significant ) . There was no difference in the quality of healing , as reflected in the incidence of recurrence within 12 weeks . Likewise , there was no difference in the incidence of adverse events , although a greater proportion of those r and omised to the non-adherent dressings were withdrawn from the study ( 34.9 % versus 29.1 % Aquacel and 19.4 % Inadine ; p = 0.038 ) . The only statistically significant difference found in the health economic analysis was the cost associated with the provision of dressings ( mean cost per patient : N-A 14.85 pounds , Inadine 17.48 pounds , Aquacel 43.60 pounds ) . The higher cost of Aquacel was not offset by the fewer dressings required . There was no difference in measures of either generic or condition-specific measures of quality of life . However , there was a significant difference in the change in pain associated with dressing changes between the first and second visits , with least pain reported by those receiving non-adherent dressings ( p = 0.012 ) . There was no difference in the costs of professional time , and this may relate to the number of dressing changes undertaken by non-professionals . Fifty-one per cent of all participants had at least one dressing change undertaken by themselves or a non-professional carer , although this ranged from 22 % to 82 % between the different centres . CONCLUSIONS As there was no difference in effectiveness , there is no reason why the least costly of the three dressings could not be used more widely across the UK National Health Service , thus generating potentially substantial savings . The option of involving patients and non-professional carers in changing dressings needs to be assessed more formally and could be associated with further significant reductions in health-care costs . TRIAL REGISTRATION Current Controlled Trials IS RCT N78366977 OBJECTIVE To compare the healing response of sequential topically applied cytokines to that of each cytokine alone and to a placebo in pressure ulcers , and to evaluate the molecular and cellular responses . SUMMARY BACKGROUND DATA Because of a deficiency of cytokine growth factors in chronic wounds and the reversal of impaired healing in animal models , pressure ulcer trials have been performed with several exogenously applied growth factors . Because single-factor therapy has not been uniformly successful , combination or sequential cytokine therapy has been proposed . Laboratory data have suggested that sequential treatment with granulocyte-macrophage/colony-stimulating factor (GM-CSF)/basic fibroblast growth factor ( bFGF ) might augment the previously reported effect of bFGF alone . METHODS A masked , r and omized pressure ulcer trial was performed comparing sequential GM-CSF/bFGF therapy with that of each cytokine alone and with placebo during a 35-day period . The primary measure was wound volume decrease over time . Cytokine wound levels and mRNA levels were serially determined . Fibroblast-populated collagen lattices ( FPCLs ) were constructed from serial fibroblast biopsies . Cellular ultrastructure was evaluated by electron microscopy . Changes in ease of surgical closure and its relative cost were determined . RESULTS Ulcers treated with cytokines had greater closure than those in placebo-treated patients . Patients treated with bFGF alone did the best , followed by the GM-CSF/bFGF group . Patients treated with GM-CSF or bFGF had higher levels of their respective cytokine after treatment . Patients with the greatest amount of healing showed higher levels of platelet-derived growth factor ( PDGF ) on day 10 and transforming growth factor beta ( TGFbeta1 ) on day 36 . Message for the bFGF gene was upregulated after treatment with exogenous bFGF , suggesting autoinduction of the cytokine . FPCLs did not mimic the wound responses . Ultrastructure of wound biopsies showed response to bFGF . Treatment with any of the cytokines improved the wound by allowing easier wound closure . This was most marked for the bFGF-alone treatment , with a cost savings of $ 9,000 to $ 9,200 . CONCLUSIONS Treatment with bFGF result ed in significantly greater healing than the other treatments in this trial . The clinical response appeared to be related to upregulation of the bFGF message and to increased levels of PDGF-AB , bFGF , and TGFbeta1 in the wounds and changes in ultrastructure . The result ant improvements could be correlated with cost savings The study investigated the cost‐effectiveness of four‐layer and short‐stretch compression b and ages for treating venous leg ulcers OBJECTIVE : Evaluate the effectiveness of telemedicine ( TM ) with digital cameras in treating wounds in a home care setting . DESIGN : R and omized controlled study . PARTICIPANTS AND SETTING : One hundred three subjects with 160 pressure ulcers ( PrUs ) or nonhealing surgical wounds referred to a metropolitan Visiting Nurse Agency . INTERVENTIONS : Subjects were r and omly assigned to 1 of 3 groups . Group A ( n = 40 ) : weekly visits with TM and wound care specialist ( WCS ) consults ; group B ( n = 28 ) : weekly visits with weekly consults with WCSs ; and group C ( n = 35 ) : usual and customary care . MAIN OUTCOME MEASURES : Outcome measures were time to heal , costs , length of stay ( LOS ) , nursing visits , wound status , and change in size . RESULTS : There was a similar distribution of subject characteristics in all 3 groups , but group A had disproportionally larger and more numerous PrUs and larger nonhealing surgical wounds . Group A had increased time to heal , LOS , costs , and visits compared with groups B and C ; wound status was similar in all groups . CONCLUSIONS : Uneven distribution of severity and type of wounds among groups , with greatest percentage of large wounds in TM group . Larger wounds consume more re sources . TM is a useful communication tool in wound management but with limited power when r and omization does not include wound size or type . Two important benchmarks were established for home care . First , it took 51 days , on average , to heal or improve PrUs and 34 days to heal or improve surgical wounds regardless of group . Second , nearly 90 % of wounds improved or healed OBJECTIVE —This study was design ed to test the safety , effectiveness , and costs of off-loading with a novel , off-the-shelf irremovable device in the management of diabetic foot ulceration ( DFU ) . RESEARCH DESIGN AND METHODS —We prospect ively evaluated off-loading of neuropathic plantar ulcers in 40 diabetic out patients attending our diabetic foot clinic and compared healing rates at the 12-week follow-up , number and severity of adverse events , healing time , costs and applicability of the device , and patients ’ satisfaction between those r and omly assigned to total contact casting ( TCC ; group A ) or to the Optima Diab walker ( group B ) . Deep or infected ulcers were excluded . RESULTS —No difference between groups A and B was observed in healing rates at 12 weeks ( 95 vs. 85 % ) , healing time ( 6.5 ± 4.4 vs. 6.7 ± 3.4 weeks ) , and number of adverse events ( six versus four ) . Treatment was significantly less expensive in group B , which showed a mean reduction of costs of 78 % compared with group A ( P < 0.001 ) . Practicability was more favorable in group B , with a reduction of 77 and 58 % of the time required for application and removal of the devices , respectively ( P < 0.001 ) . Patients ’ satisfaction with the treatment was higher in group B ( P < 0.01 ) . CONCLUSIONS —The Optima Diab walker is as safe and effective as TCC in the management of DFU , but its lower costs and better applicability may be of help in spreading the practice of off-loading among the centers that manage the diabetic foot Abstract Objectives : To establish the relative cost effectiveness of community leg ulcer clinics that use four layer compression b and aging versus usual care provided by district nurses . Design : R and omised controlled trial with 1 year of follow up . Setting : Eight community based research clinics in four trusts in Trent . Subjects : 233 patients with venous leg ulcers allocated at r and om to intervention ( 120 ) or control ( 113 ) group . Interventions : Weekly treatment with four layer b and aging in a leg ulcer clinic ( clinic group ) or usual care at home by the district nursing service ( control group ) . Main outcome measures : Time to complete ulcer healing , patient health status , and recurrence of ulcers . Satisfaction with care , use of services , and personal costs were also monitored . Results : The ulcers of patients in the clinic group tended to heal sooner than those in the control group over the whole 12 month follow up ( log rank P=0.03 ) . At 12 weeks , 34 % of patients in the clinic group were healed compared with 24 % in the control . The crude initial healing rate of ulcers in intervention compared with control patients was 1.45 ( 95 % confidence interval 1.04 to 2.03 ) . No significant differences were found between the groups in health status . Mean total NHS costs were £ 878.06 per year for the clinic group and £ 859.34 for the control ( P=0.89 ) . Conclusions : Community based leg ulcer clinics with trained nurses using four layer b and aging is more effective than traditional home based treatment . This benefit is achieved at a small additional cost and could be delivered at reduced cost if certain service configurations were used . Key messages Leg ulcer clinics based in the community using four layer compression b and aging can be more clinical ly effective than usual care provided by the district nursing service Community based leg ulcer clinics could be provided more cost effectively than usual home based care for venous leg ulcers Recurrence of venous leg ulcers is an important variable that should be measured in future trials of venous leg ulcer care It is difficult to measure improvements in health related quality of life among people with venous leg " Least costly but most effective " has never been more important to healthcare delivery than in the current healthcare environment of changing reimbursement systems . In wound care , the high costs associated with renting advanced support surfaces may be an area where expenses can be decreased if similar outcomes can be attained by using more affordable mattresses . This article compares the healing rates and eventual outcomes of wounds among two groups of patients r and omly assigned to one of two support surfaces . A commonly used low-air-loss mattress was compared with the study mattress , an advanced , non-powered , air and foam surface . Subjects were patients admitted to either of two long-term healthcare setting s for the treatment of wounds . The result ing two groups of 10 patients each were evenly matched for average age and percentage of patients who were nutritionally deficient as indicated by albumin or pre-albumin levels . The presence of gastrointestinal tubes and ventilator dependency also was recorded . Consistent wound care protocol s were used on both groups , including turning schedules , nutrition , topical medication , and dressings . The study period covered a maximum of 8 weeks ; interest was centered on the rate of wound healing and progress toward a goal rather than the length of time to completely close a wound . After 8 weeks , or upon discharge from the study pressure ulcers in the study mattress group closed at an average rate per week of 9.0 % + /- 4.8 versus 5.0 % + /- 3.7 in the low-air-loss mattress group . This study indicates that the study mattress can provide benefits to the wound healing process similar to or better than low-air-loss mattresses at a substantially reduced cost OBJECTIVE ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications . The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers . METHOD eighteen diabetic patients with ischaemic , non-healing lower-extremity ulcers were recruited in a double-blind study . Patients were r and omly assigned either to receive 100 % oxygen ( treatment group ) or air ( control group ) , at 2.4 atmospheres of absolute pressure for 90 min daily ( total of 30 treatments ) . RESULTS healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group . The median decrease of the wound areas in the treatment group was 100 % and in the control group was 52 % ( p=0.027 ) . Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen , there was a potential saving in the total cost of treatment for each patient during the study . CONCLUSION hyperbaric oxygen enhanced the healing of ischaemic , non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible A cost-effectiveness analysis was performed following a double-blind , r and omized study of ampicillin/sulbactam ( A/S ) versus imipenem/cilastatin ( I/C ) for the treatment of limb-threatening foot infections in 90 diabetic patients . There were no significant differences between the treatments in terms of clinical success rate , adverse-event frequency , duration of study antibiotic treatment , or length of hospitalization . Costs of the study antibiotics , treatment of failures and adverse events , and hospitalization were calculated . Mean per-patient treatment cost in the A/S group was $ 14,084 , compared with $ 17,008 in the I/C group ( P = .05 ) , primarily because of lower drug and hospitalization costs and less-severe adverse events in the A/S group . Sensitivity analyses varying drug prices or hospital costs demonstrated that A/S was consistently more cost-effective than I/C. Varying the clinical success rate for each drug revealed that I/C would have to be 30 % more effective than A/S to change the economic decisions Background Venous leg ulcers , affecting approximately 1 % of the population , are costly to manage due to poor healing and high recurrence rates . We evaluated an evidence -informed leg ulcer care protocol with two frequently used high compression systems : ‘ four-layer b and age ’ ( 4LB ) and ‘ short-stretch b and age ’ ( SSB ) . Methods We conducted a cost-effectiveness analysis using individual patient data from the Canadian B and aging Trial , a publicly funded , pragmatic , r and omized trial evaluating high compression therapy with 4LB ( n = 215 ) and SSB ( n = 209 ) for community care of venous leg ulcers . We estimated costs ( in 2009–2010 Canadian dollars ) from the societal perspective and used a time horizon corresponding to each trial participant ’s first year . Results Relative to SSB , 4LB was associated with an average 15 ulcer-free days gained , although the 95 % confidence interval [ −32 , 21 days ] crossed zero , indicating no treatment difference ; an average health benefit of 0.009 QALYs gained [ −0.019 , 0.037 ] and overall , an average cost increase of $ 420 [ $ 235 , $ 739 ] ( due to twice as many 4LB b and ages used ) ; or equivalently , a cost of $ 46,667 per QALY gained . If decision makers are willing to pay from $ 50,000 to $ 100,000 per QALY , the probability of 4LB being more cost effective increased from 51 % to 63 % . Conclusions Our findings differ from the emerging clinical and economic evidence that supports high compression therapy with 4LB , and therefore suggest another perspective on high compression practice , namely when delivered by trained registered nurses using an evidence -informed protocol , both 4LB and SSB systems offer comparable effectiveness and value for money . Trial registration Clinical Trials.gov Identifier : OBJECTIVES To compare the effects of topical collagen and hydrocolloid on pressure ulcer healing . DESIGN R and omized ( allocation concealed ) , single-blind ( outcome assessors ) , controlled trial with 8-week follow-up . SETTING Eleven nursing homes in central Illinois . PARTICIPANTS Sixty-five patient-residents with Stage II or III pressure ulcers : median age 83.1 , median Braden score 12 , 63 % female , 80 % Stage II ulcers , and 20 % Stage III ulcers . Exclusion criteria included cellulitis and osteomyelitis . INTERVENTION Thirty-five patients were allocated to topical collagen daily , 30 to topical hydrocolloid twice weekly . MEASUREMENTS The primary outcome was complete healing within 8 weeks . Secondary outcomes were time to heal , ulcer area healed per day , linear healing of wound edge , and cost of therapy . RESULTS Analysis by intention to treat revealed similar complete ulcer healing within 8 weeks in collagen ( 51 % ) and hydrocolloid ( 50 % ) recipients ( difference 1 % , 95 % confidence interval ( CI ) = 26 - 29 % ) . Mean healing time was similar : collagen healed in 5 weeks ( 95 % CI = 4 - 6 ) , hydrocolloid healed in 6 weeks ( 95 % CI = 5 - 7 ) . Mean area healed per day was 6 mm(2)/d in both treatment groups . Mean linear healing of the wound edge was 3 mm in both groups . In multivariate analysis , baseline ulcer depth was the only independent predictor of complete ulcer healing within 8 weeks ( odds ratio = 0.56 , 95 % CI = 0.38 - 0.81 ) . Cost analysis favored hydrocolloid . CONCLUSIONS There were no significant differences in healing outcome between collagen and hydrocolloid . Collagen was more expensive and offered no major benefits to patients otherwise eligible for hydrocolloid treatment Venous ulcers are the most common chronic wounds of the lower leg . Skin substitutes recently have been introduced to stimulate nonhealing wounds . To conduct an incremental cost-effectiveness analysis , a model was developed to compare the four-layer b and age system , with and without one application of skin substitute , for the outpatient treatment of venous leg ulcers . The model estimated the costs and consequences of treatment with and without the skin substitute application . Two analytic horizons were explored : 3 months and 6 months . Determined by seven physicians , data and assumptions for the 3-month model were based on information from a clinical trial , published studies , and clinical experience . Data for the 6-month model were extrapolated from the shorter model . The model results indicate that over 3 months , the use of the skin substitute provided a benefit of 22 ulcer days averted per patient at an incremental cost of $ 304 ( societal ) . The incremental cost-effectiveness ratio was $ 14 per ulcer day averted . Over 6 months , the incremental cost-effectiveness ratio was less than $ 5 per ulcer-day averted . The skin substitute plus a four-layer b and age was more costly and more effective than the four-layer b and age alone . The skin substitute is increasingly cost-effective over a longer analytic horizon and in a subgroup of patients with ulcers of long duration ( greater than 1-year duration at baseline ) . The results come from a model that is based on a series of estimates and assumptions , and accordingly , confirmation of this finding in a prospect i ve study is encouraged OBJECTIVE To compare the performance of two compression systems , ( multilayer elastic [ Profore ] , Smith and Nephew ) and ( short stretch [ Comprilan ] , Beiersdorf ) , in the treatment of venous leg ulcers in a r and omised controlled trial . METHOD Eighty-nine patients with venous leg ulcers were r and omised to receive treatment with Profore ( 44 patients ) or short-stretch ( 45 patients ) compression b and ages . Allevyn ( Smith and Nephew ) was used as the wound contact layer under both systems . RESULTS Patients treated with Profore healed significantly faster than those treated with short stretch ( p = 0.03 ) and were 2.9 times more likely to heal at any given time during the study period . Younger wounds healed significantly faster than older wounds ( p = 0.01 ) . CONCLUSION Patients treated with Profore healed faster than those treated with short-stretch b and ages . In addition , treatment costs are lower with Profore . In this trial the average cost per patient was [ symbol : see text ] 1345 ( short stretch ) and [ symbol : see text ] 587 ( Profore ) Modern dressings such as hydrocolloids , gels , and foams are typically more expensive than traditional dressings such as gauze . However , if modern dressings require fewer changes , the overall cost of treatment may be lower despite the higher initial purchase price . If healing rates are comparable or better , modern dressings also may be cost-effective . A 4-week , prospect i ve , r and omized clinical trial to assess differences in treatment costs and cost-effectiveness between a modern foam dressing and saline-soaked gauze was conducted among 36 patients ( 22 men , 14 women , mean age 72.8 years ) with a Stage II pressure ulcer ( mean duration 35 weeks ) at five centers in the United States . Participants were r and omized to treatment with a self-adhesive polyurethane foam ( n = 20 ) or saline-soaked gauze dressing ( n = 16 ) . No difference in time to wound closure was observed ( P = 0.817 ) . Patients in the foam group had less frequent dressing changes ( P < 0.001 ) . Total cost over the study period was lower by $ 466 per patient ( P = 0.055 ) and spending on dressings was lower by $ 92 per patient in the foam group ( P = 0.025 ) . Cost per ulcer healed was lower by $ 1,517 and cost per ulcer-free day was lower by $ 80 for patients in the foam group . On the evidence of this study , the foam dressing is a more cost-effective treatment than saline-soaked gauze for the treatment of Stage II pressure ulcers BACKGROUND Controlling infection and promoting healing should be aims of pressure ulcer treatment along with improving a patient 's general condition and relieving pressure . Many pressure ulcers present with cavities , tracks or a combination of these . A new silver mesh dressing ( Tegaderm Ag Mesh dressing ) has the ability to contour around and conform to irregular surfaces of a wound bed . OBJECTIVE To evaluate the efficacy of a silver mesh dressing compared with silver sulfadiazine cream for pressure ulcer treatment . MATERIAL AND METHOD A prospect i ve , r and omized , clinical trial was conducted in patients with pressure ulcers grade III or IV . The patients were divided r and omly by computer into two 20 patient-groups . The study period was eight weeks for each patient . Demographic data , wound size , wound photography , and bacterial wound culture were recorded at the beginning of the study and every two weeks thereafter . Wound beds were covered with silver sulfadiazine cream in the control group and silver mesh dressing in the experimental group . Dressings were changed twice a day in the control group and every three days in the experimental group . RESULTS Forty-five patients enrolled in the present study but only 40 patients finished the study . Twenty patients in each group finished the eight-week study . The mean healing rates and the percentage of reduction in PUSH score at eight-week were better in the study group than in the control group but they were not statistically significant . Better changing in bacteriological study after the treatment was shown in both groups . The estimated average cost of the treatment in the mesh group was 263 USD per patient while it was 1812 USD in the cream one ( p = 0.0001 ) . Silver mesh dressing can be adapted very well on the bed , can control infection , and promote wound healing . Wound reduction was greater in the experimental group than the control group . The cost of treatment , using silver mesh was cheaper than using silver sulfadiazine cream significantly . CONCLUSION Silver mesh dressings is one of the choices for pressure ulcer treatment with good healing rate , minimal care and lower overall cost OBJECTIVE The majority of leg ulcer patients in Sweden are managed by primary health care personnel . To compare , in a primary care setting , the healing results and the expenses of two commonly used wound dressings for leg ulcers . DESIGN Thirty patients with leg ulcers of venous or mixed venous/arterial aetiology were r and omized to treatment with saline-soaked gauze or with the hydrocolloidal dressing [ HCD : DuoDERM ( ConvaTec , A Bristol-Myers Squibb Company , Princeton ) ] . All patients were b and aged with the same compression of low-stretch-type [ Comprilan ( Beiersdorf AG , Hamburg ) ] . SETTING Vård central en Marieberg , Primary Health Care Centre , Motala , Sweden . OUTCOME MEASURES Healing/reduction of ulcer area , pain , costs for material , nursing time , kilometres driven were registered during a six-week period . RESULTS Two patients dropped out of the study , one in the gauze-group due to erysipelas , and one in the HCD-group for social reasons . A total of 1234 dressing changes were analysed . Costs for material were similar in the two groups . When the total care including nursing- and travelling time and kilometres driven were analysed , the mean cost for treatment with gauze dressings was 4126 Swedish Kronor ( SEK ) , and with HCD , 1565 SEK . Seven patients in the HCD-group and two in the gauze-group healed during the study . The reduction of the ulcer area was 19 % in the gauze-group and 51 % in the HCD-group ( p < 0.16 ) . CONCLUSION The total care , analysed in an authentic clinical setting , must be considered when different wound-care methods are discussed . In this study the use of HCD showed lower costs than use of gauze-dressings . As regards healing there was a tendency to improved healing with HCD , but no significant difference . Patients in the HCD-group reported significantly less pain at dressing changes ( p < 0.003 ) than patients in the gauze-group Abstract Objective : To conduct a Bayesian value-of-information analysis of the cost effectiveness of pentoxifylline ( vs placebo ) as an adjunct to compression for venous leg ulcers . Methods : A probabilistic Markov model was developed to estimate mean clinical benefits and costs associated with oral pentoxifylline ( 400 mg three times daily ) and placebo . Clinical data were obtained from a systematic review and synthesis ed using Bayesian methods . The decision uncertainty associated with the adoption of pentoxifylline as well as the maximum value associated with further research were estimated before and after the completion of the largest ‘ definitive ’ treatment trial . Re source use was obtained from a UK national audit and unit costs applied ( £ , 2004 values ) . Results : The prior and posterior analyses suggest that pentoxifylline is a dominant therapy versus placebo . In the prior analysis , patients in the pentoxifylline group healed an average of 8.28 weeks quicker than patients in the placebo group ( 95 % credibility interval [ CI ] 1.89 , 14.56 ) , had a 0.02 gain in QALYs ( 95 % CI −0.12 , 0.17 ) and an average reduction in cost of £ 153.4 ( 95 % CI −53.11 , 354.9).Estimates of the uncertainty surrounding the cost effectiveness of pentoxifylline and the value of perfect information in both analyses did not suggest further research was justified . In the prior analysis , for willingness-to-pay values of £ 0 , £ 100 and £ 500 per QALY gained , the estimated values of perfect information were £ 128 200 , £ 127 100 and £ 126 700 , respectively . Incorporation of the information from the largest r and omised controlled trial on pentoxifylline did improve the estimate of the clinical effect associated with this drug ; however , the variation was not large enough to reverse either the decision regarding the dominance of pentoxifylline or the maximum value associated with further research . Conclusion : Bayesian value-of-information analysis represents a valuable tool for healthcare decision making . Had the results from this analysis been available before the largest trial was funded , a more efficient allocation of research and development re sources could have been made OBJECTIVES To compare the clinical and cost-effectiveness of two different compression b and ages for the healing of venous leg ulcers . DESIGN A pragmatic , r and omised controlled trial with an economic evaluation . SETTING Community , district nurse-led services ; community leg ulcer clinics ; hospital leg ulcer clinics with community outreach . A range of urban and rural setting s in Engl and and Scotl and . PARTICIPANTS Patients with a venous leg ulcer of at least 1-week 's duration , at least 1 cm in length or width and an ankle : brachial pressure index of at least 0.8 . INTERVENTIONS The four-layer b and age ( 4LB ) ( which is multilayer elastic compression ) compared with the short-stretch b and age ( SSB ) ( multilayer , inelastic compression ) . MAIN OUTCOME MEASURES The primary end-point was complete healing of all the ulcers on the trial leg . Secondary outcomes were the proportion of patients healed at 12 and 24 weeks , rate of recurrence , costs of leg ulcer treatment and quality of life . RESULTS Between April 1999 and December 2000 the trial recruited 387 people aged from 23 to 97 years at trial entry . The majority of patients in this trial ( 82 % ; 316/387 ) had a reference ulcer of area < /=10 cm(2 ) . To test the difference over time of Kaplan -- Meier curves for the two b and age groups , the distribution of the cumulative times to healing of individuals in the two trial groups was compared using the log-rank test . The difference in the distribution of cumulative healing times between the individuals in the two groups was not statistically significant at the 5 % level . Adjusting for the effects of variables which may influence healing ( centre , baseline ulcer area , duration , episodes , ankle mobility , weight ) in a Cox proportional hazards model , a statistically significant treatment effect in favour of the 4LB was identified . At any point in time , the probability of healing for individuals in the SSB treatment arm is significantly lower than that for people treated with the 4LB . Our base case economic analysis showed that the 4LB is the dominant strategy , that is , it is associated with a greater health benefit and lower costs than the SSB , although the differences are not statistically significant . This result is explained largely by the greater number of community nurse visits required by participants in the short-stretch arm . CONCLUSIONS The 4LB , which is currently the UK st and ard compression b and age for people with venous leg ulcers , was more clinical ly and cost-effective than the SSB . The b and age costs were less important than the costs of treatment visits , and patients in SSBs required more treatment overall . Generally , this trial supports the use of the 4LB in preference to the SSB . Recommendations for future research include : exploration of the relationship between b and ager skill , application technique and ulcer healing ; the relative cost-effectiveness of community leg ulcer clinics ; and the study of nurse decision-making in venous ulcer management The aim of this study was to compare the cost‐effectiveness of four‐layer compression b and aging for venous leg ulcers with that of other available treatments OBJECTIVES To evaluate the cost-effectiveness of a multidisciplinary wound care team in the nursing home setting from a health system perspective . METHODS Pseudo-r and omized pragmatic cluster trial with 20-week follow-up involving 342 uncomplicated leg and pressure ulcers in 176 residents located in 44 high-care nursing homes in Melbourne , Australia in 1999 - 2000 . Twenty-one nursing homes ( 180 wounds in 94 residents ) were assigned to the intervention arm and 23 to the control arm ( 162 wounds in 82 residents ) . Residents in the intervention arm received st and ardized treatment from a wound care team comprising of trained community pharmacists and nurses . Residents in the control arm received usual care . RESULTS More wounds healed during the trial in the intervention arm than in the control arm ( 61.7 % versus 52.5 % , P = 0.07 ) . A Cox regression with shared frailty predicted that the chances of healing increased 73 % for intervention wounds [ 95 % confidence interval ( CI ) 20 - 150 % , P = 0.003 ] . The mean treatment cost was $ A616.4 for intervention and $ A977.9 for control patients ( P = 0.006 ) . Most cost reduction was obtained from decreases in nursing time and waste disposal . The mean cost saving per wound , adjusted for baseline wound severity and r and om censoring , was $ A277.9 ( 95 % CI $ A21.6-$A534.1 ) . CONCLUSIONS St and ardized treatment provided by a multidisciplinary wound care team saved costs and improved chronic wound healing in nursing homes . The main source of saving was in the cost of nursing time in applying traditional dressings and in the cost of their disposal This study compares the costs of dressings used in the treatment of patients with a variety of wound aetiologies . The two dressings investigated were a hydrocolloid dressing and a hydrocellular dressing . Secondary objectives included a comparison of dressing durability , time to complete healing , ease of wound cleansing and dressing removal . The study was an open prospect i ve single-centre r and omised parallel group trial involving 100 patients , treated in the community , who were r and omised to the two dressing groups . For all aetiologies except pressure sores , the costs of the hydrocolloid dressing were less than the costs of the hydrocellular dressings . Similar healing rates were observed in the leg ulcer and ' other wound ' groups . There were , however , significant differences in the number of healed wounds observed in patients with pressure sores treated with the hydrocellular dressing OBJECTIVES To compare the clinical effectiveness and cost-effectiveness of low-dose ultrasound delivered in conjunction with st and ard care against st and ard care alone in the treatment of hard-to-heal venous ulcers . DESIGN A multicentre , pragmatic , two-armed r and omised controlled trial with an economic evaluation . SETTING Community nurse services ; community leg ulcer clinics ; hospital outpatient leg ulcer clinics , among both urban and rural setting s in Engl and , Scotl and , Northern Irel and and Irel and . PARTICIPANTS Patients with a venous leg ulcer of > 6 months ' duration or > 5 cm2 and an ankle-brachial pressure index of ≥ 0.8 . In total , 337 patients were recruited to the study . INTERVENTIONS Participants in the intervention group received low-dose ultrasound ( 0.5 W/cm2 ) delivered at 1 MHz , pulsed pattern of 1 : 4 , applied to periulcer skin ( via a water-based contact gel ) weekly for up to 12 weeks alongside st and ard care . St and ard care consisted of low-adherent dressings and compression therapy , renewed as recommended by the patient 's nurse and modified if required to reflect changes in ulcer and skin condition . The output of the ultrasound machines was checked every 3 months to confirm intervention fidelity . MAIN OUTCOME MEASURES The primary end point was time to healing of the largest eligible ulcer ( reference ulcer ) . Secondary outcomes were time to healing of all ulcers , proportion of patients healed , percentage and absolute change in ulcer size , proportion of time patients were ulcer free , cost of treatments , health-related quality of life ( HRQoL ) , adverse events , withdrawal and loss to follow-up . RESULTS There was a small , and statistically not significant , difference in the median time to complete ulcer healing of all ulcers in favour of st and ard care [ median 328 days , 95 % confidence interval ( CI ) 235 days , inestimable ] compared with ultrasound ( median 365 days , 95 % CI 224 days , inestimable ) . There was no difference between groups in the proportion of patients with ulcers healed at 12 months ( 72/168 in ultrasound vs 78/169 st and ard care ) , nor in the change in ulcer size at 4 weeks . There was no evidence of a difference in recurrence of healed ulcers . There was no difference in HRQoL [ measured using the Short Form question naire-12 items ( SF-12 ) ] between the two groups . There were more adverse events with ultrasound than with st and ard care . Ultrasound therapy as an adjuvant to st and ard care was found not to be a cost-effective treatment when compared with st and ard care . The mean cost of ultrasound was £ 197.88 ( bias-corrected 95 % CI -£35.19 to £ 420.32 ) higher than st and ard care per participant per year . There was a significant relationship between ulcer healing and area and duration at baseline . In addition , those centres with high recruitment rates had the highest healing rates . CONCLUSIONS Low-dose ultrasound , delivered weekly during dressing changes , added to the package of current best practice ( dressings , compression therapy ) did not increase ulcer healing rates , affect quality of life ( QoL ) or reduce recurrence . It was associated with higher costs and more adverse events . There is no evidence that adding low-dose ultrasound to st and ard care for ' hard-to-heal ' ulcers aids healing , improves QoL or reduces recurrence . It increases costs and adverse events . The relationship between ulcer healing rates and patient recruitment is worthy of further study . TRIAL REGISTRATION Current Controlled Trials IS RCT N21175670 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 15 , No. 13 . See the HTA programme website for further project information Diabetic foot ulcers with exposure of tendon , muscle , or bone imply a high probability for deep infections and amputations . Delayed healing times are often described . The aim of this study was to compare the clinical effect and economic cost of cadexomer iodine with st and ard treatment in diabetic feet with cavity ulcers . Patients with deep , exudative foot ulcers were included in a 12-week open , r and omised , comparative study . When ulcers stopped exudating , vaseline gauze was used in both groups until the end of the study . Costs were estimated for dressing material , staff and transportation . Clinical ly relevant improvement was seen in 12 patients treated with cadexomer iodine and in 13 patients treated with st and ard treatment . The average weekly cost was SEK 903 and SEK 1,421 , respectively , of which the major part was costs for staff and transportation related to frequency of dressing changes . Treatment with cadexomer iodine ointment ( Iodosorb ) showed no clinical difference compared to topical treatment consisting of gentamicin solution , streptodornase/streptokinase , or dry saline gauze but was associated with considerably lower weekly treatment costs OBJECTIVES The objective of this study was to develop a model capable of assessing the cost-effectiveness in Sweden of treating diabetic neuropathic lower extremity ulcers with becaplermin gel ( Regranex ) plus good wound care ( GWC ) relative to treating them with GWC alone . METHODS A Markov simulation model was developed that includes six health states : Uninfected Ulcer , Infected Ulcer , Gangrene , Healed Ulcer , Healed Ulcer-History of Amputation , and Deceased . To predict clinical outcomes , information was taken from a specially design ed prospect i ve 9-month follow-up study of 183 neuropathic patients in the US treated with GWC . Cost of treatment data were taken primarily from a study of a cohort of 314 patients in Sweden . The efficacy of becaplermin was assumed equal to that achieved in a pooled analysis of four r and omized clinical trials . A model application provides expected clinical outcomes for a cohort of patients . Annual treatment costs per patient were estimated using treatment practice and unit prices from Sweden . RESULTS Due to a higher rate of healing and a shorter average healing time , treatment with becaplermin gel was predicted to increase the average number of months spent in the healed state over the first year following development of an ulcer by 24 % relative to GWC alone . In addition , the corresponding number of amputations was 9 % lower for the becaplermin-treated cohort . The average expected cost of $ 12,078 US for an individual treated with GWC alone declines to $ 11,708 US for one treated with becaplermin , in spite of $ 1262 becaplermin costs . Expenses related to topical treatment and inpatient care account for 83 % of the re sources conserved . CONCLUSIONS Our results suggest that in Sweden treatment with becaplermin in conjunction with GWC consumes fewer re sources and generates better outcomes than treatment with GWC alone for diabetic neuropathic ulcers . In light of the high and increasing incidence of such ulcers , the potential savings in costs and suffering may be important . Results are difficult to extrapolate internationally because they are strongly related to country-specific treatment practice s and price levels This prospect i ve r and omized study was conducted in the home care setting to compare healing rates and costs of two different dressings for pressure ulcers : the gauze and tape dressing and the transparent moisture vapor permeable dressing ( MVP ) . Demographic variables , healing rates , and cost of treatment were statistically analyzed for 77 pressure ulcers ( 48 patients ) . Each wound was r and omly assigned to either a gauze dressing or a MVP dressing . Initial ulcer grade ( Shea criteria ) and measurements were determined at the start of treatment and weekly for an eight-week period . Photographs of the wound were taken at the beginning and end of treatment . The same protocol for irrigating the wound and relieving pressure was followed for both dressing groups . The median improvement for the grade II group was 100 % for the MVP ( n = 22 ) and 52 % for gauze ( n = 12 ) , p less than 0.05 ( Wilcoxon rank sum test ) . The healing rates for grade III ulcers were not significantly different in the two dressing groups . The mean ( eight-week ) labor and supply cost per ulcer using the MVP was $ 845 , while that for gauze treatments was $ 1359 , p less than 0.05 ( Wilcoxon rank sum test ) . The cost difference for grade III ulcers was not significant in the two dressing groups . The MVP improved the healing rate and was more cost effective for grade II ulcers . Both gauze and MVP dressings proved effective for the treatment of grade III ulcers OBJECTIVES To compare the clinical effectiveness and cost-effectiveness of larval therapy with a st and ard debridement technique ( hydrogel ) . DESIGN A pragmatic , three-arm , r and omised controlled trial with an economic evaluation . SETTING Community nursing services , community leg ulcer clinics and hospital outpatient leg ulcer clinics . A range of urban and rural setting s. PARTICIPANTS Patients with venous or mixed venous/arterial ulcers ( minimum ankle brachial pressure index of 0.6 ) where a minimum of 25 % of ulcer area was covered by slough and /or necrotic material . INTERVENTIONS Loose larval therapy and bagged larval therapy compared with hydrogel . MAIN OUTCOME MEASURES The primary end point was complete healing of the largest eligible ulcer . The primary outcome was time to complete healing of the reference ulcer . Secondary outcomes were : time to debridement , cost of treatments , health-related quality of life ( including ulcer-related pain ) , bacterial load , presence of methicillin-resistant Staphylococcus aureus and staff and patient attitudes to and beliefs about larval therapy . RESULTS Between July 2004 and May 2007 the trial recruited 267 people aged 20 - 94 years at trial entry . There were more female ( n = 158 ) than male ( n = 109 ) participants and most ulcers were classified by the nurse as having an area greater than 5 cm(2 ) . The time to healing for the three treatment arms was compared using the log rank test . The difference in time to healing in the three treatments was not statistically significant at the 5 % level . Adjustment was then made for stratification and prespecified prognostic factors ( centre , baseline ulcer area , ulcer duration and type of ulcer ) using a Cox proportional hazards model . No difference was found in healing rates between the loose and bagged larvae groups . Results for larvae ( loose and bagged pooled ) compared with hydrogel showed no evidence of a difference in time to healing . When the same analytical steps were used to investigate time to debridement , larvae-treated ulcers debrided significantly more rapidly than hydrogel-treated ulcers ; however , the difference in time to debridement between loose and bagged larvae was not significant . The adjusted analysis reported the hazard of debriding at any time for those in loose and bagged larvae groups as approximately twice that of the hydrogel group . No differences in health-related quality of life or bacteriology were observed between trial arms . Larval therapy was associated with significantly more ulcer-related pain than hydrogel . Our base-case economic evaluation showed large decision uncertainty associated with the cost-effectiveness of larval therapy compared with hydrogel , suggesting that larval therapy and hydrogel therapy have similar costs and effects in the treatment of sloughy and /or necrotic leg ulcers . CONCLUSIONS Larval therapy significantly reduced the time to debridement of sloughy and /or necrotic , chronic venous and mixed venous/arterial leg ulcers , compared with hydrogel ; however , larval therapy did not significantly increase the rate of healing of the ulcers . It was impossible to distinguish between larval therapy and hydrogel in terms of cost-effectiveness . Future research should investigate the association of debridement and healing and the value of debridement as a clinical outcome for patients and clinicians . To inform decision-makers ' selection of debriding agents where debridement is the treatment goal , decision analytic modelling of all alternative debridement treatments is required . TRIAL REGISTRATION Current Controlled Trials IS RCT N55114812 OBJECTIVE To examine the effectiveness and cost-effectiveness of antimicrobial silver-donating dressings for venous leg ulcers compared with simple non-adherent ( also known as low-adherent ) dressings . DESIGN A pragmatic , prospect i ve r and omised controlled trial ( RCT ) and cost-effectiveness analysis of silver-donating versus low-adherent dressings in the treatment of venous leg ulcers . A non-r and omised observational group was also recruited . SETTING Primary and secondary care services in the north and south of Engl and ( Sheffield and Exeter ) . PARTICIPANTS Consenting patients with active ulceration of the lower leg that had been present for a period of greater than 6 weeks . INTERVENTIONS Patients were r and omised to receive either a silver-donating or non-silver low-adherent dressing applied beneath compression b and ages or hosiery . The choice of dressing within these groups was left to clinician preference . Evaluation was by clinical assessment , supplemented by evaluation of quality of life and cost-effectiveness . MAIN OUTCOME MEASURES The primary outcome measure was complete ulcer healing at 12 weeks in the index limb . Secondary measures were costs and quality -adjusted life-years ( QALYs ) , cost-effectiveness , time to healing , and recurrence rate at 6 months and 1 year . RESULTS In total , 304 participants were recruited to the clinical trial : 213 to the RCT and 91 to the observational arm . Within the RCT 107 were r and omised to antimicrobial dressings and 106 to the control dressings . There were no significant differences ( p > 0.05 ) between the two groups for the primary outcome measure of proportion of ulcers healed at 12 weeks ( 59.6 % for silver and 56.7 % for control dressings ) . The overall median time to healing was also not significantly different between the two groups ( p = 0.408 ) . A total of 24 patients had recurrent ulcers within 1 year ; the recurrence rates of 11.6 % ( n = 11 ) for the antimicrobial and 14.4 % ( n = 13 ) for the control dressings were not significant . Mean utility valuations for both the EuroQol 5 dimensions ( EQ-5D ) quality of life question naire and Short Form 6 dimensions ( SF-6D ) utility index showed no differences for either group at 1 , 3 , 6 or 12 months . Compared with the control group , the antimicrobial group had an incremental cost of 97.85 pounds and an incremental QALY gain of 0.0002 , giving an incremental cost-effectiveness ratio for the antimicrobial dressings of 489,250 pounds . Cost-effectiveness modelling of the results of the RCT showed that antimicrobial dressings were not cost-effective . CONCLUSIONS No significant differences in either primary or secondary end points were found between the use of antimicrobial silver-donating dressings and the control group of low-adherent dressings . Modelling showed that antimicrobial silver dressings were not cost-effective . TRIAL REGISTRATION Current Controlled Trials IS RCT N72485131 OBJECTIVE This study aim ed to estimate the cost-effectiveness of treating non-superficial diabetic foot ulcers with Promogran plus good wound care ( GWC ) compared with GWC alone in four European countries ( France , Germany , Switzerl and and UK ) . METHODS An existing Markov-based health economic model of non-superficial diabetic foot ulcers was adapted to incorporate the relative efficacy of Promogran compared with GWC alone as demonstrated in a r and omised controlled trial . Treatment with Promogran was modelled for a maximum of three months . Country-specific treatment costs were used to estimate the incremental cost per ulcer-free day gained over 12 months . Some parameter assumptions were changed to assess the sensitivity of the results . RESULTS Within the first three months of treatment , 26 % of ulcers in the Promogran cohort healed compared with 20.7 % in the GWC cohort . Over the 12 months , the average number of months spent in the healed state was 3.41 ( GWC ) and 3.75 ( Promogran ) . Promogran treatment was found to be cost-saving in all four countries , using year 2000 Euro values . CONCLUSION Promogran with GWC may be cost-effective , perhaps even cost-saving , under a wide variety of assumptions for the treatment of neuropathic foot ulcers . DECLARATION OF INTEREST This study was funded by Ethicon Gmbh ( Johnson and Johnson ) , Germany An open comparative r and omised study comparing the performance of hydrocolloid dressings ( DuoDERM CGF ) to saline gauze dressings in the treatment of pressure ulcers was done to evaluate the overall dressing performance , wound healing and cost effectiveness . Thirty-four subjects were enrolled at the University Hospital , Kuala Lumpur over a 643 days period . Inclusion criteria were Stage II or III pressure ulcers , at least 18 years of age and written informed consent . Only one pressure ulcer per subject was enrolled in the study . Patients with infected pressure ulcers , diabetes mellitus , an immuno-compromised status and known sensitivity to the study dressings were excluded . Subjects who met the enrollment criteria were r and omised to one of the two dressing regimes . They were expected to participate in the study for a maximum of eight weeks or until the pressure ulcer healed , which ever occurred first . Overall subject age averaged 58 years and the mean duration of pressure ulcer existence was about 1 month . Twenty-one of the thirty-four ulcers enrolled were stage II and thirteen were stage III . The majority of the ulcers ( 88 % ) were located in the sacral area and seventeen subjects ( 50 % ) were incontinent . In the evaluation of dressing performance in terms of adherence to wound bed , exu date h and ling ability , overall comfort and pain during dressing removal ; all favoured the hydrocolloid dressing by a statistically significant margin ( p < 0.001 ) . Subjects assigned the hydrocolloid dressing experienced a mean 34 % reduction from their baseline surface area measurement compared to a mean 9 % increase by subjects assigned gauze dressings . This was not statistically significant ( p = 0.2318 ) . In cost evaluation of the study products , there was no statistical significance in the total cost of wound management per subject . When only labour time and cost was evaluated , there was a statistically significant advantage towards hydrocolloid dressings OBJECTIVE To evaluate the effectiveness and cost-effectiveness of new incentive system for pressure ulcer management , which focused on skilled nurse staffing in terms of rate of healing and medical costs . DESIGN , SETTING AND PARTICIPANTS A prospect i ve cohort study included two types of groups : 39 institutions , which introduced the new incentive system , and 20 non-introduced groups ( control ) . Sixty-seven patients suffering from severe pressure ulcers in the introduced group and 38 patients in the non-introduced group were included . Wound healing and medical costs were monitored weekly for three weeks by their skilled nurses in charge . MAIN OUTCOME MEASURES Healing status and related medical costs . RESULTS The introduced group showed significantly higher rate of healing compared with the control group at each weekly assessment . Multiple regression analysis revealed that the introduction of the new incentive system was independently associated with the faster healing rate ( beta=3.44 , P<.001 ) . The budget impact analysis demonstrated that introducing this system could reduce cost of treating severe pressure ulcers by 1.776 billion yen per year . CONCLUSIONS The new incentive system for the management of pressure ulcers , which focused on staffing with skilled nurses can improve healing rate with reduced medical cost In many centers the st and ard treatment for venous stasis ulcers consists of UB dressings . A new dressing , DuoDERM hydroactive dressing ( HD ) , has recently been used extensively for the treatment of venous stasis ulcers . Because of this trend , a prospect i ve , r and omized trial of these two dressings was undertaken . Sixty-nine ulcers ( 39 HD and 30 UB ) were r and omized . End points were complete healing and development of complications necessitating cessation of treatment . Time to healing , cost of treatment , and patient convenience were also evaluated . Twenty-one of 30 ulcers ( 70 % ) healed with UB therapy compared with 15 of 39 ulcers ( 38 % ) treated with HD ( p less than 0.01 , CST ) . Life-table healing rates at 15 weeks were 64 % for UB compared with 35 % for HD ( p = 0.01 , log rank test ) . Ten of 39 patients ( 26 % ) receiving HD had complications compared with no complications in the UB group ( p = 0.004 , FET ) . For those patients whose ulcers healed , there was no significant difference ( p = 0.51 , STT ) in the mean time required for healing or the average weekly cost of dressing material s between the HD group ( 7.0 weeks at + 11.50 per week ) and the UB group ( 8.4 weeks at + 12.60 per week ) . Those patients treated with HD reported a significantly greater level of convenience than those patients with UB ( p = 0.004 , STT ) . Although treatment with HD led to better patient acceptance , those patients receiving UB therapy had a significantly greater rate of healing and a significantly lesser incidence of complications than those patients treated with HD The cost effectiveness of using hydrocolloid dressings versus nonsterile saline-gauze wet-to-moist dressings for treatment of pressure ulcers in a long-term care setting was evaluated . During 21 months , 39 subjects were enrolled , and treatment was r and omly assigned . Eighty-nine percent of the hydrocolloid subjects and 86 % of the saline-gauze subjects healed . Median healing time was shorter for the hydrocolloid group ( nine days ) than for the saline-gauze group ( 11 days ) , although the difference did not reach statistical significance ( p = .12 ) . Presence of exu date at baseline was associated with a prolonged time to healing . For the hydrocolloid treatment , the median nursing time was one eighth that of the saline-gauze treatment , but its material s cost was 3.3 times higher . Using local nursing wages , median total cost for treatment with hydrocolloid dressing was $ 15.58 ; for the saline gauze , it was $ 22.65 . Using national nursing wages , these costs were $ 15.90 and $ 25.31 , respectively . The cost savings of the hydrocolloid treatment using local wages did not reach statistical significance . However , using national wages , the cost of the hydrocolloid treatment was significantly less expensive . Nursing home treatment of pressure ulcers was inexpensive overall . Consequently , the absolute cost savings of using hydrocolloid dressings instead of nonsterile saline-gauze dressing , although real , was relatively modest . Physicians can use local nursing wages to calculate the magnitude of savings in their area Abstract Objective : To compare the outcome and cost of care for leg ulcers in community leg ulcer clinics in Stockport District Health Authority with Trafford District Health Authority as a control . Design : Detailed cost and efficacy studies conducted prospect ively over a three month period in both districts both before and one year after the introduction of five leg ulcer clinics in Stockport . Setting : Two large district health authorities of broad socioeconomic mix and total population of 540 000 . Patients : All patients receiving treatment for an active leg ulcer , irrespective of the profession or location of their carer . Main outcome measures : The proportion of ulcerated limbs completely healed within three months and total cost of leg ulcer care . Results : The introduction of community clinics in Stockport improved healing of leg ulcers from 66/252 ( 26 % ) in 1993 to 99/233 ( 42 % ) in 1994 ( P<0.001 ) compared with in Trafford , where 47/203 ( 23 % ) healed in 1993 and only 43/213 ( 20 % ) in 1994 . This improved result in Stockport was achieved while the annual expenditure on care of leg ulcers was reduced from £ 409 991 to only £ 253 371 . In the same year the cost of leg ulcer care in Trafford increased from £ 556 039 to £ 673 318 . Conclusion : In the first year after the introduction of community clinics , before most patients in Stockport had access to these clinics , healing of leg ulcers was already improved whereas costs were reduced . Key messages The introduction of community leg ulcer clinics improved care and result ed in lower costs than the traditional approach that the clinics replaced Planned and coordinated programmes of care can reduce costs substantially while improving healing rates Community units and general practitioners should be encouraged to seek alternatives to the st and ard care for leg OBJECTIVE To determine whether staged management of foot ulcers reduces health care costs and utilization . DESIGN Nonr and omized retrospective study using data from 1998 - 1999 in the Louisiana public hospital system . SETTING Louisiana public hospital system . PARTICIPANTS Forty-five patients with diabetes foot ulcer who received staged management foot care and 169 patients with diabetes foot ulcer who received st and ard foot care . INTERVENTIONS Staged management of foot ulcers consisting of devices to offload pressure ; self-care education ; and , after healing , custom-fabricated orthoses and footwear , and monitored progressive ambulation . MAIN OUTCOME MEASURES One-year levels of the number of foot-related inpatient hospitalizations , number of amputation-related hospitalizations , total number of foot-related inpatient days , total charges for foot-related inpatient hospitalizations , all-cause outpatient visits , total charges for all-cause outpatient visits , and combined outpatient and foot-related inpatient charges . RESULTS Over the 12-month study period , the staged management group had a lower foot-related hospitalization rate than did the comparison group ( .09 admissions per person vs.50 admissions per person , P=.0002 ) ; lower foot-related inpatient days ( .91d per person vs 3.97d per person , P=.0289 ) ; lower foot-related inpatient charges ( $ 1321 per person vs $ 5411 per person , P=.0151 ) ; fewer amputation-related hospitalizations ( .04 per person vs.19 per person , P=.0351 ) ; fewer emergency department visits ( .60 visits per person vs 1.22 visits per person , P=.0043 ) ; lower emergency department charges ( $ 104 per person vs $ 208 per person , P=.0057 ) ; and lower total charges ( $ 4776 per person vs $ 9402 per person , P=.0141 ) . The staged management group had a higher number of outpatient visits ( 24.91 per person vs 8.04 per person , P<.0001 ) and higher outpatient charges ( $ 2169 per person vs $ 1471 per person , P<.0001 ) . CONCLUSIONS A staged management diabetes foot program significantly reduced emergency department and hospital utilization and charges in a statewide public hospital system The purpose of our study was the evaluation of the therapeutic benefit and the economical profit of low-frequency pulsed current applied to therapy-resistant venous leg ulcers . We investigated 39 patients in a prospect i ve , placebo-controlled , double blind study on the effect of low-frequency pulsed current ( Dermapulse ) on healing in chronic venous ulcers during a 4-month course of treatment . All patients had chronic venous ulcers . The following criteria were recorded : ulcer size , pain , capillary density , and transcutaneous oxygen partial pressure . In verum group 3 , ulcers healed and ulcer area was reduced significantly . In placebo group two ulcers healed . Ulcer size was reduced significantly in each group ( paired test ) , the difference of ulcer area reduction between the " verum " and the placebo group ( unpaired test ) was not significant . Capillary density in the ulcer increased in both groups . In verum group , electrical stimulation led to rapid and lasting reduction of pain ( unpaired test , p=0.049 ) . By means of the process calculation method for the subgroup of out patients this treatment method was economically effective . Electrical stimulation seems to be a viable treatment option for therapy-resistant venous leg ulcers |
1,754 | 24,817,609 | The review identified aerobic-based tests of performance benefit from STHA training .
Peak anaerobic power efforts have not been demonstrated to improve .
Conclusions The review identified that aerobic-based tests of performance benefit from STHA training .
This is possibly through a number of cardiovascular , thermoregulatory , and metabolic adaptations improving the perception of effort and fatigue through a reduction in anaerobic energy release and elevation of the anaerobic threshold .
STHA training can be applied in the team-sport environment during a range of instances within the competitive season .
A mixed high-intensity protocol may only require five sessions with a duration of 60 min to potentially improve aerobic-based performance in trained athletes | Background Studies have demonstrated that longer-term heat acclimation training ( ≥8 heat exposures ) improves physical performance .
The physiological adaptations gained through short-term heat acclimation ( STHA ) training suggest that physical performance can be enhanced within a brief timeframe .
Objective The aim of this systematic review was to determine if STHA training ( ≤7 heat exposures ) can improve physical performance in healthy adults . | Abstract A key element of the physical preparation of athletes is the taper period in the weeks immediately preceding competition . Existing research has defined the taper , identified various forms used in contemporary sport , and examined the prescription of training volume , load , intensity , duration , and type ( progressive or step ) . Current limitations include : the lack of studies on team , combative , racquet , and precision ( target ) sports ; the relatively small number of r and omized controlled trials ; the narrow focus on a single competition ( single peak ) compared with multiple peaking for weekly , multi-day or multiple events ; and limited underst and ing of the physiological , neuromuscular , and biomechanical basis of the taper . Future research should address these limitations , together with the influence of prior training on optimal tapering strategies , and the interactions between the taper and long-haul travel , heat , and altitude . Practitioners seek information on how to prescribe tapers from season to season during an athlete 's career , or a team 's progression through a domestic league season , or multi-year Olympic or World Cup cycle . Practical guidelines for planning effective tapers for the Vancouver 2010 and London 2012 Olympics will evolve from both experimental investigations and modelling of successful tapers currently employed in a wide range of sports OBJECTIVES To investigate the physical dem and s of professional rugby league match-play using microtechnology , and to compare these dem and s with typical training activities used to prepare players for competition . DESIGN Prospect i ve cohort study . METHODS Thirty elite rugby league players participated in this study . Seven hundred and eighty-six . training data sets and 104 data sets from National Rugby League matches were collected over one playing season . Movement was recorded using a commercially available microtechnology unit ( minimaxX , Catapult Innovations ) , which provided information on speeds , distances , accelerations , physical collisions and repeated high-intensity efforts . RESULTS Mean distances covered during match-play by the hit-up forwards , wide-running forwards , adjustables , and outside backs were 3,569 m , 5,561 m , 6,411 m , and 6,819 m , respectively . Hit-up forwards and wide-running forwards were engaged in a greater number of moderate and heavy collisions than the adjustables and outside backs , and more repeated high-intensity effort bouts per minute of play ( 1 bout every 4.8 - 6.3 min ) . The physical dem and s of traditional conditioning , repeated high-intensity effort exercise , and skill training activities were all lower than the physical dem and s of competition . CONCLUSIONS These results demonstrate that absolute distances covered during professional rugby league matches are greater for outside backs , while the collision and repeated high-intensity effort dem and s are higher for hit-up forwards and wide-running forwards . The specific physical dem and s of competitive play , especially those dem and s associated with collisions and repeated high-intensity efforts , were not well matched by those observed in traditional conditioning , repeated high-intensity effort exercise , and skills training activities . Further research is required to investigate whether modifications need to be made to these training activities to better prepare players for the dem and s of National Rugby League competition Background —A classic , unresolved physiological question is whether central cardiorespiratory and /or local skeletal muscle circulatory factors limit maximal aerobic capacity ( & OV0312;o2max ) in humans . Severe heat stress drastically reduces & OV0312;o2max , but the mechanisms have never been studied . Methods and Results —To determine the main contributing factor that limits & OV0312;o2max with and without heat stress , we measured hemodynamics in 8 healthy males performing intense upright cycling exercise until exhaustion starting with either high or normal skin and core temperatures ( + 10 ° C and + 1 ° C ) . Heat stress reduced & OV0312;o2max , 2-legged & OV0312;o2 , and time to fatigue by 0.4±0.1 L/min ( 8 % ) , 0.5±0.2 L/min ( 11 % ) , and 2.2±0.4 minutes ( 28 % ) , respectively ( all P < 0.05 ) , despite heart rate and core temperature reaching similar peak values . However , before exhaustion in both heat stress and normal conditions , cardiac output , leg blood flow , mean arterial pressure , and systemic and leg O2 delivery declined significantly ( all 5 % to 11 % , P < 0.05 ) , yet arterial O2 content and leg vascular conductance remained unchanged . Despite increasing leg O2 extraction , leg & OV0312;o2 declined 5 % to 6 % before exhaustion in both heat stress and normal conditions , accompanied by enhanced muscle lactate accumulation and ATP and creatine phosphate hydrolysis . Conclusions —These results demonstrate that in trained humans , severe heat stress reduces & OV0312;o2max by accelerating the declines in cardiac output and mean arterial pressure that lead to decrements in exercising muscle blood flow , O2 delivery , and O2 uptake . Furthermore , the impaired systemic and skeletal muscle aerobic capacity that precedes fatigue with or without heat stress is largely related to the failure of the heart to maintain cardiac output and O2 delivery to locomotive muscle In order to compare the effectiveness of a daily to an intermittent acclimation protocol , 14 competitive rowers ( mean + /- SD VO2peak = 48 + /- 7 ml x kg x min(-1 ) ) were r and omly assigned to either a consecutive ( 10 consecutive days ) or intermittent acclimation group ( 10 sessions over 3 weeks ) . For every heat exposure , subjects in each group exercised for 30 min at 70 % VO2peak in an environmental chamber set at 38 degrees C and 70 % relative humidity . Acclimation state was monitored by measuring heart rate ( HR ) , rectal and skin temperature ( Tre and Tsk ) , ratings of perceived exertion ( RPE ) and whole body sweat rate ( SR ) during each heat exposure . Final exercise Tre decreased significantly by 0.6 + /- 0.7 degrees C with intermittent heat exposure but the decrease was significantly larger ( p < 0.05 ) with consecutive day heat exposure ( 1.0 + /- 0.1 degrees C ) . Final exercise HR also decreased significantly by 13 + /- 12 bpm ( p < 0.05 ) in the consecutive group , and non-significantly by 5 + /- 13 bpm in the intermittent group . RPE decreased with daily ( 5 + /- 1 , p < 0.05 ) but did not significantly decrease with intermittent heat exposure ( 1 + /- 3 ) . Similarly , Tsk significantly decreased with consecutive ( 0.4 + /- 0.2 degrees C , p < 0.05 ) but not intermittent exposure ( 0.2 + /- 0.3 degrees C ) and SR did not change in either group . Minimal adaptation occurs with intermittent heat exposure and it appears that daily heat exposure is the most effective acclimation strategy We tested the hypothesis that local sweat rates would not display a systematic postadaptation redistribution toward the limbs after humid heat acclimation . Eleven nonadapted males were acclimated over 3 wk ( 16 exposures ) , cycling 90 min/day , 6 days/wk ( 40 degrees C , 60 % relative humidity ) , using the controlled-hyperthermia acclimation technique , in which work rate was modified to achieve and maintain a target core temperature ( 38.5 degrees C ) . Local sudomotor adaptation ( forehead , chest , scapula , forearm , thigh ) and onset thresholds were studied during constant work intensity heat stress tests ( 39.8 degrees C , 59.2 % relative humidity ) conducted on days 1 , 8 , and 22 of acclimation . The mean body temperature ( Tb ) at which sweating commenced ( threshold ) was reduced on days 8 and 22 ( P < 0.05 ) , and these displacements paralleled the resting thermoneutral Tb shift , such that the Tb change to elicit sweating remained constant from days 1 to 22 . Whole body sweat rate increased significantly from 0.87 + /- 0.06 l/h on day 1 to 1.09 + /- 0.08 and 1.16 + /- 0.11 l/h on days 8 and 22 , respectively . However , not all skin regions exhibited equivalent relative sweat rate elevations from day 1 to day 22 . The relative increase in forearm sweat rate ( 117 + /- 31 % ) exceeded that at the forehead ( 47 + /- 18 % ; P < 0.05 ) and thigh ( 42 + /- 16 % ; P < 0.05 ) , while the chest sweat rate elevation ( 106 + /- 29 % ) also exceeded the thigh ( P < 0.05 ) . Two unique postacclimation observations arose from this project . First , reduced sweat thresholds appeared to be primarily related to a lower resting Tb , and more dependent on Tb change . Second , our data did not support the hypothesis of a generalized and preferential trunk-to-limb sweat redistribution after heat acclimation This study determined the influence of exercise intensity , protective clothing level , and climate on physiological tolerance to uncompensable heat stress . It also compared the relationship between core temperature and the incidence of exhaustion from heat strain for persons wearing protective clothing to previously published data of unclothed persons during uncompensable heat stress . Seven heat-acclimated men attempted 180-min treadmill walks at metabolic rates of approximately 425 and 600 W while wearing full ( clo = 1.5 ) or partial ( clo = 1.3 ) protective clothing in both a desert ( 43 degrees C dry bulb , 20 % relative humidity , wind 2.2 m/s ) and tropical ( 35 degrees C dry bulb , 50 % relative humidity , wind 2.2 m/s ) climate . During these trials , the evaporative cooling required to maintain thermal balance exceeded the maximal evaporative capacity of the environment and core temperature continued to rise until exhaustion from heat strain occurred . Our findings concerning exhaustion from heat strain are 1 ) full encapsulation in protective clothing reduces physiological tolerance as core temperature at exhaustion was lower ( P < 0.05 ) in fully than in partially clothed persons , 2 ) partial encapsulation results in physiological tolerance similar to that reported for unclothed persons , 3 ) raising metabolic rate from 400 to 600 W does not alter physiological tolerance when subjects are fully clothed , and 4 ) physiological tolerance is similar when subjects are wearing protective clothing in desert and tropical climates having the same wet bulb globe thermometer . These findings can improve occupational safety guidelines for human heat exposure , as they provide further evidence that the incidence of exhaustion from heat strain can be predicted from core temperature UNLABELLED Cricketers are often required to play in hot/humid environments with little time for heat adaptation . PURPOSE We examined the effect of a short 4-d hot/humid acclimation program on classical physiological indicators of heat acclimation . METHODS Male club cricketers were r and omly assigned into heat acclimation ( ACC , n = 6 ) or control ( CON , n = 6 ) groups , and 30 min treadmill trials ( 10 km/h , approx . 30 ± 1.0 ° C , approx . 65 ± 6 % RH ) were conducted at baseline and postacclimation . The ACC group completed four high intensity ( 30 - 45 min ) acclimation sessions on consecutive days at approx . 30 ° C and approx . 60 % RH using a cycle ergometer . The CON group completed matched cycle training in moderate conditions ( approx . 20 ° C , approx . 60 % RH ) . Physiological measures during each treadmill trial included heart rate ; core and skin temperatures ; sweat Na+ , K+ and Cl- electrolyte concentrations ; and sweat rate . RESULTS After the 4-d intervention , the ACC group had a moderate decrease of -11 ( 3 to -24 beats/min ; mean and 90 % CI ) in the 30 min heart rate , and moderate to large reductions in electrolyte concentrations : Na+ -18 % ( -4 to -31 % ) , K+ -15 % ( 0 to -27 % ) , Cl- -22 % ( -9 to -33 % ) . Both ACC and CON groups had only trivial changes in core and skin temperatures and sweat rate . After the intervention , both groups perceived they were more comfortable exercising in the heat . The 4-d heat intervention had no detrimental effect on performance . CONCLUSIONS Four 30 - 45 min high intensity cycle sessions in hot/humid conditions elicited partial heat acclimation . For full heat acclimation a more intensive and extensive ( and modality-specific ) acclimation intervention is needed for cricket players Abstract The aim of this study was to determine the effect of 10 days of heat acclimation with and without pre-cooling on intermittent sprint exercise performance in the heat . Eight males completed three intermittent cycling sprint protocol s before and after 10 days of heat acclimation . Before acclimation , one sprint protocol was conducted in control conditions ( 21.8 ± 2.2 ° C , 42.8 ± 6.7 % relative humidity ) and two sprint protocol s in hot , humid conditions ( 33.3 ± 0.6 ° C , 52.2 ± 6.8 % relative humidity ) in a r and omized order . One hot , humid condition was preceded by 20 min of thigh pre-cooling with ice packs ( −16.2 ± 4.5 ° C ) . After heat acclimation , the two hot , humid sprint protocol s were repeated . Before heat acclimation , peak power output declined in the heat ( P < 0.05 ) but pre-cooling prevented this . Ten days of heat acclimation reduced resting rectal temperature from 37.8 ± 0.3 ° C to 37.4 ± 0.3 ° C ( P < 0.01 ) . When acclimated , peak power output increased by ∼2 % ( P < 0.05 , main effect ) and no reductions in individual sprint peak power output were observed . Additional pre-cooling offered no further ergogenic effect . Unacclimated athletes competing in the heat should pre-cool to prevent reductions in peak power output , but heat acclimate for an increased peak power output The aim of this study was to examine the effect of intermittent high-intensity shuttle running and fluid ingestion on the performance of a soccer skill . Nine semi-professional soccer players volunteered to participate in the study . Their mean ( + /- s(x ) ) age , body mass and maximal oxygen uptake were 20.2+/-0.4 years , 73.2+/-1.8 kg and 59.1+/-1.3 ml x kg(-1 ) min(-1 ) respectively . The players were allocated to two r and omly assigned trials : ingesting or abstaining from fluid intake during a 90 min intermittent exercise protocol ( Loughborough Intermittent Shuttle Test : LIST ) . This test was design ed to simulate the minimum physical dem and s faced by soccer players during a game . Before and immediately after performance of the test , the players completed a soccer skill test and a mental concentration test . Performance of the soccer skill test after the ' no-fluid ' trial deteriorated by 5 % ( P<0.05 ) , but was maintained during the fluid trial . Mean heart rate , perceived exertion , serum aldosterone , osmolality , sodium and cortisol responses during the test were higher ( P<0.05 ) in the ' no-fluid ' trial than in the fluid trial . The results of this study suggest that soccer players should consume fluid throughout a game to help prevent a deterioration in skill performance Background To examine whether short-term , ie , five daily sessions , vigorous dynamic cycling exercise and heat exposure could achieve heat acclimation in trained athletes and the effect of heat acclimation on cutaneous blood flow in the active and nonactive limb . Methods Fourteen male badminton and table tennis athletes ( age = 19.6 ± 1.2 years ) were r and omized into a heat acclimation ( EXP , n = 7 ) or nonheat acclimation ( CON , n = 7 ) group . For 5 consecutive days , the EXP group was trained using an upright leg cycle ergometer in a hot environment ( 38.4 ° C ± 0.4 ° C ) , while the CON group trained in a thermoneutral environment ( 24.1 ° C ± 0.3 ° C ) . For both groups , the training intensity and duration increased from a work rate of 10 % below ventilatory threshold ( VT ) and 25 minutes per session on day 1 , to 10 % above VT and 45 minutes per session on day 5 . Subjects performed two incremental leg cycle exercise tests to exhaustion at baseline and post-training in both hot and thermoneutral conditions . Study outcome measurements include : maximum oxygen uptake ( VO2max ) ; exercise heart rate ( HR ) ; O2 pulse ; exercise time to exhaustion ( tmax ) ; skin blood flow in the upper arm ( SkBFa ) and quadriceps ( SkBFq ) ; and mean skin ( Tsk ) . Results The significant heat-acclimated outcome measurements obtained during high-intensity leg cycling exercise in the high ambient environment are : ( 1 ) 56%–100 % reduction in cutaneous blood flow to the active limbs during leg cycling exercise ; ( 2 ) 28 % drop in cutaneous blood flow in nonactive limbs at peak work rate ; ( 3 ) 5%–10 % reduction in heart rate ( HR ) ; ( 4 ) 10 % increase in maximal O2 pulse ; and ( 5 ) 6.6 % increase in tmax . Conclusion Heat acclimation can be achieved with five sessions of high-intensity cycling exercise in the heat in trained athletes , and redistribution of cutaneous blood flow in the skin and exercising muscle , and enhanced cardiovascular adaptations provide the heat-acclimated athletes with the capability to increase their endurance time in the hot environment Objective : To determine whether moderate water loss ( ∼1.5–2 % of body mass ( BM ) ) represents a significant impairment to soccer match-play and the related fitness variables . Methods : 11 moderately active male soccer players ( mean ( SD ) age 24.4 ( 3 ) years , BM 74.03 ( 10.5 ) kg , peak oxygen consumption 50.91 ( 4.0 ) ml/kg/min ) volunteered to participate . The experimental procedure comprised : ( 1 ) a 45 min pre-match period of cycle ergometry exercise ( 90 % of individual ventilatory threshold ) ; ( 2 ) the completion of a 45 min soccer match ; and ( 3 ) the immediate post-match performance of sport-specific and mental concentration tests . The subjects completed the procedure on three occasions each in a different experimental condition ( fluid intake ( FL ) , no fluid ( NF ) and mouth rinse ( MR ) ) in an individually r and omised order . Core temperature ( Tc ) , heart rates , plasma and urine osmolalities , BM , sweat rates and heat storage were all measured . Results : The only condition-dependent difference during the match-play element of the protocol was a significantly increased Tc in the NF condition compared with the FL condition ( 39.28 ° C ( 0.35 ° C ) and 38.8 ° C ( 0.47 ° C ) , respectively ; p<0.05 ) . The immediate post-match performance of a sport-specific fitness test was significantly impaired where FL had been denied ( p<0.01 ) . The post-test evaluation of rating of perceived exertion and thirst indicated that the NF condition was perceived to be the most challenging ( p<0.05 ) . Conclusions : The condition-dependent differences in match-play and post-match tests demonstrate that moderate dehydration is detrimental to soccer performance . However , it remains unclear whether this could be attributable to water loss in itself or the negative psychological associations derived from a greater perception of effort in that condition Two experiments examined the influences of endurance training and heat acclimation on ratings of perceived exertion ( RPE ) and thermal discomfort ( RTD ) during exercise in the heat while wearing two types of clothing . In experiment 1 , young men underwent 8 weeks of physical training [ 60 - 80 % of maximal aerobic power ( VO2max ) for 30 - 45 min day-1 , 3 - 4 days week-1 at 20 - 22 degrees C dry bulb ( db ) temperature ] followed by 6 days of heat acclimation [ 45 - 55 % VO2max for 60 min day-1 at 40 degrees C db , 30 % relative humidity ( rh ) ] ( n = 7 ) or corresponding periods of control observation followed by heat acclimation ( n = 9 ) . In experiment 2 , young men were heat-acclimated for 6 or 12 days ( n = 8 each ) . Before and after each treatment , subjects completed bouts of treadmill exercise ( 1.34 m s-1 , 2 % grade in experiment 1 and 0 % grade in experiment 2 ) in a climatic chamber ( 40 degrees C db , 30 % rh ) , wearing in turn normal light clothing ( continuous exercise at 37 - 45 % VO2max for a tolerated exposure of 116 - 120 min in experiment 1 and at 31 - 34 % VO2max for 146 - 150 min in experiment 2 ) or clothing protective against nuclear , biological , and chemical agents ( continuous exercise at 42 - 51 % VO2max for a tolerated exposure of 47 - 52 min in experiment 1 and intermittent exercise at 23 % VO2max for 97 - 120 min in experiment 2 ) . In experiment 1 , when wearing normal clothing , endurance training and /or heat acclimation significantly decreased RPE and /or RTD at a fixed power output . There were concomitant reductions in relative work intensity ( % VO2max ) [ an unchanged oxygen consumption ( VO2 ) but an increased VO2max , or a reduced VO2 with no change of VO2max ] , rectal temperature ( Tre ) , mean skin temperature ( Tsk ) , and /or heart rate ( HR ) . When wearing protective clothing , in contrast , there were no significant changes in RPE or RTD . Although training and /or acclimation reduced % VO2max or Tre , any added sweat that was secreted did not evaporate through the protective clothing , thus increasing discomfort after training or acclimation . Tolerance times were unchanged in either normal or protective clothing . In experiment 2 , when wearing normal clothing , heat acclimation significantly decreased RPE and RTD at a fixed power output , with concomitant reductions in Tre , Tsk , and HR ; the response was greater after 12 than after 6 days of acclimation , significantly so for RPE and HR . When wearing protective clothing , the subjects exercised at a lower intensity for a longer duration than in the moderate exercise trial . Given this tactic , either 6 or 12 days of heat acclimation induces significant reductions RPE and /or RTD , accompanied by reductions in Tre , Tsk , and /or HR . Tolerance times in protective clothing were also increased by 11 - 15 % after acclimation , despite some increase of sweat accumulation in the protective clothing . The results suggest that ( 1 ) neither endurance training nor heat acclimation reduce psychological strain when protective clothing is worn during vigorous exercise , because increased sweat accumulation adds to discomfort , and ( 2 ) in contrast to the experience during more vigorous exercise , heat acclimation is beneficial to the subject wearing protective clothing if the intensity of effort is kept to a level that allows permeation of sweat through the clothing . This condition is likely to be met in most modern industrial applications PURPOSE To investigate the effect of ingesting a carbohydrate-electrolyte solution ( CHO-E ) , in subjects with reduced carbohydrate stores , during an intermittent shuttle running test ( LIST ) on soccer passing ( LSPT ) and shooting ( LSST ) performance . METHODS Sixteen healthy male university soccer players ingested either a 6.4 % CHO-E or placebo ( PLA ) solution during 90 min of the LIST ( 5 mL x kg(-1 ) BM before and 2 mL x kg(-1 ) BM every 15 min of exercise ) , in a double-blind , r and omized , crossover design , with each trial separated by at least 7 d. On the evening before the main trial ( 17:00 h ) , subjects performed the glycogen-reducing cycling exercise ( approximately 80 min at 70 % VO2max ) . They were then fed a low-carbohydrate evening meal and reported to the laboratory the following morning after a 10-h fast . Blood was collected at rest and after every 30 min of exercise ; skill tests were performed before and after the LIST . RESULTS The change in mean LSST performance from pre- to post-LIST was better in the CHO-E trial ( 11 + /- 45 vs -16 + /- 42 % ; P < 0.01 ) but not significantly different for the LSPT performance ( -1 + /- 10 % ( CHO-E ) vs -6 + /- 13 % ( PLA ) , P = 0.13 ) . Sprint performance during the LIST was quicker in the CHO-E trial ( 2.50 + /- 0.13 vs 2.53 + /- 0.13 s , P < 0.01 ) . Plasma glucose was higher in the CHO-E trial after 90 min of exercise ( 5.2 + /- 0.3 vs 3.9 + /- 0.4 mM , P < 0.01 ) . CONCLUSIONS Ingestion of a carbohydrate-electrolyte solution during exercise enabled subjects with compromised glycogen stores to better maintain skill and sprint performance than when ingesting fluid alone Plasma volume ( PV ) expansion by endurance training and /or heat acclimatization is known to increase aerobic and thermoregulatory capacities in humans . Also , higher erythrocyte volume ( EV ) fractions in blood are known to improve these capacities . We tested the hypothesis that training in a hypobaric hypoxic and warm environment would increase peak aerobic power ( VO(2)(peak ) ) and forearm skin vascular conductance ( FVC ) response to increased esophageal temperature ( T(es ) ) more than training in either environment alone , by increasing both PV and EV . Twenty men were divided into four training regimens ( n = 5 each ) : low-altitude cool ( 610-m altitude , 20 degrees C ambient temperature , 50 % relative humidity ) , high-altitude cool ( 2,000 m , 20 degrees C ) , low-altitude warm ( 610 m , 30 degrees C ) , and high-altitude warm ( HW ; 2,000 m , 30 degrees C ) . They exercised on a cycle ergometer at 60 % VO(2)(peak ) for 1 h/day for 10 days in a climate chamber . After training , PV increased in all trials , but EV increased in only high-altitude trials ( both P < 0.05 ) . VO(2)(peak ) increased in all trials ( P < 0.05 ) but without any significant differences among trials . FVC response to increased T(es ) was measured during exercise at 60 % of the pretraining VO(2)(peak ) at 610 m and 30 degrees C. After the training , T(es ) threshold for increasing FVC decreased in warm trials ( P < 0.05 ) but not in cool trials and was significantly lower in HW than in cool trials ( P < 0.05 ) . The slope of FVC increase/T(es ) increase increased in all trials ( P < 0.05 ) except for high-altitude cool ( P > 0.4 ) and was significantly higher in HW than in cool trials ( P < 0.05 ) . Thus , against our hypothesis , the VO(2)(peak ) for HW did not increase more than in other trials . Moreover , slope of FVC increase/T(es ) increase in HW increased most , despite the similar increase in blood volume , suggesting that factors other than blood volume were involved in the highest FVC response in HW This study investigated the influence of 6 versus 12 days of heat acclimation on the tolerance of low-intensity exercise in the heat while wearing protective clothing . Sixteen young men were acclimated by treadmill walking ( 50 % of each subject 's maximal aerobic power for 60 min -day- ' ) in a climatic chamber [ 40 ° C dry bulb ( db ) , 30 % relative humidity ] for either 6 consecutive days or two 6-day periods , separated by a 1-day rest . Before and after heat acclimation , the subjects performed a heat-exercise test ( 1.34m·s−1 , 0 % grade ; 40 ° C db , 30 % relative humidity ) , either under control conditions [ wearing normal light combat clothing ( continuous exercise;n = 5 ) ] or when wearing protective clothing resistant against nuclear , biological , and chemical ( NBC ) agents ( repeated bouts of 15-min walk + 15-min rest;n = 8) . Criteria for halting the test exercise were a rectal temperature ( Tre ) of 39.3 ° C , a heart rate ( fc ) ≥ 95 % of the subject 's observed maximum , unwillingness of the subject to continue , or the elapse of 150 min . Heat acclimation decreased overall test values ofTre , fc , and mean skin temperature for both control and protective clothing conditions . When wearing normal combat clothing , acclimation responses were about twice as large after 12 than after 6 days , but the response was not increased by longer acclimation when wearing NBC protective clothing . Both 6 and 12 days of acclimation increased tolerance times in NBC protective clothing by about 15 min [ from 97 ( 4 ) to 112 ( 6 ) min and from 108 ( 10 ) to 120 ( 10 ) min for 6 and 12 days , respectively ] . We conclude that the physiological strain and limitation of heat-exercise tolerance imposed by wearing NBC protective clothing are not reduced if heat acclimation is prolonged from 6 to 12 days |
1,755 | 27,591,466 | Intraoperative goal directed hemodynamic therapy with minimally invasive monitoring decreases postoperative complications in noncardiac surgery , although it was not able to show a significant decrease in mortality rate | BACKGROUND The goal directed hemodynamic therapy is an approach focused on the use of cardiac output and related parameters as end-points for fluids and drugs to optimize tissue perfusion and oxygen delivery .
Primary aim : To determine the effects of intraoperative goal directed hemodynamic therapy on postoperative complications rates . | BACKGROUND Some observational studies suggest that the use of pulmonary-artery catheters to guide therapy is associated with increased mortality . METHODS We performed a r and omized trial comparing goal -directed therapy guided by a pulmonary-artery catheter with st and ard care without the use of a pulmonary-artery catheter . The subjects were high-risk patients 60 years of age or older , with American Society of Anesthesiologists ( ASA ) class III or IV risk , who were scheduled for urgent or elective major surgery , followed by a stay in an intensive care unit . Outcomes were adjudicated by observers who were unaware of the treatment-group assignments . The primary outcome was in-hospital mortality from any cause . RESULTS Of 3803 eligible patients , 1994 ( 52.4 percent ) underwent r and omization . The base-line characteristics of the two treatment groups were similar . A total of 77 of 997 patients who underwent surgery without the use of a pulmonary-artery catheter ( 7.7 percent ) died in the hospital , as compared with 78 of 997 patients in whom a pulmonary-artery catheter was used ( 7.8 percent)--a difference of 0.1 percentage point ( 95 percent confidence interval , -2.3 to 2.5 ) . There was a higher rate of pulmonary embolism in the catheter group than in the st and ard-care group ( 8 events vs. 0 events , P=0.004 ) . The survival rates at 6 months among patients in the st and ard-care and catheter groups were 88.1 and 87.4 percent , respectively ( difference , -0.7 percentage point [ 95 percent confidence interval , -3.6 to 2.2 ] ; negative survival differences favor st and ard care ) ; at 12 months , the rates were 83.9 and 83.0 percent , respectively ( difference , -0.9 percentage point [ 95 percent confidence interval , -4.3 to 2.4 ] ) . The median hospital stay was 10 days in each group . CONCLUSIONS We found no benefit to therapy directed by pulmonary-artery catheter over st and ard care in elderly , high-risk surgical patients requiring intensive care Introduction Several studies have shown that goal -directed hemodynamic and fluid optimization may result in improved outcome . However , the methods used were either invasive or had other limitations . The aim of this study was to perform intraoperative goal -directed therapy with a minimally invasive , easy to use device ( FloTrac/Vigileo ) , and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a st and ard management protocol . Methods In this r and omized , controlled trial 60 high-risk patients scheduled for major abdominal surgery were included . Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol ( FloTrac/Vigileo device , GDT-group , n = 30 ) or a st and ard management group ( Control-group , n = 30 ) , based on st and ard monitoring data . Results The median duration of hospital stay was significantly reduced in the GDT-group with 15 ( 12 - 17.75 ) days versus 19 ( 14 - 23.5 ) days ( P = 0.006 ) and fewer patients developed complications than in the Control-group [ 6 patients ( 20 % ) versus 15 patients ( 50 % ) , P = 0.03 ] . The total number of complications was reduced in the GDT-group ( 17 versus 49 complications , P = 0.001 ) . Conclusions In high-risk patients undergoing major abdominal surgery , implementation of an intraoperative goal -directed hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a st and ard management protocol .Trial Registration Clinical trial registration information : Unique identifier : BACKGROUND Patients with proximal femoral fracture ( PFF ) are at high risk of postoperative complications . Goal -directed haemodynamic treatment ( GDHT ) in other high-risk surgical patients reduces postoperative complications . We aim ed to compare effects of GDHT and routine fluid treatment ( RFT ) on postoperative outcomes after PFF surgery . METHODS PFF patients ( ≥70 yr ) were enrolled in this single-centre , open , r and omized , controlled , parallel-group superiority trial with concealed allocation using computer-generated r and omization . TREATMENTS ( i ) GDHT to attain oxygen delivery index > 600 ml min(-1 ) m(-2 ) using fluids and dobutamine and ( ii ) a protocol -guided RFT . After 150 enrolled patients , the trial was stopped due to slow recruitment . The short-term primary outcome measure was the relative risk ( RR ) of postoperative complications ; secondary measures were ( i ) administered fluid levels , ( ii ) vasopressor requirements , and ( iii ) haemodynamic responses . RESULTS For the GDHT group , 74 and for the RFT group 75 patients were design ated . The RR of postoperative complications ( GDHT vs RFT ) was 0.79 ( 95 % confidence interval 0.54 - 1.16 ) ; the volumes of i.v . fluids decreased ( 1078 vs 1440 ml , P=0.01 ) ; fewer patients required treatment of hypotension ( 18.5 % vs 75 % , P<0.005 ) ; there were more patients with increased oxygen delivery at the end of operation ( 28 % vs 8 % , P=0.04 ) , but the haemodynamic goal was achieved in only 27 % of patients in the GDHT group . CONCLUSIONS The magnitude of risk reduction of postoperative complications is clinical ly relevant , but the trial was underpowered and the null hypothesis can not be rejected Introduction Little is known about mortality rates following general surgical procedures in the United Kingdom . Deaths are most common in the ' high-risk ' surgical population consisting mainly of older patients , with coexisting medical disease , who undergo major surgery . Only limited data are presently available to describe this population . The aim of the present study was to estimate the size of the high-risk general surgical population and to describe the outcome and intensive care unit ( ICU ) re source use . Methods Data on inpatient general surgical procedures and ICU admissions in 94 National Health Service hospitals between January 1999 and October 2004 were extracted from the Intensive Care National Audit & Research Centre data base and the CHKS data base . High-risk surgical procedures were defined prospect ively as those for which the mortality rate was 5 % or greater . Results There were 4,117,727 surgical procedures ; 2,893,432 were elective ( 12,704 deaths ; 0.44 % ) and 1,224,295 were emergencies ( 65,674 deaths ; 5.4 % ) . A high-risk population of 513,924 patients was identified ( 63,340 deaths ; 12.3 % ) , which accounted for 83.8 % of deaths but for only 12.5 % of procedures . This population had a prolonged hospital stay ( median , 16 days ; interquartile range , 9–29 days ) . There were 59,424 ICU admissions ( 11,398 deaths ; 19 % ) . Among admissions directly to the ICU following surgery , there were 31,633 elective admissions with 3,199 deaths ( 10.1 % ) and 24,764 emergency admissions with 7,084 deaths ( 28.6 % ) . The ICU stays were short ( median , 1.6 days ; interquartile range , 0.8–3.7 days ) but hospital admissions for those admitted to the ICU were prolonged ( median , 16 days ; interquartile range , 10–30 days ) . Among the ICU population , 40.8 % of deaths occurred after the initial discharge from the ICU . The highest mortality rate ( 39 % ) occurred in the population admitted to the ICU following initial postoperative care on a st and ard ward . Conclusion A large high-risk surgical population accounts for 12.5 % of surgical procedures but for more than 80 % of deaths . Despite high mortality rates , fewer than 15 % of these patients are admitted to the ICU Background Our aim was to determine whether substitution of goal -directed fluid therapy ( GDT ) ( perioperative fluid administration ) for traditional therapy to manage elderly patients with coronary heart disease scheduled for gastrointestinal ( GI ) surgery was advantageous . We determined if it would reduce cardiac complications and shorten time to recovery and discharge . Methods Altogether , 60 of these elderly patients were r and omized into GDT ( n = 30 ) and control ( n = 30 ) groups . In the GDT group , fluid management was carried out under guidance of hemodynamic status indicators . Types and quantities of fluids administered , blood loss , intraoperative urine output , time of extubation , intensive care unit ( ICU ) stay , hospital stay , postoperative adverse cardiac events , and GI complications were recorded . Results Total fluids infused were 2,910 ± 645 ml ( GDT group ) and 3,640 ± 771 ml ( control group ) ( p < 0.05 ) . Numbers of adverse cardiac events in the two groups were not significantly different ( p = 0.121 ) . Return of GI function was significantly faster in the GDT group ( p < 0.001 ) . Median ICU stay was 32.5 h in the GDT group and 47.5 h in the control group ( p < 0.001 ) . Median hospital stay was 18 days in the GDT group and 22 days in the control group ( p < 0.001 ) . Conclusions GDT was associated with shorter ICU stay and time to discharge and faster return of GI function compared to traditional fluid therapy . The number of adverse cardiac events was similar in the two groups OBJECTIVES : This pilot study was design ed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies . METHODS : Eighty patients undergoing thoracoscopic lobectomy were r and omized into either a goal -directed therapy group or a control group . In the goal -directed therapy group , the stroke volume variation was controlled at 10%±1 % , and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2 . In the control group , the MAP was maintained at between 65 mm Hg and 90 mm Hg , heart rate was maintained at between 60 BPM and 100 BPM , and urinary output was greater than 0.5 mL/kg-1/h-1 . The hemodynamic variables , arterial blood gas analyses , total administered fluid volume and side effects were recorded . RESULTS : The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal -directed therapy group was significantly higher than that of the control group , but there were no differences between the goal -directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia . The extubation time was significantly earlier in the goal -directed therapy group , but there was no difference in the length of hospital stay . Patients in the control group had greater urine volumes , and they were given greater colloid and overall fluid volumes . Nausea and vomiting were significantly reduced in the goal -directed therapy group . CONCLUSION : The results of this study demonstrated that an optimization protocol , based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device , increased the PaO2/FiO2-ratio and reduced the overall fluid volume , intubation time and postoperative complications ( nausea and vomiting ) in thoracic surgery patients requiring one-lung ventilation BACKGROUND A prospect i ve , r and omized controlled trial comparing conventional intraoperative fluid management with two differing methods of invasive haemodynamic monitoring to optimize intraoperative fluid therapy , in patients undergoing proximal femoral fracture repair under general anaesthesia . METHODS Ninety patients r and omized to three groups ; conventional intraoperative fluid management ( Gp CON , n=29 ) , and two groups receiving additional repeated colloid fluid challenges guided by central venous pressure ( Gp CVP , n=31 ) or oesophageal Doppler ultrasonography ( Gp DOP , n=30 ) . Primary outcome measures were time to medical fitness to discharge , hospital stay and postoperative morbidity . RESULTS The fluid challenge result ed in significantly greater perioperative changes in central venous pressure between Gp CVP and Gp CON ( mean 5 ( 95 % confidence interval 3 - 7 ) mm Hg ) ( P<0.0001 ) . Important perioperative changes were also shown in Gp DOP with increases of 49.4 ms ( 19.7 - 79.1 ms ) in the corrected flow time , 13.5 ml ( 7.4 - 19.6 ml ) in stroke volume , and 0.9 ( 0.49 - 1.39 ) litre min(-1 ) in cardiac output . As a result , fewer patients in Gp CVP and Gp DOP experienced severe intraoperative hypotension ( Gp CON 28 % ( 8/29 ) , Gp CVP 9 % ( 3/31 ) , Gp DOP 7 % ( 2/30 ) , P=0.048 ( chi-squared , 2 degrees of freedom ( df ) . No differences were seen between the three groups when major morbidity and mortality were combined , P=0.24 ( chi-squared , 2 df ) . Postoperative recovery for survivors , as defined by time to be deemed medically fit for discharge , was significantly faster , in comparison with Gp CON , in both the Gp CVP ( 10 vs 14 ( 95 % confidence interval 8 - 12 vs 12 - 17 ) days , P=0.008 ( t-test ) ) , and Gp DOP ( 8 vs 14 ( 95 % confidence interval 6 - 12 vs 12 - 17 ) days , P=0.023 ( t-test ) . There were no significant differences between groups , for survivors , with respect to acute orthopaedic hospital and total hospital stay . CONCLUSIONS Invasive intraoperative haemodynamic monitoring with fluid challenges during repair of femoral fracture under general anaesthetic shortens time to being medically fit for discharge This systematic review and meta- analysis summarizes the clinical effects of increasing perioperative blood flow using fluids with or without inotropes/vasoactive drugs to explicit defined goals in adults . We included r and omized controlled trials of adult patients ( aged 16 years or older ) undergoing surgery . We included 31 studies of 5292 participants . There was no difference in mortality at the longest follow-up : 282/2615 ( 10.8 % ) died in the control group and 238/2677 ( 8.9 % ) in the treatment group , RR of 0.89 ( 95 % CI : 0.76 - 1.05 ; P=0.18 ) . However , the results were sensitive to analytical methods and withdrawal of studies with method ological limitations . The intervention reduced the rate of three morbidities ( renal failure , respiratory failure , and wound infections ) but not the rates of arrhythmia , myocardial infa rct ion , congestive cardiac failure , venous thrombosis , and other types of infections . The number of patients with complications was also reduced by the intervention . Hospital length of stay was reduced in the treatment group by 1.16 days . There was no difference in critical care length of stay . The primary analysis of this review showed no difference between groups but this result was sensitive to the method of analysis , withdrawal of studies with method ological limitations , and was dominated by a single large study . Patients receiving this intervention stayed in hospital 1 day less with fewer complications . It is unlikely that the intervention causes harm . The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced Introduction Total hip replacement is one of the most commonly performed major orthopaedic operations . Goal -directed therapy ( GDT ) using haemodynamic monitoring has previously demonstrated outcome benefits in high-risk surgical patients under general anaesthesia . GDT has never been formally assessed during regional anaesthesia . Methods Patients undergoing total hip replacement while under regional anaesthesia were r and omised to either the control group ( CTRL ) or the protocol group ( GDT ) . Patients in the GDT group , in addition to st and ard monitoring , were connected to the FloTrac sensor/Vigileo monitor haemodynamic monitoring system , and a GDT protocol was used to maximise the stroke volume and target the oxygen delivery index to > 600 mL/minute/m2 . Results Patients r and omised to the GDT group were given a greater volume of intravenous fluids during the intraoperative period ( means ± st and ard deviation ( SD ) : 6,032 ± 1,388 mL vs. 2,635 ± 346 mL ; P < 0.0001 ) , and more of the GDT patients received dobutamine ( 0 of 20 CTRL patients vs. 11 of 20 GDT patients ; P < 0.0003 ) . The GDT patients also received more blood transfused during the intraoperative period ( means ± SD : 595 ± 316 mL vs. 0 ± 0 mL ; P < 0.0001 ) , although the CTRL group received greater volumes of blood replacement postoperatively ( CTRL patients 658 ± 68 mL vs. GDT patients 198 ± 292 mL ; P < 0.001 ) . Overall blood consumption ( intraoperatively and postoperatively ) was not different between the two groups . There were an increased number of complications in the CTRL group ( 20 of 20 CTRL patients ( 100 % ) vs. 16 of 20 GDT patients ( 80 % ) ; P = 0.05 ) . These outcomes were predominantly due to a difference in minor complications ( 20 of 20 CTRL patients ( 100 % ) vs. 15 of 20 GDT patients ( 75 % ) ; P = 0.047 ) . Conclusions GDT applied during regional anaesthesia in patients undergoing elective total hip replacement changes intraoperative fluid management and may improve patient outcomes by decreasing postoperative complications . Larger trials are required to confirm our findings .Trial registration S RCT Introduction Several single-center studies and meta-analyses have shown that perioperative goal -directed therapy may significantly improve outcomes in general surgical patients . We hypothesized that using a treatment algorithm based on pulse pressure variation , cardiac index trending by radial artery pulse contour analysis , and mean arterial pressure in a study group ( SG ) , would result in reduced complications , reduced length of hospital stay and quicker return of bowel movement postoperatively in abdominal surgical patients , when compared to a control group ( CG ) . Methods 160 patients undergoing elective major abdominal surgery were r and omized to the SG ( 79 patients ) or to the CG ( 81 patients ) . In the SG hemodynamic therapy was guided by pulse pressure variation , cardiac index trending and mean arterial pressure . In the CG hemodynamic therapy was performed at the discretion of the treating anesthesiologist . Outcome data were recorded up to 28 days postoperatively . Results The total number of complications was significantly lower in the SG ( 72 vs. 52 complications , p = 0.038 ) . In particular , infection complications were significantly reduced ( SG : 13 vs. CG : 26 complications , p = 0.023 ) . There were no significant differences between the two groups for return of bowel movement ( SG : 3 vs. CG : 2 days postoperatively , p = 0.316 ) , duration of post anesthesia care unit stay ( SG : 180 vs. CG : 180 minutes , p = 0.516 ) or length of hospital stay ( SG : 11 vs. CG : 10 days , p = 0.929 ) . Conclusions This multi-center study demonstrates that hemodynamic goal -directed therapy using pulse pressure variation , cardiac index trending and mean arterial pressure as the key parameters leads to a decrease in postoperative complications in patients undergoing major abdominal surgery . Trial registration Clinical Trial.gov , NCT01401283 Introduction Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and /or low dose inotropic therapy . The mechanisms underlying this benefit remain uncertain . The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery . Methods R and omised , controlled , single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery . For eight hours after surgery , intra-venous fluid therapy was guided by measurements of central venous pressure ( CVP group ) , or stroke volume ( SV group ) . In a third group stroke volume guided fluid therapy was combined with dopexamine ( 0.5 mcg/kg/min ) ( SV & DPX group ) . Results 135 patients were recruited ( n = 45 per group ) . In the SV & DPX group , increased global oxygen delivery was associated with improved sublingual ( P < 0.05 ) and cutaneous microvascular flow ( P < 0.005 ) ( sublingual microscopy and laser Doppler flowmetry ) . Microvascular flow remained constant in the SV group but deteriorated in the CVP group ( P < 0.05 ) . Cutaneous tissue oxygen partial pressure ( PtO2 ) ( Clark electrode ) improved only in the SV & DPX group ( P < 0.001 ) . There were no differences in serum inflammatory markers . There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group ( CVP group ten patients ( 22 % ) ; pooled SV and SV & DPX groups seven patients ( 8 % ) ; P = 0.03 ) ( post hoc analysis ) . Conclusions Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery , microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery . These observations may explain improved clinical outcomes associated with this treatment in previous trials . Trial registration numberIS RCT N Objective : To evaluate the influence of stroke volume variation (SVV)-based goal -directed therapy ( GDT ) on splanchnic organ functions and postoperative complications in orthopedic patients . Subjects and Methods : Eighty patients scheduled for major orthopedic surgery under general anesthesia were r and omly allocated to one of two equal groups to receive either intraoperative volume therapy guided by SVV ( GDT ) or st and ard fluid management ( control ) . In the SVV group , patients received colloid boluses of 4 ml/kg to maintain an SVV < 10 % when in the supine position or an SVV < 14 % if prone . In the control group , fluids were given to maintain a mean arterial pressure > 65 mm Hg , a heart rate < 100 bpm , a central venous pressure of 8 - 14 mm Hg , and a urine output > 0.5 ml/kg/h . Intraoperative organ perfusion , hemodynamic data , hospitalization , postoperative complications , and mortality were recorded . Results : The heart rate at the end of surgery was significantly lower ( p < 0.05 ) , there were fewer hypotensive episodes ( p < 0.05 ) , the arterial and gastric intramucosal pH were higher ( p < 0.05 for both ) , the gastric intramucosal PCO2 was lower ( p < 0.05 ) , the intraoperative infused colloids and the total infused volume were lower ( p < 0.05 for both ) , and the postoperative time to flatus was shorter ( p < 0.05 ) in the GDT group than in the control group . No differences in the length of hospital stay , complications , or mortality were found between the groups . Conclusion : SVV-based GDT during major orthopedic surgery reduced the volume of the required intraoperative infused fluids , maintained intraoperative hemodynamic stability , and improved the perioperative gastrointestinal function Objective To evaluate the effects of maximizing the oxygen delivery on morbidity and mortality in patients > 60 yrs of age and /or with chronic diseases of vital organs who underwent major elective surgery . Design Prospect i ve , r and omized , controlled trial . Setting A 24-bed general intensive care unit of a teaching hospital . Patients Thirty-seven high-risk patients who underwent major surgery . Interventions The hemodynamic and oxygen transport variables and outcomes in 18 patients ( control group ) treated to maintain normal values of oxygen delivery were compared with 19 patients ( protocol group ) treated to maintain “ supranormal ” values . Therapy in both groups consisted of volume expansion and , when necessary , dobutamine to reach target values , during the surgery and 24 hrs postoperatively . Measurements and Main Results We interrupted the study because of a significant difference in the 60-day mortality rate . The mortality rate in the control group was significantly higher when compared with the protocol group ( 9/18 [ 50 % ] vs. 3/19 [ 15.7 % ] , p < .05 ) . The prevalence of clinical and infectious complications was higher in the control group than in the protocol group ( 67 % and 31 % respectively ; relative risk , 0.47 ; 95 % confidence interval , 0.226–0.991;p < .05 ) and there was a trend toward more severe organ dysfunction in nonachievers patients ( 17/24 [ 71 % ] vs. 6/13 [ 46 % ] , relative risk , 0.65 ; 95 % confidence interval , 0.343–1.237 ; NS ) . Conclusion Older patients with existing cardiorespiratory illness undergoing major surgery have a reduced morbidity and mortality when dobutamine is used to maximize oxygen transport BACKGROUND We aim ed to investigate whether fluid therapy with a goal of near-maximal stroke volume ( SV ) guided by oesophageal Doppler ( ED ) monitoring result in a better outcome than that with a goal of maintaining bodyweight ( BW ) and zero fluid balance in patients undergoing colorectal surgery . METHODS In a double-blinded clinical multicentre trial , 150 patients undergoing elective colorectal surgery were r and omized to receive fluid therapy after either the goal of near-maximal SV guided by ED ( Doppler , D group ) or the goal of zero balance and normal BW ( Zero balance , Z group ) . Stratification for laparoscopic and open surgery was performed . The postoperative fluid therapy was similar in the two groups . The primary endpoint was postoperative complications defined and divided into subgroups by protocol . Analysis was performed by intention-to-treat . The follow-up was 30 days . The trial had 85 % power to show a difference between the groups . RESULTS The number of patients undergoing laparoscopic or open surgery and the patient characteristics were similar between the groups . No significant differences between the groups were found for overall , major , minor , cardiopulmonary , or tissue-healing complications ( P-values : 0.79 ; 0.62 ; 0.97 ; 0.48 ; and 0.48 , respectively ) . One patient died in each group . No significant difference was found for the length of hospital stay [ median ( range ) Z : 5.00 ( 1 - 61 ) vs D : 5.00 ( 2 - 41 ) ; P=0.206 ] . CONCLUSIONS Goal -directed fluid therapy to near-maximal SV guided by ED adds no extra value to the fluid therapy using zero balance and normal BW in patients undergoing elective colorectal surgery Background Intraoperative hypovolemia is common and is a potential cause of organ dysfunction , increased postoperative morbidity , length of hospital stay , and death . The objective of this prospect i ve , r and omized study was to assess the effect of goal -directed intraoperative fluid administration on length of postoperative hospital stay . Methods One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were r and omly assigned to a control group ( n = 50 ) that received st and ard intraoperative care or to a protocol group ( n = 50 ) that , in addition , received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume . Length of postoperative hospital stay and postoperative surgical morbidity were assessed . Results Groups were similar with respect to demographics , surgical procedures , and baseline hemodynamic variables . The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group . Patients in the protocol group had a shorter duration of hospital stay compared with the control group : 5 ± 3 versus 7 ± 3 days ( mean ± SD ) , with a median of 6 versus 7 days , respectively ( P = 0.03 ) . These patients also tolerated oral intake of solid food earlier than the control group : 3 ± 0.5 versus 4.7 ± 0.5 days ( mean ± SD ) , with a median of 3 versus 5 days , respectively ( P = 0.01 ) . Conclusions Goal -directed intraoperative fluid administration results in earlier return to bowel function , lower incidence of postoperative nausea and vomiting , and decrease in length of postoperative hospital stay Introduction Several studies have shown that maximizing stroke volume ( or increasing it until a plateau is reached ) by volume loading during high-risk surgery may improve post-operative outcome . This goal could be achieved simply by minimizing the variation in arterial pulse pressure ( ΔPP ) induced by mechanical ventilation . We tested this hypothesis in a prospect i ve , r and omized , single-centre study . The primary endpoint was the length of postoperative stay in hospital . Methods Thirty-three patients undergoing high-risk surgery were r and omized either to a control group ( group C , n = 16 ) or to an intervention group ( group I , n = 17 ) . In group I , ΔPP was continuously monitored during surgery by a multiparameter bedside monitor and minimized to 10 % or less by volume loading . Results Both groups were comparable in terms of demographic data , American Society of Anesthesiology score , type , and duration of surgery . During surgery , group I received more fluid than group C ( 4,618 ± 1,557 versus 1,694 ± 705 ml ( mean ± SD ) , P < 0.0001 ) , and ΔPP decreased from 22 ± 75 to 9 ± 1 % ( P < 0.05 ) in group I. The median duration of postoperative stay in hospital ( 7 versus 17 days , P < 0.01 ) was lower in group I than in group C. The number of postoperative complications per patient ( 1.4 ± 2.1 versus 3.9 ± 2.8 , P < 0.05 ) , as well as the median duration of mechanical ventilation ( 1 versus 5 days , P < 0.05 ) and stay in the intensive care unit ( 3 versus 9 days , P < 0.01 ) was also lower in group I. Conclusion Monitoring and minimizing ΔPP by volume loading during high-risk surgery improves postoperative outcome and decreases the length of stay in hospital . Trial registration Purpose Goal -directed therapy in the perioperative setting has been shown to be associated with short-term improvements in outcome . This study assesses the longer-term survival of patients from a previous r and omized controlled trial of goal -directed therapy in high-risk surgical patients . Methods All patients from a previous r and omized controlled study were followed up for 15 years following r and omization to ascertain their length of survival following surgery . Factors that may be associated with increased survival were evaluated to determine what influenced long-term outcomes . Results Data from 106 of the original 107 patients ( 99 % ) were available for analysis . At 15 years , 11 ( 20.7 % ) of the goal -directed therapy patients versus 4 ( 7.5 % ) of the control group were alive ( p = 0.09 ) . Median survival for the goal -directed group was increased by 1,107 days ( 1,781 vs. 674 days , p = 0.005 ) . Long-term survival was associated with three independent factors : age [ hazard ratio ( HR ) 1.04 ( 1.02–1.07 ) , p < 0.0001 ] , r and omization to the goal -directed group of the study [ HR 0.61 ( 0.4–0.92 ) , p = 0.02 ] , and avoidance of a significant postoperative cardiac complication [ HR 3.78 ( 2.16–6.6 ) , p = 0.007 ] . Conclusions Long-term survival after major surgery is related to a number of factors , including patient age and avoidance of perioperative complications . Short-term goal -directed therapy in the perioperative period may improve long-term outcomes , in part due to its ability to reduce the number of perioperative complications BACKGROUND The concept of drug titration emerged recently for intraoperative fluid administration during Fast-Track colonic surgery to avoid hypovolemia as well as excessive crystalloid administration . The Pleth Variability Index ( PVI ) is an oximeter-derived parameter . It allows a continuous monitoring of the respiratory variation of the perfusion index . OBJECTIVE To investigate if applying the concept of fluid titration with PVI-guided colloid administration conjointly with restricted crystalloids administration changes the amount of fluid administered . DESIGN , SETTING S AND PATIENTS : Twenty one ASA 2 patients scheduled for Fast-Track colonic surgery were r and omized in two groups : the PVI-guided the fluid management group and the the control group . INTERVENTION AND MAIN OUTCOME MEASURES After the induction of general anesthesia , the PVI group received a 10 mL.kg- 1.h-1 infusion of crystalloid during the first hour , reduced to 2 mL.kg-1.h-1 thereafter . Colloids 250 mL were administered if necessary to maintain a PVI value of 10 to 13 % . In the control group , a 10 mL.kg-1.h-1 infusion of crystalloid during the first hour was followed by a 5 mL.kg-1.h-1 infusion . Boluses of 250 mL of colloids were administered if required to maintain the mean arterial pressure above 65 mmHg . RESULTS Intraoperative crystalloids infused volume were significantly lower in the PVI group ( 925+/-262 mL vs 1129+/- 160 mL ; P=0.04 ) . In contrast , the infused amounts of colloids was higher in the PVI group ( 725+/-521 mL vs 250+/-224 mL ; P=0.01 ) . Interestingly , total fluid amount infused intra- ant postoperatively were similar between the groups ( 1650+/- 807 mL vs 1379+/-186 mL ; P=0.21 ) . CONCLUSION PVI-guided fluid management in Fast-Track colonic surgery is not necessarily associated with different total volume infused Introduction Stroke volume variation ( SVV ) is a good and easily obtainable predictor of fluid responsiveness , which can be used to guide fluid therapy in mechanically ventilated patients . During major abdominal surgery , inappropriate fluid management may result in occult organ hypoperfusion or fluid overload in patients with compromised cardiovascular reserves and thus increase postoperative morbidity . The aim of our study was to evaluate the influence of SVV guided fluid optimization on organ functions and postoperative morbidity in high risk patients undergoing major abdominal surgery . Methods Patients undergoing elective intraabdominal surgery were r and omly assigned to a Control group ( n = 60 ) with routine intraoperative care and a Vigileo group ( n = 60 ) , where fluid management was guided by SVV ( Vigileo/FloTrac system ) . The aim was to maintain the SVV below 10 % using colloid boluses of 3 ml/kg . The laboratory parameters of organ hypoperfusion in perioperative period , the number of infectious and organ complications on day 30 after the operation , and the hospital and ICU length of stay and mortality were evaluated . The local ethics committee approved the study . Results The patients in the Vigileo group received more colloid ( 1425 ml [ 1000 - 1500 ] vs. 1000 ml [ 540 - 1250 ] ; P = 0.0028 ) intraoperatively and a lower number of hypotensive events were observed ( 2[1 - 2 ] Vigileo vs. 3.5[2 - 6 ] in Control ; P = 0.0001 ) . Lactate levels at the end of surgery were lower in Vigileo ( 1.78 ± 0.83 mmol/l vs. 2.25 ± 1.12 mmol/l ; P = 0.0252 ) . Fewer Vigileo patients developed complications ( 18 ( 30 % ) vs. 35 ( 58.3 % ) patients ; P = 0.0033 ) and the overall number of complications was also reduced ( 34 vs. 77 complications in Vigileo and Control respectively ; P = 0.0066 ) . A difference in hospital length of stay was found only in per protocol analysis of patients receiving optimization ( 9 [ 8 - 12 ] vs. 10 [ 8 - 19 ] days ; P = 0.0421 ) . No difference in mortality ( 1 ( 1.7 % ) vs. 2 ( 3.3 % ) ; P = 1.0 ) and ICU length of stay ( 3 [ 2 - 5 ] vs. 3 [ 0.5 - 5 ] ; P = 0.789 ) was found . Conclusions In this study , fluid optimization guided by SVV during major abdominal surgery is associated with better intraoperative hemodynamic stability , decrease in serum lactate at the end of surgery and lower incidence of postoperative organ complications . Trial registration Current Controlled Trials IS RCT N95085011 BACKGROUND Evidence for the benefit of an intraoperative use of a goal -directed haemodynamic management has grown . We compared the oesophageal Doppler monitor ( ODM , CardioQ-ODM ™ ) with a calibrated pulse contour analysis ( PCA , PiCCO2 ™ ) with regard to assessment of stroke volume ( SV ) changes after volume administration within a goal -directed haemodynamic algorithm during non-cardiac surgery . METHODS The data were obtained prospect ively in patients with metastatic ovarian carcinoma undergoing cytoreductive surgery . During surgery , fluid challenges were performed as indicated by the goal -directed haemodynamic algorithm guided by the ODM . Monitors were compared regarding precision and trending . Clinical characteristics associated with trending were studied by extended regression analysis . RESULTS A total of 762 fluid challenges were performed in 41 patients result ing in 1524 paired measurements . The precision of ODM and PCA was 5.7 % and 6.0 % ( P=0.80 ) , respectively . Polar plot analysis revealed a poor trending between ODM and PCA with an angular bias of -7.1 ° , radial limits of agreement of -58.1 ° to 43.8 ° , and an angular concordance rate of 67.8 % . Dose of norepinephrine ( NE ) ( scaled 0.1 µg kg(-1 ) min(-1 ) ) [ adjusted odds ratio ( OR ) 0.606 ( 95 % confidence interval , CI : 0.404 - 0.910 ) ; P=0.016 ] and changes in mean arterial pressure ( MAP ) to a fluid challenge ( scaled 10 % ) [ adjusted OR 0.733 ( 95 % CI : 0.635 - 0.845 ) ; P<0.001 ] were associated with trending between ODM and PCA , whereas there was no relation to type of i.v . solution . CONCLUSIONS Despite a similar precision , ODM and PCA were not interchangeable with regard to measuring SV changes within a goal -directed haemodynamic algorithm . A decrease in interchangeability coincided with increasing NE levels and greater changes of MAP to a fluid challenge OBJECTIVE : The optimal strategy for fluid management during gastrointestinal surgery remains unclear . Minimizing the variation in arterial pulse pressure , which is induced by mechanical ventilation , is a potential strategy to improve postoperative outcomes . We tested this hypothesis in a prospect i ve , r and omized study with lactated Ringer 's solution and 6 % hydroxyethyl starch solution . METHOD : A total of 60 patients who were undergoing gastrointestinal surgery were r and omized into a restrictive lactated Ringer 's group ( n = 20 ) , a goal -directed lactated Ringer 's group ( n = 20 ) and a goal -directed hydroxyethyl starch group ( n = 20 ) . The goal -directed fluid treatment was guided by pulse pressure variation , which was recorded during surgery using a simple manual method with a Date x Ohmeda S/5 Monitor and minimized to 11 % or less by volume loading with either lactated Ringer 's solution or 6 % hydroxyethyl starch solution ( 130/0.4 ) . The postoperative flatus time , the length of hospital stay and the incidence of complications were recorded as endpoints . RESULTS : The goal -directed lactated Ringer 's group received the greatest amount of total operative fluid compared with the two other groups . The flatus time and the length of hospital stay in the goal -directed hydroxyethyl starch group were shorter than those in the goal -directed lactated Ringer 's group and the restrictive lactated Ringer 's group . No significant differences were found in the postoperative complications among the three groups . CONCLUSION : Monitoring and minimizing pulse pressure variation by 6 % hydroxyethyl starch solution ( 130/0.4 ) loading during gastrointestinal surgery improves postoperative outcomes and decreases the discharge time of patients who are grade d American Society of Anesthesiologists physical status I/II Background : The optimal amount and method for monitoring intravenous fluid in surgical patients is unresolved . Central venous oxygen saturation ( Scvo2 ) has been used to guide therapy and predict outcome in high-risk and intensive-care patients . The aim of this prospect i ve , r and omized trial was to compare the rate of postoperative complications in patients receiving fluid therapy guided by Scvo2 and those treated with a traditional effluent fluid scheme . Methods : Patients undergoing open colorectal and lower intestinal surgery ( n = 241 ) were r and omized to the Scvo2 group or the control group . The Scvo2 group received perioperatively crystalloid infusion 100 ml/h . When Scvo2 was less than 75 % , a bolus of 3 ml/kg hydroxyethyl starch was given . The bolus was repeated if Scvo2 increased by 1 percentage point or more . The control group was maintained with crystalloid 800 ml/h and given extra fluid if there were clinical signs of hypovolemia . The participating surgeon , unaware of the group allocation , registered complications within day 30 . Results : Until 8:00 am on the first postoperative day , the Scvo2 group had received 3,869 ± 992 ml ( mean ± SD ) intravenous fluid compared with 6,491 ± 1,649 ml in the control group . Increase in weight was 0.8 ± 1.8 kg and 2.5 ± 1.6 kg in the two groups , respectively . The postoperative complication rate was 42 % in both groups . Conclusion : Clinical outcomes among patients receiving Scvo2-guided perioperative fluid therapy were similar to those for patients treated with a traditional fluid regimen . Limitations in study design prevent full interpretation of these findings , and further large trials of this treatment algorithm are still required BACKGROUND Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements . Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay . We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery . METHODS This single centre , blinded , prospect i ve controlled trial r and omized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based ( conventional ) intraoperative fluid management . The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aim ing for a CVP between 12 and 15 mm Hg . RESULTS The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05 . The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001 . Doppler patients achieved significantly higher cardiac output , stroke volume , and oxygen delivery . Twenty-nine ( 45.3 % ) control patients suffered gastrointestinal morbidity compared with nine ( 14.1 % ) in the Doppler guided fluid group P<0.001 , overall morbidity was also significantly higher in the control group P=0.05 . CONCLUSIONS Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay . Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity BACKGROUND Dynamic variables , for example , systolic pressure variation ( SPV ) , are superior to filling pressures for assessing fluid responsiveness . We analysed the effects of SPV-guided intraoperative fluid management on organ function and perfusion when compared with routine care . METHODS Eighty patients ( 44 female and 36 male ) undergoing elective major abdominal surgery were r and omly assigned to a control group [ n=40 , mean age 66 ( sd 10 ) , range 40 - 84 yr ] or SPV group [ n=40 , age 61 ( 16 ) , range 26 - 100 yr ] in which intraoperative fluid management was guided by SPV ( trigger : SPV>10 % ) . Central venous O2 saturation ( ScvO2 ) , lactate and bilirubin , creatinine , indocyanine green plasma disappearance rate ( ICG-PDR ) , and gastric mucosal CO(2 ) tension were measured after induction of anaesthesia , after 3 , 6 , 12 , and 24 h. RESULTS Patient characteristics , duration of surgery [ 5.8 ( 2.5 ) vs 5.4 ( 2.5 ) h ] , and infusion volumes ( median 4865 vs 4330 ml ) were comparable between the groups . At 3 and 6 h , SPV ( P=0.04 , P=0.01 ) and Deltadown ( P=0.005 , P=0.01 ) were significantly higher in the control group . Oxygen transport and organ function were comparable : baseline and 24 h values for ICG-PDR : 28.5 ( 7.9 ) and 22.7 ( 7.8 ) vs 23.9 ( 6.9 ) and 26.1 (5.9)% min(-1 ) , 77.7 ( 6.6 ) and 72.6 ( 5.5 ) vs 79.3 ( 7.1 ) and 72.8 (6.7)% for ScvO2 and 1.0 ( 0.4 ) and 1.2 ( 0.6 ) vs 0.9 ( 0.2 ) and 1.3 ( 0.5 ) mmol litre(-1 ) for lactate . Length of mechanical ventilation , ICU stay , and mortality were comparable . CONCLUSIONS In comparison with routine care , intraoperative SPV-guided treatment was associated with slightly increased fluid adminstration whereas organ perfusion and function was similar INTRODUCTION : No consensus exists regarding the optimal fluid ( crystalloid or colloid ) or strategy ( liberal , restricted , or goal directed ) for fluid management after colectomy . Prior assessment s have used normal saline . This is the first assessment of st and ard , goal -directed perioperative fluid management with either lactated Ringer ’s or hetastarch/lactated Ringer ’s , with use of esophageal Doppler for guidance , in laparoscopic colectomy with an enhanced recovery protocol . METHODS : A double-blinded , prospect i ve , r and omized , three-armed study with Institutional Review Board approval was used for patients undergoing laparoscopic segmental colectomy assigned to the st and ard , goal -directed/lactated Ringer ’s and goal -directed/hetastarch groups . A st and ard anesthesia and basal fluid administration protocol was used in addition to the goal -directed strategies guided by esophageal Doppler . RESULTS : Sixty-four patients undergoing laparoscopic colectomy ( 22 st and ard , 21 goal -directed/lactated Ringer ’s , 21 goal -directed/hetastarch ) had similar operative times ( st and ard , 2.3 hours ; goal -directed/lactated Ringer ’s , 2.5 hours ; goal -directed/hetastarch , 2.3 hours ) . The lactated Ringer ’s group received the greatest amount of total and milliliters per kilogram per hour of operative fluid ( st and ard , 2,850/18 ; goal -directed/lactated Ringer ’s , 3,800/23 ; and goal -directed/hetastarch , 3,300/17 ; P < 0.05 ) . The hetastarch group had the longest stay ( st and ard , 64.9 hours ; goal -directed/lactated Ringer ’s , 71.8 hours ; goal -directed/hetastarch , 75.5 hours ; P < 0.05 ) . The st and ard group received the greatest amount of fluid during hospitalization ( st and ard , 2.5 ml/kg/h ; goal -directed/lactated Ringer ’s , 1.9 ml/kg/h ; goal -directed/hetastarch , 2.1 ml/kg/h ; P < 0.05 ) . There was one instance of operative mortality in the goal -directed/hetastarch group . CONCLUSIONS : Goal -directed fluid management with a colloid/balanced salt solution offers no advantage and is more costly . However , goal -directed , individualized intraoperative fluid management with crystalloid should be evaluated further as a component of enhanced recovery protocol s following colectomy because of reduced overall fluid administration Background and objective We hypothesized that , in vascular surgery patients , the application of a goal -directed strategy based on a pulse contour-derived cardiac index would be associated with a better haemodynamic status than the application of routine perioperative care and that the amount of fluid and /or inotropes required in such a goal -directed therapy depended on the general anaesthetic technique used . Methods Patients undergoing peripheral arterial bypass grafting were r and omly assigned to three groups . In group 1 , haemodynamic management was performed according to routine clinical practice . In the two other groups ( groups 2 and 3 ) a goal -directed therapy was applied aim ing to maintain the pulse contour-derived cardiac index above 2.5 l m−2 min−1 . Patients in groups 1 and 2 received sevoflurane-based anaesthesia and patients in group 3 propofol-based anaesthesia . Haemodynamic variables , amount of fluid and administration of inotropes were assessed at different time intervals . Results The amount of fluid administered was not significantly different between the groups . Two patients in group 1 , 13 patients in group 2 and 12 patients in group 3 were treated with dobutamine ( P < 0.001 ) . None of the patients anaesthetized with sevoflurane ( groups 1 and 2 ) experienced postoperative cardiovascular complications , whereas four patients in the total intravenous group ( group 3 ) experienced major postoperative cardiovascular complications ( P = 0.005 ) . Conclusion In the conditions of the present study , the application of a goal -directed therapy aim ing to maintain the cardiac index above 2.5 l min−1 m−2 did not result in a higher tissue oxygen delivery than when applying the st and ard haemodynamic strategy nor did it depend on the anaesthetic technique used A r and omized controlled trial was conducted to test the hypothesis that there is no difference in complications in patients receiving intravenous ( iv ) water and electrolyte , based on either stroke volume or clinical indicators at bowel surgery Objectives To determine CO and gastric mucosal perfusion in patients during elective major surgery ; to seek a relationship with subsequent outcome . Design Prospect i ve descriptive study . Setting University hospital . Patients 51 patients undergoing elective major surgery of an anticipated duration of greater than 2 h who were at risk of developing gut mucosal hypoperfusion and postoperative organ failure . Measurements and results CO was determined by oesophageal Doppler measurement of aortic blood flow . Gastric mucosal perfusion was determined by tonometric assessmment of gastric mucosal pH ( pHi ) . Blood pressure and urine flow were measured . At the end of surgery no patients were oliguric or hypotensive . Post-operatively morbidity , mortality , duration and cost of stay in the ITU and hospital were assessed . There were 32 patients with evidence of gastric mucosal ischaemia at the end of surgery ( pHi<7.32 ) despite maintenance of CO . This group of patients spent a mean of 4.7 ( range 0–33 ) days in the ITU , 14 developed major complications ( 7 with multiple organ failure [ MOF ] and 6 died . In 19 patients gut mucosal perfusion was maintained during surgery ( pHi≥7.32 ) ; these patients demonstrated an increase in CO of 48.4 % ( 95 % confidence interval 21.3–75.6 ) and spent a mean of 1.0 ( range 0–4 ) days in the ITU . Only one developed a major complication and none died . The total cost of post-operative care for the 51 patients was estimated at £ 356650 . Mean cost per patient in the low pHi group was significantly greater at £ 8 845 ( range £ 600–£42 700 ) compared to £ 3 874 ( range £ 2 600–£9 600 ) in the normal pHi group . The total·cost of post-operative care for the 7 patients who developed MOF was £ 171 450 i.e. 48 % of the total cost . Conclusion A low gastric pHi measured during the intraoperative period in a group of patients undergoing major ( mainly cardiovascular ) surgery is associated with increased post-operative complications and cost Perioperative hemodynamic optimisation improves postoperative outcome for patients undergoing high-risk surgery ( HRS ) . In this prospect i ve r and omized multicentre study we studied the effects of an individualized , goal -directed fluid management based on continuous stroke volume variation ( SVV ) and stroke volume ( SV ) monitoring on postoperative outcomes . 64 patients undergoing HRS were r and omized either to a control group ( CON , n = 32 ) or a goal -directed group ( GDT , n = 32 ) . In GDT , SVV and SV were continuously monitored ( FloTrac/Vigileo ) and patients were brought to and maintained on the plateau of the Frank-Starling curve ( SVV < 10 % and SV increase < 10 % in response to fluid loading ) . Organ dysfunction was assessed using the SOFA score and re source utilization using the TISS score . Patients were followed up to 28 days for postoperative complications . Main outcome measures were the number of complications ( infectious , cardiac , respiratory , renal , hematologic and abdominal post-operative complications ) , maximum SOFA score and cumulative TISS score during ICU stay , duration of mechanical ventilation , length of ICU stay , and time until fit for discharge . 12 patients had to be excluded from final analysis ( 6 in each group ) . During surgery , GDT received more colloids than CON ( 1,589 vs. 927 ml , P < 0.05 ) and SVV decreased in GDT ( from 9.0 to 8.0 % , P < 0.05 ) but not in CON . The number of postoperative wound infections was lower in GDT ( 0 vs. 7 , P < 0.01 ) . Although not statistically significant , the proportion of patients with at least one complication ( 46 vs. 62 % ) , the number of postoperative complications per patient ( 0.65 vs. 1.40 ) , the maximum sofa score ( 5.9 vs. 7.2 ) , and the cumulative TISS score ( 69 vs. 83 ) tended to be lower . This multicentre study shows that fluid management based on a SVV and SV optimisation protocol is feasible and decreases postoperative wound infections . Our findings also suggest that a goal -directed strategy might decrease postoperative organ dysfunction Patients with limited cardiac reserve are less likely to survive and develop more complications following major surgery . By augmenting oxygen delivery index ( DO2I ) with a combination of intravenous fluids and inotropes ( goal directed therapy ( GDT ) ) , postoperative mortality and morbidity of high-risk patients may be reduced . However , although most studies suggest that GDT may improve outcome in high-risk surgical patients , it is still not widely practice d. We set out to test the hypothesis that GDT results in greatest benefit in terms of mortality and morbidity in patients with the highest risk of mortality and have undertaken a systematic review of the current literature to see if this is correct . We performed a systematic search of Medline , Embase and CENTRAL data bases for r and omized controlled trials ( RCTs ) and review s of GDT in surgical patients . To minimize heterogeneity we excluded studies involving cardiac , trauma , and paediatric surgery . Extremely high risk , high risk and intermediate risks of mortality were defined as > 20 % , 5 to 20 % and < 5 % mortality rates in the control arms of the trials , respectively . Meta analyses were performed and Forest plots drawn using RevMan software . Data are presented as odd ratios ( OR ; 95 % confidence intervals ( CI ) , and P-values ) . A total of 32 RCTs including 2,808 patients were review ed . All studies reported mortality . Five studies ( including 300 patients ) were excluded from assessment of complication rates as the number of patients with complications was not reported . The mortality benefit of GDT was confined to the extremely high-risk group ( OR = 0.20 , 95 % CI 0.09 to 0.41 ; P < 0.0001 ) . Complication rates were reduced in all subgroups ( OR = 0.45 , 95 % CI 0.34 to 0.60 ; P < 0.00001 ) . The morbidity benefit was greatest amongst patients in the extremely high-risk subgroup ( OR = 0.27 , 95 % CI 0.15 to 0.51 ; P < 0.0001 ) , followed by the intermediate risk subgroup ( OR = 0.43 , 95 % CI 0.27 to 0.67 ; P = 0.0002 ) , and the high-risk subgroup ( OR 0.56 , 95 % CI 0.36 to 0.89 ; P = 0.01 ) . Despite heterogeneity in trial quality and design , we found GDT to be beneficial in all high-risk patients undergoing major surgery . The mortality benefit of GDT was confined to the subgroup of patients at extremely high risk of death . The reduction of complication rates was seen across all subgroups of GDT patients BACKGROUND Postoperative organ failures commonly occur after major abdominal surgery , increasing the utilization of re sources and costs of care . Tissue hypoxia is a key trigger of organ dysfunction . A therapeutic strategy design ed to detect and reverse tissue hypoxia , as diagnosed by an increase of oxygen extraction ( O2ER ) over a predefined threshold , could decrease the incidence of organ failures . The primary aim of this study was to compare the number of patients with postoperative organ failure and length of hospital stay between those r and omized to conventional vs a protocol ized strategy design ed to maintain O2ER < 27 % . METHODS A prospect i ve , r and omized , controlled trial was performed in nine hospitals in Italy . One hundred thirty-five high-risk patients scheduled for major abdominal surgery were r and omized in two groups . All patients were managed to achieve st and ard goals : mean arterial pressure > 80 mm Hg and urinary output > 0.5 mL/kg/h . The patients of the " protocol group " ( group A ) were also managed to keep O2ER < 27 % . MEASUREMENTS AND MAIN RESULTS In group A , fewer patients had at least one organ failure ( n = 8 , 11.8 % ) than in group B ( n = 20 , 29.8 % ) [ p < 0.05 ] , and the total number of organ failures was lower in group A than in group B ( 27 failures vs 9 failures , p < 0.001 ) . Length of hospital stay was significantly lower in the protocol group than in the control group ( 11.3 + /- 3.8 days vs 13.4 + /- 6.1 days , p < 0.05 ) . Hospital mortality was similar in both groups . CONCLUSIONS Early treatment directed to maintain O2ER at < 27 % reduces organ failures and hospital stay of high-risk surgical patients . Clinical trials.gov reference No. NCT00254150 BACKGROUND Intraoperative fluid therapy regimens using oesophageal Doppler monitoring ( ODM ) to optimize stroke volume ( SV ) ( goal -directed fluid therapy , GDT ) have been associated with a reduction in length of stay ( LOS ) and complication rates after major surgery . We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge ( RfD ) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients . METHODS In this double-blinded controlled trial , 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically ' fit ' ( n=123 ) or ' unfit ' ( n=56 ) on the basis of their performance during a cardiopulmonary exercise test . Within these fitness strata , patients were r and omized to receive a st and ard fluid regimen with or without ODM-guided intraoperative GDT . RESULTS GDT patients received an average of 1360 ml of additional intraoperative colloid . The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls . Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance ( median 6.8 vs 4.9 days , P=0.09 , and median 8.8 vs 6.7 days , P=0.09 , respectively ) . Fit GDT patients had an increased RfD ( median 7.0 vs 4.7 days ; P=0.01 ) and LOS ( median 8.8 vs 6.0 days ; P=0.01 ) compared with controls . CONCLUSIONS Intraoperative SV optimization conferred no additional benefit over st and ard fluid therapy . In an aerobically fit subgroup of patients , GDT was associated with detrimental effects on the primary outcome . TRIAL REGISTRY UK NIHR CRN 7285 , IS RCT N 14680495 . http://public.ukcrn.org.uk/ Search / Study Detail.aspx ? Study ID=7285 BACKGROUND : Dynamic variables predict fluid responsiveness and may improve fluid management during surgery . We investigated whether displaying the variability in the pulse oximeter plethysmogram ( pleth variability index ; PVI ) would guide intraoperative fluid management and improve circulation as assessed by lactate levels . METHODS : Eighty-two patients scheduled for major abdominal surgery were r and omized into 2 groups to compare intraoperative PVI-directed fluid management ( PVI group ) versus st and ard care ( control group ) . After the induction of general anesthesia , the PVI group received a 500-mL crystalloid bolus and a crystalloid infusion of 2 mL · kg−1 · h−1 . Colloids of 250 mL were administered if the PVI was > 13 % Vasoactive drug support was given to maintain the mean arterial blood pressure above 65 mm Hg . In the control group , an infusion of 500 mL of crystalloids was followed by fluid management on the basis of fluid challenges and their effects on mean arterial blood and central venous pressure . Perioperative lactate levels , hemodynamic data , and postoperative complications were recorded prospect ively . RESULTS : Intraoperative crystalloids and total volume infused were significantly lower in the goal -directed PVI group . Lactate levels were significantly lower in the PVI group during surgery and 48 hours after surgery ( P < 0.05 ) . CONCLUSIONS : PVI-based goal -directed fluid management reduced the volume of intraoperative fluid infused and reduced intraoperative and postoperative lactate levels Summary Oesophageal Doppler monitoring allows non‐invasive estimation of stroke volume and cardiac output . We studied the impact of Doppler guided fluid optimisation on haemodynamic parameters , peri‐operative morbidity and hospital stay in patients undergoing major bowel surgery . Fifty‐seven patients were r and omly assigned to Doppler ( D ) or control ( C ) groups . All patients received intra‐operative fluid therapy at the discretion of the non‐investigating anaesthetist . In addition , Group D were given fluid challenges ( 3 ml.kg−1 ) guided by oesophageal Doppler . Group D received significantly more intra‐operative colloid than Group C ( mean 28 ( SD 16 ) vs. 19.4 ( SD 14.7 ) ml.kg−1 , p = 0.02 ) . Cardiac output increased significantly for Group D whilst that of controls remained unchanged . The mean difference between the groups in final cardiac output was 0.87 l.min−1 ( 95 % confidence interval 0.31–1.43 l.min−1 , p = 0.003 ) . Five control patients required postoperative critical care admission . Fluid titration using oesophageal Doppler during bowel surgery can improve haemodynamic parameters and may reduce critical care admissions postoperatively A new quantitative method for measuring the prognosis and severity of illness in terms of probability of survival was developed from 224 studies in an index population of 220 critically ill surgical patients . Patients were selected preoperatively to eliminate pre-existing cardiac disease , cirrhosis , nutritional debility , shock or sepsis , in order to evaluate the physiologic relationships of surgical trauma to outcome free of confounding associated medical disorders . The empirically derived numeric severity index was calculated from the probability of survival for each of 28 hemodynamic and oxygen transport variables at each time period after surgery . The score correctly indicated patient outcome in 96 % of the index population and 94 % of an independent , prospect i ve population . The survivors ' score consistently predicted survival within 21.6 ± 4.4 ( SEM ) h after the end of surgery . The severity score of those who died consistently predicted nonsurvival within 37 ± 11 ( SEM ) h after the end of surgery . We conclude that the score provides a useful , objective , physiologic measure of the severity of illness and prognosis Intra‐operative oesophageal Doppler monitor‐guided fluid management has been associated with improved postoperative length of hospital stay and morbidity in gastrointestinal and orthopaedic surgery . We design ed a r and omised controlled trial to test the hypothesis that this approach to intra‐operative fluid management in major elective open gynaecological surgery would shorten the length of postoperative stay , defined as time to readiness for hospital discharge . Postoperative morbidity was evaluated as a secondary outcome . The oesophageal Doppler monitor group underwent intra‐operative fluid management using an oesophageal Doppler‐guided stroke volume optimisation algorithm . Control group ( conventional fluid therapy ) intra‐operative fluid management was based on conventional haemodynamic indices . In a single centre , 102 patients were r and omly assigned : 51 to the oesophageal Doppler monitor group ( 51 analysed ) and 51 to the control group ( 50 analysed ) . Evaluators who were blinded to patient assignment collected postoperative outcome data . There was no difference in the length of postoperative hospital stay between the groups : median ( IQR [ range ] ) number of days until ready for discharge was 6 ( 5–8 [ 4–25 ] ) days in the oesophageal Doppler monitor group compared with 7 ( 5–9 [ 4–42 ] ) days in the control group , p = 0.5 . There was no difference between the groups in postoperative morbidity survey scores on postoperative days 1 , 3 or 5 . Seven patients in the oesophageal Doppler monitor group and 11 in the control group experienced postoperative complications ( p = 0.41 ) . These findings question whether intra‐operative oesophageal Doppler‐guided fluid therapy is of benefit in patients undergoing open gynaecological surgery Abstract Objectives : To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture . Design : Prospect i ve , r and omised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period . Setting : Teaching hospital , London . Subjects : 40 patients undergoing repair of proximal femoral fracture under general anaesthesia . Interventions : Patients were r and omly assigned to receive either conventional intraoperative fluid management ( control patients ) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period ( protocol patients ) . Main outcome measures : Time declared medically fit for hospital discharge , duration of hospital stay ( in acute bed ; in acute plus long stay bed ) , mortality , perioperative haemodynamic changes . Results : Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume ( median 15 ml ( 95 % confidence interval 10 to 21 ml ) ) and cardiac output ( 1.2 l/min ( 0.1 to 2.3 l/min ) ) than in the conventionally managed group ( −5 ml ( −10 to 1 ml ) and −0.4 l/min ( −1.0 to 0.2 l/min ) ) ( P<0.001 and P<0.05 , respectively ) . One protocol patient and two control patients died in hospital . In the survivors , postoperative recovery was significantly faster in the protocol patients , with shorter times to being declared medically fit for discharge ( median 10 ( 9 to 15 ) days v 15 ( 11 to 40 ) days , P<0.05 ) and a 39 % reduction in hospital stay ( 12 ( 8 to 13 ) days v 20 ( 10 to 61 ) days , P<0.05 ) . Conclusions : Proximal femoral fracture repair constitutes surgery in a high risk population . Intraoperative intravascular volume loading to optimal stroke volume result ed in a more rapid postoperative recovery and a significantly reduced hospital stay . Key messages Patients undergoing hip fracture repair constitute a high risk group with considerable mortality and morbidity and an often protracted postoperative hospital stay These patients often have depleted intravascular volume in the perioperative period and rarely receive either invasive haemodynamic monitoring or high dependency care Haemodynamic optimisation guided by pulmonary artery catheter in the perioperative period has been shown to improve outcome in high risk patients undergoing major surgery , but this is not considered routinely practicable for hip fracture repair Intravascular volume optimisation directed by minimally invasive oesophageal Doppler monitoring in the intraoperative period significantly reduces hospital |
1,756 | 17,468,985 | Conclusions Operating room costs are greater for laparoscopic colorectal surgery than open surgery .
Total hospital costs are similar .
There may be societal benefits associated with lower indirect costs for laparoscopic colorectal surgery . | Purpose Recent studies have confirmed the clinical efficacy of laparoscopic colorectal surgery ; however , its use has not become widespread .
One reason for this is perceived economic implication s. A systematic review was undertaken examining the costs of laparoscopic colorectal surgery . | PURPOSE In carefully matched patients , the length of hospital stay after laparoscopic colectomy is shorter than after open surgery . Higher operating room costs for laparoscopic surgery are offset by lower costs for hospitalization because of less utilization of pharmacy , laboratory , and nursing services . Clinical outcome is comparable . We examined the effect of the surgical approach for colectomy ( open vs. laparoscopic ) regarding the reasons for disease-related group assignment to disease-related group 148 , and institutional cost under Part A of the U.S. Medicare system . METHODS Colectomy patients were assigned to either disease-related group 148 ( colorectal resection with complications ) or disease-related group 149 ( colorectal resection without complications ) with significant institutional reimbursement implication s ( disease-related group 149 , $ 8,310 ; disease-related group 148 , $ 20,291 ) . A total of 100 consecutive disease-related group 148 patients undergoing laparoscopic colectomy from July 2000 to September 2002 were identified from a prospect i ve data base and case-matched with 100 patients undergoing open colectomy . Patients were matched for gender , age , operative procedure , and pathology . A certified coder determined the reason(s ) for disease-related group 148 assignment , which were grouped into : preoperative comorbidity , a combination of preoperative comorbidity/postoperative complications , or postoperative complications alone . RESULTS Significantly more lapararoscopy patients were assigned to disease-related group 148 solely because of preoperative comorbidities ( 62 percent vs. 21 percent ; P < 0.0001 ) . Significantly more patients in the open surgery group were classified as disease-related group 148 solely because of postoperative complications ( 22 percent vs. 42 percent ; P < 0.0001 ) . An additional group of patients were assigned to the disease-related group 148 category based on a combination of preoperative and postoperative diagnoses ( 16 percent vs. 37 percent ) . The mean direct hospital costs were significantly less for laparoscopy patients ( $ 3971 vs. $ 5997 ; P = 0.0095 ) . Increased cost to Part A of Medicare for 20 open surgery patients who “ migrated ” to disease-related group 148 because of postoperative complications was $ 239,620 . CONCLUSIONS Our data are the first to demonstrate that disease related group assignment can change solely because of a differential rate of postoperative complications for two competing operative techniques . This change occurred at twice the rate for open colectomy and result ed in significantly increased cost to the insurer under a prospect i ve payment program . The savings to the institution coupled with the shortened length of stay offset the potential loss in revenue to the institution Abstract Background : The role and feasibility of laparoscopic assisted colectomy ( LAC ) in both benign and malignant disease of the colon are not clear . We have review ed our series in an effort to further delineate whether or not LAC is appropriate in the treatment of colonic disease . Methods : This is a retrospective view of a personal series focusing on feasibility , cure of malignant disease , and length of stay ( LOS ) . Results : One hundred and two LACs were completed out of 104 attempts ( 98 % ) . There were no wound or trocar implants in the Dukes A , B and C patients . Lymph node retrieval was similar in the laparoscopic and open historical controls . The LOS was 5.9 days in the LAC group as compared with 11 days in the open group . There was a 4.8 % major morbidity rate and a 1 % mortality rate in this series . Conclusions : LAC is technically feasible in a high percentage of patients . While a definite statement regarding its use in malignant disease can not be ascertained from this review , the preliminary results are encouraging . A r and omized trial comparing open and LAC is warranted Robotic laparoscopic surgery is postulated to result in better surgical results by allowing improved instrument manipulation and three-dimensional vision . The authors ’ experience performing robot-assisted laparoscopic colorectal surgery is reported . METHOD : St and ard laparoscopic procedures with robot-assisted laparoscopic colon mobilization and vascular ligation were performed . Data relating to the operative procedure , hospital stay , and direct costs were collected . Results were compared with age , gender , and procedure case-matched controls taken from a prospect i ve laparoscopic colorectal surgery data base . RESULTS : Six robot-assisted laparoscopic surgeries ( 2 right hemicolectomies , 3 sigmoid colectomies , and 1 Wells rectopexy ) were performed between December 2001 and June 2002 . There was no associated morbidity . Operative time was increased from a median time of 108 minutes for st and ard laparoscopic colorectal surgery to 165 minutes for robot-assisted laparoscopic surgeries ( P = 0.0313 ; Wilcoxon matched-pairs signed-rank test for non-parametric data ) . This was primarily a result of the time required for robot set-up . Blood loss , length of stay , and hospital cost were not significantly different between groups . Additional direct equipment costs for RAC cases included robotic laparoscopic instruments and sterile drapes ( approximately US $ 350 per case ) , without including acquisition and maintenance costs for the robot . CONCLUSION : Robot-assisted laparoscopic colectomy is a feasible and safe procedure . Although three-dimensional vision and dexterity are facilitated , operative time is increased and the overall additional expense of robotics is of concern . Robot-assisted laparoscopic colectomy requires further evaluation to establish clinical and financial benefits before introduction to routine practice . Such techniques may , in the future , facilitate complex laparoscopic techniques BACKGROUND Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and r and omly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P<0.001 ) and briefer use of parenteral narcotics ( three days vs. four days , P<0.001 ) and oral analgesics ( one day vs. two days , P=0.02 ) . The rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer BACKGROUND The appropriateness of laparoscopic colon resection ( LCR ) as treatment for malignancy has been question ed . METHODS From 1992 to 1997 , 91 patients were entered into a prospect i ve study of LCR for cancer . Clinical , pathologic , and economic parameters of LCR were compared in a cohort of patients matched for age , tumor stage , and type of colectomy who underwent open colon resection ( OCR ) during the same time period . RESULTS With a median follow-up of 26 months , there were no significant differences in survival rate for patients in the LCR , converted colon resection , and OCR groups . There were no port-site recurrences and the number of lymph nodes harvested was similar among the procedures . Hospital stay was significantly shorter if laparoscopic resection was successful . Total hospital costs were similar for LCR and OCR ; however , the costs were significantly higher for converted colon resection . CONCLUSIONS LCR is a sound oncologic procedure that can be performed with costs similar to OCR Objective The authors studied the results of laparoscopic colectomies performed by a surgical team on 80 consecutive patients and compared these results with st and ard open colectomies . Methods Eighty consecutive laparoscopic-assisted colectomies were performed by Norfolk Surgical Group in a 14-month period and compared to 53 patients who had a conventional open colectomies . Analysis included indications for surgery , types of procedure , complications , incidence and causes for conversion , length of procedure , duration of postoperative ileus , hospital stay , operating room and total hospital charges , and examination of the pathologic specimens . Results Many different types of colectomies were performed successfully and safely for a variety of surgical indications . The conversion rate was 22.5 % , which decreased to 15 % in the second half of the series . Complications in patients who underwent laparoscopic operations were not severe in number or type . The length of the operative procedure , operating room charge , and the total hospital charge were greater for patients undergoing laparoscopic-assisted colectomies . Patients who underwent laparoscopic operations had a shorter period of postoperative ileus and less pain , resumed a regular diet sooner , and were discharged from the hospital sooner than patients who underwent open colectomies . There was no significant difference in the pathology specimens obtained by laparoscopic-assisted colectomies compared with conventional open colectomies for length of specimen , surgical margins , and number of lymph nodes retrieved . Conclusions This study indicated that laparoscopic techniques can be applied safely and effectively to a broad range of colonic operations . Laparoscopic-assisted colectomies take longer to perform and are more costly , but are associated with less paralytic ileus , less pain , and reduced hospital stay . Laparoscopic colectomies for the treatment of malignancy are achievable technically , but will require careful long-term study 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 The objectives of this study were to compare both subjective clinical outcomes and the objective stress response of laparoscopic and open abdominal rectopexy in patients with full‐thickness rectal prolapse . Abdominal rectopexy for patients with rectal prolapse is well suited for a laparoscopic approach as no resection or anastomosis is necessary PURPOSE : This study was undertaken to compare morbidity , mortality , and pathology after laparoscopically assisted right hemicolectomy ( LARHC ) or open right hemicolectomy ( ORHC ) for cancer of the right colon . METHODS : Patients undergoing either LARHC or ORHC for invasive carcinoma of the right colon during a 30-month period were studied . Data were collected from two sources . All morbidity , mortality , and pathology data were collected prospect ively in a form suitable for computer storage and analysis as part of the ongoing Concord Hospital Colorectal Cancer Registry . Data concerning in hospital course were obtained by casenote review . RESULTS : Twenty-eight patients underwent LARHC , and 33 had an ORHC during the study period . The two groups were well matched with respect to age , sex , weight , associated comorbidities , and tumor stage . Mean operating room use time was significantly higher for LARHC ( LARHC=261 minutes ; ORHC=203 minutes;P<0.001 ) . Mean hospital stay from date of resection was the same in both groups ( LARHC=12 days ; ORHC=12.2 days ) . There was no significant difference between procedures with respect to postoperative complications , return of gastrointestinal function , or narcotic analgesic requirements . There was a significant shorter distal margin of resection in the LARHC group ( ORHC=13.4 cm ; LARHC=10 cm;P=0.03 . ) . Total cost was significantly greater for LARHC ( $ 9,064vs.$7,881 (Australian);P<0.001 ) . Median follow-up was 23.4 months for the LARHC group and 23.9 months for the ORHC group . To date , there have been no local or port site recurrences . CONCLUSION : Although there is no difference in morbidity and mortality following LARHC or ORHC , there is no apparent benefit for LARHC Abstract This study evaluated outcome in patients undergoing laparoscopically assisted sigmoid resection for diverticular disease . A total of 29 consecutive patients were treated surgically for colonic diverticulitis ; in 27 of these laparoscopy was performed . The review of medical records from a control group of 34 patients undergoing open resection were used for comparison . The conversion rate was 7.5 % . Using the laparoscopic technique the duration of surgery was longer ( 165 vs. 121 min , P<0.05 ) , blood loss less ( 182 vs. 352 ml , P<0.05 ) , and subsequent blood transfusion less ( 0 vs. 61 % ) . The incidence of complications following laparoscopic resection was lower ( two anastomotic leakages , two wound infections ) than in the conventional group . Convalescence in the laparoscopic group was more rapid and hospital stay shorter ( 7.9 vs. 14.3 days , P<0.05 ) . In the laparoscopic group patients expressed less pain at rest and in motion . The cost of the laparoscopically assisted procedure was less than that of conventional resection ( 7185 vs. 8975 DM ) . In this series laparoscopically assisted sigmoid resection for diverticulitis proved safe . Recovery was faster , hospital stay was shorter , and patients expressed less pain than in conventional open surgery . Résumé Le but de cette étude est d'évaluer le devenir des patients ayant subi une sigmoïdectomie laparoscopique pour maladie diverticulaire . Vingt-neuf patients consécutifs ont été traités chirurgicalement pour une diverticulite colique . Vingt-sept des cas ont pu être opérés par laparoscopie , L'étude des dossiers cliniques d'un groupe-contrôle de 34 patients subissant une résection ouverte a servi de comparaison . Le taux de conversion est de 7,5 % . Par laparoscopie , la durée de l'intervention chirurgicale a été plus longue ( 165 vs 121 minutes , P<0,05 ) , les pertes sanguines ( 182 vs 352 ml , P<0,05 ) et les transfusions sanguines moindres ( 0 vs 16 % ) . L'incidence des complications suivant la laparoscopie a été inférieure ( 2 fuites anastomotiques , 2 infections de plaie ) en comparaison à la chirurgie conventionnelle . La convalescence du groupe laparoscopique a été plus rapide et la durée d'hospitalisation réduite ( 7,9 vs 14,3 jours , P<0,05 ) . Dans le groupe laparascopique , les douleurs au repos et aux mouvements ont été inférieures . Let coût du geste chirurgical laparoscopique a été inférieur en comparaison à la résection conventionelle ( 7185 vs 8975 DM ) . Dans cette série , la résection sigmoïdienne par laparoscopie pour maladie diverticulaire est sûre et plus rapide , la durée de guérison est plus rapide , la durée d'hospitalisation plus brève et les patients ont présenté moins de douleurs dans le groupe laparoscopique en comparaison avec la chirurgie conventionelle BACKGROUND H and -assisted laparoscopic surgery ( HALS ) represents a useful alternative to conventional laparoscopic surgery ( LS ) . Its potential advantages--(a quicker , safer procedure and less need to convert to open surgery ) are due to the recovery of tactile feedback . However , HALS requires the performance of a mini-laparotomy when surgery commences , and the wound is stretched and compressed throughout the procedure . In addition , it is associated with a more intense manipulation of the intraabdominal viscera . All of these factors increase the surgical trauma , it is not known whether HALS maintains the minimally invasive characteristics of conventional LS . Therefore , we set out to study the applicability , immediate clinical outcome , inflammatory response , and cost of HALS compared with conventional LS using colectomy as a model . METHODS We performed a prospect i ve r and omized trial comparing laparoscopic-assisted colectomy with HAL colectomy . The aims of the study were to assess ( a ) perioperative features , including time , advantages , and conversion ; ( b ) the patient 's immediate clinical response , including recovery of bowel sounds , refeeding time , postoperative pain , local and general morbidity , and hospital stay ; ( c ) the effect on the inflammatory response , using interleukin-6 ( ILG ) and C-reactive protein ( CRP ) measurements ; ( d ) oncological issues , including intraoperative cytology and features of the specimen ; and ( d ) the relative costs of the two procedures . RESULTS A total of 54 patients were enrolled in the study , 27 laparoscopic and 27 HALS . The operative times were similar , but HALS was associated with a far lower conversion rate--7 % vs 23 % . Immediate clinical outcomes , oncological features , and costs were similar for the two procedures , but HALS was associated with a significantly greater increase in IL6 and CRP than the conventional laparoscopic procedure . CONCLUSION This comparative study shows that HALS simplifies difficult intraoperative situations , reducing the need for conversion . Although it is a more aggressive procedure , HALS preserves the features of a minimally invasive approach , maintains all of the oncological features of conventional laparoscopic surgery , and does not increase the cost . HALS should therefore be considered as a useful adjunct when difficult situations arise during conventional laparoscopic colectomy BACKGROUND Although laparoscopic resection of colorectal carcinoma improves post-operative recovery , long-term survival and disease control are the determining factors for its application . We aim ed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer . METHODS From Sept 21 , 1993 , to Oct 21 , 2002 , 403 patients with rectosigmoid carcinoma were r and omised to receive either laparoscopic assisted ( n=203 ) or conventional open ( n=200 ) resection of the tumour . Survival and disease-free interval were the main endpoints . Patients were last followed-up in March , 2003 . Perioperative data were recorded and direct cost of operation estimated . Data were analysed by intention to treat . FINDINGS The demographic data of the two groups were similar . After curative resection , the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1 % ( SE 3.7 % ) and 72.9 % ( 4.0 % ) respectively . The probabilities of being disease free at 5 years were 75.3 % ( 3.7 % ) and 78.3 % ( 3.7 % ) , respectively . The operative time of the laparoscopic group was significantly longer , whereas postoperative recovery was significantly better than for the open resection group , but these benefits were at the expense of higher direct cost . The distal margin , the number of lymph nodes found in the resected specimen , overall morbidity and operative mortality did not differ between groups . INTERPRETATION Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients . The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes The introduction of new laparoscopic techniques has important cost implication s. The aim of this study was to compare the cost effectiveness of laparoscopic rectopexy with that of open abdominal rectopexy for full‐thickness rectal prolapse Background Open total colectomy and ileorectal anastomosis ( OTC ) is a major colorectal procedure which would preclude laparoscopy in many centers because of technical difficulty and the fact that laparoscopic total colectomy ( LTC ) takes much longer than st and ard laparoscopic proctosigmoidectomy ( LPS ) . This study compares OTC with LTC and LPS . Methods In this study , 34 LTC patients ( May 1999 to August 2003 ) were matched for age , diagnosis , operative period , and procedure with patients undergoing OTC . Patients with a previous major laparotomy were excluded from the open group . Groups were compared for gender , American Society of Anesthesiology ( ASA ) classification , operating time , estimated blood loss , length of hospital stay ( LOS ) , complications including readmissions , and costs . The LPS cases were picked r and omly from the laparoscopic data base ( every eighth patient ) , and the OT and LOS were noted . Results The LTC and OTC groups were matched for age ( mean , 31 vs 34 years ; p = 0.2 ) , sex ( 14 vs 13 females ; p = 0.8 ) , ASA ( 8/23/3/0 vs 8/22/4/0 , class 1/2/3/4 ) . The body mass index was higher in the open group ( 23.8 vs 27.9 ; p = 0.04 ) . The operating time was significantly longer ( 187 vs 126 min ; p = 0.0001 ) and the median LOS shorter in the LTC group ( 3 days [ IQR , 2.5 - 5 days ] vs 6 days [ IQR 4 - 8 days ] ; p = 0.0001 ) . The estimated blood loss was significantly less in the LTC group ( 168 [ 50 - 700 ] ml ) vs 238 [ 50 - 800 ] ml ) ; p = 0.001 , but there was no significant difference in the complication ( 26.5 % vs 38.2 % ; p = 0.4 ) readmission ( 11.8 % vs 14.7 % ; p = 1.0 ) , reoperative rates ( 8.8 % vs 11.8 % ; p = 1.0 ) , or direct costs ( $ 4,578 vs $ 4,562 ; p = 0.3 ) . One LTC patient died expired on postoperative day 2 of a cardiac event . Four patients ( 11.8 % ) required conversion for obesity ( n = 2 ) , adhesions ( n = 1 ) , or intraoperative hemorrhage ( n = 1 ) . The operating times were 36 min longer in the LTC group than in the LPS group ( 151 vs 187 min ; p = 0.02 ) , but there was no significant difference in the LOS . ( 3 vs 3 days , p = 0.2 ) . Conclusions The findings show that LTC provides a significant decrease in the LOS over OTC , with increased operating time , but without any change in other parameters . A laparoscopic approach to subtotal colectomy is recommended for suitable patients when an experienced team is available Objective Comparison of outcome and costs after laparoscopic and open colectomy . Summary Background Data Previous studies comparing laparoscopic and open colectomy report conflicting results with regard to clinical outcome and costs . Methods Laparoscopic colectomy patients from a prospect i ve data base were matched for age , gender , and disease-related grouping to patients who underwent the same operation by the open approach over the same period ( 2000 to 2001 ) . Data for the latter group was gathered by retrospective analysis and the 2 groups were compared for outcome and direct costs . Results Laparoscopic colectomy patients ( n = 150 ) were compared with the same number of open colectomy patients . American Society of Anesthesiologists classification ( P = 0.09 ) , body mass index ( P = 0.17 ) , diagnosis ( P = 0.12 ) , complications ( P = 0.14 ) , and rate of readmission within 30 days ( P = 0.44 ) were similar for both groups . Operating room costs were significantly higher after laparoscopic colectomy ( P < 0.0001 ) , but length of hospital stay was significantly lower ( P < 0.0001 ) . This result ed in significantly lower total costs ( P = 0.0007 ) owing to lower pharmacy ( P < 0.0001 ) , laboratory ( P < 0.0001 ) , and ward nursing costs ( P = 0.0004 ) . Conclusions Laparoscopic colectomy results in significantly lower direct costs compared with open colectomy for carefully matched patients PURPOSE The benefits of early postoperative recovery , reduced postoperative pain , pulmonary dysfunction , and hospitalization after laparoscopic colectomy may improve outcome over open colectomy in obese patients . This case-matched study compares outcomes after open and laparoscopic colectomy . METHODS A total of 94 laparoscopic colectomy patients with a body mass index > 30 ( Jan 1999–June 2003 ) were identified from a prospect i ve data base and matched to open colectomy cases for age , gender , body mass index , American Society of Anesthesiologists class , procedure , indication , and date of surgery . Operating time , length of stay , conversion , intraoperative and postoperative complications , reoperation , 30-day readmission rate , and costs were compared . Data are presented as means ± st and ard deviations , and appropriate statistical tests were used . RESULTS The two groups were matched for age ( P = 0.06 ) , gender ( P = 1 ) , American Society of Anesthesiologists class ( P = 0.2 ) , body mass index ( P = 0.4 ) , indication for surgery ( P = 1 ) , and procedure ( P = 1 ) . By using intention-to-treat – type analysis , there was no difference in median operating time ( 100 vs. 110 ( mean , 123 vs. 112 ) minutes ; P = 0.1 ) , complications ( 21 vs. 24 percent ; P = 0.74 ) , readmission ( 17 vs. 10.6 percent ; P = 0.3 ) , reoperation rates ( 6.4 vs. 4.3 percent ; P = 0.75 ) , or direct costs ( median , $ 3,368 vs. $ 3,552 ; mean , $ 4,003 vs. $ 4,037 ; P = 0.14 ) between laparoscopic colectomy or open colectomy ; however , the median length of stay ( 3 vs. 5.5 ( mean , 3.8 vs. 5.8 ) days ; P = 0.0001 ) was significantly shorter after laparoscopic colectomy . Twenty-eight patients required conversion for adhesions ( n = 11 ) , bleeding ( n = 3 ) , obesity-hindering vision or dissection ( n = 9 ) , large phlegmon or tumor ( n = 4 ) , and ureteric injury ( n = 1 ) . The mean operating time for conversions was 142 minutes and length of stay was 6.4 days . Compared with laparoscopically completed cases , the median length of stay ( 5 vs. 2 ( mean , 6.4 vs. 2.8 ) days ; P = 0.0001 ) and median operating times ( 150 vs. 95 ( mean , 142 vs. 115 ) minutes ; P = 0.02 ) were significantly higher in the converted group , but there was no difference in the complication ( P = 0.8 ) , readmission ( P = 1 ) , or reoperation ( P = 0.7 ) rates . Compared with open colectomy , the operating time ( P = 0.02 ) was significantly higher in the converted group but there were no significant differences in the length of stay ( P = 0.18 ) , complication ( P = 1 ) , readmission ( P = 0.35 ) , or reoperative ( P = 1 ) rates . CONCLUSIONS Laparoscopic colectomy can be performed safely in obese patients , with shorter postoperative recovery than that with open colectomy . Although obesity is associated with a high conversion rate , outcome in these converted cases is comparable to the matched open cases Objective : The aim of the study was to evaluate postoperative recovery after h and -assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a r and omized controlled trial . Methods : Sixty patients were r and omized for h and -assisted laparoscopic ( n = 30 ) or open surgery ( n = 30 ) . Primary outcome parameter was postoperative recovery in the 3 months after surgery , measured by quality of life question naires ( SF-36 and GIQLI ) . Secondary parameters were postoperative morphine requirement and surgical parameters , viz . operating time , morbidity , hospital stay , and costs . Results : There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery . There was a significant decline in quality of life on all scales of the SF-36 ( P < 0.001 ) and total GIQLI score ( P < 0.001 ) in the first 2 weeks in both groups ( no significant difference between the groups ) . Quality of life returned to baseline levels after 4 weeks . Operating times were longer in the laparoscopic group compared with the open group ( 210 and 133 minutes , respectively ; P < 0.001 ) . No significant differences were found in morphine requirement . Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group ( 20 % versus 17 % , in 10 versus 11 days , respectively ) . Median overall costs were & U20AC ; 16.728 for the h and -assisted laparoscopic procedure and & U20AC ; 13.406 for the open procedure ( P = 0.095 ) . Conclusions : Recovery measured using quality of life question naires is comparable for h and -assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis . The laparoscopic approach is as safe , but more costly than the open procedure HYPOTHESIS Laparoscopic ileocolectomy can reduce the length of hospital stay and hospital charges compared with conventional surgery in the treatment of primary Crohn disease . DESIGN Nonr and omized , comparative , retrospective analysis of a prospect i ve data base . SETTING University hospital tertiary care center for inflammatory bowel disease . PATIENTS Forty patients , 20 in the laparoscopic group ( group A ) and 20 in the conventional group ( group B ) . INTERVENTION From July 1 , 1996 , to June 30 , 2001 , we collected data on the following demographic clinical end points : age , sex , duration of disease , preoperative medical treatment , previous abdominal surgery , procedure performed , conversions to open surgery , operating time , number of trocars used , size of incision , blood loss , time to resolution of ileus , time to starting solid food diet , duration of hospital stay , hospital charges , morbidity , and mortality . MAIN OUTCOME MEASURES Surgical results , length of hospital stay , hospital charges , and recurrences . RESULTS The mean age of the patients was 34.7 years ( range , 20 - 68 years ) in group A vs 40.0 years ( range , 18 - 75 years ) in group B. The male-female ratio was 1:2 in group A vs 1:1 in group B. The morbidity was 5 % in group B. There was no mortality . Operating time was longer in group A ( mean , 145.0 minutes ; range , 45 - 270 minutes ) compared with group B ( mean , 133.5 minutes ; range , 98 - 177 minutes ) ( P = .36 ) . Blood loss was significantly higher in group B ( mean , 265.5 mL ; range , 100 - 400 mL ) compared with group A ( 77.2 mL ; range , 25 - 350 mL ) ( P<.001 ) . Also , the size of the incision was significantly longer in group B ( mean , 13.5 cm ; range , 8 - 18 cm ) compared with group A ( mean , 5.5 cm ; range , 3 - 12 cm ) ( P<.001 ) . Bowel function returned more quickly in the laparoscopic group vs the conventional group in terms of return of bowel movements ( 1.70 vs 2.63 days ) ( P<.001 ) and resumption of a regular diet ( 1.35 vs 2.73 days ) ( P<.001 ) . The mean length of stay was significantly shorter in the laparoscopic group ( 4.25 days ) vs the conventional group ( 8.25 days ) ( P<.001 ) . The mean hospital charges were US $ 9614 in group A vs US $ 17 079 in group B ( P<.05 ) . The mean follow-up was 17.2 months in group A ( range , 2.3 - 59.9 months ) vs 18.7 months in group B ( range , 1.0 - 37.5 months ) . CONCLUSIONS Laparoscopic-assisted ileocolectomy for primary Crohn disease of the terminal ileum and /or cecum is safe and successful in most cases . Laparoscopic surgery for Crohn disease should be considered as the preferred operative approach for primary resections Abstract Objectives To assess the extent and pattern of implementation of guidance issued by the National Institute for Clinical Excellence ( NICE ) . Design Interrupted time series analysis , review of case notes , survey , and interviews . Setting Acute and primary care trusts in Engl and and Wales . Participants All primary care prescribing , hospital pharmacies ; a r and om sample of 20 acute trusts , 17 mental health trusts , and 21 primary care trusts ; and senior clinicians and managers from five acute trusts . Main outcome measures Rates of prescribing and use of procedures and medical devices relative to evidence based guidance . Results 6308 usable patient audit forms were returned . Implementation of NICE guidance varied by trust and by topic . Prescribing of some taxanes for cancer ( P < 0.002 ) and orlistat for obesity ( P < 0.001 ) significantly increased in line with guidance . Prescribing of drugs for Alzheimer 's disease and prophylactic extraction of wisdom teeth showed trends consistent with , but not obviously a consequence of , the guidance . Prescribing practice often did not accord with the details of the guidance . No change was apparent in the use of hearing aids , hip prostheses , implantable cardioverter defibrillators , laparoscopic hernia repair , and laparoscopic colorectal cancer surgery after NICE guidance had been issued . Conclusions Implementation of NICE guidance has been variable . Guidance seems more likely to be adopted when there is strong professional support , a stable and convincing evidence base , and no increased or unfunded costs , in organisations that have established good systems for tracking guidance implementation and where the professionals involved are not isolated . Guidance needs to be clear and reflect the clinical context The aim of this study was to estimate and compare the costs of open right hemicolectomy ( ORHC ) versus laparoscopically assisted right hemicolectomy ( LARHC ) performed for cancer . A retrospective cost analysis of 61 consecutive patients operated on between January 1992 and August 1994 for right-sided colonic cancer by either LARHC ( n = 28 ) or ORHC ( n = 33 ) was performed . The analysis focused on the cost ( in Australian dollars ) incurred from the date of operation to the date of discharge . LARHC was significantly more expensive than ORHC ( total cost LARHC $ 9064 , ORHC $ 7881 ; p < 0.001 ) . LARHC was associated with a significantly longer operating room utilization time ( LARHC 261 minutes , ORHC 203 minutes ; p < 0.001 ) and a greater cost of disposables ( LARHC $ 854 , ORHC $ 189 ; p < 0.001 ) . This study demonstrates no cost benefit for LARHC compared to ORHC when performed for cancer . RésuméLe but de cette étude a été d’évaluer et de comparer les coûts de la colectomie droite effectuée par laparoscopie de celle réaliséc de façon traditionnelle . On a ainsi étudié une série de 61 patients consécutifs opérés entre Janvier 1992 et Août 1994 pour un cancer du colon droit soit par laparoscopie assistée ( LARHC , n = 28 ) soit de façon traditionnelle ( ORHC , n = 33 ) . L’analyse était centrée sur les coûts ( en dollars australiens [ $ Au ] ) à partir de la date de l’opération jusqu’à la date de la sortie . Les coûts de la LARHC étaient significativement plus élevés que ceux de l’ORHC ( coûts totaux de la LARHC = 9064 $ Au vs ORHC = 7881 $ Au ; p < 0.01 ) . La durée de l’intervention était significativement plus longue ( LARHC : 261 minutes vs ORHC : 203 minutes ; p < 0.001 ) et on a utilisé significativement plus d’instruments à usage unique avec une différence de coûts de 854 $ Au vs 189 $ Au , p < 0.001 ) . Cette étude démontre que la colectomie sous laparoscopie pour cancer colique ne présente aucun avantage économique par rapport à la colectomie classique . ResumenEl propósito del presente estudio fue el de estimar y comparar los costos de la hemicolectomía derecha abierta versus la operación asistida por laparoscopia en pacientes con cáncer . Se hizo un análisis retrospectivo de 61 paciente consecutivos operados entre enero de 1992 y agosto de 1994 por cáncer del colon derecho : hemicolectomía derecha asistida por laparoscopia ( HCDAL , n = 28 ) o hemicolectomía derecha abierta ( HCDA , n = 33 ) . El análisis se enfocó hacia e costo ( en $ AU ) causados desde la fecha de la operación hasta la fecha del egreso . La HCDAL result ó significativamente más costosa que la HCDA ( costo total de la HCDAL $ 9064 , HCDA $ 7881 ; p < 0.001 ) . La HCDAL se asoció con un tiempo más prolongado en la sala de operaciones ( HCDAL 261 minutos , HCDA 203 minutos ; p < 0.001 ) y un mayor costo de los elementos desechables ( HCDAL $ 854 , HCDA $ 189 ; p < 0.001 ) . El estudio demuestra que no hay beneficio en cuanto a costo para la HCDAL en comparación con la HCDA , realizadas por cáncer Objective The primary endpoint was to compare the impact of laparoscopic and open colorectal surgery on 30-day postoperative morbidity . Lymphocyte proliferation to mitogens and gut oxygen tension were surrogate endpoints . Summary Background Data Evidence -based proof of the effect of laparoscopic colorectal surgery on immunometabolic response and clinical ly relevant outcome variables is scanty . Further r and omized trials are desirable before proposing laparoscopy as a superior technique . Methods Two hundred sixty-nine patients with colorectal disease were r and omly assigned to laparoscopic ( n = 136 ) or open ( n = 133 ) colorectal resection . Four trained members of the surgical staff who were not involved in the study registered postoperative complications . Lymphocyte proliferation to C and ida albicans and phytohemagglutinin was evaluated before and 3 and 15 days after surgery . Operative gut oxygen tension was monitored continuously by a polarographic microprobe . Results In the laparoscopic group the conversion rate was 5.1 % . The overall morbidity rate was 20.6 % in the laparoscopic group and 38.3 % in the open group . Postoperative infections occurred in 15 of the 136 patients in the laparoscopic group and 31 of the 133 patients in the open group . The mean length of hospital stay was 10.4 ± 2.9 days in the laparoscopic group and 12.5 ± 4.1 days in the open group . On postoperative day 3 , lymphocyte proliferation was impaired in both groups . Fifteen days after surgery , the proliferation index returned to baseline values only in the laparoscopic group . Intraoperative gut oxygen tension was higher in the laparoscopic than in the open group . Conclusions Laparoscopic colorectal surgery result ed in a significant reduction of 30-day postoperative morbidity . Lymphocyte proliferation and gut oxygen tension were better preserved in the laparoscopic group than in the open group There has been no r and omized clinical trial of the costs of laparoscopic colonic resection ( LCR ) compared with those of open colonic resection ( OCR ) in the treatment of colonic cancer 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 |
1,757 | 26,740,336 | Our meta- analysis indicates that RASIs plus CCBs provide a superior safety and prevention of CV events to RASIs plus diuretics , whereas this combination is also safer than CCBs plus diuretics . | Many r and omized clinical trials ( RCTs ) have investigated the efficacy and safety of renin – angiotensin system inhibitors ( RASIs ) plus calcium channel blockers ( CCBs ) , compared with other two-drug combinations , but systematic assessment in this aspect is still lacking .
We carried out the present meta- analysis of r and omized controlled trials to evaluate the long-term effect and safety of RASIs plus CCBs . | The Chinese Hypertension Intervention Efficacy Study ( CHIEF ) is a multi-centre r and omized controlled clinical trial comparing the effects of amlodipine+angiotensin II receptor blocker and amlodipine+diuretics on the incidence of cardiovascular events , represented as a composite of non-fatal stroke , non-fatal myocardial infa rct ion and cardiovascular death events in high-risk Chinese hypertensive patients . The study also evaluates the long-term effects of lipid-lowering treatment and lifestyle modification . From October 2007 to October 2008 , 13 542 patients were enrolled into the study in 180 centres in China . Patients will be followed up for 4 years . There was no difference in baseline characteristics between the two blood pressure arms Many patients with hypertension require ≥3 agents to achieve target blood pressure ( BP ) . The efficacy/safety of the dual combinations of valsartan (Val)/hydrochlorothiazide ( HCTZ ) and amlodipine (Aml)/Val in hypertension are well established . This r and omized , double-blind study evaluated the efficacy/safety of triple therapy with Aml/Val/HCTZ for moderate or severe hypertension ( mean sitting systolic BP : ≥145 mm Hg ; mean sitting diastolic BP : ≥100 mm Hg ) . The study included a single-blind , placebo run-in period , followed by double-blind treatment for 8 weeks ; patients were r and omly assigned to 1 of 4 groups titrated to Aml/Val/HCTZ 10/320/25 mg , Val/HCTZ 320/25 mg , Aml/Val 10/320 mg , or Aml/HCTZ 10/25 mg once daily . Dual-therapy recipients received half of the target doses of both agents for the first 2 weeks , titrating to target doses during week 3 . Those on triple therapy received Val/HCTZ 160.0/12.5 mg during week 1 , Aml/Val/HCTZ 5.0/160.0/12.5 mg during week 2 , and target doses of all 3 of the agents during week 3 . Of the 4285 patients enrolled , 2271 were r and omly assigned to treatment , and 2060 completed the study . Triple therapy was significantly superior to all of the dual therapies in reducing mean sitting systolic BP and mean sitting diastolic BP from baseline to end point ( all P<0.0001 ) . Significantly more patients on triple therapy achieved overall BP control ( < 140/90 mm Hg ; P<0.0001 ) and systolic and diastolic control ( P≤0.0002 ) compared with each dual therapy . Aml/Val/HCTZ was well tolerated . The benefits of triple therapy over dual therapy were observed regardless of age , sex , race , ethnicity , or baseline mean sitting systolic BP . In conclusion , this study demonstrates the efficacy/safety of treating moderate and severe hypertension with Aml/Val/HCTZ 10/320/25 mg The purpose of this study was to compare the combination treatments of manidipine/delapril and olmesartan/hydrochlorothiazide ( HCTZ ) in elderly diabetic hypertensives . After a 4-week placebo period , 158 hypertensive patients with type 2 diabetes ( age range : 66 to 74 years ) were r and omized to receive combination treatment of 10 mg manidipine plus 30 mg delapril or 20 mg olmesartan plus 12.5 mg HCTZ for 48 weeks in a prospect i ve , parallel arm trial . After 12 weeks , manidipine or HCTZ was doubled in nonresponders ( systolic blood pressure [ SBP ] ≥130 mmHg and /or diastolic blood pressure [ DBP ] ≥80 mmHg ) . Patients were checked at the end of the placebo period and every 12 weeks thereafter . At each visit , lying , sitting and st and ing BP as well as fasting glycemia , glycosylated hemoglobin ( HbA1c ) , electrolytes , uric acid , total cholesterol ( TC ) , high-density lipoprotein-cholesterol ( HDL-C ) and triglycerides ( TG ) were evaluated . Both combinations reduced sitting SBP ( −27.7 and −28.3 mmHg , respectively ; both p<0.001 ) and DBP ( −15.1 and −14.8 mmHg , respectively ; both p<0.01 ) with no difference between the two treatments . St and ing DBP was more markedly reduced by olmesartan/HCTZ ( −19.5 mmHg ; p<0.001 ) than by manidipine/delapril ( −14.7 mmHg ; p<0.05 vs. olmesartan/HCTZ ) . No changes in metabolic parameters were observed with manidipine/delapril , whereas an increase in HbA1c ( + 0.7 % ; p<0.05 ) , uric acid ( + 0.4 mg/dL ; p<0.05 ) and TG ( + 41.3 mg/dL ; p<0.05 ) , and a decrease in serum potassium ( −0.3 mmol/L ; p<0.05 ) and HDL-C ( −3.4 mg/dL ; p<0.05 ) were found in the olmesartan/HCTZ group . In conclusion , both combinations were similarly effective in reducing BP in elderly hypertensive diabetic patients . However , manidipine/delapril offered some advantages in terms of the less-pronounced BP orthostatic changes and absence of metabolic adverse effects . ( Hypertens Res 2008 ; 31 : 43−50 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 The & bgr;-blocker atenolol is less effective than angiotensin-receptor blockers and calcium-channel blockers for reducing central blood pressure ( BP ) . The trial was design ed to determine whether the advantages of angiotensin-receptor blockers over atenolol remained significant when both were combined with the calcium-channel blocker amlodipine . A prospect i ve , r and omized , blinded endpoint ( PROBE design ) parallel group , multicenter trial including 393 patients with essential hypertension resistant to 4 weeks of 5 mg of amlodipine was set out . Central systolic BP , augmentation index ( AIx ; either rough or adjusted on heart rate ) , and carotid-to-femoral pulse wave velocity were measured with applanation tonometry ( SphygmoCor ) at inclusion and after 8 and 24 weeks of active treatment with an amlodipine-valsartan combination ( 5/80 mg and then 10/160 mg ) or an amlodipine-atenolol combination ( 5/50 mg and then 10/100 mg ) . From baseline to week 24 , central systolic BP decreased significantly more in the amlodipine-valsartan group ( −13.70±1.15 mm Hg ; P<0.0001 ) than in the amlodipine-atenolol group ( −9.70±1.10 mm Hg ; P<0.0001 ; difference : −4.00 mm Hg [ 95 % CI : −7.10 to −0.90 ] ; P=0.013 ) , despite similar changes in brachial systolic BP . The difference in rough AIx reduction was −6.5 % ( 95 % CI : −8.3 to −4.7 ; P<0.0001 ) in favor of amlodipine-valsartan . AIx adjusted on heart rate was significantly reduced in favor of amlodipine-valsartan ( −2.8 % [ 95 % CI : −4.92 to −0.68 ] ; P<0.01 ) . Heart rate decreased significantly more with amlodipine-atenolol ( difference : −11 bpm [ 95 % CI : −14 to −8 bpm ] ; P<0.001 ) . Pulse wave velocity decreased by 0.95 m/s in both groups with no significant difference . Differences in central systolic BP and rough AIx remained significant after adjustment to the changes in heart rate . The amlodipine-valsartan combination decreased central ( systolic and pulse ) pressure and AIx more than the amlodipine-atenolol combination Angiotensin receptor blockers ( ARBs ) with calcium channel blockers ( CCBs ) or diuretics are a widely used combination therapy for hypertensive patients . The present study aim ed to determine which combination was better for elderly hypertension patients aged ≧ 65 years . We design ed a multicentre , r and omized , open-label , parallel comparison study . Hypertensive out patients aged ≧ 65 years who did not achieve the target blood pressure ( BP < 140/90 mmHg ) with usual dosages of ARBs were r and omly assigned to switch treatment to losartan 50 mg/hydrochlorothiazide 12.5 mg or amlodipine 5 mg in addition to ARBs . The primary endpoint was a change in the systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) after the 3-month treatment period , while secondary endpoints were changes in the BP , albuminuria , laboratory values , and cognitive function with the mini-mental state examination ( MMSE ) at baseline and after one year . The results from the CAMUI trial should provide new evidence for selecting optimal combination therapies for elderly hypertensive patients Objectives Current guidelines recommend the use of multiple medications for hypertension . The present study was aim ed at determining which combination was optimal to prevent cardiovascular events . Methods We conducted a prospect i ve , r and omized , open-label , blinded-endpoint trial . Hypertensive out patients aged between 40 and 85 years who did not achieve target blood pressure ( BP<140/90 mmHg ) with calcium channel blocker ( CCB ) benidipine 4 mg/day were r and omly assigned to receive angiotensin receptor blocker ( ARB ) , & bgr;-blocker , or thiazide diuretic in addition to benidipine . Results Among a total of 3501 patients ( 1167 , benidipine-ARB ; 1166 , benidipine-&bgr;-blocker ; and 1168 , benidipine-thiazide ) , 3293 patients ( 1110 , 1089 , and 1094 , respectively ) who received each combination treatment were included in the analysis . Median follow-up was 3.61 years . At the end of the treatment , 64.1 , 66.9 , and 66.0 % of patients in the benidipine-ARB , benidipine-&bgr;-blocker , and benidipine-thiazide groups achieved target BP , respectively . The cardiovascular composite endpoint occurred in 41 ( 3.7 % ) , 48 ( 4.4 % ) , and 32 ( 2.9 % ) patients , respectively : the hazard ratio was 1.26 in the benidipine-ARB ( P = 0.3505 ) and 1.54 in the benidipine-&bgr;-blocker ( P = 0.0567 ) groups compared with the benidipine-thiazide group . The secondary analyses revealed that benidipine and thiazide diuretic significantly reduced the incidence of fatal or nonfatal strokes ( P = 0.0109 ) and benidipine and ARB significantly reduced new-onset diabetes ( P = 0.0240 ) compared with benidipine and & bgr;-blocker . All trial treatments were safe and well tolerated . Conclusion CCB combined with ARB , & bgr;-blocker , or thiazide diuretic was similarly effective for the prevention of cardiovascular events and the achievement of target BP BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure Background The most effective and accurate treatment of hypertensive patients reduces cardiovascular events and improves the quality of life . Objective This study compared the efficacy and safety of combined ( combination therapy ) with an angiotensin-receptor blocker ( ARB ) a calcium-channel blocker ( CCB ) ( Losartan / Amloidipine 50/10 mg ) vs maximal combination doses of ARB with hydrochlorothiazide ( Losartan /HCTZ 100/25 mg ) and maximal combination doses of CCB with HCTZ ( Amlodipine /HCTZ 10/25 mg ) in the management of stage 2 hypertension . Methods This r and omized clinical trial ( RTC ) comprised 478 hypertensive patients with mean age 50.5±5.21 years , and took place between January 2010 and December 2011 in Vasei Hospital clinic in Sabzevar . Antihypertensive drugs were washed out after 5 days of discontinuation of drugs and the patients with mean blood pressure in sitting position ≥ 160 and < 200 mmHg in systole and ≥ 100 and < 110 mmHg in diastole were r and omized into three groups : Losartan / Amlodipine 50/10 mg ( n = 164 ) , Losartan / HCTZ 100/25 mg ( n = 155 ) and Amlodipine / HCTZ 10/25 mg ( n = 159 ) . The end point was reaching the blood pressure below 140/90 within 56 days of treatment in each group . Results There was a significant difference in systolic blood pressure reductions between treatment groups ( P<0.001 ) and also there was a significant difference between groups in reducing diastolic blood pressure ( P<0.01 ) . The highest systolic and diastolic blood pressure reduction respectively was found in Amlodipine/losartane and losartane/HTCZ group . The ANCOVA analysis revealed that only treatment regimen had a significant effect ( P=0.01 ) and other factor including Age , Gender , Diabetes Mellitus , Smoking and High serum cholesterol did n’t have significant effect on blood pressure reduction . Conclusion ARB/CCB combination therapy reduced blood pressure more effectively than the maximal doses of ARB or CCB with HCTZ in stage 2 hypertensive patients within this period of study BACKGROUND Despite treatment , there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals . Inadequate reduction of their blood pressure is a likely cause , but the optimum target blood pressure is not known . The impact of acetylsalicylic acid ( aspirin ) has never been investigated in patients with hypertension . We aim ed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension . METHODS 18790 patients , from 26 countries , aged 50 - 80 years ( mean 61.5 years ) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg ( mean 105 mm Hg ) were r and omly assigned a target diastolic blood pressure . 6264 patients were allocated to the target pressure < or = 90 mm Hg , 6264 to < or = 85 mm Hg , and 6262 to < or = 80 mm Hg . Felodipine was given as baseline therapy with the addition of other agents , according to a five-step regimen . In addition , 9399 patients were r and omly assigned 75 mg/day acetylsalicylic acid ( Bamycor , Astra ) and 9391 patients were assigned placebo . FINDINGS Diastolic blood pressure was reduced by 20.3 mm Hg , 22.3 mm Hg , and 24.3 mm Hg , in the < or = 90 mm Hg , < or = 85 mm Hg , and < or = 80 mm Hg target groups , respectively . The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg ; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg . Further reduction below these blood pressures was safe . In patients with diabetes mellitus there was a 51 % reduction in major cardiovascular events in target group < or = 80 mm Hg compared with target group < or = 90 mm Hg ( p for trend=0.005 ) . Acetylsalicylic acid reduced major cardiovascular events by 15 % ( p=0.03 ) and all myocardial infa rct ion by 36 % ( p=0.002 ) , with no effect on stroke . There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group , and 129 versus 70 non-fatal major bleeds in the two groups , respectively ( p<0.001 ) . INTERPRETATION Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events . The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg . Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infa rct ion . There was no effect on the incidence of stroke or fatal bleeds , but non-fatal major bleeds were twice as common Diabetic nephropathy is the leading cause of end-stage renal disease ( ESRD ) . The early stage of nephropathy is manifested by the presence of low levels of urinary albumin ( microalbuminuria or urinary albumin excretion ⩾30 and < 299 mg/day ) . Albuminuria is a marker for development of nephropathy in type II diabetes and for increased cardiovascular morbidity and mortality . Recent studies have demonstrated the importance of antihypertensive agents that inhibit the renin – angiotensin – aldosterone ( RAA ) system to reduce the risk and slow down the progression of renal disease . A new clinical trial , GUARD ( Gauging Albuminuria Reduction With Lotrel in Diabetic Patients With Hypertension ) , is design ed to compare the change in urinary albumin to creatinine ratio after 1 year of initial treatment with either amlodipine besylate/benazepril HCl or benazepril HCl/hydrochlorothiazide . Other objectives include a comparison of the proportion of patients who progress to overt diabetic nephropathy and the safety of these two combination therapies in these high-risk patients BACKGROUND The apparent shortfall in prevention of coronary heart disease ( CHD ) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used . For a given reduction in blood pressure , some suggested that newer agents would confer advantages over diuretics and beta blockers . Our aim , therefore , was to compare the effect on non-fatal myocardial infa rct ion and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril . METHODS We did a multicentre , prospect i ve , r and omised controlled trial in 19 257 patients with hypertension who were aged 40 - 79 years and had at least three other cardiovascular risk factors . Patients were assigned either amlodipine 5 - 10 mg adding perindopril 4 - 8 mg as required ( amlodipine-based regimen ; n=9639 ) or atenolol 50 - 100 mg adding bendroflumethiazide 1.25 - 2.5 mg and potassium as required ( atenolol-based regimen ; n=9618 ) . Our primary endpoint was non-fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) and fatal CHD . Analysis was by intention to treat . FINDINGS The study was stopped prematurely after 5.5 years ' median follow-up and accumulated in total 106 153 patient-years of observation . Though not significant , compared with the atenolol-based regimen , fewer individuals on the amlodipine-based regimen had a primary endpoint ( 429 vs 474 ; unadjusted HR 0.90 , 95 % CI 0.79 - 1.02 , p=0.1052 ) , fatal and non-fatal stroke ( 327 vs 422 ; 0.77 , 0.66 - 0.89 , p=0.0003 ) , total cardiovascular events and procedures ( 1362 vs 1602 ; 0.84 , 0.78 - 0.90 , p<0.0001 ) , and all-cause mortality ( 738 vs 820 ; 0.89 , 0.81 - 0.99 , p=0.025 ) . The incidence of developing diabetes was less on the amlodipine-based regimen ( 567 vs 799 ; 0.70 , 0.63 - 0.78 , p<0.0001 ) . INTERPRETATION The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen . On the basis of previous trial evidence , these effects might not be entirely explained by better control of blood pressure , and this issue is addressed in the accompanying article . Nevertheless , the results have implication s with respect to optimum combinations of antihypertensive agents Introduction : The optimal combination treatment for hypertension has not been established . We investigated the effect of a calcium channel blocker or a diuretic added to angiotensin II receptor blockers ( ARBs ) on the augmentation index ( AI ) , as a marker of arterial stiffness and wave reflection , in hypertensive patients . Methods : Thirty-seven patients treated with ARBs were r and omly allocated to either of the 2 groups receiving an ARB plus azelnidipine ( AZ group ) or trichlormethiazide ( TCM group ) . Changes in brachial blood pressure ( BP ) , AI , high-sensitive C-reactive protein ( hsCRP ) , and serum asymmetric dimethylarginine , as an endogenous nitric oxide synthase inhibitor , were determined . Results : Systolic and diastolic blood pressure after 6 months were significantly reduced in both the groups similarly ; however , after adjustment for baseline covariates , the extent of the reduction in AI ( % ) in the AZ group was significantly greater than in the TCM group ( between-group difference was 3.2 ; 95%CI : 0.2–6.3 ; P = 0.03 ) . The reduction of high-sensitive C-reactive protein ( mg/L ) and serum asymmetric dimethylarginine ( & mgr;mol/L ) was significantly greater in the AZ group than in the TCM group ( between-group difference was 0.18 and 0.05 ; 95%CI : −0.01 to 0.36 and −0.01 to 0.11 ; P = 0.04 and 0.02 , respectively ) . Further , when patients were analyzed according to age younger than 60 years or older than 60 years , the reduction in AI in the AZ group aged older than 60 years was significantly greater than in the TCM group . Conclusion : The results suggest that azelnidipine has a more beneficial effect on vascular properties in combination therapy with ARB than trichlormethiazide Objective : The aim of the present study was to compare the cardiovascular effects of olmesartan , an angiotensin II receptor blocker , combined with a calcium channel blocker ( CCB ) or a diuretic , in a prospect i ve , r and omized , open-label , blinded endpoint trial . Methods : Japanese hypertensive patients aged at least 65 to less than 85 years with SBP at least 140 mmHg and /or DBP at least 90 mmHg with antihypertensive treatment , or SBP at least 160 mmHg and /or DBP at least 100 mmHg without antihypertensive treatment were r and omized to receive olmesartan with either a dihydropyridine CCB or a low-dose diuretic . If SBP and /or DBP remained at least 140 and /or at least 90 mmHg , the other antihypertensive drug was added . The primary endpoint was a composite of fatal and nonfatal cardiovascular events . The median follow-up time was 3.3 years . Results : Blood pressure decreased similarly in both groups . The primary endpoint occurred in 116/2568 patients ( 4.5 % ) in the olmesartan plus CCB group and in 135/2573 patients ( 5.3 % ) in the olmesartan plus diuretic group [ hazard ratio 0.83 , 95 % confidence interval ( CI ) 0.65–1.07 , P = 0.16 ] . Rates of all-cause death and cardiovascular deaths were similar . Among patients aged at least 75 years , the incidence of stroke tended to be lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group ( hazard ratio 0.63 , 95 % CI 0.38–1.02 , P = 0.059 , interaction P = 0.019 ) . Fewer patients in the olmesartan plus CCB group ( 8.2 % , 211/2568 ) than in the olmesartan plus diuretic group ( 9.8 % , 253/2573 ; P = 0.046 ) experienced serious adverse events . Conclusion : Despite no significant difference in cardiovascular events , the different safety profiles suggest that the combination of olmesartan and CCB may be preferable to that of olmesartan and diuretic Objective : Combination therapy with angiotensin receptor blockers ( ARBs ) and calcium channel blockers or diuretics is common for hypertensive patients . This study aim ed to determine which combination is better for elderly hypertensive patients . Methods : In this prospect i ve , r and omized , open-label trial , hypertensive out patients aged at least 65 years who had not achieved their target blood pressure ( BP ) with st and ard ARB dosages were r and omly assigned to receive either a fixed-dose combination of losartan ( 50 mg ) and hydrochlorothiazide ( 12.5 mg ) ( ARB+D ; n = 72 ) or a combination of amlodipine ( 5 mg ) and the typical dosage of ARBs ( ARB+C ; n = 68 ) to evaluate the change in the BP , laboratory values and cognitive function . Results : At 3 months , the SBP/DBP was found to have significantly decreased from 156/83 ± 15/11 mmHg to 139/76 ± 14/10 mmHg in the ARB+D group and 155/83 ± 11/10 mmHg to 132/72 ± 14/10 mmHg in the ARB+C group . The BP reduction efficacy was greater in the ARB+C group than in the ARB+D group . At 6 months , the SBP/DBP reached the same level in both groups . At 12 months , the urine albumin/creatinine ratio was significantly decreased from the geometric mean of 17.1 to 9.6 mg/g in the ARB+D group , whereas it was increased from 19.8 to 23.7 mg/g in the ARB+C group . Conversely , the estimated glomerular filtration rate tended to show a decrease in the ARB+D group . There was no significant difference in mini-mental state examination after 1 year . Conclusion : ARB+amlodipine ( 5 mg ) yielded a greater BP reduction , whereas ARB+HCTZ ( 12.5 mg ) result ed in a greater reduction in the albuminuria , suggesting that each combination therapy is advantageous in a different manner for elderly hypertensive patients |
1,758 | 28,404,558 | Education , perceived health status , quality of life , affective judgements , self-efficacy , intention , self-regulation behaviours , subjective norm and programme leadership were associated with RT .
Conclusion Low education levels and poor health status were associated with low participation rates in RT .
Intrapersonal factors including affective judgements , self-efficacy , and self-regulation behaviours , and interpersonal factors including subjective norms and programme leadership may be important for promoting RT behaviours | Objective Regular participation in resistance training ( RT ) is critical to health and recommended in most international physical activity guidelines .
Few people , however , participate in RT .
The purpose of this review was to assess the demographic , behavioural , intrapersonal , interpersonal and environmental factors associated with participating in RT . | Self-efficacy is arguably the strongest correlate of physical activity , yet some research ers suggest this is because the construct confounds ability with motivation . We examine a more circumscribed construct , called perceived capability ( PC ) , meant to measure ability but not motivation and propose that the construct will not be related to unskilled physical activities but may be linked to skilled behaviors . The purpose of this paper was to examine whether a PC construct can be stripped of motivation using a vignette approach in both walking and resistance training behaviors . Participants were a r and om sample of 248 university students , who were then r and omly assigned to either answer resistance training or walking behavior questions . Both groups completed a PC measure and reasons for their answer before and after reading a vignette that clarified the phrasing of capability to a literal use of the term . PC was significantly ( p < .01 ) higher post- compared to pre-vignette and the differences were greater ( p < .01 ) for walking than for resistance training . PC had significantly ( p < .01 ) smaller correlations with intention and self-reported behavior post-disambiguation , which result ed in a null relationship with walking but a small correlation with resistance training behavior . When PC was combined with intention to predict behavior , however , there was no significant ( p > .05 ) difference in the amount of variance explained pre- to post-vignette . Thought listing showed that participants did not report capability barriers to walking and over half of the sample construed capability as motivation/other priorities pre-vignette . The findings support use of a vignette approach for research ers who wish to disentangle the assessment of PC from motivation while creating no overall loss in explained variance of physical activity Background Physical activity and consuming a healthy diet have clear benefits to the physical and psychosocial health of cancer survivors , with guidelines recognising the importance of these behaviors for cancer survivors . Interventions to promote physical activity and improve dietary behaviors among cancer survivors and carers are needed . The aim of this study was to determine the effects of a group-based , face-to-face multiple health behavior change intervention on behavioral outcomes among cancer survivors of mixed diagnoses and carers . Methods The Exercise and Nutrition Routine Improving Cancer Health ( ENRICH ) intervention was evaluated using a two-group pragmatic r and omized controlled trial . Cancer survivors and carers ( n = 174 ) were r and omly allocated to the face-to-face , group-based intervention ( six , theory-based two-hour sessions delivered over 8 weeks targeting healthy eating and physical activity [ PA ] ) or wait-list control ( after completion of 20-week data collection ) . Assessment of the primary outcome ( pedometer-assessed mean daily step counts ) and secondary outcomes ( diet and alcohol intake [ Food Frequency Question naire ] , self-reported PA , weight , body mass index , and waist circumference ) were assessed at baseline , 8- and 20-weeks . Results There was a significant difference between the change over time in the intervention group and the control group . At 20 weeks , the intervention group had increased by 478 steps , and the control group had decreased by 1282 steps ; this represented an adjusted mean difference of 1761 steps ( 184 to 3337 ; P = 0.0028 ) . Significant intervention effects for secondary outcomes , included a half serving increase in vegetable intake ( difference 39 g/day ; 95 % CI : 12 to 67 ; P = 0.02 ) , weight loss ( kg ) ( difference -1.5 kg ; 95 % CI , -2.6 to -0.3 ; P = 0.014 ) and change in body mass index ( kg/m2 ) ( difference -0.55 kg/m2 ; 95 % CI , -0.97 to -0.13 ; P = 0.012 ) . No significant intervention effects were found for self-reported PA , total sitting time , waist circumference , fruit , energy , fibre , alcohol , meat , or fat consumption . Conclusions The ENRICH intervention was effective for improving PA , weight , body mass index , and vegetable consumption even with the inclusion of multiple cancer types and carers . As an example of successful research translation , the Cancer Council NSW has subsequently adopted ENRICH as a state-wide program . Trial registration Australian New Zeal and Clinical Trials Register identifier : ANZCTRN1260901086257 Background : In terms of motivation and long-term adherence , low-resistance exercise might be more suitable for older adults than high-resistance exercise . However , more data are needed to support this cl aim . Objective : The objective was to investigate the effect of low- and high-resistance exercise protocol s on long-term adherence and motivation . Methods : This study was design ed as an exploratory 24-week follow-up of a r and omized 12-week resistance training intervention in older adults . Participants were free to decide whether or not they continued resistance training at their own expense following the intervention . Fifty-six older adults were r and omly assigned to HIGH [ 2 × 10 - 15 repetitions at 80 % of one repetition maximum ( 1RM ) ] , LOW ( 1 × 80 - 100 repetitions at 20 % of 1RM ) , or LOW+ ( 1 × 60 repetitions at 20 % of 1RM + 1 × 10 - 20 repetitions at 40 % 1RM ) . Motivation , self-efficacy and the perceived barriers for continuing resistance exercise were measured after cessation of each supervised intervention and at follow-up , while long-term adherence was probed retrospectively at follow-up . Results : Participants reported high levels of self-determined motivation before , during , and after the supervised intervention , with no differences between groups ( p > 0.05 ) . Nevertheless , only few participants continued strength training after the intervention : 17 % in HIGH , 21 % in LOW+ , and 11 % in LOW ( p > 0.05 ) . The most commonly reported barriers for continuing resistance exercise were perceived lack of time ( 46 % ) , being more interested in other physical activities ( 40 % ) , seasonal reasons ( 40 % ) , and financial cost ( 28 % ) . Conclusion : The results suggest no difference in long-term adherence after the end of a supervised exercise intervention at high or low external resistances . Long-term adherence was limited despite high levels of self-determined motivation during the interventions . These findings highlight the importance of further research on developing strategies to overcome barriers of older adults to adhere to resistance exercise without supervision OBJECTIVE Progressive resistance training ( PRT ) counteracts sarcopenia and has been demonstrated to improve physical function and quality of life in older adults . Despite the clear benefits of PRT , participation remains low . The core self-evaluation ( CSE ) construct is theoretically antecedent to four personality traits : locus of control , self-esteem , neuroticism ( emotional stability ) , and generalized self-efficacy . We have examined the association of CSE with exercise adoption among older adults invited to participate in a PRT trial . We hypothesized that CSE would positively predict adoption of PRT . STUDY DESIGN All residents of two retirement communities were invited to complete question naires with items on demographics , physical activity , CSE , and general health . Following completion of question naires , residents were invited to take part in an on-site , 10-week r and omized controlled trial of a PRT-based exercise trial . RESULTS Thirty-eight of 358 residents ( 63.2 % women ; 76.6±6.1 year ; range 58 - 92 ) enrolled and 118 residents completed the question naires . Multiple regression analysis predicting PRT adoption indicated that the demographic variables accounted for 38 % of the variance . Inclusion of CSE ( β=.405 ) accounted for an additional 10 % of the variance in PRT adoption . CONCLUSION CSE was predictive of PRT adoption in this cohort , adding significantly to the predictive efficacy of known demographic predictors . This is the first study to show that CSE may influence adoption of PRT in any cohort A poor underst and ing of behaviour change mechanisms has hindered the development of effective physical activity interventions . The aim of this study was to identify potential mediators of change in a home-based resistance training ( RT ) program for obese individuals with type 2 diabetes . Obese individuals with type 2 diabetes ( N = 48 ) were r and omly allocated to either an RT intervention ( n = 27 ) or a control group ( n = 21 ) for the 16-week study period . The study sample included 16 men and 32 women and the mean age of participants was 54.4 ( ±11.7 ) years . Participants in the RT group received a multi-gym and dumbbells and home supervision from a certified personal trainer . RT behaviour was measured using a modified Godin Leisure Time Question naire . Social-cognitive constructs were measured and tested in a mediating variable framework using a product-of-coefficients test . The intervention had a significant effect on RT behaviour ( p < 0.001 ) and muscular strength ( p < 0.001 ) . The intervention had a significant effect on RT planning strategies ( p < 0.01 ) , which mediated the effect of the intervention on RT behaviour . The home-based RT program successfully targeted participants ’ RT planning strategies which contributed to their exercise adherence This study identified factors associated with exercise participation and adherence in a sample of 102 sedentary , functionally limited , community-dwelling adults aged 60 to 94 years who participated in a home-based resistance training program . Stepwise regression analyses revealed that baseline physical factors ( i.e. , higher levels of mobility , weaker muscle strength , and fewer numbers of new medical conditions ) were associated with higher rates of participation in the home program . Positive attitudes and a sense of control toward exercise , lower levels of confusion and depressive moods , and the development of fewer new medical problems during the program were related to higher levels of adherence to the program . Findings revealed that although physical health variables were the primary indicators of an older person 's overall participation in the program , it was the psychological factors that were most important to adherence to this home-based program Background Reaction time , coordination , and cognition performance typically diminish in older adults , which may lead to gait impairments , falls , and injuries . Regular strength – balance exercises are highly recommended to reduce this problem and to improve health , well-being , and independence in old age . However , many older people face a lack of motivation in addition to other strong barriers to exercise . We developed ActiveLifestyle , an information technology (IT)-based system for active and healthy aging aim ing at improving balance and strength . ActiveLifestyle is a training app that runs on a tablet and assists , monitors , and motivates older people to follow personalized training plans autonomously at home . Objective The objectives were to ( 1 ) investigate which IT-mediated motivation strategies increase adherence to physical exercise training plans in older people , ( 2 ) assess the impact of ActiveLifestyle on physical activity behavior change , and ( 3 ) demonstrate the effectiveness of the ActiveLifestyle training to improve gait speed . Methods A total of 44 older adults followed personalized , 12-week strength and balance training plans . All participants performed the exercises autonomously at home . Question naires were used to assess the technological familiarity and stage of behavior change , as well as the effectiveness of the motivation instruments adopted by ActiveLifestyle . Adherence to the exercise plan was evaluated using performance data collected by the app and through information given by the participants during the study . Pretests and posttests were performed to evaluate gait speed of the participants before and after the study . Results Participants were 75 years ( SD 6 ) , predominantly female ( 64 % ) , held a trade or professional diploma ( 54 % ) , and their past profession was in a sitting position ( 43 % ) . Of the 44 participants who enrolled , 33 ( 75 % ) completed the study . The app proved to assist and motivate independently living and healthy older adults to autonomously perform strength – balance exercises ( median 6 on a 7-point Likert scale ) . Social motivation strategies proved more effective than individual strategies to stimulate the participants to comply with the training plan , as well as to change their behavior permanently toward a more physically active lifestyle . The exercises were effective to improve preferred and fast gait speed . Conclusions ActiveLifestyle assisted and motivated independently living and healthy older people to autonomously perform strength – balance exercises over 12 weeks and had low dropout rates . The social motivation strategies were more effective to stimulate the participants to comply with the training plan and remain on the intervention . The adoption of assistive technology devices for physical intervention tends to motivate and retain older people exercising for longer periods of time Background Aerobic physical activity ( PA ) and resistance training are paramount in the treatment and management of type 2 diabetes ( T2D ) , but few studies have examined the determinants of both types of exercise in the same sample . Objective The primary purpose was to investigate the utility of the Theory of Planned Behavior ( TPB ) in explaining aerobic PA and resistance training in a population sample of T2D adults . Methods A total of 244 individuals were recruited through a r and om national sample which was created by generating a r and om list of household phone numbers . The list was proportionate to the actual number of household telephone numbers for each Canadian province ( with the exception of Quebec ) . These individuals completed self-report TPB constructs of attitude , subjective norm , perceived behavioral control and intention , and a 3-month follow-up that assessed aerobic PA and resistance training . Results TPB explained 10 % and 8 % of the variance respectively for aerobic PA and resistance training ; and accounted for 39 % and 45 % of the variance respectively for aerobic PA and resistance training intentions . Conclusion These results may guide the development of appropriate PA interventions for aerobic PA and resistance training based on the TPB The aim of this study was to determine the efficacy and feasibility of a resistance-training ( RT ) and lifestyle-activity program for sedentary older adults . Eligible participants ( N = 44 ) were r and omized to an 8-wk intervention or a control group . The primary outcome was lower body muscle strength , and participants completed a range of secondary outcomes . There was a significant group-by-time interaction for lower body muscle strength ( difference = 3.9 repetitions [ reps ] , 95 % CI = 2.0 - 5.8 reps ; p < .001 ; d = 1.0 ) . Changes in secondary outcomes were generally small and not statistically significant . Attendance and program satisfaction were both high . A combined elastic-tubing RT and lifestyle-activity program delivered in the community setting is an efficacious and feasible approach to improve health in sedentary older adults INTRODUCTION The prevalence and risk of Type 2 Diabetes ( T2D ) has dramatically increased over the past decade . Physical activity ( PA ) has significant benefits for the treatment and prevention of T2D . The aim of this study is to develop , implement and evaluate a community-based PA intervention to improve aerobic and muscular fitness among adults at risk of , or diagnosed with T2D . RESEARCH DESIGN AND METHODS The eCoFit pilot intervention will be evaluated using a r and omized controlled trial ( RCT ) design . The 20-week ( Phases 1 and 2 ) multi-component intervention was guided by Social Cognitive Theory , Health Action Process Approach Model , and Cognitive Behavior Therapy strategies . Phase 1 ( Weeks 1 - 10 ) includes : i ) 5 group face-to-face sessions consisting of outdoor training and cognitive mentoring ; and ii ) the use of the eCoFit smartphone application with a description of where and how to use the outdoor environment to be more physically active . Phase 2 ( Weeks 11 - 20 ) includes the use of the eCoFit smartphone application only . Assessment s are to be conducted at baseline , 10-weeks ( primary end-point ) and 20-weeks ( secondary end-point ) post-baseline . Primary outcomes are cardio-respiratory fitness and muscular fitness ( lower body ) . Secondary outcomes include physical , behavioral , mental health and quality of life , and social-cognitive outcomes . DISCUSSION eCoFit is an innovative , multi-component intervention , which integrates smartphone technology , social support and the outdoor physical environment to promote aerobic and resistance training PA among adults at risk of , or diagnosed with T2D . The findings will be used to guide future interventions and to develop and implement effective community-based prevention programs . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry No : ACTRN12615000990527 OBJECTIVES The purpose of this study was to explore potential moderators and mediators of intervention effects in the Physical Activity Leaders ( PALs ) obesity prevention program for adolescent boys from disadvantaged secondary schools . DESIGN Group r and omized controlled trial . METHODS One hundred adolescent boys ( mean age=14.3 ( 0.6 ) years ) from four schools were r and omized to the PALs intervention or a control group for the 6-month study period . The primary outcome was change in BMI and secondary outcomes were physical activity assessed using pedometers and constructs from Social Cognitive Theory ( SCT ) assessed using a question naire . RESULTS Moderation analyses revealed a significant weight status interaction for BMI ( p=0.04 ) , indicating stronger intervention effects for youth classified as overweight/obese at baseline . The intervention had a significant effect on resistance training self-efficacy ( p<0.001 ) , but none of the SCT constructs satisfied the criteria for mediation . The number of intervention sessions attended was associated with changes in BMI ( r=-0.38 , p=0.001 ) , resistance training self-efficacy ( r=0.42 , p<0.001 ) and physical activity behavioral strategies ( r=0.26 , p=0.018 ) . Changes in BMI were also associated with changes in resistance training self-efficacy ( r=-0.21 , p=0.06 ) and physical activity behavioral strategies ( r=-0.29 , p=0.009 ) . CONCLUSIONS A school-based intervention incorporating student leadership increased adolescent boys ' resistance training self-efficacy , but changes in physical activity were not detected and none of the SCT constructs satisfied the criteria for mediation . Baseline weight status was a moderator of intervention effect with the strongest intervention effects observed among overweight and obese adolescent boys Abstract The purpose of this study was to examine the mediating effect of resistance training skill competency on percentage of body fat , muscular fitness and physical activity among a sample of adolescent boys participating in a school-based obesity prevention intervention . Participants were 361 adolescent boys taking part in the Active Teen Leaders Avoiding Screen-time ( ATLAS ) cluster r and omised controlled trial : a school-based program targeting the health behaviours of economically disadvantaged adolescent males considered “ at-risk ” of obesity . Body fat percentage ( bioelectrical impedance ) , muscular fitness ( h and grip dynamometry and push-ups ) , physical activity ( accelerometry ) and resistance training skill competency were assessed at baseline and post-intervention ( i.e. , 8 months ) . Three separate multi-level mediation models were analysed to investigate the potential mediating effects of resistance training skill competency on each of the study outcomes using a product-of-coefficients test . Analyses followed the intention-to-treat principle . The intervention had a significant impact on the resistance training skill competency of the boys , and improvements in skill competency significantly mediated the effect of the intervention on percentage of body fat and the combined muscular fitness score . No significant mediated effects were found for physical activity . Improving resistance training skill competency may be an effective strategy for achieving improvements in body composition and muscular fitness in adolescent boys OBJECTIVE We conducted a qualitative investigation of patients with type 2 diabetes to determine their perceived facilitators and barriers to exercise at multiple time points while enrolled in a r and omized exercise trial including aerobic , resistance or combined exercise . We explored differences in these themes over time , between intervention groups and by adherence level after intervention . METHODS Interviews were conducted by telephone at 3 weeks ( run-in period ) , and at 3 ( midintervention ) , 6 ( end of intervention ) and 9 months ( maintenance ) after enrollment to assess factors that facilitated and hampered adherence to the exercise program . Audiotapes were transcribed verbatim and subjected to content analysis . RESULTS Participants ( n=28 ) with type 2 diabetes engaged in the interviews . Social support from family and the trainer , future health benefits , a sense of well-being and perceived fitness improvements were exercise facilitators . Experiencing illness or injury , work commitments and inclement weather were highlighted barriers . A sense of well-being , fitness improvements and enjoyment frequently were expressed by participants assigned to the combined and resistance exercise conditions . Participants who maintained prescribed exercise levels tended to be engaged in resistance exercise , and spoke of support from their personal trainers , the importance of strategies and enjoyment more frequently than those who did not maintain their exercise level . Exercise maintainers also cited more facilitators ; no differences were found for barriers . CONCLUSIONS Patients with type 2 diabetes require social support , including continued contact with exercise specialists . Patients need assistance with motivational enhancement and strategies to increase facilitators to maintain exercise behaviour . Incorporating resistance exercise improves well-being and enjoyment-2 important factors linked to exercise maintenance OBJECTIVE To examine predictors of adherence in a r and omized controlled trial of resistance exercise training ( RET ) in prostate cancer survivors receiving and rogen deprivation therapy . STUDY DESIGN AND SETTING A r and omized controlled trial conducted at fitness centers in Ottawa and Edmonton , Canada . Prostate cancer survivors ( n=155 ) completed measures of social cognitive variables , quality of life ( QOL ) , behavior , and fitness before being r and omized to either an exercise ( n=82 ) or control ( n=73 ) group . The exercise group was asked to perform supervised RET three times per week for 12 weeks . RESULTS The exercise group attended 28.2 of the 36 ( 78.3 % ) RET sessions . Univariate analyses revealed eight different significant ( Ps < .05 ) predictors of exercise adherence including exercise stage of change , intention , age , QOL , fatigue , subjective norm , leg-press test , and perceived behavioral control . A multivariate analysis indicated that there were three independent predictors of adherence that explained 20.4 % of the variance : exercise stage of change ( beta=0.26 ; P=.013 ) , age ( beta=-0.22 ; P=.037 ) , and intention ( beta=0.19 ; P=.073 ) . CONCLUSION Exercise adherence in the trial was very good but not optimal . Adherence was predicted by variables from many different categories including social cognitive , QOL , behavioral , fitness , and demographic . These findings may have important implication s for maximizing adherence during clinical trials of exercise in prostate cancer survivors OBJECTIVE To test the theory of planned behavior ( TPB ) in aerobic versus resistance training in a prospect i ve design . Relationships between TPB variables , extroversion , and perceived health were examined . METHODS College students ( 210 ) completed an initial measurement and a 3-month follow-up assessment . Reasons for exercising were assessed . RESULTS TPB variables , extroversion , and perceived health collectively accounted for substantial variance in aerobic ( 19 % ) and resistance exercise ( 40 % ) . Reasons for exercise included physical , psychological , and social concerns . CONCLUSION Differences in the predictive validity of model constructs suggest potential differential intervention foci for aerobic versus resistance exercise Background Strength exercise improves many health outcomes in cancer survivors but the prevalence and correlates of strength exercise have not been well-described . Moreover , no study has examined the critical intention-behavior gap for exercise in cancer survivors . Purpose The aims of this study are to quantify the intention-behavior gap for strength exercise in hematologic cancer survivors ( HCS ) and examine correlates of both intention formation and translation using the multi-process action control framework ( M-PAC ) . Methods A r and om sample of 2100 HCS in Alberta , Canada , were mailed a survey assessing strength exercise behavior , the M-PAC , and demographic/medical variables . Separate logistic regressions were used to analyze the relationships between the correlates and intention formation and translation . Results Surveys were completed by 606 HCS with 58 % ( n = 353 ) intending to do strength exercise . HCS who were not retired ( OR = 1.56 , p = 0.001 ) , were highly educated ( OR = 1.32 , p = 0.001 ) , and had a favorable attitude ( OR = 1.56 , p < 0.001 ) , descriptive norm ( OR = 1.38 , p = 0.006 ) , injunctive norm ( OR = 1.45 , p = 0.004 ) , and perceived control ( OR = 1.38 , p < 0.001 ) , were more likely to form an exercise intention . Of those with an exercise intention , 51 % ( n = 181 ) reported regular strength exercise . HCS with a detailed plan ( OR = 1.86 , p < 0.001 ) , favorable attitude ( OR = 1.68 , p = 0.001 ) , sense of obligation ( OR = 1.38 , p = 0.010 ) , and self-regulated their affinity for competing activities ( OR = 1.35 , p = 0.012 ) , were more likely to translate their intention into behavior . Conclusion Just over half of HCS intended to do strength exercise and only half of intenders translated that intention into behavior . Implication s for Cancer Survivors Interventions targeting both intention formation and translation may provide the best approach for increasing strength exercise in HCS PURPOSE : Exercise is an important treatment modality for persons with chronic obstructive pulmonary disease ( COPD ) , but factors influencing adherence have been examined infrequently . The purpose of this investigation was to explore adherence factors to a progressive resistance exercise program for persons with COPD . METHODS : Persons with COPD enrolled in a 12-week trial of progressive resistance exercise were invited to participate in 2 semistructured qualitative interviews exploring program adherence . Interviews were audio-taped , transcribed , and then coded independently by 2 research ers . Themes relating to short-term and long-term adherence were then developed and described . RESULTS : Twenty-two participants were interviewed at the conclusion of the intervention ( 12 weeks ) , and 19 completed a second interview at 24 weeks . Short-term exercise adherence was facilitated by expected outcomes , self-motivation , supervision , and group support , whereas health and weather factors were the major barriers to adherence . The barriers to exercise remained unchanged at 24 weeks despite a large decline in exercise adherence . Removal of environmental support at 12 weeks may have contributed to poor long-term exercise maintenance , with participants identifying group support and regular monitoring by a therapist as the most important strategies for maintaining exercise . CONCLUSIONS : The provision of external support in training program design appears important for persons with COPD . Longer-term adherence declined when group support and regular monitoring by a therapist was removed , despite the major perceived exercise barriers remaining unchanged . Therefore , further investigation is required to determine effective strategies for maximizing longer-term exercise adherence in this population ABSTRACT The present study examined factors associated with adherence to a strength training ( ST ) intervention in a r and omized controlled intervention trial testing whether twice-weekly strength training over 2 years could prevent age-associated increases in body fat in 80 overweight to mildly obese women , aged 25 - 44 years . Two sets of focus groups ( FGs ) were conducted with 25 women of color and 24 Caucasian participants , representing 60 % of intervention participants . Fifty-five percent of FG participants had low adherence ( defined as ≤80 % adherence to twice-weekly gym-based strength training ) . Demographic data indicated that marital status and childcare responsibilities affected adherence . Participants ' perceptions of experiences in the ST intervention did not correspond to adherence levels or vary by race/ethnicity . Major impediments to adherence included competing obligations and related scheduling difficulties ; life transitions ; and declining or insufficient social motivators BACKGROUND Although several studies have examined associations of perceived benefits and barriers with physical activity , no studies have focused on them corresponding to strength-training recommendations for older adults . This study examined the associations among the perceived health benefits of strength training , perceived barriers to strength straining , and stages of change for strength-training behavior in older Japanese adults . METHODS This cross-sectional survey included a r and om sample of 1144 adults ( 60 - 74 years ) from the city of Tokorozawa . Stage of change was the independent variable , with perceived health benefits ( eg , strength training can reduce body pain ) and perceived barriers ( eg , facilities are needed for strength training ) as dependent variables . Data were analyzed by analysis of covariance and Bonferroni 's multiple comparison . RESULTS After adjusting for demographic variables , the perceived health-benefit score for precontemplation was significantly lower than for the other four stages . The perceived barrier scores in the precontemplation and contemplation stages were significantly higher than those in the preparation and maintenance stages . CONCLUSIONS These results suggest that information about the health benefits for older adults and about the recommended type of strength training might be useful for the development of strategies to promote strength training among older adults Background The core components of physical activity , cardiovascular endurance , muscular strength , balance and flexibility can provide many health benefits and potentially slow declines associated with aging . Aerobic exercise message to the public has been widely promoted by national health authorities , although the promotion of resistance training has received far less attention . Objectives n this research , the prevalence of resistance training in a sample of adults living in regional Australia was primarily assessed . Design A computer-assisted telephone interview survey ( n=1230 ) was conducted by the Population Research Laboratory at Central Queensl and University on Queensl and adults in October to November 2006 . Respondents were asked to report the frequency with which they engaged in resistance training . Participants Respondents were 18 years or older that could be contacted by direct-dialled , l and -based telephone service . A telephone data base using a computer program to select , with replacement , a simple r and om sample of phone numbers selected respondents . Results Almost 14 % of the population did some form of gym-based resistance training in the week before the survey . There was a significant ( p<0.05 ) reduction in participation levels with age . Participation was highest amongst the youngest 18–34-year-olds ( 23.8 % ) , steadily declining with age to a low of 7 % in the 55 years and older age group . There was no significant association between sexes and participation in resistance training . Conclusions The findings underscore the need to increase overall education on the benefits of resistance training with an emphasis among targeted adult population s to increase participation in resistance training Numerous studies have reported that exercise is safe and beneficial for breast cancer survivors ; however , long-term adherence to exercise programs is not easy to accomplish . This secondary analysis examined the demographic and clinical characteristics , adherence to exercise , and cognitive — behavioral intervention components data collected on 120 postmenopausal women with a history of breast cancer and bone loss who had been r and omized to the exercise group in a 24-month study . Hierarchical regression was used to identify variables that predicted adherence to exercise . Mean adherence to exercises was 61.89 % . Feedback and support were the most frequently used cognitive — behavioral intervention components . In hierarchical regression , predictors for adherence to exercise were feedback ( β = .40 , p < .001 ) and adherence to exercise in the previous time period ( β = .31 , p < .001 ) . Participants receiving more frequent feedback had higher adherence to exercise Background and Objective : Resistance training offers clinical and functional benefits to cardiac patients , yet exercise adherence after cardiac rehabilitation ( CR ) is problematic . This study examined effects of an intervention targeting self-efficacy , outcome expectations , and adherence to upper-body resistance exercise after CR . Participants and Methods : Cardiac patients ( N = 40 ) were r and omly allocated to receive either st and ard exercise recommendations ( wait-list control ) or an intervention involving a theory-based instructional manual and Thera-B and resistive b and s for upper-body resistance exercise . Self-efficacy and outcome expectations were assessed at baseline and 4 weeks later . Participation in resistance exercise was measured at 4 weeks postbaseline and at 3-month follow-up . Results and Conclusions : The intervention group reported higher levels of self-efficacy , outcome expectations , and resistance exercise volume compared with the control group at the 4-week follow-up . Adherence differences were sustained at 3-month follow-up , with some support that self-efficacy for adhering to resistance training mediated the effects of the intervention on follow-up exercise training frequency . Findings support the use of a theory-based motivational manual and Thera-B and resistive b and s to increase self-efficacy and outcome expectations for , and adherence to , resistance training after CR 326 MMWR / May 3 , 2013 / Vol . 62 / No. 17 The 2008 Physical Activity Guidelines for Americans states that aerobic and muscle-strengthening physical activities provide substantial health benefits for adults ( 1 ) . To assess participation in aerobic physical and muscle-strengthening activities among adults in the United States , the Behavioral Risk Factor Surveillance System ( BRFSS ) included new questions in 2011 . * CDC analyzed the 2011 BRFSS survey data for U.S. states and the District of Columbia ( DC ) and found that the selfreported activities of 20.6 % of adult respondents met both aerobic and muscle-strengthening guidelines . Among U.S. states and DC , the prevalence of adults meeting both aerobic and muscle-strengthening guidelines ranged from 12.7 % to 27.3 % . Nationwide , 51.6 % of U.S. adults met the aerobic activity guideline , and 29.3 % met the muscle-strengthening guideline . State public health officials can use these data to establish new baselines for measuring progress toward meeting the physical activity guidelines . BRFSS is a state-based , r and om-digit – dialed telephone survey of the noninstitutionalized U.S. civilian population aged ≥18 years . Data for the 2011 BRFSS survey were collected from 497,967 respondents and reported by the 50 states and DC . Response rates were calculated using st and ards set by the American Association of Public Opinion Research .† The response rate is the number of respondents who completed the survey as a proportion of all eligible and likely eligible persons . The median survey response rate for combined l and line and cellular telephone respondents for all states and DC in 2011 was 49.7 % ( range : 33.8%–64.1 % ) . The assessment of the aerobic activity guideline excluded 39,879 respondents because of missing information , leaving 458,088 usable responses , and the assessment of the musclestrengthening guideline excluded 28,655 respondents for the same reason , leaving 469,312 usable responses . The assessment of the proportions of persons meeting both the aerobic and muscle-strengthening guidelines excluded 44,246 respondents with missing physical activity data , leaving 453,721 usable responses . Persons with missing educational attainment or body mass index ( BMI ) data were excluded from education and BMI analyses . In 2011 , to assess participation in aerobic physical activity , respondents were asked to report the frequency and duration of the two aerobic physical activities , outside of regular job duties , at which they spent the most time during the past month or week . To assess participation in muscle-strengthening activities , respondents were asked to report the frequency of their participation in activities to strengthen their muscles during the past month or week . Minutes of activity per month were converted into minutes of activity per week by dividing monthly minutes by the number of weeks in a month . Respondents were classified as meeting both the aerobic and muscle-strengthening guidelines if they met 1 ) the aerobic activity guideline ( ≥150 minutes per week of moderate-intensity aerobic activity , or ≥75 minutes of vigorous-intensity aerobic activity , or an equivalent combination of moderate and vigorous-intensity aerobic activity [ where vigorous-intensity minutes are multiplied by 2 ] totaling ≥150 minutes per week ) and 2 ) the muscle-strengthening guideline ( muscle-strengthening activities at least two times per week ) ( 1 ) . To count toward meeting the aerobic activity guideline , activities had to be classified as aerobic and had to be performed for ≥10 minutes per episode ( 2 ) . Consistent with earlier ( 1984–2000 ) BRFSS classification of aerobic intensity for specific physical activities ( 3,4 ) , the cut point for defining vigorous-intensity activities in the 2011 BRFSS was ≥60 % of a respondent ’s estimated aerobic capacity , based on age and sex ( 3 ) . Moderate-intensity activities were defined as activities using ≥3.0 metabolic equivalents§ and less than the respondent ’s vigorous-intensity cut point ( 2,3 ) . Data were analyzed by demographic characteristics and weighted to provide prevalence estimates ; 95 % confidence intervals were calculated for each estimate . Orthogonal polynomial contrasts and pairwise t-tests were used to identify significant trends and differences by subgroups . For 2011 , 20.6 % of U.S. adults were classified as meeting both the aerobic and muscle-strengthening guidelines , including 23.4 % of men and 17.9 % of women ( Table 1 ) . By age group , the prevalence of meeting both aerobic and muscle-strengthening guidelines ranged from 30.7 % among persons aged 18–24 years to 15.9 % among those aged ≥65 years . Among racial/ethnic groups , prevalence was lower among Hispanic adults ( 18.4 % ) than among non-Hispanic blacks ( 21.2 % ) ( p<0.001 ) and non-Hispanic whites ( 20.7 % ) ( p<0.001 ) . By education level , college graduates had the highest prevalence of adults meeting both aerobic and Adult Participation in Aerobic and Muscle-Strengthening Physical Activities — United States , OBJECTIVE To estimate the prevalence and correlates of meeting the public health strength exercise guidelines ( ≥2 days/week ) in colorectal cancer ( CRC ) survivors . METHODS A r and om sample of 600 CRC survivors in Alberta , Canada , completed a mailed question naire assessing medical , demographic , and behavioral variables and participation in strength exercise . RESULTS About a quarter ( 25.5 % ) of CRC survivors were meeting strength exercise guidelines . In multivariate analysis , meeting guidelines was associated with being male ( p = .052 ) , married ( p = .079 ) , a drinker ( p = .006 ) , in better health ( p < .001 ) , nonsmoking ( p = .023 ) , and nonobese ( p = .010 ) . CONCLUSIONS Interventions to increase strength exercise participation in CRC survivors are needed BACKGROUND The factors influencing exercise adherence are not well characterized in women in their premenopausal years . METHODS The purpose of this report is to provide an analysis of demographic factors contributing to women 's adherence to a 2-year twice-weekly weight training intervention . Overweight and obese premenopausal women were r and omized to a control or intervention group . RESULTS During the supervised period of the intervention ( months 1 to 4 ) , adherence was significantly lower among those with a higher level of education and among unmarried women with children aged 6 to 12 compared with married women without children ( F = 4.83 , P = .004 ) . Overall adherence during the supervised and unsupervised periods was 95.4 % and 64.5 % , respectively ( unadjusted mean ) . During year 1 , white women were significantly more adherent to the intervention ( 70.3 % ) than women of color ( 48.6 % ) . Non-married women with children 13 years or older were significantly less adherent than married women with children 5 years or younger ( 36.3 % versus 75.4 % , respectively , P < .007 ) . Overall adherence was 51.4 % in year 2 . CONCLUSIONS Interventions and public health recommendations need to further consider how to engage communities to provide effective support for long-term adherence to fitness center based exercise of all women , regardless of demographics INTRODUCTION / PURPOSE Many women who have been treated for breast cancer are at increased risk for bone loss . Strength/weight training exercises ( SWTE ) may be effective in preventing bone loss and subsequent fractures . The purpose of this exploratory study was to examine psychological factors ( self-efficacy , perceived benefits vs. costs , and processes of change ) and their relationship to adherence and progression in use of heavier weights in breast cancer survivors ( BCS ) . SAMPLE Twenty-three BCS with mean age of 54.8 ( SD = 7.2 ) years , mean time since menopause of 5.8 ( SD = 5.3 ) years , and mean time since cancer treatment completion of 4.1 ( SD = 3.0 ) years . METHODS Exploratory one-group design with multicomponent intervention inclusive of medication , calcium with vitamin D supplement , and home-based SWTE with facilitative strategies by nurses and personal exercise trainers based on the Transtheoretical Model . FINDINGS BCS doing SWTE for 6 months : ( 1 ) maintain a high level of self-efficacy , ( 2 ) perceive increasing benefits for 6 months , ( 3 ) use cognitive processes more frequently than behavioral ones , ( 4 ) were highly adherent to the SWTE , and ( 5 ) demonstrate that behavioral processes are positively related to increase in pounds lifted . DISCUSSION / CLINICAL IMPLICATION S Larger r and omized trials studies are needed to determine the most effective strategies for assuring adherence to and progression of SWTE in this population at risk for osteoporosis Effectively preventing and treating chronic diseases through health behavior changes often require intensive theory- and evidence -based intervention including long-term maintenance components . We assessed the efficacy of theory-based maintenance approaches varying by dose for persistently performing resistance training ( RT ) with the hypothesis that a higher-dose social cognitive theory ( SCT ) approach would produce greater RT adherence than lower-dose St and ard . The Resist-Diabetes study first established 2 × /week resistance training ( RT ) in a 3-month supervised intervention in older ( 50–69 years , N = 170 ) , overweight to obese ( BMI 25–39.9 kg/m2 ) previously inactive adults who fit prediabetes criteria ( fasting glucose concentration = 95–125 mg/dl ; oral glucose tolerance test 2-h glucose concentration = 140–199 mg/dl or both ) . After the supervised phase , participants ( N = 159 ) were then r and omly assigned to one of two conditions for transition ( 3 weeks ) and then RT alone in community setting s for extended contact , maintenance ( 6 months ) , and then no contact ( 6 months ) . SCT featured continued tailored , interactive personal , and web-based check-ups focused on RT , self-regulation , and a barrier/strategies approach . St and ard involved low-dose , generic personal , and web-based check-ups within the same theoretical approach . SCT and St and ard both result ed in similar RT , 2 × /week adherence during maintenance ( 74.4 % ) and no-contact phases ( 53.1 % ) . Cost analysis indicated the St and ard intervention for transition and maintenance was inexpensive ( $ 160 ) . St and ard can be translated into practice with the potential for continuous contact and persistence in RT beyond the typical program maintenance phase |
1,759 | 24,567,053 | No evidence was found of a treatment effect of fibrin sealant as an adherence compound .
Evidence suggests improved clinical pregnancy and live birth rates with the use of functional concentrations of HA as an adherence compound in ART cycles .
The increase in multiple pregnancy rate may be the result of use of a combination of an adherence compound and a policy of transferring more than one embryo . | BACKGROUND This is an up date of a Cochrane review first published in The Cochrane Library ( 2010 , Issue 7).To increase the success rate of assisted reproductive technologies ( ART ) , adherence compounds such as hyaluronic acid ( HA ) and fibrin sealant have been introduced into subfertility management .
Adherence compounds are added to the embryo transfer medium to increase the likelihood of embryo implantation , with the potential for higher clinical pregnancy and live birth rates .
OBJECTIVES To determine whether embryo transfer media containing adherence compounds improved live birth and pregnancy rates in ART cycles . | OBJECTIVE To investigate the efficacy of hyaluronan-enriched transfer media in cleavage-stage frozen embryo transfer cycles . DESIGN Two commercially available transfer media were prospect ively compared in an observational study . SETTING Hospital-based in vitro fertilization clinic . PATIENT(S ) Patients ( n = 425 ) undergoing frozen-thawed embryo transfer ( FET ) . The embryos transferred were included in either a study group ( high hyaluronic acid [ HA ] , n = 199 ) or a control group ( low HA , n = 226 ) . INTERVENTION(S ) Delivery rate per FET ; positive hCG rate , biochemical pregnancy rate , clinical pregnancy rate , implantation rate , and clinical abortion rate were secondary outcomes . RESULT ( S ) The use of HA in the transfer media significantly increased the positive hCG rate ( 37.2 % vs. 25.2 % ) and implantation rate ( 23.1 % vs. 15.8 % ) without increasing the delivery rate ( 21.6 % vs. 21.2 % ) . More subjects in the study group with a positive hCG test experienced biochemical pregnancy ( 28.4 % vs. 8.9 % ) . CONCLUSION ( S ) Addition of HA to transfer media seems to favor attachment of early embryos in FETs without increasing the delivery rate Purpose To ascertain whether the use of hyaluronan-enriched transfer medium ( HETM ) improves pregnancy and implantation rates among embryo transfer patients with a history of multiple implantation failures . Methods Patients ( n = 314 ) under the age of 40 and with a history of multiple unsuccessful embryo transfers were enrolled . There were three groups of patients : those undergoing fresh embryo transfer ( fresh ET [ n = 111 ] ) , those undergoing vitrified-warmed ET in the natural cycle ( WET-N [ n = 101 ] ) and those undergoing WET in a hormone replacement cycle ( WET-H [ n = 102 ] ) . On the day of ET , patients were r and omized to HETM ( 0.5 mg/ml hyaluronan ) or control medium containing no hyaluronan . Only patients with good quality embryos on day 3 were included . Results For all three patients groups ( fresh ET , WET-N and WET-H ) pregnancy rates ( 37.5 % , 31.4 % and 41.2 % , respectively ) were significantly higher when using HETM compared with control medium ( 10.9 % , 10.0 % and 15.7 % , respectively ; p < 0.05 ) , and implantation rates when using HETM were also significantly higher compared with control medium ( p < 0.05 ) . Miscarriage rates were similar in both groups . Conclusion HETM significantly increased pregnancy and implantation rates among embryo transfer patients with a history of multiple unsuccessful implantations – regardless of method used to prepare the endometrium Purpose : The aim of this prospect i ve , r and omized trial was to evaluate the efficacy of Embryo-Glue ® as a human embryo transfer medium in IVF/ICSI cycles . Method : A total of 815 nonselected patients undergoing IVF/ICSI treatment between September 2003 and February 2004 were r and omly allocated into the test ( 417 patients ) and the control ( 398 patients ) groups . In both groups , embryos were cultured in G-1 ™ ver 3 , supplemented with 10 % recombinant human albumin . On the day of embryo transfer ( day 3 ) , the best or good quality embryos were selected for intrauterine transfer . In the test group , the selected embryos were treated with EmbryoGlue ® prior to the transfer , whereas in the control group they were transferred without any treatment . Results : The patients ’ characteristics such as age and the number of ART cycles and also the number of patients in each indication of infertility and the number of embryos selected for transfer were all similar between the two groups . In the test group , the clinical pregnancy rate in the tubal factors and the implantation rate in the tubal factors and recurrent implantation failures increased significantly compared with those in the control group . In the test group , life birth and the triplet delivery rates increased significantly compared with those in the control group . Conclusion : EmbryoGlue ® is a useful embryo transfer medium , and at least in some infertile patients it can improve clinical implantation and ongoing pregnancy rates OBJECTIVE To analyze whether the use of a hyaluronan-enriched transfer medium ( HETM ) increases rates of implantation ( IRs ) and clinical pregnancy ( CPRs ) , compared with the use of a conventional transfer medium after day 3 and day 5 embryo transfers . DESIGN Prospect i ve r and omized controlled trial . SETTING An assisted reproduction program in a private tertiary-care hospital in Turkey . PATIENT(S ) A total of 1,282 consecutive fresh embryo transfer cycles ( 825 day 3 and 457 day 5 ) were r and omly allocated into two groups . In 639 women , ET was effected with HETM , and in 643 , it was effected with a conventional embryo transfer medium . INTERVENTION(S ) Embryo transfer using HETM or conventional embryo transfer medium . MAIN OUTCOME MEASURE(S ) Clinical pregnancy rates and IRs were compared with regard to day of embryo transfer , women 's age , quality of the transferred embryos , and presence of previous implantation failures . RESULT ( S ) Overall CPRs and IRs significantly increased with the use of HETM ( CPR : 54.6 % vs. 48.5 % , odds ratio : 1.28 , 95 % confidence interval : 1.03 - 1.59 ; IR : 32 % vs. 25 % , odds ratio : 1.43 , 95 % confidence interval : 1.23 - 1.66 , for HETM and control groups , respectively ) . The number needed to treat ( NNT ) for one additional pregnancy with routine use of HETM was 17 . The beneficial effect was more prominent in women who were > 35 years of age ( NNT = 7 ) , in women who had previous failed cycles ( NNT = 7 ) , and in women who had poor- quality embryos ( NNT = 8) . CONCLUSION ( S ) The enrichment of transfer medium with hyaluronan increases CPRs and IRs , both for day 3 and day 5 embryo transfers . The beneficial effect was most evident in women who were > 35 years of age , in women who had only poor- quality embryos available for transfer , and in women who had previous implantation failures BACKGROUND We aim ed to examine the efficacy of using an embryo transfer medium enriched with hyaluronan ( HA ) to improve implantation in a selected group of patients aged < 43 years with repeated ( > 4 ) implantation failures after IVF-embryo transfer . METHODS About 101 patients , meeting our selection criteria , were r and omly allocated to undergo embryo transfer either using our routine embryo transfer medium without HA ( control group ) or a HA enriched commercial embryo transfer medium ( study group ) . The primary outcome was clinical pregnancy rate . RESULTS After a similar treatment protocol , the ovarian hormonal response , the mean number of ova retrieved and injected per patient , fertilization and cleavage rates and mean embryo quality were comparable between the study and control groups . Although a similar number of embryos was transferred in both groups ( 3.1 + /- 0.7 versus 2.9 + /- 0.6 , mean + /- SD ) , a significantly higher implantation rate ( 16.3 % versus 4.8 % , P = 0.002 ) and clinical pregnancy rate ( 35.2 % versus 10.0 % , P = 0.004 ) and delivered or ongoing pregnancy rate ( 31.3 % versus 4.0 % , P = 0.0005 ) were observed in the study group . When mean implantation rate per patient was calculated , the difference between the study ( 0.148 + /- 0.23 ) and control ( 0.04 + /- 0.13 ) group was significant ( P = 0.003 ) . CONCLUSIONS In this selected group of patients after multiple IVF-embryo transfer failures , the use of HA enriched embryo transfer medium is beneficial This study was undertaken to compare the outcome of day 3 , day 5 , and frozen-thawed embryo transfer cycles where embryo culture was undertaken using the G1.2-G2.2 versus GIII series sequential media . A total of 400 day 3 , 73 day 5 and 126 frozen-thawed embryo transfer cycles were analysed . Treatment cycles were quasi-r and omized on the day of oocyte retrieval to embryo culture in G1.2-G2.2 versus GIII series sequential media . R and omization was undertaken according to alternating weekdays . Significantly more embryos were of grade 1 or 2 quality on day 3 in the GIII group ( P < 0.05 ) . Likewise , more embryos in the GIII group had eight blastomeres on day 3 ( P < 0.05 ) and were able to hatch spontaneously ( P < 0.05 ) . For day 3 embryo transfer cycles , implantation and clinical pregnancy rates were 14.4 and 25.7 % versus 37.8 and 50.3 % in G1.2-G2.2 and GIII groups respectively ( P < 0.05 ) . For day 5 embryo transfer cycles , implantation rates were significantly higher ( 29 versus 45 % ; P < 0.05 ) in the GIII group . There was a trend towards higher pregnancy rates ; however , this did not reach statistical significance due to fewer cycles analysed in this group . In-vitro culture in GIII series sequential media yields better quality embryos that implant more efficiently , compared with culture in G1.2-G2.2 media The purpose of this prospect i ve r and omized study was to evaluate use of a hyaluronan-rich transfer medium in fresh and frozen-thawed single blastocyst transfer . The study included 279 single blastocyst transfers in women aged<37 years in their first , second or third treatment cycle . According to the type of single blastocyst transfer ( fresh elective or frozen-thawed ) the women were divided into two study and two control groups . In both study groups ( n=130 ) transfers were performed using hyaluronan and in the control groups ( n=149 ) a conventional transfer medium was used . The results indicate that fresh elective single blastocyst transfer with hyaluronan results in significantly higher pregnancy rates in a selected subgroup of women ; those with > or=2 blastocysts developed to day 5 and a previous implantation failure ( 55 % versus 10 % ; P=0.012 ) . Overall pregnancy rates after fresh elective and frozen-thawed single blastocyst transfer were similar in both study and control groups Purpose To compare the effects of 2 different media on embryo morphology and development at days 2/3 . MethodS ix hundred seventy-six attempts from 512 couples were included in this prospect i ve auto-controlled study . Sibling oocytes of all couples undergoing an IVF ( n = 286 ) or ICSI ( n = 390 ) attempt were r and omly assigned to either GIII series ( Vitrolife ) or ISM ( Medicult ) media . Primary end points were fertilization and embryo morphology rates . Results Fertilization rates in GIII series and ISM ( IVF : 59.9 vs 62.0 % and ICSI : 65.7 vs 66.8 % ) respectively were not different . GIII series showed an increase , compared to ISM , of early cleavage rate , ( IVF : 25.8 vs 16.2 % ( p = 0.005 ) ; ICSI : 40.8 vs 25.5 % ( p < 0.0001 ) , and good embryo morphology rate at day 2 [ IVF : 64.6 vs 57.3 % ( p = 0.01 ) ; ICSI : 74.2 vs 69.4 ( p = 0.03 ) ] and at day 3 [ IVF : 57.5 vs 49.0 % ( p = 0.02 ) ; ICSI : 67.2 vs 61.6 % ( p = 0.01 ) ] . Conclusions Embryo morphology at days 2/3 was significantly enhanced when the embryos were cultured in GIII series OBJECTIVE To evaluate the role of fibrin sealant for embryo transfer ( ET ) and the effect of patient mobilization after ET on pregnancy rates . DESIGN A prospect i ve , r and omized , controlled study . METHODS Two hundred eleven patients who were admitted to the IVF Unit over a period of 6 months participated in the study . Patients who had three or more embryos were r and omly divided into two groups : group 1 ( study group ) , in which ET was performed using fibrin sealant , and group 2 , who served as the controls . Ovulation induction was carried out using the long GnRH-a suppression protocol . RESULTS Comparison of the results regarding the implantation and pregnancy rates and ectopic pregnancy rate revealed a nonsignificant difference between the two groups . However , analysis of the results according to the patients ' age revealed a significant increase in pregnancy ( P < .05 ) and implantation ( P < .01 ) rate in elderly patients ( aged 39 - 42 ) using fibrin sealant for ET as compared with controls . Furthermore , we found that bed rest has no advantage over patient mobilization after ET . CONCLUSION The use of fibrin sealant for ET is advantageous in elderly women , but has no apparent effect on the success rate or ectopic pregnancy rate in younger patients . Immediate mobilization does not jeopardize the results of IVF-ET Many embryo transfers after in-vitro fertilization may fail because of expulsion of the embryos from the uterus . Approximately 5 - 8 % of pregnancies result ing from embryo transfer are ectopic . The aim of our study was to find a technique to avoid ectopic pregnancies and to improve the pregnancy rate . We used a two-component fibrin sealant which also contains a fibrinolysis inhibitor ( aprotinin ) at various concentrations . After gaining experience with mouse embryos , the sealant was used in human embryo transfer with great success . The results of a pilot study encouraged us to perform a prospect i ve r and omized study on 546 patients ( 270 with fibrin sealant , 276 conventional embryo transfers ) . There were 47 ( 17.0 % ) orthotopic pregnancies and 6 ( 2.2 % ) ectopic pregnancies in the control group , whereas there were 51 ( 18.9 % ) intrauterine and no ectopic pregnancies in the treatment group . The difference in ectopic pregnancies was statistically significant ( P less than 0.05 ) . With regard to the aprotinin concentration , there was a trend towards better results with 100 - 150 kIU ( 28.5 % clinical pregnancies ) in comparison to 250 - 300 kIU ( 19.2 % ) or no aprotinin ( 20.4 % ) ( not significant ) . Further improvements of the technique may raise the pregnancy rate when fibrin sealant is used . As shown in our prospect i ve r and omized study , ectopic pregnancies may be completely avoided Routine use of EmbryoGlue did not significantly improve pregnancy or implantation rates in nonselected patients receiving either a day 3 or day 5 embryo transfer compared with st and ard culture media . Future prospect i ve r and omized studies need to be performed to determine whether EmbryoGlue is beneficial in a selected patient population OBJECTIVE To determine the efficacy of single blastocyst transfer . DESIGN Prospect i ve r and omized trial . SETTING Private assisted reproductive technology unit . PATIENT(S ) Forty-eight women undergoing IVF-embryo transfer with day 3 FSH < or=10 mIU/mL and at least 10 follicles > 12 mm in diameter on day of hCG administration . INTERVENTION(S ) Embryo culture to the blastocyst stage in sequential media G1/G2 followed by transfer of either one or two blastocysts . MAIN OUTCOME MEASURE(S ) Implantation rate , ongoing pregnancy rate , and twinning . RESULT ( S ) The transfer of a single blastocyst result ed in an implantation and ongoing pregnancy rate of 60.9 % with no twins . The transfer of two blastocysts result ed in an implantation rate of 56 % , an ongoing pregnancy rate of 76 % with a 47.4 % incidence of twins . CONCLUSION ( S ) Single blastocyst transfer is an effective method of eliminating multiple births while maintaining high pregnancy rates in this selected group of patients This is a report of our preliminary experience using fibrin sealant with a series of 38 patients undergoing IVF and ET . We used a two-component fibrin sealant to create a fibrin plug in the uterine cavity at the time of ET to decrease the possibility of embryo expulsion and also ectopic pregnancy . Our preliminary report proves that it is possible to obtain 26 % pregnancies using this two-component biological glue instead of serum or culture medium for uterine embryo replacement . A prospect i ve r and omized study will be undertaken to evaluate whether the use of fibrin sealant could significantly improve IVF and ET results We compared the implantation and pregnancy rate through in vitro fertilization ( IVF ) using hyaluronic acid and albumin as transfer medium in 60 women r and omly allocated to 2 groups . In treatment group A ( n = 30 ) , embryos were transferred to medium supplemented with hyaluronic acid . In the control group B ( n = 30 ) , embryos were transferred to medium containing albumin . There were no significant differences between the groups in terms of mean age of the females , mean duration of infertility and mean number of embryos . The pregnancy rate in groups A and B were 81.8 % and 71.4 % respectively , a non-statistically significant difference . Hyaluronic acid can successfully replace albumin as transfer medium BACKGROUND The quality of clinical trials has received increasing attention with the growth of evidence -based medicine and systematic review s. We aim ed to identify whether errors and omissions commonly encountered when undertaking Cochrane review s in this field are still passing peer review . METHODS We undertook a review of trials published in 2001 by two major journals . We selected from Medline only trials in which authors compared pregnancy rates under two interventions by allocating women to different groups . RESULTS We identified 39 trials meeting our criteria . Six trials were fatally flawed by design , either by inappropriate use of a cross-over design or by systematic allocation described by the authors as ' r and om ' . Only six reports cl aim ed to apply the intention-to-treat principle , and the principle was misunderstood by four of these . Only five trials reported live birth rates sufficiently to allow valid meta- analysis . Most trials ( 82 % ) included at least one ' unit of analysis ' error . CONCLUSIONS We selected simple trials from respected journals , assuming that our sample would represent trials of highest method ological quality in the field . Nevertheless , the st and ards of design , analysis and reporting of many subfertility trials are not sufficient to allow reliable interpretation of results , or inclusion in meta-analyses OBJECTIVE To examine the effect on pregnancy and implantation rates when highly purified , fermentation-based hyaluronic acid was the only macromolecule supplement to the transfer medium in a human IVF program . DESIGN Prospect i ve r and omized study . SETTING In vitro fertilization center in an academic medical institution . PATIENT(S ) Eighty patients were included in this prospect i ve r and omized double blind study . Inclusion criteria were age < /=35 years , the availability of at least three embryos eligible for transfer on day 3 after fertilization , and no more than three previous embryo transfer attempts . INTERVENTION(S ) All embryos were cultured in P1 medium containing 10 % synthetic serum substitute ( SSS ) until day 3 . Patients were r and omly allocated to two groups ; in treatment group A ( 40 patients ) , embryos were transferred to P1 medium supplemented with 0.5 mg/mL hyaluronic acid for 5 - 10 min before their intrauterine transfer . In the control group B ( 40 patients ) , embryos were transferred , as routinely performed , in P1 medium containing 10 % SSS . MAIN OUTCOME MEASURES Clinical pregnancy and implantation rates . RESULT ( S ) The mean age of the female partner was 28.7 + /- 3.3 years and 29.7 + /- 3.8 years for groups A and B , respectively . In group A , 103 embryos were transferred and in group B , 97 embryos were transferred for a similar mean number of 2.6 + /- 0.6 and 2.4 + /- 0.5 embryos/transfer , respectively . Twenty-five pregnancies were achieved in group A , and 21 pregnancies in group B. This led to a comparable clinical pregnancy and implantation rates of 62.5 % and 34 % as compared to 52 % and 26.8 % for groups A and B , respectively . CONCLUSION ( S ) Hyaluronic acid can successfully replace albumin as a sole macromolecule in a human embryo transfer medium and result in high pregnancy and implantation rates . The use of this supplement is an important step in the development of human embryo culture media free of blood-derived additives |
1,760 | 20,556,780 | Moderate quality evidence shows that patients with acute LBP may experience small benefits in pain relief and functional improvement from advice to stay active compared to advice to rest in bed ; patients with sciatica experience little or no difference between the two approaches .
Low quality evidence suggests little or no difference between those who received advice to stay active , exercises or physiotherapy . | BACKGROUND Acute low-back pain ( LBP ) is a common reason to consult a general practitioner .
Debate continues on the comparative effectiveness of advice on bed rest and staying active as part of the primary care management .
OBJECTIVES To determine the effects of advice to rest in bed or stay active for patients with acute low-back pain or sciatica . | 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 RésuméLe repos au lit est habituellement considéré comme un traitement efficace de la lombalgie aiguë . Cependant la durée optimale de cette mise au repos au lit est encore discutée , variant selon les écoles de 2 jours à 2 semaines . C'est un paramètre imporant à considérer , compte tenu des préjudices économiques et fonctionnels d'une inactivité prolongée . Le but de ce travail est de faire une évaluation objective de l'efficacité de deux durées de repos différentes , à l'aide d'une mesure dynamométrique de la fonction musculaire du tronc pratiquée à la suite d'une mise au repos plus ou moins longue . Cinquante et un patients , étudiants ou travaillant à leur propre compte , consultant pour des lombalgies aiguës , ont été r and omisés en deux groupes . Au groupe I a été prescrit un repos au lit de 3 jours et au groupe II un repos de 7 jours . Nous avons utilisé un appareil dynamométrique ( Isostation B200 , Isotechnologies , USA ) pour l'évaluation isoinertielle de la fonction musculaire du tronc dans les différents plans . Les patients ont été évalués au ler et au 5e jour dans le groupe I ; la seconde évaluation a été reportée au 9e jour dans le groupe II . Les variables mesurées dans le plan sagittal ont été les forces isometriques en flexion et extension , l'amplitude des mouvements sans résistance , la valeur moyenne des forces développées dans les mouvements de flexion et d'extension ainsi que les vitesses moyennes . On a également dem and é aux patients de situer sur une échelle graphique l'intensité de la douleur ressentie le jour de l'évaluation . L'amélioration de tous les paramètres mesurées a été importante et hautement significative ( P<0,001 ) dans les deux groupes . Les résultats du testing fonctionnel et de l'échelle des douleurs n'ont pas montré de différences significatives entre ces deux groupes . Chez ces patients relativement jeunes et motivés , un repos au lit de trois jours a abouti à la même amélioration de la fonction et de la douleur que le repos de sept jours . Compte tenu des résultats objectifs identiques et aussi des avantages physiologiques et économiques indiscutables , il est préférable de prescrire une mise au repos plus brève . Summary Bed rest is usually considered an efficient treatment for acute low back pain . However , the optimal duration of bed rest is still being discussed . The recommended periods vary from 2 days to 2 weeks . The duration of optimum length is an important topic given the economical and physiological drawbacks of prolonged inactivity . The purpose of this work is to measure objective ly the efficacy of two different duration s of bed rest through a dynamometric measure of trunk function . Some 51 male patients , students or self-employed , being treated for acute low back pain were r and omized into two groups . Group I was prescribed a bed rest period of 3 days and group II , a period of 7 days . We used a multiaxis isoinertial trunk testing dynamometric device ( Isostation B200 , Isotechnologies , USA ) . Patients were all assessed on day 1 and also on day 5 for group I or on day 9 for group II . The variables measured in the sagittal plane were isometric torques in flexion and extension , unresisted range of motion , average dynamic torques and average velocities . Patients were also asked to fill in a visual analogue pain scale on both assessment days . The improvement of all performance measures were important and highly significant ( P<0.001 ) in both groups . The results of the functional testing and the visual analogue pain scale showed no significant differences between the groups . In these relatively young and motivated patients , a duration of bed rest of 3 days result ed in the same objective functional improvement of trunk function and pain rating as a period of 7 days . This shorter duration should be considered as preferable , given the same objective results but important physiological and economical advantages The roles of bedrest , antiinflammatory medication , and analgesic medication in the treatment of acute back strain were objective ly analyzed to determine whether they have a measurable effect on the return of patients to full daily activities as well as on the relief of pain . Two hundred patients were studied prospect ively . Each patient had the diagnosis of acute back strain , which was defined as nonradiating low-back pain . The results of the patient 's neurologic examination , straight leg raising test , and lumbosacral spine roentgenograms had to be within normal limits for the patient to be included in the study . The results showed that bedrest , as compared with ambulation , will decrease the amount of time lost from work by 50 % . Bedrest will also decrease the amount of discomfort by 60 % . Analgesic medication , when combined with bedrest , will further decrease the amount of pain incurred , particularly when used in the first three days of the healing process . However , analgesic medication will not allow a more prompt return to work . Antiinflammatory medication , when added to bedrest in the treatment of lumbago , does not provide an advantage over bedrest alone OBJECT The authors conducted a study to compare the efficacies of three nonsurgical treatment strategies in patients with sciatica . Their hypothesis was that bed rest , physiotherapy , and continuation of activities of daily living ( ADLs ) ( control treatment ) are each of equivalent efficacy . METHODS This r and omized controlled trial was design ed for comparison of bed rest , physiotherapy , and continuation of ADLs . The setting was an outpatient clinic . General practitioners were asked to refer patients for treatment as soon as possible . The authors enrolled 250 patients ( < 60 years of age ) with sciatica of less than 1-month 's duration and who had not yet been treated with bed rest or physiotherapy . Primary outcome measures were radicular pain ( based on a visual analog pain scale [ VAPS ] ) and hampered ADLs ( Quebec Disability Scale [ QDS ] ) . Secondary outcome measures were the rates of treatment-related failure and surgical treatment . Measures were assessed at baseline and during follow up at 1 , 2 , and 6 months . Mean differences in VAPS and QDS scores between bed rest and control treatment were 2.5 ( 95 % confidence interval [ CI ] -6.4 to 11.4 ) and -4.8 ( 95 % CI -10.6 to 0.9 ) at 1 month and 0.9 ( 95 % CI -8.7 to 10.4 ) and -2.7 ( 95 % CI -9.9 to 4.4 ) at 2 months , respectively . The respective differences between physiotherapy and control treatment were 0.8 ( 95 % CI -8.2 to 9.8 ) and -0.5 ( 95 % CI -6.3 to 5.3 ) at 1 month and -0.3 ( 95 % CI -9.4 to 10 ) and 0.0 ( 95 % CI -7.2 to 7.3 ) at 2 months . The respective odds ratios for treatment failure and surgical treatment of bed rest compared with control treatment were 1.6 ( 95 % CI 0.8 - 3.5 ) and 1.5 ( 95 % CI 0.7 - 3.6 ) at 6 months . When physiotherapy was compared with control treatment , these ratios were 1.5 ( 95 % CI 0.7 - 3.2 ) and 1.2 ( 95 % CI 0.5 - 2.9 ) at 6 months , respectively . CONCLUSIONS Bed rest and physiotherapy are not more effective in acute sciatica than continuation of ADLs A controlled trial of continuous lumbar traction in the treatment of back pain and sciatica showed similar improvements in both the treated group ( weighted traction ) and the control group ( simulated traction ) . The findings of this study question the justification of admitting patients with back pain into hospitals for purpose s of traction alone The results of a multicentered r and omised clinical trial are reported of bed rest and of a physiotherapy and education programme for patients who presented in family practice with an acute episode of low back pain . No beneficial effect of either treatment was observed on several clinical outcome measures , including straight leg raising , lumbar flexion , activities of daily living , and pain . In fact the results favoured early mobilisation over bed rest and suggested that the physiotherapy and education programme was doing more harm than good . Moreover , additional analyses , which focused on clinical ly interesting patient subgroups , discovered no subset of patients who benefited from either of the treatments under study . Having failed to identify any clinical ly important benefits , or other explanations for these negative results , we can only conclude that family doctors have little reason to prescribe either bed rest or isometric exercises to patients who suffer from low back pain Background . The management of common low back pain has two principal objectives : to relieve acute pain and to attempt prevention of transition to chronicity . Several studies have shown the ineffectiveness of prolonged periods of bed rest . Objective . To compare 4 days of bed rest with continued normal daily activity in acute low back pain , taking into account the type of work ( physical or sedentary labor ) . Methods . This open , comparative multicenter study enrolled 281 ambulatory patients , ages 18 to 65 years , with low back pain ( onset < 72 hours ) . The subjects did not have pain radiating below the buttocks and did not have work-related injuries . They were r and omized into two treatment groups : one instructed to continue normal activity ( insofar as the pain allowed ) , and the other prescribed 4 days of bed rest . After inclusion , patients were seen at three visits : on day 6 or 7 , after 1 month , and after 3 months . Results . On day 6 or 7 , pain intensity was similar for both groups , as was the overall judgment of the treatment by patients and physicians . At 1 and 3 months , the groups again had equivalent intensity of back pain , functional disability , and vertebral stiffness . A higher proportion of patients in the bed rest group than in the normal activity group had an initial sick leave ( 86%vs 52%;P < 0.0001 ) . This difference was greater for the patients whose work was sedentary . Conclusions . For patients with acute low back pain , normal activity is at least equivalent to bed rest . The findings of this study indicate that prescriptions for bed rest , and thus for sick leaves , should be limited when the physical dem and s of the job are similar to those for daily life activities Bed rest is usually recommended for acute low back pain . Although the optimal duration of bed rest is uncertain , a given prescription may directly affect the number of days lost from work or other activities . In a r and omized trial , we compared the consequences of recommending two days of bed rest ( Group I ) with those of recommending seven days ( Group II ) . The subjects were 203 walk-in patients with mechanical low back pain ; 78 percent had acute pain ( less than or equal to 30 days ) , and none had marked neurologic deficits . Follow-up data were obtained at three weeks ( 93 percent ) and three months ( 88 percent ) . Although compliance with the recommendation of bed rest was variable , patients r and omly assigned to Group I missed 45 percent fewer days of work than those assigned to Group II ( 3.1 vs. 5.6 days , P = 0.01 ) , and no differences were observed in other functional , physiologic , or perceived outcomes . For many patients without neuromotor deficits , clinicians may be able to recommend two days of bed rest rather than longer periods , without any perceptible difference in clinical outcome . If widely applied , this policy might substantially reduce absenteeism from work and the result ing indirect costs of low back pain for both patients and employers BACKGROUND AND METHODS Bed rest is widely advocated for sciatica , but its effectiveness has not been established . To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks , we r and omly assigned 183 subjects to either bed rest or watchful waiting for this period . The primary outcome measures were the investigator 's and patient 's global assessment s of improvement after 2 and 12 weeks , and the secondary outcome measures were changes in functional status and in pain scores ( after 2 , 3 , and 12 weeks ) , absenteeism from work , and the need for surgical intervention . Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients ' treatment assignments . RESULTS After two weeks , 64 of the 92 patients in the bed-rest group ( 70 percent ) reported improvement , as compared with 59 of the 91 patients in the control ( watchful-waiting ) group ( 65 percent ) ( adjusted odds ratio for improvement in the bed-rest group , 1.2 ; 95 percent confidence interval , 0.6 to 2.3 ) . After 12 weeks , 87 percent of the patients in both groups reported improvement . The results of assessment s of the intensity of pain , the bothersomeness of symptoms , and functional status revealed no significant differences between the two groups . The extent of absenteeism from work and rates of surgical intervention were similar in the two groups . CONCLUSIONS Among patients with symptoms and signs of a lumbosacral radicular syndrome , bed rest is not a more effective therapy than watchful waiting 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 BACKGROUND Bed rest and back-extension exercises are often prescribed for patients with acute low back pain , but the effectiveness of these two competing treatments remains controversial . METHODS We conducted a controlled trial among employees of the city of Helsinki , Finl and , who presented to an occupational health care center with acute , nonspecific low back pain . The patients were r and omly assigned to one of three treatments : bed rest for two days ( 67 patients ) , back-mobilizing exercises ( 52 patients ) , or the continuation of ordinary activities as tolerated ( the control group ; 67 patients ) . Outcomes and costs were assessed after 3 and 12 weeks . RESULTS After 3 and 12 weeks , the patients in the control group had better recovery than those prescribed either bed rest or exercises . There were statistically significant differences favoring the control group in the duration of pain , pain intensity , lumbar flexion , ability to work as measured subjectively , the Oswestry back-disability index , and number of days absent from work . Recovery was slowest among the patients assigned to bed rest . The overall costs of care did not differ significantly among the three groups . CONCLUSIONS Among patients with acute low back pain , continuing ordinary activities within the limits permitted by the pain leads to more rapid recovery than either bed rest or back-mobilizing exercises BACKGROUND Bed rest is a traditional treatment for back pain , yet only in recent years has the therapeutic benefit of this been question ed . AIM The aim of this pilot study was to ascertain whether or not 48 hours ' bed rest had an effect on the outcome of acute low back pain . METHOD The study was conducted as a r and omized controlled trial to compare a prescription of 48 hours ' strict bed rest with controls ; the control subjects were encouraged to remain mobile and to have no daytime rest . Nine general practitioners from practice s in the West Midl and s recruited patients in the age range 16 - 60 years who presented with low back pain of less than seven days ' duration , with or without pain radiation . The outcome measures assessed were : change in straight leg raise and lumbar flexion after seven days , Oswestry and Rol and -Morris disability scores after seven days and 28 days , and time taken from work . RESULTS Forty two patients were recruited : 20 were allocated to bed rest and 22 as controls . Compared with the bed rest group the control group had statistically better Rol and -Morris scores at day seven ( P < 0.05 ) but not at day 28 . At day seven , there were no statistically significant differences between groups in straight leg raise or lumbar flexion measurements although the control group had a better mean lumbar flexion than the bed rest group . The improvement in disability scores at day seven compared with day one was similar for the two groups but more of the control group had fully recovered ( defined as scores of one or zero on the Rol and -Morris disability scale and five or less on the Oswestry disability scale ) by day seven . Remaining mobile did not appear to cause any adverse effects . The number of days lost from work in both groups was equal . A large number of self-remedies and physical therapies were recorded by subjects from both groups . CONCLUSION The results of this pilot study did not indicate whether bed rest or remaining mobile was superior for the treatment of acute low back pain ; however , the study sample was small . Subjects in the control group possibly fared better as they appeared to have better lumbar flexion at day seven . It appears that 48 hours ' bed rest can not be recommended for the treatment of acute low back pain on the basis of this small study . Large-scale definitive trials are required to detect clinical ly significant differences |
1,761 | 25,003,310 | AUTHORS ' CONCLUSIONS The results did not show a difference in efficacy between trifluoperazine and low-potency antipsychotics .
Trifluoperazine produced more movement disorders . | BACKGROUND Antipsychotic drugs are the core treatment for schizophrenia .
Treatment guidelines state that there is no difference in efficacy between any other antipsychotic compounds , however , low-potency antipsychotic drugs are often perceived as less efficacious than high-potency compounds by clinicians , and they also seem to differ in their side-effects .
OBJECTIVES To review the effects in response to treatment of trifluoperazine and low-potency antipsychotics for people with schizophrenia . | Taking even this restricted group of patients , the aim of establishing clear cut differences between the drugs has not been achieved . The most clear cut finding was that no statistically significant difference was found between the ability of the two drugs , chlorpromazine and trifluoperazine , to improve motor activity in underactive schizophrenic patients . There were however , a number of observations which may be of interest . For the more active patients an overall measure of performance at the factory task showed an inconstant and non-significant initial improvement with both active drugs with maximum effect at the end of six weeks . There-after performance deteriorated , and when active drugs were reintroduced this deterioration was not reversed . The less active behaved differently . At the factory task they improved progressively through-out the experiment , but the greatest increment in their performance occurred during the Pl phase . No group 's speed of work was changed differentially by the two drugs . The least active group A increased their speed of work more during the six weeks Pl phase than at any other time ; Group B showed similar improvement during the P1 phase , but did not improve further when drugs were reintroduced ; Group C showed virtually no change in speed of work during the three phases of the experiment . When on drugs there was a small but highly statistically significant improvement over pre-drug scores on the Venables scale , indicating that the two drugs were effective . No significant difference between drugs was found , and after the first six weeks of treatment the maximum response was reached , with some worsening thereafter . There is a strong suggestion that the worsening in behaviour during the intervening placebo phase seen on the Venables scale occurs only in those previously treated with chlorpromazine . To this extent , therefore , trifluoperazine is to be preferred as a treatment . On this scale , as with the factory task , gains in behaviour obtained during the first six weeks of treatment were not repeated during the latter part of the cross-over . Strenuous attempts were made to maintain the environment constant for all groups , so that it is unlikely that chance environmental stimulation could be the sole explanation for these changes . A more likely explanation seems to be that , for the very inactive , once new patterns of behaviour have been initiated with the aid of drugs further improvement may occur without continuous medication . For the more active , however , starting drugs may also produce a temporary improvement , but the improvement is inconstant , it does not last as long and may be lost even when drugs are continued . Intermittent medication is evidently effective for inactive patients and may be advantageous . The more active seem to be improved to a much smaller extent by these drugs . The correlation , steadily increasing with treatment , between the two factors of the Venables scale suggests that both drugs have a beneficial effect on another puzzling aspect of the chronic schizophrenic : the differences between tests within individuals which they show on most measures of behaviour . This is an area of performance of importance therapeutically , but one which hitherto has been neglected in drug studies . We found no evidence to suggest that intermittent medication would have an adverse effect on this aspect of behaviour The attempt in one hospital to model a drug study after the NIMH nine-hospital collaborative study result ed in a useful modification in which relatively small numbers of newly admitted , acutely exacerbated chronic schizophrenic patients were studied for a period of four weeks . Statistically significant drug : placebo differences were easily detected on most psychiatric and behavioral variables , but not on the psychological performance tasks used . The overall design appears to be suitable for sequential analysis and might provide the basis for an early screening program for antipsychotic drugs in which very small numbers of subjects would be required for relatively short periods of observation . A possible differential drug response favoring thioridazine over chlorpromazine hydrochloride and fluphenazine hydrochloride on several variables was not statistically significant • Presently marketed antiparkinsonism drugs are potent anticholinergic agents that , while effective in treating extrapyramidal symptoms ( EPS ) , also are productive of or can exacerbate a number of side effects associated with psychotropic drugs . Some of these include gastrointestinal disturbances , visual difficulties , and tardive dyskinesia . A double-blind study was carried out to assess the efficacy ( and adverse effects ) of amantadine hydrochloride — an agent without appreciable anticholinergic activity — for the treatment of drug-induced EPS . Amantadine was found to be comparable in effect to benztropine mesylate , but with fewer side effects . The potential role of amantadine may be in the treatment of patients with druginduced EPS for whom medication with anticholinergic properties is contraindicated Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness , 120 entered a r and omised placebo-controlled trial of maintenance neuroleptic medication on discharge ; they were followed to relapse or loss to follow-up , for two years or to the end of the study . Of those on active medication , 46 % relapsed , as did 62 % of those on placebo ; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication . This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis , or because susceptibility to relapse is reduced by early institution of treatment . The study provides no data on which a decision between these alternative explanations can be based OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate A double-blind , placebo-controlled trial was carried out to determine the value of maintenance therapy with phenothiazines in a population of out patients who had recently recovered from an acute episode of schizophrenia . The drug was shown to be significantly more effective than the placebo in preventing relapse . The relationship of the trial patients to the population from which they were selected was defined in terms of clinical , historical , and social data . Maintenance therapy seems of little value in patients with a good prognosis and in the severely ill , but it is of value in the indeterminate group between these two extremes Poor neuroleptic response is a major unresolved clinical problem . Precise data concerning the frequency of poor neuroleptic response are not available . The implementation of treatment modalities that are specifically recommended for non‐responders ( such as clozapine ) increases the desirability of such data . This study evaluated the proportion of acutely exacerbated schizophrenics who remained unimproved by consecutive administration of haloperidol , chlorpromazine and perphenazine , in r and omly determined order . The overall improvement rate was 95 % . The frequency of good responses to the first , second and third drug were 67 % , 55 % , and 67 % respectively . Differences in receptor affinity profile might explain the added beneficial effect of a second or third drug CONTEXT Second-generation ( atypical ) antipsychotics ( SGAs ) are more expensive than first-generation ( typical ) antipsychotics ( FGAs ) but are perceived to be more effective , with fewer adverse effects , and preferable to patients . Most evidence comes from short-term efficacy trials of symptoms . OBJECTIVE To test the hypothesis that in people with schizophrenia requiring a change in treatment , SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs . DESIGN A noncommercially funded , pragmatic , multisite , r and omized controlled trial of antipsychotic drug classes , with blind assessment s at 12 , 26 , and 56 weeks using intention-to-treat analysis . SETTING Fourteen community psychiatric services in the English National Health Service . PARTICIPANTS Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects . INTERVENTIONS R and omized prescription of either FGAs or SGAs ( other than clozapine ) , with the choice of individual drug made by the managing psychiatrist . MAIN OUTCOME MEASURES Quality of Life Scale scores , symptoms , adverse effects , participant satisfaction , and costs of care . RESULTS The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded . Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores . Participants reported no clear preference for either drug group ; costs were similar . CONCLUSIONS In people with schizophrenia whose medication is changed for clinical reasons , there is no disadvantage across 1 year in terms of quality of life , symptoms , or associated costs of care in using FGAs rather than nonclozapine SGAs . Neither inadequate power nor patterns of drug discontinuation accounted for the result The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years ( mean ) . The role of adding an anti-depressant was also studied . Following a 4 week placebo period , high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks . Statistical analyses of the various change measures revealed that patients worsened significantly on placebo , all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration . No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage The efficacy of oral concentrate in the rapid tranquilization of 159 acutely disturbed patients in a psychiatric emergency service was evaluated . Patients were r and omly assigned to 1 of 10 treatment groups : 7 oral groups and 3 comparison intramuscular groups . Although intramuscular medication produced a faster response , concentrate also proved to be effective for rapid tranquilization . Side effects were benign and minimal . Age , sex , race , and diagnosis had no effect on outcome . The use of concentrate as a paradigm for treating acutely psychotic patients is discussed Research on strategies using low doses of neuroleptics in the long-term maintenance and /or prophylactic treatment of schizophrenia is review ed . The evidence available from prospect i ve controlled trials suggests that substantial dosage reduction is feasible for a subgroup of outpatient schizophrenics and that the incidence of abnormal involuntary movements might be reduced by such a strategy . In addition , lowering dosages may bring about some improvement in psychosocial adjustment . Further work is clearly needed to explore fully the benefit to risk ratio of this strategy and to identify those patients for whom it is most appropriate Urinary MHPG excretion in patients with acute schizophrenia was studied before and during a trial of the isomers of flupenthixol and placebo . Pretrial MHPG excretion was not related to severity of illness before the trial or to other pretrial clinical variables . In male subjects higher pretrial MHPG excretion was associated with a better outcome 1 year post-trial . However in females no relationship between MHPG excretion and outcome was established . During the trial there was a reduction in MHPG excretion in patients treated with β-flupenthixol but no decrease in the group treated with α-flupenthixol or chlorpromazine . In patients on placebo there was a reduction in MHPG excretion in those who dit well clinical ly , but not in those who did poorly . Thus low MHPG excretion may be a predictor of poor outcome in schizophrenia , but MHPG excretion also changes both as a function of clinical state and of neuroleptic drug administration Subjects Thirty-four newly admitted acute schizophrenic patients were studied : they included first admissions and others undergoing acute exacerbations with a history of previous acute schizophrenic episodes . None of these patients had received tranquillizing medication for at least one month prior to admission to hospital , or electroconvulsive therapy for at least two months . They ranged in age from seventeen to fifty-four years with a mean age of thirty-four . Some preliminary . findings with the first twenty subjects in this series have already been published ( 4 ) . coefficient of variation ( CV ) than the other fifty-five patients who were receiving a variety of drugs . The procedure described here permitted a more detailed analysis of the effects of two antipsychotic agents ( quite different in chemical structure ) upon the integrated EEG measures in a more systematic comparative design of shortterm drug effects . It also permitted a comparison of effects , both clinical and EEG , over a time period ( seven days ) similar to that in which the clinician might ordinarily decide whether his patient was showing satisfactory response , leading him to continue a particular antipsychotic compound or switch to another Because the importance of tranquilizing drugs has been difficult to assess precisely , the author undertook a study on the effect of the withdrawal of chlorpromazine and trifluoperazine on hospitalized male schizophrenics in Engl and . Although there were no major relapses among the placebo group , changes occurred that were sometimes disabling The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas In a double-blind , cross-over study , the comparative therapeutic effects of 6-week courses of two prototypic neuroleptics — haloperidol and chlorpromazine — and the reversal of those effects with benztropine were investigated in a group of 18 schizophrenics . Periodic measurements were made for 32 dimensions of psychopathology , social participation , span of attention , sleeplessness , pulse rate and neurological side effects . The results showed that haloperidol was generally a more effective drug over the period studied . This was particularly apparent in terms of social and emotional responsiveness , communicativeness and cognitive processes . The only superiority of chlorpromazine seemed to be that patients felt less dysphoric on it than they did on haloperidol . Haloperidol also proved to be more rapid in its action . The data failed to support the clinical validity of the distinction often made between “ sedative ” and “ activating ” neuroleptics . Consistent with previous reports , benztropine had the effect of diminishing therapeutic response to both neuroleptics . However , haloperidol again proved less susceptible to this effect . The slowness and lesser therapeutic efficiency of chlorpromazine and its greater susceptibility to benztropine reversal were all considered to be due to its built-in anticholinergic properties acting in opposition to its antipsychotic activity . The low potency of chlorpromazine-like drugs was attributed to their inherent anticholinergic characteristics . It was suggested that one of the factors determining potency differences among neuroleptics may be the degree of built-in anticholinergic activity Summary In a double-blind study of the comparative effectiveness of eight phenothiazines , 322 newly-admitted state psychiatric hospital patients requiring tranquilizing drug therapy were r and omly assigned to treatment with one of the following drugs : chlorpromazine , thioridazine , triflupromazine , prochlorperazine , perphenazine , thiopropazate , trifluoperazine , and fluphenazine . The design of the study permitted flexible dosages , and treatment , unless prematurely terminated , lasted 30 days . Psychological and /or psychiatric assessment s were made prior to treatment and at the end of 5 , 15 , and 30 days . Although results again substantiated the effectiveness of the phenothiazine compounds as a whole , evidence of differential drug effectiveness was equivocal using raw scores derived from st and ard rating scales and traditional methods of statistical analysis . Such analyses suggested negligible treatment differences in terms of means . Non-constant , non-additive treatment effects were greatly in evidence , however ; and the high incidence of heterogeneity of variance and of regression indicated that the drugs were neither equivalent nor interchangeable . Subsequent analyses of MSRPP Total Morbidity , involving the more severely ill patients and using a scale transformation to achieve homogeneity of variance , yielded significant treatment differences at every evaluation period . In these analyses , the drugs found to be consistently effective over the 30-day treatment period were prochlorperazine , perphenazine , and fluphenazine . Those found to be less effective were thioridazine , triflupromazine , and thiopropazate . For the less severely ill patients , significant mean differences among the eight drugs were not obtained ; however , there was a tendency for the rank order of drug efficacy in this group to be the reverse of that obtained with the severely ill patients In a double-blind trial in which 45 patients with acute schizophrenia took part the alpha-isomer of flupenthixol ( which blocks the dopamine receptor ) was found to be significantly more effective than both beta-flupenthixol ( which does not ) and placebo . The drug effect was confined to the " positive " symptoms -- delusions , hallucinations , and though disorder-- and appeared only in the 3rd and 4th weeks of the trial . It was as great in patients with evidence of deterioration ( Feighner-positive patients ) as in patients without deterioration and was less in patients who had affective disturbance in addition to schizophrenia symptoms . The findings are consistent with the hypothesis that dopamine-receptor blockade is the only requirement for antipsychotic activity and suggest that the antipsychotic effect occurs in patients with typically schizophrenic illnesses but may be limited to positive symptoms We are conducting a prospect i ve study of tardive dyskinesia ( TD ) in psychiatric patients over age 45 , a large proportion of whom have had less than 1 month of total lifetime neuroleptic exposure . Patients are treated with the lowest effective dose of either haloperidol ( usually 1 - 3 mg daily ) or thioridazine ( usually 25 - 75 mg daily ) . Patients are reexamined 1 month and 3 months after initial assessment and then at 3-month intervals . To date , a total of 68 patients ( mean age 69.5 years ) have been evaluated . Survival analysis showed a 27 percent cumulative incidence of TD ( the 95 % confidence interval being 14 % to 40 % ) with 6 months of neuroleptic treatment in the study . The TD and non-TD patients did not differ on demographic and baseline clinical measures . Instrumental assessment showed that a greater proportion of TD patients had sub clinical evidence of dyskinesia prior to the institution of neuroleptics , compared with non-TD patients A study design ed to assess the relative efficacy of chlorpromazine and Serenace in the control of chronic schizophrenics is described . Twenty-five cases were selected for the study and were r and omly allocated to treatment . The condition of the patients was assessed at fortnightly intervals over the eight-week duration of trial period . No significant differences in side-effects emerged in patients on chlorpromazine and Serenace in the dosages administered . The statistically significant trends all showed a superiority of Serenace above chlorpromazine which was in accord with the clinical picture The schizophrenic patient 's early psychological response to neuroleptic treatment has been demonstrated to be a significant predictor of treatment response . The validity of the construct of subjective response is evaluated by comparison of two measures . Fifty-five recently admitted and unmedicated schizophrenic patients were r and omly allocated to chlorpromazine or haloperidol . Subjective responses at 24 and 48 hours as assessed by two different scales , the Van Putten & May scale and the self-administered Drug Attitude Inventory , were strongly correlated with outcome at three weeks . Early emergence of extrapyramidal symptoms was not related to subjective response , but dysphoric patients had a greater incidence of EPS by the end of treatment than did non-dysphoric patients . The two measures showed high concordance in identification of early drug dysphoria In a double-blind study the therapeutic efficacy of sulpiride was compared to that of haloperidol — an established neuroleptic agent . A total of 30 female patients with a diagnosis of chronic schizophrenia were initially stabilised on the dosage of haloperidol which produced optimum therapeutic response when given once or twice daily . The patients were then r and omly allocated to receive either sulpiride or haloperidol over a period of 12 weeks . Plasma drug concentrations and prolactin levels were determined . Clinical effects were evaluated by Brief Psychiatric Rating Scale ( BPRS ) , Wing Rating Scale , and Extrapyramidal Symptoms Rating Scale ( EPS ) . A st and ardised side-effects checklist was used . Treatment with sulpiride was associated with a significant rise in plasma prolactin level , but paradoxically these patients had significantly reduced extrapyramidal symptoms . No significant correlation was found between plasma sulpiride concentration and prolactin level or any of the clinical variables . The study confirms the antipsychotic activity of sulpiride BACKGROUND There are cl aims that the extra costs of atypical ( second-generation ) antipsychotic drugs over conventional ( first-generation ) drugs are offset by improved health-related quality of life . AIMS To determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia . METHOD Cost-effectiveness acceptability analysis integrated clinical and economic r and omised controlled trial data of conventional and atypical antipsychotics in routine practice . RESULTS Conventional antipsychotics had lower costs and higher quality -adjusted life-years ( QALYs ) than atypical antipsychotics and were more than 50 % likely to be cost-effective . CONCLUSIONS The primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics The subjects were 62 patients hospitalized for acute exacerbations of schizophrenia and were r and omly assigned to receive risperidone ( mean dose , 7.4 mg/day ) , haloperidol ( 7.6 mg/day ) , or methotrimeprazine ( 100 mg/day ) for 4 weeks . Clinical improvement , defined a priori as a 20 % reduction in total Positive and Negative Syndrome Scale ( PANSS ) scores at end point , was attained by 81 % of the risperidone patients , 60 % of the haloperidol patients , and 52 % of the methotrimeprazine patients ( p < 0.05 ) . The reductions in total PANSS and Clinical Global Impression Scale severity scores from baseline to end point were significantly greater in the risperidone patients than in the other two groups . Reductions in scores on the Psychotic Anxiety Scale were significantly greater in the risperidone patients than the methotrimeprazine patients ; the difference between haloperidol and methotrimeprazine was not significant . Extrapyramidal symptoms ( scores on the Extrapyramidal Symptom Rating Scale ) were more severe in the haloperidol patients than in the other two groups , but few differences were apparent between risperidone and methotrimeprazine patients . It is concluded that risperidone is an effective antipsychotic and anxiolytic agent in schizophrenic patients Conventional clinical trials involve tests of hypotheses with statistics computed from values of dependent variables alone . An alternative is to test hypotheses with statistics computed from benefit/harm scores that measure longitudinal associations between dose and values of the dependent variables . The proposed st and ardized measure of benefit/harm quantifies the strength of evidence that a patient did either better or worse while on treatment . A benefit/harm score , particularly when obtained from a r and omized , N-of-1 trial , indicates a beneficial or harmful treatment effect for the individual . Benefit/harm scores from sample s of patients are evaluated with st and ard statistical tests , with or without group comparisons , to make inferences about population s. The proposed alternative strategy can yield within-patient indicators of treatment effect that are more reliable , valid , comprehensive , and detailed . This , in turn , could help make many population -based clinical trials more informative , cost-effective , and clinical ly useful for participants Neurochemical distinctions have been made between neuroleptic drugs that affect D-1 receptors as well as D-2 receptors , compared with those neuroleptic drugs that affect only D-2 receptors . However , a controlled double-blind study of haloperidol vs. chlorprothixene in schizophrenic patients found no significant differences BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism OBJECTIVE To assess the effectiveness of olanzapine for treating schizophrenia and to assess if olanzapine promotes a better quality of life than first-generation antipsychotics ( FGAs ) . METHOD Multicenter , naturalistic , r and omized controlled study , comparing olanzapine with FGAs , at hospitalization and during a 9-month follow-up . Outcome assessors were blind to the allocated drug . The dose of antipsychotic was determined by doctors according to their clinical practice routines . Data collection was performed from April 1999 to August 2001 . RESULTS 197 patients with DSM-IV-diagnosed schizophrenia were allocated to olanzapine ( N = 104 ) and FGA ( N = 93 ) . Patients taking olanzapine showed greater improvements in Positive and Negative Syndrome Scale ( PANSS ) negative symptoms ( mean difference = 2.3 , 95 % CI = 0.6 to 4.1 ) and general psychopathology ( mean difference = 4.0 , 95 % CI = 0.8 to 7.2 ) sub-scales and fewer incidences of tardive dyskinesia ( RR = 2.4 , 95 % CI = 1.4 to 4.2 , p < .0001 ) . Olanzapine was also associated with greater improvement in a number of health-related quality -of-life outcomes on the Medical Outcomes Study 36-item Short-Form Health Survey , including physical functioning ( mean difference = 6.6 , 95 % CI = 1.2 to 11.9 ) , physical role limitations ( mean difference = 13.7 , 95 % CI = 3.0 to 24.3 ) , and emotional role limitations ( mean difference = 12.1 , 95 % CI = 0.7 to 23.5 ) . Patients taking olanzapine gained significantly more weight during the trial than patients taking FGAs , with a correspondent endpoint increase in the body mass index ( BMI ) of 28.7 versus 25.3 ( p < .001 ) . CONCLUSION Compared with FGAs , olanzapine has advantages in terms of improvements of negative symptoms and quality of life . It is also associated with fewer incidences of tardive dyskinesia and greater increases in weight and BMI . These findings are highlighted by the naturalistic approach adopted in this trial OBJECTIVE Long-term efficacy of asenapine in preventing schizophrenia relapse was assessed in a 26-week double-blind , placebo-controlled trial that followed 26 weeks of open-label treatment . METHOD Stable schizophrenia patients ( DSM-IV-TR criteria ) who were cross-titrated from previous medication to sublingual asenapine and remained stable during 26 weeks of open-label treatment were eligible for 26 weeks of double-blind treatment , with r and omization to continued asenapine or switch to placebo . Time to relapse/impending relapse ( primary endpoint , as usually determined by specific scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Severity of Illness Scale ) and discontinuation for any reason ( key secondary endpoint ) were assessed by survival analyses for asenapine versus placebo . The study was conducted from May 2005 through June 2008 . RESULTS Of 700 enrolled patients treated with open-label asenapine , 386 entered ( asenapine , n = 194 ; placebo , n = 192 ) and 207 completed ( n = 135 ; n = 72 ) the double-blind phase . Times to relapse/impending relapse and discontinuation for any reason were significantly longer with asenapine than with placebo ( both P < .0001 ) . Incidence of relapse/impending relapse was lower with asenapine than placebo ( 12.1 % vs 47.4 % , P < .0001 ) . The modal dosage of asenapine was 10 mg twice daily in both phases . During the double-blind phase , the incidence of adverse events ( AEs ) considered serious with asenapine and placebo was 3.1 % and 9.9 % , respectively ; incidence of extrapyramidal symptom-related AEs was 3.1 % and 4.7 % , respectively . The most frequently reported AEs with asenapine versus placebo were anxiety ( 8.2 % ; 10.9 % ) , increased weight ( 6.7 % ; 3.6 % ) , and insomnia ( 6.2 % ; 13.5 % ) . The incidence of clinical ly significant weight gain ( ≥ 7 % increase from double-blind baseline ) was 3.7 % with asenapine and 0.5 % with placebo . CONCLUSIONS Long-term treatment with asenapine was more effective than placebo in preventing relapse of schizophrenia and appeared to be safe and well tolerated . TRIAL REGISTRATION clinical trials.gov Identifier NCT00150176 • Prolixin ( Fluphenazine ) Enanthate , an injectible esterified trifluoromethyl phenothiazine derivative with an extended duration of action , was design ed for use with schizophrenic patients who are unreliable in taking oral medications . The magnitude of the problem is indicated by the estimate that 46 % of out- patients ~O,~1 and 20 % of in- patients ll have difficulties in this area . A number of studies ' · ' ; ' ; " " , 15,1 ; , , ' have reported the usefulness of Prolixin Enanthate in the treatment of schizophrenics in both inpatient and outpatient setting s , although some1,~. " indicated difficulty with side effects . All of these studies , however , were clinical rather than experimental evaluations . Only one ' used a control group and this was comprised of patients known to be or suspected of not taking oral medication . None of In a double-blind cross-over trial , 20 chronic schizophrenic patients were treated with sulpiride and haloperidol in two 12-week periods . The final median dose of sulpiride was 2000 mg/day ( range 800 - 3200 ) and of haloperidol 12 mg/day ( range 6 - 24 ) . Sulpiride had an antipsychotic effect and therapeutic profile not significantly different from that of haloperidol . In spite of the high doses of sulpiride , extrapyramidal side-effects were seen less frequently during the first four weeks of the sulpiride period than during the corresponding haloperidol period ( P less than 0.05 ) , whereas autonomic side-effects were equally rare for both drugs . A positive correlation was found between daily dose and plasma concentration of both sulpiride ( P less than 0.001 ) and haloperidol ( P less than 0.05 ) , but no correlation could be established between clinical effects and plasma levels of either neuroleptic Of 253 patients from nine medical centres identified with first episodes of schizophrenic illness , 17 did not achieve discharge during the period of trial recruitment . 120 entered a r and omised controlled trial of neuroleptic medication and were followed-up , as were 116 who were eligible for the trial but did not enter it . Overall , 60 % of the sample had relapsed within two years of discharge ; age , sex , ethnic origin , duration of admission , social withdrawal before admission , and type of onset of illness were not significantly related to relapse . Relapse rates were lower on active trial or st and ard medication than placebo , but however assessed , outcome at this early stage was poor for many patients Trade names of drugs mentioned in this paper : haloperidol , Haldol ( McNeil Laboratories , Fort Washington , Pa. ) ; ehlorpromazine , Thorazine ( Smith Kline and French , Philadelphia , Pa. ) ; benztropine , Cogentin ( Merck Sharp and Dohme , West Point , Pa. ) ; diphenhydramine , Benadryl ( Parke-Pavis , Detroit , Mich. ) . The effect of an anticholinergic antiparkinsonism drug , benztropine , on the therapeutic course of neuroleptie treatment in 18 schizophrenics was investigated in a double blind cross-over study involving haloperidol and ehlorpromazine . Significant therapeutic reversal was observed with benztropine in terms of the social , affective , and cognitive dysfunctions characteristically seen in schizophrenic psychosis . The hallucinatory behavior and disturbed attention were not so affected . The aspects of the clinical picture to show significant nontherapeutic change with benztropine differed with the stage of treatment and seemed to be determined by the kinetics of the therapeutic process . The effect was one of exacerbation of the disorder and not a toxic confusional state sometimes associated with anticholinergic drugs . The practical and theoretical significance of these findings was discussed . It was suggested that the benztropine reversal of therapeutic changes provided a valuable pharmacological model for underst and ing the neurobiological basis of schizophrenic decompensation and its restitution with neuroleptics . The reported data were considered as indirect evidence suggesting that cholinergic neuronal mechanisms are involved in both of these processes . It was speculated that these mechanisms may well be the cholinergic suppressor systems , such as the periventricular system , which function in reciprocal relationship with the facilitatory catecholamine pathways in the limbic organization and basal ganglia known to be affected by neuroleptics A small study was carried out to compare the clinical effects of the two butyrophenone compounds , triperidol and haloanisone to those of trifluoperazine , in a population of chronically hospitalized long-term schizophrenics in a closed ward setting . Twenty-seven patients were r and omly assigned to one of the three compounds , and treated for a twelve-week period under double-blind conditions . Observations with a modified PRP rating scale , based on ward nurses ' monthly ratings , revealed an over-all improvement after one month of treatment , but differences between the three drugs were not apparent and the over-all decrease of this PRP morbidity score was not sustained in subsequent ratings . Psychiatrist 's ratings on the IMPS revealed several symptom-factor differences with treatment . Between-drug differences on these factors were apparent . They are discussed in terms of the possible differences in type of drug action which they may reflect . The incidence of parkinsonistic side effects with each drug is presented . In no case did the side effects prevent continued treatment with the compound In a cross-over trial 16 elderly psychiatric patients with tardive dyskinesia were treated with thioridazine ( median dose , 267.5 mg/day ) for three months , followed by haloperidol ( 5.25 mg/day ) , haloperidol ( 5.25 mg/day ) + biperiden ( 6 mg/day ) , thioridazine ( 267.5 mg/day ) , and clozapine ( 62.5 mg/day , only 7 patients ) , all for periods of 4 weeks with 4-week drug-free intervals . The tardive dyskinesia syndrome and the parkinsonism were evaluated blind according to a self-constructed rating scale and a modified Webster scale from weekly video-tape recordings . At the end of the treatment periods the hyperkinesia score was lower during haloperidol than during either thioridazine for 3 months ( total score , 2.2 vs. 3.2 , P<0.05 ) , thioridazine for 4 weeks ( total score , 2.2 vs. 4.8 , P<0.02 ) , or haloperidol + biperiden ( score , 2.2 vs. 6.2 , P<0.01 ) . Clozapine had no significant antihyperkinetic effect , but in one patient it exerted a clear antiparkinsonian effect . After withdrawal of the initial thioridazine treatment , the hyperkinesia score was lower than after the subsequent haloperidol treatment ( 6.5 vs. 9.0 , P<0.01 ) , but after the second thioridazine period the hyperkinesia was of the same magnitude as after the preceding haloperidol periods . Biperiden increased the tardive dyskinesia syndrome during treatment , but did not significantly influence the syndrome after withdrawal of the treatment . It is concluded that ( 1 ) haloperidol ( a strong antidopaminergic neuroleptic ) has a more pronounced antihyperkinetic effect than thioridazine and clozapine ( weaker antidopaminergic neuroleptics ) ; ( 2 ) haloperidol might have a greater tendency to induce tardive dyskinesia than thioridazine ; ( 3 ) administration of anticholinergics concomitant with neuroleptic drugs antagonizes the antihyperkinetic effect of haloperidol , but may not influence the intensity of tardive dyskinesia after withdrawal of the treatment One of the main unsolved problems , and one which produces divergent results in clinical psychopharmacology , is that concerning the selection of patients and their diagnostic definition . An automated diagnostic procedure ( PDA ) was set up in order to classify each patient into one nosographic category on the basis of a cross-sectional examination of his mental state . Such diagnostic procedure appears particularly suitable for multicenter drug trials , since it gives a profile and a diagnostic definition of patients , assessed by investigators from different areas and with different cultural , and clinical background s. In a multicenter trial ( sulpiride versus haloperidol ) PDA offered a chance to re-examine and analyze the characteristics of each patient and therefore to control the criteria followed for the sample selection in the various experimental setting s. The agreement between clinician and computer diagnosis was 78.9 % ; this agreement rises to 85.5 % if the computerlabelled schizo-affective syndromes are considered within the schizophrenic group . Moreover , and attempt has been made to relate psychopathological patterns to drug responses In an attempt to begin to establish minimum effective dosage requirements for the maintenance treatment of schizophrenia , we undertook a double-blind comparison of low-dose fluphenazine decanoate ( 1.25 to 5.0 mg/2 wk ) with the st and ard-dose regimen ( 12.5 to 50.0 mg/2 wk ) in outpatient schizophrenics . For the first 126 patients studied , cumulative relapse rates at one year for the low dose were 56 % and for the st and ard dose 7 % , a significant difference . Despite the fact that very little dyskinetic symptomatology developed in the sample as a whole , the low-dose treatment appeared to have a significant advantage in producing fewer early signs of tardive dyskinesia . Severity of relapse and total cumulative dosage were also considered THE FACT that neuroleptic drugs can cause dyskinesias other than parkinsonism or acute dystonia has been well documented by more than 50 papers . I review ed the literature on this subject in 1968 1 ; Schmidt and Jarcho , among others , described the most important manifestations of these abnormalities in an issue of the Archives in 1966 . 2 It suffices to mention here that this type of disorder , also called tardive dyskinesia , is characterized by complex repetitive involuntary motility , localization in the oral region ( bucco-lingual syndrome ) or in the distal parts of the extremities , rocking of the pelvis and shifting of weight from foot to foot , late onset in the course of drug therapy , persistence for months or years after drug withdrawal , and failure to respond to antiparkinsonian drugs . In addition , cases have been reported in which the syndrome resembles Huntington 's chorea , dystonia deformans , choreo-athetosis and various types of tics . The Clinical trials with psychopharmaca ought to be part of the routine in every hospital actively concerned with pharmacotherapy , in order to ascertain the clinical value of new drugs , to gain experience in evaluation of drug effects under st and ardized conditions , 2nd to attain knowledge of target symptoms , patterns of effect and side effects of each drug . Only extensive clinical experience collected under scientific conditions and critically evaluated , will enable us to replace “ feeling ” with rationally founded therapy . As part of the elaboration of methods for clinical drug trials at our hospital , we have chosen to do a controlled study of fluphenazine compared with chlorpromazine in the treatment of schizophrenia and schizophrenia-like psychoses . I n this country fluphenazine has mostly been used as an anxiolyticum in the dosage range of 9’2 - 2 mg a day . ( 2 . ) Both from Europe and U.S.A. there are several clinical reports characterizing fluphenazine as an active phenothiazine , especially in the treatment of schizophrenia , and with good tolerance . ( 1 , 3 , 4 , 5 , 11 . ) Fluphenazine is the trifluoromethyl-analogue to perphenazine , that is a piperazine-phenothiazine , and has the characteristics of this group . ( Fig. 1 . ) As to the effect per mg , fluphenazine is the most potent phenothiazine as of today ( 12 . ) We wanted to compare this drug with chlorpromazine , partly because the latter belongs to the opposite group of phenothiazines , partly because chlorpromazine has been well known for several years and has status as a reference drug . We also nra ~ ited to compare a new phenothiazine with an old one Abstract Sixteen out of 25 hebephrenic and paranoid schizophrenic patients completed a double‐blind cross‐over study with sulpiride and haloperidol . The patient sample was relatively chronic : Median age was 35 years ( range 26–53 years ) , median duration of illness 10 years ( 4–35 years ) , and median duration of neuroleptic treatment 5 years ( 1–28 years ) . Each patient was treated with sulpiride/haloperidol in r and om order for 12 weeks with a drug‐free period before each treatment phase A double-blind trial was conducted which attempted to compare and contrast the therapeutic effects of haloperidol and thioridazine in a chronic schizophrenic population . The psychiatric use of these two drugs , one a butyrophenone , the other a phenothiazine , is discussed with reference to the management of this clinical population This collaborative study on the efficacy of high doses of trifluoperazine in chronic schizophrenia showed that treatment response was related to length of hospitalization ; short-term patients benefited most . High doses of trifluoperazine were most effective with those short-term patients who had been on a piperazine phenothiazine prior to the study . Also , most placebo patients who had been receiving low doses of phenothiazines before the study did not suffer deleterious effects while they were off medication . Treatment implication s are discussed These guidelines for the biological treatment of schizophrenia were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry ( WFSBP ) . The goal during the development of these guidelines was to review systematic ally all available evidence pertaining to the treatment of schizophrenia , and to reach a consensus on a series of practice recommendations that are clinical ly and scientifically meaningful based on the available evidence . These guidelines are intended for use by all physicians seeing and treating people with schizophrenia . The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for schizophrenia , as well as from meta-analyses , review s and r and omised clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE data base and Cochrane Library . The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into four levels of evidence ( A – D ) . This first part of the guidelines covers disease definition , classification , epidemiology and course of schizophrenia , as well as the management of the acute phase treatment . These guidelines are primarily concerned with the biological treatment ( including antipsychotic medication , other pharmacological treatment options , electroconvulsive therapy , adjunctive and novel therapeutic strategies ) of adults suffering from schizophrenia Six hundred forty newly-admitted schizophrenic men in 35 VA hospitals were r and omly assigned to chlorpromazine , triflupromazine , mepazine , prochlorperazine , perphenazine and phenobarbital groups . Treatment followed a double blind procedure for 12 weeks . Patients were started on low " equivalent " doses of each drug which were gradually increased in a predetermined manner during the first 4 weeks . During the final 8 weeks , each prescribing physician adjusted the dose for each of his patients in order to evoke an optimal therapeutic response . Average daily doses during the flexible period were : chlorpromazine , 635 mg . ; triflupromazine , 175 mg . ; mepazine , 190 mg . ; prochlorperazine , 90 mg . ; and perphenazine , 50 mg . Clinical evaluations using two rating scales provided 24 criteria of change . For each criterion , the mean of each of the 6 treatment groups adjusted for the net effect of 12 control variables was compared by analysis of multiple covariance with the mean of every other treatment group at each of thr In a double blind chlorpromazine-controlled trial , high dosage haloperidol ( 100 mg daily ) given for three months , appreciably improved the mental state of male chronic ' drug resistant ' schizophrenic in patients in the rehabilitation/long-stay unit of one psychiatric hospital . The results of a three-month follow-up suggested that the improvement could be maintained in some patients on lower doses of the drug . Serious extrapyramidal side effects were not seen at high doses . However , the majority of patients on haloperidol showed a deterioration in ward behaviour , possibly related to drowsiness , and developed raised serum alkaline phosphatase levels . These side effects disappeared in the follow-up period when either the drug was discontinued or the dose of haloperidol reduced This investigation was carried out as a double-blind cross-over comparison between the effects of three low-dosage neuroleptic drugs on chronic schizophrenics suffering mainly from autism , anhedonia and loss of vitality but with no marked productive symptoms . An attempt was also made to evaluate the effects of amphetamine when given in combination with a neuroleptic drug . The effects of the treatment were judged clinical ly and by experimentalpsychological methods chiefly design ed to measure the arousal level In this research we investigated the effects of 4 antipsychotic drugs with different anticholinergic components on different memory functions of schizophrenic patients . Drugs were administrated in cumulative doses and memory was tested 90 min after each drug was administered . The results show that chlorpromazine and thioridazine impaired short‐term verbal memory after 6 h of sequential administration . Trifluoperazine and haloperidol improved short‐term verbal memory from the third to the fifth administration . Immediate memory , long‐term memory and visual short‐term memory were not impaired by any drug The emergence of depression , parkinsonism , and akathisia after neuroleptic therapy was associated with increased length of hospital-stay in schizophrenics with affective heredity only . In schizophrenics with schizophrenic heredity , increased length of hospital-stay was associated with residual hallucinations and apathy . In the former patients , findings were theoretically attributed to a putative biogenetic abnormality sensitive to the effects of neuroleptic drugs The treatment process with two prototypic neuroleptics — haloperidol and chlorpromazine— and the nontherapeutic effects of trihexyphenidyl on this process were studied in carefully matched groups of ten schizophrenics each , using a “ double-blind ” , repeated-measure , longitudinal research design . Measurements of various aspects of psychopathology , social participation and clinical indices of arousal were made periodically and objective tests of cognition and attention were given . The two treatment groups were highly comparable in epidemiological and clinical terms and differed significantly during the baseline period in only one of the 39 parameters . Longitudinal nonparametric analyses showed that significant therapeutic changes tended to occur more quickly and involved a wider spectrum of schizophrenic phenomena with haloperidol than with chlorpromazine . Parametric analyses also indicated that at the completion of the study , haloperidol-treated patients had significant improvement in many more dimensions than the chlorpromazine-treated patients and that the changes with haloperidol were generally of greater magnitude . At the same time , chlorpromazine treatment seemed to be more susceptible to the antagonistic effects of trihexyphenidyl . No differential patterns of responses were noted for the two neuroleptics to provide any clinical validity to the distinction often made between “ sedative ” and “ activating ” neuroleptics . These data were in agreement with those from a previous comparative study which had a very different research design and a somewhat different type of schizophrenic population . The clinical and potency differences between the two neuroleptics were again explained on the basis of the fact that chlorpromazine has much stronger built-in anticholinergic properties , which may be acting in opposition to the antipsychotic activity . It was suggested that the degree of inherent anticholinergic activity may be an important determinant of potency differences among presently known neuroleptics . The possible role of cholinergic mechanisms in schizophrenia was discussed In order to evaluate the influence of some neuroleptics on unproductive symptoms of schizophrenic process , first hospitalized patients with paranoid schizophrenia underwent monotherapy with perazine , fluphenazine , trifluoroperazine , chlorpromazine , and haloperidol . All the drugs eliminated the productive activity of the disease process within 2 months in both women and men aged 18 - 40 years . However , drugs showed different qualitative and quantitative effects on unproductive symptoms of schizophrenic process ; this fact allows the suggestion regarding the particular usefulness of drugs in the out-patient care A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors In a double-blind placebo controlled clinical trial in chronic schizophrenic patients , haloperidol and clopenthixol were found to be effective antipsychotic agents , favorably altering behavior as observed by the psychiatrist , the nurse , and ward attendants . In this respect they appeared to compare adequately to the st and ard drug , chlorpromazine . In this experiment , neither the st and ard drug nor the investigational drugs affected psychological test performance . The expected side effects such as extrapyramidal signs and sedation did occur and in some instances required dose reduction for alleviation . One case of possible hepatoxicity in the CX group occurred at the end of the study and was considered of serious import requiring cessation of medication . It was concluded that these chemically unrelated antipsychotics could be used in practice as therapeutic alternatives , the particular choice depending on side effects and possibly symptomatology In a double-blind comparison of haloperidol and mesoridazine in the treatment of 39 recently hospitalized schizophrenic patients , the two drug treatment groups showed comparable antipsychotic effects , though they did differ in side effects in expected manners . Analysis of the Brief Psychiatric Rating Scale to calculate an index of dysphoric response previously found predictive of poor ultimate outcome failed to predict outcome in this 4-week trial though patients with a dysphoric response to neuroleptics did prove to include a higher proportion of process schizophrenics , who might ultimately show poorer outcome , than did nondysphoric responders BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials Consenting schizophrenic patients ranging in age from 18 to 63 years were withdrawn from antipsychotics for at least 1 week and r and omly assigned to receive identical capsules of thioridazine ( n = 13 ) , molindone ( n = 10 ) , or haloperidol ( n = 12 ) for a minimum of 6 weeks . Compared with the molindone- and haloperidol-treated patients , the thioridazine-treated patients were significantly improved over time as measured by Brief Psychiatric Rating Scale ( BPRS ) and Hamilton Rating Scale for Depression ( HAM-D ) total scores . Improvement in BPRS scores was due largely to improvement in symptoms of anxiety and depression . Subjects did not differ significantly on other measures , with the important exception of weight . On average , molindone patients lost 5 pounds over the 6 weeks of treatment , whereas thioridazine patients gained 6 pounds . Haloperidol-treated patients had no significant weight changes Several investigators have found that the initial improvement of acute schizophrenia after some days of neuroleptic treatment is correlated in a statistically significant way to the outcome after four weeks . In all these studies the question arises as to whether the correlation between early response and subsequent outcome is due to a specific response to a certain neuroleptic , or whether patients who respond early simply have a better prognosis . In order to isolate the specific drug effect from prognostic influences we performed a controlled double-blind study in 50 newly admitted schizophrenic in patients . All patients were treated over three days with 15 mg haloperidol i.v . , following which they were classified as ' early responders ( ER ) ' ( markedly improved or improved ) or as ' early nonresponders ( EN ) ' and then r and omly assigned to group 1 ( 3 x 5 mg haloperidol p.o./d ) or to group 2 ( 3 x 100 mg perazin p.o./d ) . If there was a specific drug effect on the correlation between early response and subsequent outcome a therapeutic superiority of perazin in EN and no superiority in ER was expected . Independently of the treatment condition the mean BPRS score had decreased from 61.2 ( Sx = 12.1 ) to 38.1 ( Sx = 13.9 ) at the end of the study . ER and EN were evenly distributed in the haloperidol and perazin group . The analysis of variance revealed no significant interactions of the factors ' treatment condition ' x ' duration ' x ' early response ' ( p = 0.27 ) and ' treatment condition ' x ' early response ' ( p = 0.88 ) on the outcome ( BPRS , CGI ) . This means that the initial hypothesis of this study has to be rejected . ( ABSTRACT TRUNCATED AT 250 WORDS A total of 320 newly admitted schizophrenic men were r and omly assigned to either an aliphatic , piperidine , or piperazine phenothiazine . Physicians chose drugs within the class assigned and used them to maximal clinical advantage . None of the drug classes was superior to another in total efficacy . Finer differences were that piperazines were more effective in patients who were older and who were categorized as having " core " or " nonparanoid " types of schizophrenia , characterized chiefly by thought disorders . The prevailing belief that these drugs are more specific antipsychotic agents was given some support . Past difficulties in replicating specific indications for antipsychotic drugs , as well as the few differences found in this study , force the clinician still to choose drugs empirically . Differing reactions of individual patients to various drugs are more likely due to differences in drug kinetics than to any important pharmacological differences A group of 80 newly admitted schizophrenics were placed at r and om in 4 treatment groups . Group A received ECT and had a 55 % improvement rate . Group B received fluphenazine and Group C received chlorpromazine with each having a 45 % improvement rate . Group D received ECT and chlorpromazine and had an 80 % improvement rate Sixty-two chronic schizophrenics in hospital were studied . There were 32 male and 30 female patients ; their mean ages were 53.6 years and 60.4 years respectively . They had all been on regular phenothiazines , principally trifluoperazine , for a mean of 9.4 years . Placebo capsules were substituted r and omly for 32 patients . Within the 16 drug-free weeks that followed , 9 ( 28 per cent ) patients relapsed sufficiently to require reinstatement on active phenothiazines . The mean drug-free period for those 9 patients was 5 weeks . They were significantly younger , had consumed larger quantities of phenothiazines over the years , and were originally receiving larger daily doses of trifluoperazine than the 23 patients who did not relapse . The patients were rated for the three main extra-pyramidal syndromes — motor restlessness parkinsonian rigidity and tremor and oral dyskinesia-tremor , before and after trifluoperazine was withdrawn . The mean drug-free period was 16 weeks . Comparisons were made between before and after ratings , as well as between placebo and control trifluoperazine groups . Parkinsonian rigidity and tremor , and oral-dyskinesia-tremor did not appreciably change in the placebo or control groups . Motor restlessness worsened significantly in the placebo , but not the trifluoperazine group . Of the 23 placebo patients who were without trifluoperazine for 16 weeks , 8 remained free from motor restlessness , 1 patient continued unchanged , 3 patients improved , 6 patients became worse , and 5 patients developed the disorder for the first time . There was no significant difference in any of the variables tested between the patients who deteriorated and those who remained the same or improved . Trifluoperazine withdrawal , in this study , was therefore followed by a psychiatric relapse in 28 per cent of the patients , persistence of parkinsonian rigidity and tremor and oral dyskinesia-tremor , and worsening of motor restlessness . The implication s of these findings are discussed Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials 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 |
1,762 | 25,099,824 | There was limited evidence for added rest breaks result ing in improved productivity at the end of a workday and in reductions of perceived discomfort in various body regions at the end of the workday .
Conclusion This review presents evidence for the effectiveness of a variety of workplace interventions .
There was limited evidence for effectiveness of ergonomic interventions , moderate evidence of a skin protection intervention , and strong evidence for Q fever vaccination | Abstract Objective To investigate the effectiveness of occupational health interventions in the meat processing industry on work and health-related outcomes . | Background Sustained employability and health are generating awareness of employers in an aging and more complex work force . To meet these needs , employers may offer their employees health surveillance programs , to increase opportunities to work on health and sustained employability . However , evidence for these health surveillance programs is lacking . The FLESH study ( Functional Labour Evaluation for Sustained Health and employment ) was developed to evaluate a comprehensive workers ’ health promotion program on its effectiveness , cost-benefit , and process of the intervention . Methods The study is design ed as a cluster r and omised stepped wedge trial with r and omisation at company plant level and is carried out in a large meat processing company . Every contracted employee is offered the opportunity to participate in the POSE program ( Promotion Of Sustained Employability ) . The main goals of the POSE program are 1 ) providing employee ’s insight into their current employability and health status , 2 ) offering opportunities to improve employability and decrease health risks and 3 ) improving employability and health sustainably in order to keep them healthy at work . The program consists of a broad assessment followed by a counselling session and , if needed , a tailored intervention . Measurements will be performed at baseline and will be followed up at 20 , 40 , 60 , 80 , 106 and 132 weeks . The primary outcome measures are work ability , productivity and absenteeism . Secondary outcomes include health status , vitality , and psychosocial workload . A cost-benefit study will be conducted from the employers ’ perspective . A process evaluation will be conducted and the satisfaction of employer and employees with the program will be assessed . Discussion This study provides information on the effectiveness of the POSE program on sustained employment . When the program proves to be effective , employees benefit by improved work ability , and health . Employers benefit from healthier employees , reduced sick leave ( costs ) and higher productivity . The study can expose key elements for a successful implementation and execution of the POSE program and may serve as an example to other companies inside and outside the industry . Trial registration The trial is registered at the Dutch Trial Register ( http://www.trialregister.nl ) : The study presented is a r and omized , controlled intervention study with the purpose of implementing an evidence ‐based skin disease prevention programme . The hypothesis explored in this article is whether a high‐fat petrolatum‐based moisturizer can be an alternative to protective gloves in wet‐work occupations . The study population was all gut cleaners in Danish swine slaughterhouses , and data were collected by telephone interviews using a st and ardized question naire – The Nordic Occupational Skin Question naire ( NOSQ‐2002 ) . At baseline , 644 ( 88 % ) gut cleaners responded and at 1‐year follow‐up 622 ( 72 % ) . 135 gut cleaners in the intervention and 277 in the comparison group responded at both telephone interviews . In the intervention group , the eczema frequency was reduced significantly . Detailed analyses revealed that protective gloves are the overall most effective protective means and did not indicate that a high‐fat moisturizer could be an alternative . Furthermore , the most extensive improvements could not be explained by combinations of protective behaviour but was found among those who had received information on , and was having discussion s on prevention of skin problems . This only applied to the intervention group . A continuous focus on prevention of skin problems with information and discussion s on the shop floor therefore seemed to be most important for reducing skin problems Objectives : The objective of the present implementation study is to document how an intervention to reduce work-related skin problems by means of implementing an evidence -based skin protection programme in six gut-cleaning departments in swine slaughterhouses was understood , accepted and carried out . The association between the degree of implementation and the reduction of work-related skin problems in each department is examined . The intervention included a top-down strategy with establishment of a management system focusing on skin risks and a bottom-up strategy with participation of a selected group of shop floor workers and the safety representative , as change agents , as well as an empowerment-based educational programme , where the middle management and representatives from the top management also participated . Methods : The study design was a r and omized controlled intervention study with a 1-year study period . The outcome of the intervention was evaluated by telephone interviews . Data on the implementation process consisted of self-administered question naires , focus interviews and compiled written material s. Four indexes referring to the management system and the change agents ’ intervention activities were constructed . Finally , the Pearson correlation coefficient was used to test the correlation between the degree of implementation and the eczema frequency at 1-year follow-up . Results : There was a statistically significant association ( p < 0.05 ) between both the index for the combined implementation method and the eczema frequency after 1 year of intervention , and between the activities of the change agents and the eczema frequency . In contrast to this there was only a weak association between the establishment of a formal management system alone and the outcome . Conclusion : The study evidence s that a combination of a top-down and a bottom-up implementation method is effective to reduce work-related skin problems , and that the process of implementation is a significant determinant of the overall results This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence A novel procedure is described to establish knife steeling schedules for poultry and meat- processing operations based on increased force due to knife dullness from repetitive use to minimize operator exertions and physical stress associated with work-related musculoskeletal disorders . Knife dullness was quantified using a novel apparatus described in this article that measures the area cut by a knife into a carrageenan gel target for a controlled dynamic load at the knife h and le . Two meat-cleaning jobs in a poultry-processing plant were studied . One job required significantly more force and a greater number of cuts than the other . Eight experienced operators participated in the study . Four freshly ground and honed knives were r and omly used by each operator for 4 , 45 , 75 , or 125 cutting cycles , measured for dullness and reconditioned by the operator using a steel sharpening rod . An empirical model for knife dulling and reconditioning was developed , and the corresponding increase in force was predicted for various cutting and reconditioning frequencies . The model showed that it took 57 and 125 cutting cycles for the high- and low-force jobs , respectively , to achieve a similar reduction in target surface area of 30 % . This reduction in target surface area corresponded to a similar percentage increase in force needed for the same cut in carrageenan gel as compared to a freshly honed knife as measured using strain gages . This method may be used in meat processing plants for determining effective reconditioning schedules that reduce operator exertions with minimum effect on quality and productivity Aims : To evaluate the effect of an intervention to reduce work related skin problems in gut cleaning departments in Danish swine slaughterhouses . The intervention consisted of an evidence based prevention programme and a documented method for implementation . Methods : R and omised controlled intervention study with a one year follow up . The intervention included educational activities and evidence based recommendations . The effect of the intervention was evaluated by telephone interviews using a st and ardised question naire based on the Nordic Occupational Skin Question naire ( NOSQ-2002 ) with modified and additional questions on exposure , preventive measures , information , and discussion s on prevention of skin problems , etc . Results : A total of 644 ( 87.5 % ) responded at the baseline interview and 622 ( 71.6 % ) at the one year follow up interview . A total of 495 participated in both interviews ( 67.3 % ) . In the intervention departments the frequency of eczema on h and s or forearms within the past three months at follow up was reduced significantly from 56.2 % at baseline to 41.0 % at follow up , while a slight non-significant increase was observed in the comparison departments ( from 45.9 % to 50.2 % ) . The intervention activities result ed in more frequent use of protective gloves in general and the use of cotton gloves worn underneath rubber and plastic gloves . At follow up three times as many in the intervention departments used the recommended high fat skin care products introduced as part of the intervention activities . At follow up , discussion of skin problems was increased in the intervention group while no changes were observed in the comparison group . Conclusions : A significant 27 % relative reduction of occupational eczema in a high risk group was feasible through implementation of an evidence based prevention programme A limited , r and omized , blind , placebo-controlled trial of Q fever and influenza vaccines has been conducted in three Queensl and abattoirs on a sequential analysis design . Ninety-eight subjects were given Q fever vaccine and 102 influenza vaccine . Q fever cases were observed in unvaccinated workers in all three abattoirs during the period of observation . A total of seven Q fever cases in one group , one more than the number required to achieve statistical significance between the two vaccine groups , was reached after 15 months with the cases coming from two of the abattoirs . These Q fever cases were in the group which had been given influenza vaccine and none in that given Q fever vaccine . Symptomless seroconversion rates of 24 % were found in the remaining influenza virus vaccinees , and those without immunity were given Q fever vaccine OBJECTIVES A program called the Project on Research and Intervention in Monotonous Work ( PRIM ) was initiated in 1994 as a prospect i ve cohort study of work-related musculoskeletal disorders . The group-based exposure assessment strategy , focusing on task-related exposure and used to obtain baseline measures of physical exposures , is reported in this paper . METHODS Monotonous , repetitive worktasks were evaluated at 19 factories . Tasks with an estimated similarity in physical exposure were aggregated before 103 exposure groups were formed . Subjects from the exposure groups were r and omly sample d for measurements , and task-related exposure levels were quantified by 43 single exposure items using a real-time video-based observation method that allowed computerized estimates of repetitiveness , body postures , force , and velocity . In combination with question naire-based data on task distribution , the duration of exposure was calculated at the individual level . RESULTS The video-based observational method and the large number of exposure variables enabled the establishment of detailed quantitative exposure profiles in 103 task-based exposure groups . However , method ological problems associated with the use of grouped exposure assessment were revealed . Despite efforts to optimize group homogeneity , the within-group variance was larger than the between-group variance for several shoulder postural variables . CONCLUSIONS A task-based exposure- assessment strategy can be successful in solving some of the main problems associated with the assessment of physical workplace exposures . The large within-group variance in exposure to nonneutral shoulder postures may eventually require individual assessment or the inclusion of groups with maximal contrast in exposure or both |
1,763 | 27,228,266 | ( S ) The present results suggest that orlistat leads to significant reduction in BMI /body weight in PCOS .
In addition , the available evidence indicates that orlistat and metformin have similar effects in reducing BMI , HOMA , testosterone and insulin in overweight/obese PCOS women . | AIMS The aim of this study was to assess the effects of orlistat on weight loss-related clinical variables in overweight/obese women with polycystic ovary syndrome ( PCOS ) and to compare treatment with orlistat vs. metformin in this group . | We prospect ively estimated the prevalence of the polycystic ovary syndrome ( PCOS ) , as defined by the NIH/NICHHD 1990 endocrine criteria , in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation . Anthropometric data ; the presence of hirsutism , acne , and and rogenic alopecia ; and the menstrual history were recorded by a single investigator . In 145 women , blood sample s were also obtained for measurement of serum and rogen levels . PCOS was defined by the presence of 1 ) oligomenorrhea , 2 ) clinical and /or biochemical hyper and rogenism , and 3 ) exclusion of hyperprolactinemia , thyroid disorders , and nonclassic 21-hydroxylase deficiency . Hirsutism was defined by a modified Ferriman-Gallwey score of 8 or more , acne was considered as a sign of hyper and rogenism when persistent after the second decade of life , and hyper and rogenemia was defined by an increase in circulating testosterone or dehydroepi and rosterone sulfate or an increase in the free and rogen index above the 95th percentile of the control values derived from the nonhirsute , nonacneic women having regular menses who were not receiving hormonal therapy . PCOS was present in 10(6.5 % ) , hirsutism was present in 11 ( 7.1 % ) , and acne was present in 19 ( 12.3 % ) of the 154 women . Our results demonstrate a 6.5 % prevalence of PCOS , as defined , in a minimally biased population of Caucasian women from Spain . The polycystic ovary syndrome , hirsutism , and acne are common endocrine disorders in women OBJECTIVE : Polycystic ovary syndrome ( PCOS ) is characterized by obesity and insulin resistance ( IR ) , which result in elevated plasminogen activator inhibitor-1 ( PAI-1 ) levels . We aim ed to assess the changes in PAI-1 levels in PCOS during treatment with metformin and during weight loss . DESIGN : Twenty-three normal weight women with PCOS were given metformin 850 mg bid for 6 months . Fifty overweight/obese women with PCOS were prescribed an energy-restricted diet , were instructed to exercise and were r and omized to orlistat 120 mg tid or sibutramine 10 mg qd for 6 months . RESULTS : In normal weight women , treatment with metformin reduced the body mass index ( BMI ) and circulating and rogens , improved markers of IR and lowered PAI-1 levels . In overweight/obese women , sibutramine and orlistat yielded comparable reductions in BMI and markers of IR . In contrast , the effects on the free and rogen index ( FAI ) differed ( p=0.027 ) : sibutramine reduced the FAI ( p=0.005 ) , whereas orlistat had no effect . The effects of sibutramine and orlistat on PAI-1 levels also differed ( p=0.042 ) : sibutramine reduced PAI-1 levels ( p<0.001 ) , whereas orlistat had no effect . CONCLUSIONS : Metformin and sibutramine , but not orlistat , reduce PAI-1 levels in PCOS . The reduction in circulating and rogens during metformin and sibutramine treatment might be implicated in this decline BACKGROUND This prospect i ve study evaluated the effect of weight reduction on anthropometric indices and ovarian morphology in anovulatory overweight patients with polycystic ovary syndrome ( PCOS ) . METHODS Thirty-three anovulatory overweight patients with PCOS were enrolled in the study . All had patent Fallopian tubes and chronic anovulation : 27 of them were oligo-amenorrhoeic . The partners were normospermic . Patients were prescribed a 1200 kcal/day diet , and physical exercise was recommended . Anthropometric indices and ovarian imaging parameters were assessed at baseline and after weight loss of 5 and 10 % . RESULTS Twenty-five patients ( 76 % ) lost at least 5 % of their body weight . Eleven of these patients ( 33 % ) reached a 10 % decrease in weight . Waist circumference at the umbilical level , hip circumference , four skin folds , body mass index and fatty mass ratio were significantly reduced after 5 and 10 % weight loss . Ovarian morphology changed during the diet : we observed a significant reduction in ovarian volume and in the number of microfollicles per ovary . Among the 27 patients with oligo-amenorrhoea , 18 had a resumption of regular cycles and 15 experienced spontaneous ovulation ; 10 spontaneous pregnancies occurred in patients who lost at least 5 % of their weight . CONCLUSIONS Weight loss through a controlled low-calorie diet improves anthropometric indices in obese PCOS patients , reduces ovarian volume and microfollicle number and can restore ovulatory cycles , allowing spontaneous pregnancy The effect of orlistat , a nonabsorbed inhibitor of gastric and pancreatic lipases , was examined in patients with primary hyperlipidaemia ( serum cholesterol ≥6.2 mmol·l−1 and triglycerides ≤5.0 mmol·l−1 ) not responsive to dietary change alone . In a multicentre , r and omised , double-blind study , 103 men and 70 women received 30 , 90 , 180 , or 360 mg of orlistat or placebo for 8 weeks . Total and low-density lipoprotein cholesterol levels were reduced by 4 % and 5 % with 30 mg orlistat , by 7 % and 8 % with 90 mg orlistat , by 7 % and 7 % with 180 mg orlistat and by 11 % and 10 % with 360 mg orlistat compared to placebo . High density lipoprotein cholesterol levels significantly decreased in the 360 mg orlistat group . Triglyceride levels significantly increased in the placebo group but not in the drug groups . Body weight decreased by 1.2 kg with 360 mg orlistat , despite a weight maintenance diet . Decreases in vitamin E and D levels occurred , although both vitamins remained within the normal range . Adverse effects from the gastrointestinal tract were frequent , but led to discontinuation of therapy in only seven patients . Orlistat is a new therapeutic drug for the treatment of hyperlipidaemia that may be particularly useful among overweight patients . Its potential place in therapy will await long-term studies . Vitamin supplementation should be considered during treatment CONTEXT The polycystic ovary syndrome ( PCOS ) is the commonest endocrine abnormality in women of reproductive age . OBJECTIVE To determine the rate of hospital admissions for women with PCOS in Western Australian population in comparison to women without PCOS . DESIGN A population -based retrospective cohort study using data linkage in a statewide hospital morbidity data base system . SETTING All hospitals within Western Australia . PARTICIPANTS A total of 2566 women with PCOS hospitalized from 1997 - 2011 and 25 660 r and omly selected age-matched women without a PCOS diagnosis derived from the electoral roll . MAIN OUTCOME MEASURES Hospitalizations by ICD-10-M diagnoses from 15 years were compared . RESULTS Hospitalizations were followed until a median age of 35.8 years ( interquartile range , 31.0 - 39.9 ) . PCOS was associated with more nonobstetric and non-injury-related hospital admissions ( median , 5 vs 2 ; P < .001 ) , a diagnosis of adult-onset diabetes ( 12.5 vs 3.8 % ) , obesity ( 16.0 vs 3.7 % ) , hypertensive disorder ( 3.8 vs 0.7 % ) , ischemic heart disease ( 0.8 vs 0.2 % ) , cerebrovascular disease ( 0.6 vs 0.2 % ) , arterial and venous disease ( 0.5 vs 0.2 % and 10.4 vs 5.6 % , respectively ) , asthma ( 10.6 vs 4.5 % ) , stress/anxiety ( 14.0 vs 5.9 % ) , depression ( 9.8 vs 4.3 % ) , licit/illicit drug-related admissions ( 8.8 vs 4.5 % ) , self-harm ( 7.2 vs 2.9 % ) , l and transport accidents ( 5.2 vs 3.8 % ) , and mortality ( 0.7 vs 0.4 % ) ( all P < .001 ) . Women with PCOS had a higher rate of admissions for menorrhagia ( 14.1 vs 3.6 % ) , treatment of infertility ( 40.9 vs 4.6 % ) , and miscarriage ( 11.1 vs 6.1 % ) and were more likely to require in vitro fertilization ( 17.2 vs 2.0 % ) . CONCLUSION PCOS has profound medical implication s for the health of women , and health care re sources should be directed accordingly Purpose : To implement an evidence ‐based lifestyle modification intervention , guided by motivational interviewing , among a sample of infertile overweight and obese women with polycystic ovary syndrome to increase chances of conception while improving overall health . Data sources : A prospect i ve quantitative design was utilized ( n = 12 ) . Infertile overweight and obese women with polycystic ovary syndrome at an infertility practice completed question naires to assess diet and exercise practice s at study onset and completion . Body mass index and weight measurements were obtained on participants at study onset and completion of intervention . Menstrual history was assessed by interview . Conclusions : There was a mean weight loss ( p = .005 ) of 7(±5 ) pounds although a 5 % weight reduction did not occur . Mean daily calorie ( p = .005 ) , fat ( p = .006 ) , and carbohydrate intake ( p = .014 ) were significantly reduced . Frequency in brisk walking exercise significantly increased ( p = .024 ) . Frequency in home or gym exercise increased ( p = .050 ) . Menstrual cyclicity improved by 50 % among prior amenorrheic subjects . Implication s for practice : An evidence ‐based lifestyle modification guideline could prove to be a cost effective intervention for infertile women with polycystic ovary syndrome ( PCOS ) who desire pregnancy . This intervention could be integrated into the primary care and reproductive medicine visits as sole therapy or in conjunction with infertility treatment Obesity can affect ovulation and the chances of pregnancy . In this prospect i ve study , a weight loss programme was assessed to determine whether it could help infertile overweight anovulatory women to establish ovulation and assist in achieving pregnancy , ideally without further medical intervention . The subjects acted as their own historical controls . They underwent a weekly programme of behavioural change in relation to exercise and diet over 6 months ; those who did not complete the 6 months were treated as the comparison group . Women in the study group lost an average of 6.3 kg , with 12 of the 13 subjects resuming ovulation and 11 becoming pregnant , five of these spontaneously . Fitness , diet and psychometric measurements all improved . Fasting insulin and testosterone concentrations dropped significantly , while sex hormone binding globulin concentrations rose . None of these changes occurred in the comparison group . Thus , weight loss with a result ant improvement in ovulation , pregnancy outcome , self-esteem and endocrine parameters is the first therapeutic option for women who are infertile and overweight Purpose Comparing the effects of metformin or orlistat on hormone , lipid profile and ovulation status in obese women with polycystic ovary syndrome . Methods A total of 80 women were prospect ively recruited to receive either metformin ( n = 40 ) or orlistat ( n = 40 ) . Weight , BMI , waist , serum LH , total serum testosterone and lipid profile were assessed at baseline and after 3 months . The subjects ’ ovulatory status was assessed after 3 months . Results There was no significant difference in ovulation between the two treatment groups ( 30 % vs 15 % ) . Treatment with either drug showed a significant decline in body weight , BMI ( Body Mass Index ) , and waist circumference , but the degree of decline in both groups was the same . Patients who were treated with orlistat , showed a significant reduction in total testosterone and serum lipid . Women in metformin group showed a significant reduction in serum LH . Conclusions Both metformin and orlistat showed a similar effect on weight loss and ovulation rates OBJECTIVE It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity . A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated . We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight , and thus the incidence of type 2 diabetes , in obese patients . RESEARCH DESIGN AND METHODS In a 4-year , double-blind , prospect i ve study , we r and omized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo , three times daily . Participants had a BMI > /=30 kg/m2 and normal ( 79 % ) or impaired ( 21 % ) glucose tolerance ( IGT ) . Primary endpoints were time to onset of type 2 diabetes and change in body weight . Analyses were by intention to treat . RESULTS Of orlistat-treated patients , 52 % completed treatment compared with 34 % of placebo recipients ( P < 0.0001 ) . After 4 years ' treatment , the cumulative incidence of diabetes was 9.0 % with placebo and 6.2 % with orlistat , corresponding to a risk reduction of 37.3 % ( P = 0.0032 ) . Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT . Mean weight loss after 4 years was significantly greater with orlistat ( 5.8 vs. 3.0 kg with placebo ; P < 0.001 ) and similar between orlistat recipients with impaired ( 5.7 kg ) or normal glucose tolerance ( NGT ) ( 5.8 kg ) at baseline . A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group ( 3.6 vs. 1.4 kg ; P < 0.001 ) . CONCLUSIONS Compared with lifestyle changes alone , orlistat plus lifestyle changes result ed in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinical ly representative obese population . Difference in diabetes incidence was detectable only in the IGT subgroup ; weight loss was similar in subjects with IGT or NGT [ correction ] BACKGROUND : The effects of exercise , metformin , and orlistat on anthropometric parameters , lipid profile , endocrine parameters , and ovulation in polycystic ovarian syndrome ( PCOS ) women were compared . AIM : The aim was to study the efficacy of orlistat compared with metformin and exercise in PCOS . DESIGN : R and omized control trial . METHODS : A total of 90 eligible PCOS women were r and omly assigned to receive either of the two drugs ( orlistat or metformin ) in combination with lifestyle interventions or as controls where they received lifestyle interventions alone . Anthropometric parameters were assessed at baseline and 4 weekly intervals for 3 months . And rogen levels , insulin resistance , ovulation and conception rates and lipid profile were also assessed at the end of study . STATISTICAL ANALYSIS : Statistical analysis was performed using the SPSS version 17.0 . RESULTS : The levels of fasting blood sugar , fasting insulin and homeostatic model assessment insulin resistance were comparable in three treatment groups . Mean total testosterone , serum hormone binding globulin , free and rogen index , dehydroepi and rosterone sulfate in all arms were comparable and statistically nonsignificant . However , orlistat and metformin were more effective in reducing weight , body mass index , waist circumference and waist-hip ratio . However , side-effects were less with orlistat . Ovulation rate was 33.3 % , 23.35 % with orlistat and metformin group respectively , but were not statistically significant . In orlistat group , significant improvement was observed in lipid profile at the end of 3 months . Conception rates were 40 % and 16.7 % and 3.3 % in orlistat , metformin group and control group respectively ( P - 0.003 ) . Weight loss was found to be the best predictor of ovulation with sensitivity with good sensitivity . CONCLUSION : Orlistat is as effective as metformin in reducing weight and achieves similar ovulation rates in obese PCOS patients . However , orlistat has minimal side-effects and is better tolerated compared with metformin CONTEXT Orlistat , a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30 % , may promote weight loss and reduce cardiovascular risk factors . OBJECTIVE To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years . DESIGN R and omized , double-blind , placebo-controlled study conducted from October 1992 to October 1995 . SETTING AND PARTICIPANTS Obese adults ( body mass index [ weight in kilograms divided by the square of height in meters ] , 30 - 43 kg/m2 ) evaluated at 18 US research centers . INTERVENTION Subjects received placebo plus a controlled-energy diet during a 4-week lead-in . On study day 1 , the diet was continued and subjects were r and omized to receive placebo 3 times a day or orlistat , 120 mg 3 times a day , for 52 weeks . After 52 weeks , subjects began a weight-maintenance diet , and the placebo group ( n = 133 ) continued to receive placebo and orlistat-treated subjects were rer and omized to receive placebo 3 times a day ( n = 138 ) , orlistat , 60 mg ( n = 152 ) or 120 mg ( n = 153 ) 3 times a day , for an additional 52 weeks . MAIN OUTCOME MEASURES Body weight change and changes in blood pressure and serum lipid , glucose , and insulin levels . RESULTS A total of 1187 subjects entered the protocol , and 892 were r and omly assigned on day 1 to double-blind treatment . For intent-to-treat analysis , 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated . During the first year orlistat-treated subjects lost more weight ( mean + /- SEM , 8.76+/-0.37 kg ) than placebo-treated subjects ( 5.81+/-0.67 kg ) ( P<.001 ) . Subjects treated with orlistat , 120 mg 3 times a day , during year 1 and year 2 regained less weight during year 2 ( 3.2+/-0.45 kg ; 35.2 % regain ) than those who received orlistat , 60 mg ( 4.26+/-0.57 kg ; 51.3 % regain ) , or placebo ( 5.63+/-0.42 kg ; 63.4 % regain ) in year 2 ( P<.001 ) . Treatment with orlistat , 120 mg 3 times a day , was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels . CONCLUSIONS Two-year treatment with orlistat plus diet significantly promotes weight loss , lessens weight regain , and improves some obesity-related disease risk factors Obesity is frequently present in women with the polycystic ovary syndrome ( PCOS ) and aggravates insulin resistance ( IR ) and hyper and rogenemia . We aim ed to assess the effects of orlistat combined with lifestyle changes in overweight and obese women with PCOS and body mass index ( BMI ) ‐matched controls The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinical ly evident and rogen excess and to document the degree of long-term success of suppressive and /or anti and rogen hormonal therapy in a large consecutive population of patients . All patients presenting for evaluation of symptoms potentially related to and rogen excess between October 1987 and June 2002 were evaluated , and the data were maintained prospect ively in a computerized data base . For the assessment of therapeutic response , a retrospective review of the medical chart was performed , after the exclusion of those patients seeking fertility therapy only , or with inadequate follow-up or poor compliance . A total of 1281 consecutive patients were seen during the study period . Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status , determine ovulatory status , or find any evidence of and rogen excess . In the remaining population of 873 patients , the unbiased prevalence of and rogen-secreting neoplasms was 0.2 % , 21-hydroxylase-deficient classic adrenal hyperplasia ( CAH ) was 0.6 % , 21-hydroxylase-deficient nonclassic adrenal hyperplasia ( NCAH ) was 1.6 % , hyper and rogenic insulin-resistant acanthosis nigricans ( HAIRAN ) syndrome was 3.1 % , idiopathic hirsutism was 4.7 % , and polycystic ovary syndrome ( PCOS ) was 82.0 % . Fifty-nine ( 6.75 % ) patients had elevated and rogen levels and hirsutism but normal ovulation . A total of 257 patients were included in the assessment of the response to hormonal therapy . The mean duration of follow-up was 33.5 months ( range , 6 - 155 ) . Hirsutism improved in 86 % , menstrual dysfunction in 80 % , acne in 81 % , and hair loss in 33 % of patients . The major side effects noted were irregular vaginal bleeding ( 16.1 % ) , nausea ( 13.0 % ) , and headaches ( 12.6 % ) ; only 36.6 % of patients never complained of side effects . In this large study of consecutive patients presenting with clinical ly evident and rogen excess , specific identifiable disorders ( NCAH , CAH , HAIRAN syndrome , and and rogen-secreting neoplasms ) were observed in approximately 7 % of subjects , whereas functional and rogen excess , principally PCOS , was observed in the remainder . Hirsutism , menstrual dysfunction , or acne , but not alopecia , improved in the majority of patients treated with a combination suppressive therapy ; although more than 60 % experienced side effects Background Women with polycystic ovary syndrome ( PCOS ) exhibit elevated serum advanced glycation end‐products ( AGE ) compared with healthy subjects . Short‐term administration of orlistat has been shown to reduce the postmeal increase in serum AGE levels in women with PCOS and in controls BACKGROUND Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance , but how long these benefits extend beyond the period of active intervention , and whether such interventions reduce the risk of cardiovascular disease ( CVD ) and mortality , is unclear . We aim ed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes , diabetes-related macrovascular and microvascular complications , and mortality . METHODS In 1986 , 577 adults with impaired glucose tolerance from 33 clinics in China were r and omly assigned to either the control group or to one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) . Active intervention took place over 6 years until 1992 . In 2006 , study participants were followed-up to assess the long-term effect of the interventions . The primary outcomes were diabetes incidence , CVD incidence and mortality , and all-cause mortality . FINDINGS Compared with control participants , those in the combined lifestyle intervention groups had a 51 % lower incidence of diabetes ( hazard rate ratio [ HRR ] 0.49 ; 95 % CI 0.33 - 0.73 ) during the active intervention period and a 43 % lower incidence ( 0.57 ; 0.41 - 0.81 ) over the 20 year period , controlled for age and clustering by clinic . The average annual incidence of diabetes was 7 % for intervention participants versus 11 % in control participants , with 20-year cumulative incidence of 80 % in the intervention groups and 93 % in the control group . Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group . There was no significant difference between the intervention and control groups in the rate of first CVD events ( HRR 0.98 ; 95 % CI 0.71 - 1.37 ) , CVD mortality ( 0.83 ; 0.48 - 1.40 ) , and all-cause mortality ( 0.96 ; 0.65 - 1.41 ) , but our study had limited statistical power to detect differences for these outcomes . INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention . However , whether lifestyle intervention also leads to reduced CVD and mortality remains unclear OBJECTIVE Severe obesity ( body mass index [ BMI ] ≥40 kg/m(2 ) ) is a serious public health concern . Although bariatric surgery is an efficacious treatment approach , it is limited in reach ; thus , nonsurgical treatment alternatives are needed . We examined the 4-year effects of an intensive lifestyle intervention on body weight and cardiovascular disease risk factors among severely obese , compared with overweight ( 25 ≤ BMI < 30 ) , class I ( 30 ≤ BMI < 35 ) , and class II obese ( 35 ≤ BMI < 40 ) participants . METHODS There were 5145 individuals with type 2 diabetes ( 45 - 76 years , BMI ≥25 kg/m(2 ) ) r and omized to an intensive lifestyle intervention or diabetes support and education . The lifestyle intervention group received a behavioral weight loss program that included group and individual meetings , a ≥10 % weight loss goal , calorie restriction , and increased physical activity . Diabetes support and education received a less intense educational intervention . Four-year changes in body weight and cardiovascular disease risk factors were assessed . RESULTS Across BMI categories , 4-year changes in body weight were significantly greater in lifestyle participants compared with diabetes support and education ( Ps < .05 ) . At year 4 , severely obese lifestyle participants lost 4.9%±8.5 % , which was similar to class I ( 4.8%±7.2 % ) and class II obese participants ( 4.4%±7.6 % ) , and significantly greater than overweight participants ( 3.4%±7.0 % ; P < .05 ) . Four-year changes in low-density-lipoprotein cholesterol , triglycerides , diastolic blood pressure , HbA(1c ) , and blood glucose were similar across BMI categories in lifestyle participants ; however , the severely obese had less favorable improvements in high-density-lipoprotein cholesterol ( 3.1±0.4 mg/dL ) and systolic blood pressure ( -1.4±0.7 mm Hg ) compared with the less obese ( Ps < .05 ) . CONCLUSION Lifestyle interventions can result in important long-term weight losses and improvements in cardiovascular disease risk factors among a significant proportion of severely obese individuals BACKGROUND We undertook a r and omised controlled trial to assess the efficacy and tolerability of orlistat , a gastrointestinal lipase inhibitor , in promoting weight loss and preventing weight regain in obese patients over a 2-year period . METHODS 743 patients ( body-mass index 28 - 47 kg/m2 ) , recruited at 15 European centres , entered a 4-week , single-blind , placebo lead-in period on a slightly hypocaloric diet ( 600 kcal/day deficit ) . 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg ( three times a day ) or placebo for 1 year in conjunction with the hypocaloric diet . In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance ( eucaloric ) diet . FINDINGS From the start of lead-in to the end of year 1 , the orlistat group lost , on average , more bodyweight than the placebo group ( 10.2 % [ 10.3 kg ] vs 6.1 % [ 6.1 kg ] ; LSM difference 3.9 kg [ p<0.001 ] from r and omisation to the end of year 1 ) . During year 2 , patients who continued with orlistat regained , on average , half as much weight as those patients switched to placebo ( p<0.001 ) . Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2 , compared with a mean regain of 2.5 kg in patients who continued on placebo ( p<0.001 ) . Total cholesterol , low-density lipoprotein ( LDL ) cholesterol , LDL/high-density lipoprotein ratio , and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group . Gastrointestinal adverse events were more common in the orlistat group . Other adverse symptoms occurred at a similar frequency during both treatments . INTERPRETATION Orlistat taken with an appropriate diet promotes clinical ly significant weight loss and reduces weight regain in obese patients over a 2-year period . The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events BACKGROUND We undertook a r and omised controlled trial to assess the efficacy and tolerance of orlistat , a gastrointestinal lipase inhibitor , in promoting weight loss and preventing weight regain in obese patients over a 2-year period . METHODS 743 patients ( body-mass index 28 - 47 kg/m2 ) , recruited at 15 European centres , entered a 4-week , single-blind , placebo lead-in period on a slightly hypocaloric diet ( 600 kcal/day deficit ) . 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg ( three times a day ) or placebo for 1 year in conjunction with the hypocaloric diet . In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance ( eucaloric ) diet . FINDINGS From the start of lead-in to the end of year 1 , the orlistat group lost , on average , more bodyweight than the placebo group ( 10.2 % [ 10.3 kg ] vs 6.1 % [ 6.1 kg ] ; LSM difference 3.9 kg [ p < 0.001 ] from r and omisation to the end of year 1 ) . During year 2 , patients who continued with orlistat regained , on average , half as much weight as those patients switched to placebo ( p < 0.001 ) . Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2 , compared with a mean regain of 2.5 kg in patients who continued on placebo ( p < 0.001 ) . Total cholesterol , low-density lipoprotein ( LDL ) cholesterol , LDL/high-density lipoprotein ratio , and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group . Gastrointestinal adverse events were more common in the orlistat group . Other adverse symptoms occurred at a similar frequency during both treatments . INTERPRETATION Orlistat taken with an appropriate diet promotes clinical ly significant weight loss and reduces weight regain in obese patients over a 2-year period . The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events Aims /hypothesisThis study aim ed to determine whether lifestyle intervention lasting for 4 years affected diabetes incidence , body weight , glycaemia or lifestyle over 13 years among individuals at high risk of type 2 diabetes . Methods Overweight , middle-aged men ( n = 172 ) and women ( n = 350 ) with impaired glucose tolerance were r and omised in 1993–1998 to an intensive lifestyle intervention group ( n = 265 ) , aim ing at weight reduction , dietary modification and increased physical activity , or to a control group ( n = 257 ) that received general lifestyle information . The primary outcome was a diagnosis of diabetes based on annual OGTTs . Secondary outcomes included changes in body weight , glycaemia , physical activity and diet . After active intervention ( median 4 years , range 1–6 years ) , participants still free of diabetes and willing to continue their participation ( 200 in the intervention group and 166 in the control group ) were further followed until diabetes diagnosis , dropout or the end of 2009 , with a median total follow-up of 9 years and a time span of 13 years from baseline . Results During the total follow-up the adjusted HR for diabetes ( intervention group vs control group ) was 0.614 ( 95 % CI 0.478 , 0.789 ; p < 0.001 ) . The corresponding HR during the post-intervention follow-up was 0.672 ( 95 % CI 0.477 , 0.947 ; p = 0.023 ) . The former intervention group participants sustained lower absolute levels of body weight , fasting and 2 h plasma glucose and a healthier diet . Adherence to lifestyle changes during the intervention period predicted greater risk reduction during the total follow-up . Conclusions /interpretationLifestyle intervention in people at high risk of type 2 diabetes induces sustaining lifestyle change and results in long-term prevention of progression to type 2 diabetes . Trial registration Clinical Trials.gov NCT00518167 Funding The DPS study has been financially supported by the Academy of Finl and ( 128315 , 129330 ) , Ministry of Education , Novo Nordisk Foundation , Yrjö Jahnsson Foundation , Juho Vainio Foundation , Finnish Diabetes Research Foundation , Finnish Foundation for Cardiovascular Research , Unilever , and Competitive Research Funding from Tampere , Kuopio and Oulu University Hospitals . The study sponsors had no role in the design and conduct of the study ; the collection , analysis and interpretation of the data ; or the preparation , review or approval of the manuscript CONTEXT The frequency of remission of type 2 diabetes achievable with lifestyle intervention is unclear . OBJECTIVE To examine the association of a long-term intensive weight-loss intervention with the frequency of remission from type 2 diabetes to prediabetes or normoglycemia . DESIGN , SETTING , AND PARTICIPANTS Ancillary observational analysis of a 4-year r and omized controlled trial ( baseline visit , August 2001-April 2004 ; last follow-up , April 2008 ) comparing an intensive lifestyle intervention ( ILI ) with a diabetes support and education control condition ( DSE ) among 4503 US adults with body mass index of 25 or higher and type 2 diabetes . INTERVENTIONS Participants were r and omly assigned to receive the ILI , which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 ( n=2241 ) or the DSE , which was an offer of 3 group sessions per year on diet , physical activity , and social support ( n=2262 ) . MAIN OUTCOME MEASURES Partial or complete remission of diabetes , defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia ( fasting plasma glucose < 126 mg/dL and hemoglobin A1c < 6.5 % with no antihyperglycemic medication ) . RESULTS Intensive lifestyle intervention participants lost significantly more weight than DSE participants at year 1 ( net difference , -7.9 % ; 95 % CI , -8.3 % to -7.6 % ) and at year 4 ( -3.9 % ; 95 % CI , -4.4 % to -3.5 % ) and had greater fitness increases at year 1 ( net difference , 15.4 % ; 95 % CI , 13.7%-17.0 % ) and at year 4 ( 6.4 % ; 95 % CI , 4.7%-8.1 % ) ( P < .001 for each ) . The ILI group was significantly more likely to experience any remission ( partial or complete ) , with prevalences of 11.5 % ( 95 % CI , 10.1%-12.8 % ) during the first year and 7.3 % ( 95 % CI , 6.2%-8.4 % ) at year 4 , compared with 2.0 % for the DSE group at both time points ( 95 % CIs , 1.4%-2.6 % at year 1 and 1.5%-2.7 % at year 4 ) ( P < .001 for each ) . Among ILI participants , 9.2 % ( 95 % CI , 7.9%-10.4 % ) , 6.4 % ( 95 % CI , 5.3%-7.4 % ) , and 3.5 % ( 95 % CI , 2.7%-4.3 % ) had continuous , sustained remission for at least 2 , at least 3 , and 4 years , respectively , compared with less than 2 % of DSE participants ( 1.7 % [ 95 % CI , 1.2%-2.3 % ] for at least 2 years ; 1.3 % [ 95 % CI , 0.8%-1.7 % ] for at least 3 years ; and 0.5 % [ 95 % CI , 0.2%-0.8 % ] for 4 years ) . CONCLUSIONS In these exploratory analyses of overweight adults , an intensive lifestyle intervention was associated with a greater likelihood of partial remission of type 2 diabetes compared with diabetes support and education . However , the absolute remission rates were modest . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00017953 |
1,764 | 26,192,563 | It found that both the CABG and medical groups had small to moderate improvements in memory versus baseline at 1 year and no changes versus baseline at 6 years for all neuropsychological tests measured .
Further , there were no between-group differences at any follow-up or in change from baseline to any follow-up . | Approximately 200000 coronary artery bypass graft ( CABG ) surgeries , 50000 carotid revascularizations , 50000 cardiac valve replacements or repairs , and 10000 catheter ablations for atrial fibrillation are performed annually in U.S. adults aged 65 years or older ( 16 ) .
The older U.S. population also has a high rate of cognitive impairment and dementia , with a combined incidence of 77.5 cases per 1000 person-years in adults aged 72 years or older with normal cognition at baseline ( 7 ) .
However , great uncertainty surrounds the relationship between these cardiovascular interventions and subsequent cognitive outcomes in older patients .
Most attention has addressed the possible relationship between CABG and cognitive impairment .
Early studies reported a high prevalence of cognitive impairment after CABG , possibly attributable to surgical factors , such as anesthesia and cardiopulmonary bypass ( 8 , 9 ) .
Later studies suggested that much cognitive impairment after CABG pre date d the procedure ( 10 ) and was related to patient factors , such as age , education , and vascular disease ( 8 , 1114 ) .
Studies of cardiac valve procedures and catheter ablation for atrial fibrillation commonly report imaging-detected cerebral emboli , but cognitive outcomes have been less clear ( 16 , 17 ) .
Meanwhile , older adults , who have the highest risk for intermediate- and long-term cognitive impairment , increasingly are having these procedures .
Therefore , improved underst and ing of any relationship between these cardiovascular procedures and cognitive outcomes in older patients could enhance physicianpatient clinical decision making .
This systematic review evaluates the evidence from r and omized , controlled trials ( RCTs ) and prospect i ve cohort studies on the association of coronary and carotid revascularization , cardiac valve replacement and repair , and ablation for atrial fibrillation on intermediate- and long-term cognitive outcomes in adults aged 65 years or older .
We further sought to evaluate whether these associations were modified by procedural and patient characteristics and by procedure-related stroke or transient ischemic attack ( TIA ) . | OBJECTIVE Age is considered to be the strongest predictive factor of postoperative cognitive dysfunction ( POCD ) after cardiac surgery . Coronary artery bypass grafting ( CABG ) without the use of cardiopulmonary bypass is considered to be less harmful to the patient , especially in terms of neurological complications . METHODS The study was a sub- study of the r and omized best bypass surgery trial that compares off-pump to on-pump treatment , with respect to peri- and postoperative morbidity in patients with a moderate to high-predicted preoperative risk . We investigated cognitive outcomes . A total of 120 elderly patients ( mean age 76 years , SD 4.5 years ) underwent cognitive testing before surgery , of which 90 patients ( 47 vs 43 ) were available for retesting at 1 year ( mean 370 days ) postoperatively , using a neuropsychological test battery that included seven parameters from four tests . POCD was defined as the occurrence of at least two deficits out of the seven possible scores . Secondary analysis was performed based on definition of 20 % decline in cognitive scores compared to baseline , and using z-score analysis . RESULTS The incidence of POCD was 19 % ( 95 % CI 9 - 33 ) in the off-pump group and 9 % ( 95 % CI 3 - 22 ) in the on-pump group ( p=0.18 ) . There were no significant differences in the incidence of cognitive decline between the off-pump and on-pump group regardless of the definition applied . CONCLUSIONS We were unable to detect that CABG surgery without cardiopulmonary bypass was associated with significantly better cognitive outcome in elderly high-risk patients 1 year after the operation BACKGROUND The objective of this r and omized clinical trial of elective coronary artery bypass grafting was to investigate whether intraoperative mean arterial pressure below autoregulatory limits of the coronary and cerebral circulations was a principal determinant of postoperative complications . The trial compared the impact of two strategies of hemodynamic management during cardiopulmonary bypass on outcome . Patients were r and omized to a low mean arterial pressure of 50 to 60 mm Hg or a high mean arterial pressure of 80 to 100 mm Hg during cardiopulmonary bypass . METHODS A total of 248 patients undergoing primary , nonemergency coronary bypass were r and omized to either low ( n = 124 ) or high ( n = 124 ) mean arterial pressure during cardiopulmonary bypass . The impact of the mean arterial pressure strategies on the following outcomes was assessed : mortality , cardiac morbidity , neurologic morbidity , cognitive deterioration , and changes in quality of life . All patients were observed prospect ively to 6 months after the operation . RESULTS The overall incidence of combined cardiac and neurologic complications was significantly lower in the high pressure group at 4.8 % than in the low pressure group at 12.9 % ( p = 0.026 ) . For each of the individual outcomes , the trend favored the high pressure group . At 6 months after coronary bypass for the high and low pressure groups , respectively , total mortality rate was 1.6 % versus 4.0 % , stroke rate 2.4 % versus 7.2 % , and cardiac complication rate 2.4 % versus 4.8 % . Cognitive and functional status outcomes did not differ between the groups . CONCLUSION Higher mean arterial pressures during cardiopulmonary bypass can be achieved in a technically safe manner and effectively improve outcomes after coronary bypass OBJECTIVE In a r and omized trial of 223 patients undergoing coronary artery surgery with cardiopulmonary bypass , we have reported a neuroprotective effect of mild hypothermia . To determine whether the beneficial effect of mild hypothermia was long-lasting , we repeated the psychometric tests in 131 patients after 5 years . METHODS Patients were cooled to 32 degrees C during aortic crossclamping and then r and omized to rewarming to either 34 degrees C or 37 degrees C , with no further rewarming until arrival in intensive care unit . Cognitive function was measured preoperatively and 1 week and 5 years postoperatively with a battery of 11 psychometric tests interrogating verbal memory , attention , and psychomotor speed and dexterity . RESULTS Patients who had greater cognitive decline 1 week after surgery showed poorer performance 5 years later . The magnitude of cognitive decline over 5 years was modest . The incidence of deficits defined as a 1 st and ard deviation [ SD ] decline in at least 1 of 3 factors was not different between temperature groups . Fewer patients in the hypothermic group had deficits that persisted over the 5 years , but this difference did not attain statistical significance ( RR = 0.64 , P = .16 ) . CONCLUSIONS The effect of surgery on cognitive function observed early after surgery is an important predictor of cognitive performance 5 years later . Although there was evidence of a neuroprotective effect of mild hypothermia early after surgery in the original cohort , the results after 5 years were inconclusive . In general , the magnitude of cognitive changes over 5 years was modest . We believe that further trials investigating the efficacy of mild hypothermia in patients having cardiac surgery are warranted BACKGROUND AND PURPOSE Percutaneous transluminal angioplasty ( PTA ) is currently being assessed for the treatment of carotid stenosis . In comparison with carotid endarterectomy ( CEA ) , there is evidence of an increased risk of cerebral microembolism during the procedure . We have sought evidence of any neuropsychological sequelae of carotid PTA and compared it with CEA to demonstrate the relative safety of the 2 treatment options . METHODS The neuropsychological outcomes after CEA and PTA were compared in 2 matched groups of patients with severe symptomatic carotid stenosis , 96 % of whom had been r and omized in the Carotid and Vertebral Artery Transluminal Angioplasty Study ( CAVATAS ) , at a single center . Transcranial Doppler insonation of the middle cerebral artery was used to measure cerebral reactivity in response to carbon dioxide inhalation before treatment and then to detect microembolization of the ipsilateral cerebral hemisphere and measure changes in blood flow velocity during the procedures . The performance on a neuropsychological test battery administered before , 6 weeks after , and 6 months after the procedure was compared in 20 patients undergoing PTA and 26 having CEA . RESULTS At 6 weeks , 5 patients in each group showed a similar decline in neuropsychological performance ; global measures showed no significant difference between the 2 procedures , despite a significantly higher incidence of microemboli during PTA . Both groups showed a marked reduction in anxiety after treatment . CONCLUSIONS The findings provide some reassurance that PTA is not associated with greater cerebral complications than CEA , despite the higher embolic load recorded by transcranial Doppler ultrasonography during angioplasty OBJECTIVE To investigate cognitive outcome after on and off pump coronary artery bypass grafting . METHODS Seventy patients between 50 and 80 years with stable angina pectoris , ejection fraction > 30 % , serum creatinine < 150 micromol/l , and lack of tight main stem stenosis were r and omized to on or off pump coronary artery bypass grafting . St and ardized neuropsychological tests evaluated attention , verbal and visuo-spatial short-term and working memory , verbal learning , delayed recall , visuo-motor speed , and aspects of executive functions . Levels of anxiety and depression were also investigated . Testing was performed before and at 1 week , 1 and 6 months after surgery . RESULTS There was no difference in cognitive impairment ( defined as a 20 % reduction in at least 20 % of the tests ) between groups . The incidence at 1 week post-operatively was 57 % in the on pump group and 58 % in the off pump group , after 1 month 30 % and 12 % and after 6 months 19 % and 15 % , respectively ( p for interaction=0.19 ) . There was no difference between groups in anxiety ( p=0.18 ) or depression ( p=0.48 ) . CONCLUSIONS This prospect i ve , r and omized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients BACKGROUND Previously , we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death , myocardial infa rct ion , stroke , or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting ( CABG ) performed with a beating-heart technique ( off-pump ) and those who underwent CABG performed with cardiopulmonary bypass ( on-pump ) . We now report results on quality of life and cognitive function and on clinical outcomes at 1 year . METHODS We enrolled 4752 patients with coronary artery disease who were scheduled to undergo CABG and r and omly assigned them to undergo the procedure off-pump or on-pump . Patients were enrolled at 79 centers in 19 countries . We assessed quality of life and cognitive function at discharge , at 30 days , and at 1 year and clinical outcomes at 1 year . RESULTS At 1 year , there was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG ( 12.1 % and 13.3 % , respectively ; hazard ratio with off-pump CABG , 0.91 ; 95 % confidence interval [ CI ] , 0.77 to 1.07 ; P=0.24 ) . The rate of the primary outcome was also similar in the two groups in the period between 31 days and 1 year ( hazard ratio , 0.79 ; 95 % CI , 0.55 to 1.13 ; P=0.19 ) . The rate of repeat coronary revascularization at 1 year was 1.4 % in the off-pump group and 0.8 % in the on-pump group ( hazard ratio , 1.66 ; 95 % CI , 0.95 to 2.89 ; P=0.07 ) . There were no significant differences between the two groups at 1 year in measures of quality of life or neurocognitive function . CONCLUSIONS At 1 year after CABG , there was no significant difference between off-pump and on-pump CABG with respect to the primary composite outcome , the rate of repeat coronary revascularization , quality of life , or neurocognitive function . ( Funded by the Canadian Institutes of Health Research ; CORONARY Clinical Trials.gov number , NCT00463294 . ) 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 BACKGROUND Neurologic and clinical morbidity after coronary artery bypass grafting ( CABG ) can be significant . By avoiding cardiopulmonary bypass , off-pump CABG ( OPCAB ) may reduce morbidity . METHODS Sixty patients ( 30 CABG and 30 OPCAB ) were prospect ively r and omized . Neurocognitive testing was performed before the operation and 2 weeks and 1 year after the operation . Neurologic testing to detect stroke and (99m)Tc-HMPAO whole-brain single photon emission computed tomography scanning to assess cerebral perfusion were performed before the operation and 3 days afterward . Bilateral middle cerebral artery transcranial Doppler scanning was performed intraoperatively to detect cerebral microemboli . All examiners were blinded to treatment group . Clinical morbidity and costs were compared . RESULTS Coronary artery bypass grafting was associated with more cerebral microemboli ( 575 + /- 278.5 CABG versus 16.0 + /- 19.5 OPCAB ( median + /- semiinterquartile range ) and significantly reduced cerebral perfusion after the operation to the bilateral occipital , cerebellar , precunei , thalami , and left temporal lobes ( p < or = 0.01 ) . Cerebral perfusion with OPCAB was unchanged . Compared with base line , OPCAB patients performed better on the Rey Auditory Verbal Learning Test ( total and recognition scores ) at both 2 weeks and at 1 year ( p < or = 0.05 ) , whereas CABG performance was statistically unchanged for all cognitive measures . Patients who underwent CABG had more chest tube drainage ( 1389 + /- 1256 mL CABG versus 789 + /- 586 mL OPCAB , p = 0.02 ) and required more blood ( 3.9 + /- 5.8 U CABG versus 1.2 + /- 2.2 U OPCAB , p = 0.02 ) , fresh frozen plasma ( 3.0 + /- 6.0 U CABG versus 0.5 + /- 2.2 U OPCAB , p = 0.03 ) , and hours of postoperative use of dopamine ( 16.3 + /- 21.2 hours CABG versus 7.3 + /- 9.7 hours OPCAB , p = 0.04 ) . These differences culminated in higher costs for CABG ( $ 23,053 + /- $ 5,320 CABG versus $ 17,780 + /- $ 4,390 OPCAB , p < 0.0001 ) . One stroke occurred with CABG , compared with none with OPCAB ( p = NS ) . One OPCAB patient died because of a pulmonary embolus ( p = NS ) . CONCLUSIONS Compared with CABG , OPCAB may reduce neurologic and clinical morbidity as well as cost Background — It has been suggested that the risk of cerebral dysfunction is less with off-pump coronary artery bypass grafting ( OPCAB ) than with conventional coronary artery bypass grafting ( CCAB ) . However , evidence for this statement is preliminary , and additional insight is needed . Methods and Results — The study was a sub study of the r and omized Best Bypass Surgery trial that compared OPCAB with CCAB treatment with respect to intraoperative and postoperative mortality and morbidity in patients with a moderate to high level of predicted preoperative risk . The outcome was cognitive function . A total of 120 elderly patients ( mean age 76 years , SD 4.5 years ) underwent psychometric testing before surgery and at a mean of 103 ( SD 15 ) days postoperatively with a neuropsychological test battery that included 7 parameters from 4 tests . Cognitive dysfunction was defined as the occurrence of at least 2 of the 7 possible deficits . Secondary analysis was performed on the basis of the definition of a 20 % decline in cognitive scores compared with baseline , and with z score analysis . Cognitive dysfunction was identified in 4 of the 54 patients ( 7.4 % , 95 % confidence interval [ CI ] 2.1 % to 17.9 % ) in the OPCAB group and 5 of the 51 patients ( 9.8 % , 95 % CI 3.3 % to 21.4 % ) in the CCAB group . We found no difference in incidence of cognitive dysfunction between the groups regardless of the definition applied . Conclusions — In elderly high-risk patients , no significant difference was found in the incidence of cognitive dysfunction 3 months after either OPCAB or CCAB Background — Atrial fibrillation is common among older persons . Catheter ablation is increasingly used in patients for whom medical therapy has failed . Methods and Results — We conducted a retrospective cohort study of all fee-for-service Medicare beneficiaries ≥65 years of age who underwent catheter ablation for atrial fibrillation between July 1 , 2007 , and December 31 , 2009 . The main outcome measures were major complications within 30 days and mortality , heart failure , stroke , hospitalization , and repeat ablation within 1 year . A total of 15 423 patients underwent catheter ablation for atrial fibrillation . Mean age was 72 years ; 41 % were women ; and > 95 % were white . For every 1000 procedures , there were 17 cases of hemopericardium requiring intervention , 8 cases of stroke , and 8 deaths within 30 days . More than 40 % of patients required hospitalization within 1 year ; however , atrial fibrillation or flutter was the primary discharge diagnosis in only 38.4 % of cases . Eleven percent of patients underwent repeat ablation within 1 year . Renal impairment ( hazard ratio , 2.07 ; 95 % confidence interval , 1.66–2.58 ) , age ≥80 years ( hazard ratio , 3.09 ; 95 % confidence interval , 2.32–4.11 ) , and heart failure ( hazard ratio , 2.54 ; 95 % confidence interval , 2.07–3.13 ) were major risk factors for 1-year mortality . Advanced age was a major risk factor for all adverse outcomes . Conclusions — Major complications after catheter ablation for atrial fibrillation were associated with advanced age but were fairly infrequent . Few patients underwent repeat ablation . R and omized trials are needed to inform risk-benefit calculations for older persons with drug-refractory , symptomatic atrial fibrillation OBJECTIVE Animal studies have shown that pretreatment with hyperbaric oxygen can induce central nervous system ischemic tolerance and also modulate the inflammatory response . We evaluated this therapy in patients undergoing cardiopulmonary bypass . METHODS Sixty-four patients were prospect ively r and omized to group A ( n = 31 ; atmospheric air , 1.5 atmospheres absolute ) or group B ( n = 33 ; hyperbaric oxygen , 2.4 atmospheres absolute ) before on-pump coronary artery bypass grafting . Age , sex , body mass index , diabetes , hypertension , smoking , coronary disease severity , left ventricular function , Parsonnet score , Euroscore , bypass time , myocardial ischemia time , and number of grafts were comparable in both groups . Canadian Cardiovascular Society angina , New York Heart Association dyspnea , and previous myocardial infa rct ion were significantly higher in group B. Inflammatory markers were analyzed before surgery and 2 and 24 hours after bypass . Neuropsychometric testing was performed 48 hours before surgery and 4 months after surgery and included trail making A and B , the Rey auditory verbal learning test , grooved peg board , information processing table A , and digit span forward and backward . Neuropsychometric dysfunction was defined as more than 1 SD deterioration in more than 2 neuropsychometric tests . Chi-square tests , Fisher tests , t tests , and analysis of variance were used as appropriate for statistical analysis . RESULTS Group A had a significant postoperative increase in the inflammatory markers soluble E-selectin , CD18 , and heat shock protein 70 . This was not observed in group B. Neuropsychometric dysfunction was also significantly higher in group A compared with group B. There was no difference in any other early postoperative clinical outcome . CONCLUSIONS Our results seem to indicate that pretreatment with hyperbaric oxygen can reduce neuropsychometric dysfunction and also modulate the inflammatory response after cardiopulmonary bypass . However , further multicenter r and omized trials are needed to clinical ly evaluate this form of therapy OBJECTIVES Reports on adverse neurological events following transcatheter aortic valve implantation ( TAVI ) have focused on strokes , while more subtle postoperative cognitive decline has not yet been systematic ally investigated . In this study , we prospect ively examined neurological and cognitive outcomes in patients undergoing transapical ( TA ) and surgical aortic valve replacement ( AVR ) . METHODS A total of 64 patients with severe symptomatic aortic stenosis were investigated between January 2008 and July 2009 . Clinical neurological examination and comprehensive neuropsychological testing were performed before and after the procedure , at discharge and at 3-month follow-up . Diffusion-weighted magnetic resonance imaging ( DW-MRI ) was applied to detect morphological brain injury . RESULTS TA-TAVI patients ( n = 27 ) were older and at higher surgical risk compared with surgical AVR patients ( n = 37 ; mean age 82.2 ± 4.7 vs 67.5 ± 8.9 years ; log EuroSCORE 36.4 ± 13.2 vs 2.6 ± 8.5 % , both P < 0.001 ) . There was one stroke in each group ( 3.7 vs 2.7 % , P = 0.49 ) , both classified as embolic based on imaging characteristics . After TA-TAVI , cognitive tests showed no decline during follow-up , while , after AVR , 7 of 11 tests showed a decline early after surgery . Similarly , with-in patient analysis showed that the rate of individuals with clinical ly relevant cognitive decline was increased early after AVR ( TA-TAVI vs AVR : 18 vs 46 % at discharge [ P = 0.03 ] ; 28 vs 6 % at 3 months [ P = 0.04 ] ) . New focal ischaemic cerebral lesions were detected on DW-MRI in 58 % ( 7 of 12 ) of patients after TA-TAVI vs 34 % ( 12 of 35 ) after AVR ( P = 0.13 ) . The number of brain lesions per patient and cumulative embolic load per patient were similar between groups . An association between postoperative cerebral ischaemia and cognitive dysfunction was not found ( odds ratio 2.37 , 95 % confidence interval 0.05 - 113.75 , P = 0.66 ) . CONCLUSIONS Cognitive function was only mildly impaired after TA-TAVI when compared with a marked , albeit transient , decline after surgical AVR . Focal embolic brain injury tended to occur more frequently after TA-TAVI , but this was not related to cognitive decline during the 3-month follow-up BACKGROUND Carotid endarterectomy ( CEA ) reduces the risk of stroke in selected patients with symptomatic and asymptomatic carotid disease , but its beneficial influence on cognitive performance in the elderly remains debatable . This prospect i ve study sought to determine early and long-term neurocognitive outcomes after CEA for severe unilateral carotid artery stenosis . METHODS From July 2006 to December 2008 , 75 symptomatic ( group A ) and 70 asymptomatic patients ( group B ) aged 65 years and older underwent CEA under general anesthesia . Sixty-eight age- and sex-matched individuals who underwent laparoscopic cholecystectomy during the same period at our institution served as a control group ( group H ) . Patients with contralateral severe carotid stenosis or occlusion and those with dementia , depression , or a history of major stroke were excluded . Cognitive function was assessed using 2 neuropsychological tests ( the Mini-Mental State Examination [ MMSE ] and the Montreal Cognitive Assessment [ MoCA ] ) performed preoperatively ( T0 ) and then 3 ( T1 ) and 12 months ( T2 ) after operation . A change of at least 2 points between the scores at T0 and T2 was arbitrarily considered as clinical ly significant . RESULTS At T0 , group A revealed significant cognitive impairments in both mean test scores by comparison with group H ( P = .005 and P < .01 , respectively ) , whereas there were no significant differences between groups A and B , or between groups B and H. Postoperatively , symptomatic patients had significant improvements in their mean cognitive performance scores in both tests ( P < .01 and P < .01 , respectively ) , whereas there were no changes in the asymptomatic and control patients ' scores . No significant differences emerged for the MMSE scores in the 3 groups , whereas there was a marginally significant difference in the MoCA scores between groups A and H ( P = .08 ) , but not for A versus B or B versus H when clinical ly significant scores were considered . CONCLUSION Our study showed that only elderly symptomatic patients with severe carotid lesions had a significant improvement in cognitive performance scores after CEA , although the benefit was considered clinical ly not significant . This suggests that CEA does not diminish neurocognitive functions , but it might provide some protection against cognitive decline in the elderly Objective : To compare the effect on cognition of carotid artery stenting ( CAS ) and carotid endarterectomy ( CEA ) for symptomatic carotid artery stenosis . Methods : Patients r and omized to CAS or CEA in the International Carotid Stenting Study ( ICSS ; IS RCT N25337470 ) at 2 participating centers underwent detailed neuropsychological examinations ( NPE ) before and 6 months after revascularization . Ischemic brain lesions were assessed with diffusion-weighted imaging before and within 3 days after revascularization . Cognitive test results were st and ardized into z scores , from which a cognitive sumscore was calculated . The primary outcome was the change in cognitive sumscore between baseline and follow-up . Results : Of the 1,713 patients included in ICSS , 177 were enrolled in the 2 centers during the sub study period , of whom 140 had an NPE at baseline and 120 at follow-up . One patient with an unreliable baseline NPE was excluded . CAS was associated with a larger decrease in cognition than CEA , but the between-group difference was not statistically significant : −0.17 ( 95 % CI −0.38 to 0.03 ; p = 0.092 ) . Eighty-nine patients had a pretreatment MRI and 64 within 3 days after revascularization . New ischemic lesions were found twice as often after CAS than after CEA ( relative risk 2.1 ; 95 % CI 1.0 to 4.4 ; p = 0.041 ) . Conclusions : Differences between CAS and CEA in effect on cognition were not statistically significant , despite a substantially higher rate of new ischemic lesions after CAS than after CEA . Classification of Evidence : This study provides Class III evidence that any difference between the effects of CAS and CEA on cognition at 6 months after revascularization is small AIM Aim of this study was to eluci date if postoperative neurocognitive function after biological aortic valve replacement ( AVR ) can be influenced by temperature management during cardiopulmonary bypass ( CPB ) . METHODS In this prospect i ve r and omized study , we measured the effect of mild hypothermic ( 32 ° C , N.=30 ) vs. normothermic ( 37 ° C , N.=30 ) CPB on neurocognitive function . All patients underwent elective isolated biological AVR ( mean age 67 ± 8 years , mean additional EuroSCORE 5.6 ± 2.4 ) . Neurocognitive function was objective ly measured by means of objective P300 auditory-evoked potentials before surgery , one week and four months after surgery . Clinical data and outcome were monitored . RESULTS P300 evoked potentials were comparable between patients operated with mild hypothermic ( 370 ± 30 ms ) and normothermic CPB ( 373 ± 32 ms ) before surgery ( P=0.85 ) . P300 peak latencies were prolonged ( = impaired ) in patients operated with normothermic ( 402 ± 29 , P<0.0001 ) as well as with mild hypothermic CPB ( 405 ± 30 ms , P<0.0001 ) one week after surgery . Even four months after surgery , still impairment of P300 peak latencies could be documented in either patients operated with normothermic ( 394 ± 28 ms ) and mild hypothermic CPB ( 400 ± 33 ms , ) in repeated measures analysis of variance ( P=0.042 ) . Group comparison revealed no difference between patients operated with normothermic and mild hypothermic CPB at one week ( P=0.54 ) and four months ( P=0.67 ) after surgery . Clinical data as well as postoperative adverse events were comparable between the two groups . CONCLUSION Normothermic temperature management during CPB is non-inferior to hypothermic in means of neuroprotection . Since patients after biological aortic valve replacement show a sub clinical but measurable cognitive deficit up to four months after surgery , other factors have to be addressed to add further benefit to the extremely good results of open biological AVR Background Decline in renal and cognitive function may complicate early recovery after coronary-artery bypass grafting . AT1-receptor antagonists have been demonstrated to be neuro- and renoprotective . Aim of ARTA , a prospect i ve , double-blind , r and omised and placebo controlled study , was to detect whether preoperative treatment with c and esartan influences postoperative cognitive and renal function . Study protocol One hundred and five patients eligible for coronary artery bypass graft surgery ( 65–85 years old , all suffering from hypertension and coronary artery disease , with stable kidney function ) were r and omized to c and esartan ( 8 mg od ) or placebo for between 8 and 11 days prior to surgery . Existing ACE-inhibitor/angiotensin receptor antagonist-therapy had to be stopped prior to the study . Vali date d cognitive function tests ( trail making , Horn ’s perfomance III und VI , divided attention and change of reaction , memory - immediate and delayed recall , digit span ) were performed preoperatively , 1 week and 3 months after surgery . Renal function was assessed by creatinine clearance on the day before , 1 week and 3 months after surgery . Results Eighty-seven patients ( n = 43 C and esartan , n = 44 placebo ) were included in the ITT- population for analysis . Drug treatment had no adverse effect on perioperative blood pressure . Only five patients experienced a period of hypotension during introduction of anaesthesia ( C and esartan 1/44 , placebo 4/44 ) . One week as well as three months after surgery , there were no differences in relevant cognitive function parameters compared to the status prior to surgery , independent from treatment . Creatinine clearance showed a clear decrease one week after surgery with a minor further reduction observed 3 months after surgery , but there was no difference between C and esartan and placebo treated patients . Between both groups , there were no significant differences in the number of adverse events and number of patients with adverse events nor in the incidence of renal failure with consecutive dialysis and cerebral strokes ( c and esartan 2 , placebo 5 ) and possibly drug related severe adverse events . Conclusion This r and omised placebo-controlled and prospect i ve study in elderly patients does not support previous reports suggesting a substantial impairment of cognitive function after coronary artery bypass graft surgery . Preservation of cognitive and renal function was independent of pre-surgical administration of c and esartan BACKGROUND Many patients with severe aortic stenosis and coexisting conditions are not c and i date s for surgical replacement of the aortic valve . Recently , transcatheter aortic-valve implantation ( TAVI ) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis . METHODS We r and omly assigned patients with severe aortic stenosis , whom surgeons considered not to be suitable c and i date s for surgery , to st and ard therapy ( including balloon aortic valvuloplasty ) or transfemoral transcatheter implantation of a balloon-exp and able bovine pericardial valve . The primary end point was the rate of death from any cause . RESULTS A total of 358 patients with aortic stenosis who were not considered to be suitable c and i date s for surgery underwent r and omization at 21 centers ( 17 in the United States ) . At 1 year , the rate of death from any cause ( Kaplan – Meier analysis ) was 30.7 % with TAVI , as compared with 50.7 % with st and ard therapy ( hazard ratio with TAVI , 0.55 ; 95 % confidence interval [ CI ] , 0.40 to 0.74 ; P<0.001 ) . The rate of the composite end point of death from any cause or repeat hospitalization was 42.5 % with TAVI as compared with 71.6 % with st and ard therapy ( hazard ratio , 0.46 ; 95 % CI , 0.35 to 0.59 ; P<0.001 ) . Among survivors at 1 year , the rate of cardiac symptoms ( New York Heart Association class III or IV ) was lower among patients who had undergone TAVI than among those who had received st and ard therapy ( 25.2 % vs. 58.0 % , P<0.001 ) . At 30 days , TAVI , as compared with st and ard therapy , was associated with a higher incidence of major strokes ( 5.0 % vs. 1.1 % , P=0.06 ) and major vascular complications ( 16.2 % vs. 1.1 % , P<0.001 ) . In the year after TAVI , there was no deterioration in the functioning of the bioprosthetic valve , as assessed by evidence of stenosis or regurgitation on an echocardiogram . CONCLUSIONS In patients with severe aortic stenosis who were not suitable c and i date s for surgery , TAVI , as compared with st and ard therapy , significantly reduced the rates of death from any cause , the composite end point of death from any cause or repeat hospitalization , and cardiac symptoms , despite the higher incidence of major strokes and major vascular events . ( Funded by Edwards Lifesciences ; Clinical Trials.gov number , NCT00530894 . ) OBJECTIVE To compare the incidence of neuropsychologic deficits 1 week and 6 months after coronary artery bypass graft ( CABG ) surgery ( extracardiac ) and valve surgery with or without CABG surgery ( intracardiac ) using reliable change indices to define the incidence of neuropsychologic deficits . DESIGN Prospect i ve study . SETTING Cardiac surgical unit in a university teaching hospital . PARTICIPANTS Patients scheduled for elective multiple-graft ( > or =3 grafts ) CABG surgery ( n = 59 ) , or elective valve surgery ( with or without concomitant CABG surgery ) ( n = 50 ) and a matched sample of nonsurgical controls ( n = 53 ) . INTERVENTIONS Neuropsychologic assessment s were performed 1 day before surgery , 7 days and 6 months after surgery . MEASUREMENTS AND MAIN RESULTS The 7-day assessment showed no significant differences between valve surgery patients and CABG surgery patients in the incidence of neuropsychologic deficits . When reassessed 6 months postoperatively , the valve group displayed a significantly higher incidence of deficits on the digit symbol test compared with the CABG group ( valve 26.7 % v CABG 6.8 % ) . In the CABG group , there was a significant change in the incidence of deficits per patient from 7 days to 6 months ( p = 0.03 ) that was not evident in the valve group . CONCLUSION There are some differences in the neuropsychologic outcome of extracardiac and intracardiac surgery . Patients undergoing isolated CABG surgery showed a greater reduction in the incidence of persisting deficits at 6 months than patients undergoing valve surgery with or without CABG surgery . This finding warrants further investigation , with particular attention to patients undergoing combined valve and coronary artery procedures INTRODUCTION Atrial fibrillation ( AF ) adversely impacts mortality , stroke , heart failure , and dementia . AF ablation eliminates AF in most patients . We evaluated the long-term impact of AF ablation on mortality , heart failure ( HF ) , stroke , and dementia in a large system-wide patient population . METHODS A total of 4,212 consecutive patients who underwent AF ablation were compared ( 1:4 ) to 16,848 age/gender matched controls with AF ( no ablation ) and 16,848 age/gender matched controls without AF . Patients were enrolled from the large ongoing prospect i ve Intermountain AF study and were followed for at least 3 years . RESULTS Of the 37,908 patients , mean age 65.0 ± 13 years , 5,667 ( 14.9 % ) died , 1,296 ( 3.4 % ) had a stroke , and 1,096 ( 2.9 % ) were hospitalized for HF over > 3 years of follow-up . AF ablation patients were less likely to have diabetes , but were more likely to have hypertension , HF , and significant valvular heart disease . AF ablation patients had a lower risk of death and stroke in comparison to AF patients without ablation . Alzheimer 's dementia occurred in 0.2 % of the AF ablation patients compared to 0.9 % of the AF no ablation patients and 0.5 % of the no AF patients ( P < 0.0001 ) . Other forms of dementia were also reduced significantly in those treated with ablation . Compared to patients with no AF , AF ablation patients had similar long-term rates of death , dementia , and stroke . CONCLUSIONS AF ablation patients have a significantly lower risk of death , stroke , and dementia in comparison to AF patients without ablation . AF ablation may eliminate the increased risk of death and stroke associated with AF Background : Postoperative cognitive dysfunction ( POCD ) after coronary artery bypass graft surgery is a common complication for which , despite many clinical investigations , no definitive etiology has been found . The current use of both high- and low-dose fentanyl as anesthetic techniques allowed us to investigate the effect of fentanyl on the incidence of POCD . Methods : Three hundred fifty patients scheduled to undergo elective coronary artery bypass graft surgery were r and omized to receive either high-dose fentanyl ( 50 & mgr;g/kg ) or low-dose fentanyl ( 10 & mgr;g/kg ) as the basis of the anesthetic . All patients underwent neuropsychological testing before surgery and at 1 week , 3 months , and 12 months after surgery . Results : One hundred sixty-eight patients in the low-dose group and 158 patients in the high-dose group were included in the final analysis . Neuropsychological testing was performed on 88 % , 93 % , and 92 % of patients at 1 week , 3 months , and 12 months , respectively . There was no difference between group mean scores at any of the three testing times . Analysis of individual patients by the 20 % rule did not detect any differences between groups . The one SD rule , which has fewer false-positive results , detected significantly more patients with POCD in the low-dose group than in the high-dose group at 1 week ( 23.6 % vs. 13.7 % ; P = 0.03 ) but not at the other testing times . Patients with POCD spent an average of 1.2 days longer in the hospital than those without POCD ( P = 0.021 ) . Conclusions : High-dose fentanyl is not associated with a difference in the incidence of POCD at 3 or 12 months after surgery . Low-dose fentanyl leads to shorter postoperative ventilation times and may be associated with a greater incidence of POCD 1 week after surgery . Early POCD is associated with an increased duration of stay in the hospital BACKGROUND The purpose of this study was to examine the comparative effects of propofol and fentanyl on cerebral oxygenation during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction . METHODS One hundred eighty patients scheduled for elective coronary artery bypass grafting were r and omly divided into two groups : propofol group ( n = 90 ) and fentanyl group ( n = 90 ) . After induction of anesthesia , a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to monitor jugular venous oxygen hemoglobin saturation continuously . Hemodynamic measurements and arterial and jugular venous blood gases were measured at seven time points . All patients underwent a battery of neurologic and neuropsychological tests on the day before the operation and at 6 months after the operation . RESULTS Cerebral desaturation ( defined as a jugular venous oxygen hemoglobin saturation value less than 50 % ) during cardiopulmonary bypass was more frequent in the fentanyl group than in the propofol group . Cerebral desaturation time ( duration when jugular venous oxygen hemoglobin saturation was less than 50 % ) and the ratio of cerebral desaturation time to total cardiopulmonary bypass time in the fentanyl group differed significantly from those in the propofol group ( fentanyl group : 27 + /- 14 minutes , 20 % + /- 9 % ; propofol group : 18 + /- 11 minutes , 14 % + /- 7 % , respectively , p < 0.05 ) . There was no significant difference in postoperative cognitive dysfunction at 6 months after operation between the two groups ( propofol group : 5 of 77 , 6 % ; fentanyl group : 5 of 75 , 7 % ) . CONCLUSIONS Propofol preserved cerebral oxygenation state estimated by jugular venous oxygenation during cardiopulmonary bypass compared with the fentanyl group . However , propofol did not affect postoperative cognitive dysfunction OBJECTIVE Neurocognitive deficits occur frequently in patients undergoing cardiac surgery and may be caused , in part , by ischemic cerebral injury . Cerebral hypothermia has been proposed as a neuroprotective strategy to reduce ischemic injury in animal studies , in postcardiac arrest , and during cardiac surgery . We sought to evaluate the effects of sustained mild intraoperative hypothermia , without rewarming , on neurocognitive function after coronary artery bypass surgery . METHODS Patients ( aged > /= 60 years ) undergoing non-urgent coronary surgery were r and omized to an intraoperative nasopharyngeal temperature of 34 degrees C ( hypothermic ; n = 133 ) or 37 degrees C ( normothermic ; n = 134 ) , maintained using water-circulating thermal control pads . No active rewarming was used . Transcranial Doppler was used intraoperatively to monitor middle cerebral artery emboli . Neuropsychometric testing , consisting of a battery of 16 tests , was performed by blinded observers preoperatively , before discharge , and at 3 months , and tests were divided into 4 cognitive domains . A deficit was prospect ively defined as a 1 st and ard deviation decrease in individual scores from baseline in 1 or more domains . RESULTS The number of intraoperative cerebral emboli was similar between the control and the treated groups ( 188 [ 115 - 331 ] vs 182 [ 100 - 305 ] , P = .71 ) . At discharge , neurocognitive deficits were present in 45 % of control patients and in 49 % of treated patients ( P = .49 ) and at 3 months decreased to 8 % in control patients and 4 % in treated patients ( P = .28 ) . There was no correlation between the total number of cerebral emboli and the occurrence of neurocognitive deficits ( r = -0.01 ; P = .88 ) . Hypothermic patients demonstrated trends toward reduced intensive care unit stay ( 1.4 + /- 1.0 days vs 1.2 + /- 0.7 days , P = .06 ) and increased chest tube output ( 655 + /- 327 mL/24 h vs 584 + /- 325 mL/24 h , P = .09 ) . CONCLUSIONS Mild intraoperative hypothermia has no major adverse effects but does not decrease the incidence of neurocognitive deficits in patients undergoing coronary artery bypass surgery . In the absence of rewarming and cerebral hyperthermia , sustained mild hypothermia does not improve cognitive outcome BACKGROUND Off-pump coronary artery bypass grafting surgery reduces the intraoperative cerebral embolic load and may therefore cause less brain injury . The main aim of this study was to compare off-pump and on-pump surgery with regard to the frequency of new postoperative cerebral ischemic lesions and the prevalence of postoperative cognitive impairment . We also assessed whether preoperative cerebral ischemic injury predicts the risk for cognitive dysfunction after surgery . METHODS One hundred twenty patients with ischemic coronary artery disease were prospect ively r and omized to undergo off-pump or on-pump surgery . A detailed neuropsychological assessment and a cerebral magnetic resonance imaging examination were performed on the day before and at 3 months postoperatively . The neuropsychological assessment was repeated at 12 months . RESULTS There was no significant ( p = 0.17 ) difference between off-pump ( 8.2 % ) and on-pump ( 17.3 % ) surgery with regard to new postoperative cerebral lesions . The prevalence of cognitive impairment after surgery was also similar in the two groups ( 3 months : off-pump 20.4 % , on-pump 23.1 % , p = 0.74 ; 12 months : off-pump 24.1 % , on-pump 23.1 % , p = 0.90 ) . The degree of preoperative cerebral ischemic injury was significantly associated with cognitive dysfunction after on-pump ( p = 0.02 ) but not after off-pump ( p = 0.22 ) surgery . None of the patients with normal preoperative radiologic findings were found to have cognitive impairment at 3 months postoperatively ( p = 0.04 ) . CONCLUSIONS Long-term cognitive function and magnetic resonance imaging evidence of brain injury were similar after off-pump and on-pump coronary artery bypass grafting surgery . Preoperative cerebral magnetic resonance imaging can be used to predict the risk for cognitive dysfunction after coronary artery bypass grafting surgery Background —Neuropsychological deficits occur in 30 % to 80 % of patients undergoing heart surgery and are due in part to ischemic cerebral injury during cardiopulmonary bypass . We tested whether mild hypothermia , the most efficacious neuroprotective strategy found in laboratory studies , improved cognitive outcome in patients undergoing coronary artery surgery . Methods and Results — Patients 60 years or older scheduled for coronary artery surgery were enrolled . During cardiopulmonary bypass , patients were initially cooled to 32 ° C then r and omly assigned to rewarming to 37 ° C ( control ) or 34 ° C ( hypothermic ) , with no further intraoperative warming . Testing was scheduled preoperatively and 1 week and 3 months postoperatively . Eleven tests were combined into 3 cognitive domains : memory , attention , and psychomotor speed and dexterity . A patient was classified as having a cognitive deficit if a decrease of ≥0.50 SD was realized in 1 or more domains . The incidence of cognitive deficits 1 week after surgery , which was the primary outcome , was 62 % ( 62/100 ) in the control group and 48 % ( 45/94 ) in the hypothermic group ( relative risk 0.77 , P = 0.048 ) . In the hypothermic group , the magnitude of deterioration in attention and in speed and dexterity was reduced by 55.6 % ( P = 0.038 ) and 41.3 % ( P = 0.042 ) , respectively . At 3 months , the hypothermic group still performed better on one test of speed and dexterity ( grooved pegboard ) . There was no difference in morbidity or mortality . Conclusions —Our findings support a neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery and should encourage physicians and perfusionists to pay careful attention to brain temperature during cardiopulmonary bypass BACKGROUND All neurologic events in the PARTNER r and omized trial comparing transcatheter aortic valve replacement ( TAVR ) with surgical aortic valve replacement ( AVR ) were analyzed . METHODS High-risk patients with aortic stenosis were stratified into transfemoral ( TF , n = 461 ) or transapical ( TA , n = 196 ) strata based on their arterial anatomy and r and omized : 657 received treatment assigned ( " as treated " ) , 313 underwent AVR , and 344 TAVR . Neurologic events were prospect ively adjudicated by an independent Clinical Events Committee . Multivariable , multiphase hazard analysis eluci date d factors associated with increased likelihood of neurologic events . RESULTS Forty-nine neurologic events ( 15 transient ischemic attacks , 34 strokes ) occurred in 47 patients ( TAVR , n = 31 ; AVR , n = 16 ) . An early peaking high hazard phase occurred within the first week , which declined to a constant late hazard phase out to 2 years . The risk in the early phase was higher after TAVR than AVR , and in the TAVR arm in patients with a smaller aortic valve area index . In the late risk phase , the likelihood of neurologic event was linked to patient-related factors in both arms ( " non-TF c and i date , " history of recent stroke or transient ischemic attack , and advanced functional disability ) , but not by treatment ( TAVR vs AVR ) or any intraprocedural variables . The likelihood of sustaining a neurologic event was lowest in the AVR subgroup in the TF stratum during all available follow-up . CONCLUSIONS After either treatment , there were 2 distinct hazard phases for neurologic events that were driven by different risk factors . Neurologic complications occurred more frequently after TAVR than AVR early , but thereafter the risk was influenced by patient- and disease-related factors |
1,765 | 23,704,701 | Most primary accuracy studies lack statistical power to do this , particularly because of the small absolute number of disease events per test included in the diagnostic work .
Synthesis using their raw data can overcome this problem , but meta-analysts will have limited success if there are difficulties in obtaining the large majority of valid studies , without ' missing ' data on the tests relevant in clinical decision-making . | Individual patient data meta-analyses using the raw data from primary diagnostic accuracy studies are taking hold in systematic review s evaluating tests .
Conventional review s and meta-analyses that summarise study -level data on test accuracy ( sensitivity and specificity ) have several disadvantages .
The most fundamental limitation of this approach is that it estimates the rates of test result -given disease ( sensitivity is probability of positive test result -given disease is present ; and specificity is probability of negative test result -given disease is absent ) .
This may be addressed by summarising predictive values , but estimating accuracy for individual tests without consideration of other tests in the test chains that make up everyday diagnostic work-ups remain a problem . | In the evaluation of a diagnostic imaging test for the diagnosis of a particular illness in a particular category of patients , the test should be construed as leading to a test result in the sense of a set of descriptive readings from the image(s ) , not interpretation of these ; and in the evaluation of the test , therefore , the first challenge is the translation of each test result ( set of readings ) into the corresponding probability that the illness is present . This interpretive translation should not be subjective , nor should it be based on an objective algorithm founded on clinical judgments . Instead , a suitable diagnostic probability function ( of the elements in the test result ) should be derived empirically by logistic regression analysis of suitable data . We illustrate this alternative outlook by re analysis of the data from the Prospect i ve Investigation of Pulmonary Embolism Diagnosis The performance of a predictive model is overestimated when simply determined on the sample of subjects that was used to construct the model . Several internal validation methods are available that aim to provide a more accurate estimate of model performance in new subjects . We evaluated several variants of split- sample , cross-validation and bootstrapping methods with a logistic regression model that included eight predictors for 30-day mortality after an acute myocardial infa rct ion . R and om sample s with a size between n = 572 and n = 9165 were drawn from a large data set ( GUSTO-I ; n = 40,830 ; 2851 deaths ) to reflect modeling in data sets with between 5 and 80 events per variable . Independent performance was determined on the remaining subjects . Performance measures included discriminative ability , calibration and overall accuracy . We found that split- sample analyses gave overly pessimistic estimates of performance , with large variability . Cross-validation on 10 % of the sample had low bias and low variability , but was not suitable for all performance measures . Internal validity could best be estimated with bootstrapping , which provided stable estimates with low bias . We conclude that split- sample validation is inefficient , and recommend bootstrapping for estimation of internal validity of a predictive logistic regression model Abstract Objective : To assess the extent to which different forms of summarising diagnostic test information influence general practitioners ' ability to estimate disease probabilities . Design : Controlled question naire study . Setting : Three Swiss conferences in continuous medical education . Participants : 263 general practitioners . Intervention : Question naire with multiple choice questions about terms of test accuracy and a clinical vignette with the results of a diagnostic test described in three different ways ( test result only , test result plus test sensitivity and specificity , test result plus the positive likelihood ratio presented in plain language ) . Main outcome measures : Doctors ' knowledge and application of terms of test accuracy and estimation of disease probability in the clinical vignette . Results : The correct definitions for sensitivity and predictive value were chosen by 76 % and 61 % of the doctors respectively , but only 22 % chose the correct answer for the post-test probability of a positive screening test . In the clinical vignette doctors given the test result only overestimated its diagnostic value ( median attributed likelihood ratio (aLR)=9.0 , against 2.54 reported in the literature ) . Providing the scan 's sensitivity and specificity reduced the overestimation ( median aLR=6.0 ) but to a lesser extent than simple wording of the likelihood ratio ( median aLR=3.0 ) . Conclusion : Most general practitioners recognised the correct definitions for sensitivity and positive predictive value but did not apply them correctly . Conveying test accuracy information in simple , non-technical language improved their ability to estimate disease probabilities accurately . What is already known on this topic Many doctors confuse the sensitivity of clinical tests and their positive predictive value Doctors tend to overestimate information derived from such tests and underestimate information from a patient 's clinical history Most primary research on diagnostic accuracy is reported using sensitivity and specificity or likelihood ratios What this study adds In a cohort of experienced Swiss general practitioners most were unable to interpret correctly numerical information on the diagnostic accuracy of a screening test When presented with a positive result alone they grossly overestimated its value Adding information on the test 's sensitivity and specificity moderated these overestimates , and expressing the same numerical information as a positive likelihood ratio in simple , non-technical language brought the estimates still closer to their true Each year 1.5 million patients are admitted to coronary-care units ( CCUs ) for suspected acute ischemic heart disease ; for half of these , the diagnosis is ultimately " ruled out . " In this study , conducted in the emergency rooms of six New Engl and hospitals ranging in type from urban teaching centers to rural nonteaching hospitals , we sought to develop a diagnostic aid to help emergency room physicians reduce the number of their CCU admissions of patients without acute cardiac ischemia . From data on 2801 patients , we developed a predictive instrument for use in a h and -held programmable calculator , which requires only 20 seconds to compute a patient 's probability of having acute cardiac ischemia . In a prospect i ve trial that included 2320 patients in the six hospitals , physicians ' diagnostic specificity for acute ischemia increased when the probability value determined by the instrument was made available to them . Rates of false-positive diagnosis decreased without any increase in rates of false-negative diagnosis . Among study patients with a final diagnosis of " not acute ischemia , " the number of CCU admissions decreased 30 per cent , without any increase in missed diagnoses of ischemia . The proportion of CCU admissions that represented patients without acute ischemia dropped from 44 to 33 per cent . Widespread use of this predictive instrument could reduce the number of CCU admissions in this country by more than 250,000 per year OBJECTIVE To determine the accuracy of ultrasound scan in the diagnosis of endometrial hyperplasia and cancer in postmenopausal bleeding . DESIGN A prospect i ve diagnostic accuracy study ( 1996 - 97 ) . SETTING Minimal access surgical training centers in two large teaching hospitals . METHODS Ultrasound scan and outpatient endometrial sampling were performed on 96 patients with postmenopausal bleeding . Patients unable to have these outpatient procedures had a formal inpatient hysteroscopy and curettage . Test performance characteristics were computed for ultrasound scan comparing its estimate of endometrial thickness with histologic diagnosis that served as a ' gold ' st and ard . OUTCOME MEASURES Accuracy of the ultrasonic endometrial thickness was estimated using sensitivity , specificity and predictive values for binary data . For multilevel data , the diagnostic accuracy was computed using likelihood ratios ( LRs ) . An LR < decreased the probability that endometrial hyperplasia/cancer was present , whereas an LR > 1 increased the probability that such lesion was present . RESULTS Using endometrial thickness > or = 4 mm , the sensitivity of ultrasound to detect the endometrial malignancy was 92.9 % , the specificity was 500 % , and the positive and negative predictive values were 24.1 % and 97.6 % respectively . Analysis using likelihood ratio ( LR ) revealed that LR was 0.14 for endometrial thickness > or = 4.0 mm , 0.94 for endometrial thickness 4.1 - 9.0 mm , and 3.3 for endometrial thickness > 9.0 mm . CONCLUSION In women with postmenopausal bleeding , malignancy can probably be safely excluded if sonographic endometrial thickness is < or = 4.0 mm . However , the probability of endometrial hyperplasia/cancer is not particularly altered by the knowledge that endometrial thickness on scan is > 4.0 mm BACKGROUND Systematic review s that " compare " the accuracy of 2 or more tests often include different sets of studies for each test . PURPOSE To investigate the availability of direct comparative studies of test accuracy and to assess whether summary estimates of accuracy differ between meta-analyses of noncomparative and comparative studies . DATA SOURCES Systematic review s in any language from the Data base of Abstract s of Review s of Effects and the Cochrane Data base of Systematic Review s from 1994 to October 2012 . STUDY SELECTION 1 of 2 assessors selected review s that evaluated at least 2 tests and identified meta-analyses that included both noncomparative studies and comparative studies . DATA EXTRACTION 1 of 3 assessors extracted data about review and study characteristics and test performance . DATA SYNTHESIS 248 review s compared test accuracy ; of the 6915 studies , 2113 ( 31 % ) were comparative . Thirty-six review s ( with 52 meta-analyses ) had adequate studies to compare results of noncomparative and comparative studies by using a hierarchical summary receiver-operating characteristic meta-regression model for each test comparison . In 10 meta-analyses , noncomparative studies ranked tests in the opposite order of comparative studies . A total of 25 meta-analyses showed more than a 2-fold discrepancy in the relative diagnostic odds ratio between noncomparative and comparative studies . Differences in accuracy estimates between noncomparative and comparative studies were greater than expected by chance ( P < 0.001 ) . LIMITATION A paucity of comparative studies limited exploration of direction in bias . CONCLUSION Evidence derived from noncomparative studies often differs from that derived from comparative studies . Robustly design ed studies in which all patients receive all tests or are r and omly assigned to receive one or other of the tests should be more routinely undertaken and are preferred for evidence to guide test selection . PRIMARY FUNDING SOURCE National Institute for Health Research ( United Kingdom ) |
1,766 | 28,185,212 | Conclusions The economic analyses showed reasonable consistency in the model structures used and the events captured .
The results strongly suggested that NOACs are cost effective alternatives to low molecular-weight heparin .
Dabigatran appeared to be the least cost effective NOAC . | Background Total hip replacement ( THR ) and total knee replacement ( TKR ) surgeries are being performed with increasing regularity and are associated with a high risk of developing a venous thromboembolism ( VTE ) .
New oral anticoagulants ( NOACs ) may be more effective at preventing VTEs but are associated with more bleeding events versus traditional anticoagulants .
Objective The objective of this systematic review was to identify published economic analyses of NOACs for primary VTE prophylaxis following THR and TKR surgeries , and to summarise the modelling techniques used and the cost-effectiveness results . | Venous thromboembolism ( VTE ) has a significant impact on healthcare costs but is largely preventable with anticoagulant prophylaxis using low-molecular-weight heparins ( LMWHs ) , such as enoxaparin or dalteparin . Rivaroxaban and dabigatran etexilate are two new oral anticoagulants ( NOACs ) both compared with enoxaparin in separate trials . A decision analytic model with a healthcare and national payer perspective over a five-year time horizon was used to evaluate the cost-effectiveness of the NOACs for VTE prophylaxis after total hip replacement ( THR ) or total knee replacement ( TKR ) in France , Italy and Spain . Efficacy and safety data were obtained from r and omised controlled trials of rivaroxaban vs enoxaparin and an indirect statistical comparison for rivaroxaban vs dabigatran . Rivaroxaban demonstrated dominance across all comparisons , indications and countries . In THR , total per-patient costs were reduced by up to € 160 in the enoxaparin comparison and € 115 in the dabigatran comparison , respectively . In addition , quality -adjusted life-years ( QALYs ) were increased by up to 0.0011 and 0.0012 in each comparison , respectively . Similarly , total costs were reduced in TKR by up to € 137 and € 28 in the enoxaparin and dabigatran comparisons , respectively . The total number of QALYs was increased by up to 0.0014 in the enoxaparin comparison and 0.0005 in the dabigatran comparison . The results were driven by costs since the incremental benefits were minimal . Rivaroxaban use could result in substantial healthcare cost savings and improved quality of life . The results are applicable across three European countries with differing healthcare systems so , potentially , could be generalised to a much wider population BACKGROUND After hip replacement surgery , prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism . Our aim was to assess the oral , direct thrombin inhibitor dabigatran etexilate for such prophylaxis . METHODS In this double-blind study , we r and omised 3494 patients undergoing total hip replacement to treatment for 28 - 35 days with dabigatran etexilate 220 mg ( n=1157 ) or 150 mg ( 1174 ) once daily , starting with a half-dose 1 - 4 h after surgery , or subcutaneous enoxaparin 40 mg once daily ( 1162 ) , starting the evening before surgery . The primary efficacy outcome was the composite of total venous thromboembolism ( venographic or symptomatic ) and death from all causes during treatment . On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo , the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7 % . Efficacy analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT00168818 . FINDINGS Median treatment duration was 33 days . 880 patients in the dabigatran etexilate 220 mg group , 874 in the dabigatran etexilate 150 mg group , and 897 in the enoxaparin group were available for the primary efficacy outcome analysis ; the main reasons for exclusion in all three groups were the lack of adequate venographic data . The primary efficacy outcome occurred in 60 ( 6.7 % ) of 897 individuals in the enoxaparin group versus 53 ( 6.0 % ) of 880 patients in the dabigatran etexilate 220 mg group ( absolute difference -0.7 % , 95 % CI -2.9 to 1.6 % ) and 75 ( 8.6 % ) of 874 people in the 150 mg group ( 1.9 % , -0.6 to 4.4 % ) . Both doses were thus non-inferior to enoxaparin . There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin ( p=0.44 for 220 mg , p=0.60 for 150 mg ) . The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups . INTERPRETATION Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery , with a similar safety profile BACKGROUND Chronic thromboembolic pulmonary hypertension ( CTPH ) is associated with considerable morbidity and mortality . Its incidence after pulmonary embolism and associated risk factors are not well documented . METHODS We conducted a prospect i ve , long-term , follow-up study to assess the incidence of symptomatic CTPH in consecutive patients with an acute episode of pulmonary embolism but without prior venous thromboembolism . Patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography and , if supportive findings were present , ventilation-perfusion lung scanning and pulmonary angiography . CTPH was considered to be present if systolic and mean pulmonary-artery pressures exceeded 40 mm Hg and 25 mm Hg , respectively ; pulmonary-capillary wedge pressure was normal ; and there was angiographic evidence of disease . RESULTS The cumulative incidence of symptomatic CTPH was 1.0 percent ( 95 percent confidence interval , 0.0 to 2.4 ) at six months , 3.1 percent ( 95 percent confidence interval , 0.7 to 5.5 ) at one year , and 3.8 percent ( 95 percent confidence interval , 1.1 to 6.5 ) at two years . No cases occurred after two years among the patients with more than two years of follow-up data . The following increased the risk of CTPH : a previous pulmonary embolism ( odds ratio , 19.0 ) , younger age ( odds ratio , 1.79 per decade ) , a larger perfusion defect ( odds ratio , 2.22 per decile decrement in perfusion ) , and idiopathic pulmonary embolism at presentation ( odds ratio , 5.70 ) . CONCLUSIONS CTPH is a relatively common , serious complication of pulmonary embolism . Diagnostic and therapeutic strategies for the early identification and prevention of CTPH are needed BACKGROUND Oral anticoagulants , such as dabigatran etexilate , an oral , direct thrombin inhibitor , that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism ( VTE ) after total knee replacement surgery . METHODS In this r and omized , double-blind study , 2076 patients undergoing total knee replacement received dabigatran etexilate , 150 mg or 220 mg once-daily , starting with a half-dose 1 - 4 hours after surgery , or subcutaneous enoxaparin 40 mg once-daily , starting the evening before surgery , for 6 - 10 days . Patients were followed-up for 3 months . The primary efficacy outcome was a composite of total VTE ( venographic or symptomatic ) and mortality during treatment , and the primary safety outcome was the incidence of bleeding events . RESULTS The primary efficacy outcome occurred in 37.7 % ( 193 of 512 ) of the enoxaparin group versus 36.4 % ( 183 of 503 ) of the dabigatran etexilate 220 mg group ( absolute difference , -1.3 % ; 95 % CI , -7.3 to 4.6 ) and 40.5 % ( 213 of 526 ) of the 150 mg group ( 2.8 % ; 95 % CI , -3.1 to 8.7 ) . Both doses were noninferior to enoxaparin based on the pre-specified noninferiority criterion . The incidence of major bleeding did not differ significantly between the three groups ( 1.3 % versus 1.5 % and 1.3 % respectively ) . No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or follow-up . CONCLUSIONS Dabigatran etexilate ( 220 mg or 150 mg ) was at least as effective and with a similar safety profile as enoxaparin for prevention of VTE after total knee-replacement surgery This trial compared the efficacy and safety of oral dabigatran , a direct thrombin inhibitor , versus subcutaneous enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty . A total of 2,055 patients were r and omised to 28 - 35 days treatment with oral dabigatran , 220 mg once-daily , starting with a half-dose 1 - 4 hours after surgery , or subcutaneous enoxaparin 40 mg once-daily , starting the evening before surgery . The primary efficacy outcome was a composite of total venous thromboembolism [ VTE ] ( venographic or symptomatic ) and death from all-causes . The main secondary composite outcome was major VTE ( proximal deep-vein thrombosis or non-fatal pulmonary embolism ) plus VTE-related death . The main safety outcome was major bleeding . In total , 2,013 were treated , of whom 1,577 operated patients were included in the primary efficacy analysis . The primary efficacy outcome occurred in 7.7 % of the dabigatran group versus 8.8 % of the enoxaparin group , risk difference ( RD ) -1.1 % ( 95%CI -3.8 to 1.6 % ) ; p<0.0001 for the pre-specified non-inferiority margin . Major VTE plus VTE-related death occurred in 2.2 % of the dabigatran group versus 4.2 % of the enoxaparin group , RD -1.9 % ( -3.6 % to -0.2 % ) ; p=0.03 . Major bleeding occurred in 1.4 % of the dabigatran group and 0.9 % of the enoxaparin group ( p=0.40 ) . The incidence of adverse events , including liver enzyme elevations and cardiac events , during treatment was similar between the groups . Extended prophylaxis with oral dabigatran 220 mg once-daily was as effective as subcutaneous enoxaparin 40 mg once-daily in reducing the risk of VTE after total hip arthroplasty , and superior to enoxaparin for reducing the risk of major VTE . The risk of bleeding and safety profiles were similar BACKGROUND We investigated the efficacy of rivaroxaban , an orally active direct factor Xa inhibitor , in preventing venous thrombosis after total knee arthroplasty . METHODS In this r and omized , double-blind trial , 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban , 10 mg once daily , beginning 6 to 8 hours after surgery , or subcutaneous enoxaparin , 40 mg once daily , beginning 12 hours before surgery . The primary efficacy outcome was the composite of any deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause within 13 to 17 days after surgery . Secondary efficacy outcomes included major venous thromboembolism ( i.e. , proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death related to venous thromboembolism ) and symptomatic venous thromboembolism . The primary safety outcome was major bleeding . RESULTS The primary efficacy outcome occurred in 79 of 824 patients ( 9.6 % ) who received rivaroxaban and in 166 of 878 ( 18.9 % ) who received enoxaparin ( absolute risk reduction , 9.2 % ; 95 % confidence interval [ CI ] , 5.9 to 12.4 ; P<0.001 ) . Major venous thromboembolism occurred in 9 of 908 patients ( 1.0 % ) given rivaroxaban and 24 of 925 ( 2.6 % ) given enoxaparin ( absolute risk reduction , 1.6 % ; 95 % CI , 0.4 to 2.8 ; P=0.01 ) . Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin ( P=0.005 ) . Major bleeding occurred in 0.6 % of patients in the rivaroxaban group and 0.5 % of patients in the enoxaparin group . The incidence of drug-related adverse events , mainly gastrointestinal , was 12.0 % in the rivaroxaban group and 13.0 % in the enoxaparin group . CONCLUSIONS Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty , with similar rates of bleeding . ( Clinical Trials.gov number , NCT00361894 . BACKGROUND Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement . Apixaban , an orally active factor Xa inhibitor , might be as effective , have lower bleeding risk , and be easier to use than is enoxaparin . We assessed efficacy and safety of these drugs after elective total knee replacement . METHODS In ADVANCE-2 , a multicentre , r and omised , double-blind phase 3 study , patients undergoing elective unilateral or bilateral total knee replacement were r and omly allocated through an interactive central telephone system to receive oral apixaban 2.5 mg twice daily ( n=1528 ) or subcutaneous enoxaparin 40 mg once daily ( 1529 ) . The r and omisation schedule was generated by the Bristol-Myers Squibb r and omisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four . Investigators , patients , statisticians , adjudicators , and steering committee were masked to allocation . Apixaban was started 12 - 24 h after wound closure and enoxaparin 12 h before surgery ; both drugs were continued for 10 - 14 days , when bilateral ascending venography was scheduled . Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis , non-fatal pulmonary embolism , and all-cause death during treatment . The statistical plan required non-inferiority of apixaban before testing for superiority ; analysis was by intention to treat for non-inferiority testing . The study is registered at Clinical Trials.gov , number NCT00452530 . FINDINGS 1973 of 3057 patients allocated to treatment ( 1528 apixaban , 1529 enoxaparin ) were eligible for primary efficacy analysis . The primary outcome was reported in 147 ( 15 % ) of 976 apixaban patients and 243 ( 24 % ) of 997 enoxaparin patients ( relative risk 0.62 [ 95 % CI 0.51 - 0.74 ] ; p<0.0001 ; absolute risk reduction 9.3 % [ 5.8 - 12.7 ] ) . Major or clinical ly relevant non-major bleeding occurred in 53 ( 4 % ) of 1501 patients receiving apixaban and 72 ( 5 % ) of 1508 treated with enoxaparin ( p=0.09 ) . INTERPRETATION Apixaban 2.5 mg twice daily , starting on the morning after total knee replacement , offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin , without increased bleeding . FUNDING Bristol-Myers Squibb ; Pfizer BACKGROUND This phase 3 trial compared the efficacy and safety of rivaroxaban , an oral direct inhibitor of factor Xa , with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty . METHODS In this r and omized , double-blind study , we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily , beginning after surgery , or 40 mg of enoxaparin subcutaneously once daily , beginning the evening before surgery , plus a placebo tablet or injection . The primary efficacy outcome was the composite of deep-vein thrombosis ( either symptomatic or detected by bilateral venography if the patient was asymptomatic ) , nonfatal pulmonary embolism , or death from any cause at 36 days ( range , 30 to 42 ) . The main secondary efficacy outcome was major venous thromboembolism ( proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death from venous thromboembolism ) . The primary safety outcome was major bleeding . RESULTS A total of 3153 patients were included in the superiority analysis ( after 1388 exclusions ) , and 4433 were included in the safety analysis ( after 108 exclusions ) . The primary efficacy outcome occurred in 18 of 1595 patients ( 1.1 % ) in the rivaroxaban group and in 58 of 1558 patients ( 3.7 % ) in the enoxaparin group ( absolute risk reduction , 2.6 % ; 95 % confidence interval [ CI ] , 1.5 to 3.7 ; P<0.001 ) . Major venous thromboembolism occurred in 4 of 1686 patients ( 0.2 % ) in the rivaroxaban group and in 33 of 1678 patients ( 2.0 % ) in the enoxaparin group ( absolute risk reduction , 1.7 % ; 95 % CI , 1.0 to 2.5 ; P<0.001 ) . Major bleeding occurred in 6 of 2209 patients ( 0.3 % ) in the rivaroxaban group and in 2 of 2224 patients ( 0.1 % ) in the enoxaparin group ( P=0.18 ) . CONCLUSIONS A once-daily , 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily , 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty . The two drugs had similar safety profiles . ( Clinical Trials.gov number , NCT00329628 . BACKGROUND The optimal strategy for thromboprophylaxis after major joint replacement has not been established . Low-molecular-weight heparins such as enoxaparin predominantly target factor Xa but to some extent also inhibit thrombin . Apixaban , a specific factor Xa inhibitor , may provide effective thromboprophylaxis with a low risk of bleeding and improved ease of use . METHODS In a double-blind , double-dummy study , we r and omly assigned patients undergoing total knee replacement to receive 2.5 mg of apixaban orally twice daily or 30 mg of enoxaparin subcutaneously every 12 hours . Both medications were started 12 to 24 hours after surgery and continued for 10 to 14 days . Bilateral venography was then performed . The primary efficacy outcome was a composite of asymptomatic and symptomatic deep-vein thrombosis , nonfatal pulmonary embolism , and death from any cause during treatment . Patients were followed for 60 days after anticoagulation therapy was stopped . RESULTS A total of 3195 patients underwent r and omization , with 1599 assigned to the apixaban group and 1596 to the enoxaparin group ; 908 subjects were not eligible for the efficacy analysis . The overall rate of primary events was much lower than anticipated . The rate of the primary efficacy outcome was 9.0 % with apixaban as compared with 8.8 % with enoxaparin ( relative risk , 1.02 ; 95 % confidence interval , 0.78 to 1.32 ) . The composite incidence of major bleeding and clinical ly relevant nonmajor bleeding was 2.9 % with apixaban and 4.3 % with enoxaparin ( P=0.03 ) . CONCLUSIONS As compared with enoxaparin for efficacy of thromboprophylaxis after knee replacement , apixaban did not meet the prespecified statistical criteria for noninferiority , but its use was associated with lower rates of clinical ly relevant bleeding and it had a similar adverse-event profile . ( Clinical Trials.gov number , NCT00371683 . BACKGROUND There are various regimens for thromboprophylaxis after hip replacement . Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree . Orally active , specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis with a lower risk of bleeding and improved ease of use . METHODS In this double-blind , double-dummy study , we r and omly assigned 5407 patients undergoing total hip replacement to receive apixaban at a dose of 2.5 mg orally twice daily or enoxaparin at a dose of 40 mg subcutaneously every 24 hours . Apixaban therapy was initiated 12 to 24 hours after closure of the surgical wound ; enoxaparin therapy was initiated 12 hours before surgery . Prophylaxis was continued for 35 days after surgery , followed by bilateral venographic studies . The primary efficacy outcome was the composite of asymptomatic or symptomatic deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause during the treatment period . Patients were followed for an additional 60 days after the last intended dose of study medication . RESULTS A total of 1949 patients in the apixaban group ( 72.0 % ) and 1917 patients in the enoxaparin group ( 71.0 % ) could be evaluated for the primary efficacy analysis . The primary efficacy outcome occurred in 27 patients in the apixaban group ( 1.4 % ) and in 74 patients in the enoxaparin group ( 3.9 % ) ( relative risk with apixaban , 0.36 ; 95 % confidence interval [ CI ] , 0.22 to 0.54 ; P<0.001 for both noninferiority and superiority ; absolute risk reduction , 2.5 percentage points ; 95 % CI , 1.5 to 3.5 ) . The composite outcome of major and clinical ly relevant nonmajor bleeding occurred in 129 of 2673 patients assigned to apixaban ( 4.8 % ) and 134 of 2659 assigned to enoxaparin ( 5.0 % ) ( absolute difference in risk , -0.2 percentage points ; 95 % CI , -1.4 to 1.0 ) . CONCLUSIONS Among patients undergoing hip replacement , thromboprophylaxis with apixaban , as compared with enoxaparin , was associated with lower rates of venous thromboembolism , without increased bleeding . ( Funded by Bristol-Myers Squibb and Pfizer ; Clinical Trials.gov number , NCT00423319 . ) BACKGROUND The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge . Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin . METHODS 2509 patients scheduled to undergo elective total hip arthroplasty were r and omly assigned , stratified according to centre , with a computer-generated r and omisation code , to receive oral rivaroxaban 10 mg once daily for 31 - 39 days ( with placebo injection for 10 - 14 days ; n=1252 ) , or enoxaparin 40 mg once daily subcutaneously for 10 - 14 days ( with placebo tablet for 31 - 39 days ; n=1257 ) . The primary efficacy outcome was the composite of deep-vein thrombosis ( symptomatic or asymptomatic detected by m and atory , bilateral venography ) , non-fatal pulmonary embolism , and all-cause mortality up to day 30 - 42 . Analyses were done in the modified intention-to-treat population , which consisted of all patients who had received at least one dose of study medication , had undergone planned surgery , and had adequate assessment of thromboembolism . This study is registered at Clinical Trials.gov , number NCT00332020 . FINDINGS The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group . The primary outcome occurred in 17 ( 2.0 % ) patients in the rivaroxaban group , compared with 81 ( 9.3 % ) in the enoxaparin group ( absolute risk reduction 7.3 % , 95 % CI 5.2 - 9.4 ; p<0.0001 ) . The incidence of any on-treatment bleeding was much the same in both groups ( 81 [ 6.6 % ] events in 1228 patients in the rivaroxaban safety population vs 68 [ 5.5 % ] of 1229 patients in the enoxaparin safety population ; p=0.25 ) . INTERPRETATION Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of venous thromboembolism , including symptomatic events , in patients undergoing total hip arthroplasty |
1,767 | 26,075,234 | These effects also appeared with improvement in mood and stress relief and were influenced by time-on-task effect .
Further studies are needed , but chewing could be useful for modifying cognitive function | Chewing is crushing food not only to aid swallowing and digestion , but also to help stress relief and regulate cognitive function , especially in attention .
It is well known that chewing gum is used for sleepiness prevention during work , learning , and driving , suggesting a link between chewing and sustained attention .
We hypothesized that chewing elevates attention and /or alertness , leading to improvements in cognitive performance . | Abstract Rationale : Recent research suggests that chewing gum may improve aspects of cognitive function and mood . There is also evidence suggesting that chewing gum reduces stress . It is important , therefore , to examine these two areas and to determine whether context ual factors ( chewing habit , type of gum , and personality ) modify such effects . Objectives : The aims of the present study were : ( i ) to determine whether chewing gum improved mood and mental performance ; ( ii ) to determine whether chewing gum had benefits in stressed individuals ; and ( iii ) to determine whether chewing habit , type of gum and level of anxiety modified the effects of gum . Subjects and methods : A cross-over study involving 133 volunteers was carried out . Each volunteer carried out a test session when they were chewing gum and without gum , with order of gum conditions counterbalanced across subjects . Baseline sessions were conducted prior to each test session . Approximately half of the volunteers were tested in 75 dBA noise ( the stress condition ) and the rest in quiet . Volunteers were stratified on chewing habit and anxiety level . Approximately , half of the volunteers were given mint gum and half fruit gum . The volunteers rated their mood at the start and end of each session and had their heart rate monitored over the session . Saliva sample s were taken to allow cortisol levels ( good indicator of alertness and stress ) to be assayed . During the session , volunteers carried out tasks measuring a range of cognitive functions ( aspects of memory , selective and sustained attention , psychomotor speed and accuracy ) . Results : Chewing gum was associated with greater alertness and a more positive mood . Reaction times were quicker in the gum condition , and this effect became bigger as the task became more difficult . Chewing gum also improved selective and sustained attention . Heart rate and cortisol levels were higher when chewing which confirms the alerting effect of chewing gum . Conclusions : Overall , the results suggest that chewing gum produces a number of benefits that are generally observed and not context -dependent . In contrast to some previous research , chewing gum failed to improve memory . Further research is now required to increase our knowledge of the behavioral effects of chewing gum and to identify the underlying mechanisms RATIONALE Recent research has shown that even small doses ( < 40 mg ) of caffeine can improve alertness and increase performance efficiency on attention tasks . Previous studies have given the caffeine in a variety of beverages or in capsules and it was of interest to see whether similar effects could be observed when the caffeine was given in gum . In addition , chewing gum has been shown to have behavioural effects and the present study extended our knowledge of this topic . OBJECTIVES To compare the effects of caffeinated gum ( 40 mg ) , placebo gum and no gum conditions on mood and attention . METHODS A double blind placebo controlled study was conducted with volunteers being r and omly assigned to one of the three conditions . Baseline measures of mood and attention were taken prior to chewing and a test session was then conducted . One hundred and eighteen young adults participated in the study . RESULTS Caffeinated gum was associated with a more positive mood and better performance on tasks requiring sustained attention . The caffeine improved the speed of encoding of new information which is consistent with previous findings . Chewing placebo gum was also found to be associated with more positive mood , both shortly after chewing and at the end of the study . CONCLUSIONS The implication s of the present study are that chewing caffeinated gum has been shown to improve performance efficiency and mood by its alerting and energising effects . The profile of caffeine effects is what one would predict from the existing caffeine literature and such effects may be extremely beneficial in real-life situations . Prior chewing of placebo gum was associated with a more positive mood and this also confirms previous findings This study tests the hypothesis that chewing gum leads to cognitive benefits through improved delivery of glucose to the brain , by comparing the cognitive performance effects of gum and glucose administered separately and together . Participants completed a battery of cognitive tests in a fully related 2 x 2 design , where one factor was Chewing Gum ( gum vs. mint sweet ) and the other factor was Glucose Co-administration ( consuming a 25 g glucose drink vs. consuming water ) . For four tests ( AVLT Immediate Recall , Digit Span , Spatial Span and Grammatical Transformation ) , beneficial effects of chewing and glucose were found , supporting the study hypothesis . However , on AVLT Delayed Recall , enhancement due to chewing gum was not paralleled by glucose enhancement , suggesting an alternative mechanism . The glucose delivery model is supported with respect to the cognitive domains : working memory , immediate episodic long-term memory and language -based attention and processing speed . However , some other mechanism is more likely to underlie the facilitatory effect of chewing gum on delayed episodic long-term memory Chewing has been shown to alleviate feelings of sleepiness and improve cognitive performance during the day . This study investigated the effect of chewing on alertness and cognitive performance across one night without sleep as well as the possible mediating role of cardiac autonomic activity . Fourteen adults participated in a r and omized , counterbalanced protocol employing a chewing , placebo and caffeine condition . Participants completed tasks assessing psychomotor vigilance , tracking , grammatical reasoning , alertness and sleepiness each hour across the night . All participants received either placebo or caffeine ( 200 mg ) , while the chewing condition also chewed on a tasteless and odorless substance for 15 min each hour . Heart rate ( HR ) , root mean square of the successive differences in R-R intervals on the ECG ( RMSSD ) , and preejection period ( PEP ) were simultaneously recorded . Alertness and cognitive performance amongst the chewing condition did not differ or were in fact worse when compared with placebo . Similarly , measures of HR and RMSSD remained the same between these two conditions ; however , PEP was reduced in the later part of the night in the chewing condition compared with a relative increase for placebo . Caffeine led to improved speed and accuracy on cognitive tasks and increased alertness when compared with chewing . Relative increases in RMSSD and reductions in HR were demonstrated following caffeine ; however , no change in PEP was seen . Strong associations between cardiac parasympathetic activity and complex cognitive tasks , as well as between subjective alertness and simpler cognitive tasks , suggest a differential process mediating complex versus simple cognitive performance during sleep deprivation The present study aim ed to examine the psychosomatic effect in the chewing of marketed gum using electroencephalogram ( EEG ) as an index . The EEG were taken in two sets : ( i ) a resting period before chewing ( control recording ) and a resting record ( post-resting recording ) for examining reproducibility ; and ( ii ) a control recording and resting period after gum-chewing for 3 min ( post-chewing recording ) . The ratio of each frequency b and to the total frequency power , the mean frequency of the alpha b and and laterality of the frequency power was calculated . In the examination of the reproducibility , no statistically significant differences were observed between control recording and post-resting recording in all indices . In the reflection of EEG after gum-chewing , there were no significant differences between control recording and the post-chewing recording . However , a significant interaction was observed among these indices by analysis of variance . In addition , the alpha power in the post-chewing recording was significantly higher than that in the control recording at almost all the positions . In conclusion , the intra-individual reproducibility of EEG was confirmed in the recording method . Furthermore , it was suggested that a significant interaction and a rising trend of the mean frequency of the alpha b and after gum-chewing reflected ' arousal ' psychosomatic responses by the chewing of marketed gum OBJECTIVES To investigate the relationship between periodontal disease and cognitive decline . DESIGN Analysis of a prospect i ve cohort study . SETTING The Health , Aging and Body Composition ( Health ABC ) Study . PARTICIPANTS One thous and fifty-three participants who were administered the Modified Mini-Mental State Examination ( 3MS ) at Year 1 ( baseline ) and Year 3 and had participated in a comprehensive periodontal examination at Year 2 . MEASUREMENTS The prospect i ve association between a range of oral health parameters and cognitive function was examined . Decline in 3MS score from Year 3 to 5 was investigated in 947 ( 89.9 % ) participants . Covariates included age , sex , education , race , cardiovascular disease and risk , and depressive symptoms . RESULTS Most indicators of adverse oral health at Year 2 were associated with cognitive impairment based on averaged 3MS scores less than 80 for Years 1 and 3 , but education and race substantially confounded these associations . Higher gingival index , a measure of gingival inflammation , at Year 2 remained independently associated with this definition of cognitive impairment and , in fully adjusted analyses , was also an independent predictor of a more-than-5-point cognitive decline from Year 3 to 5 . CONCLUSION Periodontitis may be a risk factor for cognitive decline . Gingivitis is reversible , and periodontitis to some degree is preventable and controllable when manifest . Therefore , further research is needed to clarify potential underlying mechanisms and oral health interventions that might ameliorate cognitive decline CognitiveDrug Research Ltd.,ReadingRG301EA , UKMany people chew gum partly due to the belief that itincreases aspects of mental performance , including concen-tration . To the best of our knowledge no empirical evidence exists to support this contention . The present experiment , therefore , examined the effects of chewing gum using acomprehensive and sensitive cognitive assessment battery and two tasks manipulating cognitive load . Heart rateresponses were also measured . Seventy-five healthy adult participants ( mean age 246years ) were r and omly assigned to one of three experimentalconditions ( N‹25 per group ) : ‘ ‘ chewing ’ ’ – a piece of sugar-free chewing gum ( Wrigley ’s Extra Spearmint ) was chewednaturally and constantly throughout the procedure ; ‘ ‘ shamchewing ’ ’ – participants mimicked chewing movements in theabsence of gum ; ‘ ‘ quiet control ’ ’ – no chewing behaviour wasperformed . Aspects of attention , working memory and long-termmemory were assessed using the Cognitive Drug Research ( CDR ) computerised battery . Stimuli were presented on acolour monitor and , except for two written word recall tasks , responses were collected automatically using a ‘ ‘ Yes’’/‘‘No’’responsemodule . Thetaskswerepresentedintheorder : Wordpresentation , Immediate Word Recall , Picture Presentation , SimpleReactionTime , DigitVigilance , ChoiceReactionTime , Spatial Working Memory , Numeric Working Memory , Delayed Word Recall , Word Recognition and PictureRecognition ( for details , e.g. see Kennedy et al. 2000).Following the CDR battery , participants performed compu-terised Serial Subtractions tasks . These assess concentration and working memory and allow manipulation of cognitiveload ( see Scholey et al. , 2001 for details ) . In the present study SerialThrees(involvingtherepeatedsubtractionofthreefroma r and omly generated starting number using the computer’snumerickeypad)thenSerialSevens(subtractionofseven)wereused , each for 2min . Eachcognitive task outcome measurewasanalysedby one-way analysis ofvariance , withDunnettcomparisonstoisolatebetween-group effects where appropriate . The most strikingfindingwasasignificanteffectonbothimmediate and delayedword recall , with more words being recalled in the chewingconditioncomparedwiththequietcontrolcondition(Table1).The Spatial Working Memory sensitivity index and Numericworkingmemoryreactiontimeweresimilarlyimprovedinthechewingcondition , and alsointheshamchewingconditionforthe latter measure ( which reflects the efficiency of workingmemory operations ) . In addition , simple reaction times wereslowerintheshamchewingconditionthaninthequietcontrolcondition . Baseline heart rate recordings ( sample d at 30-s intervals)began 240s prior to treatment and continued during a 180-speriod of chewing , sham chewing or sitting quietly prior tocognitive assessment ( which lasted about 30min in all ) . Heartrate ( mean bpm ) was calculated during baseline , treatment , each of the 10 CDR tasks and both Serial Subtraction tasks . Heart rate changes relative to baseline were subjected to a3(Condition ) 14(Phase ) factorial ANOVA with repeated measures on the latter factor . The main effect of conditionapproached significance , F(2,936)‹30 , p‹006 ; heart ratesweresignificantlyhigherinthechewingconditionthaninquietcontrols , p<005 ( Fig. 1 ) . There was also a significant maineffect oftask , F(13,936)‹130,p<001:with theexceptionofSimple Reaction Time and Delayed Word Recall , all taskphasesofthe study wereassociatedwithsignificantincreasesinheart rate . There was also a significant task conditioninteraction , F(26,936)‹256 , p<001.These results providedthefirst evidence thatthechewingofgum can improve episodic memory ( involving the learning , storage and retrieval of information ) and working memory(where information is held ‘ ‘ on line ’ ’ ) . They did not indicatethat gum-chewing improves aspects of attention , at least asmeasured here . The impaired Simple Reaction Time during sham chewingmay reflect diversion of attentional re sources during initialstages of performing this unfamiliar behaviour . This is con-sistent with the elevated heart rate observed while shamchewing in earlierphases of the experiment ( Fig. 1 ) . Althoughanactivecontrolisimportant , shamchewingmaynotbeidealfor this purpose , because most cognitive scores ( except , nota-E-mail : [email protected] bly , Numeric Working Memory Reaction Time ) in this group0195–6663/02/$ – see front matter # 2002 Elsevier Science Ltd. All rights reserved The notion that chewing gum may relieve stress was investigated in a controlled setting . A multi-tasking framework which reliably evokes stress and also includes performance measures was used to induce acute stress in the laboratory . Using a r and omised crossover design forty participants ( mean age 21.98 years ) performed on the multi-tasking framework at two intensities ( on separate days ) both while chewing and not chewing . Order of workload intensity and chewing conditions were counterbalanced . Before and after undergoing the platform participants completed the state portion of the State-Trait Anxiety Inventory , Bond-Lader visual analogue mood scales , a single Stress Visual Analogue Scale and provided saliva sample s for cortisol measurement . Baseline measures showed that both levels of the multi-tasking framework were effective in significantly reducing self-rated alertness , calmness and contentment while increasing self-rated stress and state anxiety . Cortisol levels fell during both levels of the stressor during the morning , reflecting the predominance of a.m. diurnal changes , but this effect was reversed in the afternoon which may reflect a measurable stress response . Pre-post stressor changes ( Delta ) for each measure at baseline were subtracted from Delta scores under chewing and no chewing conditions . During both levels of stress the chewing gum condition was associated with significantly better alertness and reduced state anxiety , stress and salivary cortisol . Overall performance on the framework was also significantly better in the chewing condition . The mechanisms underlying these effects are unknown but may involve improved cerebral blood flow and /or effects secondary to performance improvement during gum chewing The effects of three principal constituents ( sugar , spearmint , and gumbase ) in chewing gum on EEG findings in 20 normal subjects were investigated . After they chewed the gumbase , theta activity decreased significantly at Fp2 , O1 , T3 , T4 , F4 , P3 , and Pz ; alpha activity increased significantly at O1 and decreased significantly at Fpl , and beta activity increased significantly at Fpl , Fp2 , O1 , T3 , T4 , P3 and Pz . After they inhaled the spearmint , alpha activity decreased significantly at 02 , F3 , P4 , and Fz , and beta increased significantly at 02 , F3 , P4 , and Fz . The mean frequency of the alpha b and was significantly higher than after 1 min at rest without inhalation . After the subjects chewed the gumbase with sucrose , theta activity increased at Fp2 and Fz ; alpha activity increased significantly at T3 ; and beta activity decreased significantly at Fpl , Fp2 , F4 , P3 , P4 , Fz , and Pz . The mean frequency of the alpha b and was significantly lower than after 1 min at rest without it at almost all the positions . These results suggest that the gumbase with sucrose induced relaxed concentration effects while inhalation of spearmint induced arousal effects . The chewing of gumbase showed arousal tendency |
1,768 | 22,736,403 | CONCLUSION Based on the available evidence , oral antibacterial antibiotics and prolonged macrolide antibiotics are considered therapeutic options in the treatment of CRS while the use of topical antibacterial antibiotics , intravenous antibacterial antibiotics and oral , topical , or intravenous antifungals would be recommended against . | BACKGROUND Chronic rhinosinusitis ( CRS ) is characterized by inflammation of the mucosa of the nose and paranasal sinuses .
The role of bacterial or fungal infection in CRS is unclear , yet antimicrobials are commonly prescribed for this condition .
Published guidelines offer little direction regarding antibiotic strategies for CRS .
The purpose of this article is to provide an evidence -based approach to the use of antibacterial and antifungal antibiotics in the management of CRS . | OBJECTIVE effects of Fosfomycin ( FOM ) nebulizer therapy were studied in patients with chronic sinusitis . METHODS about 28 patients with chronic sinusitis were administered 2 ml of FOM sodium ( 3 % w/v ) by nebulizer three times per week for 4 weeks . Levels of IL-1 beta , IL-6 , IL-8 , and TNF-alpha in nasal lavage were also measured before and at the end of treatment . RESULTS the overall efficacy of this treatment on the basis of both subjective and objective symptoms , was ' excellent ' for 28.6 % , ' good ' for 10.7 % , ' fair ' for 39.4 % , and yield ' no change ' for 21.4 % of the patients . Both IL-1 beta and IL-6 concentrations were significantly decreased after treatment . Although the IL-8 level did not significantly decrease , it seems to be related to the overall efficacy . TNF-alpha was not detected in all of the sample s. CONCLUSION FOM nebulization therapy is highly effective in treatment for chronic sinusitis , and efficacy may be due to an immunomodulatory mechanism , as well as its bactericidal effect BACKGROUND Chronic rhinosinusitis ( CRS ) is one of the most common chronic diseases . Recently , it has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of the disease . On the basis of this hypothesis , intranasal treatment with amphotericin B should benefit patients with CRS . Data from 2 uncontrolled and 2 controlled trials are conflicting , however . OBJECTIVE To clarify the role of intranasal antifungal drugs in the treatment of CRS , we conducted a large , double-blind , placebo-controlled , multicenter study comparing the effectiveness of amphotericin B nasal lavages with placebo . METHODS A total of 116 r and omly selected patients with CRS were instructed to instill 25 mL amphotericin B ( 100 microg/mL ) or placebo to each nostril twice daily for 3 months . Primary outcomes included a reduction in total visual analog scale ( VAS ) score and nasal endoscopy score . Secondary outcome measures included peak nasal inspiratory flow , polyp score , quality of life ( Short Form-36 , Rhinosinusitis Outcome Measure-31 ) , and individual VAS scores . RESULTS Analysis was based on intention to treat and involved all patients r and omly assigned . Mean VAS scores , Short Form-36 and Rhinosinusitis Outcome Measure-31 data , peak nasal inspiratory flow values , nasal endoscopy scores , and polyp scores were similar in both treatment groups at the time of r and omization , and no significant differences were observed after 13 weeks of treatment . CONCLUSION Amphotericin B nasal lavages in the described dosing and time schedule do not reduce clinical signs and symptoms in patients with CRS . CLINICAL IMPLICATION S Amphotericin B nasal lavages in the described dosing and time schedule are ineffective and therefore not advised in the treatment of patients with CRS Efficacy and safety of a new oral third generation Cephalosporin , Cefotiam Hexetil ( CTM ) 200 mg bid were compared with those of Cefixime ( CX ) 200 mg bid over 10 day duration of treatment . One hundred and twenty two ambulatory adults suffering from chronic sinusitis were r and omized by ENT specialists in this multicentre prospect i ve double blind , doubled dummy study . Sinusitis diagnosis evocated in front of fascial pain , purulent nasal discharge and /or obstruction was confirmed with sinus X-ray . Use of antibiotics or corticosteroids concomitantly or 15 days prior inclusion represented one of the major exclusion criterion . One hundred and seventy one patients were evaluated for efficacy analysis ( 62 and 59 respectively in CTM and CX groups ) . Regarding demographic data , clinical and radiological signs , the two population s were comparable at inclusion excepted for sex and weight ( female : 73 % in CTM group versus 47 % in CX group ) . The overall clinical success rate at the end of treatment ( cure+improvement ) was not significantly different between the two groups ( CTM : 82 % versus CX : 80 % ) . The incidence of adverse events was less frequent in the CTM group ( 14.5 % versus 19 % ) . In conclusion , CTM 200 mg bid is as efficacious and as well tolerated as CX 200 mg bid in the treatment of chronic sinusitis in adults BACKGROUND There is little scientific evidence to support the current practice of using oral glucocorticosteroids and antibiotics to treat patients with chronic rhinosinusitis and nasal polyps . OBJECTIVE We evaluated the effects of oral glucocorticoids and doxycycline on symptoms and objective clinical and biological parameters in patients with chronic rhinosinusitis and nasal polyps . METHODS In a double-blind , placebo-controlled , multicenter trial , we r and omly assigned 47 participants with bilateral nasal polyps to receive either methylprednisolone in decreasing doses ( 32 - 8 mg once daily ) , doxycycline ( 200 mg on the first day , followed by 100 mg once daily ) , or placebo for 20 days . Participants were followed for 12 weeks . Patients were assessed for nasal peak inspiratory flow and symptoms and by nasal endoscopy . Markers of inflammation such as eosinophilic cationic protein ( ECP ) , IL-5 , myeloperoxidase , matrix metalloproteinase 9 , and IgE were measured in nasal secretions . Concentrations of eosinophils , ECP , and soluble IL-5 receptor alpha were measured in peripheral blood sample s. RESULTS Methylprednisolone and doxycycline each significantly decreased nasal polyp size compared with placebo . The effect of methylprednisolone was maximal at week 3 and lasted until week 8 , whereas the effect of doxycycline was moderate but present for 12 weeks . Methylprednisolone significantly reduced levels of ECP , IL-5 , and IgE in nasal secretions , whereas doxycycline significantly reduced levels of myeloperoxidase , ECP , and matrix metalloproteinase 9 in nasal secretions . CONCLUSION This is the first double-blind , placebo-controlled study to show a significant effect of oral methylprednisolone and doxycycline on size of nasal polyps , nasal symptoms , and mucosal and systemic markers of inflammation BACKGROUND Recently , fungal elements were suspected to be the causative agent of chronic rhinosinusitis , and benefits of topical amphotericin B therapy have been reported . OBJECTIVE The effects of amphotericin B versus control nasal spray on chronic rhinosinusitis were compared in a double-blind , r and omized clinical trial . METHODS Patients with chronic rhinosinusitis were administered 200 microL per nostril amphotericin B ( 3 mg/mL ) or saline nasal spray 4 times daily over a period of 8 weeks . The response rate , defined as a 50 % reduction of pretreatment computed tomography score , was the primary outcome variable . Additional outcome variables included a symptom score , a quality of life score , and an endoscopy score . Before and after treatment , nasal lavages were pretreated with dithiothreitol and examined for fungal elements by PCR and st and ard culture techniques . RESULTS Seventy-eight patients were included , and 60 patients finished the study per protocol . In the control group , no positive response ( 0 of 32 ) was observed , and 2 of 28 patients responded in the amphotericin B group ( P>.2 ) . The symptom scores were distinctly worse after amphotericin B therapy ( P < .005 ) . The other parameters investigated did not differ remarkably between the treatment groups . CONCLUSION Nasal amphotericin B spray in the described dosing and time schedule is ineffective and deteriorates patient symptoms OBJECTIVES /HYPOTHESIS To examine the efficacy and tolerability of topical mupirocin for the management of surgically recalcitrant chronic rhinosinusitis ( CRS ) associated with Staphylococcus aureus infection . STUDY DESIGN Prospect i ve open-label pilot study . METHODS Patients with surgically recalcitrant CRS who had positive nasendoscopically guided cultures for Staphylococcus aureus were treated with twice daily nasal lavages containing 0.05 % Mupirocin and lactated ringers salts . The duration of treatment was 3 weeks . Patients were assessed before and after treatment in terms of nasendoscopic findings , microbiology results , and Sinonasal Outcome Test ( SNOT-20 ) and visual analogue scale question naires . RESULTS Fifteen of 16 patients had improved nasendoscopic findings after treatment . Twelve of 16 patients noted overall symptom improvement . Fifteen of 16 patients had negative swab results for Staphylococcus aureus after treatment . Only minimal adverse effects were experienced . CONCLUSIONS Nasal Lavage with 0.05 % Mupirocin may represent an effective and well tolerated alternative treatment for postsurgical recalcitrant CRS OBJECTIVES Conventional management of allergic fungal rhinosinusitis ( AFRS ) after surgery consists of the use of steroids to immunomodulate the body 's response to fungi . However , there are many side effects to prolonged steroid use , and some patients are unresponsive to st and ard treatment . The role of systemic antifungal drugs in AFRS is still largely unknown . This was a pilot study to evaluate the effectiveness of itraconazole , an oral antifungal drug , in the treatment of refractory AFRS . METHOD Thirty-two patients with AFRS who had had surgery and were refractory to prednisone , steroid , and amphotericin B nasal sprays were treated with itraconazole for at least 3 months . They were evaluated with pre- and posttreatment endoscopic examinations , serum immunoglobulin E ( IgE ) , and the 31-Item Rhinosinusitis Outcome Measure ( RSOM-31 ) question naires . Monthly liver function tests were done to monitor for the hepatic side effects of itraconazole . RESULTS Twelve cases had endoscopic improvement . Fifteen had no difference , and five had a worse endoscopic stage after 3 months . One patient had to stop treatment due to abnormal liver function tests . The mean pre- and posttreatment IgE levels were 581 microg/L and 766 microg/L , respectively . Subjectively , 9 patients ( 28 % ) reported a significant improvement , 9 ( 28 % ) had moderate improvements , and 14 ( 44 % ) reported little or no change . There was no correlation between the subjective and the endoscopic changes . CONCLUSION Itraconazole may be useful as an adjunct in the management of AFRS . However , more studies , including a prospect i ve r and omized clinical trial , are required to determine if itraconazole is effective in the management of AFRS BACKGROUND It has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of chronic rhinosinusitis ( CRS ) . Based on this rationale , the use of topical antifungals ( amphotericin B ) has been advocated . Studies on its clinical effectiveness are , however , contradictory . OBJECTIVES To examine the effect of nasal antifungal treatment on secreted mediators in sample s of nasal lavage fluid from patients with CRS with or without nasal polyps ( NP ) . METHODS Part two of a prospect i ve double-blind , placebo-controlled multicenter clinical trial investigating the effect of 13 weeks of treatment with amphotericin B or placebo on the levels of pro-inflammatory cytokines , chemokines and growth factors ( i.e. , IL-1beta , IL-1RA , IL-2 , IL-2R , IL-3 , IL-4 , IL-5 , IL-6 , IL-7 , IL-8 , IL-10 , IL-12 ( p40/p70 subunits ) , IL-13 , IL-15 , IL-17 , TNF-alpha , IFN-alpha , IFN-gamma , G-CSF , GM-CSF , MIP-1alpha , MIP-1beta , IP-10 , MIG , eotaxin , RANTES , MCP-1 , MCP-2 , MCP-3 , VEGF , EGF , FGF-basic , HGF , Gro-alpha ) and albumin via a fluorescent enzyme immunoassay in nasal lavage specimens of CRS patients with or without NP . RESULTS Topical amphotericin B had no significant effect on the level of any of the tested pro-inflammatory cytokines , chemokines , and growth factors in CRS nasal lavage sample s. Treatment with placebo , however , increased the level of MIP-1alpha and MIP-1beta , which are mediators involved in wound healing . CONCLUSIONS Topical amphotericin B has no significant effect on activation markers of nasal inflammatory cells in chronic rhinosinusitis with or without nasal polyps BACKGROUND The treatment of acute , recurrent , and chronic sinusitis remains controversial because of the presence of a wide variety of aerobic and anaerobic bacteria in the sinuses . DESIGN This double-blind , r and omized trial compared cefaclor with amoxicillin in the treatment of acute , recurrent , and chronic maxillary sinusitis using clinical evaluation , roentgenography , and microbiologic evaluation of antral aspirates . SETTING Outpatient office of five otorhinolaryngologists in Salt Lake City , Utah . PATIENTS One hundred eight adult patients with acute , recurrent , or chronic maxillary sinusitis . INTERVENTION Oral treatment with cefaclor ( 500 mg ) twice daily or amoxicillin ( 500 mg ) three times daily for 10 days . MAIN OUTCOME MEASURE Clinical response to treatment with cefaclor vs amoxicillin . RESULTS Fifty-six patients with acute sinusitis , 25 with recurrent sinusitis , and 15 with chronic sinusitis were evaluable . Although multiple organisms were common in each group , patients with acute sinusitis were more likely to have Haemophilus influenzae or Streptococcus pneumoniae , and patients with recurrent or chronic sinusitis were more likely to have anaerobes in sinus aspirate . Whether treated with cefaclor or amoxicillin , clinical improvement occurred in 86 % of patients with acute sinusitis and 56 % of patients with recurrent sinusitis . Patients with chronic sinusitis were too few to allow statistical analysis of the differences in outcome between them and patients with recurrent or acute sinusitis . Resistance of the cultured organisms to the study drug used was unrelated to treatment outcome . CONCLUSIONS The rate of clinical improvement was high in patients with acute sinusitis but was less favorable in those with recurrent and chronic disease regardless of the study drug used . The susceptibility of organisms isolated to the study drugs was unrelated to outcome BACKGROUND Fungal infection may be secondary to nasal polyposis or represent a real etiopathogenic factor in the infection itself . OBJECTIVE The aim of this study was to evaluate the effectiveness of a combined treatment with lysine acetylsalicylate ( LAS ) and amphotericin B in preventing recurrence in patients with nasal polyposis with accompanying mycotic infection in comparison with a control group with nasal polyposis and fungal infection who did not receive antifungal therapy . PATIENTS AND METHODS A total of 115 patients with nasal polyposis were r and omly assigned to 4 different groups and treated as follows : ( 1 ) group A , 25 patients were first surgically treated and then treated with LAS ; ( 2 ) group B , 25 patients received 40 mg of triamcinolone retard intramuscularly 3 times every 10 days ( total dose 120 mg ) and then they were treated with LAS ; ( 3 ) group C , 16 patients were surgically treated and then treated with LAS and amphotericin B ; ( 4 ) group D : 23 patients were treated with a medical polypectomy and steroids ( as in the group B ) and then with LAS and amphotericin B. RESULTS We found no significant differences between groups C and D , groups C and A , or groups B and D. However , the recurrence of nasal polyps in the groups treated with amphotericin B plus LAS ( C and D ) was significantly lower ( P = .018 ) than in the 2 groups treated only with LAS ( A and B ) . CONCLUSION Our results indicate that long term topical treatment with LAS and amphotericin B may be clinical ly effective in the treatment of patients with nasal polyposis associated with fungal infection OBJECTIVE Evidence surrounding systemic absorption of gentamicin during intraoperative irrigation of the paranasal sinuses is lacking . The objectives of this study were to determine ( 1 ) if topical gentamicin is absorbed from the paranasal sinuses , ( 2 ) if hearing loss occurs following topical administration of gentamicin , and ( 3 ) if gentamicin placed within the sinuses travels retro grade ( against mucociliary clearance ) up the auditory tube to the middle ear . DESIGN Consecutive , prospect i ve case series . SETTING Tertiary centre . METHODS A series of patients undergoing sinus surgery were identified . Fluorescein-stained gentamicin was used to irrigate the sinus cavities intraoperatively . Otoscopy using a filtered light source was performed 30 minutes postoperatively . MAIN OUTCOME MEASURES ( 1 ) Serum gentamicin levels preirrigation and at 30 minutes postirrigation and ( 2 ) change in pure-tone average and threshold at 8 kHz pre- and postoperative audiograms . RESULTS Twenty patients were enrolled . Serum gentamicin levels were detectable in three patients . Fluorescein irrigation solution was not visualized in the middle ear space . No significant hearing loss was observed in any of the patients . CONCLUSIONS Gentamicin may be absorbed from the nasal mucosa during intraoperative irrigation of the sinuses . However , detectable serum levels were well below therapeutic levels . The clinical significance of this finding requires further study to determine if topical sinus irrigation with gentamicin is a safe procedure OBJECTIVES The antiinflammatory effect of macrolide antibiotics has been well-established , as has their role in the treatment of certain disorders of chronic airway inflammation . Several studies have suggested that long-term , low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis ; however , these studies have lacked a control group . To date , this effect has not been tested in a r and omized , placebo-controlled study . METHOD The authors conducted a double-blind , r and omized , placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis . Subjects received either 150 mg roxithromycin daily for 3 months or placebo . Outcome measures included the Sinonasal Outcome Test-20 ( SNOT-20 ) , measurements of peak nasal inspiratory flow , saccharine transit time , olfactory function , nasal endoscopic scoring , and nasal lavage assays for interleukin-8 , fucose , and a2-macroglobulin . RESULTS There were statistically significant improvements in SNOT-20 score , nasal endoscopy , saccharine transit time , and IL-8 levels in lavage fluid ( P<.05 ) in the macrolide group . A correlation was noted between improved outcome measures and low IgE levels . No significant improvements were noted for olfactory function , peak nasal inspiratory flow , or lavage levels for fucose and a2-macroglobulin . No improvement in any outcome was noted in the placebo-treated patients . CONCLUSION These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis , particularly in patients with low levels of IgE , and supports the in vitro evidence of their antiinflammatory activity . Additional studies are required to assess their place in clinical practice BACKGROUND Eosinophils and nasal polyps are believed to affect the surgical outcome of chronic rhinosinusitis ( CRS ) . CRS is classified based on the presence of nasal polyps in western countries . The majority of patients with CRS with nasal polyps ( CRS with NP ) are characterized by predominantly eosinophilic inflammation . However , Asian patients with CRS with NP show characteristics indicative of neutrophilic inflammation . Therefore , are eosinophils or nasal polyps more important for the classification of CRS ? METHODS A prospect i ve cohort study conducted from April 2007 to March 2008 classified patients with CRS based on the presence of nasal polyps and mucosal eosinophilia . The recurrence rate of nasal polyps was compared between the groups . Recurrence rate was analysed as a time-dependent variable by the Kaplan-Meier method . RESULTS Eosinophilic inflammation was found in 59.6 % of patients with CRS with NP . Patients with mucosal eosinophilia had higher polyp recurrence rate than patients without mucosal eosinophilia , whereas patients with nasal polyps did not have higher polyp recurrence rate than patients without nasal polyps . CONCLUSIONS Presence of mucosal eosinophilia is a more important factor than nasal polyps for classifying CRS in terms of the surgical outcome Evidence -based clinical practice guidelines can reduce the delivery of inappropriate care and support the introduction of new knowledge into clinical practice ( 1 - 3 ) . In many cases , guidelines encapsulate the most current knowledge about best practice s. Rigorously developed guidelines can translate complicated research findings into actionable recommendations for clinical care ( 4 ) . Over the past decade , a plethora of guidelines has been created and published by a multitude of organizations at substantial cost . Despite the enormous energies invested in guideline authoring , the quality of individual guidelines varies considerably . In its l and mark report , the Institute of Medicine ( IOM ) defined 8 desirable attributes of clinical practice guidelines : validity , reliability and reproducibility , clinical applicability , clinical flexibility , clarity , documentation , development by a multidisciplinary process , and plans for review ( 5 ) . However , critical information that would attest to validity or would document fulfillment of the other IOM criteria is regularly absent from published guidelines . In an evaluation of 279 guidelines developed by U.S. medical specialty societies , Shaneyfelt and colleagues ( 6 ) found that guidelines published in the peer- review ed medical literature do not adhere to established method ologic st and ards . Likewise , Grilli and colleagues ( 7 ) found that of 431 guidelines produced by specialty societies , 82 % did not apply explicit criteria to grade the scientific evidence that supported their recommendations , 87 % did not report whether a systematic literature search was performed , and 67 % did not describe the type of professionals involved in guideline development . Systematic review s of guidelines for drug therapy ( 8) , management of depression ( 9 ) , and osteoporosis ( 10 ) have confirmed marked variation in quality . Both nonadherence to method ologic st and ards and failure to document development activities contribute to this variation . We convened the Conference on Guideline St and ardization ( COGS ) to define a st and ard for guideline reporting that would promote guideline quality and facilitate implementation . The proposed st and ard provides a checklist of components necessary for evaluation of validity and usability . The checklist is intended to minimize the quality defects that arise from failure to include essential information and to promote development of recommendation statements that are more easily implemented . In contrast to other instruments that have been developed for post hoc evaluation of guideline quality , the COGS checklist is intended to be used prospect ively by developers to improve their product by improving documentation . The COGS panel used a systematic and rigorous process to define content of the proposed st and ard and to achieve consensus . The COGS panel also included a wide variety of perspectives , deliberately bringing together representatives from medical specialty societies , government agencies , and private groups that develop guidelines ; journal editors and the National Guideline Clearinghouse ( NGC ) , which disseminate guidelines ; guideline implementers , including managed care representatives and informaticians ; and academicians . Methods We actively sought people with diverse background s from wide-ranging geographic areas to participate in the meeting . Selection criteria for participants were 1 ) activity in a wide variety of guidelines initiatives , 2 ) recognition as leaders in their field , and 3 ) willingness to collaborate . To maximize interaction , the number of participants in the Conference was limited . We set as a task for the panelists the specification and definition of a set of necessary guideline components that should be considered for reporting in all evidence -based practice guidelines . We defined necessary items as those that establish the validity of the guideline recommendations or facilitate practical application of the recommendations . We noted that many additional items might be considered appropriate components in guidelines , but sought to define a minimal set of essential elements . We assembled a list of c and i date guideline components from the IOM Provisional Instrument for Assessing Clinical Guidelines ( 5 ) , the NGC ( 11 ) , and the Guideline Elements Model ( 12 ) , a hierarchical model of guideline content that was created from a systematic review of published guideline descriptions . These items were supplemented with items highlighted in the literature , for example , structured abstract ( 13 ) and conflict of interest ( 14 ) . We applied a modified Delphi approach to help focus group discussion . This approach has been widely applied for evaluation of expert opinion on appropriateness ( 15 ) and medical necessity ( 16 ) , for policy development ( 17 ) , and for prioritization ( 18 ) . The technique has been described in detail ( 19 ) . In brief , after we secured agreement to participate in the COGS panel , we gave all participants a bibliography of re sources regarding guideline quality and its appraisal , guideline implementation , and the modified Delphi consensus development approach . Panelists were asked to rate their agreement with the statement that [ Item name ] is a necessary component of practice guidelines on a 9-point scale . Rating an item with a 9 indicated strong agreement with the statement that this item was necessary . Rating an item with a 1 indicated strong disagreement with the statement and suggested that the item was absolutely unnecessary in a guideline . A rating of 5 indicated neutrality or indifference . We developed a password-protected Web site that panelists used to complete the first round of ratings online before the meeting . Online rating permitted accurate and efficient data capture and analysis . For each item , the median rating and the disagreement index ( defined as the Interpercentile Range divided by the Interpercentile Range Adjusted for Symmetry ) were calculated ( 19 ) . The disagreement index , which can be calculated for panels of any size , describes the dispersion of ratings more effectively than the mean absolute deviation from the median . Index values greater than 1 indicate disagreement . We displayed summary statistics for each item on a form that was individualized for each panelist . The COGS meeting was held on 26 and 27 April 2002 in New Haven , Connecticut . In a colloquy facilitated by 2 of the authors , each c and i date item was discussed to ensure that all participants agreed on its definition and potential contribution to the COGS checklist and to highlight empirical evidence of its value . When appropriate , additional items were added to the list . The group determined that in the second round of ratings , it would be valuable to rate each item 's necessity on 2 subscales : necessity to establish validity and necessity for practical application . The participants then rated each item on these 2 dimensions . Analysis We tallied the median score and the disagreement index for each item . We retained items with median scores of 7 or higher and disagreement indexes less than 1.0 on either scale as necessary guideline components on the checklist . To interpret necessity , the 9-point scale is divided into 3 ranges : items scoring 1 to 3 are considered unnecessary , items scoring 4 to 6 are neutral , and items scoring 7 to 9 are considered necessary ( 20 ) . In this study , the threshold of 7 was chosen because it represented the lowest rating at which the participants indicated that an item was necessary for inclusion in guidelines . Pilot Review To field test the proposed checklist , we surveyed organizations that were active in guideline development . We identified all organizations that met the NGC Web site criteria for guideline display on 12 July 2002 . From that list , we selected organizations that had developed 10 or more guidelines displayed on the NGC Web site . We excluded 1 ) organizations that participated in development of the COGS checklist [ because of potential bias ] and 2 ) government agencies and organizations based outside the United States ( for logistic reasons ) . A draft COGS checklist and a brief survey were sent to the people identified as being responsible for guideline development at each eligible organization . Results All 23 panelists su bmi tted first- and second-round ballots . During the discussion , participants suggested consideration of 10 new items in the second round of balloting and refined definitions of several items . Thirty-six discrete items were considered necessary to establish guideline validity ; they received ratings of 7 or greater and had disagreement indexes of less than 1 . Twenty-four items were considered necessary for practical application of the guideline , each with a disagreement index less than 1 . Several items were rated necessary on both dimensions . Overall , 44 discrete items were considered necessary . Closely related items were then consoli date d into 18 topics to create the COGS checklist for reporting clinical guidelines ( Table ) . Appendix Tables 1 and 2 present a complete listing of all items rated and their scores . Table . The COGS Checklist for Reporting Clinical Practice Guidelines Appendix Table 1 . Items Ranked Necessary for Guideline Validity , Median Ratings , Distribution of Ratings by Tertiles , and Disagreement Index Appendix Table 2 . Items Ranked Necessary for Guideline Usability , Median Ratings , Distribution of Ratings by Tertiles , and Disagreement Index Twenty-two organizations met eligibility criteria for evaluation of the draft checklist , and all completed the survey ( 100 % response rate ) . Sixteen organizations ( 73 % ) responded that they believed the checklist would be helpful for creating more comprehensive practice guidelines , and an additional 2 organizations ( 9 % ) responded that it might be helpful . Nineteen respondents ( 86 % ) indicated that documenting the proposed items would fit within their organizations ' guideline development methods . Fifteen ( 68 % ) stated that they would use the proposed checklist in guideline OBJECTIVE To examine the effect of nasal antifungal treatment on eosinophil cationic protein ( ECP ) and tryptase levels in sample s of nasal lavage fluid from patients with chronic rhinosinusitis and nasal polyps . DESIGN Prospect i ve double-blind placebo-controlled clinical trial . SETTING Tertiary surgical center . PATIENTS Subjects with severe chronic rhinosinusitis and nasal polyps . Of 120 screened patients , 76 were eligible . Six patients withdrew because of minor adverse events , and 10 dropped out for other reasons . In total , 60 patients completed the study according to the study protocol . INTERVENTIONS Nasal treatment with amphotericin B or saline control for 8 weeks . MAIN OUTCOME MEASURES Nasal lavages were performed before and after treatment . Fungal elements were assessed by culture and with different polymerase chain reaction assays . Levels of ECP and tryptase were determined by fluorescent enzyme immunoassay . RESULTS No correlation between cell activation markers and fungus detection was observed before treatment ( all P>.20 ) . Nasal amphotericin B treatment had no effect on levels of ECP ( P = .17 ) or tryptase ( P = .09 ) in nasal lavage sample s. Moreover , successful fungus eradication , defined as fungus detection before but not after treatment , did not influence nasal ECP or tryptase levels ( all P>.40 ) . CONCLUSION Neither topical amphotericin B therapy nor fungal state before and after treatment had any significant influence on activation markers of nasal inflammatory cells in chronic rhinosinusitis STUDY OBJECTIVE Inhaled colistin is used for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis ( CF ) patients despite reports of chest tightness and bronchospasm . The main objective of the study was to assess whether bronchospasm occurred in pediatric CF patients with or without clinical evidence of airway hyperreactivity . DESIGN AND METHODS A prospect i ve placebo-controlled clinical trial with crossover design was devised using challenge tests with 75 mg colistin in 4 mL saline solution and a placebo solution of the same osmolarity using a breath-enhanced nebulizer for administration . Subjects were recruited as follows : high risk ( HR ) for bronchospasm due to a personal history of recurrent wheezing , a family history of asthma and /or atopy , or bronchial lability , as demonstrated in pulmonary function tests ; or low risk ( LR ) without these characteristics . RESULTS The mean FEV(1 ) ( expressed as the mean [ + /- SD ] fall from baseline ) of the HR group ( n = 12 ) fell 12 + /- 9 % after placebo was administered , and fell 17 + /- 10 % after colistin was administered . For the LR group ( n = 8) , the mean FEV(1 ) fell 9 + /- 4 % following placebo administration and 13 + /- 8 % following colistin administration . There was a greater number of subjects in the HR group compared to the LR group , which had a mean fall in FEV(1 ) of > /= 15 % ( p < 0.01 ) after inhaling colistin . The differences between placebo and colistin therapy in the LR group were not significant . CONCLUSION The results demonstrated that colistin can cause bronchospasm , particularly in those patients with coexisting CF and asthma OBJECTIVES A rational approach in the treatment of chronic rhinosinusitis ( CRS ) is the intranasal application of antiseptic agents , due to the pathogenetic role of bacteria and fungi . N-Chlorotaurine ( NCT ) , a mild endogenous oxidant with broad-spectrum antimicrobial activity , has been tested for the first time in CRS . METHODS This one-arm phase IIa clinical study is the first step in the clinical development of this promising substance for local therapy of CRS . The nasal and paranasal cavities of 12 patients were rinsed with 10 - 20 ml of 1 % aqueous NCT solution , applied via a novel catheter system ( YAMIK ) . Treatment consisted of three lavages per week for 4 weeks . RESULTS NCT caused neither alterations of the mucosa nor burning pain during application . Nevertheless , the insertion of the catheter , the insufflation of the posterior cuff and the overpressure inside the sinuses after infiltration led to moderate pain in some patients . Mucosal swelling decreased in all subjects , nasal breathing could be improved in nine patients and impaired olfaction in seven . Polyps did not disappear within the 1-month period of the study . CONCLUSIONS The good tolerability and possible beneficial effects of NCT encourage its further investigation in CRS . Despite some limitations the YAMIK catheter proved to be a convenient and safe device for rinsing the nasal and paranasal sinuses Objective —Although chronic rhinosinusitis ( CRS ) is one of the most frequently reported chronic diseases its etiology is not well understood . Recently , fungi have been proposed to influence the chronicity of rhinosinusitis . If fungi do play an important role then topical antifungal treatment may improve the inflammatory process of CRS . Therefore , in this study we measured inflammatory cytokine levels in nasal polyps after intranasal antifungal irrigation . Material and Methods —Nasal polyps were collected before and 4 weeks after treatment with 100 mg/l topical amphotericin B ( n=16 ) , 50 mg/l topical amphotericin B ( n=14 ) or normal saline ( n=11 ) . The cytokine — IL-5 , IL-8 , interferon-γ , RANTES — protein content of polyp homogenates were determined by means of ELISA . Results —Nasal polyps were found to contain large amounts of cytokines ( IL-5 , IL-8 and RANTES ) compared with normal inferior turbinates . After 4 weeks of treatment with topical agents , IL-5 levels tended to decrease in comparison with those of the other cytokines , but this difference was not statistically significant . Conclusions —Topical amphotericin B treatment and nasal saline irrigation both influence the expression of nasal polyp cytokines . Topical nasal irrigation may influence the inflammatory process of CRS OBJECTIVES To evaluate antifungal terbinafine in patients with chronic rhinosinusitis . STUDY DESIGN R and omized , double-blind , placebo-controlled multicenter pilot study . METHODS Fifty-three adults with chronic rhinosinusitis received terbinafine 625 mg/day ( n = 25 ) or placebo ( n = 28 ) once daily for 6 weeks . Sinus secretions were collected at screening for mycology . Computed tomography was grade d for extent of opacification at baseline and at week 6 using a modification of the Lund-Mackay scoring system . Patients recorded rhinosinusitis symptoms on a visual analogue scale and completed the Rhinosinusitis Disability Index . RESULTS Positive fungal cultures were found in 41 of 53 patients ( 17 terbinafine , 24 placebo ) . ( Two subjects from the Terbinafine group and one subject from the control group had no week 6 data ) . The mean opacification scores pre- and posttreatment for the entire study group improved from 24.2 to 22.5 in placebo ( n = 26 ) and from 26.3 to 24.2 in terbinafine group ( n = 23 ) . The least squares means for percent change from baseline ( SE ) were -6.0 ( 8.7 ) for placebo compared with -7.2 ( 8.1 ) for terbinafine ; 95 % confidence interval for treatment difference ( -18.9 , 21.1 ) ; P = .91 . Results were similar when only patients with positive fungal cultures were evaluated in the efficacy analysis . Investigator therapeutic evaluations and sinus symptom scores were not significantly different between the two groups at baseline or at treatment completion . CONCLUSION Treatment with terbinafine failed to improve the symptoms or radiographic appearance of chronic rhinosinusitis even when nasal irrigation sample s were positive for fungus on culture . One consideration is that the fungi isolated were not a major pathologic factor in this cohort . It is also possible that , even at high dose , terbinafine may not have maintained therapeutic levels in the nasal secretions BACKGROUND Chronic rhinosinusitis ( CRS ) is one of the most common chronic diseases . Its etiology is unknown , and there is a paucity of effective medical treatments . OBJECTIVE We tested the hypothesis that intranasal antifungal treatment improves the objective computed tomography ( CT ) findings ( inflammatory mucosal thickening ) , nasal endoscopy stages , and symptoms of CRS . METHODS A r and omized , placebo-controlled , double-blind , single-center trial used amphotericin B to treat 30 r and omly selected patients with CRS . Patients were instructed to instill 20 mL amphotericin B ( 250 mug/mL ) or placebo to each nostril twice daily for 6 months . The primary outcome was a quantitative reduction in inflammatory mucosal thickening on CT scans of a st and ardized coronal cut . Secondary outcome measures were endoscopic scores , patient symptom scores , and levels of intranasal inflammatory mediators . RESULTS Twenty-four patients completed the 6 months of treatment . Patients receiving amphotericin B achieved a relative reduction in the percentage of mucosal thickening on CT scans ( n = 10 ; -8.8 % ) compared with placebo ( n = 14 ; + 2.5 % ; P = .030 ) . Likewise , the changes in the endoscopic scores improved in the amphotericin B group compared with placebo ( P = .038 ) . Between-group comparisons of the changes in the intranasal mucus levels of eosinophil-derived neurotoxin showed a reduction in the amphotericin B group and an increase in the placebo group ( P = .046 ) ; levels of IL-5 showed similar tendencies ( P = .082 ) . CONCLUSION Intranasal amphotericin B reduced inflammatory mucosal thickening on both CT scan and nasal endoscopy and decreased the levels of intranasal markers for eosinophilic inflammation in patients with CRS Background Fungus-driven inflammation is proposed to play an important role in the pathogenesis of chronic rhinosinusitis ( CRS ) . Previous studies tested the efficacy of intranasal antifungal agents for patients with nasal polyps . The purpose of this study was to evaluate the efficacy of intranasal amphotericin B ( AMB ) in patients who have CRS without nasal polyps ( CRSsNP ) . Methods Patients diagnosed with CRSsNP were enrolled in this study . They were assigned r and omly to receive irrigation with AMB solution ( 20 mg of AMB in 500 mL of normal saline ) or placebo ( yellowish dye in 500 mL of normal saline ) for 4 weeks . The outcome measures included the Chinese version of the Rhinosinusitis Outcome Measure 31 ( CRSOM-31 ) , nasal endoscopy , and bacterial and fungal cultures . Results Seventy patients were enrolled and 64 patients completed this study . There was significant improvement in the AMB group ( n = 32 ) both in endoscopic ( p = 0.013 ) and CRSOM-31 scores ( p < 0.0001 ) . The placebo group ( n = 32 ) showed significant improvement in CRSOM-31 scores ( p < 0.0001 ) . CRSOM-31 scores were significantly lower in the AMB group than in the placebo group after 2-week treatment ( p = 0.018 ) and remained lower after 4-week treatment , although the difference was not significant ( p = 0.091 ) . There were no significant differences in endoscopic scores and bacterial or fungal culture rates between two groups after treatment . Conclusion Our results showed that AMB irrigation improved symptoms and endoscopic scores but did not show superiority to saline irrigation alone in patients who have CRSsNP OBJECTIVES To correlate objective and subjective clinical parameters with molecular , cellular , and histologic markers and to acknowledge the importance of these basic science parameters in a severity classification system for chronic rhinosinusitis ( CRS ) . STUDY DESIGN Retrospective analysis of prospect ively collected data of consecutive patients undergoing endoscopic sinus surgery for CRS in an academic institution . METHODS The preoperative computed tomography ( CT ) scans of all patients with CRS scheduled for surgery were grade d according to Lund and Mackay . The patients completed a Sino-Nasal Outcome Test (SNOT)-20 question naire and had a preoperative nasal endoscopy performed , which was grade d by assigning an endoscopy score according to Lanza and Kennedy . Subjects had a medical question naire regarding presence of aspirin sensitivity , allergic rhinitis , asthma , and medication usage . Subjects also underwent pulmonary function testing and had skin tests for allergies . At the time of surgery , blood was drawn to determine the level of peripheral eosinophilia and the degree of polymorphisms of the leukotriene C4 synthase gene . Sinus mucosal and polyp tissue was examined pathologically for the number of eosinophils per high-powered filed ( HPF ) and was stained for EG2 to determine the portion of activated eosinophils . Leukotriene C4 levels ( pg/g of tissue ) were determined using a sensitive competitive enzyme immunoassay . Endoscopy and SNOT-20 scores were reevaluated 1 year after surgery . Data were analyzed for disease-severity correlation to recommend a severity classification system for CRS that incorporates the contribution of clinical , molecular , cellular , and histologic parameters . RESULTS The presence of polyps result ed in higher preoperative CT scores and higher preoperative and postoperative symptom scores . Average preoperative CT scores were significantly higher in asthmatics and allergy patients and correlated with endoscopy scores . Patients with more than five eosinophils/HPF of sinus tissue had higher frequency of polyps and asthma and higher CT and endoscopy scores than patients without sinus tissue eosinophilia ( less than or equal to 5 cells/HPF sinus tissue ) . The subgroup of patients with eosinophilic nasal polyps ( eosinophilic hyperplastic rhinosinusitis ) had more severe disease by CT and endoscopy than the subgroup of patients with nasal polyps ( hyperplastic rhinosinusitis ) but without eosinophilia . Similarly , patients without polyps but with tissue eosinophilia had more severe disease than patients without polyps and without eosinophilia . Leukotriene C4 levels were elevated in all patient groups . Symptom scores did not correlate with any of the parameters . CONCLUSION We suggest the following severity classification system for CRS : 1 ) eosinophilic chronic hyperplastic rhinosinusitis ( ECHRS ) : patients with polyps and sinus tissue eosinophilia ; 2 ) noneosinophilic chronic hyperplastic rhinosinusitis ( NECHRS ) : patients with polyps but without sinus tissue eosinophilia ; 3 ) eosinophilic chronic rhinosinusitis ( ECRS ) : patients without polyps but with sinus tissue eosinophilia ; 4 ) noneosinophilic chronic rhinosinusitis ( NECRS ) : patients without polyps and without sinus tissue eosinophilia 50 patients with chronic mucopurulent rhinosinusitis were r and omly allocated to treatment with nasal sprays of dexamethasone , tramazoline , and neomycin , dexamethasone and tramazoline with no antibiotic , or matched placebo ( propellant alone ) four times daily to both nostrils for 2 weeks . The patients were assessed in a double-blind manner for symptomatic response and improvement in nasal mucociliary clearance , nasal airway resistance , sinus radiographs , and intranasal bacteriology and appearance . Both active preparations ( with antibiotic 14 of 20 patients responded ; without antibiotic 12 of 20 patients responded ) were more effective than the placebo ( 2 of 10 patients responded ) . There was no significant difference in response between the active preparations with and without antibiotic . Thus , in treatment of chronic mucopurulent rhinosinusitis , reduction of the inflammatory response and decongestion make topical antibiotic unnecessary , probably by allowing host clearance mechanisms to recover OBJECTIVE : Assess whether the presence of mucosal eosinophilia correlates with surgical outcomes in patients with chronic rhinosinusitis . STUDY DESIGN : Prospect i ve cohort . SETTING : Tertiary medical center . SUBJECTS AND METHODS : Adult patients with chronic rhinosinusitis were prospect ively enrolled , and demographic data and medical comorbidities were recorded . Preoperative quality of life ( QOL ) was measured by the Chronic Sinusitis Survey ( CSS ) , Rhinosinusitis Disability Index ( RSDI ) , and Short Form-36 General Health Survey ( SF-36 ) . Sinus mucosal specimens were collected at the time of surgery and the degree of eosinophilia quantified . Postoperative QOL was measured , and differences in QOL improvement were compared between those with and without eosinophilia . RESULTS : A total of 102 patients had both histopathological and QOL outcome data available for review . Follow-up averaged 16.5 months . Patients with eosinophilia showed significantly less improvement in the RSDI total ( 17.9 vs 25.0 ; P = 0.044 ) , RSDI functional ( 5.7 vs 8.8 ; general health subscale ; P = 0.018 ) , CSS medication ( 3.6 vs 17.3 ; P = 0.013 ) , SF-36 general health ( 0.6 vs 9.6 ; P = 0.008 ) , SF-36 physical role ( 16.1 vs 34.7 ; P = 0.036 ) , and SF-36 vitality ( 11.9 vs 21.2 ; P = 0.034 ) scales than those without eosinophilia . The greatest improvement in QOL was seen in patients without eosinophilia or polyps , with the least improvement seen in those with eosinophilia but without polyps . CONCLUSION : The presence of mucosal eosinophilia at the time of surgery consistently predicted less improvement in both disease-specific and general QOL compared with patients without eosinophilia . The impact of eosinophilia on outcomes was greatest for patients without nasal polyposis , a group that demonstrated the least improvement in QOL measures BACKGROUND Chronic rhinosinusitis ( CRS ) is the most common chronic disease that is frequently refractory to treatment . OBJECTIVE We sought to establish the safety and demonstrate the clinical efficacy of intranasal antifungal drug therapy in patients with CRS in a pilot trial . METHODS A prospect i ve open-label trial used amphotericin B as a medical treatment in 51 r and omly selected patients with CRS . The antifungal agent was applied intranasally as 20 mL of a 100 microg/mL solution twice daily . The outcome was measured by using their symptoms and by using an endoscopic scoring system in all patients . In addition , pretreatment and posttreatment coronal computed tomographic scans of the nose and sinuses were available for evaluation in 13 patients . RESULTS By using amphotericin B , improvement of sinusitis symptoms was observed in 38 ( 75 % ) of 51 patients . Endoscopically , 18 ( 35 % ) of 51 patients became disease free , and an additional 20 ( 39 % ) of 51 had improvement of at least one stage ( P < .001 ) . No effect was seen in 13 ( 25 % ) of 51 patients . The available computed tomographic scans before and after treatment demonstrated a significant reduction in the inflammatory mucosa thickening that had occluded the paranasal sinuses ( P < .0001 in maxillary sinus ) . CONCLUSION This open-label pilot trial demonstrates that direct mucoadministration of an antifungal drug appears to be both safe and effective in the treatment of patients with CRS . Therefore controlled and blinded trials are indicated to clarify the novel role of intranasal antifungal drugs in the treatment of CRS In a phase IV , open-label study , 25 patients with clinical ly stable chronic sinusitis and persistent maxillary sinus inflammation were treated for 14 days with clarithromycin 500 mg twice daily . Biopsy specimens of the maxillary sinus mucosa were obtained pretreatment and evaluated for macrophages ( CD68 ) , eosinophils ( MBP ) , elastase , interleukin-6 ( IL-6 ) , IL-8 , tumor necrosis factoralpha ( TNF-α ) , and activity of eosinophils ( EG2 ) , as well as edema score . Clinical signs and symptoms were assessed pretreatment , at the end of treatment , and 1 and 2 weeks later . Statistically significant reductions ( P≤.05 ) from pretreatment were observed for all markers of sinus mucosal inflammation , including CD68 , EG2 , elastase , IL-6 , IL-8 , TNF-α , and edema score , with a trend to decreased total eosinophil count . Improvement was observed for all clinical signs and symptoms of chronic sinusitis — sinus pain , sinus headache , nasal congestion , nasal discharge , and mucopurulent discharge — up to 14 days after the end of treatment . Cultures to evaluate persistent infection withChlamydia pneumoniae showed negative results . Significant reductions in various markers of sinus mucosal inflammation support the role of clarithromycin in modulating immunologic responses . Improvement of clinical signs and symptoms in patients with chronic inflammatory sinusitis not meeting criteria for known or presumed bacterial infection was also noted up to 2 weeks after completion of a 14-day course of clarithromycin OBJECTIVE : To study the efficacy of nebulized topical saline-tobramycin solution in patients with chronic rhinosinusitis refractory to medical and surgical therapy . STUDY DESIGN AND SETTING : Twenty patients in whom endoscopic sinus surgery failed to relieve symptoms entered a r and omized , double-blind trial of tobramycin-saline solution or saline-only solution administered thrice daily to the nasal passages by means of a large-particle nebulizer apparatus for 4 weeks , followed by a 4-week observation period . Outcome measures of symptoms , quality of life , and endoscopic aspect of sinus mucosa were assessed . RESULTS : Both treatments were well tolerated and produced equivalent improvement in symptoms , quality of life , and mucosal aspect . Treatment with the tobramycin-saline solution gave more rapid improvement of pain , but led to the development of nasal congestion . CONCLUSION : Therapy with a 4-week course of large-particle nebulized aerosol therapy improves symptomatology and objective parameters of rhinosinusitis in patients refractory to surgical and medical therapies . Addition of tobramycin appears of minimal benefit . The mechanism of this effect is unexplained . SIGNIFICANCE : Large-particle nebulized aerosol therapy may offer a safe and effective management alternative for patients with refractory rhinosinusitis Summary A multicentric study was conducted to evaluate the clinical efficacy and tolerance of ofloxacin in the treatment of chronic sinusitis and chronic otitis ( CSOM ) in out patients . Two hundred milligrams of ofloxacin was administered twice a day orally for 12 days in 198 patients with chronic sinusitis and 215 patients with CSOM . Cultures for bacteriology were carried out before treatment . The spectrum of pathogens sensitive to ofloxacin includedStaphylococcus aureus , Pseudomonas aeruginosa , Proteus mirabilis and Haemophilus influenzae . Higher concentrations of ofloxacin were obtained at sites of infection than in serum . Favorable results were achieved clinical ly in 93.7 % of chronic sinusitis cases and 93.9 % of CSOM cases . Adverse effects occurred in only 4.1 % of cases . These results support the use of ofloxacin as the drug of first choice in the treatment of chronic sinusitis and CSOM in adult out patients OBJECTIVE : In 17 patients with chronic sinusitis persistent after sinus surgery , long-term , low-dose erythromycin therapy was tested . The aim of the investigation was to study the clinical outcome and effects on nasal nitric oxide ( NO ) , ciliary beat frequency ( CBF ) , and mucociliary transport ( saccharine transit time ) . STUDY DESIGN AND SETTING : We conducted a prospect i ve open study at a tertiary teaching hospital . Symptoms were assessed using visual analog scales . NO was measured using a chemiluminescence analyzer , and mucociliary transport was measured with the saccharine crystal technique . CBF was measured in nasal brush sample s using a phase contrast microscope . All patients were treated with erythromycin succinate 250 mg 2x daily or clarithromycin 250 mg 1x daily and were assessed after 3 months . In cases where there was no response , treatment was ab and oned . The remaining patients ( responders ) were reassessed after 12 months of treatment . RESULTS : Of 17 patients , 12 responded to treatment . The 12-month follow-up showed an improvement in saccharine transit time ( P < 0.05 ) but no significant change in CBF . There was a trend toward an increase in NO ( P = 0.12 ) . Endoscopic nasal examination scoring improved significantly ( P < 0.01 ) . In the visual analog scale scoring , the most pronounced improvements were seen in nasal congestion , sticky secretion , and runny nose at 3 and 12 months ( P < 0.01 ) . Improvements were also seen in headache ( P < 0.05 ) . CONCLUSION : The present study suggests that long-term , low-dose treatment with erythromycin is effective in persistent chronic sinusitis that does not respond to sinus surgery or systemic steroid/antibiotic treatment . SIGNIFICANCE : Long-term , low-dose erythromycin therapy seems to be a promising alternative when more conventional therapy fails . However , placebo-controlled studies are needed to vali date the potential of this treatment In this study efficacy and tolerability of flurithromycin ethylsuccinate ( FE ) were evaluated in ear , nose and throat infections . One hundred and three patients were treated with FE tablets 375 mg 12-hourly for a mean duration of treatment of 8.2 days and they were divided into groups according to the pathology : pharyngitis/tonsillitis ( chronic 7 , acute 38 ) , rhinosinusitis ( chronic 7 , acute 12 ) , otitis ( chronic 6 , acute 32 ) and sialadenitis ( acute 1 ) . Patients evaluable for clinical efficacy were 101 , among them a complete recovery was registered in 88.2 % , an improvement in 9.9 % and a treatment failure in 1.9 % . Bacteriological evaluation was possible in 95 patients , showing the eradication of the pathogen in 94.7 % . Tolerability was judged to be excellent in 81.6 % , good in 15.5 % and discrete in 2.9 % . These results demonstrate that FE is safe and effective in the treatment of infections established on acute or chronic inflammatory states Nasal polyps and chronic rhinosinusitis are the products of an inflammatory process . Recently , fungal involvement has been thought to stimulate the development of polyps , and administration of antifungal agents was therefore considered a potential treatment . Several studies have been published indicating amphotericin B as an effective treatment for nasal polyps and chronic rhinosinusitis . The aim of our investigation was to evaluate the efficacy of intranasal applied amphotericin B on the growth of nasal polyps in a three-month , prospect i ve , open trial . Our results show that nasal amphotericin B spray is not effective for nasal polyps and may even cause deterioration Chronic rhinosinusitis ( CRS ) affects 1–4 % of the adult population . The etiology of this multifactorial , chronic disease , which leads to a significant impairment of the quality of life , often accompanied by nasal polyposis , is not fully understood . In the past decade , it was presumed that the disease , which causes characteristic eosinophilic infiltration of the nasal mucosa , is triggered by an enhanced ( but not classical allergic IgE-type ) immune response against fungal organisms in the nasal mucus . If this supposition is correct , then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients , and might even reduce the number of recurrent cases . To check on this assumption , we conducted a prospect i ve r and omized placebo-controlled trial involving 33 patients , 30 of whom remained in the study throughout . Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006 ; group A ( 14 r and omly selected patients ) were treated with a nasal spray containing 5 mg/ml amphotericin B , while the placebo group B ( 16 r and omly selected patients ) received a nasal spray lacking amphotericin B. We evaluated our results with the aid of a modified Lund – Mackay CT score , the SNAQ-11 test ( which assesses changes in the symptoms ) , a quality of life test and endoscopy . The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and 1 year postoperatively . The CT scores of the group A patients 1 year after the operation exhibited wide scattering , without signs of recovery . The CT scores of the group B patients indicated a slight improvement , though this did not prove significant relative to group A. Both the SNAQ-11 test and the quality of life test revealed a significant improvement in each group , but the degrees of change in these tests did not differ significantly between the two groups of patients . The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation . These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in either CT score , clinical symptoms , or quality of life . The more favorable clinical aspects observed in the amphotericin B-treated group during the endoscopic follow-up did not correspond to an improvement in the symptoms . In connection with the conclusions drawn from this study , the authors discuss the controversial data available on the fungal etiology of CRS . They critically analyze the contradictory observations and conclusions of seven recent clinical studies The authors describe a prospect i ve pilot study design ed to investigate the use of topical nasal antifungal spray in addition to systemic steroids and itraconazole in the treatment of allergic fungal sinusitis . Sixteen patients with a history of allergic fungal sinusitis were given fluconazole nasal spray and followed for 3 months . Stabilization or improvement of disease without significant side effects was observed in 12 of the 16 patients who were treated with this protocol . These results indicate that topical fluconazole application may help patients with allergic fungal sinusitis ; however , a larger multicenter study with longer patient follow-up is required to vali date these initial findings A total of 251 adults with chronic sinusitis were enrolled into this prospect i ve multicentre , double-blind , double-placebo comparison of ciprofloxacin ( 500 mg twice daily ) with amoxycillin/clavulanic acid ( 500 mg three times daily ) . The diagnosis of chronic sinusitis ( persistence of clinical symptoms for at least 3 months ) was confirmed by computerized tomography scan and /or sinusoscopy prior to therapy . Patients at inclusion had purulent or muco-purulent rhinorrhoea . Staphylococcus aureus ( n = 45 ) , Haemophilus influenzae ( n = 35 ) , Streptococcus pneumoniae ( n = 32 ) and enterobacteriaceae ( n = 31 ) were isolated from pre-treatment aspirates of the middle meatus . Treatment lasted 9 days , at the end of which nasal discharge disappeared in 71/118 ( 60.2 % ) patients of the ciprofloxacin group and 69/123 ( 56.1 % ) of those in the amoxycillin/clavulanic acid group . The clinical cure and bacteriological eradication rates were 58.6 % versus 51.2 % and 88.9 % versus 90.5 % for ciprofloxacin and amoxycillin/clavulanic acid , respectively . These differences were not significant , however , amongst patients who had a positive initial culture and who were evaluated 40 days after treatment . Ciprofloxacin recipients had a significantly higher cure rate than those treated with amoxycillin/clavulanic acid ( 83.3 % vs. 67.6 % , p = 0.043 ) . Clinical tolerance was significantly better with ciprofloxacin ( p = 0.012 ) , essentially due to a large number of gastro-intestinal related side-effects in the amoxycillin/clavulanic acid group ( n = 35 ) . Ciprofloxacin proved to be at least as effective as amoxycillin/clavulanic acid . The superior safety profile , a twice daily dosage regimen , suggests that ciprofloxacin may be a useful therapeutic alternative for the treatment of chronic sinusitis To cite this article : Videler WJ , Badia L , Harvey RJ , Gane S , Georgalas C , van der Meulen FW , Menger DJ , Lehtonen MT , Toppila‐Salmi SK , Vento SI , Hytönen M , Hellings PW , Kalogjera L , Lund VJ , Scadding G , Mullol J , Fokkens WJ . Lack of Efficacy of long‐term , low‐dose azithromycin in chronic rhinosinusitis : a r and omized controlled trial . Allergy 2011 ; 66 : 1457–1468 |
1,769 | 27,662,041 | There was no difference in the risk of all-cause mortality and adverse cardiovascular ( CV ) events between Insulin and non-insulin GLTs .
Insulin was associated with superior reduction in HbA1c ; least reduction in weight and higher risk of hypoglycaemia .
Both showed similar proportion of patients achieving HbA1c target .
Non-insulin GLTs were associated with a higher risk in reported adverse drug events | OBJECTIVES To compare the cardiovascular and metabolic outcomes of Insulin versus non-insulin glucose lowering therapy ( GLT ) . | A total of 5082 men and women in the Framingham Heart Study population who were free of any glucose abnormality and aged 33 to 67 years were followed prospect ively over 14 years for the occurrence of glucose intolerance . The diagnosis of glucose intolerance was defined as developing documented hyperglycemia or being placed on justified treatment by a physician . The 14-year incidence was 6.7 % in men and 5.5 % in women . Multivariate analysis was used and future glucose intolerance in men and women was highly associated with casual blood glucose , Metropolitan Relative Weight and very low density lipoproteins at the baseline exam . Other factors showed only sex-specific or univariate associations . Obesity and lipoprotein abnormalities were shown to be independent markers in the prediction of future glucose intolerance OBJECTIVE Traditional blood glucose – lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients . Pre clinical studies with exenatide have suggested sustained improvements in β-cell function . We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp – derived measures of β-cell function , glycemic control , and body weight . RESEARCH DESIGN AND METHODS Sixty-nine metformin-treated patients with type 2 diabetes were r and omly assigned to exenatide ( n = 36 ) or insulin glargine ( n = 33 ) . β-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0 , at week 52 , and after a 4-week off-drug period . Additional end points included effects on glycemic control , body weight , and safety . RESULTS Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold ( 95 % CI 2.09–2.90 , P < 0.0001 ) greater after a 52-week exenatide treatment compared with insulin glargine treatment . Both exenatide and insulin glargine reduced A1C similarly : −0.8 ± 0.1 and −0.7 ± 0.2 % , respectively ( P = 0.55 ) . Exenatide reduced body weight compared with insulin glargine ( difference −4.6 kg , P < 0.0001 ) . β-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period . A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy . CONCLUSIONS Exenatide significantly improves β-cell function during 1 year of treatment compared with titrated insulin glargine . After cessation of both exenatide and insulin glargine therapy , β-cell function and glycemic control returned to pretreatment values , suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy OBJECTIVE Intensive glucose-lowering therapy ( INT ) did not reduce macrovascular events in the recent r and omized trials , possibly because it did not improve or worsen other traditional or novel cardiovascular risk factors . RESEARCH DESIGN AND METHODS St and ard plasma lipids , cholesterol content of lipoprotein subfractions , and plasma inflammatory and prothrombotic markers were determined in a subgroup of the Veterans Affairs Diabetes Trial ( VADT ) participants ( n = 266 ) at baseline and after 9 months of INT or st and ard therapy . RESULTS INT lowered glycated hemoglobin ( by a median of 2 % vs. a median of 0.7 % by st and ard treatment ; P < 0.0001 ) ; increased BMI ( 4 vs. 1 % ; P < 0.001 ) , total HDL ( 9 vs. 4 % ; P < 0.05 ) , HDL2 ( 14 vs. 0 % ; P = 0.009 ) , LDL2 ( 36 vs. 1 % ; P < 0.0001 ) , and plasma adiponectin ( 130 vs. 80 % ; P < 0.01 ) ; and reduced triglycerides ( −13 vs. −4 % ; P = 0.02 ) and small , dense LDL4 ( −39 vs. −13 % ; P < 0.001 ) , but had no effect on levels of plasma apolipoproteins B-100 and B-48 , C-reactive protein , interleukin-6 , lipoprotein-associated phospholipase A2 , myeloperoxidase , fibrinogen , and plasminogen activator inhibitor 1 . Incident macrovascular events were associated with baseline interleukin-6 ( hazard ratio per each quartile increase 1.33 [ 95 % CI 1.06–1.66 ] ) , total LDL ( 1.25 [ 1.01–1.55 ] ) , apolipoprotein B-100 ( 1.29 [ 1.01–1.65 ] ) , and fibrinogen ( 1.26 [ 1.01–1.57 ] ) but not changes in any cardiovascular risk factors at 9 months . CONCLUSIONS INT was associated with improved adiponectin , lipid levels , and a favorable shift in LDL and HDL subfractions after 9 months . These data suggest that the failure of INT to lower cardiovascular outcomes occurred despite generally favorable changes in st and ard and novel risk factors early in the study Abstract Background : An increase in body weight is a commonly perceived effect of insulin therapy for type 2 diabetes mellitus , and this may serve as a barrier to insulin initiation and usage . Objective : To investigate the baseline clinical and demographic factors associated with weight gain during insulin glargine therapy , and the implication s of weight change on clinical outcomes . Methods : This was a retrospective analysis of patient-level data from phase 3 or 4 r and omized controlled , treat-to-target ( fasting plasma glucose [ FPG ] ≤ 100 mg/dL ) trials evaluating basal insulin glargine for ≥ 24 weeks . The Pearson correlation coefficient and Cochran-Armitage trend statistic were used to calculate the existence of a trend between absolute and relative weight change , and relative glycated hemoglobin ( HbA1c ) change from baseline ; likelihood of achieving target HbA1c < 7.0 % ; change from baseline FPG ; insulin dose requirements ; incidence of hypoglycemia ; and adverse events . Results : Eleven studies were included , encompassing a total of 2140 patients . Patients starting insulin glargine treatment gained a mean ± st and ard deviation 1.8 ± 3.7 kg ( 4.0 ± 8.2 lb ) . Most patients had limited weight change ( ± 2.5 kg or 5.5 lb ) . Younger age , higher baseline HbA1c , and higher baseline FPG were predictive of greater weight gain ( P < 0.0001 ) . Those who gained more weight experienced the largest decrease from baseline in HbA1c and FPG . More weight gain was associated with higher insulin dose requirements , an increased risk of experiencing either symptomatic or glucose-confirmed ( < 70 mg/dL ) hypoglycemia , and more adverse events . Older patients ( > 65 years ) were less likely to gain weight or to experience glucose-confirmed hypoglycemia , but more likely to experience severe hypoglycemia . Conclusions : In this retrospective analysis of patient-level data , most patients had a stable weight ( defined as ± 2.5 kg ) after 24 weeks of insulin glargine , and weight gain varied with patient demographics . Therefore , insulin glargine can be used in these patient groups with type 2 diabetes without expectation of significant weight gain Background Both insulin and thiazolidinediones ( TZDs ) are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention . The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure . The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight , haemoglobin and natriuretic peptides . Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were r and omised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks . Echocardiographic data and blood sample s were collected from the two groups before the start of the treatment and after 26 weeks . Left ventricular end-diastolic and left atrial end-systolic volumes were quantified , weight measured and blood sample s analyzed . Results After 26 weeks of treatment , the changes in HbA1c , weight and haemoglobin were similar between the two groups . HDL increased significantly in the pioglitazone group . While there was an increase in natriuretic peptides in the pioglitazone group ( NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0 , p = 0.046 ) , the difference between the treatment groups was not significant . Left ventricular end-diastolic volume increased by 11 % and left atrial end-systolic volume by 17 % in the pioglitazone group ( Both , p < 0.05 , between treatment groups ) . There was a borderline significant increase in ejection fraction in the pioglitazone group . Conclusion This r and omised pilot- study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size . These changes were not observed with insulin glargine , which also is known to induce fluid retention . Larger r and omised trials are warranted to confirm these findings AIM We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus ( T2DM ) treated with liraglutide versus comparator diabetes therapies . METHODS Twenty-six-week data from seven phase 3 , r and omized trials in the liraglutide T2DM development programme were analysed by trial and treatment group : liraglutide ( 1.2 and 1.8 mg ) , active comparator and placebo . Outcome measures included proportions of subjects in various weight change categories and their percentage weight change from baseline ; impact of body mass index ( BMI ) and gastrointestinal ( GI ) adverse events ( AEs ) on weight change and correlation of weight change with change in glycosylated haemoglobin ( HbA1c ) . RESULTS A number of subjects experienced > 5 % weight loss during the trials ( 24.4 % liraglutide 1.8 mg and 17.7 % liraglutide 1.2 mg ; 17.7 % exenatide , 10.0 % sitagliptin , 3.6 - 7.0 % sulphonylurea , 2.6 % thiazolidinedione and 2.6 % glargine ; 9.9 % placebo ) . More weight loss was seen with liraglutide 1.2 and 1.8 mg than with active comparators except exenatide . Across trials , higher initial BMI was associated with slightly greater weight loss with liraglutide . Mean weight loss increased slightly the longer GI AEs persisted . Although HbA1c reduction was slightly larger in higher weight loss categories across treatments ( including placebo ) , sample sizes were small and no clear correlation could be determined . Liraglutide-treated subjects experienced additional HbA1c reduction beyond that which appeared weight induced ; thus , not all HbA1c-lowering effect appears weight mediated . CONCLUSIONS The majority of liraglutide-treated T2DM subjects experienced weight loss in this analysis . Weight loss was greater and occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than in active comparator-treated subjects OBJECTIVE Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient . However , this complex regimen is associated with weight gain and hypoglycemia . This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration . RESEARCH DESIGN AND METHODS In this 30-week , open-label , multicenter , r and omized , noninferiority trial with 12 weeks prior insulin optimization , 627 patients with insufficient postoptimization glycated hemoglobin A1c ( HbA1c ) were r and omized to exenatide ( 10–20 µg/day ) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6–6.0 mmol/L , both added to insulin glargine ( mean 61 units/day at r and omization ) and metformin ( mean 2,000 mg/day ) . RESULTS R and omization HbA1c and fasting glucose ( FG ) were 8.3 % ( 67 mmol/mol ) and 7.1 mmol/L for exenatide and 8.2 % ( 66 mmol/mol ) and 7.1 mmol/L for lispro . At 30 weeks postr and omization , mean HbA1c changes were noninferior for exenatide compared with lispro ( –1.13 and –1.10 % , respectively ) ; treatment differences were –0.04 ( 95 % CI –0.18 , 0.11 ) in per- protocol ( n = 510 ) and –0.03 ( 95 % CI –0.16 , 0.11 ) in intent-to-treat ( n = 627 ) population s. FG was lower with exenatide than lispro ( 6.5 vs. 7.2 mmol/L ; P = 0.002 ) . Weight decreased with exenatide and increased with lispro ( −2.5 vs. + 2.1 kg ; P < 0.001 ) . More patients reported treatment satisfaction and better quality of life with exenatide than lispro , although a larger proportion of patients with exenatide experienced treatment-emergent adverse events . Exenatide result ed in fewer nonnocturnal hypoglycemic episodes but more gastrointestinal adverse events than lispro . CONCLUSIONS Adding exenatide to titrated glargine with metformin result ed in similar glycemic control as adding lispro and was well tolerated . These findings support exenatide as a noninsulin addition for patients failing basal insulin BACKGROUND Evidence supporting the addition of specific insulin regimens to oral therapy in patients with type 2 diabetes mellitus is limited . METHODS In this 3-year open-label , multicenter trial , we evaluated 708 patients who had suboptimal glycated hemoglobin levels while taking metformin and sulfonylurea therapy . Patients were r and omly assigned to receive biphasic insulin aspart twice daily , pr and ial insulin aspart three times daily , or basal insulin detemir once daily ( twice if required ) . Sulfonylurea therapy was replaced by a second type of insulin if hyperglycemia became unacceptable during the first year of the study or subsequently if glycated hemoglobin levels were more than 6.5 % . Outcome measures were glycated hemoglobin levels , the proportion of patients with a glycated hemoglobin level of 6.5 % or less , the rate of hypoglycemia , and weight gain . RESULTS Median glycated hemoglobin levels were similar for patients receiving biphasic ( 7.1 % ) , pr and ial ( 6.8 % ) , and basal ( 6.9 % ) insulin-based regimens ( P=0.28 ) . However , fewer patients had a level of 6.5 % or less in the biphasic group ( 31.9 % ) than in the pr and ial group ( 44.7 % , P=0.006 ) or in the basal group ( 43.2 % , P=0.03 ) , with 67.7 % , 73.6 % , and 81.6 % , respectively , taking a second type of insulin ( P=0.002 ) . [ corrected ] Median rates of hypoglycemia per patient per year were lowest in the basal group ( 1.7 ) , higher in the biphasic group ( 3.0 ) , and highest in the pr and ial group ( 5.7 ) ( P<0.001 for the overall comparison ) . The mean weight gain was higher in the pr and ial group than in either the biphasic group or the basal group . Other adverse event rates were similar in the three groups . CONCLUSIONS Patients who added a basal or pr and ial insulin-based regimen to oral therapy had better glycated hemoglobin control than patients who added a biphasic insulin-based regimen . Fewer hypoglycemic episodes and less weight gain occurred in patients adding basal insulin . ( Current Controlled Trials number , IS RCT N51125379 . AIMS The study evaluated the associations between glycometabolic parameters at admission and during hospitalization and 2 year all-cause mortality risk in an unselected cohort of consecutive patients with diabetes admitted for unstable angina or non-Q-wave myocardial infa rct ion to a university hospital during 1988 - 98 . METHODS AND RESULTS A total of 713 consecutive patients with diabetes were included . During 2 years of follow-up , 242 ( 34 % ) patients died . All analyses were retrospective using prospect ively collected clinical data . The primary study endpoint was 2 year all-cause mortality collected from the Swedish cause-specific mortality register . In unadjusted analyses , high admission blood glucose ( highest vs. lowest quartile : hazard ratio ( HR ) 2.66 ; 95 % confidence interval ( CI ) 1.83 , 3.86 ) and hypoglycaemia recorded during hospitalization ( hypoglycaemia vs. normal : HR 1.77 ; 95 % CI 1.09 , 2.86 ) were both significantly associated with increased 2 year all-cause mortality risk . These associations remained significant after multivariable adjustment . CONCLUSION In the setting of acute coronary syndromes ( ACS ) among patients with diabetes , hyperglycaemia on arrival and hypoglycaemia during hospitalization are both independently associated with worse adjusted all-cause 2 year mortality risk . These observations suggest that the avoidance of both hyper- and hypoglycaemia during ACS events may be of similar importance , and glucose modulation remains an important objective to address in future r and omized trials Aim The efficacy and safety of insulin degludec ( IDeg ) , a new basal insulin with an ultra-long duration of action , was compared to sitagliptin ( Sita ) in a 26-week , open-label trial . Methods Insulin-naïve subjects with type 2 diabetes [ n = 458 , age : 56 years , diabetes duration : 7.7 years , glycosylated haemoglobin (HbA1c):8.9 % ( 74 mmol/mol ) ] were r and omized ( 1:1 ) to once-daily IDeg or Sita ( 100 mg orally ) as add-on to stable treatment with 1 or 2 oral antidiabetic drugs ( OADs ) . Results Superiority of IDeg to Sita in improving HbA1c and fasting plasma glucose ( FPG ) was confirmed [ estimated treatment difference ( ETD ) IDeg – Sita for HbA1c : −0.43%-points [ 95 % confidence interval ( CI ) : −0.61 ; −0.24 , p < 0.0001 ] and for FPG : −2.17 mmol/l ( 95 % CI : −2.59 ; −1.74 , p < 0.0001 ) ] . HbA1c < 7 % ( < 53 mmol/mol ) was achieved by 41 % ( IDeg ) versus 28 % ( Sita ) of patients , estimated odds ratio IDeg/Sita : 1.60 ( 95 % CI : 1.04 ; 2.47 , p = 0.034 ) . There was no statistically significant difference in the rate of nocturnal confirmed hypoglycaemia between IDeg and Sita [ 0.52 vs. 0.30 episodes/patient-year , estimated rate ratio ( ERR ) : IDeg/Sita : 1.93 ( 95 % CI : 0.90 ; 4.10 , p = 0.09 ) ] . Rates of overall confirmed hypoglycaemia were higher with IDeg than with Sita [ 3.1 vs. 1.3 episodes/patient-year , ERR IDeg/Sita : 3.81 ( 95 % CI : 2.40 ; 6.05 , p < 0.0001 ) ] . IDeg was associated with a greater change in body weight than Sita [ ETD IDeg – Sita : 2.75 kg ( 95 % CI : 1.97 ; 3.54 , p < 0.0001 ) ] . The overall rates of adverse events were low and similar for both groups . Conclusions In patients unable to achieve good glycaemic control on OAD(s ) , treatment intensification with IDeg offers an effective , well-tolerated alternative to the addition of a second or third OAD BACKGROUND In people with type 2 diabetes , a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor is one choice as second-line treatment after metformin , with basal insulin recommended as an alternative . We aim ed to compare the efficacy , tolerability , and safety of insulin glargine and sitagliptin , a DPP-4 inhibitor , in patients whose disease was uncontrolled with metformin . METHODS In this comparative , parallel , r and omised , open-label trial , metformin-treated people aged 35 - 70 years with glycated haemoglobin A(1c ) ( HbA(1c ) ) of 7 - 11 % , diagnosis of type 2 diabetes for at least 6 months , and body-mass index of 25 - 45 kg/m(2 ) were recruited from 17 countries . Participants were r and omly assigned ( 1:1 ) to 24-week treatment with insulin glargine ( titrated from an initial subcutaneous dose of 0·2 units per kg bodyweight to attain fasting plasma glucose of 4·0 - 5·5 mmol/L ) or sitagliptin ( oral dose of 100 mg daily ) . R and omisation ( via a central interactive voice response system ) was by r and om sequence generation and was stratified by centre . Patients and investigators were not masked to treatment assignment . The primary outcome was change in HbA(1c ) from baseline to study end . Efficacy analysis included all r and omly assigned participants who had received at least one dose of study drug and had at least one on-treatment assessment of any primary or secondary efficacy variable . This trial is registered at Clinical Trials.gov , NCT00751114 . FINDINGS 732 people were screened and 515 were r and omly assigned to insulin glargine ( n=250 ) or sitagliptin ( n=265 ) . At study end , adjusted mean reduction in HbA(1c ) was greater for patients on insulin glargine ( n=227 ; -1·72 % , SE 0·06 ) than for those on sitagliptin ( n=253 ; -1·13 % , SE 0·06 ) with a mean difference of -0·59 % ( 95 % CI -0·77 to -0·42 , p<0·0001 ) . The estimated rate of all symptomatic hypoglycaemic episodes was greater with insulin glargine than with sitagliptin ( 4·21 [ SE 0·54 ] vs 0·50 [ SE 0·09 ] events per patient-year ; p<0·0001 ) . Severe hypoglycaemia occurred in only three ( 1 % ) patients on insulin glargine and one ( < 1 % ) on sitagliptin . 15 ( 6 % ) of patients on insulin glargine versus eight ( 3 % ) on sitagliptin had at least one serious treatment-emergent adverse event . INTERPRETATION Our results support the option of addition of basal insulin in patients with type 2 diabetes inadequately controlled by metformin . Long-term benefits might be expected from the achievement of optimum glycaemic control early in the course of the disease . FUNDING Sanofi AIM To compare safety and efficacy of insulin glargine and liraglutide in patients with type 2 diabetes ( T2DM ) . METHODS This r and omized , multinational , open-label trial included subjects treated for T2DM with metformin ± sulphonylurea , who had glycated haemoglobin ( HbA1c ) levels of 7.5 - 12 % . Subjects were assigned to 24 weeks of insulin glargine , titrated to target fasting plasma glucose of 4.0 - 5.5 mmol/L or liraglutide , escalated to the highest approved clinical dose of 1.8 mg daily . The trial was powered to detect superiority of glargine over liraglutide in percentage of people reaching HbA1c < 7 % . RESULTS The mean [ st and ard deviation ( s.d . ) ] age of the participants was 57 ( 9 ) years , the duration of diabetes was 9 ( 6 ) years , body mass index was 31.9 ( 4.2 ) kg/m(2 ) and HbA1c level was 9.0 (1.1)% . Equal numbers ( n = 489 ) were allocated to glargine and liraglutide . Similar numbers of subjects in both groups attained an HbA1c level of < 7 % ( 48.4 vs. 45.9 % ) ; therefore , superiority of glargine over liraglutide was not observed ( p = 0.44 ) . Subjects treated with glargine had greater reductions of HbA1c [ -1.94 % ( 0.05 ) and -1.79 % ( 0.05 ) ; p = 0.019 ] and fasting plasma glucose [ 6.2 ( 1.6 ) and 7.9 ( 2.2 ) mmol/L ; p < 0.001 ] than those receiving liraglutide . The liraglutide group reported a greater number of gastrointestinal treatment-emergent adverse events ( p < 0.001 ) . The mean ( s.d . ) weight change was + 2.0 ( 4.0 ) kg for glargine and -3.0 ( 3.6 ) kg for liraglutide ( p < 0.001 ) . Symptomatic hypoglycaemia was more common with glargine ( p < 0.001 ) . A greater number of subjects in the liraglutide arm withdrew as a result of adverse events ( p < 0.001 ) . CONCLUSION Adding either insulin glargine or liraglutide to subjects with poorly controlled T2DM reduces HbA1c substantially , with nearly half of subjects reaching target levels of 7 % Aims /hypothesisThis post hoc analysis from the Diabetes Mellitus Insulin – Glucose Infusion in Acute Myocardial Infa rct ion ( DIGAMI ) 2 trial reports on extended long-term outcome in relation to glucose-lowering agents in patients with myocardial infa rct ion and type 2 diabetes . Methods Patients were r and omised as follows : group 1 , insulin-based treatment ; group 2 , insulin during hospitalisation followed by conventional glucose control ; and group 3 , conventional treatment . Treatment according to the above protocol lasted 2.1 years . Using the total DIGAMI 2 cohort as an epidemiological data base , this study presents mortality rates in the r and omised groups , and mortality and morbidity rates by glucose-lowering treatment during an extended period of follow-up ( median 4.1 and max 8.1 years ) . Results Follow-up data were available in 1,145 of the 1,253 patients . The mortality rate was 31 % ( 72 % cardiovascular ) without significant differences between treatment groups . The total number of fatal malignancies was 37 , with a trend towards a higher risk in group 1 . The HR for death from malignant disease , compared with group 2 , was 1.77 ( 95 % CI 0.87–3.61 ; p = 0.11 ) and 3.60 ( 95 % CI 1.24–10.50 ; p = 0.02 ) compared with group 3 . Insulin treatment was associated with non-fatal cardiovascular events ( OR 1.89 95 % CI 1.35–2.63 ; p = 0.0002 ) , but not with mortality ( OR 1.30 , 95 % CI 0.93–1.81 ; p = 0.13 ) . Metformin was associated with a lower mortality rate ( HR 0.65 , 95 % CI 0.47–0.90 ; p = 0.01 ) and a lower risk of death from malignancies ( HR 0.25 , 95 % CI 0.08–0.83 ; p = 0.02 ) . Conclusions /interpretation Patients with type 2 diabetes and myocardial infa rct ion have a poor prognosis . Glucose-lowering drugs appear to be of prognostic importance . Insulin may be associated with an increased risk of non-fatal cardiac events , while metformin seems to be protective against risk of death INTRODUCTION We explored the safety and efficacy of exenatide BID v. insulin glargine in a subgroup of Polish patients with type 2 diabetes sub-optimally controlled with metformin plus a sulfonylurea , participating in a 26-week r and omised , controlled open-label trial . MATERIAL AND METHODS In Pol and , 80 patients ( HbA1c 7 - 10 % , BMI 25 - 45 kg/m(2 ) ) were r and omised to exenatide 10 μg BID ( n = 40 ) or insulin glargine once daily ( n = 40 ) . We present exploratory analyses on HbA1c , glucose profiles , body weight , hypoglycaemia and adverse events ( AEs ) . RESULTS Mean ( SD ) baseline HbA1c was 7.9 % ( 0.86 ) for exenatide and 7.8 % ( 1.02 ) for insulin glargine . At Week 26 , LS mean ( SEM ) HbA1c decreased in both groups ( exenatide -0.72 % [ 0.12 ] ; glargine -0.64 % [ 0.12 ] ) , as did fasting glucose . Postpr and ial glucose excursions after breakfast and dinner were smaller in patients treated with exenatide . LS mean ( SEM ) body weight decreased by -1.9 ( 0.48 ) kg with exenatide and increased by 1.6 ( 0.48 ) kg with glargine ( group difference [ 95%CI ] : -3.5 kg [ -4.9 to -2.2 ] ) . Hypoglycaemia was low in both groups ; nocturnal hypoglycaemia was reported for three v. seven patients ( three v. 24 episodes ) in the exenatide and glargine groups , respectively . Adverse events were more common with exenatide ( nausea n = 22 v. n = 1 , vomiting n = 5 v. n = 0 , headache n = 8 v. n = 2 ) . CONCLUSION This exploratory analysis confirms that findings from the global study apply to patients treated with exenatide BID and glargine in Pol and , showing that exenatide BID was as effective as insulin glargine . Data suggested that changes in HbA1c were similar , with fasting glucose changes greater in the glargine group and postpr and ial changes greater in the exenatide BID group . Exenatide BID was associated with weight reduction , less nocturnal hypoglycaemia , but more gastrointestinal events compared to glargine Context Are both exenatide and insulin glargine reasonable additions for patients with type 2 diabetes that is suboptimally controlled despite metformin and sulfonylurea therapy ? Contribution This multicenter , 26-week , r and omized trial compared the addition of exenatide or insulin glargine to regimens of 551 patients with suboptimally controlled type 2 diabetes . Both additions led to similar reductions in hemoglobin A1c levels . Exenatide best reduced postpr and ial glucose excursions ; insulin glargine best reduced fasting glucose concentrations . Exenatide patients experienced weight loss and increased gastrointestinal symptoms , such as nausea and vomiting . Implication s Adding either exenatide or insulin glargine to oral hypoglycemic regimens may improve glycemic control in patients with suboptimally controlled type 2 diabetes . The Editors Progressive -cell dysfunction and insulin resistance are the core defects of type 2 diabetes , result ing in hyperglycemia and a host of devastating microvascular and cardiovascular complications . When diet and exercise modifications no longer maintain glycemic targets , oral blood glucoselowering drugs are usually administered . However , the long-term effectiveness of these drugs can be unsatisfactory because of modest or short-lived efficacy , adverse effects and tolerability issues , and an inability to affect the progressive decline in -cell function ( 1 ) . When 1 or more oral blood glucoselowering drugs no longer adequately control escalating hyperglycemia , addition of basal insulin is common practice ( 2 ) . Although basal insulin can improve glycemic control , its use can be complicated by inadequate control of postpr and ial hyperglycemia , an increased risk for hypoglycemia compared with that observed with oral blood glucoselowering drugs alone , and the need for complicated dose-titration regimens ( 3 , 4 ) . In addition , insulin therapy often causes weight gain , compounding any preexisting obesitya common contributing factor to insulin resistance that is difficult to manage effectively ( 5 - 7 ) . A recent advance in insulin therapy was the introduction of insulin glargine , an analogue of human insulin design ed to have an extended duration of action ( 8) . Titrated to target fasting glucose levels ( treat-to-target ) , insulin glargine provides greater convenience and reduced incidence of hypoglycemia than neutral protamine Hagedorn ( NPH ) insulin ( 9 - 16 ) . However , insulin glargine still maintains many drawbacks of insulin therapy , including the need for dose titration , increased hypoglycemia , weight gain , and the persistence of postpr and ial glucose excursions ( 9 - 16 ) . Glucagon-like peptide-1 ( GLP-1 ) , an incretin hormone , is an essential component of normal glucose homeostasis ( 17 ) . The actions of GLP-1 include enhancement of glucose-dependent insulin secretion and regulation of glucagon release and the rate of gastric emptying , thereby reducing hyperglycemia ( 18 ) . In addition , GLP-1 enhances -cell function and promotes satiety , result ing in reduced caloric intake and weight reduction ( 18 ) . These activities have generated interest in GLP-1 as a potential therapy for diabetes . However , GLP-1 is rapidly inactivated by dipeptidyl peptidase-IV , and the active forms of GLP-1 have a circulating half-life of only 1 to 2 minutes ( 19 ) . The limited duration of action for exogenously administered GLP-1 limits its utility in a chronic disease like type 2 diabetes . Therefore , agents that may mimic or enhance the activities of GLP-1 are of great clinical interest . The incretin mimetics are an emerging class of compounds that elicit glucoregulatory actions similar to those of GLP-1 . Exenatide ( exendin-4 ) , a 39amino acid peptide that belongs to this class , shares many of the same glucoregulatory , -cell , and body weight effects that have been observed with GLP-1 ( 18 , 20 - 23 ) . However , exenatide is resistant to degradation by dipeptidyl peptidase-IV and has a pharmacokinetic profile that is more amenable to long-term administration . Exenatide injection is approved by the U.S. Food and Drug Administration as adjunctive therapy to improve glycemic control in patients with type 2 diabetes who are taking metformin , a sulfonylurea , or a combination of metformin and a sulfonylurea but have not achieved adequate glycemic control . In phase 3 , 30-week controlled clinical trials , exenatide improved glycemic control ( as demonstrated by statistically significant reductions in fasting and postpr and ial plasma glucose levels and hemoglobin A1c levels ) and reduced body weight compared with placebo in patients with inadequately controlled type 2 diabetes ( 20 - 22 ) . Given the effects of exenatide in these clinical trials and the common practice of adding basal insulin to existing regimens of oral agents , we design ed our study to compare the effects of adding either exenatide or insulin glargine to treatment regimens of patients whose blood glucose levels were inadequately controlled with oral agents alone . Methods Study Protocol The primary objective of our r and omized , open-label , phase 3 clinical trial was to compare the effects of exenatide and insulin glargine on glycemic control ( defined as reduction in hemoglobin A1c level ) over 26 weeks in patients with type 2 diabetes who could not achieve adequate glycemic control with combination metformin and sulfonylurea therapy at maximally effective doses . Exenatide ( before morning and evening meals ) or insulin glargine ( at bedtime ) was added to each patient 's current therapy regimen . One group of patients received exenatide at a fixed dosage of 5 g twice daily for 4 weeks ; the dose was increased to 10 g twice daily for the remainder of the study . A second group of patients was assigned to receive insulin glargine at an initial dosage of 10 U/d ; then , using a fixed-dose algorithm to adjust the dose , they self-titrated the dose in 2-U increments every 3 days to achieve a fasting blood glucose target level of less than 5.6 mmol/L ( < 100 mg/dL ) on daily glucose monitoring . Daily glucose monitoring was not required for patients r and omly assigned to receive exenatide . Metformin and sulfonylurea doses were fixed at pre study levels unless patients experienced hypoglycemia ; in these instances , we recommended a 50 % reduction in sulfonylurea dose . Adverse events , except for hypoglycemia , were assessed at each visit by using an open-ended question naire . Patients were asked at each visit whether they had experienced hypoglycemia since their previous visit . Severity of each event ( mild , moderate , or severe ) and its attribution to therapy ( yes or no ) were assessed by the investigator . Symptomatic hypoglycemia was defined as a blood glucose measurement less than 3.4 mmol/L ( < 60 mg/dL ) or hypoglycemia accompanied by such symptoms as sweating , shaking , pounding heart , or confusion . Severe hypoglycemia was defined as a hypoglycemic episode in which the patient required assistance from another person and had a blood glucose measurement less than 2.8 mmol/L ( < 50 mg/dL ) or had promptly recovered after an oral carbohydrate or glucagon injection or intravenous glucose . A common clinical protocol was approved for each site by the institutional review board and in accordance with the principles described in the Declaration of Helsinki . Patients were recruited according to local investigators ' practice s and advertising , and all participants gave informed written consent before participation . Study Participants At 82 sites in 13 countries , 551 patients took part in the study between June 2003 and April 2004 . Of these participants , 549 made up the intention-to-treat sample and 2 were lost to follow-up . Patients were 30 to 75 years of age and were treated with stable and maximally effective doses of metformin and a sulfonylurea for at least 3 months before screening . General inclusion criteria included a hemoglobin A1c level ranging from 7.0 % to 10.0 % at the time of screening , body mass index ranging from 25 kg/m2 to 45 kg/m2 , and a history of stable body weight ( 10 % variation for 3 months before screening ) . Patients were excluded if they 1 ) had participated in an interventional medical , surgical , or pharmaceutical study within 30 days before screening ; 2 ) had more than 3 episodes of severe hypoglycemia within 6 months before screening ; 3 ) were undergoing therapy for a malignant disease other than basal-cell or squamous-cell skin cancer ; 4 ) had cardiac disease that was class III or IV according to the New York Heart Association criteria ; 5 ) had a serum creatinine concentration of greater than 135 mol/L ( > 1.5 mg/dL ) for men or greater than 110 mol/L ( > 1.2 mg/dL ) for women or had obvious clinical signs or symptoms of liver disease ; 6 ) were receiving long-term ( lasting longer than 2 weeks ) systemic glucocorticoid therapy or had received such therapy within 2 weeks immediately before screening ; 7 ) had used any prescription drug to promote weight loss within 3 months before screening ; or 8) had been treated ( for more than 2 consecutive weeks ) with insulin within 3 months before screening , with thiazolidinediones within 4 months before screening , with -glucosidase inhibitors within 3 months before screening , or with meglitinides within 3 months before screening . Within 2 weeks after screening , patients who met the inclusion criteria were r and omly assigned ( with equal probability ) to receive exenatide or insulin glargine according to a central r and omization table that was generated by the sponsor and administered by an automated interactive voice-response system . R and omization was stratified by investigative site ( block size of 4 ) . Study Measurements Hemoglobin A1c level was measured at screening ; at time of r and omization ( baseline , week 0 ) ; at weeks 12 and 26 ( end point ) ; and , if possible , at the time of early withdrawal from the study . Blood chemistries were assessed at screening and at weeks 0 and 26 . Fasting plasma glucose levels were assessed at week 0 and week 26 . A central laboratory performed all hemoglobin A1c , Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) BACKGROUND Diabetes treatments are needed that are convenient , provide effective glycaemic control , and do not cause weight gain . We aim ed to test the hypothesis that improvement in haemoglobin A(1c ) ( HbA(1c ) ) achieved with once weekly exenatide was superior to that achieved with insulin glargine titrated to glucose targets . METHODS In this 26-week , open-label , r and omised , parallel study , we compared exenatide with insulin glargine in adults with type 2 diabetes who had suboptimum glycaemic control despite use of maximum tolerated doses of blood-glucose-lowering drugs for 3 months or longer . Patients were r and omly assigned to add exenatide ( 2 mg , once-a-week injection ) or insulin glargine ( once-daily injection , starting dose 10 IU , target glucose range 4.0 - 5.5 mmol/L ) to their blood-glucose-lowering regimens . R and omisation was with a one-to-one allocation and block size four , stratified according to country and concomitant treatment ( 70 % metformin only ; 30 % metformin plus sulphonylurea ) . Participants and clinical investigators were not masked to assignment , but investigators analysing data were . The primary endpoint was change in HbA(1c ) from baseline , and analysis of this outcome was by modified intention to treat for all patients who received at least one dose of study drug . This trial is registered at Clinical Trials.gov , number NCT00641056 . FINDINGS 456 patients were r and omly allocated to treatment and were included in the modified intention-to-treat analysis ( 233 exenatide , 223 insulin glargine ) . Participants who received at least one dose of study drug and for whom baseline and at least one postbaseline measurement of HbA(1c ) were available were included in the primary efficacy analysis . Change in HbA(1c ) at 26 weeks was greater in patients taking exenatide ( n=228 ; -1.5 % , SE 0.05 ) than in those taking insulin glargine ( n=220 ; -1.3 % , 0.06 ; treatment difference -0.16 % , 0.07 , 95 % CI -0.29 to -0.03 ) . 12 ( 5 % ) of 233 patients allocated to exenatide and two ( 1 % ) of 223 taking insulin glargine discontinued participation because of adverse events ( p=0.012 ) . A planned extension period ( up to 2.5 years ' duration ) is in progress . INTERPRETATION Once weekly exenatide is an important therapeutic option for patients for whom risk of hypoglycaemia , weight loss , and convenience are particular concerns . FUNDING Amylin Pharmaceuticals ; Eli Lilly and Company BACKGROUND The efficacy of thiazolidinediones , as compared with other oral glucose-lowering medications , in maintaining long-term glycemic control in type 2 diabetes is not known . METHODS We evaluated rosiglitazone , metformin , and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind , r and omized , controlled clinical trial involving 4360 patients . The patients were treated for a median of 4.0 years . The primary outcome was the time to monotherapy failure , which was defined as a confirmed level of fasting plasma glucose of more than 180 mg per deciliter ( 10.0 mmol per liter ) , for rosiglitazone , as compared with metformin or glyburide . Prespecified secondary outcomes were levels of fasting plasma glucose and glycated hemoglobin , insulin sensitivity , and beta-cell function . RESULTS Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15 % with rosiglitazone , 21 % with metformin , and 34 % with glyburide . This represents a risk reduction of 32 % for rosiglitazone , as compared with metformin , and 63 % , as compared with glyburide ( P<0.001 for both comparisons ) . The difference in the durability of the treatment effect was greater between rosiglitazone and glyburide than between rosiglitazone and metformin . Glyburide was associated with a lower risk of cardiovascular events ( including congestive heart failure ) than was rosiglitazone ( P<0.05 ) , and the risk associated with metformin was similar to that with rosiglitazone . Rosiglitazone was associated with more weight gain and edema than either metformin or glyburide but with fewer gastrointestinal events than metformin and with less hypoglycemia than glyburide ( P<0.001 for all comparisons ) . CONCLUSIONS The potential risks and benefits , the profile of adverse events , and the costs of these three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00279045 [ Clinical Trials.gov ] . ) Human insulin synthesis ed by recombinant DNA technology was compared with highly purified porcine insulin in healthy men . Intracutaneous injection over a wide range of concentrations of both insulins into five subjects gave rise to no local reactions over a 48 h period . The glycaemic response to st and ard subcutaneous injection at high and low dose levels was measured with both insulins in each of six men . Plasma glucose decrement with the two insulins was similar but human insulin was perhaps slightly more potent than porcine insulin at the low dose , and slightly less so at the high . The glycaemic response to the isulins , each infused intravenously at high and low concentrations for 1 h in a further six subjects , showed a similar trend . Depression of glycaemia with human insulin slightly exceeded that with porcine insulin at the low concentration infusion and fell slightly short of it at the high . Genetically synthesis ed human insulin seems to be safe and effective in man . Its dose-response relationship may differ from that of porcine insulin PREDICTIVE ( Predictable Results and Experience in Diabetes through Intensification and Control to Target : An International Variability Evaluation ) is a large , multi-national , open-label , prospect i ve , observational study assessing the safety and efficacy of insulin detemir in clinical practice . A total of 20,531 patients with type 1 or 2 diabetes from 11 countries were prescribed insulin detemir and followed up after a mean of 14.4 weeks . The primary endpoint was incidence of serious adverse drug reactions ( SADRs ) , including major hypoglycaemia . Secondary endpoints were : haemoglobin A(1c ) ( HbA(1c ) ) , mean self-monitored fasting glucose , within-patient fasting glucose variability and body weight change . Two hundred and fourteen patients ( 1 % ) reported SADRs , including major hypoglycaemia . The incidence of major hypoglycaemic episodes was reduced from 3.0/patient-year at baseline to 0.7/patient-year at follow-up in type 1 patients ( p < 0.0001 ) , and from 0.8 to 0.1/patient-year in type 2 patients ( p < 0.0001 ) . Insulin detemir improved glycaemic control in type 1 and type 2 patients , with reductions in mean HbA(1c ) ( 0.5 % and 0.9 % , respectively , p < 0.0001 for both ) , fasting glucose ( 1.7 and 2.6 mmol/l , p < 0.0001 for both ) and within-patient fasting glucose variability ( 0.7 and 0.5 mmol/l , p < 0.0001 for both ) . There was a small decrease in mean body weight in both type 1 and 2 patients ( -0.1 kg , p < 0.01 and -0.4 kg , p < 0.0001 respectively ) . Insulin detemir was used once- or twice-daily in 49 % and 50 % of type 1 patients , and 77 % and 23 % of type 2 diabetes patients , respectively . The 14-week observations from PREDICTIVE support clinical trial data showing that insulin detemir improves glycaemic control , with a lowered risk of hypoglycaemia and no weight gain OBJECTIVE This study was conducted to compare the efficacy and safety profiles of exenatide and insulin glargine therapy in patients with type 2 diabetes who had not achieved glucose control with metformin or sulfonylurea monotherapy . METHODS This multinational , r and omized , open-label , crossover noninferiority study compared the efficacy of exenatide 10 pg BID and insulin glargine QD ( titrated targeting a fasting serum glucose ( FSG ) level < or = 5.6 mmol/L ) in patients with type 2 diabetes treated with a single oral antidiabetic agent . The study included two 16-week treatment periods . The primary a priori outcome variable was the change in glycosylated hemoglobin ( HbA(lc ) ) . Secondary outcomes included the proportion of patients achieving the American Diabetes Association ( ADA ) target HbA(lc ) of < or = 7 % and the European Association for the Study of Diabetes target of < or = 6.5 % , the change in FSG , end-point values and change in the 7-point self-monitored glucose profile , and change in body weight . Adverse events were assessed based on st and ard laboratory tests and patient reports . RESULTS One hundred thirty-eight patients were r and omized to study treatment ( 52.9 % female , 47.1 % male ; 79.7 % white ; mean [ SEM ] age , 54.9 [ 0.8 ] years ; duration of diabetes , 7.4 [ 0.4 ] years ; body mass index , 31.1 [ 0.4 ] kg/m(2 ) ; weight , 84.8 [ 1.4 ] kg ) while continuing to receive metformin ( 55.1 % ) or a sulfonylurea ( 44.9 % ) . The population had a baseline least squares ( LS ) mean ( SEM ) HbA(lc ) of 8.95 % ( 0.09 % ) and an LS mean FSG concentration of 12.0 ( 0.3 ) mmol/L. Both exenatide and titrated insulin glargine therapy were associated with similar significant changes from baseline in HbA(1c ) ( both , -1.36 % [ 0.09 % ] ; P < 0.001 ) ; the difference between groups was not statistically significant . The LS mean HbA(1c ) at end point was above the ADA target with both treatments ( exenatide , 7.57 % [ 0.09 % ] ; insulin glargine , 7.58 % [ 0.09 % ] ) . Similar proportions of patients achieved an HbA(1c ) < or = 7 % ( 37.5 % and 39.8 % , respectively ; P = NS ) or < or = 6.5 % ( 21.5 % and 13.6 % ) . Patients lost weight during exenatide treatment , whereas they gained weight during insulin glargine treatment ; the between-group difference in weight change was statistically significant ( LS mean difference , -2.2 [ 0.3 ] kg ; 95 % CI , -2.8 to-1.7 ; P < 0.001 ) . Both exenatide and insulin glargine were associated with significant reductions from baseline in FSG ( -2.9 [ 0.2 ] and -4.1 [ 0.2 ] mmol/L , respectively ; both , P < 0.001 ) , although the reduction was significantly greater with insulin glargine compared with exenatide ( LS mean difference , 1.2 [ 0.3 ] mmol/L ; 95 % CI , 0.7 to 1.7 ; P < 0.001 ) . Compared with insulin glargine , exenatide was associated with significantly lower 2-hour postpr and ial glucose ( PPG ) excursions ( P < 0.016 ) and total daily mean glucose excursion ( P < 0.001 ) . The proportions of patients reporting nausea during exenatide and insulin glargine treatment were 42.6 % and 3.1 % , respectively ; the proportions reporting vomiting were 9.6 % and 3.1 % . The incidence of hypoglycemia in the 2 groups was 14.7 % and 25.2 % ( P = NS ) . CONCLUSIONS In this open-label , crossover study , treatment with exenatide or insulin glargine for 16 weeks was associated with similar significant improvements from baseline in HbA(1c ) , independent of treatment order . The improvements in HbA(1c ) from baseline did not differ significantly between treatment groups . Exenatide therapy was associated with significant reductions in body weight and PPG excursions compared with insulin glargine , whereas insulin glargine was associated with a significantly greater reduction in FSG compared with exenatide . These findings provide additional information to guide treatment decisions in patients with type 2 diabetes who are potential c and i date s for either therapy |
1,770 | 29,025,431 | Any cut-offs are proposed for single cow ’s milk proteins and for baked milk allergy in children younger than 2 years .
In Children ≥ 2 years of age it is hard to define practical cut-offs for allergy to fresh and baked cow ’s milk .
Conclusions None of the cut-offs proposed in the literature can be used to definitely confirm cow ’s milk allergy diagnosis , either to fresh pasteurized or to baked milk . | Background The diagnosis of IgE-mediated cow ’s milk allergy is often based on anamnesis , and on specific IgE ( sIgE ) levels and /or Skin Prick Tests ( SPT ) , which have both a good sensitivity but a low specificity , often causing positive results in non-allergic subjects .
Thus , oral food challenge is still the gold st and ard test for diagnosis , though being expensive , time-consuming and possibly at risk for severe allergic reactions .
Aim The aim of the present study was to perform a systematic review of the studies that have so far analyzed the positive predictive values for sIgE and SPT in the diagnosis of allergy to fresh and baked cow ’s milk according to age , and to identify possible cut-offs that may be useful in clinical practice . | BACKGROUND The double-blind , placebo-controlled food challenge ( DBPCFC ) is the " gold st and ard " for diagnosis of food hypersensitivity . Skin prick tests and RASTs are sensitive indicators of food-specific IgE antibodies but poor predictors of clinical reactivity . Previous studies suggested that high concentrations of food-specific IgE antibody were predictive of food-induced clinical symptoms . Because the CAP System FEIA ( Pharmacia Diagnostics , Uppsala , Sweden ) provides a quantitative assessment of allergen-specific IgE antibody , this study was undertaken to determine the potential utility of the CAP System FEIA in diagnosis of IgE-mediated food hypersensitivity . METHODS Sera from 196 patients with food allergy were analyzed for specific IgE antibodies to egg , milk , peanut , soy , wheat , and fish by CAP System FEIA . Sera were r and omly selected from 300 stored sample s of children and adolescents who had been evaluated by history , skin prick tests , and DBPCFCs . The study population was highly atopic ; all patients had atopic dermatitis , and approximately 50 % had asthma and allergic rhinitis at the time of initial evaluation . The performance characteristics of the CAP System FEIA were compared with those of skin prick tests and the outcome of DBPCFCs or " convincing " histories of anaphylactic reactions . RESULTS The prevalence of specific food allergies in the study population varied from 22 % for wheat to 73 % for egg . Allergy to egg , milk , peanut , and soy accounted for 87 % of confirmed reactions . The performance characteristics of skin prick tests and CAP System FEIA ( egg , milk , peanut , fish ) were comparable , with excellent sensitivity and negative predictive accuracy but poor specificity and positive predictive accuracy . The performance characteristics of the CAP System FEIA for soy and wheat were poor . For egg , milk , peanut , and fish allergy , diagnostic levels of IgE , which could predict clinical reactivity in this population with greater than 95 % certainty , were identified : egg , 6 kilounits of allergen-specific IgE per liter ( kU[A]/L ) ; milk , 32 kU(A)/L ; peanut , 15 kU(A)/L ; and fish , 20 kU(A)/L. CONCLUSIONS When compared with the outcome of DBPCFCs , results of CAP System FEIA are generally comparable to those of skin prick tests in predicting symptomatic food hypersensitivity . Furthermore , by measuring the concentrations of food-specific IgE antibodies with the CAP System FEIA , it is possible to identify a subset of patients who are highly likely ( > 95 % ) to experience clinical reactions to egg , milk , peanut , or fish . This could eliminate the need to perform DBPCFCs in a significant number of patients suspected of having IgE-mediated food allergy BACKGROUND Little is known about the cause of food-induced anaphylaxis in children or about the factors that might affect its clinical severity . OBJECTIVE The aim of this study was to investigate the cause of food-induced anaphylaxis in children in Italy and to identify factors that could influence the appearance of symptoms and the severity of anaphylaxis . METHODS One hundred and sixty-three children with anaphylaxis consecutively attending 29 outpatient allergy clinics throughout Italy were enrolled in this prospect i ve study . Information about past anaphylaxis episodes was collected with a st and ardized question naire . Food sensitization was evaluated by skin-prick test . RESULTS A clinical history of asthma increased the risk of wheezing [ odds ratio ( OR ) 2.2 ; 95 % confidence interval ( CI ) 1.1 - 4.5 ] and respiratory arrest ( OR 6.9 ; 95 % CI 1.4 - 34.2 ) . A clinical history of chronic/relapsing gastrointestinal symptoms increased the risk of vomiting ( OR 2.1 ; 95 % CI 0.9 - 4.3 ) , hypotension ( OR 7.9 ; 95 % CI 1.9 - 32.0 ) , and bradycardia/cardiac arrest ( OR 9.2 ; 95 % CI 0.9 - 91.3 ) . The severity of present and previous episodes was similar only in patients with mild or moderate anaphylaxis . Peanut and egg were the most frequent causes of severe anaphylaxis . CONCLUSIONS A clinical history of asthma and chronic/relapsing gastrointestinal symptoms ( probably linked to food allergy ) may predict the development of respiratory and gastrointestinal symptoms and the severity of anaphylaxis Background : The objective of the present study was to evaluate the relevance of skin tests and the concentration of cow 's milk‐specific IgE antibodies in correlation with oral cow 's milk challenge in infants with suspected cow 's milk allergy Five children aged 12‐40 months with IgE‐mediated adverse reactions to cow milk ( immediate onset clinical pattern of cow milk allergy ) were orally challenged double‐blind in r and om order with three different milk preparations processed from the same batch of milk 1 ) raw untreated cow milk , 2 ) pasteurized cow milk , 3 ) homogenized and pasteurized cow milk , and 4 ) Nutramigen ® (a commercial hypoallergenic infant formula based on hydrolysed casein ) as placebo . Skin prick tests with the same preparations were also performed . On oral challenge the three different processed milk types provoked significant and similar allergic reactions in each child , and no adverse reactions followed the challenge with placebo ( Nutramigen ) . Skin prick test with the same milk products were positive in all children and comparable to the results with an extract of purified raw cow milk protein ( Soluprickreg ; ) , whereas Nutramigen did not elicit any skin reactions . A tendency towards a lower threshold of reaction and larger skin reactions induced by the processed milk preparations might indicate an increased ability of pasteurized and homogenized/pasteurized milk to evoke allergic reactions in patients allergic to milk BACKGROUND A milk-free diet with substitute formula should be established when immediate symptomatic hypersensitivity to cows ' milk protein ( CMP ) is diagnosed , and therefore an accurate diagnosis is very important . OBJECTIVE This study aims to find the optimal cutoff values for specific IgE antibody levels that discriminate between allergic and tolerant infants by using cows ' milk and its principal proteins as allergens . METHODS A prospect i ve study was carried out on 170 patients under 1 year old ( mean , 4.8 months ) . These patients were seen consecutively over a 4-year period in our outpatient clinic and for the first time because of a reaction suggesting immediate hypersensitivity after ingestion of cows ' milk formula . A clinical history , prick test with cows ' milk and its proteins ( alpha-lact-albumin , beta-lactoglobulin , and casein ) , determination of specific IgE antibodies with the CAP system FEIA for the same allergens as for the prick test , and a challenge test according to the diagnostic protocol were performed in all of the children . A study of validity of the prick test ( cutoff point , 3 mm ) and CAP system by using different cutoff points in the specific IgE values for cows ' milk and its proteins were also analyzed . RESULTS Prevalence of immediate symptomatic hypersensitivity to CMP in this study was 44 % . When both the whole milk and its principal milk proteins were used in the prick test , the negative predictive value was very high , and a negative value excluded allergy in 97 % of the patients . When the different cutoff points of the specific IgE for milk were analyzed , 2.5 KU(A)/L had a positive predictive value of 90 % and 5 KU(A)/L had a positive predictive value of 95 % . CONCLUSIONS When diagnosing immediate hypersensitivity to CMP in infants , negative skin test responses exclude allergy in most of the patients . If the prick test response is positive , specific IgE levels for cows ' milk may be helpful . If these values are 2.5 KU(A)/L or greater , the challenge test should not be performed because of its high positive predictive value ( 90 % ) Skin Prick Test ( SPT 's ) are performed to identify the causes of allergy . However , low diagnostic accuracy is a limitation to SPT , for which many possible causes have been suggested . The protein composition and allergenicity of crude allergen extracts from foods and commercial allergen extracts for SPT were analyzed . Clinical significance s of SPT using crude allergen extracts from foods were compared with those using commercial allergen extracts . A total of 292 atopic dermatitis patients were involved in this study . Crude allergen extracts were prepared from milk , egg white , egg yolk , and soybean . The protein composition of food allergen extracts and commercial allergen extracts of milk , whole egg , white , egg yolk , and soybean were compared by SDS-PAGE . The allergenicity was tested by the immunoblotting method using immune sera . SPTs were performed using crude and commercial allergen . Double-blind placebo- controlled food challenge ( DBPCFC ) was performed to verify the SPT results and to compare the clinical significance of crude and commercial allergen extracts . Protein composition differed markedly between crude and commercial allergen extracts . By immunoblotting , crude and commercial allergen extracts showed different allergenicity . The SPT results using crude and commercial allergen extracts showed significant differences . The prevalence of milk , egg and soybean allergy was over 35 % in atopic dermatitis . The accuracy of SPT using crude allergen extracts from foods was significantly higher than that using commercial allergen extracts . In the case of soybeans , the result of SPT using commercial allergen extract was clinical ly insignificant for the prediction of soybean allergy . The source of allergen extract was very important for the appropriate SPT in food allergy . The accuracy of SPT might be improved using the appropriate allergen source for food allergy We evaluated the value of the patch test , skin prick test , and milk‐specific IgE by CAP RAST in 301 infants with suspected hypersensitivity to cow 's milk . The patch test was carried out with milk powder , and the skin prick test with cow 's milk‐based formula . Hypersensitivity to cow 's milk was determined with double‐blind , placebo‐controlled challenge . An immediate reaction to cow 's milk challenge was observed in 100 infants ( 33 % ) , a delayed reaction in 76 ( 25 % ) , and a negative result in 125 ( 42 % ) . Skin prick test wheals were significantly greater in infants with immediate reactions than in infants with delayed or negative reactions . Milk‐specific IgE was correlated with the skin prick test ( r=0.78 , P<0.001 , n=268 ) but did not contribute to further discrimination of immediate reactions from delayed or negative reactions compared to skin prick test alone . In our study population , the skin prick test ( diameter ≥3 mm ) showed a specificity and sensitivity of 91 % and 69 % ; the results for milk‐specific IgE ( ≥0.7 kU/l ) were 88 % and 58 % , respectively . The patch test did not distinguish subjects with immediate or delayed reactions from those with negative reactions BACKGROUND The double-blind , placebo-controlled food challenge is considered the gold st and ard for diagnosing food allergy . However , in a retrospective analysis of children and adolescents with atopic dermatitis and food allergy , discrete food-specific IgE concentrations were established that could predict clinical reactivity to egg , milk , peanut , and fish with greater than 95 % certainty . OBJECTIVE The purpose of this investigation was to determine the utility of these 95 % predictive decision points in a prospect i ve evaluation of food allergy . METHODS Sera from 100 consecutive children and adolescents referred for evaluation of food allergy were analyzed for specific IgE antibodies to egg , milk , peanut , soy , wheat , and fish by using the Pharmacia CAP System FEIA . Food-specific IgE values were compared with history and the results of skin prick tests and food challenges to determine the efficacy of previously established 95 % predictive decision points in identifying patients with increased probability of reacting during a specific food challenge . RESULTS One hundred children ( 62 % male ; median age , 3.8 years ; range , 0.4 - 14.3 years ) were evaluated for food allergy . The diagnosis of food allergy was established by means of history or oral food challenge . On the basis of the previously established 95 % predictive decision points for egg , milk , peanut , and fish allergy , greater than 95 % of food allergies diagnosed in this prospect i ve study were correctly identified by quantifying serum food-specific IgE concentrations . CONCLUSION In a prospect i ve study of children and adolescents referred for evaluation of food allergy , previously established 95 % predictive decision points of food-specific IgE antibody concentrations for 4 major food allergens were effective in predicting clinical reactivity . Quantification of food-specific IgE is a useful test for diagnosing symptomatic allergy to egg , milk , peanut , and fish in the pediatric population and could eliminate the need to perform double-blind , placebo-controlled food challenges in a significant number of children |
1,771 | 10,781,465 | Clonidine appears to have significant analgesic benefit and to cause minimal adverse effects when used in doses up to 150 microg . | This article review s current evidence for the efficacy of adding novel analgesic adjuncts to brachial plexus block , the goal of which is to prolong analgesic effect without the disadvantage of systemic side effects or prolonged motor block .
It may also allow for a reduction in the total dose of local anesthetic used .
Novel adjuncts studied to date include opioids , clonidine , neostigmine , and tramadol . | This study assessed the minimum dose of clonidine required to prolong the duration of both anesthesia and analgesia after axillary brachial plexus blockade . Eighty patients scheduled for elective h and surgery were divided into eight groups in a r and omized , double-blind fashion . An axillary brachial plexus block was performed with 40 mL 1 % mepivacaine plus 1:200,000 epinephrine . The control group received no clonidine . In the other groups , increasing doses of clonidine ( 0.1 , 0.2 , 0.3 , 0.4 , 0.5 , 1 , and 1.5 micro g/kg ) were added to the local anesthetic solution . Onset time , duration of anesthesia and analgesia , postoperative pain score , intake of analgesics , and adverse effects were recorded . The eight groups were comparable in terms of onset time , postoperative pain score , and analgesic requirement . The minimum dose of clonidine required to significantly prolong the duration of analgesia and anesthesia was , respectively , 0.1 and 0.5 micro g/kg . No side effects ( sedation , drowsiness , bradycardia , arterial hypotension ) were reported . We conclude that the dose of clonidine required to prolong significantly the duration of both anesthesia and analgesia after axillary brachial plexus blockade is 0.5 micro g/kg and that , at this dose , clonidine may be used without important reported side effects even in out patients . ( Anesth Analg 1996;83:1046 - 50 STUDY OBJECTIVE To determine whether the addition of morphine to the axillary block local anesthetic solution provides improved or prolonged postoperative analgesia . DESIGN Prospect i ve , r and omized , double-blind clinical trial with 24-hour follow-up . SETTING Ambulatory unit of a large academic referral center . PATIENTS Consecutive healthy volunteers scheduled for elective upper extremity surgery . INTERVENTIONS Patients in the treatment group ( AX ) were given intravenous ( IV ) saline and had morphine 0.1 mg/kg added to their axillary block solution . Control subjects ( CT ) received morphine 0.1 mg/kg IV and had saline added to their axillary block solution . All axillary blocks were performed using 0.55 ml/kg of 1.5 % lidocaine with epinephrine 1:200,000 . MEASUREMENTS AND MAIN RESULTS During the first 24 hours after surgery , visual analog scale ( VAS ) scores , supplementary analgesic ( oxycodone 5 mg with acetaminophen 500 mg ) use , and complications were recorded . Both groups had similar VAS scores throughout the study . In the 24-hour postoperative study period , AX patients required approximately half as many doses ( median , 2 doses ; range , 0 to 7 doses of supplemental analgesic as CT patients ( median , 4 doses ; range , 0 to 12 doses ) . There were no major complications in either group . CONCLUSIONS The addition of morphine 0.1 mg/kg to the local anesthetic axillary block solution provided improved postoperative analgesia without an increased frequency of side effects or major complications We have reported recently that continuous administration of butorphanol into the brachial plexus sheath provided analgesia of a quality superior to that of continuous i.v . administration . In the present study , we have compared postoperative pain relief produced by continuous infusion of one of three types of solution into the axillary sheath : opioid alone , local anaesthetic alone or a mixture of local anaesthetic and opioid . In patients undergoing upper extremity surgery with continuous axillary brachial plexus block , we injected one of the three solutions into the axillary neurovascular sheath : butorphanol 2 mg ( group B ) , 0.5 % mepivacaine alone ( group M ) and 0.5 % mepivacaine-butorphanol ( group MB ) ; the volume of each solution was 50 ml , administered at a rate of 50 ml per 24 h. At 3 h after operation , visual analogue scale ( VAS ) scores were significantly higher in group M than in group MB ( P < 0.01 ) , and higher in group B than in group MB ( P < 0.05 ) Background : Although addition of clonidine to local anesthetics can prolong pain relief after peripheral nerve block , a dose‐range effect has not been determined . Methods : Fifty‐six out patients undergoing carpal tunnel release were r and omly assigned to receive in a double‐blind fashion 45 ml of a mixture containing either 400 mg lidocaine plus saline or 400 mg lidocaine plus 30 , 90 or 300 micro gram clonidine for axillary nerve block . In each group ( n = 14 ) , blocks were evaluated at regular time intervals to determine sensory and motor functions in the five nerve regions of the h and and forearm . Also , adequacy of the block for surgery , postoperative pain intensity , and side effects were evaluated . Results : Compared with saline , each dose of clonidine reduced the onset time of sensory block and extended the field of adequate anesthesia . Ten minutes after injection , 30 micro gram clonidine was more effective than 90 micro gram clonidine in producing sensory blockade . Sedation occurred with clonidine 30 and 300 micro gram . Clonidine reduced the use of supplementary intravenous anesthetic agents for surgery and produced dose‐dependent prolongation of analgesia , reaching a mean 770 min ( range , 190–1440 min ) for the largest dose . Clonidine also produced a dose‐dependent decrease in systolic arterial pressure of up to ‐22.5 % ( range , ‐6.0–29.9 % ) of baseline . With clonidine , 300 micro gram , three patients had mean arterial pressure of < 55 mmHg ; four patients had episodes of arterial oxyhemoglobin saturation of < 90 % , and two others were not discharged because of hypotension . Conclusion : This study suggests that a small dose of clonidine enhances the quality of the peripheral blocks from lidocaine and limits the classical alpha2 ‐agonist side effects to sedation The effectiveness of buprenorphine and morphine , administered into the brachial plexus sheath , was evaluated in 40 patients , aged 18 - 90 years . All patients received 40 ml of 0.5 % bupivacaine , injected into the brachial plexus sheath using the supraclavicular technique . In addition , the 20 patients in Group I received morphine hydrochloride ( 50 μg/kg ) , while the 20 patients in Group II received buprenorphine hydrochloride ( 3 μg/kg ) . Using a three-point pain scale , the quality of analgesia was evaluated every hour for six hours , every two hours for the next six hours , and then at 12 , 24 , 36 and 48 hours . A significant difference in the quality of analgesia was found ; and was consistently superior with buprenorphine as compared with morphine . The duration of analgesia was nearly twice as long in the buprenorphine group as in the morphine group ( 35.05 ± 1.95 hour versus 18.25 ± 1.15 hour ) . We conclude that buprenorphine injection into the brachial plexus sheath is an efficient way to assure control of postoperative pain after upper limb surgery We have studied 40 patients undergoing elective shoulder surgery for chronically painful conditions . Patients were allocated r and omly to two groups and received interscalene brachial plexus block with 0.5 % bupivacaine and adrenaline 1/200,000 40 ml either alone or with the addition of morphine 5 mg . All patients also received a general anaesthetic . The quality of the block , analgesic requirements and any complications or side effects were noted in the intraoperative period and during the 48 h after operation . No significant difference was seen in quality of analgesia or patient satisfaction between the two groups Peripheral administration of opioids has been suggested as a means of improving regional block . We studied 60 patients receiving axillary brachial plexus anaesthesia , allocated r and omly to receive either normal saline 10 ml or normal saline 10 ml with alfentanil 10 micrograms/kg body weight through an axillary cannula . All patients received 1.5 % lignocaine at a dose of 7 mg/kg body weight with adrenaline 1 in 200,000 . The incidence of satisfactory block was similar in both groups . Although the percentage of patients with complete anaesthesia in the median nerve distribution was greater in the alfentanil group , there was no significant difference in any other distribution . The time to return of sensation and motor function was prolonged significantly in the alfentanil group ( P < 0.05 ) . After return of normal sensation , there was no significant difference between groups in postoperative analgesia . In a second part of the study , there was no significant increase in plasma concentrations of alfentanil in 10 patients given lignocaine and alfentanil , as outlined above . These observations suggest that alfentanil may have a peripheral local anaesthetic action The effects of clonidine and epinephrine , administered into the brachial plexus sheath , were evaluated in 60 patients who underwent surgery of the upper limb . All patients received 40 to 50 ml of 0.25 % bupivacaine , injected into the brachial plexus sheath , using the supraclavicular technique . The patients were r and omly allocated to two groups so that 30 patients received 150 μg clonidine hydrochloride ( Group I ) , and 30 received 200 μg epinephrine ( Group II ) . The quality and the duration of analgesia were assessed as well as , the possible side-effects . The block produced with the addition of clonidine was longer ( 994.2±34.2 vs 728.3±35.8 min ) and superior to that with epinephrine ( P<0.001 ) . No major side-effects were recorded . We conclude that the injection of clonidine into the brachial plexus sheath is an attractive alternative to epinephrine to prolong the duration of analgesia following upper limb surgery under conduction anaesthesia . RésuméLes effets de l’addition d’agents agonistes alpha-adrénergiques à la bupivacaïne lors de blocs du plexus brachial ont été évalués chez soixante patients ayant une intervention chirurgicale sur le membre supérieur . L’ensemble des patients a reçu 40 à 50 ml de bupivacaïne à 0.25 % pour réaliser un bloc du plexus brachial par voie sus-claviculaire . Les patients du groupe I ( n=30 ) recevaient par la même voie 150 μg de clonidine , ceux du groupe II ( n=30 ) 200 μg d ’ adrénaline . La durée et la qualité de l’analgésie sont ensuite étudiées ainsi que les éventuels effets adverses . Une différence statistiquement significative a été retrouvée en ce qui concerne la durée d’analgésie qui était supérieure dans le groupe clonidine ( 994,2±34,2 min vs 728,3 ±35,8 min ; P<0.001 ) . Aucun effet adverse majeur n’est retrouvé . Les auteurs concluent à l’intérêt particulier de la clonidine pour prolonger la durée d ’ analgésie après chirurgie du membre supérieur réalisée sous anesthésie régionale The admixture of clonidine or epinephrine to lidocaine for brachial plexus block was studied with regard to duration of block , postoperative analgesia , and plasma concentrations of lidocaine . Thirty-three patients of ASA physical status I and II received an admixture of either clonidine ( 150 micrograms ; n = 15 ) or epinephrine ( 200 micrograms ; n = 18 ) to 40 mL of 1 % lidocaine in a r and omized , double-blind fashion . Bone surgery predominated in those patients receiving clonidine and soft-tissue surgery in those receiving epinephrine ( P less than 0.05 ) . Onset and duration of block were not different between the groups . With the admixture of clonidine , fewer patients were completely pain free for greater than 12 h ( 13.3 % ) and pain scores ( visual analogue scale 0 - 10 ) were higher 6 h after the block ( median 4 ; range 0 - 6 ) than with epinephrine ( 61.1 % ; median 2 ; range 0 - 7 , respectively ; P less than 0.05 ) . In patients who had received clonidine , peak plasma concentrations of lidocaine were higher ( 10.29 + /- 2.96 mumol/L ) and occurred earlier ( 23.7 + /- 9.3 min ; mean + /- SD ) than in those treated with epinephrine ( 6.9 + /- 1.71 mumol/L ; 72.5 + /- 56.2 min ; P less than 0.05 ) . This indicates the absence of a local vasoconstrictor effect of clonidine and implies a reduced margin of safety with regard to local anesthetic toxicity . Although clonidine does not offer advantages compared with epinephrine , it may be a useful adjunct to local anesthetics in those patients in whom the administration of epinephrine is contraindicated BACKGROUND Intrathecal neostigmine induces analgesia but also several side effects . Recently , 500 microg neostigmine administered intraarticularly was shown to produce postoperative analgesia without side effects . The authors ' goal was to determine whether 500 microg neostigmine added to mepivacaine in axillary plexus block prolongs postoperative analgesia . In addition , they wanted to determine the incidence of side effects in patients undergoing h and surgery . METHODS Sixty-nine out patients scheduled for carpal tunnel syndrome repair with axillary plexus block were r and omly assigned to one of three groups that received saline solution in the axillary plexus and subcutaneously ( group 1 ) , 500 microg neostigmine in the axillary plexus and saline solution subcutaneously ( group 2 ) , or saline solution in the axillary plexus and 500 microg neostigmine subcutaneously ( group 3 ) . Sensory and motor block in the four h and nerve distributions were assessed every 5 min for 30 min The duration of the sensory and motor blocks were assessed after operation . Side effects were also recorded . RESULTS Neostigmine had no effect on sensory and motor block in any of the four nerve distributions , nor did it increase the median duration of sensory block ( 215 min ; range , 120 - 330 min ) compared with group 1 ( 247 min ; range , 190 - 287 min ) or group 3 ( 236 min ; range , 160 - 280 min ) . Motor block was slightly shorter ( P = 0.045 ) in group 3 ( 190 min ; range , 135 - 285 min ) compared with group 1 ( 218 min ; range , 145257 min ) and group 2 ( 215 min ; range , 105 - 343 min ) . Gastrointestinal side effects occurred in 30 % of patients in both neostigmine groups but not in group 1 ( P < 0.05 ) . CONCLUSIONS This study suggests that 500 microg neostigmine added to mepivacaine in axillary plexus block does not prolong postoperative sensory block , but it does cause a relatively high incidence of side effects . These two findings raise doubts about the use of neostigmine associated with local anesthetics for plexus neural block The possible potentiating effect of phentanyl on mepivacaine in brachial plexus blockade was evaluated , both for operative anesthesia and postoperative analgesia . Sixty ASA I patients , scheduled for upper limb surgery , were selected and distributed in 3 groups : 1 ) Mepivacaine 1 % 40 ml ( control group ) ; 2 ) Mepivacaine 1 % 40 ml + phentanyl 100 micrograms ; 3 ) Mepivacaine 1 % 40 ml + subcutaneous phentanyl 100 micrograms . The latency time and the quality of anesthesia were evaluated . The duration of analgesia was evaluated on the basis of the time from the administration of the first analgesic . There were no significant differences between the 3 groups in the latency times of the development of blockade nor in the quality of surgical anesthesia . Also , there were no significant differences in the duration of postoperative analgesia ( 307 , 316 and 326 minutes , respectively , in each group ) . It was concluded that the addition of phentanyl 100 micrograms to the local anesthetic in the axillary blockade of the brachial plexus does not change the anesthetic characteristics nor the time of postoperative analgesia BACKGROUND AND OBJECTIVES The acetylcholinesterase inhibitor neostigmine has shown peripherally mediated analgesic action in recent pre clinical and clinical studies . The present study investigates the effectiveness of adding neostigmine to a local anesthetic , mepivacaine , in patients receiving axillary brachial plexus block for upper extremity surgery . METHODS In a double-blind , r and omized study 34 patients were assigned to the treatment group : Neostigmine ( NM ) ( 500 microg ) + mepivacaine ( M ) ( 500 mg ) ( NM , n = 17 ) as drugs for the plexus block , or to control group : mepivacaine ( 500 mg ) + saline ( 0.9 % , 1 mL ) ( M , n = 17 ) . RESULTS The onset and duration of sensory and motor block was similar in both groups . Patients receiving NM had significantly lower pain ratings [ visual analogue scores ( VAS ) : 14.7 + /- 9.9 vs 32.4 + /-23.5 ; P < .05 ] 24 hours after surgery , and a lower number of patients in the NM group needed supplemental analgesics during the first 24 hours postoperatively . No adverse events were recorded for either group . CONCLUSIONS Peripherally administered neostigmine improves postoperative analgesia in axillary brachial plexus block UNLABELLED Tramadol is an analgesic drug that is antagonized by alpha2-adrenoceptor antagonists , as well as opioid antagonists . We hypothesized that tramadol might produce effects on an axillary brachial plexus blockade similar to those of clonidine . We design ed a prospect i ve , controlled , double-blinded study to assess the impact of tramadol added to mepivacaine on the duration of an axillary brachial plexus blockade . After institutional approval and informed consent , 60 patients ( ASA physical status I or II ) scheduled for forearm and h and surgery after trauma under brachial plexus anesthesia were included in the study . Patients were r and omly assigned to receive either 40 mL of mepivacaine 1 % with 2 mL of isotonic sodium chloride solution ( Group A , n = 20 ) ; 40 mL of mepivacaine 1 % with 100 mg of tramadol ( Group B , n = 20 ) ; or 40 mL of mepivacaine 1 % with 2 mL of isotonic sodium chloride solution and 100 mg of tramadol i.v . ( Group C , n = 20 ) . Sensory block , motor block , and hemodynamics were recorded before and 5 , 10 , 30 , 60 , 120 , 180 , and 360 min after local anesthetic injection . Duration of sensory and motor block was significantly longer ( P < 0.01 ; P < 0.05 ) in Group B ( 299 + /- 84 and 259 + /- 76 min ) than in Group A ( 194 + /- 35 and 181 + /- 24 min ) and Group C ( 187 + /- 35 and 179 + /- 16 min ) . There was no difference in onset of sensory and motor blockade among groups . Hemodynamics remained unchanged in all patients throughout the study period . We conclude that the addition of tramadol prolongs the duration of brachial plexus block without side effects . Tramadol may be an alternative to epinephrine or clonidine as an adjuvant to local anesthesia for an axillary block . IMPLICATION S This study demonstrates that the admixture of 100 mg of tramadol with mepivacaine 1 % for brachial plexus block provides a pronounced prolongation of blockade without side effects . Our data support a specific analgesic effect of tramadol on peripheral nerves In a r and omized , double-blind , controlled study , we have compared two groups of patients receiving either continuous systemic i.v . or continuous brachial plexus infusion of butorphanol for analgesia after operations on the upper extremities . Twenty-two patients undergoing elective upper extremity surgery were allocated r and omly to one of two groups to receive either butorphanol i.v . and saline injected into the brachial plexus sheath ( i.v . group ) or butorphanol injected into the brachial plexus sheath and saline i.v . ( brachial plexus group ) . After surgery on the upper extremity under continuous axillary brachial plexus block , each patient received a continuous infusion of butorphanol either i.v . or into the brachial plexus sheath at a dose of 83.3 micrograms h-1 . Concurrently , a saline infusion was given via the alternate route . Patients rated their pain on a 10-cm visual analogue scale ( VAS ) . VAS scores in the two groups did not differ up to 6 h and 24 h after operation . From 9 h until 24 h after operation , pain scores were significantly higher in the i.v . group than in the brachial plexus group . The VAS score 9 h after operation was 3.3 ( SD 2.7 ) in the i.v . group and 0.6 ( 0.9 ) in the brachial plexus group ( P < 0.01 ) ; 12 h after operation 2.7 ( 1.8 ) in the i.v . group and 0.6 ( 0.9 ) in the brachial plexus group ( P < 0.01 ) ; 18 h after operation 1.7 ( 1.0 ) in the i.v . group and 0.7 ( 1.0 ) in the brachial plexus group ( P < 0.05 ) ; and 24 h after operation 3.2 ( 2.4 ) in the i.v . group and 0.7 ( 1.2 ) in the brachial plexus group ( P < 0.01 ) . We conclude that continuous injection of butorphanol into the brachial plexus sheath provided superior analgesia compared with continuous i.v . injection Background and Objectives . This r and omized , double-blind study was design ed to evaluate the effects of the addition of fentanyl ( F ) to lidocaine ( L ) on the onset , duration , and success rate of axillary brachial plexus block . Methods . After institutional approval and informed consent , 53 ASA 1 and ASA 2 patients scheduled for orthopedic surgery using brachial plexus anesthesia were included in the study . Axillary brachial plexus block was performed using a peripheral nerve stimulator to localize one nerve of the major plexus . The patients were r and omly allocated to two groups . The L + F group ( n = 27 ) were administered 38 mL of 1.5 % L with 1/200,000 epinephrine and 100 μg of F , and the L + S group ( n = 26 ) were administered 38 mL of 1.5 % L with 1:200,000 epinephrine and 2 mL of normal saline . The onset ( monitored every 5 minutes ) and duration ( monitored every 30 minutes ) of surgical anesthesia , defined as the total abolition of the pinprick response , were evaluated in each nerve territory . Results . The patients were similar with regard to demographic data and the nerve trunks stimulated . In the L + F group , the onset time was only reduced ( P = .012 ) for the musculocutaneous nerve . The duration of surgical anesthesia and the motor block were similar in both groups . The frequency of complete plexus block and the frequency of anesthesia for each nerve trunk were similar in both groups . Conclusion . There is no clinical benefit result ing from the addition of fentanyl to the local anesthetic for axillary brachial plexus block A r and omized , double-blind study was performed on 50 patients scheduled for elective h and and forearm surgery under axillary plexus block to evaluate the effect of perineuronal morphine on the quality of postoperative analgesia . Patients were divided into two groups . In group A(n = 25 ) 5 mg of preservative-free morphine in 1.0 mL of 0.9 % saline was added to the local anesthetic solution ( 20 mL of 1 % plain lignocaine , 20 mL of 0.5 % plain bupivacaine ) . They also received an intramuscular placebo injection of 1.0 mL of 0.9 % saline in the upper thigh . In group B ( n = 25 ) , 1.0 mL of 0.9 % saline was added to the local anesthetic solution and patients received an intramuscular injection of 5 mg of preservative-free morphine in 1.0 mL of 0.9 % saline in the thigh . The addition of morphine to the local anesthetic solution for the axillary block did not shorten the onset time of the block , improve the quality of postoperative pain relief , or provide longer lasting analgesia than that obtained with intramuscular morphine Background and Objectives . The study examined the effects of adding fentanyl to mepivacaine supraclavicular blocks on block characteristics and postoperative analgesia . Methods . Twenty patients undergoing upper extremity surgery with supraclavicular blocks were prospect ively r and omized to receive 75 μg fentanyl either added to the local anesthetic ( 30 mL mepivacaine 1.5 % with epinephrine 5 μg/mL ) or given intramuscularly . An equivalent volume of normal saline was given in one of the two sites as a control in a double-blind fashion . Sensory and motor block onset , time to completion , and duration were measured . After the operation , patient-controlled analgesia with morphine was administered and the total dose used over 24 hours recorded . Visual analog pain scale ( VAS : 0 = no pain , 10 cm = worst pain ) was measured at 0 , 1 , 2 , 3 , 4 , and 12 hours after the operation . Results . There was no statistically significant difference between the two groups in sensory or motor block characteristics . There was a significantly lower VAS score among the patients with fentanyl added to their blocks within the first hour after the operation ( 1.3 ± 1.5 cm versus 3.8 ± 3.1 cm ; P < .05 ) , but subsequent VAS scores and total 24-hour patient-controlled analgesia requirements were no different . Conclusions . Adding fentanyl 75 μg to mepivacaine supraclavicular blocks has no significant effects on block characteristics . It may enhance postoperative analgesia , but the duration of this effect is too brief to be clinical ly useful Background and Objectives . This study evaluates the effects of clonidine added to mepivacaine on the duration of anesthesia and analgesia after axillary brachial plexus block . Methods . Thirty patients scheduled for elective h and surgery were divided into three equal groups in a r and omized , double-blinded fashion . An axillary perivascular brachial plexus block was performed with 40 ml 1 % mepivacaine plus 1:200,000 epinephrine in the three groups . Group B also received 150 μg clonidine subcutaneously and Group C had the same dose of clonidine mixed with the local anesthetic and injected into the plexus sheath . The following variables were recorded : onset time , duration of anesthesia , duration of analgesia , postoperative pain score , intake of analgesics , and adverse effects . Results . The three groups were comparable in terms of age , sex , weight , height , onset time of anesthesia , postoperative pain score , and analgesic requirement . The duration of anesthesia and analgesia was comparable in Groups A and B , but both variables were significantly increased in Group C : the duration of anesthesia and analgesia were prolonged , respectively , by 37 ± 6 % and 103 ± 16 % when compared to Group A and by 32 ± 7 % and 89 ± 15 % when compared to Group B. No side effects were reported . Conclusions . One hundred fifty micrograms clonidine added to mepivacaine for brachial plexus block prolongs the duration of anesthesia and analgesia . Our results suggest that this effect of clonidine is local rather than systemic We compared the duration of analgesia produced by a mixture of lignocaine and bupivacaine , either alone or combined with morphine ( 75 μgkg−1 ) , buprenorphine ( 3 μgkg−1 ) or sufentanil ( 0.2 μgkg−1 ) in 80 patients after brachial plexus block for orthopaedic surgery of the upper limb . The characteristics of analgesia were evaluated hourly using a visual analogue scale . The analgesia was considered satisfactory for scores of 30 or less . The median duration ( range ) of satisfactory analgesia was : 11.5 ( 8–15 ) h without an opioid , 21 ( 9–27 ) h with morphine , 20 ( 14–34 ) h with buprenorphine and 24.5 ( 11–38 ) h with sufentanil . We conclude that the addition of an opioid to a local anaesthetic mixture lengthens the duration of analgesia |
1,772 | 26,068,958 | It is not clear if any one dressing or securement device is better than any other in securing peripheral venous catheters . | BACKGROUND A peripheral venous catheter ( PVC ) is typically used for short-term delivery of intravascular fluids and medications .
It is an essential element of modern medicine and the most frequent invasive procedure performed in hospitals .
However , PVCs often fail before intravenous treatment is completed : this can occur because the device is not adequately attached to the skin , allowing the PVC to fall out , leading to complications such as phlebitis ( irritation or inflammation to the vein wall ) , infiltration ( fluid leaking into surrounding tissues ) or occlusion ( blockage ) .
An inadequately secured PVC also increases the risk of catheter-related bloodstream infection ( CRBSI ) , as the pistoning action ( moving back and forth in the vein ) of the catheter can allow migration of organisms along the catheter and into the bloodstream .
Despite the many dressings and securement devices available , the impact of different securement techniques for increasing PVC dwell time is still unclear ; there is a need to provide guidance for clinicians by review ing current studies systematic ally .
OBJECTIVES To assess the effects of PVC dressings and securement devices on the incidence of PVC failure . | Unplanned recannulations are a common occurrence in a number of hospitals both in the UK and worldwide ( Schwengel , 2004 ; Jackson , 2007 ) . In May 2008 the Clinical Nurse Specialist in IV Therapy at Brighton and Sussex University Hospital ( BSUH ) NHS Trust initiated a clinical audit to assess i.v . practice and determine the impact of recannulations within the Trust . The audit , which was initially carried out on 1000 sequential cannula insertions , and is currently ongoing , showed that 69.2 % of the cannulas failed well before the routine change of 72 hours , and that 36.3 % were removed because they had infiltrated . With the aim of reducing these numbers of unscheduled recannulations , the Nurse Specialist initiated a real-time , prospect i ve clinical evaluation of a new cannula stabilization device at BSUH . This assessed the impact of the device alongside the currently used securement strategy ( i.v . dressing ) on unscheduled i.v . restarts in 50 cannulas compared with the baseline data . During the clinical evaluation , all i.v.s were tracked every 4 hours and all complication/ reasons for removal were noted . On initiation of the use of the stabilization device , the infiltration rate was reduced from the baseline level by 100%.There was also an 81 % reduction in the rate of unscheduled i.v . restarts . The data from the clinical evaluation demonstrated the considerable benefits of using a cannula stabilization device compared with the current hospital practice of using i.v . dressings only for securement with regard to infiltration levels and unplanned restarts . This device may have significant future benefits in terms of improving patient care and reducing healthcare expenditure A prospect i ve r and omized clinical trial has been conducted to compare the clinical performance , with prolonged use , of two film-type transparent dressings used over subclavian and jugular single-lumen venous catheters . ' OpSite ' , a traditional dressing with a moderate moisture vapour permeability was compared with a new dressing of high moisture vapour permeability , ' OpSite IV3000 ' . Information was collected daily to assess the nature and incidence of complications , dressing durability and the ease of application and removal . One hundred and one patients provided two well-matched population s receiving a total of 153 dressings for a total of 780 catheter-days . No differences between the two dressings were noted with respect to the incidence of complications , such as moisture accumulation or lifting , and dressing durability . The low incidence of catheter-related sepsis ( ' OpSite ' group three episodes and ' OpSite IV3000 ' group one episode ) suggests that transparent dressings do not increase this risk . This clinical study demonstrated the new ' OpSite IV3000 ' to be easier to h and le , leading to better application , improved catheter fixation and easy removal Background Peripheral intravenous device ( IVD ) complications were traditionally thought to be reduced by limiting dwell time . Current recommendations are to resite IVDs by 96 hours with the exception of children and patients with poor veins . Recent evidence suggests routine resite is unnecessary , at least if devices are inserted by a specialised IV team . The aim of this study was to compare the impact of peripheral IVD ' routine resite ' with ' removal on clinical indication ' on IVD complications in a general hospital without an IV team . Methods A r and omised , controlled trial was conducted in a regional teaching hospital . After ethics approval , 362 patients ( 603 IVDs ) were r and omised to have IVDs replaced on clinical indication ( 185 patients ) or routine change every 3 days ( 177 patients ) . IVDs were inserted and managed by the general hospital medical and nursing staff ; there was no IV team . The primary endpoint was a composite of IVD complications : phlebitis , infiltration , occlusion , accidental removal , local infection , and device-related bloodstream infection . Results IVD complication rates were 68 per 1,000 IVD days ( clinical ly indicated ) and 66 per 1,000 IVD days ( routine replacement ) ( P = 0.86 ; HR 1.03 ; 95 % CI , 0.74 - 1.43 ) . Time to first complication per patient did not differ between groups ( KM with log rank , P = 0.53 ) . There were no local infections or IVD-related bloodstream infections in either group . IV therapy duration did not differ between groups ( P = 0.22 ) , but more ( P = 0.004 ) IVDs were placed per patient in the routine replacement ( mean , 1.8 ) than the clinical indication group ( mean , 1.5 ) , with significantly higher hospital costs per patient ( P < 0.001 ) . Conclusions Resite on clinical indication would allow one in two patients to have a single cannula per course of IV treatment , as opposed to one in five patients managed with routine resite ; overall complication rates appear similar . Clinical ly indicated resite would achieve savings in equipment , staff time and patient discomfort . There is growing evidence to support the extended use of peripheral IVDs with removal only on clinical indication . Registration numberAustralian New Zeal and Clinical Trials Registry ( ANZCTR ) Number ACTRN12608000421336 Four dressing regimens for peripheral venous catheters were studied in a prospect i ve r and omized clinical trial with 2088 Teflon catheters : ( 1 ) sterile gauze , replaced every other day , and three dressings left on for the lifetime of the catheter ; ( 2 ) gauze ; ( 3 ) a transparent polyurethane dressing ; and ( 4 ) an iodophor-transparent dressing . The four dressings provided comparable coverage , except moisture accumulated more frequently under the transparent dressings ( 26 % to 28 % vs 20 % to 21 % ) . Cutaneous colonization under the dressing was low level and comparable with all four dressings ( range , 10(0.58 ) to 10(0.70 ) colony-forming units ) . The rate of local catheter-related infection ( greater than or equal to 15 colony-forming units ) was also low and did not differ significantly ( range , 4.6 % to 5.9 % ) ; no catheter caused bacteremia . Stepwise logistic multivariate analysis showed cutaneous colonization of the insertion site ( relative risk [ RR ] of infection , 3.86 ) , contamination of the catheter hub ( RR , 3.78 ) , moisture under the dressing ( RR , 2.48 ) , and prolonged catheterization ( RR , 1.75 ) to be significant risk factors for catheter-related infection . These data indicate that it is not cost-effective to redress peripheral venous catheters at periodic intervals ; for most patients , either sterile gauze or a transparent dressing can be used and left on until the catheter is removed The use of a sterile transparent dressing ( Venigard , Consoli date d Medical Equipment , London ) was compared to the use of a non-sterile tape ( Mefix , Molnlycke , Sweden ) for securing peripheral cannulae in paediatric patients . Children from all medical specialties were prospect ively r and omised into one of two groups . The failure of a cannula ( defined as the removal of the cannula before treatment was completed ) was plotted against duration in each of the two groups . Statistical tests ( life table analysis ) suggested no significant difference ( p = > 0.05 ) . The authors conclude that the use of a sterile transparent dressing secures peripheral cannula as effectively as non-sterile tape A prospect i ve , controlled study was undertaken in a skilled nursing facility to determine whether a sterile catheter securement device ( StatLock i.v . , Venetec International , Mission Viejo , CA ) would provide better intravenous therapy outcomes than a st and ard securement technique . The StatLock-device result ed in significantly longer average catheter dwell times ( 3.95 days versus 2.45 days ) and significantly fewer total complications ( 65 versus 155 ) . In addition , the securement device reduced the total time spent managing a vascular access device by 13.5 minutes per patient . Thus , the StatLock i.v . device improved overall clinical outcomes of i.v . therapy and the quality of care OBJECTIVE To identify risk factors for infusion-related phlebitis with peripheral intravenous catheters . DESIGN A r and omized trial of two catheter material s , with consideration of 21 potential risk factors . SETTING A university hospital . PATIENTS Hospitalized adults without granulocytopenia who received a peripheral intravenous catheter . INTERVENTIONS House officers or ward nurses inserted the catheters , and each insertion was r and omized to a catheter made of tetrafluoroethylene-hexafluoropropylene ( FEP-Teflon ) or a novel polyetherurethane without leachable additives ( PEU-Vialon ) . MEASUREMENTS Research nurses scored insertion sites each day for inflammation and cultured catheters at removal . RESULTS The Kaplan-Meier risk for phlebitis exceeded 50 % by day 4 after catheterization . intravenous antibiotics ( relative risk , 2.00 ) , female sex ( relative risk , 1.88 ) , prolonged ( greater than 48 hours ) catheterization ( relative risk , 1.79 ) , and catheter material ( PEU-Vialon : FEP-Teflon ) ( relative risk , 0.73 ) strongly predicted phlebitis in a Cox proportional hazards model ( each , P less than 0.003 ) . The best-fit model for severe phlebitis identified the same predictors plus catheter-related infection ( relative risk , 6.19 ) , phlebitis with a previous catheter ( relative risk , 1.54 ) , and anatomic site ( h and : forearm , relative risk , 0.71 ; wrist : forearm , relative risk , 0.60 ) . The low incidence of local catheter-related infection was comparable with the two catheter material s ( 5.4 % [ 95 % CI , 3.8 % to 7.6 % ] and 6.9 % [ CI , 4.9 % to 9.6 % ] ) ; none of the 1054 catheters prospect ively studied caused bacteremia . CONCLUSIONS Multiple factors , including the infusate and the duration of cannulation , contribute to the development of infusion-related phlebitis . The use of peripheral intravenous catheters made of PEU-Vialon appears to pose the same risk for catheter-related infection as the use of catheters made of FEP-Teflon , and PEU-Vialon can permit longer cannulation with less risk for phlebitis . The risk for catheter-related bacteremia with FEP-Teflon and PEU-Vialon catheters is sufficiently low that it no longer seems justifiable to recommend the use of small steel needles for most peripheral intravenous therapy STUDY OBJECTIVES To prospect ively assess the relative risk for phlebitis in a series of consecutive patients with pneumonia and to identify risk factors that predict an increased risk for phlebitis . SETTING Internal medicine department of a tertiary teaching hospital . PATIENTS Seven hundred sixty-six consecutive patients with acute pneumonia receiving IV therapy . INTERVENTIONS Only the first catheter was taken into account . There were 308 short lines ( a 51-mm , 18-gauge Teflon catheter ) ; 307 midsized lines ( a 28-cm , 16-gauge polyvinyl chloride catheter ) ; and 151 long lines ( 71-cm , 14-gauge plain polyurethane catheter ) . Eighteen variables were prospect ively evaluated in an open , nonr and omized study for their contribution to the occurrence of phlebitis . RESULTS The overall phlebitis rate was 39 % . Phlebitis developed in 53 % of patients with short lines , in 41 % of patients with midsized lines , and in 10 % of patients with long lines , and these catheters remained in place an average ( + /- SD ) of 3.0+/-2.4 days , 4.6+/-3.4 days , and 7.8+/-6.6 days , respectively . The variables that influenced the development of phlebitis , as determined by multivariate analysis , were the following : type of catheter ; blood hemoglobin levels ; and IV therapy with either corticosteroids or erythromycin . CONCLUSIONS According to our data , when the use of a catheter is expected to be required for < or = 36 h , a short line can be used . If a longer duration is expected , a longer line is warranted . Ours is the first study in which the relationship between blood hemoglobin levels and phlebitis has been reported . Because the use of intravascular devices is increasingly common , a more complete knowledge of the factors that influence their acceptance has become essential Previous studies of various br and s of polyurethane dressings have noted differences in the rates of catheter colonization . We compared Bioclusive transparent polyurethane ( TP ) dressing with a cotton gauze ( CG ) dressing on peripheral intravenous ( IV ) access sites for the incidence of phlebitis , catheter tip colonization , skin colonization , and catheter-related bacteremia . The study , involving 598 ward patients , was case controlled , prospect i ve , and r and omized for a period of 4 months . Each patient was entered into the study only once , and all dressings were applied by a member of the IV therapy team . No significant difference was seen for phlebitis rate ( TP : 9.8 % vs. CG : 7.6 % ) or catheter tip colonization , defined as greater than 15 colony forming units ( CFU ) ( 5.7 % vs. 4.4 % ) by a semiquantitative technique . Cultures of specimens from the skin and catheter tips of the majority of patients ( 91 % ) showed no growth . An association was found between those patients with greater than 15 CFU isolated from catheter tips and those with phlebitis ( p = 0.022 ) . No documented catheter-related bacteremia occurred in either study group BACKGROUND The millions of peripheral intravenous catheters used each year are recommended for 72 - 96 h replacement in adults . This routine replacement increases health-care costs and staff workload and requires patients to undergo repeated invasive procedures . The effectiveness of the practice is not well established . Our hypothesis was that clinical ly indicated catheter replacement is of equal benefit to routine replacement . METHODS This multicentre , r and omised , non-blinded equivalence trial recruited adults ( ≥18 years ) with an intravenous catheter of expected use longer than 4 days from three hospitals in Queensl and , Australia , between May 20 , 2008 , and Sept 9 , 2009 . Computer-generated r and om assignment ( 1:1 ratio , no blocking , stratified by hospital , concealed before allocation ) was to clinical ly indicated replacement , or third daily routine replacement . Patients , clinical staff , and research nurses could not be masked after treatment allocation because of the nature of the intervention . The primary outcome was phlebitis during catheterisation or within 48 h after removal . The equivalence margin was set at 3 % . Primary analysis was by intention to treat . Secondary endpoints were catheter-related bloodstream and local infections , all bloodstream infections , catheter tip colonisation , infusion failure , catheter numbers used , therapy duration , mortality , and costs . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12608000445370 . FINDINGS All 3283 patients r and omised ( 5907 catheters ) were included in our analysis ( 1593 clinical ly indicated ; 1690 routine replacement ) . Mean dwell time for catheters in situ on day 3 was 99 h ( SD 54 ) when replaced as clinical ly indicated and 70 h ( 13 ) when routinely replaced . Phlebitis occurred in 114 of 1593 ( 7 % ) patients in the clinical ly indicated group and in 114 of 1690 ( 7 % ) patients in the routine replacement group , an absolute risk difference of 0·41 % ( 95 % CI -1·33 to 2·15 % ) , which was within the prespecified 3 % equivalence margin . No serious adverse events related to study interventions occurred . INTERPRETATION Peripheral intravenous catheters can be removed as clinical ly indicated ; this policy will avoid millions of catheter insertions , associated discomfort , and substantial costs in both equipment and staff workload . Ongoing close monitoring should continue with timely treatment cessation and prompt removal for complications . FUNDING Australian National Health and Medical Research Council This prospect i ve , r and omized and controlled study verified the influence of three dressing regimens on the dwell time of peripheral intravenous catheters ( PIC ) in children . The study groups were composed of dressings with sterile gauze ( EG 1 ) , with sterile transparent film ( EG 2 ) and with hypoallergenic adhesive tape ( CG ) . Variables were selected to control for variables related to children , professionals and intravenous therapy characteristics . The 150 PIC that composed the sample were inserted in 68 children , predominantly of preschool age , male , with brown skin color , eutrophic and with gastrointestinal system diseases . The majority of the PIC was installed by nursing auxiliaries in veins of the dorsal arch of the h and . The type of dressing exerted a significant influence ( p = 0.022 ) on the average dwell time of the studied PIC : EG 1 ( 46.12 hours ) , EG 2 ( 29.53 hours ) and CG ( 38.18 hours ) , concluding that the dressing with sterile gauze maintained the catheter inserted for a longer time A prospect i ve , sequential clinical trial was undertaken to determine whether any of 3 methods of peripheral IV catheter ( PIV ) securement could extend the average survival time of such catheters sufficiently to allow the implementation of a 96-hour PIV change- protocol . Nonsterile tape , StatLock , and Hub-Guard were evaluated . The use of nonsterile tape securement result ed in an 8 % PIV survival rate , HubGuard produced a 9 % PIV survival rate , and Statlock produced a 52 % PIV survival rate ( P < .001 ) . Although this study was not a r and omized , controlled trial , it strongly suggests that a mechanical catheter securement device , as opposed to tape or die-cut tape , can render practicable the implementation of the 96-hour PIV change protocol that was sanctioned by the Centers for Disease Control and Prevention BACKGROUND Before a meta- analysis by Hoffman et al was published , polyurethane dressings were used at insertion sites for peripheral i.v . catheters at our institution . On the basis of the results of the meta- analysis , we began to use gauze dressings . The change from polyurethane dressings to gauze dressings limited direct observation of the i.v . insertion site , and i.v . catheters were anecdotally reported not to be anchored as securely as before . OBJECTIVES The purpose of this study was to compare the effects of the use of transparent polyurethane dressings and gauze dressings at insertion sites for peripheral i.v . catheters on the frequency of phlebitis , infiltration , and catheter dislodgment by patients . METHODS Two hundred twenty-nine patients were r and omized to receive either gauze ( n = 121 ) or transparent polyurethane ( n = 108 ) dressings , and observations were recorded . RESULTS The frequency of catheter dislodgment by the patient was significantly higher ( P < .05 ) in patients with the gauze dressing ( 15 % ) than in patients with the transparent polyurethane dressing ( 6 % ) . A trend toward lower frequencies of phlebitis ( 1.8 % vs 3.3 % ) and infiltration ( 17.6 % vs 20.7 % ) was noted in the patients with the transparent polyurethane dressings . DISCUSSION The clinical advantages of the transparent polyurethane dressings lie in the ease of direct visualization of the i.v . insertion site and the securement of the i.v . catheter . CONCLUSION At our institution , given the decreased disruption of the i.v . therapy with the transparent polyurethane dressings and the lack of differences in the rates of phlebitis or infiltration with the two types of dressings , we prefer to use transparent polyurethane rather than gauze dressings at insertion sites for peripheral i.v . catheters Previous studies have examined complications with short peripheral catheters , although focus on securement techniques and the relation to catheter dislodgment as an early indicator of potential intravenous complications is limited . The purpose of this study was to examine two methods of peripheral catheter securement : transparent dressing and tape ( control group ) versus transparent dressing and StatLock i.v./PICC ( study group ) and their effects on i.v . complications . One hundred five peripheral catheters were evaluated . The use of transparent dressing and StatLock showed a 45 % reduction in overall i.v . therapy complications when compared with that of transparent dressing and tape ( P = 0.025 ) . In addition , catheter dislodgment episodes were reduced by 40 % ( P = 0.002 ) with the average dwell time extended by 21 hours Objective To compare routine replacement of intravenous peripheral catheters with replacement only when clinical ly indicated . Design R and omised controlled trial . Setting Tertiary hospital in Australia . Participants 755 medical and surgical patients : 379 allocated to catheter replacement only when clinical ly indicated and 376 allocated to routine care of catheter ( control group ) . Main outcome measure A composite measure of catheter failure result ing from phlebitis or infiltration . Results Catheters were removed because of phlebitis or infiltration from 123 of 376 ( 33 % ) patients in the control group compared with 143 of 379 ( 38 % ) patients in the intervention group ; the difference was not significant ( relative risk 1.15 , 95 % confidence interval 0.95 to 1.40 ) . When the analysis was based on failure per 1000 device days ( number of failures divided by number of days catheterised , divided by 1000 ) , no difference could be detected between the groups ( relative risk 0.98 , 0.78 to 1.24 ) . Infusion related costs were higher in the control group ( mean $ A41.02 ; £ 19.71 ; € 24.80 ; $ 38.55 ) than intervention group ( $ A36.40 ) . The rate of phlebitis in both groups was low ( 4 % in intervention group , 3 % in control group ) . Conclusion Replacing peripheral intravenous catheters when clinical ly indicated has no effect on the incidence of failure , based on a composite measure of phlebitis or infiltration . Larger trials are needed to test this finding using phlebitis alone as a more clinical ly meaningful outcome . Registration number Australian New Zeal and Clinical Trials Registry ACTRN12605000147684 A r and omized , controlled study was implemented to verify reasons to release and adverse events related to the use of peripheral intravenous catheters in children , according to the dressing regimens The sample was set at 150 peripheral intravenous catheters , r and omly assigned to three groups : sterile gauze dressings , sterilized transparent film dressings , and non sterile hypoallergenic adhesive tape . The data was collected after consent had been obtained by the Ethics Committee , including children who had been su bmi tted to catheterization with Teflon(R ) over the needle catheters . Statistical tests were performed by applying the Pearson Chi-square test , significance level set at p < 0.05 . The results showed that dressing regimens influenced the reasons for catheter removal and occurrence of adverse events , mainly due to infiltration ( 55.3 % ) . The Sterile gauze showed the best performance ( p=0.002 ) in comparison with the other studied groups , once 40.0 % of the catheters were removed by release from treatment BACKGROUND Few guidelines exist to guide medical personnel on the most successful means of achieving sustained intravenous cannulation . This study examines the impact of gauge and site of intravenous cannulas ( IC ) on the longevity of ICs in hospitalized patients . METHODS A prospect i ve study was conducted on 500 ICs inserted into patients of St Vincent 's Private hospital from December 2005 to June 2006 . Patients were followed until the IC had been removed or changed . Statistical analysis was performed using Cox proportional hazards . RESULTS Of the 500 ICs inserted , 37 % were 18 g , 46 % were 20 g and 18 % were 22 g. Gauge of IC was the most significant predictor of increased longevity of IC ( P = 0.0002 , RR = 1.17 , 95 % CI 1.08 - 1.27 ) . The median survival of 18 , 20 and 22 g were 57 h ( 95 % CI 49 - 72 ) , 43 h ( 95 % CI 36 - 48.5 ) and 29 h ( 95 % CI 24 - 40.5 ) , respectively . The site of IC placement influenced the longevity of ICs ( P = 0.005 , RR= 0.7 , 95 % CI 0.55 - 0.9 ) , as did male gender ( P = 0.03 , RR = 0.76 , 95 % CI 0.6 - 0.97 ) . However in subgroup analysis , the most marked effect on IC longevity was evident in those patients with 18 g placed in the forearm/wrist ( median 72 h ) with less marked changes in other site/gauge combinations . In contrast , 22 g ICs placed in the h and had a median lifespan of 29 h. CONCLUSION IC gauge and site of placement are important factors in determining IC longevity . 18 g ICs placed in the forearm/wrist can considerably increase the longevity of ICs and should be attempted in patients who require sustained cannulation An open-label , prospect i ve , r and omized , noninferiority study was conducted at a large academic , Magnet- design ated , Level I trauma center to compare the peripheral intravenous catheter securement-related complication rates of 2 different stabilization systems . The control stabilization system included the StatLock device with a nonwinged catheter , and the investigational stabilization system included a closed catheter system with a specially design ed Tegaderm dressing . Data from 302 subjects indicated that the investigational stabilization system was noninferior or similar to the control stabilization system with respect to the overall securement-related complications . The cost of the investigational stabilization system was approximately 75 % of the cost for the control stabilization system |
1,773 | 23,919,621 | There is modest evidence to support the assumption that lack of adherence to nicotine replacement therapy regimens undermines effectiveness in clinical studies | AIMS Lack of adherence to smoking cessation medication regimens is assumed to play a significant role in limiting their effectiveness .
This study aim ed to assess evidence for this assumption . | The authors present results of a r and omized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation . Adult smokers ( N = 362 ) received open-label treatment ( 11 weeks ) that combined relapse prevention training , bupropion SR , and nicotine patch followed by extended treatment ( 14 weeks ) with bupropion SR or matching placebo . Abstinence percentages were relatively high ( week 11 : 52 % ; week 25 : bupropion , 42 % ; placebo , 38 % ; week 52 : bupropion , 33 % ; placebo , 34 % ) , but bupropion SR did not surpass placebo . Gender and baseline craving level were identified as significant , independent moderators of treatment response . Men were more likely to abstain than women ( week 11 : 59 % vs. 43 % , p = .001 ; week 25 : 48 % vs. 31 % , p = .001 ; week 52 : 39 % vs. 27 % , p = .01 ) . Because most smokers suffer relapse with any current cessation treatment , the comparatively high abstinence percentages achieved in this trial are of interest INTRODUCTION Varenicline , a first-line non-nicotine medication , has not been evaluated in Black smokers , and limited attention has been paid to pharmacotherapy adherence in smoking cessation trials . This pilot study estimated quit rates for Black smokers treated with varenicline and tested a behavioral intervention to aid varenicline adherence . METHODS Seventy-two Black smokers ( > 10 cigarettes per day ; cpd ) were r and omly assigned to adherence support ( AS ; n = 36 ) or st and ard care ( n = 36 ) . All participants received 3 months of varenicline and a single counseling session focused on making a quit plan . AS participants received 5 additional counseling sessions to encourage medication use . Outcome measures included salivary cotinine , and carbon monoxide confirmed smoking abstinence , reductions in self-reported cpd , and pill counts of varenicline adherence at Months 1 , 2 , and 3 . RESULTS Sixty-one participants ( 84.7 % ) completed follow-up at Month 3 . Participants were female ( 62.5 % ) , 46.8 years of age , and smoked 16.3 cpd . No treatment group differences were found on the smoking or adherence outcome measures ( p > .05 ) . Collapsing across treatment , varenicline adherence was adequate ( 86.1 % ) , yet despite a reduction of 12.2 ( 6.5 ) cpd from baseline to Month 3 ( p < 0.001 ) , only 23.6 % were confirmed quit at Month 3 . Participants who were quit at Month 3 had higher varenicline adherence rates ( 95.8 % ) than those who continued to smoke ( 80.8 % , p ≤ .05 ) . CONCLUSIONS Studies are needed to examine the efficacy of varenicline among Black smokers . Interventions to facilitate adherence to pharmacotherapy warrant further attention as adherence is linked to improved tobacco abstinence Rationale There are over 300 million Chinese smokers , but use of nicotine replacement therapy ( NRT ) is rare . On the other h and , data on the factors associated with quitting and adherence to NRT use are scarce in the East . Objectives To describe adherence and other predictors of quitting smoking at the 12-month follow-up amongst Chinese smokers in Hong Kong . Methods Chinese smokers ( 1186 ) who attended the Smoking Cessation Health Centre from August 2000 through January 2002 were studied . Trained counsellors provided individual counselling and carried out follow-up interviews . We used structured question naires at baseline and at 1 , 3 and 12 months and an intention-to-treat approach for analysis . Results Among those who received NRT ( 1051/1186 ) , the prevalence of adherence ( self-reported NRT use for at least 4 weeks ) was 16 % ( 95 % confidence interval 14–18 % ) . The 7-day point prevalence quit rate at 12 months ( not smoking any cigarette during the past 7 days at the 12 month follow-up ) was 27 % ( 95 % CI , CI 24–29 % ) . Stepwise logistic regression model showed that adherence to NRT use , a higher income , good perceived health and having more confidence in quitting were significant predictors of quitting . The quit rate in the adherent group ( 40 % ) was greater than that of the non-adherent group ( 25 % ) ( P<0.001 ) . Older age , male , higher education , experience of NRT use , perceiving quitting as more difficult and willingness to pay were significant predictors of adherence . Conclusions Clinical ly significant smoking cessation rates can be achieved among Chinese smokers in a clinic-based smoking cessation service . The NRT adherence was low and low adherence was associated with a lower quit rate . Trials of interventions to improve adherence and increase quit rates are needed BACKGROUND A high proportion of African-American smokers are light smokers , and they experience low smoking cessation rates and disproportionately high tobacco-related morbidity ; yet no studies have examined tobacco treatment adherence in this group . OBJECTIVES To determine the predictors of adherence to nicotine gum and counseling among African-American light smokers ( defined as smoking ≤10 cigarettes/day ) , and the effects of adherence on smoking cessation . DESIGN Data were from a 2 × 2 r and omized , placebo-controlled smoking cessation trial of nicotine gum ( 2 mg versus placebo ) and counseling ( motivational interviewing versus health education ) . PARTICIPANTS Seven hundred fifty-five African-American light smokers at a community-based clinic . MEASUREMENTS Demographic and health-related information , smoking behaviors , psychosocial variables , adherence to nicotine gum and counseling , and cotinine-verified 7-day abstinence from smoking at week-26 follow-up . RESULTS A logistic regression model showed that having a higher body mass index ( OR = 1.03 , 95 % CI = 1.01 to 1.05 ) , more quit attempts in the past year ( OR = 1.04 , 95 % CI = 1.01 to 1.07 ) , higher baseline exhaled carbon monoxide ( OR = 1.22 , 95 % CI = 1.01 to 1.48 ) , and higher perceived stress ( OR = 1.12 , 95 % CI = 1.03 to 1.22 ) increased the likelihood of adherence to nicotine gum . Being a high school graduate was a predictor of adherence to counseling ( OR = 1.58 , 95 % CI = 1.02 to 2.44 ) . Surprisingly , being adherent to nicotine gum significantly reduced the odds of smoking cessation ( OR = 0.50 , CI = 0.28 to 0.87 ) . On the other h and , adherence to counseling dramatically increased the likelihood of smoking cessation ( OR = 3.32 , CI = 1.36 to 8.08 ) . CONCLUSIONS Individual risk factors may influence adherence to nicotine gum and counseling . Improving psychological interventions and promoting adherence to counseling may increase overall smoking cessation success among African-American light smokers Nicotine gum has been shown to be effective in improving abstinence rates , and in reducing post-cessation withdrawal distress and weight gain . However , the dose effects of nicotine gum on these outcomes is not known . In the present study , we varied the amount of 2 mg nicotine gum prescribed to motivated quitters to explore the hypotheses ( a ) that motivated quitters would use more pieces of gum when coached and counseled to do so and ( b ) that there would be a dose-related effect of gum use on abstinence , withdrawal symptoms , and weight gain . One hundred seventy-seven volunteers were assigned to chew either 0 , 7 , 15 , or 30 , pieces per day of 2 mg nicotine gum . Biological verification of gum use and smoking abstinence were assessed in community volunteers who attended an intensive behavioral counseling program for smoking cessation while using nicotine gum for 3 months . In the survival analysis at 12 weeks , gum-group assignment was not related to successful abstinence . In the subset of 42 abstinent subjects , there was a strong positive relationship between pieces per day of nicotine gum used and saliva cotinine . However , there was substantial variability in groups of subjects reporting similar amounts of gum use . Withdrawal symptom reporting was not related to either gum use or cotinine levels . Weight gain was significantly related in a dose-dependent manner to salivary cotinine levels , but not to gum group assignment , with high and low cotinine subjects gaining on average , 4.0 and 6.6 pounds , respectively . Discussion of the use of high levels of nicotine gum is addressed . Consistent with earlier work , the study provided further support for the relationship between nicotine replacement level and post-cessation weight gain PURPOSE To determine the effectiveness of the 4-mg and 2-mg dosages of nicotine polacrilex vs placebo through the first 6 weeks of treatment ( during which 75 % of relapse occurs when there is no treatment ) in assisting high-dependent smokers to stop smoking when instructed to use a fixed number ( 12 pieces ) of medication daily . SUBJECTS AND METHODS Ninety high-dependent ( Fagerström Tolerance Question naire score > or = 7 plus baseline carbon monoxide level > 15 ppm ) healthy male and female smokers , highly motivated to quit smoking , were enrolled in a 6-week , r and omized , double-blind , placebo-controlled trial in which they were instructed to use 12 pieces per day of their assigned dosage formulation : 4 mg , 2 mg , or 0.5 mg ( placebo ) of nicotine polacrilex . The behavioral intervention did not depend on providing any special psychological training , skills , or services but rather employed a st and ard medical practice model that could easily be implemented by any primary care physician . RESULTS Sustained abstinence from weeks 2 through 6 , determined at each visit by absolutely no cigarette use plus a carbon monoxide level of 8 ppm or lower was 59 % ( 4-mg group ) , 30 % ( 2-mg group ) , and 39 % ( placebo group ) ( P < .02 ) . For the 55 of the 90 smokers who met the originally planned definition of high dependence ( Fagerström Tolerance Question naire score > or = 7 plus baseline smoking serum cotinine level > 250 ng/mL plus baseline carbon monoxide level > 15 ppm ) , results were 63 % ( 4-mg group ) , 25 % ( 2-mg group ) , and 25 % ( placebo group ) ( P < .02 ) . In addition , the 4-mg dose produced statistically significantly higher abstinence rates in compliant subjects ( P < .02 ) and also in subjects with high baseline serum continine levels who were compliant ( P < .01 ) than did either the 2-mg dose or placebo . CONCLUSIONS It appears that the 4-mg dose of nicotine polacrilex is the drug and dose of choice for the initial phase of tobacco dependence treatment in high-dependent smokers ; the 2-mg dose of nicotine polacrilex is not better than placebo during the first 6 weeks of treatment for high-dependent cigarette smokers , and thus should not be used for these patients during the initial treatment phase This correlational study examined the adherence rates of transdermal nicotine ( TN ) use among a population of males and females 18 years of age and older ( N = 619 ) who received varying levels of behavioral intervention . Rates of patch adherence were assessed for demographic ( e.g. , gender , ethnicity , and age ) , income- , smoking- [ e.g. , baseline carbon monoxide ( CO ) , nicotine dependence , and follow-up quit status ] , and treatment-related ( e.g. , condition , and drop status ) variables . Loglinear and logistic regression analyses were performed to assess adherence rates . Results indicated that male gender [ chi2(2 , n = 485 ) = 20.39 , P = .038 ] , not dropping out of the study [ chi2(2 , n = 485 ) = 13.94 , P < .001 ] , and intensive treatment ( compared to the st and ard care ) [ chi2(4 , n = 485 ) = 14.96 , P = .005 ] were associated with greater adherence to TN . Furthermore , patch adherence was associated with quit status at 6 months ( OR = 2.47 , CI = 1.56 - 3.91 , P < .001 ) and 12 months ( OR = 2.12 , CI = 1.34 - 3.37 , P = .001 ) . Complete and partial patch adherence ( compared to minimal/no adherence ) were associated with a greater number of telephone intervention contacts completed ( OR = 2.621 , CI = 1.421 - 4.832 , P = .002 ) . Noteworthy however , was the lack of association between level of income and patch adherence . These findings suggest characteristics of those more and less likely to adhere to TN in research and clinical setting OBJECTIVE To evaluate the efficacy of a new nicotine inhaler system for smoking cessation . DESIGN A 1-year , r and omized , double-blind , placebo-controlled study . SETTING Medical outpatient clinic with physicians experienced in smoking cessation assistance . SUBJECTS A total of 286 volunteers who smoked at least 10 cigarettes daily recruited through a local newspaper . INTERVENTION Subjects were r and omly allocated to nicotine inhalers ( n = 145 ) or placebo ( n = 141 ) to be used for 3 months followed by tapering for 3 months in the context of minimal levels of advice and support . MAIN OUTCOME MEASURE Continuous smoking abstinence at weeks 6 , 12 , 24 , and 52 , verified by measurements of carbon monoxide in expired air . RESULTS Continuous smoking abstinence was significantly higher for the active nicotine inhaler group compared with the placebo inhaler group . The respective success rates were 28 % and 12 % after 6 weeks , 21 % and 9 % after 12 weeks , 17 % and 8 % after 6 months , and 15 % and 5 % after 1 year ( P = .02 to .001 ) . The mean nicotine substitution based on cotinine determinations after 2 weeks was 43 % ( SD , 45 % ) of smoking levels . The treatment was well tolerated , and no serious adverse events were reported . CONCLUSIONS In this setting the nicotine inhaler appeared safe to use and increased success rates of smoking cessation attempts This study was conducted to replicate and extend initial positive findings on the usefulness of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance with bupropion for smoking cessation . Participants ( N=55 ) received MEMS bottles containing bupropion-SR ( 150 mg ) to be taken twice daily for 7 weeks . For participants r and omly assigned to the Enhanced Therapy group ( n=27 ) , weekly individual smoking cessation therapy sessions included an additional 10 min of MEMS feedback and compliance enhancement counseling using CBT techniques . The Usual Care group ( n=28 ) received weekly individual smoking cessation sessions only . Compliance outcomes included total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the Enhanced Therapy group . Smoking abstinence rates did not differ between the two groups , although results from the pooled sample analysis showed a significant association between level of medication compliance and abstinence status at treatment weeks 3 and 6 . Incorporating MEMS-based compliance interventions into smoking pharmacotherapy trials is recommended BACKGROUND It has been reported that the efficacy of acute forms of nicotine replacement therapy , such as nicotine gum and lozenges , improves when sufficient quantities of medication are used . OBJECTIVE This analysis examined whether adherence with daily nicotine patch wear was associated with improved rates of smoking abstinence . METHODS This was a secondary analysis of data from a double-blind study in which subjects were r and omized to receive either an active nicotine patch or a placebo patch under simulated over-the-counter conditions . Subjects were asked to complete a daily diary on their patch use and smoking . Logistic regression , controlling for smoking in the first 3 weeks of treatment , was used to evaluate the likelihood of abstinence at 6 weeks as a function of treatment assignment ( active vs placebo ) and adherence ( ie , patch wear for > or=20 of the first 21 days of treatment ) . The relationship between reported adverse events and adherence was also examined . RESULTS This analysis involved data from 371 subjects , 204 using the active patch and 167 using the placebo patch . The study population was mainly white ( 87.3 % ) , had a mean age of 42.8 years , a mean weight of 77.3 kg , had been smoking for a mean of 24.4 years , and smoked a mean of 25.2 cigarettes per day . Two hundred fifty-three subjects were classified as adherent . Rates of adherence did not differ significantly between the active and placebo groups ( 139 [ 68.1 % ] and 114 [ 68.3 % ] , respectively ) . The likelihood of experiencing an adverse event did not differ significantly between adherent and nonadherent subjects in either group . Among active patch users , 61.5 % of nonadherent subjects experienced an adverse event , compared with 59.7 % of adherent subjects ; among placebo patch users , the corresponding proportions were 41.5 % and 43.9 % . Among active patch users , the odds of abstinence at 6 weeks were more than 3 times greater for adherent versus nonadherent subjects ( 53.2 % vs 21.5 % , respectively ; adjusted odds ratio [ OR ] = 3.25 ; 95 % CI , 1.30 - 8.09 ; P = 0.011 ) ; no benefit of adherence over nonadherence was seen among users of the placebo patch ( 16.7 % vs 15.1 % ; adjusted OR = 0.60 ; 95 % CI , 0.16 - 2.31 ) . The interaction between treatment group and adherence was statistically significant ( P = 0.022 ) . CONCLUSION Under conditions simulating over-the-counter use , adherence to daily nicotine patch wear within the first 3 weeks of treatment was associated with an improved likelihood of achieving smoking abstinence at 6 weeks OBJECTIVE To assess transdermal nicotine use patterns and outcomes in a population of low-income older smokers . DESIGN A 6-month telephone follow-up survey of smokers filling prescriptions for transdermal nicotine in the first 3 months of 1992 . SETTING Pennsylvania 's Pharmaceutical Assistance Plan for the Elderly , the nation 's largest state-level prescription plan for the elderly . POPULATION A total of 1070 noninstitutionalized male and female smokers aged 65 through 74 years . MAIN OUTCOME MEASURES Self-reported physician/pharmacist advice and adjunctive treatments , concomitant smoking , and 6-month smoking abstinence . RESULTS Respondents were predominantly long-term heavy smokers . They used nicotine patches for an average of 5 weeks , with few reporting use beyond 3 months or recalling bothersome side effects . Most of those with previous quit attempts rated quitting with the patch " easier . " The 29 % self-reported 6-month quit rate observed is encouraging . However , compliance with patch use guidelines was far from ideal in this high-risk population : only 54 % of respondents received any initial advice or material s from their physicians or pharmacists , fewer than 2 % took part in a formal clinic or one-to-one treatment program , and almost half ( 47 % ) smoked while using the patch , including 20 % who smoked every day . Concomitant smoking was strongly associated with failure to achieve abstinence ( P < .001 ) . More frequent contact with physicians and /or pharmacists was associated with less concomitant smoking ( P < .001 ) and higher quit rates ( P = .005 ) . CONCLUSIONS This survey offers an important first look at problems and prospect s for nicotine patch therapy in older adults , with implication s for other groups as well . Prospect i ve studies are needed to clarify optimal treatment regimens and adjuncts The effect of different follow-up programs reinforced or not reinforced with the nicotine chewing gum Nicorette was tested by 13 physicians working in the open health care system . A total of 151 patients were advised to stop smoking , and were asked to participate in the program if judged sufficiently motivated by the physicians . After inclusion they were r and omized into short or long follow-up , and nicotine gum vs no gum . The physicians conducted the follow-up therapy in their own personal way . Short follow-up was comprised of one appointment 14 days after cessation , while long follow-up consisted of a telephone call ( 1 week ) , an appointment ( 2 weeks ) , a second appointment ( 1 month ) , and a letter ( 3 months ) . The results at 12 months were that long follow-up showed a trend ( P less than 0.12 toward being better than short follow-up , while nicotine gum was significantly better than no gum ( P less than 0.05 ) in maintaining abstinence . The group with the best outcome was the one receiving long follow-up and nicotine gum , which yielded an expired air carbon monoxide-controlled , 12-month abstinence rate of 27 % . The abstinence outcomes at 12 months for the other groups were short follow-up and nicotine gum , 22 % ; long follow-up and no gum , 15 % ; and short follow-up and no gum , 3 % . The physicians ' reactions to the smoking cessation treatment were largely positive . The nicotine gum seems to be a relatively simple , cost-effective , and practical tool for physicians to enhance and reinforce their antismoking advice . With a longer active follow-up period than was used here ( 1 month ) , even better results may be possible Eighty-nine smokers were r and omly assigned to four nicotine gum treatments for smoking cessation : behavioral treatment plus a fixed schedule of nicotine gum , behavioral treatment plus an ad lib schedule , education plus a fixed schedule , and education plus an ad lib schedule . The four treatment conditions produced similar rates of abstinence ( 40.9 % to 58.3 % ) at the end of 11 weeks of treatment . However , at 6-month follow-up , the subjects who had received behavioral treatment had a significantly better abstinence rate ( 36.7 % ) than those receiving education ( 17.5 % ) . Nicotine gum schedule had no effect on treatment outcome In a controlled trial of brief treatment for smoking using nicotine chewing gum in a workplace setting , 270 of 334 cigarette smokers who expressed interest were invited to take part in the program , which consisted of two individual consultations ; 172 attended . The remaining 64 smokers constituted a no-intervention control group . Using a criterion of sustained one-year abstinence with biochemical validation , success rates were 12 per cent among participants , 1 per cent among those who were invited but did not attend , and 2 per cent in the control group Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women . It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered . This study used a two level factorial design to examine the independent and interactive effects of medication ( bupropion 300 mg/day vs. placebo ) and psychotherapy ( cognitive-behavioral therapy [ CBT ] vs. supportive therapy [ ST ] ) . In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments , we examined medication compliance and its role in the efficacy of bupropion . Participants were 154 women , aged at least 30 years and smoking more than 10 cigarettes/day . Compliance with study medication was assessed using Medication Event Monitoring Systems ( MEMS ) over 7 weeks of treatment . Psychological interventions were delivered in 60-min weekly group sessions . Longitudinal analysis of abstinence outcomes from end of treatment ( EOT ) through 12 months after treatment revealed a significant interaction of medication and therapy . Higher abstinence rates at EOT and 3- , 6- , 9- , and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT ( 44 % , 24 % , 30 % , 23 % , 17 % ) rather than with ST ( 18 % , 1 % , 8 % , 5 % , 2 % ) . The bupropion-CBT combination , however , was not clearly superior to placebo , regardless of therapy assignment . Higher rates of medication compliance were positively predictive of abstinence , and this effect was most evident in the placebo condition . Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women INTRODUCTION Patient adherence to smoking cessation medications can impact their effectiveness . It is important to underst and the extent to which prescribed medications are actually taken by smokers , how this influences smoking cessation outcomes , and what factors may influence adherence . METHODS Smokers recruited from a large health plan were r and omized to receive different modes of cessation counseling in combination with varenicline ( Swan , G. E. , McClure , J. B. , Jack , L. M. , Zbikowski , S. M. , Javitz , H. S. , Catz , S. L. , et al. 2010.Behavioral counseling and varenicline treatment for smoking cessation . American Journal of Preventive Medicine , 38 , 482 - 490 ) . One thous and one hundred and sixty-one participants were mailed a 28-day varenicline supply when they set a quit date and were able to request up to two refills from the health plan pharmacy at no cost . Pharmacy fill records were obtained and telephone surveys completed at baseline , 21 days , 12 weeks , and 6 months post target quit date . RESULTS Good adherence to varenicline ( ≥80 % of days taken ) was associated with a twofold increase in 6-month quit rates compared with poor adherence ( 52 % vs. 25 % ) . Smokers were more likely than nonsmokers to stop varenicline early . Purpose ful nonadherence was associated with smoking at 12 weeks and was predicted in multivariate analyses by age , gender , adherence self-efficacy , and initial medication side effect severity . CONCLUSIONS Innovative methods for increasing adherence to smoking cessation medications are needed , particularly early in the quit process . Simple metrics of adherence such as number of days cessation medication is taken can and should be routinely incorporated in effectiveness trials and reported to advance future attempts to underst and and reduce nonadherence INTRODUCTION Detailed analysis of adherence to tobacco cessation medications and predictors of adherence is sparse in published literature . In this analysis , we assessed adherence to tobacco dependence treatment , association of adherence with abstinence , and predictors of adherence . METHODS We analyzed pooled results from 2 r and omized controlled trials . Adult smokers ( N = 2,045 ) who were r and omly assigned to 12 weeks of treatment and took at least 1 dose of the assigned medication ( varenicline [ 692 ] , bupropion sustained release [ 669 ] , or placebo [ 684 ] ) were included . Treatment adherence was defined as any subject who took > or=1 dose of study drug for > or=80 % days during the 12-week treatment period ( " completers " ) . Smoking abstinence was assessed using carbon monoxide-confirmed 4-week continuous abstinence rate at end of treatment ( Weeks 9 - 12 ) . RESULTS Adherence rates for completers who received varenicline , bupropion , and placebo groups , respectively , were 99.3 % , 98.8 % , and 99.2 % . There was a positive correlation between adherence to treatment and tobacco abstinence in all treatment groups . Treatment effect sizes ( odds ratios ) for active therapy compared with placebo were similar whether considering all subjects or only the completer subset . Age , cigarettes per day , and Week-2 abstinence were significant predictors of adherence for all treatment groups ( all p < .05 ) , with Week-2 abstinence the strongest predictor . DISCUSSION Adherence to pharmacotherapy for smoking cessation is highly correlated with improved tobacco abstinence . Early abstinence experience is a strong driver of adherence Smokers ( N = 224 ) were r and omized to 1 of 3 groups : ( a ) transdermal system ( TNS ) + placebo ; ( b ) TNS + paroxetine ( 20 mg ) ; ( c ) TNS + paroxetine ( 40 mg ) . Assignment to treatment was double-blind . Nicotine patch ( TNS ) treatment was provided for 8 weeks ; paroxetine or placebo was provided for 9 weeks . Abstinence rates at Weeks 4 , 10 , and 26 were as follows : ( a ) TNS + placebo : 45 % , 36 % , and 25 % ; ( b ) TNS + paroxetine ( 20 mg ) : 48 % , 33 % , and 21 % ; ( c ) TNS + paroxetine ( 40 mg ) : 57 % , 39 % , and 27 % . The differences were not statistically significant . The combined treatment was more effective in reducing both craving and depression symptoms associated with smoking cessation . A subgroup analysis comparing compliant participants was also conducted . Abstinence rates at Weeks 4 , 10 , and 26 were as follows : ( a ) TNS + placebo : 46 % , 35 % , and 24 % ; ( b ) TNS + paroxetine ( 20 mg ) : 64 % , 43 % , and 33 % ; ( c ) TNS + paroxetine ( 40 mg ) : 74 % , 51 % , and 38 % . The differences between paroxetine groups and placebo at Week 4 were statistically significant . Although paroxetine may add value to the current st and ard of care in excess of potential risk , more conclusive evidence is needed The patch adherence behavior of 101 smokers receiving 8 weeks of the nicodermal patch was examined while undergoing one of three levels of adjunctive psychosocial treatment . Additionally , regression analyses were undertaken to : ( 1 ) identify subject variables predictive of patch adherence and ( 2 ) to determine the predictive validity of patch treatment dropout , smoking and patch adherence during patch treatment to smoking 9 and 26 weeks post-treatment entry . Fifty-five percent of the patients wore the patch as prescribed for at least 50 of 56 treatment days . A multiple regression model including the Fagerström severity of dependence score , psychosocial treatment group , and the URICA commitment score predicted 18 % of the variance in days of patch use . All treatment dropouts were found to be smoking at followup . Although both smoking and low patch compliance during treatment were significant predictors subjects of week 9 and 26 smoking for the remaining subjects , at the individual variable level of analysis , only smoking during treatment predicted week 9 and 26 outcomes in a two-variable predictor model This study , which tested two motivational interviewing treatment approaches , assessed the feasibility of conducting a community-based smoking cessation intervention among homeless smokers . Participants ( N = 46 ) were recruited from multiple facilities in the Kansas City area and were r and omized to two counseling conditions in which they received five individual motivational interviewing sessions , six group meetings , and their choice of 8 weeks of 21-mg nicotine patch or 4-mg nicotine lozenge . The two counseling conditions consisted of motivational interviewing targeted either to smoking behaviors exclusively ( smoking only ) or to smoking and other addictions or life events that could affect ability to quit ( smoking plus ) . Group meetings were design ed to provide educational information and social support . Measures of feasibility assessed included the proportion of participants who returned for r and omization among those eligible , adherence to prescribed nicotine replacement therapies , retention rates at the week 26 final study visit , and biochemically verified 7-day abstinence at week 26 . Most participants ( 69.6 % ) chose nicotine patches , and 32 % of those participants reported using at least four patches per week . Carbon monoxide verified 7-day abstinence rates in the smoking-only and smoking-plus groups were 13.04 % and 17.39 % ( ns ) , respectively , at week 8 and 8.70 % and 17.39 % ( ns ) , respectively , at week 26 . Participants who used at least four patches per week were more likely to have quit at 8 weeks than were those who used fewer patches ( 33.3 % vs. 10.5 % , p = .30 ) . Results support the feasibility of conducting a smoking cessation intervention among homeless smokers . Findings also show promising effects for nicotine replacement therapy and counseling in this population . Developing programs to improve smoking cessation outcomes in underserved population s is an essential step toward achieving national health objectives and for ultimately reducing tobacco-related health disparities Heavy smokers ( N = 408 , smoking more than 25 cigarettes/day ) were r and omized to receive high-dose ( 25 mg ) or st and ard-dose ( 15 mg ) nicotine patch therapy delivered during the daytime only ( 16 hr ) for a period of 6 weeks . Treatment effects of each dose were similar . The percentages of participants not smoking at 2- , 6- , and 12-month follow-ups were 26 versus 20 , 14 versus 16 , and 14 versus 14 for the 15-mg and 25-mg doses , respectively . The higher dose was well tolerated , and adverse event profiles for both treatment doses were very similar . Stepwise Cox proportional hazards analyses indicated that initial postr and omization craving and baseline scores on the Center for Epidemiological Studies Depression Instrument predicted time-to-relapse during treatment ; only initial craving predicted relapse over the entire study interval ( 12 months ) . The results of this trial do not support the routine use of higher dose nicotine patch therapy in the treatment of nicotine dependence A total of 424 smokers were r and omized in a 2 x 2 factorial experiment . A pharmacologic factor contained 2 levels : transdermal nicotine path ( TNP ; 21 mg ) and placebo . A self-help behavioral treatment factor contained 2 levels : video-enhanced self-help treatment manual and self-help treatment manual only . At 2 months , TNP produced a higher level of abstinence ( 36 % ) than placebo ( 20 % ) , p < .001 . No other comparison was significant . In secondary analyses , ( at 2 months ) and compliance with patch treatment regimen ( at 2 , 6 , and 12 months ) were associated with less relapse . Although nicotine replacement therapy has improved our ability to produce smoking cessation , the production of sustained , longer term abstinence remains an elusive goal This article reports a series of r and omized controlled studies in four companies in the United Kingdom which were design ed to evaluate minimal smoking intervention programs based on the use of motivational videotapes or nicotine chewing gum . In the videotape studies , groups of smokers ( N = 603 ) were r and omly assigned to watch one of several different videotapes . They were followed-up , along with non participants ( N = 1,015 ) , at 3 months and again at 1 year , and a biochemical validation of abstinence was performed . There were significant differences between the videotape conditions with regard to attitudes assessed immediately after exposure ( intention and fear ) and the proportion of smokers who tried to stop , but there were no significant differences in cessation , even in the short term . Using a strict definition of abstinence , long-term abstinence rates were under 10 % in all four studies . In one company , we also investigated the effect of offering brief individual treatment based on nicotine chewing gum to a r and omly chosen 50 % sample of the videotape group ( N = 161 ) still smoking at the 3-month follow-up . The treatment course was administered by occupational health nurses and consisted of four short consultations over a 12-week period . The results were encouraging : 16 % of those who took the offer stopped during treatment and were still abstinent 1 year after the start of treatment compared with only 2 % of the r and omized no-intervention control group and 0 % of those who were invited but did not attend |
1,774 | 28,350,135 | In conclusion , available evidence supports an association of main air pollutants with increased arterial stiffness and reflected waves .
This finding may have implication s for population -based strategies for the reduction of arterial stiffness , a vascular biomarker and an intermediate endpoint for cardiovascular disease | Arterial stiffening is associated with increased cardiovascular risk .
Whether exposure to relatively high levels of air pollution is associated with arterial stiffening is unclear .
We aim ed to assess the association between exposure to major air pollutants and arterial stiffening . | Background — Aortic stiffness is a marker of cardiovascular disease and an independent predictor of cardiovascular risk . Although an association between inflammatory markers and increased arterial stiffness has been suggested , the causative relationship between inflammation and arterial stiffness has not been investigated . Methods and Results — One hundred healthy individuals were studied according to a r and omized , double-blind , sham procedure-controlled design . Each sub study consisted of 2 treatment arms , 1 with Salmonella typhi vaccination and 1 with sham vaccination . Vaccination produced a significant ( P<0.01 ) increase in pulse wave velocity ( at 8 hours by 0.43 m/s ) , denoting an increase in aortic stiffness . Wave reflections were reduced significantly ( P<0.01 ) by vaccination ( decrease in augmentation index of 5.0 % at 8 hours and 2.5 % at 32 hours ) as a result of peripheral vasodilatation . These effects were associated with significant increases in inflammatory markers such as high-sensitivity C-reactive protein ( P<0.001 ) , high-sensitivity interleukin-6 ( P<0.001 ) , and matrix metalloproteinase-9 ( P<0.01 ) . With aspirin pretreatment ( 1200 mg PO ) , neither pulse wave velocity nor augmentation index changed significantly after vaccination ( increase of 0.11 m/s and 0.4 % , respectively ; P = NS for both ) . Conclusions — This is the first study to show through a cause- and -effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness and to a decrease in wave reflections . These findings have important implication s , given the importance of aortic stiffness for cardiovascular function and risk and the potential of therapeutic interventions with antiinflammatory properties Background —Aortic pulse wave velocity ( PWV ) is a predictor of mortality in patients with end-stage renal failure ( ESRF ) . The PWV is partly dependent on blood pressure ( BP ) , and a decrease in BP can attenuate the stiffness . Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated . Methods and Results —One hundred fifty ESRF patients ( aged 52±16 years ) were monitored for 51±38 months . From entry until the end of follow-up , the changes of PWV in response to decreased BP were measured ultrasonographically . BP was controlled by adjustment of “ dry weight ” and , when necessary , with ACE inhibitors , calcium antagonists , and /or & bgr;-blockers , in combination if necessary . Fifty-nine deaths occurred , including 40 cardiovascular and 19 noncardiovascular events . Cox analyses demonstrated that independent of BP changes , the predictors of all-cause and cardiovascular mortality were as follows : absence of PWV decrease in response to BP decrease , increased left ventricular mass , age , and preexisting cardiovascular disease . Survival was positively associated with ACE inhibitor use . After adjustment for all confounding factors , the risk ratio for the absence of PWV decrease was 2.59 ( 95 % CI 1.51 to 4.43 ) for all-cause mortality and 2.35 ( 95 % CI 1.23 to 4.41 ) for cardiovascular mortality . The risk ratio for ACE inhibitor use was 0.19 ( 95 % CI 0.14 to 0.43 ) for all-cause mortality and 0.18 ( 95 % CI 0.06 to 0.55 ) for cardiovascular mortality . Conclusions —These results indicate that in ESRF patients , the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes Introduction Exposure to air pollution is associated with increased cardiovascular morbidity , although the underlying mechanisms are unclear . Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load . We determined the effect of diesel exhaust exposure on arterial compliance using a vali date d non-invasive measure of arterial stiffness . Methods In a double-blind r and omized fashion , 12 healthy volunteers were exposed to diesel exhaust ( approximately 350 μg/m3 ) or filtered air for one hour during moderate exercise . Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis ( PWA ) , as well as at the femoral and carotid arteries for pulse wave velocity ( PWV ) . PWA was performed 10 , 20 and 30 min , and carotid-femoral PWV 40 min , post-exposure . Augmentation pressure ( AP ) , augmentation index ( AIx ) and time to wave reflection ( Tr ) were calculated . Results Blood pressure , AP and AIx were generally low reflecting compliant arteries . In comparison to filtered air , diesel exhaust exposure induced an increase in AP of 2.5 mmHg ( p = 0.02 ) and in AIx of 7.8 % ( p = 0.01 ) , along with a 16 ms reduction in Tr ( p = 0.03 ) , 10 minutes post-exposure . Conclusion Acute exposure to diesel exhaust is associated with an immediate and transient increase in arterial stiffness . This may , in part , explain the increased risk for cardiovascular disease associated with air pollution exposure . If our findings are confirmed in larger cohorts of susceptible population s , this simple non-invasive method of assessing arterial stiffness may become a useful technique in measuring the impact of real world exposures to combustion derived-air pollution Background — Rheumatoid arthritis ( RA ) is associated with increased cardiovascular risk , which is not explained by traditional cardiovascular risk factors but may be due in part to increased aortic stiffness , an independent predictor of cardiovascular mortality . In the present study , our aim was to establish whether aortic stiffness is increased in RA and to investigate the relationship between inflammation and aortic stiffness . In addition , we tested the hypothesis that aortic stiffness could be reduced with anti – tumor necrosis factor-&agr ; ( TNF-&agr ; ) therapy . Methods and Results — Aortic pulse-wave velocity ( PWV ) , augmentation index , and blood pressure were measured in 77 patients with RA and in 142 healthy individuals . Both acute and chronic inflammatory measures and disease activity were determined . The effect of anti-TNF-&agr ; therapy on PWV and endothelial function was measured in 9 RA patients at 0 , 4 , and 12 weeks . Median ( interquartile range ) aortic PWV was significantly higher in subjects with RA than in control subjects ( 8.35 [ 7.14 to 10.24 ] versus 7.52 [ 6.56 to 9.18 ] m/s , respectively ; P=0.005 ) . In multiple regression analyses , aortic PWV correlated independently with age , mean arterial pressure , and log-transformed C-reactive protein ( R2=0.701 ; P<0.0001 ) . Aortic PWV was reduced significantly by anti-TNF-&agr ; therapy ( 8.82±2.04 versus 7.94±1.86 versus 7.68±1.56 m/s at weeks 0 , 4 , and 12 , respectively ; P<0.001 ) ; concomitantly , endothelial function improved . Conclusions — RA is associated with increased aortic stiffness , which correlates with current but not historical measures of inflammation , suggesting that increased aortic stiffness may be reversible . Indeed , anti-TNF-&agr ; therapy reduced aortic stiffness to a level comparable to that of healthy individuals . Therefore , effective control of inflammation may be of benefit in reducing cardiovascular risk in patients with RA AIMS Episodes of increased air pollution are associated with increases in hospital admissions for cardiovascular disease . Even modest acute phase responses are associated with increased risk of coronary heart disease . The study investigates whether induction of an acute phase response by exposure to air pollution may contribute to cardiovascular pathology . METHODS AND RESULTS A prospect i ve cohort study based on a survey in 1984/85 with a 3-year follow-up was conducted in 631 r and omly selected men aged 45 to 64 years free of cardiovascular disease at entry 1984/85 . Serum C-reactive protein concentrations were determined by a high sensitivity immunoradiometric assay . C-reactive protein concentration was increased in association with the 1985 air pollution episode . In multivariate analyses , elevated concentrations were independently associated with concentrations of total suspended particles and the sulphur dioxide episode . At ambient concentrations of pollution , as noted during the 1985 air pollution episode , the odds of observing C-reactive protein concentrations above 5.7 mg . l(-1)(>90th percentile ) tripled , and increases of 26 microg . m(-3)total suspended particles ( mean of 5 days ) raised the odds of C-reactive protein levels 50 % above the 90th percentile . CONCLUSIONS Exposure to current levels of particulate matter in the atmosphere elicits an acute phase response in r and omly selected healthy middle-aged men , which may contribute to the increased cardiovascular risk caused by air pollution |
1,775 | 30,779,976 | Very low certainty of evidence suggests that post-cardiac arrest care at CACs is associated with improved outcomes at hospital discharge . | AIM To perform a systematic review to answer ' In adults with attempted resuscitation after non-traumatic cardiac arrest does care at a specialised cardiac arrest centre ( CAC ) compared to care in a healthcare facility not design ated as a specialised cardiac arrest centre improve patient outcomes ? ' | OBJECTIVE To assess the association between favourable neurological outcome and hospital characteristics such as hospital volume and number of critical care centres ( CCMCs ) after out-of-hospital cardiac arrest ( OHCA ) . METHODS This retrospective , population -based observational study conducted in Osaka Prefecture , Japan included adult patients with OHCA , aged ≥18 years who were transported to acute care hospitals between January 2005 and December 2012 . We divided acute care hospitals into CCMCs or non-CCMCs , the latter of which were divided into the following three groups according to the annual average number of transported OHCA cases : low-volume ( ≤10 cases ) , middle-volume ( 11 - 39 cases ) , and high-volume ( ≥40 cases ) groups . R and om effects logistic regression models , with hospital treated as a r and om effect , were used to assess factors potentially associated with a favourable neurological outcome . RESULTS A total of 44,474 patients were eligible . The proportions of favourable neurological outcome from OHCA were 0.9 % ( 31/3559 ) in the low-volume group , 1.2 % ( 106/9171 ) in the middle-volume group , 1.6 % ( 222/14,007 ) in the high-volume group , and 4.3 % ( 766/17,737 ) in the CCMC group ( P<0.001 ) . In the multivariable analysis , transport to CCMCs was significantly associated with favourable neurological outcome , compared with transport to non-CCMCs ( adjusted odds ratio 1.63 ; 95 % confidence interval , 1.60 - 1.66 ) . Among the non-CCMC group , there was no significant relationship between hospital volume and favourable neurological outcome . CONCLUSIONS In this population , transport of OHCA patients to CCMCs led to significantly higher one-month survival rates with favourable neurological outcome from OHCA , whereas no significant association was noted among the hospitals with different volumes BACKGROUND Wide variation exists in inter-hospital survival from out-of-hospital cardiac arrest ( OHCA ) . Regionalisation of care into cardiac arrest centres ( CAC ) may improve this . We report a pilot r and omised trial of expedited transfer to a CAC following OHCA without ST-elevation . The objective was to assess the feasibility of performing a large-scale r and omised controlled trial . METHODS Adult witnessed ventricular fibrillation OHCA of presumed cardiac cause were r and omised 1:1 to either : ( 1 ) treatment : comprising expedited transfer to a CAC for goal -directed therapy including access to immediate reperfusion , or ( 2 ) control : comprising current st and ard of care involving delivery to the geographically closest hospital . The feasibility of r and omisation , protocol adherence and data collection of the primary ( 30-day all-cause mortality ) and secondary ( cerebral performance category ( CPC ) ) and in-hospital major cardiovascular and cerebrovascular events ( MACCE ) clinical outcome measures were assessed . RESULTS Between November 2014 and April 2016 , 118 cases were screened , of which 63 patients ( 53 % ) met eligibility criteria and 40 of the 63 patients ( 63 % ) were r and omised . There were no protocol deviations in the treatment arm . Data collection of primary and secondary outcomes was achieved in 83 % . There was no difference in baseline characteristics between the groups : 30-day mortality ( Intervention 9/18 , 50 % vs. Control 6/15 , 40 % ; P=0.73 ) , CPC 1/2 ( Intervention : 9/18 , 50 % vs. Control 7/14 , 50 % ; P>0.99 ) or MACCE ( Intervention : 9/18 , 50 % vs. Control 6/15 , 40 % ; P=0.73 ) . CONCLUSIONS These findings support the feasibility and acceptability of conducting a large-scale r and omised controlled trial of expedited transfer to CAC following OHCA to address a remaining uncertainty in post-arrest care AIM Survival after out-of-hospital cardiac arrest ( OOHCA ) varies between regions , but the contribution of different factors to this variability is unknown . This study examined whether survival to hospital discharge was related to receiving hospital characteristics , including bed number , capability of performing cardiac catheterization and hospital volume of OOHCA cases . MATERIAL AND METHODS Prospect i ve observational data base of non-traumatic OOHCA assessed by emergency medical services was created in 8 US and 2 Canadian sites from December 1 , 2005 to July 1 , 2007 . Subjects received hospital care after OOHCA , defined as either ( 1 ) arriving at hospital with pulses , or ( 2 ) arriving at hospital without pulses , but discharged or died > or = 1 day later . RESULTS A total of 4087 OOHCA subjects were treated at 254 hospitals , and 32 % survived to hospital discharge . A majority of subjects ( 68 % ) were treated at 116 ( 46 % ) hospitals capable of cardiac catheterization . Unadjusted survival to discharge was greater in hospitals performing cardiac catheterization ( 34 % vs. 27 % , p=0.001 ) , and in hospitals that received > or = 40 patients /year compared to those that received < 40 ( 37 % vs. 30 % , p=0.01 ) . Survival was not associated with hospital bed number , teaching status or trauma center design ation . Length of stay ( LOS ) for surviving subjects was shorter at hospitals performing cardiac catheterization ( p<0.01 ) . After adjusting for all variables , there were no independent associations between survival or LOS and hospital characteristics . CONCLUSIONS Some subsets of hospitals displayed higher survival and shorter LOS for OOHCA subjects but there was no independent association between hospital characteristics and outcome INTRODUCTION The aim of the EuReCa ONE study was to determine the incidence , process , and outcome for out of hospital cardiac arrest ( OHCA ) throughout Europe . METHODS This was an international , prospect i ve , multi-centre one-month study . Patients who suffered an OHCA during October 2014 who were attended and /or treated by an Emergency Medical Service ( EMS ) were eligible for inclusion in the study . Data were extracted from national , regional or local registries . RESULTS Data on 10,682 confirmed OHCAs from 248 regions in 27 countries , covering an estimated population of 174 million . In 7146 ( 66 % ) cases , CPR was started by a byst and er or by the EMS . The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year . 1735 had ROSC on arrival at hospital ( 25.2 % ) , Overall , 662/6414 ( 10.3 % ) in all cases with CPR attempted survived for at least 30 days or to hospital discharge . CONCLUSION The results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe . EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe . Using these data and analyses , different countries , regions , systems , and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events PURPOSE As post-cardiac arrest care may influence patients ' outcome , characteristics of receiving hospitals should be integrated in the evaluation of survival . We aim ed at assessing the influence of care level center on patients ' survival at hospital discharge using a regional registry of out-of-hospital cardiac arrest patients ( OHCA ) . METHODS We retrospectively analysed a Utstein and in-hospital data prospect ively collected for all non-traumatic OHCA patients , in whom a successful return of spontaneous circulation ( ROSC ) had been obtained , from a large metropolitan area ( Great Paris ) . Receiving hospitals were categorized in 3 groups as follows : A centers ( High-case volume with cath-lab 24/7 ) , B centers ( Intermediate-case volume with cath-lab partly available ) and C centers ( Low-case volume and no cath-lab ) We compared patients ' characteristics and outcome in the 3 groups and performed a multivariate logistic regression using survival to discharge as primary endpoint . RESULTS Between May 2011 and December 2013 , 1476 patients were admitted in 48 hospitals ( group A : n=917 ; group B : n=428 ; group C : n=91 ) . Overall survival rate at discharge was 433/1436 ( 30 % ) . Patients ' baseline characteristics significantly differed , as hospitals from group A received younger patients with a higher rate of shockable cardiac rhythms ( p<0.001 ) . Unadjusted survival rate differed significantly among the 3 groups of hospitals ( respectively 34 % , 25 % and 15.4 % for A-C , p<0.01 ) . In multivariate analysis , the category of receiving hospital was no longer associated with survival , even in the subgroup of witnessed arrest and shockable patients . CONCLUSION In this population -based study , characteristics of receiving hospitals are not associated with survival rate at discharge . This might be partially explained by the prehospital triage organization used in France Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies CONTEXT The health and policy implication s of regional variation in incidence and outcome of out-of-hospital cardiac arrest remain to be determined . OBJECTIVE To evaluate whether cardiac arrest incidence and outcome differ across geographic regions . DESIGN , SETTING , AND PATIENTS Prospect i ve observational study ( the Resuscitation Outcomes Consortium ) of all out-of-hospital cardiac arrests in 10 North American sites ( 8 US and 2 Canadian ) from May 1 , 2006 , to April 30 , 2007 , followed up to hospital discharge , and including data available as of June 28 , 2008 . Cases ( aged 0 - 108 years ) were assessed by organized emergency medical services ( EMS ) personnel , did not have traumatic injury , and received attempts at external defibrillation or chest compressions or resuscitation was not attempted . Census data were used to determine rates adjusted for age and sex . MAIN OUTCOME MEASURES Incidence rate , mortality rate , case-fatality rate , and survival to discharge for patients assessed or treated by EMS personnel or with an initial rhythm of ventricular fibrillation . RESULTS Among the 10 sites , the total catchment population was 21.4 million , and there were 20,520 cardiac arrests . A total of 11,898 ( 58.0 % ) had resuscitation attempted ; 2729 ( 22.9 % of treated ) had initial rhythm of ventricular fibrillation or ventricular tachycardia or rhythms that were shockable by an automated external defibrillator ; and 954 ( 4.6 % of total ) were discharged alive . The median incidence of EMS-treated cardiac arrest across sites was 52.1 ( interquartile range [ IQR ] , 48.0 - 70.1 ) per 100,000 population ; survival ranged from 3.0 % to 16.3 % , with a median of 8.4 % ( IQR , 5.4%-10.4 % ) . Median ventricular fibrillation incidence was 12.6 ( IQR , 10.6 - 5.2 ) per 100,000 population ; survival ranged from 7.7 % to 39.9 % , with a median of 22.0 % ( IQR , 15.0%-24.4 % ) , with significant differences across sites for incidence and survival ( P<.001 ) . CONCLUSION In this study involving 10 geographic regions in North America , there were significant and important regional differences in out-of-hospital cardiac arrest incidence and outcome Objective : To investigate the relationship between trauma center volume and outcome . Background : The Resuscitation Outcomes Consortium is a network of 11 centers and 60 hospitals conducting emergency care research . For many procedures , high-volume centers demonstrate superior outcomes versus low-volume centers . This remains controversial for trauma center outcomes . Methods : This study was a secondary analysis of prospect ively collected data from the Resuscitation Outcomes Consortium multicenter out-of-hospital Hypertonic Saline Trial in patients with Glasgow Coma Scale score of 8 or less ( traumatic brain injury ) or systolic blood pressure of 90 or less and pulse of 110 or more ( shock ) . Regression analyses evaluated associations between trauma volume and the following outcomes : 24-hour mortality , 28-day mortality , ventilator-free days , Multiple Organ Dysfunction Scale incidence , worst Multiple Organ Dysfunction Scale score , and poor 6-month Glasgow Outcome Scale — Extended score . Results : A total of 2070 patients were evaluated : 1251 in the traumatic brain injury cohort and 819 in the shock cohort . Overall , 24-hour and 28-day mortality was 16 % and 25 % , respectively . For every increase of 500 trauma center admissions , there was a 7 % decreased odds of 24-hour and 28-day mortality for all patients . As trauma center volume increased , nonorgan dysfunction complications increased , ventilator-free days increased , and worst Multiple Organ Dysfunction Scale score decreased . The associations with higher trauma center volume were similar for the traumatic brain injury cohort , including better neurologic outcomes at 6 months , but not for the shock cohort . Conclusions : Increased trauma center volume was associated with increased survival , more ventilator-free days , and less severe organ failure . Trauma system planning and implementation should avoid unnecessary duplication of services AIM Cardiac arrest centers have been associated with improved outcome for patients after cardiac arrest . Aim of this study was to investigate the effect on outcome depending on admission to high- , medium- or low volume centers . METHODS Analysis from a prospect i ve , multicenter registry for out of hospital cardiac arrest patients treated by the emergency medical service of Vienna , Austria . The frequency of cardiac arrest patients admitted per center/year ( low < 50 ; medium 50 - 100 ; high > 100 ) was correlated to favorable outcome ( 30-day survival with cerebral performance category of 1 or 2 ) . RESULTS Out of 2238 patients ( years 2013 - 2015 ) with emergency medical service resuscitation , 861 ( 32 % female , age 64 ( 51;73 ) years ) were admitted to 7 different centers . Favorable outcome was achieved in 267 patients ( 31 % ) . Survivors were younger ( 58 vs. 66 years ; p<0.001 ) , showed shockable initial heart rhythm more frequently ( 72 vs. 35 % ; p<0.001 ) , had shorter CPR duration s ( 22 vs. 29min ; p<0.001 ) and were more likely to be treated in a high frequency center ( OR 1.6 ; CI : 1.2 - 2.1 ; p=0.001 ) . In multivariate analysis , age below 65 years ( OR 15 ; CI : 3.3 - 271.4 ; p=0.001 ) , shockable initial heart rhythm ( OR 10.1 ; CI : 2.4 - 42.6 ; p=0.002 ) , immediate byst and er or emergency medical service CPR ( OR 11.2 ; CI : 1.4 - 93.3 ; p=0.025 ) and admission to a center with a frequency of > 100 OHCA patients /year ( OR 5.2 ; CI : 1.2 - 21.7 ; p=0.025 ) was associated with favorable outcome . CONCLUSIONS High frequency of post-cardiac arrest treatment in a specialized center seems to be an independent predictor for favorable outcome in an unselected population of patients after out of hospital cardiac arrest Objectives : To determine the longitudinal changes in functional outcome and compare ordinal outcome scale assessment s in comatose cardiac arrest survivors . Design : Prospect i ve observational study of comatose cardiac arrest survivors . Subjects who survived to 1 month were included . Setting : Academic medical center ICU . Patients : Ninety-eight consecutive patients who remained comatose after resuscitation from cardiac arrest ; 45 patients survived to 1 month . Interventions : None . Measurements and Main Results : Patients ’ functional neurologic outcomes were assessed by phone call or in-person clinic visit at 1 , 3 , 6 , and 12 months postcardiac arrest using the modified Rankin Scale , Glasgow Outcome Scale , and Barthel Index . A “ good ” outcome was defined as modified Rankin Scale 0–3 , Barthel Index 70–100 , and Glasgow Outcome Scale 4–5 . Changes in dichotomized outcomes and shifts on each outcome scale were analyzed . The mean age of survivors was 51 ± 19 years and 18 ( 40 % ) were women . Five ( 19 % ) out of 26 patients with data available at all timepoints improved to good modified Rankin Scale outcome and none worsened to poor outcome between postarrest months 1 and 6 ( p = 0.06 ) . Thirteen patients ( 50 % ) improved on the modified Rankin Scale by 1–3 points and four ( 15 % ) worsened by 1–2 points between months 1 and 6 ( overall improvement by 0.5 points ; 95 % CI , 0–1 ; p = 0.04 ) . From postarrest months 6 to 12 , there was no change in the number of patients with good versus poor outcomes . The modified Rankin Scale and Barthel Index were more sensitive to detecting changes in outcome than the Glasgow Outcome Scale . Conclusions : In initially comatose cardiac arrest survivors , improvements in functional status occur over the first 6 months after the event . There was no significant change in outcome between postarrest months 6 and 12 . The modified Rankin Scale is a sensitive outcome scale in this population STUDY OBJECTIVE The Cerebral Performance Category score is an easy to use but unvali date d measure of functional outcome after cardiac arrest . We evaluate the comparability of results from the Cerebral Performance Category scale versus those of the vali date d but more complex Health Utilities Index scale for health-related quality of life . METHODS This prospect i ve sub study of the Ontario Prehospital Advanced Life Support ( OPALS ) Study included adult out-of-hospital cardiac arrest patients treated in 20 cities . This prospect i ve cohort study included all survivors of out-of-hospital adult cardiac arrest enrolled in phase II ( rapid basic life support with defibrillation ) and phase III ( advanced life support ) of the OPALS Study , as well as the intervening run-in phase . Survivors were interviewed at 12 months for Cerebral Performance Category Score and the Health Utilities Index Mark 3 ( Health Utilities Index ) . RESULTS Of 8,196 eligible out-of-hospital cardiac arrest patients between 1995 and 2002 , 418 ( 5.1 % ) survived to discharge , and 305 ( 3.7 % ) completed the Health Utilities Index interview and had Cerebral Performance Category scored at 12 months . The 305 patients had the following data : mean age 63.9 years ; male 78.0 % ; paramedic-witnessed arrest 25.6 % ; byst and er cardiopulmonary resuscitation 32.1 % ; initial rhythm ventricular fibrillation/ventricular tachycardia 86.9 % , Cerebral Performance Category 1 267 , Cerebral Performance Category 2 26 , Cerebral Performance Category 3 12 . Overall , the median scores ( interquartile range ) were Cerebral Performance Category 1 ( 1 to 1 ) and Health Utilities Index 0.84 ( 0.61 to 0.97 ) . The Cerebral Performance Category score ruled out good quality of life ( Health Utilities Index > 0.80 ) , with a sensitivity of 100 % ( 95 % confidence interval [ CI ] 98 % to 100 % ) and specificity 27.1 % ( 95 % CI 20 % to 35 % ) ; thus , when the Cerebral Performance Category score was 2 or 3 , it was unlikely that the Health Utilities Index score would be good . The Cerebral Performance Category score had sensitivity 55.6 % ( 95 % CI 42 % to 67 % ) and specificity 96.8 % ( 95 % CI 94 % to 98 % ) for predicting poor quality of life ( Health Utilities Index > 0.40 ) ; ie , when Cerebral Performance Category was 1 , it was highly unlikely that the Health Utilities Index score would be poor . The weighted kappa was 0.39 and the interclass correlation was 0.51 . CONCLUSION This represents the largest study yet conducted of the performance of the Cerebral Performance Category score in 1-year survivors of out-of-hospital cardiac arrest . Overall , the Cerebral Performance Category score classified patients well for their quality of life , ruling out a good Health Utilities Index score with high sensitivity and ruling in poor Health Utilities Index score with high specificity . The Cerebral Performance Category is an important tool in that it indicates broad functional outcome categories that are useful for a number of key clinical and research applications but should not be considered a substitute for the Health Utilities Index Objective : To evaluate whether a Post-Arrest Consult Team improved care and outcomes for patients with out-of-hospital cardiac arrest . Design : Prospect i ve cohort study of Post-Arrest Consult Team implementation at two hospitals , with concurrent controls from 27 others . Setting : Twenty-nine hospitals within the Strategies for Post-Arrest Care Network of Southern Ontario , Canada . Patients : We included comatose adult nontraumatic out-of-hospital cardiac arrest patients surviving more than or equal to 6 hours after emergency department arrival who had no contraindications to targeted temperature management . Intervention : The Post-Arrest Consult Team was an advisory consult service to improve 1 ) targeted temperature management , 2 ) assessment for percutaneous coronary intervention , 3 ) electrophysiology assessment , and 4 ) appropriately delayed neuroprognostication . Measurements and Main Results : We used generalized linear mixed models to explore the association between Post-Arrest Consult Team implementation and performance of targeted processes . We included 1,006 patients . The Post-Arrest Consult Team was associated with a significant reduction over time in rates of withdrawal of life-sustaining therapy within 72 hours of emergency department arrival on the basis of predictions of poor neurologic prognosis ( ratio of odds ratios , 0.13 ; 95 % CI , 0.02–0.98 ) . Post-Arrest Consult Team was not associated with improved successful targeted temperature management ( ratio of odds ratios , 0.91 ; 95 % CI , 0.31–2.65 ) , undergoing angiography ( ratio of odds ratios , 1.91 ; 95 % CI , 0.17–21.04 ) , receiving electrophysiology consultation ( ratio of odds ratios , 0.93 ; 95 % CI , 0.11–8.16 ) , or functional survival ( ratio of odds ratios , 0.75 ; 95 % CI , 0.19–2.94 ) . Conclusions : Implementation of a Post-Arrest Consult Team reduced premature withdrawal of life-sustaining therapy but did not improve rates of successful targeted temperature management , coronary angiography , formal electrophysiology assessment s , or functional survival for comatose patients after out-of-hospital cardiac arrest STUDY OBJECTIVE For out-of-hospital cardiac arrest , authoritative , evidence -based recommendations have been made for regionalization of postarrest care . However , system-wide implementation of these guidelines has not been evaluated . Our hypothesis is that statewide regionalization of postarrest interventions , combined with emergency medical services ( EMS ) triage bypass , is associated with improved survival and neurologic outcome . METHODS This was a prospect i ve before-after observational study comparing patients admitted to cardiac receiving centers before implementation of the interventions ( " before " ) versus those admitted after ( " after " ) . In December 2007 , the Arizona Department of Health Services began officially recognizing cardiac receiving centers according to commitment to provide specified postarrest care . Subsequently , the State EMS Council approved protocol s allowing preferential EMS transport to these centers . Participants were adults ( ≥ 18 years ) experiencing out-of-hospital cardiac arrest of presumed cardiac cause who were transported to a cardiac receiving center . Interventions included ( 1 ) implementation of postarrest care at cardiac receiving centers focusing on provision of therapeutic hypothermia and coronary angiography or percutaneous coronary interventions ( catheterization/PCI ) ; and ( 2 ) implementation of EMS bypass triage protocol s. Main outcomes included discharged alive from the hospital and cerebral performance category score at discharge . RESULTS During the study ( December 1 , 2007 , to December 31 , 2010 ) , 31 hospitals were recognized as cardiac receiving centers statewide . Four hundred forty patients were transported to cardiac receiving centers before and 1,737 after . Provision of therapeutic hypothermia among patients with return of spontaneous circulation increased from 0 % ( before : 0/145 ; 95 % confidence interval [ CI ] 0 % to 2.5 % ) to 44.0 % ( after : 300/682 ; 95 % CI 40.2 , 47.8 ) . The post return of spontaneous circulation catheterization PCI rate increased from 11.7 % ( 17/145 ; 95 % CI 7.0 , 18.1 ) before to 30.7 % ( 210/684 ; 95 % CI 27.3 , 34.3 ) after . All-rhythm survival increased from 8.9 % ( 39/440 ) to 14.4 % ( 250/1,734 ; adjusted odds ratio [ aOR ] = 2.22 ; 95 % CI 1.47 to 3.34 ) . Survival with favorable neurologic outcome ( cerebral performance category score = 1 or 2 ) increased from 5.9 % ( 26/439 ) to 8.9 % ( 153/1,727 ; aOR = 2.26 [ 95 % CI 1.37 , 3.73 ] ) . For witnessed shockable rhythms , survival increased from 21.4 % ( 21/98 ) to 39.2 % ( 115/293 ; aOR = 2.96 [ 95 % CI 1.63 , 5.38 ] ) and cerebral performance category score = 1 or 2 increased from 19.4 % ( 19/98 ) to 29.8 % ( 87/292 ; aOR = 2.12 [ 95 % CI 1.14 , 3.93 ] ) . CONCLUSION Implementation of a statewide system of cardiac receiving centers and EMS bypass was independently associated with increased overall survival and favorable neurologic outcome . In addition , these outcomes improved among patients with witnessed shockable rhythms |
1,776 | 24,691,989 | The use of alpha-blockers in patients with ureteral stones results in a higher stone-free rate and a shorter time to stone expulsion . | BACKGROUND Urinary stone disease is one of the most common reasons for patients visiting a urology practice , affecting about 5 % to 10 % of the population .
Annual costs for stone disease have rapidly increased over the years and most patients with ureteral colic or other symptoms seek medical care .
Stone size and location are important predictors of stone passage .
In most cases medical expulsive therapy is an appropriate treatment modality and most studies have been performed with alpha-blockers .
Alpha-blockers tend to decrease intra-ureteral pressure and increase fluid passage which might increase stone passage .
Faster stone expulsion will decrease the rate of complications , the need for invasive interventions and eventually decrease healthcare costs .
A study on the effect of alpha-blockers as medical expulsive therapy in ureteral stones is therefore warranted .
OBJECTIVES This review aim ed to answer the following question : does medical treatment with alpha-blockers compared to other pharmacotherapy or placebo impact on stone clearance rate , in adult patients presenting with symptoms of ureteral stones less than 10 mm confirmed by imaging ?
Other clinical ly relevant outcomes such as stone expulsion time , hospitalisation , pain scores , analgesic use and adverse effects have also been explored . | OBJECTIVES To study the efficacy of alfuzosin compared with tamsulosin in the management of lower ureteral stones . METHODS A total of 102 patients with stones < 1 cm size and located in the lower ureter were enrolled in the present study and r and omized into 3 equal groups . Group 1 patients ( n = 34 ) received 0.4 mg tamsulosin daily , group 2 patients ( n = 34 ) received 10 mg alfuzosin daily , and group 3 patients ( n = 34 ) received placebo ( control group ) . The patients were given 75 mg diclofenac injection intramuscularly on dem and and were followed up for 4 weeks . RESULTS The average stone size for groups 1 , 2 , and 3 was comparable ( 6.17 , 6.70 , and 6.35 mm , respectively ) . Stone expulsion was observed in 28 of 34 patients ( 82.3 % ) in group 1 , 24 of 34 patients ( 70.5 % ) in group 2 , and 12 of 34 patients ( 35.2 % ) in group 3 . The average expulsion time for groups 1 , 2 , and 3 was 12.3 , 14.5 , and 24.5 days , respectively . The results of both study groups ( groups 1 and 2 ) were superior to those in the placebo group ( P = .003 and P = .001 , respectively ) , but the study failed to show any statistically significant differences between tamsulosin and alfuzosin ( P = .25 ) . Alfuzosin was associated with fewer side effects than tamsulosin , especially in terms of retro grade ejaculation . CONCLUSIONS Medical treatment of lower ureteral calculi with tamsulosin and alfuzosin result ed in a significantly increased stone expulsion rate , decreased expulsion time , and a reduced need for analgesic therapy Abstract Objective : To evaluate and compare the efficacy of tamsulosin and alfuzosin as medical expulsive therapy for ureteric stones . Patients and methods : In all , 112 patients with ureteric stones of ⩽10 mm , located along the ureter , were r and omly divided into three groups . In group I , 32 patients received no α-blockers ( controls ) , in group II 40 patients received tamsulosin 0.4 mg daily , and in group III 40 patients received alfuzosin 10 mg daily . All patients were given analgesia and antibiotics when indicated . The follow-up was weekly for 4 weeks . Results : The mean stone size and age were comparable in the three groups . The stone expulsion rate was 44 % , 85 % and 75 % in groups I , II and III , respectively . Half of the stones in group II passed within 2 weeks , half in group III passed within 3 weeks , while more than half of the stones in group I did not pass even after 4 weeks . The mean number of painful episodes was 2.45 , 1.38 and 1.64 in groups I , II and III , respectively . The drug-related side-effects reported by patients were mild and transient . Conclusion : The use of tamsulosin or alfuzosin as medical expulsive therapy for ureteric stones in the three sections of the ureter ( upper , middle and lower ) was safe and effective , as shown by the increased overall stone expulsion rate , reduced stone expulsion time and fewer pain episodes . Tamsulosin was associated with a greater rate of stone expulsion than was alfuzosin PURPOSE We evaluated the effectiveness of doxazosin in children with distal ureteral stones in terms of stone expulsion rates and time to expulsion . MATERIAL S AND METHODS A total of 39 patients 2 to 14 years old with lower ureteral stones smaller than 10 mm were enrolled and r and omly divided into 2 groups . Group 1 consisted of 20 controls receiving ibuprofen for pain and group 2 consisted of 19 patients receiving doxazosin . Doxazosin dose was approximately 0.03 mg/kg daily . All patients were evaluated with x-ray , ultrasound or spiral computerized tomography . Stone expulsion rates and time to expulsion between the groups were compared . Mean followup was 19 days . Effects of doxazosin were also evaluated by comparing subgroups with stones smaller than 5 mm and 5 to 10 mm . Results were also evaluated with special emphasis on gender and age . RESULTS Expulsion was observed in 14 patients ( 70 % ) in group 1 and 16 ( 84 % ) in group 2 ( p > 0.05 ) . Mean expulsion times for groups 1 and 2 were 6.1 and 5.9 days , respectively ( p > 0.05 ) . Although fewer pain episodes were observed in the treatment group , this finding could not be evaluated objective ly . None of the patients experienced any adverse effects . CONCLUSIONS Administration of 0.03 mg/kg doxazosin daily in children to treat distal ureteral stones up to 10 mm is not superior to analgesic alone . This result is not affected by gender , stone size or patient age . However , additional r and omized controlled studies , especially including larger stone volumes , and different doses of doxazosin and other alpha-blockers , might highlight the usefulness of alpha-blockers for ureteral stones in children BACKGROUND Using a selective α-blocker for medical expulsive therapy ( MET ) is a cost-effective treatment approach widely used for ureteral stones . OBJECTIVE To evaluate the efficacy of silodosin , a selective α-1a receptor antagonist , in this setting . DESIGN , SETTING , AND PARTICIPANTS This was a multicenter , phase 2 study conducted in adult patients with a unilateral ureteral calculus of 4 - 10 mm . Of 239 patients in the safety population , six discontinued due to adverse events . INTERVENTION Patients were r and omized 1:1 to receive silodosin 8 mg or placebo for up to 4 wk . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was spontaneous stone passage , analyzed using logistic regression . Secondary outcomes included time to stone passage , emergency room ( ER ) visits , hospital admissions , analgesic use , and incidence and severity of pain . RESULTS AND LIMITATIONS No significant differences between the silodosin and placebo groups were observed for passage rate of all stones ( 52 % vs 44 % , respectively ; p=0.2 ) . However , silodosin achieved a significantly greater rate of distal ureter stone passage than placebo ( p=0.01 ) . Significant differences were not observed for ER visits , hospital admission , or use of analgesics . The number of patients in the intent-to-treat population was slightly below the calculated sample size ( 232 vs 240 ) and sample sizes were not calculated for subgroup analyses . CONCLUSIONS This is among the first prospect i ve , r and omized , multi-institutional trials to examine the efficacy of a selective α-1a antagonist as MET in patients with ureteral calculi and did not demonstrate a benefit to the entire ureter . However , silodosin was found to be well tolerated and beneficial in facilitating the passage of distal ureteral stones , warranting additional future studies on distal stone elimination . PATIENT SUMMARY In this report , we looked at the efficacy of silodosin for the treatment of ureteral stones . We found that silodosin increased passage of distal ureteral stones BACKGROUND α-Blockers induce selective relaxation of ureteral smooth muscle with subsequent inhibition of ureteral spasms and dilatation of the ureteral lumen . The aim of the study was to evaluate the efficacy and safety of the α-blocker tamsulosin hydrochloride in patients with ureteral colic owing to a distal ureteral stone . METHODS This was a multicenter , placebo-controlled , r and omized , double-blind study . Patients with emergency admission for ureteral colic with a 2- to 7-mm-diameter radio-opaque distal ureteral stone were included in the study . They received tamsulosin ( 0.4 mg/d ) or matching placebo until stone expulsion or day 42 , whichever came first . The main end point was time to stone expulsion between inclusion and day 42 . Sequential statistical analysis was performed using the triangular test . RESULTS A total of 129 patients with acute renal colic were recruited from emergency wards between February 1 , 2002 , and December 8 , 2006 , in 6 French hospitals . Of these 129 r and omized patients ( placebo , 63 ; tamsulosin , 66 ) , 7 were excluded from analyses : 5 for major deviations from inclusion criteria , 1 for stone expulsion before the first treatment administration , and 1 for consent withdrawal . At inclusion , mean ( SD ) stone diameters were 3.2 ( 1.2 ) and 2.9 ( 1.0 ) mm in the placebo and tamsulosin groups , respectively ( P = .23 ) . Expulsion delay distributions during 42 days did not show any difference ( P = .30 ) . The numbers of patients who spontaneously expelled their stone within 42 days were 43 of 61 ( 70.5 % ) and 47 of 61 ( 77.0 % ) in the placebo and tamsulosin groups , respectively ( P = .41 ) . Corresponding delays were 10.1 ( 10.0 ) and 9.6 ( 9.8 ) days ( P = .82 ) . Other secondary end points and tolerance were not different between groups . CONCLUSION Although well tolerated , a daily administration of 0.4 mg of tamsulosin did not accelerate the expulsion of distal ureteral stones in patients with ureteral colic . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00151567 Purpose We evaluated and compared the efficacy of tamsulosin and alfuzosin in the medical treatment of symptomatic , uncomplicated distal ureteral stones . Material s and Methods A total of 87 patients with distal ureteral stones of ≤10 mm were r and omly divided into 3 groups . Group I patients ( n=29 ) received 0.4 mg tamsulosin daily , group II patients ( n=30 ) received 10 mg alfuzosin daily , and group III patients ( n=28 ) were not given tamsulosin or alfuzosin . Patients in all groups received Diclofenac sodium regularly for 1 week and then on dem and . Follow-up was done on a weekly basis for 30 days . Results The mean stone size was comparable in the 3 groups ( 4.97±2.24 , 5.47±2.13 , and 5.39±1.81 mm , respectively ) . The stone expulsion rate was 86.2 % , 76.6 % , and 50 % in groups I , II , and III , respectively . The difference in groups I and II with respect to group III was significant ( p=0.0028 and 0.035 ) . The mean expulsion time for groups I to III was 7.52±7.06 , 8.26±7.34 , and 13.90±6.99 days , respectively . The expulsion time was significantly shorter in groups I and II than in group III ( p=0.0097 and 0.026 ) . Patients taking tamsulosin and alfuzosin had fewer pain attacks than did group III patients ( 1.24±0.57 vs. 1.43±0.67 vs. 1.75±1.17 ) . Only 3 cases of drug side effects , 2 in group I and 1 in group II , were recorded . Conclusions The use of tamsulosin or alfuzosin for the medical treatment of lower ureteric stones proved to be safe and effective . Moreover , tamsulosin did not have any significant benefits over alfuzosin Background : Alpha – 1 blockers decrease the tension and release the spasm of smooth muscles and thus lessen the obstruction and irritation symptoms in the lower urinary tract ( LUTS ) . They make a faster passing of calculi from the terminal part of the ureters possible . Objectives : The goal of this study was to objective ly assess the improvement of difficulties caused by obstructions in ureterolithiasis localized in the lower part of the ureters of 104 r and omly chosen patients ( pts . ) in a double-blind study . Methods : During a period of 2 and half years ( June 1999–January 2002 ) 104 pts . suffering from ureterolithiasis of the lower urinary tract were treated and observed . Patients were divided into two groups : A ( n:53 ; later only 51 were evaluated ) which was subjected to st and ard treatment and group B ( n:51 ) where the st and ard treatment was supplemented by the alpha – 1 blocker . As alpha – 1 blocker one capsule of Tamsulosin /OMNIC 0.4 / was administered daily . Results : With alpha – 1 blocker , we have registered a more speedy passing of calculi from the terminal parts of ureters in 17.6 % of pts . Recurrence of renal colics was less frequent and occurred in one of eight pts . as compared with group A ( without the alpha – 1 blocker ) where a recurrence of the renal colic was observed in about every fifth pts . In group A ( n:51 ) , 62.8 % of the pts . passed the calculi , whereas in group B ( n:51 ) , where st and ard treatment was supplemented by the administration of the alpha – 1 blocker Tamsulosin , this percentage increased to 80.4 % . Conclusion : The treatment by alpha – 1 blockers considerably decreased not only LUTS but also helped to accelerate the passing of minor calculi from the terminal parts of the ureters of 80.4 % of pts . It seems that alpha – 1 blockers potentiate the spasmoanalgetic action of drugs used in st and ard methods of treatment BACKGROUND Numerous r and omised trials have confirmed the efficacy of medical expulsive therapy with tamsulosin in patients with distal ureteral stones ; however , to date , no r and omised , double-blind , placebo-controlled trials have been performed . OBJECTIVE The objective of this trial was to evaluate the efficacy of medical expulsive therapy with tamsulosin in a r and omised , double-blind , placebo-controlled setting . DESIGN , SETTING , AND PARTICIPANTS Patients presenting with single distal ureteral stones < or = 7 mm were included in this trial . INTERVENTION Patients were r and omised in a double-blind fashion to receive either tamsulosin or placebo for 21 d. The medication was discontinued after either stone expulsion or intervention . Abdominal computed tomography was performed to assess the initial and final stone status . MEASUREMENTS AND LIMITATIONS : The primary end point was the stone expulsion rate . Secondary end points were time to stone passage , the amount of analgesic required , the maximum daily pain score , safety of the therapy , and the intervention rate . RESULTS Ten of 100 r and omised patients were excluded from the analysis . No statistically significant differences in patient characteristics and stone size ( median : 4.1 mm [ tamsulosin arm ] vs 3.8 mm [ placebo arm ] , p=0.3 ) were found between the two treatment arms . The stone expulsion rate was not significantly different between the tamsulosin arm ( 86.7 % ) and the placebo arm ( 88.9 % ; p=1.0 ) . Median time to stone passage was 7 d in the tamsulosin arm and 10 d in the placebo arm ( log-rank test , p=0.36 ) . Patients in the tamsulosin arm required significantly fewer analgesics than patients in the placebo arm ( median : 3 vs 7 , p=0.011 ) . A caveat is that the exact time of stone passage was missing for 29 patients . CONCLUSIONS Tamsulosin treatment does not improve the stone expulsion rate in patients with distal ureteral stones < or = 7 mm . Nevertheless , patients may benefit from a supportive analgesic effect . CLINICAL TRIALS.GOV : NCT00831701 Abstract Objectives : To assess and compare , in a r and omised clinical trial , the efficacy of tamsulosin and nifedipine as medical expulsive therapy for distal ureterolithiasis . Patients and methods : In all , 128 symptomatic patients with stones in the juxtavesical tract of the ureter were r and omly divided into group 1 ( 64 patients ) receiving oral nifedipine sustained-release 30 mg/day , and group 2 ( 64 patients ) receiving tamsulosin 0.4 mg/day . Both groups received oral prednisolone 30 mg/day for 10 days and diclofenac 75 mg intramuscularly on dem and . Patients were assessed by weekly ultrasonography with or with no abdominal computed tomography , during a follow-up of 4 weeks . The stone passage rate and time , analgesic use , hospitalisation and endoscopic interventions were evaluated . The results were analysed statistically using appropriate tests . Results : The stone expulsion rate was 55 % for group 1 and 80 % for group 2 ( P = 0.004 ) . The mean stone size was 8.59 and 8.85 mm in groups 1 and 2 , respectively . The mean expulsion time was 23 days for group 1 and 9 days for group 2 ( P < 0.001 ) . The mean number of diclofenac injections was 1.19 for group 1 and 0.42 for group 2 ( P < 0.001 ) . Eleven patients in group 1 vs. two in group 2 were hospitalised ( P = 0.001 ) . Twenty-six patients in group 1 and 13 in group 2 underwent ureteroscopy ( P < 0.001 ) . Conclusions : Medical expulsive therapy with tamsulosin should be considered as a first-line treatment for index cases of distal ureterolithiasis with no complications . The use of tamsulosin provides better stone expulsion than does nifedipine Purpose To compare the safety and efficacy of naftopidil and tamsulosin with prednisolone as medical expulsive therapy for distal ureteric stones . Material s and Methods Between July 2010 and March 2012 , 120 adult patients presenting with distal ureteric stones of size 5 to 10 mm were r and omized equally to tamsulosin ( group A ) , naftopidil ( group B ) or watchful waiting ( group C ) . Tamsulosin or naftopidil was given for a maximum of four weeks . In addition patients in group A and B were given 5 mg prednisolone once daily ( maximum one week ) . Stone expulsion rate , time to stone expulsion , analgesic use , number of hospital visits for pain , follow-up and endoscopic treatment and adverse effects of drugs were noted . Statistical analyses were done using chi-square test , Mann-Whitney test and analysis of variance . Results There was a statistically higher expulsion rate in groups A ( 70 % ) and B ( 87.5 % ) as compared to group C ( 32.5 % ) ( p<0.001 ) . The expulsion rates were not statistically different between groups A and B ( p=0.056 ) . The mean time to expulsion was comparable between groups A and B but longer in group C. Analgesic use was significantly lower in groups A and B. Average number of hospital visits for pain , follow-up and endoscopic treatment was similar in all groups . There was no serious adverse event . Conclusions Medical expulsive therapy for the distal ureteric stones using either naftopidil or tamsulosin in combination with prednisolone is safe and efficacious PURPOSE To evaluate the efficacy of the addition of tamsulosin to our st and ard expulsive pharmacologic therapy for the treatment of distal-ureteral stones . PATIENTS AND METHODS A series of 96 patients referred to our department for the management of symptomatic distal-ureteral calculi were r and omly divided into group 1 ( N = 46 ) who received diclofenac ( 100 mg/daily ) plus aescin ( 80 mg/daily ) and group 2 ( N = 50 ) who received the same therapy plus tamsulosin ( 0.4 mg/daily ) for a maximum of 2 weeks . There were no differences between the groups with respect to age , sex , or stone size . The primary endpoint was the expulsion rate . Expulsion time , need for analgesics , need for hospitalization , and drug side effects were the secondary endpoints . RESULTS The expulsion rate was significantly higher in group 2 ( 90 % ) than in group 1 ( 58.7 % ; P = 0.01 ) , and group 2 achieved stone passage in a shorter time ( mean 4.4 v 7.5 days , respectively ; P = 0.005 ) . Lower analgesic use was found in group 2 ( P = 0.003 ) , as well as significantly fewer hospitalizations for recurrent colic ( P = 0.01 ) . Both groups experienced few side effects associated with expulsive therapy . CONCLUSIONS A conservative approach should be considered as an option in the management of uncomplicated distal-ureteral stones . Even if the best pharmacologic expulsive regimen remains to be established , the use of the selective alpha-blocker tamsulosin is recommended in this setting OBJECTIVES To investigate the role of tamsulosin as an adjunct to management of upper ureteric stones ( UUS ) with extracorporeal shock wave lithotripsy ( SWL ) . METHODS In this prospect i ve , r and omized , open label study , patients with single UUS ( for SWL ) were r and omly assigned into 2 groups based on whether they received 0.4 mg tamsulosin ( group A and B , respectively ) during treatment . Repeat SWL was performed at week 1 , 3 , and 5 after first session . Primary outcome variables were success rate and pain intensity . RESULTS A total of 40 patients ( 20 each group ) completed the requisite follow-up . Success rate was higher in group A after 1 SWL-session ( 55 % vs 25 % , respectively ; P = .05 ) . There was an insignificant trend of decreased number of days ( 30.7 + /- 19.7 vs 39.0 + /- 19.9 ; P = .19 ) , number of SWL sessions ( 1.6 vs 2.0 ; P = .10 ) , and pain experienced ( score on visual analog scale , 25.3 + /- 17.9 vs 38.3 + /- 28.0 , respectively ; P = .41 ) in group A. Three in group A and 6 in B developed steinstrasse ( P = .69 ) . Overall , 1 in group A required auxiliary procedures as compared with 3 in control group ( P = .60 ) . CONCLUSIONS Tamsulosin improves clearance rate of UUS after single SWL . However , it does not provide significant advantage in terms of decreasing pain associated with this treatment PURPOSE We evaluated the efficacy of alfuzosin as medical expulsive therapy for distal ureteral stone passage . MATERIAL S AND METHODS A total of 76 patients with a distal ureteral calculus provided consent for the study . Patients were r and omized between placebo and study medication , and investigators and patients were blinded to the r and omization scheme . Followup was done on a weekly basis and continued until the patient was rendered stone-free . The patient blood pressure , discomfort level , stone position on imaging , number of remaining pills and any adverse events were assessed . Statistical analysis was performed with the Student t test with p < 0.05 considered significant . RESULTS The overall spontaneous stone passage rate was 75 % , including 77.1 % for placebo and 73.5 % for alfuzosin ( p = 0.83 ) . Mean + /- SD time needed to pass the stone was 8.54 + /- 6.99 days for placebo vs 5.19 + /- 4.82 days for alfuzosin . ( p = 0.003 ) . There was no difference in the size or volume of stones that passed spontaneously between the placebo and alfuzosin arms , as measured on baseline computerized tomography ( 4.08 + /- 1.17 and 3.83 + /- 0.95 mm , p = 0.46 ) and by a digital caliper after stone expulsion ( 3.86 + /- 1.76 and 3.91 + /- 1.06 mm , respectively , p = 0.57 ) . When comparing the improvement from the baseline pain score , the alfuzosin arm experienced a greater decrease in pain score in the days after the initial emergency department visit to the date of stone passage ( p = 0.0005 ) . CONCLUSIONS Alfuzosin improves the patient discomfort associated with stone passage and decreases the time to distal ureteral stone passage but it does not increase the rate of spontaneous stone passage Introduction : Stone disease is a significant and world-wide health problem . Recently , certain drugs have been used as a supplement to observation alone in an effort to improve spontaneous stone expulsion . We evaluated the efficacy of nifedipine and alfuzosin in the medical treatment of symptomatic , uncomplicated distal ureteral stones . Material s and Methods : This was a r and omized controlled prospect i ve study to determine the efficacy of alfuzosin and nifedipine as an adjunctive medical therapy , to increases the stone-expulsion rates in distal ureteric calculus of size ≤10 mm . Investigators and patients were blinded to the r and omization scheme . Patients were r and omly divided into three equal groups of 35 patients each . Patients in Group I received tablet nifedipine 30 mg/day , Group II received alfuzosin 10 mg/day and Group III was the control group received tablet diclofenac sodium . The patient blood pressure , stone position on imaging , number of pain attacks , time of stone-expulsion , hospital re-admission and any adverse events were assessed . Patients were followed-up weekly and continued until the patient was rendered stone free or up to 28 days . Statistical analysis was performed and P < 0.05 was considered to be significant . Results : Stone-expulsion was observed in 60 % , 85.7 % and 20 % patients in Group I , II and III respectively . A statistically significant difference was noted in between Groups I versus III , Groups II versus III and Groups I versus II ( P < 0.0001 , P < 0.0001 , and P < 0.0315 respectively ) . The mean number of pain attacks was 2.91 ± 1.01 for Group I , 1.8 ± 0.83 for Group II , and 2.82 ± 1.12 for Group III , which is statistical significant in Groups II versus III , and Groups I versus II ( P < 0.001 and P < 0.001 ) . Hospital re-admission rate was less in treatment groups when compare to control group ( P < 0.0001 ) . Conclusion : The use of alfuzosin and nifedipine as a medical expulsive therapy for distal ureteric stones proved to be safe and effective in term of increased stone-expulsion rate , reduced pain attacks and decrease hospital re-admissions OBJECTIVES To prospect ively evaluate the role of tamsulosin on the stone free rate and the rate of colic episodes after ureteroscopic laser lithotripsy . The presence of alpha-1A adrenoceptor in the distal ureteral smooth muscle prompted the use of tamsulosin , a selective alpha-1 blocker , to promote spontaneous passage of distal ureteral and juxtavesical calculi . Tamsulosin also improves stone clearance after shock wave lithotripsy . METHODS Seventy-eight patients with large renal or ureteral calculi underwent ureteroscopic laser lithotripsy by a single endourologist . Stone size varied from 1 to 2 cm . After treatment , the patients were r and omly divided into 2 groups . The study group ( n = 40 ) received tamsulosin 0.4 mg and st and ard analgesia ( tylenol with codeine ) . The control group ( n = 38 ) received st and ard analgesia only . The primary endpoint was stone free rate , determined by helical computerized tomography at 4 weeks . The secondary endpoint was the rate of ureteric colic episodes during the 4-week period . RESULTS Of the 73 patients available for follow up , the stone free rate was 86.5 % in the study group , compared with 69.4 % in the control group . 22.2 % of the control group had colic episodes , whereas only 5.4 % of the study group had colic . These were statistically significant with P < .01 . CONCLUSIONS Treatment with tamsulosin improves the stone free rate and reduces the occurrence of colic episodes , after ureteroscopic laser lithotripsy of large renal and ureteric calculi . To the best of our knowledge , this is the first study to show the efficacy of adjuvant tamsulosin after ureteroscopic lithotripsy OBJECTIVES To evaluate whether alpha1-blockers have any impact on stone clearance in patients with lower ureteral stones who underwent either shock wave lithotripsy ( SWL ) or were followed up with st and ard hydration , analgesics , and anti-inflammatory treatment . METHODS A total of 78 patients ( 56 men and 22 women ) who had lower ureteral stones located at the distal 5 cm of the ureter were divided into four groups . The first group consisted of 30 patients ( 38.5 % ) with stones less than 5 mm ( range 3 to 5 ) who were r and omly divided into two subgroups . Group 1 consisted of 15 patients ( 19.2 % ) who were followed up with oral hydration and diclofenac sodium . Group 2 consisted of 15 patients ( 19.2 % ) who received tamsulosin 0.4 mg daily in addition to the st and ard regimens . The second two groups consisted of 48 patients ( 61.5 % ) with stones greater than 5 mm ( range 6 to 15 ) who underwent SWL . These patients were also r and omly divided between those who did not ( group 3 , n = 24 ) and those who did ( group 4 , n = 24 ) receive tamsulosin 0.4 mg daily . All patients were re-evaluated with plain abdominal x-rays and helical computed tomography 15 days after the beginning of treatment . RESULTS Of the 78 patients , 36 ( 46.2 % ) became stone free . The stone-free rate was 20 % , 53.3 % , 33.3 % , and 70.8 % for group 1 , 2 , 3 , and 4 , respectively . The best results were achieved in those who underwent SWL plus tamsulosin treatment ( group 4 ) . The differences between the stone-free rates for groups 3 versus 4 ( P = 0.019 ) and the tamsulosin versus control groups ( P = 0.0015 ) were statistically significant . CONCLUSIONS The addition of tamsulosin to conventional treatment seemed beneficial in terms of stone clearance of lower ureteral stones , and this effect was more evident for larger stones , especially when combined with SWL PURPOSE To evaluate hyoscine N-butyl bromide ( HBB ) and three different alpha-1 blockers in the treatment of distal ureteral stones . MATERIAL S AND METHODS A total of 140 patients with stones located in the distal tract of the ureter with stone diameters of 5 to 10 mm were enrolled in the present study and were r and omized into 4 equal groups . Group 1 received HBB , Group 2 received alfuzosin , Group 3 received doxazosin and Group 4 received terazosin . The subjects were prescribed diclofenac injection ( 75 mg ) intramuscularly on dem and for pain relief and were followed-up after two weeks with x-rays of the kidneys , ureters , bladder and urinary ultrasonography every week . The number of pain episodes , analgesic dosage and the number of days of spontaneous passage of the calculi through the ureter were also recorded . RESULTS The average stone size for groups 1 , 2 , 3 and 4 was comparable ( 6.13 , 5.83 , 5.59 and 5.48 mm respectively ) . Stone expulsion was observed in 11 % , 52.9 % , 62 % , and 46 % in groups 1 , 2 , 3 and 4 respectively . The average time to expulsion was 10.55 ± 6.21 days in group 1 , 7.38 ± 5.55 days in group 2 , 7.85 ± 5.11 days in group 3 and 7.45 ± 5.32 days in group 4 . Alpha blockers were found to be superior to HBB ( p < 0.05 ) . CONCLUSIONS Medical treatment of distal ureteral calculi with alfuzosin , doxazosin and terazosin result ed in a significantly increased stone-expulsion rate and decreased expulsion time when compared with HBB . HBB seems to have a negative effect on stone-expulsion rate Introduction : Renal stones are common disorders that affect approximately 5 % to 10 % of the population and the incidence of renal stones is rising . Treatment of ureteral stones is an important part of urologists and minimally invasive procedures such as ESWL and ureteroscopy effectiveness has been proven in various studies . However , these methods are not completely safe and are expensive and can be complicated . Purpose of this study is to evaluate the effectiveness of tamsulosin in the medical treatment of distal ureteral stones . Patients and methods : A total of 96 patients with distal ureteral stones or UVj are r and omly divided into two study group ( 50 patients ) and control group ( 46 patients ) . Patients in the control group allowed to freely consuming fluids ( hydration ) and indomethacin 100 mg PRN . Study group in addition to indomethacin and daily analgesic 0.4 mg tamsulosin was administered . All subjects in terms of analgesic dose , duration of expulsion and expulsion were studied . Results : Spontaneous expulsion of stone was occurred in 62.5 % ( 30 patients out of 46 ) of control group patients and 82 % ( 41 patients out of 50 ) that there was no significant difference ( P>0.05 ) . Average time to fix the stone in control group 4.7±8.03 days ( range 2 to 28 days ) and in the study group , 3.7±5.70 days ( range 1 to 23 days ) is significantly different ( P>0.05 ) . The average amount of analgesic consumption in the control group was 2.3±4.31 and in the study group was 1.48±2.15 that showed significant differences ( P<0.05 ) . Conclusions : In this study , although the addition of tamsulosin to conservative treatment of distal ureteral stones in the distal ureteral stone expulsion showed no significant difference between the two groups , but the reduction in the duration of expulsion , reduce pain and reduce the need for analgesic has been beneficial Purpose Typically in Korea , for a st and ard dose ( 0.4 mg ) of tamsulosin , two low doses ( 0.2 mg ) are administered . The aim of this study was to evaluate and compare the efficacy of tamsulosin ( 0.2 mg and 0.4 mg ) and alfuzosin ( 10 mg ) in the treatment of lower ureteral stones . Material s and Methods A total of 141 patients presenting with a single 4- to 10-mm sized lower ureteral stone were r and omly assigned to 4 groups . Patients in group 1 ( n=41 ) and group 2 ( n=30 ) received an oral dose of 0.2 mg tamsulosin once and twice daily , respectively , and patients in group 3 ( n=36 ) received a daily oral dose of 10 mg alfuzosin . Patients in group 4 ( n=34 ) received trospium chloride only . The spontaneous passage of stones , the stone expulsion time , and adverse effects were evaluated . Results There were no significant differences in patient background , including age , sex , BMI , stone size , stone side , and symptom duration . The spontaneous stone passage rate through the ureter was higher and the stone expulsion time was faster in groups 1 , 2 , and 3 than in group 4 . There were no statistically different changes in groups 1 , 2 , and 3 . The adverse effects observed in all groups were comparable and were mild . Conclusions Tamsulosin at 0.2 mg and 0.4 mg and alfuzosin ( 10 mg ) proved to be safe and effective . A first cycle of medical expulsive therapy with tamsulosin 0.2 mg could be considered as an option in the management of single lower ureteral stone BACKGROUND Meta-analyses of previous r and omised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic , but emphasised the need for high- quality trials with wide inclusion criteria . We aim ed to fulfil this need by testing effectiveness of these drugs in a st and ard clinical care setting . METHODS For this multicentre , r and omised , placebo-controlled trial , we recruited adults ( aged 18 - 65 years ) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals . Participants were r and omly assigned by a remote r and omisation system to tamsulosin 400 μg , nifedipine 30 mg , or placebo taken daily for up to 4 weeks , using an algorithm with centre , stone size ( ≤5 mm or > 5 mm ) , and stone location ( upper , mid , or lower ureter ) as minimisation covariates . Participants , clinicians , and trial personnel were masked to treatment assignment . The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of r and omisation , analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data . This trial is registered with the European Clinical Trials Data base , EudraCT number 2010 - 019469 - 26 , and as an International St and ard R and omised Controlled Trial , number 69423238 . FINDINGS Between Jan 11 , 2011 , and Dec 20 , 2013 , we r and omly assigned 1167 participants , 1136 ( 97 % ) of whom were included in the primary analysis ( 17 were excluded because of in eligibility and 14 participants were lost to follow-up ) . 303 ( 80 % ) of 379 participants in the placebo group did not need further intervention by 4 weeks , compared with 307 ( 81 % ) of 378 in the tamsulosin group ( adjusted risk difference 1·3 % [ 95 % CI -5·7 to 8·3 ] ; p=0·73 ) and 304 ( 80 % ) of 379 in the nifedipine group ( 0·5 % [ -5·6 to 6·5 ] ; p=0·88 ) . No difference was noted between active treatment and placebo ( p=0·78 ) , or between tamsulosin and nifedipine ( p=0·77 ) . Serious adverse events were reported in three participants in the nifedipine group ( one had right loin pain , diarrhoea , and vomiting ; one had malaise , headache , and chest pain ; and one had severe chest pain , difficulty breathing , and left arm pain ) and in one participant in the placebo group ( headache , dizziness , lightheadedness , and chronic abdominal pain ) . INTERPRETATION Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic . FUNDING UK National Institute for Health Research Health Technology Assessment Programme Purpose To compare the efficacy of α1D-receptor antagonist Naftopidil and α1A/D-receptor antagonist Tamsulosin in management of distal ureteral stones . Material s and methods A total of 131 patients with distal ureteral stones were included in the study from December 2008 to September 2010 . The patients were r and omized to 3 groups : group 1 ( 43 patients ) , those receiving 10 mg naftopidil once daily ; group 2 ( 45 patients ) , those receiving 0.4 mg tamsulosin once daily ; and group 3 ( 43 patients ) were given a watchful waiting and served as control group . All patients were followed up for 2 weeks . Ultrasonography and kidney-ureters-bladder ( KUB ) were performed on day 7 and 14 . At the end of the follow-up period , patients who failed to expel the stone were scheduled to undergo ESWL or ureteroscopy . Results Stone expulsion was observed in 31 patients in group 1 ( 72.1 % ) , 37 patients in group 2 ( 82.2 % ) , and 13 patients in group 3 ( 30.2 % ) . A statistically significant difference was noted with Chi-square testing between groups 1 and 3 , and groups 2 and 3 ( P = 0.000 and P = 0.000 , respectively ) . Average time to expulsion was 7.6 ± 2.26 days ( range 1–12 days ) in group 1 , 7.7 ± 1.94 days ( range 2–11 days ) in group 2 , and 9.4 ± 2.48 days ( range 6–14 days ) in group 3 . A statistically significant difference was observed in time to expulsion between groups 1 and 3 , and groups 2 and 3 ( P = 0.000 , P = 0.001 , respectively ) by ANOVA testing . The side effects encountered in the study groups were generally mild and did not require cessation of therapy in any patient . Conclusions Naftopidil could significantly increase spontaneous passage of distal ureteral stones with low side effects . The stone expulsion rate is similar for the tamsulosin Low-dose ( 0.2 mg/day ) and st and ard-dose ( 0.4 mg/day ) tamsulosin were studied in a r and omized controlled trial of 75 out patients with distal ureteroliths in Thail and . Group 1 ( n = 25 ; control ) received oral sodium diclofenac 50 mg twice a day for 10 days ; group 2 ( n = 25 ) received oral sodium diclofenac 50 mg twice a day for 10 days , with oral tamsulosin 0.2 mg once a day up to 28 days ; and group 3 ( n = 25 ) received oral sodium diclofenac 50 mg twice a day for 10 days , with oral tamsulosin 0.4 mg once a day up to 28 days . For groups 1 , 2 and 3 , respectively , the expulsion rates were 4 % , 40 % and 68 % ( significantly different for group 1 vs group 2 , and for group 1 vs group 3 ) and mean expulsion times were 23.00 , 9.30 and 10.76 days . Both doses of tamsulosin increased stone expulsion rate and decreased expulsion time in comparison with the control , and have been shown to be safe and effective in Asian patients PURPOSE Recent studies show the interesting efficacy of different drug combinations for the spontaneous expulsion of distal ureteral stones . We performed a r and omized , prospect i ve study to assess and compare the efficacy of 3 drugs as medical expulsive therapy for distal ureteral calculi . MATERIAL S AND METHODS A total of 210 symptomatic patients with distal ureteral calculi greater than 4 mm were r and omly allocated to home treatment with phloroglucinol , tamsulosin or nifedipine ( groups 1 to 3 , respectively ) . Each group was given a corticosteroid drug and antibiotic prophylaxis with an injectable nonsteroidal anti-inflammatory drug was also used on dem and . The primary end point was the expulsion rate and the secondary end points were expulsion time , analgesic use , need for hospitalization and endoscopic treatment as well as the number of workdays lost , quality of life and drug side effects RESULTS The expulsion rate was significantly higher in group 2 ( 97.1 % ) than in groups 1 ( 64.3 % , p < 0.0001 ) or 3 ( 77.1 % , p < 0.0001 ) . Group 2 significantly achieved stone passage in a shorter time than the other 2 groups and showed a significantly decreased number of hospitalizations as well as a better decrease in endoscopic procedures performed to remove the stone . The control of renal colic pain was significantly superior in group 2 compared with the other groups , result ing in fewer workdays lost . Group 3 showed lower analgesic use and decreased workdays lost compared with group 1 . No difference in side effects was observed among the groups . CONCLUSIONS Medical expulsive therapy should be considered for distal ureterolithiasis without complications before ureteroscopy or extracorporeal lithotripsy . The use of tamsulosin in this treatment regimen produced stone expulsion in almost all cases in a short time , allowing complete home patient treatment BACKGROUND Tamsulosin , an alpha-1 receptor antagonist , has been demonstrated effective in promoting distal ureteral stone passage and in reducing pain associated with stone expulsion . This study aim ed to evaluate the effect of tamsulosin in comparison with nifedipine and extracorporeal shock wave lithotripsy ( ESWL ) on the expulsion rate of distal ureteral stones at different sizes . METHODS We assigned 314 patients to three categories : I , the stone with maximal diameter of 4.0 - 5.9 mm ; II , 6.0 - 7.9 mm , and III , 8.0 - 9.9 mm . Patients in each category were r and omly subdivided into three treatment subgroups : group A ( nifedipine group ) , group B ( tamsulosin group ) , and group C ( ESWL group ) . Stone-free rate and the dose of analgesics were recorded weekly during the 4-week follow-up period . RESULTS Three hundred and three patients completed the study . The results showed that nifedipine and tamsulosin treatments promoted a small ( 4 - 8 mm , categories I and II ) stone expulsive rate that was comparable with ESWL treatment . Nonetheless , when the stone diameter was 8.0 - 9.9 mm , ESWL showed a greater stone free rate than nifedipine and tamsulosin treatments ; no significant difference existed between the latter two therapies . Although the ESWL treatment group required the least analgesics , tamsulosin treatments required less pain medication than nifedipine ( P < 0.05 ) . CONCLUSIONS Tamsulosin treatment is recommended for patients with the stone diameter smaller than 8 mm because of its feasibility , effectiveness and safety . ESWL is more appropriate than tamsulosin therapy for the patients whose stones are larger than 8 mm PURPOSE To evaluate the clinical role of an alpha(1a-1d)-specific blocker in the medical expulsive therapy of symptomatic lower ureteral stones . MATERIAL S AND METHODS This prospect i ve study was carried out from May 2005 to December 2006 and involved 95 patients . All patients , who had symptomatic lower ureteral stones < 10 mm diameter , were enrolled in this prospect i ve study , and were r and omly divided into three groups using the statistical software programs Plus 1.0 and Plus 2.10 . Group 1 ( 32 patients ) received tamsulosin ( 0.4 mg daily ) , group 2 ( 32 patients ) received terazosin ( 2 mg daily ) , group 3 ( 31 patients ) acted as controls . All patients were diagnosed with x-rays of the kidneys , ureters , and bladder , urinary ultrasonography , and intravenous urography . All patients received the same analgesic regimen and sublingual buprenorphine on dem and . The number of colic episodes , lower urinary tract symptoms , analgesic dosages , and the number of days required for spontaneous passage of the stones were all recorded in a diary . RESULTS Expulsion was observed in 26 of 32 patients in group 1 ( 81 % ) , 25 of 32 in group 2 ( 78 % ) , and 17 of 31 in group 3 ( 55 % ) . The average expulsion time for groups 1 , 2 , and 3 were 6.3 , 6.3 , and 10.1 days , respectively . Mean analgesic dosage per patient in groups 1 , 2 , and 3 were 231 , 256 , and 347 mg , respectively . A statistically significant difference was observed between groups 1 and 2 with respect to group 3 for all three of these parameters . Adverse effects were also seen in 5 of 32 patients in group 2 ( 16 % ) , a statistically significant difference with regard to groups 1 and 3 . CONCLUSIONS Medical treatment with alpha(1a-1d)-blocker proved to be safe and effective as demonstrated by the increased stone expulsion rate and reduced expulsion time , as well as the need for analgesics We performed a r and omized , prospect i ve study to assess the possible role of combined naftopidil and tolterodine for facilitating the spontaneous expulsion of intramural ureteral stones . A total of 76 patients with intramural ureter stones were included in the study from December 2007 to February 2011 . Patients were r and omized to one of three treatment groups . Group A patients received naftopidil 25 mg/day , group B patients received naftopidil 25 mg/day plus tolterodine 2 mg ( twice a day ) , and group C patients received tolterodine 2 mg ( twice a day ) . Both groups were followed up for 2 weeks . The stone expulsion rate and time and the number of pain episodes were obtained . Subjects rated the urgency associated with each micturition using the Urinary Sensation Scale ( USS ) . Pain descriptions were recorded by the patients using the visual analog scale ( VAS ) . A significant difference was shown for the expulsion rate between the group C and the other two groups ( P < 0.001 by log rank test ) . In groups A , B and C , the mean number of pain episodes was 2.25 ± 0.90 , 1.38 ± 1.37 and 1.54 ± 1.18 , respectively . The USS score for groups A , B and C at 3 days was 2.32 ± 0.55 , 1.4 ± 0.58 and 1.34 ± 0.49 , respectively . It was 1.75 ± 0.44 , 1.2 ± 0.41 and 1.22 ± 0.42 , respectively , at 7 days . On the other h and , a statistically significant difference was found between groups A and B , and groups A and C in relation to the visual analog scale score on days 3 and 7 , respectively . Treatment with naftopidil and tolterodine appears to be beneficial in intramural ureteral stones clearance , particularly in the intramural ureter with symptoms of vesical irritability PURPOSE Few studies have investigated the efficacy of silodosin , a recently introduced selective alpha 1-A adrenoceptor antagonist , in medical expulsive therapy ( MET ) for ureteral calculi . The results of these studies , which all evaluated the efficacy of 8 mg/day , indicate that silodosin is a potential treatment for ureteral calculi . This study investigated the efficacy of 4 mg/day of silodosin for MET of distal ureteral stones 4 to 10 mm in diameter . MATERIAL AND METHOD After 70 patients had been r and omized into 2 groups of 35 patients each , both the control and experimental groups ( groups 1 and 2 , respectively ) were advised to take 75 mg/day of diclofenacsodiumas needed for pain relief but only the experimental group to take 4 mg/day of silodosin . After 21 days , the groups were compared regarding the stone expulsion rate and duration , number of renalcolicepisodes , and analgesicdosage . RESULTS The median expulsion rates were 71.4 % and 91.4 % in groups 1 and 2 , respectively , and the difference between them was significant ( P=0.031 ) . The median expulsion duration s were 12.91±6.14 and 8.03±4.99 days , respectively , and the difference between them was significant ( P<0.001 ) . No significant differences were found regarding the median number of renal colic episodes or median analgesic dosage . While no patients in group 1 experienced side effects , 5 patients ( 14 % ) in group 2 experienced retro grade ejaculation . CONCLUSION These results indicate that 4 mg/day of silodos in facilitates the expulsion of distal ureteral stones 4 to 10 mm in diameter but does not significantly reduce the number of renal colic episodes or analgesic dosage The objective of this study is to assess the efficacy of an alpha-1 adrenergic receptor blocking agent on the spontaneous passage of proximal ureteral calculi ≤10 mm . 92 patients having single radio-opaque proximal ureteral stone ≤10 mm were r and omized into two groups . Group 1 patients ( n = 50 ) were followed with classical conservative approach and patients in Group 2 ( n = 42 ) additionally received tamsulosin , 0.4 mg/day during 4 weeks follow-up . The stone passage rates , stone expulsion time , VAS score , change in colic episodes , and hospital re-admission rates for colicky pain were compared . The patients were furthermore stratified according to stone diameters < 5 and 5–10 mm . The data of these subgroups were also compared . Stone expulsion rates showed statistically significant difference between tamsulosin receivers and non-receivers ( 35.7 vs 30 % , p = 0.04 ) . Time to stone expulsion period was also shortened in those receiving tamsulosin ( 8.4 ± 3.3 vs 11.6 ± 4.1 days , p = 0.015 ) . Likewise , the mean VAS score and renal colic episodes during follow-up period were significantly diminished in Group 2 patients ( 4.5 ± 2.3 vs 8.8 ± 2.9 , p < 0.01 and 66.6 vs 36 % , p = 0.001 , respectively ) . Among the stones < 5 mm , tamsulosin receiving patients had higher spontaneous passage rate ( 71.4 vs 50 % , p < 0.001 ) . The prominent effect of tamsulosin on the 5–10 mm stones was the relocation of the stones to a more distal part of ureter ( 39.3 vs 18.7 % , p = 0.001 ) . Administration of tamsulosin in the medical management of proximal ureteral calculi can facilitate the spontaneous passage rate in the stone < 5 mm and the relocation of the stones between 5 and 10 mm to more distal part of the ureter In this article , we investigated the effect of the combined use of tamsulosin and potassium citrate ( Uralyt-U ® ) for the treatment of uric acid stones in the distal ureter . The study was design ed as a prospect i ve , double blind r and omized controlled trial . A total of 191 adult patients with radiolucent distal ureteral calculi were recruited . We included patients with solitary stones ≥5 mm with mild or moderate hydronephrosis and a normal contralateral tract . The patients were r and omized into four equal groups ( the placebo , tamsulosin , Uralyt-U ® , and the combined treatment groups ) . The patients were treated for a maximum duration of 4 weeks or until stone expulsion . The stone size in all groups ranged from 5 to 11 mm ( 7.69 ± 1.7 mm ) . The total expulsion rate of the stones was significantly lower in the control group ( 26.1 % ) compared with that of any of the other three groups ( 68.8 , 58.7 , and 84.8 % respectively ) ( P < 0.05 ) . Meanwhile , the difference between the Uralyt-U ® group and the combined treatment group was also statistically significant ( P < 0.05 ) . When we studied the patients with stones > 8 mm as a separate subgroup to find the effect of the used drugs on the relatively large stones , we detected that the expulsion rate of these stones was significantly higher in the patients who received the combined treatment in comparison with any of the other three groups ( P < 0.05 ) . In conclusion , the use of urinary alkalization with tamsulosin can increase the frequency of spontaneous passage of distal ureteral uric acid stones especially those of 8–11 mm STUDY OBJECTIVE The alpha-adrenergic antagonist tamsulosin hydrochloride has become an increasingly common adjunct in the treatment of ureteral calculi ; however , its efficacy in a general emergency department ( ED ) population has not been investigated . METHODS We conducted a r and omized , controlled trial of adult ED patients with distal ureteral calculi diagnosed by computed tomography scan . Patients were r and omized to receive either a 10-day course of ibuprofen and oxycodone plus tamsulosin or ibuprofen and oxycodone alone . The primary outcome measure was successful spontaneous ureteral stone expulsion at 14 days . Secondary outcomes included time to stone passage , self-reported pain scores , number of colicky pain episodes , unscheduled return ED/ primary care visits , number of days of missed work/usual function , amount of analgesic used , and adverse events . RESULTS Eighty subjects were enrolled in the study , with 77 completing the trial . Mean stone size was 3.6 mm ( 95 % confidence interval [ CI ] 3.4 to 3.9 ) . Successful spontaneous stone expulsion at 14 days was similar between the groups , with 27 ( 77.1 % ) subjects in the tamsulosin group and 24 ( 64.9 % ) subjects in the st and ard therapy group reporting spontaneous stone passage , a difference of 12 % ( 95 % CI -8.4 % to 32.8 % ) . At 2- , 5- , and 14-day follow-up , there were no clinical ly important ( or statistically significant ) differences between the groups for any secondary outcome measure . No adverse events were reported in either group . CONCLUSION In this cohort of adult ED patients with distal ureteral calculi , treatment with tamsulosin did not substantially improve any of the studied outcome measures compared with treatment with ibuprofen and oxycodone alone PURPOSE Naftopidil is a specific alpha1D-adrenergic receptor antagonist . We performed the current r and omized , controlled study to determine the expulsive role of naftopidil for distal ureteral stones . MATERIAL S AND METHODS From March 2006 to January 2007 , 60 patients with distal ureteral stones were r and omly divided into groups 1 and 2 . Group 1 served as the control and underwent watchful waiting , while group 2 received 50 mg naftopidil daily in the morning . All patients were instructed to drink a minimum of 2 l water daily . The stone expulsion rate and time , potential side effects of naftopidil , number of pain episodes and requirements for pain medication were documented during the 14-day followup . RESULTS All patients in groups 1 and 2 completed the study . There was no difference between the groups in patient age , sex and stone size . The stone expulsion rate was significantly higher in group 2 than in group 1 ( 90.0 % vs 26.7 % , p < 0.01 ) . No significant difference in expulsion time was noted between the groups . No patients experienced obvious naftopidil side effects or ureteral colic . Multivariate analysis using a Cox proportional hazards model indicated that the probability of expulsion was increased 5.263 times ( 95 % CI 2.304 - 12.024 ) in group 2 compared with that in group 1 ( p < 0.001 ) . CONCLUSIONS The selective alpha1D-blocker naftopidil can significantly facilitate spontaneous passage of distal ureteral stones with few side effects , providing a new choice for medical expulsive therapy BACKGROUND Many minimally invasive interventional techniques as well as expectant treatment exist for the management of lower ureteric calculi . This study was conducted to evaluate th efficacy of tamsulosin as an expulsive pharmacologic therapy for the treatment of distal uretern stone . METHODS This r and omized control trial included 100 patients over 18 years of age wit stone Size > or = mm in distal 1/3 of ureter . Patients were r and omly assigned into two groups ( A & B Group A Patients were given Capsule Tamsulosin 0.4 mg , 1 daily up to 4 weeks while group B patients were given placebo , 1 Capsule daily up to 4 weeks . The primary endpoint was expulsio rate . A written informed consent was taken from all the patients . Expulsion time , need for analgesics , need for hospitalization and drug side effects were secondary endpoints . RESULTS A total of 49 patients in group A and 48 patients in group B reported back , therefore 97 out of 10 patients were evaluated . Mean age of the patients was 36.34 years ( range 18 - 57 years ) . Mea stone size was 5.78 mm ( range 4 - 8 mm ) in greatest dimension . A stone expulsion rate of 85.71C ( 42 patients ) was noted in group A and 54.20 % ( 26 patients ) in group B. Group A revealed statistically significant advantage in term of stone expulsion rate ( p=0.032 ) . Considering expulsio time in days group A showed statistically significant advantage ( p=0.015 ) . Regarding age , se ) stone size and stone lateralization ( right/left ) , there was no significant difference between th group A and B. No drug side effects were noted in both the groups . CONCLUSION By usin tamsulosin a higher stone expulsion rates can be achieved in a shorter time . More r and omize control trials are required to establish tamsulosin as a st and ard medical expulsive treatment OBJECTIVES To compare the efficacy of tamsulosin versus tamsulosin plus tadalafil as medical expulsive therapy for lower ureteric stones . METHODS Between January 2013 and December 2013 , 244 patients presenting with distal ureteric stones ( size 5 - 10 mm ) were r and omized equally to tamsulosin ( group A ) or tamsulosin plus tadalafil ( group B ) . Therapy was given for a maximum of 4 weeks . Stone expulsion rate , time to stone expulsion , analgesic use , number of hospital visits for pain , follow up , endoscopic treatment and adverse effects of drugs were recorded . Statistical analyses were carried out using Student 's t-test and the χ(2 ) -test . RESULTS There was a statistically significant higher expulsion rate in group B compared with group A ( 83.6 % vs 65.5 % ; P-value = 0.031 ) and a shorter time to expulsion ( 14.9 ± 4.4 days vs 16.7 ± 4.8 days ; P-value = 0.003 ) . Statistically significant differences were noted in terms of the number of hospital visits and analgesic requirement in favor of group B. There was no serious adverse event . An improvement in erectile function was noted in patients of group B compared with those of group A. CONCLUSIONS Medical expulsive therapy for distal ureteric stones using tamsulosin plus tadalafil is safe , effective and well tolerated . Furthermore , tadalafil provides the additional advantage of improving erectile dysfunction when this condition coexists with a lower ureteric stone Introduction : We assessed the efficacy of using an α-1A-specific blocker for improving the success rate in shock wave lithotripsy ( SWL ) for lower ureteral stones . Material s and Methods : This prospect i ve study was conducted from June 2005 to December 2006 and involved 107 patients . All the patients underwent SWL with the PCK Stonelith . The patients were r and omly divided into 3 groups : group 1 ( 34 patients ) received tamsulosin , group 2 ( 35 patients ) received terazosin , and group 3 ( 38 patients ) received placebo . All patients were diagnosed by kidney-ureter-bladder X-ray , abdominal ultrasonography and intravenous urography . The number of colic episodes , lower urinary tract symptoms , analgesic dosage and days for spontaneous passage of the stones through the ureter were recorded by diary . Statistical analyses were performed using ANOVA , the χ2 test , Fisher ’s exact test and the non-parametric Wilcoxon 2- sample t test . Results : There were no differences between the groups regarding age , stone size , expulsion time and expulsion rate . The number of colic episodes and the analgesic dosage were significantly lower in group 1 compared with groups 2 and 3 . A statistically significant difference was observed in lower urinary tract symptoms : lower urinary tract symptoms were observed in 4 of 34 patients in group 1 ( 12 % ) , in 8 of 35 in group 2 ( 23 % ) , and in 13 of 38 in group 3 ( 34 % ) . Adverse effects were noted in 5 of 32 patients in group 2 ( 16 % ) , which was significantly different in comparison with group 3 . Conclusions : Administration of an α-1A-specific blocker reduced analgesic dosage and colic episodes after SWL of lower ureteral stones . There was no benefit with regard to increasing stone expulsion rate or decreasing expulsion time Abstract Objective . An antispasmodic agent and a medicine that facilitates stone expulsion are given commonly as conservative therapy for ureteral stones in Japan . The goal of this study was to compare the efficacy of the addition of various α1-blockers to the conservative therapy for spontaneous passage of ureteral stones . Material and methods . The subjects were 132 patients with stones from the upper to the lower ureter who were r and omly placed into one of four groups and followed for 1 month to assess spontaneous passage of stones . The control group received daily doses of 240 mg flopropione as an antispasmodic agent and 1350 mg extract of Quercus salicina Blume/Quercus stenophylla Makino as a medicine that facilitates stone expulsion . The other three groups received this therapy and daily doses of 30 mg urapidil , 0.2 mg tamsulosin or 50 mg naftopidil , respectively . The characteristics of the stones and stone expulsion were evaluated by urinalysis , a kidney , ureter and bladder ( KUB ) X-ray , ultrasound and computed tomography . Results . All patients completed the study and there were no major side-effects . There was no difference in age , stone position or stone size among the groups . Multivariate analysis using a Cox proportional hazards model indicated that the probability of stone expulsion for 1 month was increased 2.38 times ( 95 % confidence interval 1.23–4.61 ) by naftopidil compared with control therapy alone ( p = 0.01 ) . Conclusion . Naftopidil in combination with an antispasmodic agent and a medicine that facilitates stone expulsion produces a significantly increased rate of ureteral stone expulsion PURPOSE We evaluate and compare the effectiveness of 2 different medical therapies during watchful waiting in patients with lower ureteral stones . MATERIAL S AND METHODS A total of 86 patients with stones less than 1 cm located in the lower ureter ( juxtavesical or intramural tract ) were enrolled in the study and were r and omly divided into 3 groups . Group 1 ( 30 ) and 2 ( 28 ) patients received daily oral treatment of 30 mg deflazacort , ( maximum 10 days ) . In addition group 1 patients received 30 mg nifedipine slow-release ( maximum 28 days ) and group 2 received 1 daily oral therapy of 0.4 mg tamsulosin ( maximum 28 days ) , Group 3 patients ( 28 ) were used as controls . Statistical analyses were performed using Student 's test , ANOVA test , chi-square test and Fisher 's exact test . RESULTS The average stone size for groups 1 to 3 was 4.7 , 5.42 and 5.35 mm , respectively , which was not statistically significant . Expulsion was observed in 24 of 30 patients in group 1 ( 80 % ) , 24 of 28 in group 2 ( 85 % ) and 12 of 28 in group 3 ( 43 % ) . The difference in groups 1 and 2 with respect to group 3 was significant . Average expulsion time for groups 1 to 3 was 9.3 , 7.7 and 12 days , respectively . A statistically significant difference was noted between groups 2 and 3 . Mean sodium diclofenac dosage per patient in groups 1 to 3 was 19.5 , 26 , and 105 mg , respectively . A statistical significant difference was observed between groups 1 and 2 with respect to group 3 . CONCLUSIONS Medical treatments with nifedipine and tamsulosin proved to be safe and effective as demonstrated by the increased stone expulsion rate and reduced need for analgesic therapy . Moreover medical therapy , particularly in regard to tamsulosin , reduced expulsion time PURPOSE We analyze the natural history of stone passage in patients with ureterolithiasis , and define factors predictive of spontaneous passage . MATERIAL S AND METHODS A total of 75 patients with ureteral calculi were prospect ively followed for stone passage . Clinical data included patient gender and age , stone size and location , pain medication requirements and interval to stone passage . Of the 75 patients 13 ( 17 % ) required intervention and 62 ( 83 % ) were followed until spontaneous stone passage . Stones requiring intervention were not included in the time to passage analysis . RESULTS Of the 75 patients 41 ( 55 % ) had ureteral stones 2 mm . or smaller with an average time to stone passage of 8.2 days and only 2 ( 4.8 % ) required intervention , 18 ( 24 % ) had stones between 2 and 4 mm . with an average time to stone passage of 12.2 days and 3 ( 17 % ) required intervention , and 16 had stones 4 mm . or greater with an average time to stone passage of 22.1 days and 8 required intervention . For 95 % of stones to pass it took 31 days for those 2 mm , or less , 40 days for those 2 to 4 mm . and 39 days for those 4 to 6 mm . Multivariate analysis revealed that size , location and side were statistically related to stone passage interval ( p = 0.012 ) . Stones that were smaller , more distal and on the right side were more likely to pass spontaneously and required fewer interventions . CONCLUSIONS Interval to stone passage is highly variable and dependent on stone size , location and side . Degree of pain , and patient gender and age had no bearing on the time to stone passage . Of ureteral stones 95 % 2 to 4 mm . pass spontaneously but passage may take as long as 40 days . Intervention may be required in 50 % of ureteral calculi greater than 5 mm OBJECTIVES To compare two treatment regimens in patients with ureteral calculi . One regimen ( control arm ) used routine drugs , and the second regimen ( treatment arm ) used the same routine drugs plus uncommonly used drugs . METHODS Between February and October 1998 , 70 consecutive patients were evaluated for symptomatic ureteral calculi . Thirty-five patients were r and omized to a control arm and received ketorolac , oxycodone , and acetaminophen combination tablets and prochlorperazine suppositories . Thirty-five patients were r and omized to the treatment arm and received the same medications plus nifedipine XL , prednisone , and trimethoprim/sulfa combination tablets and plain acetaminophen . Stone passage rates , work days lost , emergency room visits , surgical interventions , and possible side effects of the drugs were recorded . RESULTS The treatment arm ( addition of nifedipine XL , prednisone , trimethoprim/sulfa , and plain acetaminophen ) had higher ( 86 % versus 56 % ) stone passage rates and fewer lost work days ( mean 1.76 versus 4.9 ) , emergency room visits ( 1 versus 4 ) , and surgical interventions ( 2 versus 15 ) . Both arms exhibited similar potential drug side effects . CONCLUSIONS The addition of a calcium channel blocking agent , steroids , antibiotics , and more acetaminophen effected a higher stone passage rate and fewer lost work days , emergency room visits , and surgical interventions OBJECTIVES To assess the clinical role of corticosteroids in the medical expulsive therapy of symptomatic distal ureteral stones . METHODS Between January 2004 and September 2005 , 114 patients with symptomatic distal ureteral stones with a > /=5 mm diameter were enrolled in this prospect i ve study and divided into four groups based on the urologist ( of four ) who treated them in the emergency unit . Group A ( 33 patients ) received tamsulosin ( 0.4 mg daily ) , group B ( 24 patients ) received deflazacort ( 30 mg daily ) , group C ( 33 patients ) received both ( 0.4 mg tamsulosin+30 mg deflazacort daily ) , and control group D ( 24 patients ) received only analgesics . The treatment duration was 10 d to prevent the side-effects of prolonged corticosteroid therapy . The end points were the expulsion rate , analgesic consumption , number of ureteroscopies , and safety . RESULTS The groups were comparable in terms of age , sex , and stone location . The stone diameter was 5.96+/-0.33 mm for group A , 5.83+/-0.4 mm for group B , 5.88+/-0.23 mm for group C , and 5.71+/-0.5 mm ( p>0.05 ) for group D. The rates of expulsion for the four groups were 60 % , 37.5 % , 84.8 % , and 33.3 % , respectively . There was a significant difference between group C and the other groups ( p<0.001 ) . The mean analgesic consumption was 42.5+/-0.4 mg for group A , 50+/-0.3 mg for group B , 27.3+/-0.5 mg for group C , and 81+/-0.33 mg for group D , with a significant difference between group C and the other groups ( p<0.001 ) . During the treatment period , only two cases of drug side-effects related to tamsulosin ( without any drop-outs ) were recorded . CONCLUSION When the medical expulsive therapy for symptomatic distal ureteral stones is considered , the use of steroids ( deflazacort ) proves efficient only when administered together with alpha(1)-blockers ( tamsulosin ) . In addition , tamsulosin used on its own as a medical expulsive therapy can be considered as an alternative treatment for those patients who are not suitable for steroid therapy , as it is generally efficient Recently , we reported that α1A adrenoceptor ( AR ) is the main participant in phenylephrine-induced human ureteral contraction . We therefore decided to carry out a prospect i ve r and omized study to evaluate the effects of silodosin , a selective α1A AR antagonist , as a medical expulsive therapy for ureteral stones . A total of 187 male patients , who were referred to our department for the management of symptomatic unilateral ureteral calculi of less than 10 mm , were r and omly divided into two groups : group A ( 92 patients ) , who were instructed to drink 2 L of water daily , and group B ( 95 patients ) , who received the same instruction and were also given silodosin ( 8 mg/daily ) for a maximum of 8 weeks . Expulsion rate , mean expulsion time and need for analgesics were examined . Overall , the mean expulsion time was 15.19 ± 7.14 days for group A and 10.27 ± 8.35 days for group B ( P = 0.0058 ) . In cases involving distal ureteral stones , the mean expulsion time was 13.40 ± 5.90 and 9.29 ± 5.91 days , respectively ( P = 0.012 ) . For stones of 1 - 5 mm in diameter , the mean expulsion time was 14.28 ± 6.35 and 9.56 ± 8.45 days , respectively ( P = 0.017 ) . For stones of 6 - 9 mm in diameter , the stone expulsion rate was 30.4 % and 52.2 % ( P = 0.036 ) , and the mean expulsion time was 21.00 ± 9.9 and 11.33 ± 8.31 days , respectively ( P = 0.038 ) . Herein , we report the first on silodosin in the management of ureteral lithiasis . Our findings suggest that silodosin might have potential as a medical expulsive therapy for ureteral stones OBJECTIVES To evaluate the activity of the therapeutic agents ( tamsulosin and /or tolterodine ) used to accelerate the expulsion of stones and to reduce the probable complications during observation of the medical treatment of distal ureteral stones to allow spontaneous passage . METHODS A total of 120 patients with distal ureteral stones were included in the study . Patients with stones less than 10 mm and allowing urinary flow were included in the study . The patients were studied in four r and omly divided groups . Group 1 patients received tamsulosin 0.4 mg/day , group 2 patients received tamsulosin 0.4 mg/day plus tolterodine 2 mg ( twice a day ) , group 3 patients received tolterodine 2 mg ( twice a day ) , and group 4 patients did not receive any medical treatment ( control group ) . RESULTS Differences among the four groups in patient age and stone dimension were not statistically significant ( P > 0.05 ) . The stone expulsion rates were greater ( P < 0.05 ) in groups 1 and 2 than in groups 3 and 4 . A significant variation ( P < 0.05 ) regarding the time to stone expulsion was observed in groups 1 and 2 . CONCLUSIONS In our study , the use of tamsulosin for the expulsion of distal ureteral stones was effective ; however , the use of tolterodine provided no additional advantages Abstract We evaluated the efficacy of tamsulosin and nifedipine in medical expulsive therapy ( MET ) in patients with distal ureteral stone . In addition , we tried to determine the predictive value of Hounsfield Unit ( HU ) of the stone in the success of MET . A total of 75 patients with a distal ureteral stone of 5–10 mm diameter were r and omly divided into three groups . Group 1 ( n = 25 ) received tamsulosin 0.4 mg/d ; group 2 ( n = 25 ) received nifedipine 10 mg/day p.o and group 3 ( n = 25 ) received diclofenac sodium 50 mg p.o . when required . At the beginning of each treatment , the HU of the stone was also measured using a non-contrast computerized tomography in all the patients . The results were evaluated at week four . The mean age of the patients was 36.8 ( range , 16–68 ) years . Stone expulsion was observed in 19 ( 76 % ) patients in group 1 , 16 ( 64 % ) patients in group 2 and 9 ( 36 % ) patients in group 3 ( pgroup1 - 3 = 0.004 , pgroup2 - 3 = 0.048 and pgroup1 - 2 = 0.355 ) . The mean expulsion time was 9 , 9.1 and 10.3 d , respectively ( pgroup1 - 3 < 0.001 , pgroup2 - 3 < 0.001 and pgroup1 - 2 = 0.619 ) . The mean diclofenac sodium dose per patient was 544 , 602 and 1408 mg in groups 1 , 2 and 3 , respectively ( pgroup1 - 3 < 0.001 , pgroup2 - 3 < 0.001 and pgroup1 - 2 = 0.977 ) . The mean HU of the stone in patients with and without a successful MET was 363 and 389 , respectively ( p = 0.462 ) . Our results showed that MET with both nifedipine and tamsulosin provided a similar increase in the expulsion rate for distal ureteral stones . HU does not seem to be a predictive parameter for stone expulsion OBJECTIVES To assess the clinical efficacy of doxazosin as the medical-expulsive therapy for distal ureterolithiasis . METHODS A total of 65 patients with a symptomatic 4 - 7 mm distal ureteral stone were included in the study . Patients were r and omized to 1 of the 2 treatment groups . Group 1 ( n=32 patients ) was the control group and received diclofenac sodium 50 mg for their pain and group 2 ( n=33 patients ) received doxazosin ( 2 mg daily at the night ) along with diclofenac sodium 50 mg . The treatment duration was until stone expulsion or 28 days , whichever come first . The primary endpoint of the study was the stone expulsion rate . The secondary endpoints included time to stone expulsion , use of analgesics , and number of emergency room visits , hospitalizations , and drug side effects . Statistical analyses were performed using chi-square test and Fisher exact test . RESULTS Both groups were comparable in terms of demographic , clinical , and stone-related parameters . Stone expulsion rate was significantly higher in the treatment group ( 38 % for group 1 and 70 % for group 2 , P=.009 ) while the expulsion time was significantly lesser in group 2 patients ( P=.005 ) . During the treatment period , we observed significant differences between the 2 groups in the number of pain episodes and analgesic used ( P=.0001 ) . None of the patients in either groups reported adverse drug-related events . CONCLUSIONS Doxazosin significantly improves stone expulsion and is associated with decreased colic frequency and use of analgesia . It is also well tolerated with no adverse drug-related events Objective Recently , we reported that alpha 1A-adrenoceptor ( AR ) is the main participant in phenylephrine-induced human ureteral contraction . We therefore decided to carry out a prospect i ve r and omized study to evaluate the effects of silodosin , a selective alpha 1A AR antagonist , as a medical expulsive therapy ( MET ) for distal ureteral stones . Methods A total of 112 male patients , who were referred to our department for the management of symptomatic unilateral distal ureteral calculi of less than 10 mm , were r and omly divided into two groups : group A ( 56 patients ) who were instructed to drink 2 L of water daily and group B ( 56 patients ) who received the same instruction and were also given silodosin ( 8 mg/daily ) for a maximum of 4 weeks . Expulsion rate , expulsion time and need for analgesics were examined . Results The expulsion rate was 55.3 % ( 56 patients ) for group A and 72.7 % ( 55 patients ) for group B ( P = 0.106 ) . The expulsion rate for < 5 mm was 92.9 % ( 28 patients ) for group A and 69.2 % ( 26 patients ) for group B ( P = 0.053 ) . The expulsion rate for ≥5 mm was 17.9 % ( 28 patients ) for group A and 75.9 % ( 29 patients ) for group B ( P = 0.001 ) . The expulsion time was 13.40 ± 5.90 and 9.29 ± 5.91 days , respectively ( P = 0.012 ) . Analgesics were required 1.5 ± 3.1 and 0.3 ± 0.9 times , respectively ( P = 0.382 ) . Stone size in expulsion cases was 3.64 ± 1.25 and 5.23 ± 2.32 mm , respectively ( P = 0.003 ) . Conclusions Stone size has been identified as an important predictive factor for stone expulsion . Therefore , it is important that administration of silodosin can facilitate expulsion of 1.5 mm or larger distal ureteral stones , as compared to control . We believe that silodosin might have potential as a MET for distal ureteral stones OBJECTIVES To evaluate the effectiveness of medical therapy during watchful waiting in patients with distal ureter stones . METHODS Ninety-six patients with radiopaque stones located in the distal tract of the ureter and with stone sizes of 1 cm or smaller were involved in the study . The patients were r and omly divided into two groups . Group A ( n = 48 ) received oral treatment with 30 mg of deflazacort daily ( maximum 10 days ) plus 30 mg of slow-release nifedipine daily ( maximum 4 weeks ) . Group B ( n = 48 ) underwent a wait- and -watch approach . Both groups of patients were allowed to use diclofenac on dem and . Statistical analyses were carried out using Student 's t test , the chi-square test , and Fisher 's exact test . RESULTS The average stone size was 5.8 + /- 1.8 mm for group A and 5 . 5 + /- 1.4 mm for group B. No statistically significant difference was found in stone size . Stone expulsion was observed in 38 ( 79 % ) of 48 patients in group A and in 17 ( 35 % ) of 48 patients in group B. The average expulsion time was 7 days ( range 2 to 10 ) for group A and 20 days ( range 10 to 28 ) for group B. A statistically significant difference was observed in both the expulsion rate and the expulsion time ( P < 0.05 ) . The mean amount of sodium diclofenac used was 15 mg per patient for group A and 105 mg per patient for group B ( P < 0.05 ) . CONCLUSIONS The medical treatment proved to be effective and safe , as demonstrated by the increased stone expulsion rate , decreased expulsion time , and reduced need for analgesic therapy OBJECTIVE To evaluate the efficacy of low dose tamsulosin for facilitating spontaneous passage of ureteral stones in Japanese male patients . METHODS A total of 71 patients with symptomatic ureteral stones , 10 mm or smaller in size , were r and omly allocated into groups 1 and 2 . Group 1 received tamsulosin ( 0.2 mg/day ) for a maximum of 4 weeks and group 2 received no medication . The primary endpoint was the stone expulsion rate and the secondary endpoints were stone expulsion time and analgesic use . RESULTS There were no significant differences between the groups in terms of age , stone size and location . The stone expulsion rate was significantly higher in group 1 than in group 2 ( 77 % vs 50 % , P = 0.002 ) . No significant differences were noted in the stone expulsion time and analgesic use between the groups . CONCLUSION Low dose tamsulosin can significantly facilitate spontaneous passage of ureteral stones without significant side-effects in Japanese male patients Expulsive medical therapy of ureteral stones is not well established . To test the efficacy of a calcium antagonist ( nifedipine ) associated with a corticosteroid ( methylprednisolone ) in facilitating ureteral stone passage , we studied 86 patients with a unilateral ureteral radiopaque stone not larger than 15 mm . in maximum diameter , confirmed in each case by drop excretory urography . Patients were r and omly treated for a maximum of 45 days under double-blind conditions with 16 mg . methylprednisolone plus 40 mg . nifedipine daily ( group 1 - 13 women and 30 men , mean age 45 + /- 14 years , st and ard deviation ) and with 16 mg . methylprednisolone plus placebo daily ( group 2 - 18 women and 25 men , mean age 43 + /- 14 years ) . All patients also received 2 l. of low mineral content water daily . The average maximum diameter of the stones was 6.7 + /- 3.0 mm . in group 1 and 6.8 + /- 2.9 mm . in group 2 ( not significant ) . Partial ureteral obstruction was present in approximately half of the patients in both groups . Four patients in group 1 and 6 in group 2 dropped out of the study . In group 1 , 34 patients had successful results ( stone passage without surgical manipulation ) and 5 failed ( success rate 87 % ) , compared to 24 and 13 , respectively , in group 2 ( success rate 65 % ) . This difference was significant ( p = 0.021 , Fisher 's exact test ) . No difference was present in the maximum stone diameter among the successful cases in groups 1 and 2 ( 6.4 + /- 2.8 and 5.3 + /- 2.2 mm . , respectively , not significant ) . In both groups the maximum diameter of the stone was larger in the failed than in the successful cases ( group 1 - 10.4 + /- 3.0 versus 6.4 + /- 2.8 mm . , p = 0.005 , and group 2 - 9.3 + /- 2.5 versus 5.3 + /- 2.2 mm . , p = 0.0001 ) . In group 1 the mean interval for stone passage in the successful cases was 11.2 + /- 7.5 days , compared to 16.4 + /- 11.0 days in group 2 ( p = 0.036 , Student 's t test ) . We conclude that nifedipine associated with methylprednisolone is effective in facilitating ureteral stone passage Alpha1-adrenoblocker tamsulosin reduces muscle spasm in the ureteric wall , decreases peristalsis below and raises pressure above the stone thus facilitating stone passage . Patients on tamsulosin had spontaneous stone passage in 73.8 % cases while only 22.4 % patients on routine therapy became stone free . Tamsulosin also shortens hospital stay . Use of tamsulosin 0.4 mg daily in patients with distal ureteric stones is pathogenetically vali date d , is highly clinical ly and cost effective OBJECTIVE To investigate the effect of sexual intercourse on spontaneous passage of distal ureteral stones . MATERIAL AND METHODS The patients were r and omly divided into 3 groups with r and om number table envelope method . Patients in group 1 were asked to have sexual intercourse at least 3 - 4 times a week . Patients in group 2 were administered tamsulosin 0.4 mg/d . Patients in group 3 received st and ard medical therapy alone and acted as the controls . The expulsion rate was controlled after 2 and 4 weeks . Differences in the expulsion rate between groups were compared with the chi-square test for 3 × 2 tables . P < .05 was considered as statistically significant . RESULTS The mean stone size was 4.7 ± 0.8 mm in group 1 , 5 ± 1 mm group 2 , and 4.9 ± 0.8 mm group 3 ( P = .4 ) . Two weeks later , 26 of 31 patients ( 83.9 % ) in the sexual intercourse group , and 10 of 21 patients ( 47.6 % ) in tamsulosin group passed their stones , whereas 8 of 23 patients ( 34.8 % ) in the control group passed their stones ( P = .001 ) . The mean stone expulsion time was 10 ± 5.8 days in group 1 , 16.6 ± 8.5 days in group 2 , and 18 ± 5.5 days in group 3 ( P = .0001 ) . CONCLUSION Our results have indicated that patients who have distal ureteral stones ≤6 mm and a sexual partner may be advised to have sexual intercourse 3 - 4 times a week to increase the probability of spontaneous passage of the stones OBJECTIVE To study the impact of tamsulosin on the rate of spontaneous passage of distal ureteral stones . METHODS A total of 100 patients with stones sized 10 mm or smaller , located in the distal part of the ureter were included . Patients were r and omly assigned to 2 equal groups . Group 1 received 0.4 mg tamsulosin once daily and group 2 received placebo . The investigators and the patients were masked to the type of treatment . Patients were followed-up until passage of the stone , or for a maximum of 4 weeks . The number of pain episodes , need for analgesia , stone expulsion rate and time , and possible side effects of medications were observed in both groups . RESULTS Apart from 4 patients in the placebo group who were lost to follow-up , all patients complied with the prescribed medications and continued the study . Stone expulsion occurred in 41 of 50 patients ( 82 % ) in group 1 and in 28 of 46 patients ( 61 % ) in group 2 ( P = .02 ) . The chance of stone expulsion was 3 times higher in the tamsulosin group ( relative risk [ RR ] = 2.93 ; 95 % CI , 1.152 - 7.45 ) . In group 1 , patients with stones sized < or = 5 mm showed a significantly higher expulsion rate compared to those with larger stones ( > 5 mm ) . Age , gender , and stone laterality had no significant impact on the expulsion rate . The expulsion time was significantly shorter in the tamsulosin group ( 6.4 + /- 2.77 days vs 9.87 + /- 5.4 days for groups 1 and 2 , respectively ) . Moreover , the frequency of pain episodes , the need for diclofenac , and its total dosage were significantly lower in the tamsulosin group . Side effects observed in both groups were comparable and mild , and no patient withdrew because of them . CONCLUSIONS Tamsulosin is a safe and effective drug that enhances spontaneous passage of distal ureteral stones sized 10 mm or smaller OBJECTIVES To evaluate the effect of alfuzosin in improving symptoms in , and quality of life of , patients with indwelling double-J ureteral stents . METHODS A total of 100 patients , 50 men and 50 women ( mean age 54.2 years ) , with unilateral ureteral stone-related hydronephrosis , who had opted for conservative management with insertion of a double-J ureteral stent , were prospect ively r and omized into two groups . Group 1 included 50 patients who received 10 mg of alfuzosin , once daily for 4 weeks , and group 2 consisted of 50 patients who received placebo for the same period . All patients completed a vali date d Ureteral Stent Symptom Question naire ( USSQ ) 4 weeks after stent placement . RESULTS The mean urinary symptom index score was 21.6 in group 1 and 28.1 in group 2 ( P < 0.001 ) . Stent-related pain was reported by 44 % of patients in group 1 and 66 % of patients in group 2 ( P = 0.027 ) . The mean pain index score was 14.6 in group 1 and 17.4 in group 2 ( P = 0.047 ) . The mean general health index score was statistically greater ( P < 0.001 ) in group 1 compared with in group 2 ( 8 versus 11.4 , respectively ) . Among sexually active patients , the mean sexual score was 2.3 in group 1 and 2.9 in group 2 ( P = 0.017 ) . CONCLUSIONS Stent-related symptoms were present in 66 % of the controls ( group 2 ) . Alfuzosin improved a subset of stent-related urinary symptoms and pain . Patients receiving alfuzosin had their sexual function and general health better preserved OBJECTIVES To assess the spontaneous passage rate for patients being treated with alfuzosin 10 mg daily after presenting with an acute ureteral stone compared with a control group , and to assess the respective pain control status . METHODS This was a prospect i ve r and omized controlled trial . Patients presenting with an acute ureteral stone ( size 5 - 10 mm ) were enrolled and r and omized into a medical expulsive therapy ( MET ) group or control group . The MET group received alfuzosin slow release ( SR ) 10 mg daily for 4weeks and dologesic ( paracetamol+dextropropoxyphene , four tablets daily on dem and ) for 2weeks . The control group received the same analgesics for 2weeks only . Diclofenac sodium SR 100 mg daily for 2weeks was added in case of suboptimal pain control . All the patients were assessed through phone interview at week 2 and with kidney-ureter-bladder X-ray at week 5 to check for any evidence of stone passage . RESULTS A total of 67 patients were included in the analysis . The overall spontaneous passage rate was increased by 31.8 % with MET ( P=0.006 ) . For an upper ureteral stone , the rate was increased by 51.3 % ( P=0.01 ) . The MET group used significantly less dicolofenac sodium ( 1.5 tablets vs 6.7 tablets , P=0.031 ) . CONCLUSIONS MET using alfuzosin SR 10 mg daily is effective to enhance the ureteral stone spontaneous passage rate , particularly for upper ureteral stones . Fewer analgesic drugs are consumed and more patients can avoid ureteroscopic lithotripsy and /or extracorporeal shock wave lithotripsy OBJECTIVE To determine the efficacy of terazosin as a facilitator agent for the passage of lower ureteral stones . METHODS Since February 2004 to December 2004 , 64 patients with lower ureteral stones who came to the emergency department were enrolled in this study . Exclusion criteria were the presence of urinary tract infection , severe hydronephrosis , elevated serum creatinine , hypertension , history of peptic ulcer disease and history of spontaneous stone passage . Patients were r and omized into 2 groups of 32 . Group 1 patients received terazosin tablets , 10 mg daily and analgesic ( indomethacin capsules ) for a maximum of 4 weeks , but patients in Group 2 received only analgesic . In cases of incomplete pain control , intravenous pethidine was administered . The 2 groups were compared with regard to stone passage rate , time to stone passage , the amount of received pethidine and the need for intervention . Statistical analysis was performed by student t-test . RESULTS The mean age of Group 1 was 44 years and Group 2 was 39 years . The median stone size was 6.9 + /- 2.3 mm in Group 1 and 6.6 + /- 3.1 mm in Group 2 , which was not significantly different . Stone expulsion rate was 90.62 % in Group 1 and 62.5 % in Group 2 , with a significant statistical difference ( p=0.041 ) . The mean expulsion time was 76.3 + /- 60 hours and 141 + /- 64 hours in Groups 1 and 2 , ( p=0.001 ) . Extra analgesic ( pethidine ) requirement averaged 34.4 + /- 12.7 mg and 62.1 + /- 10.5 mg in Groups 1 and 2 ( p=0.036 ) . Seven patients in Group 1 and 15 patients in Group 2 required ureteroscopy after 4 weeks due to lack of the stone passage . CONCLUSION Terazosin is a safe and effective treatment for lower ureteral stones . By using this medication , stone passage rate increases and the time of stone passage and the need for intervention decreases STUDY OBJECTIVE We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter . METHODS This was a r and omized , double-blind , placebo-controlled , multicenter trial of adult participants with calculus on computed tomography ( CT ) . Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days . The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion . RESULTS There were 403 patients r and omized , 81.4 % were men , and the median age was 46 years . The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group . Of 316 patients who received CT at 28 days , stone passage occurred in 140 of 161 ( 87.0 % ) in the tamsulosin group and 127 of 155 ( 81.9 % ) with placebo , a difference of 5.0 % ( 95 % confidence interval -3.0 % to 13.0 % ) . In a prespecified subgroup analysis of large stones ( 5 to 10 mm ) , 30 of 36 ( 83.3 % ) tamsulosin participants had stone passage compared with 25 of 41 ( 61.0 % ) with placebo , a difference of 22.4 % ( 95 % confidence interval 3.1 % to 41.6 % ) and number needed to treat of 4.5 . There was no difference in urologic interventions , time to self-reported stone passage , pain , or analgesia requirements . Adverse events were generally mild and did not differ between groups . CONCLUSION We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage , time to stone passage , pain , or analgesia requirements . In the subgroup with large stones ( 5 to 10 mm ) , tamsulosin did increase passage and should be considered It has recently been demonstrated that specific adrenoceptors subtypes ( α1A/α1D ) are prevalent in the distal part of the ureter , a finding supporting the interesting results obtained by different groups with the use of tamsulosin in the treatment of distal ureteral calculi . We performed a prospect i ve r and omized study to evaluate the effects of the addition of tamsulosin on our st and ard pharmacological therapy for the treatment of selected ureteral stones . A total of 64 patients referred to our department for the management of symptomatic ureteral calculi were considered . Patients were r and omly divided into two treatment groups : group A ( n=32 ) who received diclofenac ( 100 mg/daily ) plus aescin ( 80 mg/daily ) and group B ( n=32 ) who received the same therapy plus tamsulosin ( 0.4 mg/daily ) for a maximum of 2 weeks . No significant differences were found between the groups for age , gender distribution and mean stone size measured in the single largest dimension at presentation . The stone expulsion rate was 60 % ( 19/32 patients ) for group A and 88 % for ( 28/32 ) for group B with a mean expulsion time of 7.4±2.2 ( range 3.5–12 ) and 4.8±2.7 days ( range 1.8–10.5 ) , respectively . Group B showed a significant advantage in terms of both expulsion rate ( P=0.01 ) and expulsion time ( P=0.005 ) . Different analgesics from those used in the st and ard treatment regimen were required in ten patients in group A ( 31 % ) but only three patients in group B ( 9 % ) . This difference was significant ( P=0.003 ) . Hospitalization for recurrent colic was needed in 21 % of patients in group A ( 7/32 ) and in 9 % in group B ( 3/32 ) ( P=0.01 ) . Only two patients in each group ( 6 % ) experienced minor side effects associated with the expulsive therapy . Our data confirm the efficacy of tamsulosin in the treatment of distal ureteral stones up to 1 cm . This selective α-blocker should therefore be included in the pharmacological regimen of patients when a conservative approach is considered in the treatment of ureteral lithiasis OBJECTIVE The objective of the study is to determine if tamsulosin initiated in the emergency department ( ED ) decreases the time to ureteral stone passage at 1 week or time to pain resolution , compared to placebo . METHODS We performed a prospect i ve , r and omized , double-blinded , placebo-controlled trial of tamsulosin vs placebo in ED patients with ureterolithiasis on computed tomography . Patients were identified and enrolled between April 2007 and February 2009 and were r and omized to either 0.4 mg of tamsulosin or placebo for 1 week . We contacted participants using a telephone survey on post-ED visit days 1 , 2 , 3 , and 7 . The primary outcome was time to stone passage , with secondary outcomes being maximum pain score and amount of pain medication required . RESULTS Of the 127 patients enrolled during this study , 15 were lost to follow-up , and 12 required surgical interventions before the 7-day mark , leaving 100 patients for analysis . Of the 100 patients , 53 received tamsulosin and 47 received placebo . There was no difference between groups in percentage of male , mean age , initial serum creatinine , average stone size , stone location , and history of prior stone . The probability that the patient did not pass a stone at 7 days was not different between tamsulosin and placebo , 62.1 % ( 95 % confidence interval , 49.1%-75.1 % ) vs 54.4 % ( 95 % confidence interval , 40.3%-68.6 % ; P = .58 ) . There was no significant difference in the high pain score ( P = .12 ) or hydrocodone/acetaminophen intake ( P = .76 ) between treatment groups at any of the time points . CONCLUSION This study reveals no difference in the proportion of stone passage or high pain score and pain medication utilization at 7 days between tamsulosin and placebo OBJECTIVES To assess the clinical efficacy of the addition of a corticosteroid drug to tamsulosin in the medical-expulsive therapy of distal ureterolithiasis . METHODS Sixty consecutive patients with a symptomatic distal ureteral stone were included in our study and r and omized to one of two home treatment groups . Group 1 patients ( n = 30 ) received tamsulosin ( 0.4 mg daily ) , and group 2 patients ( n = 30 ) were treated with a corticosteroid drug ( deflazacort , 30 mg daily ) plus tamsulosin . The treatment duration was until stone expulsion or 28 days , whichever came first . The primary endpoint of the study was the stone expulsion rate . The secondary endpoints were the expulsion time ; use of analgesics ; number of emergency room admissions , hospitalizations , and workdays lost ; drug side effects ; and quality of life of the patients ( EuroQol question naire , EQ-5D ) during treatment . RESULTS The two groups had a similar expulsion rate ( 90 % for group 1 and 96.7 % for group 2 ; P = 0.612 ) , but the expulsion time was significantly reduced in group 2 patients ( P = 0.036 ) . During the treatment period , we did not observe significant differences between the two groups in the number of emergency room visits or hospitalizations , analgesic use , number of workdays lost , or incidence of drug side effects . The quality of life of the patients during therapy , as determined using the EQ-5D , was similar in both groups . CONCLUSIONS The use of a corticosteroid drug in association with tamsulosin seemed to induce more rapid stone expulsion . In addition , tamsulosin alone as medical-expulsive therapy for distal ureteral calculi had excellent expulsive effectiveness PURPOSE alpha1-Adrenergic blockers have recently been shown to increase the rate of spontaneous passage of distal ureteral stones . We compared efficacy of 3 different alpha1-adrenergic blockers for this purpose . MATERIAL S AND METHODS A total of 114 patients between 18 and 65 years old who had lower ureteral stones were included in the study . Patients were r and omly divided into 4 groups . Group 1 consisted of 28 patients and acted as the control group . Group 2 comprised 29 patients who received tamsulosin , group 3 was 28 patients receiving terazosin and group 4 was 29 patients receiving doxazosin . These agents were given for up to a month and hydration was also recommended simultaneously . Every week patients were controlled with x-rays of the kidneys , ureters , bladder and urinary ultrasonography . Meanwhile the number of pain episodes , analgesic dosage and the number of days for spontaneous passage of the calculi through the ureter were also recorded . RESULTS There were no differences between the groups with respect to age , weight , height , sex and stone size . The calculi passed through the ureter spontaneously in 15 patients in group 1 ( 53.57 % ) , in 23 patients in group 2 ( 79.31 % ) , in 22 patients in group 3 ( 78.57 % ) , and in 22 patients in group 4 ( 75.86 % ) . In groups 2 to 4 the number of pain episodes , expulsion time and analgesic dosage were found to be lower compared with those in group 1 . CONCLUSIONS alpha1-Adrenergic blockers increase the frequency of spontaneous passage of the distal ureteral calculi . All 3 agents tested were equally efficacious PURPOSE We evaluated the efficacy of the alpha1-adrenergic antagonist tamsulosin for conservative expulsive therapy in patients with ureteral colic due to juxtavesical stones . MATERIAL S AND METHODS A total of 60 consecutive symptomatic patients with stones located in the juxtavesical tract of the ureter were r and omly divided into group 1 - -30 who received oral floroglucine-trimetossibenzene 3 times daily and group 2 - -30 who received 0.4 mg tamsulosin daily . The 2 groups received 30 mg deflazacort daily for 10 days plus cotrimoxazole 2 times daily for 8 days and 75 mg diclofenac injected intramuscularly on dem and . Ultrasound followup and medical visits were performed weekly for 4 weeks . Stone passage rate and time , analgesic use , hospitalization and endoscopical intervention were evaluated . Statistical analysis was performed using the Student t test . RESULTS The stone expulsion rate was 70 % for group 1 and 100 % for group 2 . Mean stone size was 5.8 and 6.7 mm , respectively ( p = 0.001 ) . Mean expulsion time was 111.1 hours for group 1 and 65.7 hours for group 2 ( p = 0.020 ) . The mean number of diclofenac injections was 2.83 for group 1 and 0.13 for group 2 ( p < 0.0001 ) . Ten group 1 patients were hospitalized , of whom 9 underwent ureteroscopy , compared with none in group 2 ( p < 0.0001 and 0.001 , respectively ) . CONCLUSIONS Tamsulosin used as a spasmolytic drug during renal colic due to juxtavesical calculi increased the stone expulsion rate and decreased expulsion time , the need for hospitalization and endoscopic procedures , and provided particularly good control of colic pain The aim of the present study was to compare the efficacy of the selective α(1D ) -adrenoceptor antagonist naftopidil and the selective α(1A ) -adrenoceptor antagonist silodosin ( as an example ) in the management of ureteral stones in Japanese male patients . A total of 74 patients with symptomatic ≤ 10 mm ureteral stones were enrolled in a prospect i ve study and r and omized into two groups : Group 1 received 50 mg naftopidil daily , whereas Group 2 received 8 mg silodosin daily . Patients were followed-up for up to 6 weeks . The primary endpoint was stone expulsion rate and secondary endpoints were stone expulsion time , the rate of interventions , such as transurethral ureterolithotripsy , extracorporeal shock wave lithotripsy , or ureteral stenting , and side effects . There were no significant differences between the two groups with respect to age , stone size , and location . The stone expulsion rate was 61 % and 84 % in the naftopidil and silodosin groups , respectively ( P = 0.038 ) . No significant differences were noted in stone expulsion time or the rate of interventions between the two groups . The findings suggest that α(1A)-adrenoceptor blockade was clinical ly superior for stone expulsion our study population AIM Medical expulsive therapy ( MET ) using alpha-blockers is effective for distal ureteral calculi ( UC ) . We aim ed to evaluate the efficacy of tamsulosin for proximal UC expulsion . MATERIAL S AND METHODS An open-label r and omized controlled trial was conducted with 108 patients who agreed to conservative management for single , radiopaque , proximal UC ≤ 6 mm and were r and omized into group A ( n = 54 , conservative managements only ) or B ( n = 54 , 0.2 mg tamsulosin once a day ) . The primary end-point was stone passage rates ( SPR ) in the intention-to-treat population in 4 treatment weeks . The secondary end-points were estimated in per- protocol population and were time to stone passage , post-trial Euro- quality -of-life ( EuroQOL ) score , oral analgesic requirements , and willingness to undergo conservative treatment again . RESULTS The two groups were well balanced in terms of baseline patient and stone characteristics . Seventy nine patients ( 73.2 % ; 35 of group A and 44 of group B ) completed the study protocol . The overall SPR was 60.2 % ( 65/108 ) . Group B had a higher SPR ( 74.1 % ; 40/54 ) than group A ( 46.3 % ; 25/54 ; p = 0.003 ) and a significantly shorter time to stone passage ( mean days , A : 19.6 vs. B : 14.3 , p = 0.005 ) . The groups did not differ in post-trial EuroQOL score or oral analgesic requirements , whereas 74.3 % ( 26/35 ) of group A and 90.9 % ( 40/44 ) of group B were willing to undergo conservative treatment again ( p = 0.048 ) . Univariate logistic regression analysis showed that stone size ( OR = 1.447 , p = 0.045 ) and tamsulosin treatment ( OR = 3.314 , p = 0.004 ) significantly predicted stone expulsion . On multivariate analysis , only tamsulosin was statistically significant ( OR=3.198 , p = 0.021 ) . CONCLUSIONS Tamsulosin was associated with significantly higher stone expulsion rate and shorter expulsion time in proximal UC ≤ 6 mm compared with conservative managements only . Our results indicate that similar to patients with distal UC , MET using tamsulosin is a reasonable treatment option for patients with proximal UC Purpose To compare the efficiency and spontaneous expulsion rates of tamsulosin and Rowatinex in patients with distal ureteral stones . Methods Between March and July 2009 , 90 patients with distal ureteral stones < 10 mm in size were included in the study . Patients were r and omized in 3 groups : Group 1 ( n = 31 , those received 0.4 mg tamsulosin once daily ) , Group 2 ( n = 30 , those received 100 mg Rowatinex capsules 3 times a day ) , and Group 3 ( n = 29 , those received diclofenac 100 mg once daily ) . All patients were followed up for 10 days . Results and conclusions Mean age of the patients was 42.4 ± 16.1 ( range , 22–75 ) , 46.5 ± 16.5 ( range , 22–76 ) , and 43.5 ± 16.6 ( range , 18–71 ) years in Groups 1–3 , respectively . On admission , 37.8 % had hematuria and 78.9 % had lower urinary tract symptoms ( LUTS ) . No statistically significant differences were detected between the three groups regarding patient age , gender , mean stone size , stone location , stone site , additional analgesic requirement , number of ureteral colics during the treatment , and upper urinary tract dilation . The mean stone expulsion time was 3.5 days in Group 1 , 6 days in Group 2 , and 7 days in Group 3 ( P = 0.02 ) . Stone expulsion rate was significantly high in Group 1 compared to Group 2 ( P = 0.002 ) . Similarly , stone expulsion rate was significantly high in Group 1 compared to Group 3 ( P = 0.001 ) . Medical treatment with tamsulosin seems to be effective in patients with distal ureteral stones < 10 mm in size . However , use of Rowatinex does not seem to have any significant effect on clearance rate of distal ureteral calculi Objective . To evaluate the potential role of tamsulosin in the medical treatment of distal ureteral stones . Material and methods . Ninety patients with symptomatic distal ureteral calculi were enrolled . They were r and omly divided into two groups : Group A ( n=45 ) received diclofenac 100 mg on dem and for 4 weeks plus levofloxacin 250 mg daily for the first week and were well hydrated ; and Group B ( n=45 ) received the same therapy plus tamsulosin 0.4 mg/daily for 4 weeks . Abdominal ultrasound scans and KUB X-rays were performed weekly . Stone expulsion rates , time to expulsion , pain episodes and analgesic usage were determined . Intervention by means of shock-wave lithotripsy ( SWL ) or ureteroscopy was evaluated . Results . The stone expulsion rate was 51.1 % for Group A , compared to 88.9 % for Group B ( p=0.001 ) . The average time to expulsion was 12.53±2.12 days for Group A and 7.32±0.78 days for Group B ( p=0.04 ) . The number of pain episodes was significantly lower in Group B and mean use of analgesics was lower for Group B ( 0.14±0.5 vials ) than Group A ( 2.78±2.7 vials ) . Twenty-two patients in Group A failed to pass their stones after 4 weeks but only five in Group B. Of the patients who were not stone-free , 19 were treated with SWL and eight underwent ureteroscopy . Conclusion . Our study reveals the efficacy of tamsulosin for the treatment of distal ureteral stones . Tamsulosin should be added to the st and ard medical approach for treating these stones PURPOSE To evaluate efficacy and outcome of tamsulosin therapy for 4 mm-10 mm uncomplicated distal ureteral stones . MATERIAL S AND METHODS A total of 150 patients ( adults with newly diagnosed single unilateral distal ureteral 4 mm-10 mm stones ) were double blindly r and omized into GA or GB . All patients received traditional treatment of hydration and analgesia as needed . Additionally , patients received either placebo ( GA ) or 0.4 mg tamsulosin ( GB ) oral tablets once daily . Treatment and follow up were continued for up to 4 weeks . Endpoints were spontaneous stone passage rates ( SPR ) and passage time for different stone sizes within 4 weeks study period . RESULTS Analysis included 75 patients , in each group , with comparable characteristics . Overall SPR was 56 % in GA and 81.3 % in GB ; achieving significant absolute risk reduction ( ARR = 25.3 % ; p < 0.01 ) and number needed to treat ( NNT ) of 3.95 . SPR for stones < or= 6 mm was 69.2 % in GA versus 90.7 % in GB ( ARR = 21.5 % , p < 0.01 ) . For stones 7 mm-10 mm , SPR was 26.1 % in GA and 57.1 % in GB ( ARR = 31.0 % , p < 0.01 ) . NNT for < or= 6 mm and 7 mm-10 mm stones was 4.65 and 3.23 , respectively ( p < 0.05 ) . Median time for passage of < or= 6 mm stones was 17 versus 9 days in GA and GB ; while for 7 mm-10 mm stones it was 20 versus 15 days , respectively . During the first two weeks , 77.8 % of < or= 6 mm stones in GB have passed versus 23.8 % of 7 mm-10 mm stones . Analgesia consumption was significantly less in GB ( p < 0.01 ) . No significant adverse effects were observed . CONCLUSIONS Tamsulosin therapy for uncomplicated distal ureteral calculi augments SPR , shortens passage time and decrease need for analgesia . Particularly , tamsulosin shortens the passage time for smaller stones , and augments the passage rate for larger stones To evaluate , in a prospect i ve r and omized pilot study , the effectiveness and safety of tamsulosin , administered in patients with distal ureteric stones and who have already undergone an unsuccessful first cycle of medical expulsive therapy ( MET ) OBJECTIVE To evaluate the role of 2 different α-1 blockers and 1 phosphodiesterase-5 inhibitor as medical expulsive therapy for distal ureteric calculi . MATERIAL S AND METHODS Between January 2011 and December 2012 , 285 patients presenting with distal ureteric stones of size 5 - 10 mm were on consent r and omly assigned to 1 of 3 outpatient treatment arms : tamsulosin ( group A ) , silodosin ( group B ) , and tadalafil ( group C ) . Therapy was given for a maximum of 4 weeks . Stone expulsion rate , time to stone expulsion , analgesic use , number of hospital visits for pain , follow-up , and endoscopic treatment and adverse effects of drugs were noted . All 3 groups were compared for normally distributed data by the analysis of variance , Bonferroni or Kruskal-Wallis test , and Mann-Whitney U test , as required . All the classified and categorical data were analyzed for all 3 groups by using the chi-square test . RESULTS There was a statistically significant expulsion rate of 83.3 % in group B compared with 64.4 % and 66.7 % in groups A and C , respectively , with lower time of stone expulsion ( P value = .006 and P value = .016 , respectively ) . Statistically significant differences were noted in colicky episodes and analgesic requirement in group B than groups A and C. There was no serious adverse event . CONCLUSION Medical expulsive therapy for the distal ureteric stones using tamsulosin , silodosin , and tadalafil is safe , efficacious , and well tolerated . The result of this pilot study showed that silodosin increases ureteric stone expulsion quite significantly along with better control of pain with significantly lesser analgesic requirement OBJECTIVE To evaluate the safety and efficacy of alfuzosin treatment on rate and time of stone expulsion in patients with uncomplicated distal ureteral stones . PATIENTS AND METHODS Prospect i ve , r and omized , open-label , controlled study . Patients > 18 years of age presenting to the outpatient urology clinic with uncomplicated radio-opaque stones located in the distal third of the ureter and of size ≤ 10 mm were included . Patients were r and omly assigned to either a control group ( n=26 ) and received st and ard of care management ( daily oral hydration and diclofenac 75 mg IM on dem and ) or to the alfuzosin group ( n=28 ) and received alfuzosin SR 5 mg twice daily in addition to st and ard of care management . Patients were followed weekly at office visits and twice weekly by telephone for 4 weeks or until stone expulsion . Assessment s included stone passage rate and time , and patients were monitored for occurrence of adverse drug events , complications , number of pain episodes , analgesic consumption , and number of hospital revisits . Mann-Whitney , χ(2 ) , and Fisher exact test were used for data analysis . RESULTS All 54 patients completed the study . Stone expulsion rate was higher in the alfuzosin arm ( 53.6 % , 15/28 ) compared to the control arm ( 26.9 % , 7/26 , p=0.04 ) . Median stone passage time was lower in the alfuzosin group than in the control group ( 9 vs 19 days , respectively , p=0.006 ) . Ureteral sepsis , uncontrollable pain , and hospitalization readmissions were reported in the control group only . There were no differences between groups in number of pain episodes , pain scores , or analgesic consumption . Alfuzosin therapy was tolerable with only minor adverse effects ( headache , dizziness , mild postural hypotension , and rhinitis ) . CONCLUSION Alfuzosin is safe and effective in increasing stone expulsion rates and shortening stone passage times for uncomplicated distal ureteral stones |
1,777 | 32,348,948 | Country-specific abortion laws , implementing protocol s , side-effects , rates of failures , and the need to verify the abortion shaped women 's preference for abortion methods .
Overall , women who preferred medical abortions did so because they perceived it as a ' natural ' and safe procedure that can be self-conducted at home , thereby reducing their dependency on the health system .
However , women face significant barriers to medical abortion care .
These include legal requirements around type of provider , site of service , need for follow-up , providers ' limited knowledge of the procedure , and preferences for surgical abortions .
Borderless internet-based services have enabled some women to circumvent these barriers .
Our review suggests that medical abortions are used by women either in countries where the health system is fully supportive or where the health system is completely disengaged , usually due to restricted abortion laws .
In those countries where abortions are legal but often difficult to access due to health system barriers , women tend to prefer surgical abortions | Globally , a growing proportion of induced abortions are medical abortions .
The procedure has been hailed as a revolutionary technology , which , according to experts , has the potential to transform women 's experiences of abortion and the way abortion services are accessed .
Noticeably absent in the discourse , however , are women 's voices .
More specifically , there is a lack of underst and ing about what shapes women 's preferences for medical abortion and the challenges they experience in accessing the drugs for the procedure .
We conducted a systematic review of the literature to draw attention to these important issues which exist , but are often embedded within research highlighting other dominating aspects of medical abortions . | This was a prospect i ve study involving 205 women seeking medical abortion with gestational age ⩽ 63 days . Question naires regarding expectations , experience and satisfaction with medical abortion were self-completed at the end of the procedure . Women 's satisfaction was assessed using the visual analogue scale from 0 to 10 . Satisfaction and acceptability parameters were correlated with socio-demographic and obstetric data . The mean degree of overall satisfaction was 8.3 ( range 1 – 10 ) . Around 90 % of women would select the method again and would recommend it to a friend or relative . The degree of satisfaction showed a positive correlation with women 's age ( P < 0.001 ) and number of children ( P < 0.05 ) and a significant negative correlation with gestational age ( P < 0.005 ) . Marital status , type of financial support and acceptable pain and bleeding experience also showed a correlation with the satisfaction score . On the other h and , acceptability was correlated with husb and /partner agreement and support during the procedure and adequate counselling regarding pain and bleeding Background Despite changes to the abortion legislation in South Africa in 1996 , barriers to women accessing abortion services still exist including provider opposition to abortions and a shortage of trained and willing abortion care providers . The dearth of abortion providers undermines the availability of safe , legal abortion , and has serious implication s for women 's access to abortion services and health service planning . In South Africa , little is known about the personal and professional attitudes of individuals who are currently working in abortion service provision . Exploring the factors which determine health care providers ' involvement or disengagement in abortion services may facilitate improvement in the planning and provision of future services . Methods Qualitative research methods were used to collect data . Thirty four in-depth interviews and one focus group discussion were conducted during 2006 and 2007 with health care providers who were involved in a range of abortion provision in the Western Cape Province , South Africa . Data were analysed using a thematic analysis approach . Results Complex patterns of service delivery were prevalent throughout many of the health care facilities , and fragmented levels of service provision operated in order to accommo date health care providers ' willingness to be involved in different aspects of abortion provision . Related to this was the need expressed by many providers for dedicated , st and -alone abortion clinics thereby creating a more supportive environment for both clients and providers . Almost all providers were concerned about the numerous difficulties women faced in seeking an abortion and their general quality of care . An overriding concern was poor pre and post abortion counselling including contraceptive counselling and provision . Conclusion This is the first known qualitative study undertaken in South Africa exploring providers ' attitudes towards abortion and adds to the body of information addressing the barriers to safe abortion services . In order to sustain a pool of abortion providers , programmes which both attract prospect i ve abortion providers , and retain existing providers , needs to be developed and financial compensation for abortion care providers needs to be considered OBJECTIVE To determine the acceptability of taking mifepristone at home for early medical abortion in the United States . STUDY DESIGN This prospect i ve , non-r and omized , open-label study at six Planned Parenthood centers gave women with pregnancies up to 63 days ' gestation seeking medical abortion the choice of taking mifepristone in the center or at home . Participants were interviewed at a follow-up visit 1 - 2 weeks after mifepristone administration to assess their experience with the option they selected . RESULTS Four-hundred women were enrolled between April 2013 and June 2014 of which 32 % ( n=128 ) chose to take mifepristone at home . Abortion success rates did not differ between home and center users ( 96 % and 97 % ) . Among home users , 82 % reported taking the mifepristone at the time they planned with their provider and no participant took it after 63 days ' gestation . The most common reason cited for selecting home use was scheduling flexibility and significantly more home users took misoprostol on the weekend ( 50 % vs. 36 % , p=.02 ) . Home users were more likely than center users to report missing no days of work due to the abortion ( 47 % vs. 28 % , p=.08 ) . Ninety-nine percent of home users reported that they would take mifepristone at home again and 96 % would recommend home use to a friend . Offering this option did not increase the service delivery burden on study providers , who would recommend home use in the future for most participants . CONCLUSIONS Home use of mifepristone is a highly acceptable practice for which there is current dem and , and it should be offered as part of routine medical abortion services . IMPLICATION S Offering the option of home use of mifepristone to medical abortion patients can provide women and clinics with more flexibility while maintaining a safe , effective and acceptable service . These results provide support for telemedicine or pharmacy distribution BACKGROUND The aim of the study was to compare satisfaction with medical and surgical abortion and to identify potential confounders affecting satisfaction . METHODS 1033 women with gestational age ( GA ) < or = 63 days had either a medical ( 600 mg mifepristone followed by 1 mg gemeprost ) or a surgical abortion ( vacuum aspiration in general anaesthesia ) . The procedure was determined either by r and omization ( n = 111 ) or by choice ( n = 922 ) . Data on satisfaction , side effects and expectations were collected from question naires 2 and 8 weeks after termination . RESULTS More women were very satisfied or satisfied after a surgical than a medical abortion both after choosing method ( 92 % vs 82 % , P < 0.0001 ) , and after r and omization ( 94 % vs 68 % , P < 0.001 ) . Satisfaction was higher after choosing a medical procedure than after r and omization to the same procedure ; 82 % and 68 % , respectively , P < 0.05 . Satisfaction with the medical procedure was inversely correlated with GA and the intensity of pain , nausea , vomiting and dizziness , while satisfaction with the surgical procedure was unaffected by these side effects . Fewer women with a failed medical than a failed surgical abortion were satisfied ( 17 % vs 62 % ) , P < 0.05 . CONCLUSIONS Satisfaction with both medical and surgical abortions is high , although higher with the surgical than the medical procedure , and higher after choosing method than after r and omization CONTEXT Annually , more than 700,000 women turn to menstrual regulation , or uterine evacuation with vacuum aspiration ; many more resort to unsafe abortion . Using pills for the evacuation of the uterus could increase women 's access to safe menstrual regulation services and reduce the high levels of abortion- and menstrual regulation- related morbidity in Bangladesh . METHODS At 10 facilities in Bangladesh , 651 consenting women who were seeking menstrual regulation services and who were 63 days or less past their last menstrual period received 200 mg of mifepristone followed 24 hours later by 800 mcg of buccal misoprostol , administered either at home or in the clinic . Prospect i ve data were collected to determine women 's experience and satisfaction with the procedure , menstrual regulation outcome , and the human and physical re sources required for providing the method . Focus group discussion s were conducted with a purposively sample d group of service providers at each site to underst and their attitudes about the introduction of menstrual regulation with medication . RESULTS The majority of women ( 93 % ) with known menstrual regulation outcomes evacuated the uterus without surgical intervention . Overall , most women ( 92 % ) were satisfied with use of pills for their menstrual regulation . Providers faced initial challenges and concerns , particularly related to the additional counseling requirements and lack of control over the final outcome , but became more confident after successful use of the medication regimen . CONCLUSIONS Mifepristone-misoprostol can be safely offered within existing menstrual regulation services in urban and periurban areas in Bangladesh and is highly acceptable to women . Providers ' initial concerns diminish with increased experience with the method BACKGROUND A sublingual misoprostol-alone regimen was used in 50 women requesting medical abortion at up to 12 weeks gestation . The efficacy and acceptability of this regimen were studied . METHODS The women were given 600 microg misoprostol sublingually every 3 h for a maximum of 5 doses . RESULTS The overall complete abortion rate was 86 % ( 95 % confidence interval : 74 - 93 ) . The mean number of doses of misoprostol required was 4.1 + /- 1.1 . There was no significant change in haemoglobin concentration and the median duration of vaginal bleeding was 15 days ( range : 7 - 56 ) . Diarrhoea , fever and chills were the most common side-effects . The acceptability of this regimen of misoprostol was good : 97.7 % of the women who had a complete abortion would choose this method again and 88.4 % would recommend it to others . They preferred sublingual misoprostol as it is convenient to take , avoids the painful vaginal administration and gives more privacy during the abortion process . CONCLUSION This regimen of sublingual misoprostol is an effective and acceptable method of medical abortion . R and omized controlled trials are required to compare the efficacy of various misoprostol-alone regimens of medical abortion . Pharmacokinetic studies and clinical trials are needed to find out the most appropriate dose , dosing interval and route of administration of misoprostol Please cite this paper as : Rodriguez M , Seuc A , Kapp N , von Hertzen H , Huong N , Wojdyla D , Mittal S , Arustamyan K , Shah R , the World Health Organization Research Group on Post‐Ovulatory Methods of Fertility Regulation . Acceptability of misoprostol‐only medical termination of pregnancy compared with vacuum aspiration : an international , multicentre trial . BJOG 2012;119:817–823 OBJECTIVE To test the feasibility and acceptability of a simplified mifepristone-misoprostol regimen for early abortion in 2 tertiary teaching hospitals and 2 family planning clinics in Nepal . METHODS Consenting pregnant women ( n=400 ) with amenorrhea of 56 days or less seeking termination of pregnancy received 200 mg of oral mifepristone followed 48 hours later with 400 microg of oral misoprostol , administered either at home or at the clinic . Prospect i ve data were collected to determine the women 's experience , abortion outcome , and the operational requirements for providing the method . RESULTS Most ( 91.3 % ) of the 367 women with known outcomes had successful medical abortions . Given the option , most ( 89.7 % ) women elected to administer the misoprostol at home . CONCLUSION A simplified medical abortion protocol , including home administration of misoprostol , can be successfully integrated into clinical services in Nepal , where abortion services were recently legalized OBJECTIVE To evaluate the need for and outcome of self-administered medical abortion with mifepristone and misoprostol in Brazil , provided through Women on Web , a global telemedicine abortion service . STUDY DESIGN A retrospective case review of women from Brazil who contacted Women on Web in 2011 . Information from the online consultation , follow-up question naire and emails were used to analyze data including demographics , gestational age , outcome of the medical abortion and symptoms that lead to surgical interventions . RESULTS The Women on Web website had 109779 unique visitors from Brazil , 2104 women contacted the helpdesk by email . Of the 1401 women who completed the online consultation , 602 women continued their request for a medical abortion . Of the 370 women who used the medicines , 307 women gave follow-up information about the outcome of the medical abortion . Of these , 207 ( 67.4 % ) women were 9 weeks or less pregnant , 71 ( 23.1 % ) were 10 , 11 or 12 weeks pregnant , and 29 ( 9.5 % ) women were 13 weeks or more pregnant . There was a significant difference in surgical intervention rates after the medical abortion ( 19.3 % at < 9 weeks , 15.5 % at 11 - 12 weeks and 44.8 % at > 13 weeks , p=.06 ) . However , 42.2 % of the women who had a surgical intervention had no symptoms of a complication . CONCLUSION There is large need for medical abortion in Brazil . Home use of mifepristone and misoprostol provided through telemedicine is safe and effective . However , after 13 weeks gestation , there is an increased risk of surgical intervention that may be due to the regimen used and local clinical practice s in Brazil . IMPLICATION S The current study shows that there is an unmet need for medical abortion in Brazil , a country with legal restrictions on access to safe abortion services . Telemedicine can help fulfill the need and self administration of medical abortion is safe and effective even at late first trimester abortion . Prospect i ve trials are needed to establish safety , effectiveness and acceptability of home use of medical abortion beyond 12 weeks of pregnancy OBJECTIVE To document abortion practice s and contraceptive use among women of reproductive age in an urban slum of Delhi . METHODS Data were collected as part of a cross-sectional study conducted in an urban resettlement colony in the North East District of Delhi between November 2010 and December 2011 . Systematic r and om sampling was used to enroll 200 married women aged 15 - 49 years from each of the four blocks of the colony . Participants were interviewed and data were entered into a pretested semi-structured question naire . RESULTS Among 802 participants , 284 ( 35.4 % ) reported at least one spontaneous or induced abortion , and 196 ( 24.4 % ) reported induced abortions . Unsupervised medical termination was reported by 78 ( 27.5 % ) of the 284 women . Overall , only 207 ( 25.8 % ) women practice d any type of contraception . The predominant decision maker regarding contraception was the husb and for 95 ( 45.9 % ) women and the mother-in-law for 78 ( 37.7 % ) . CONCLUSION There is a need for focused community-based education to address specific issues , particularly regarding the dangers of unsafe abortion and choosing a method of contraception in consultation with a healthcare practitioner OBJECTIVE To assess the uptake and acceptability of self-administration of mifepristone at home for medical abortion in Nepal . METHODS A prospect i ve , comparative , non-r and omized , open-label study was conducted at two hospitals in Kathm and u , Nepal , between November 11 , 2009 , and January 15 , 2011 . All women in good health and aged 18 years or older who sought medical abortion after fewer than 64 days of pregnancy were enrolled . Participants were offered the choice of taking 200 mg mifepristone orally in the clinic or at home ; all participants self-administered 400 μg of sublingual misoprostol at home 24 - 72 hours later . All participants were scheduled to return to the clinic within 14 days of mifepristone administration for follow-up . RESULTS Among 200 participants , 144 ( 72.0 % ) opted to take the mifepristone at home . Medical abortion was successful in 130 ( 95.6 % ) of 136 women in the home group who were followed up and 53 ( 94.6 % ) of 56 women in the clinic group . Only 4 ( 2.9 % ) women in the home group took the mifepristone after the scheduled time . Overall , 133 ( 97.8 % ) women in the home group stated that they would recommend home administration of mifepristone if a friend wanted a medical abortion . CONCLUSION Self-administration of mifepristone outside the clinic should be offered to all women as part of routine medical abortion services in Nepal . Clinical trials.gov : NCT00994734 BACKGROUND Most medical abortion protocol s require women to take mifepristone in the doctor 's office . We assessed the acceptability of home use of mifepristone among women and their providers . STUDY DESIGN In this multicenter trial , eligible women requesting termination of early pregnancy ( n=301 ) chose whether to take mifepristone in the office or at home . Data on safety , efficacy , acceptability and disability were collected . RESULTS One hundred thirty-nine women ( 46 % ) chose to take mifepristone at home , and 162 ( 54 % ) chose office administration . Ninety-five percent of home users said that they would take the mifepristone in the same place in the future . Home users were not more likely to call the doctor 's office or make an unplanned visit , and providers would recommend home use again for 95 % of patients who chose home use . CONCLUSIONS Home administration of mifepristone was safe and acceptable to women and providers in our study . Women should be offered this choice to allow more flexibility , comfort and privacy in their abortion experiences The aim of this study was to assess women 's preferences and acceptability of medical ( MA ) and surgical abortion ( SA ) at 10 - 13 weeks gestation . This was a partially r and omized patient preference trial . Women were offered to enter the r and omized arm of the trial . Those who expressed a strong preference for a method were entered into the preference arm . A total of 368 women were r and omized ( 188 medical and 180 surgical ) while 77 entered the preference arm ( 15 medical and 62 surgical ) . Prior to abortion , 253 women ( 72 % ) indicated a preference for MA while 98 ( 28 % ) showed a preference for surgery ( p < .0001 ) . Despite having a preference for a particular method , women were content with alternatives . Women were more likely to choose the same abortion method again if they had shown a preference for that method prior to abortion ( p = .002 and .01 for MA and SA , respectively ) . The availability of MA is an important option for many women who wish to avoid surgery or anesthesia and should now be offered routinely in the late first trimester |
1,778 | 25,793,657 | One showed greater weight gain in the etonogestrel implant group versus no method but less versus DMPA | BACKGROUND Postpartum contraception improves the health of mothers and children by lengthening birth intervals .
For lactating women , contraception choices are limited by concerns about hormonal effects on milk quality and quantity and passage of hormones to the infant .
Ideally , the contraceptive chosen should not interfere with lactation or infant growth .
Timing of contraception initiation is also important .
Immediately postpartum , most women have contact with a health professional , but many do not return for follow-up contraceptive counseling .
However , immediate initiation of hormonal methods may disrupt the onset of milk production . | To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results OBJECTIVES The objective of the study is to evaluate the effects of levonorgestrel transferred through breast milk on thyroid stimulating hormone ( TSH ) and luteinizing hormone ( LH ) levels in full breast-fed infants . METHODS Forty healthy postpartum women and their male newborns were recruited for the study . Women were r and omly allocated to two study groups : Group 1 , IUD users and group 2 , Norplant users . Blood and milk sample s were collected on the day of IUD or Norplant insertion and 3 and 6 months later for TSH and levonorgestrel measurements . RESULTS The results disclosed a significant decrease in TSH levels , and a negative relationship between LNG levels and TSH concentration in breast feeding infants at 3 months after implant insertion . The lowest TSH levels were observed at 6 months in the women from group 2 . CONCLUSIONS The overall data indicate that the LNG levels transferred to fully breast-fed infants through breast milk from Norplant users significantly modified their TSH levels 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 Eighty healthy single births born at a gestational age of 259 - 294 days were studied in an open , non-r and omized , group comparative fashion . The mothers were on average 6 weeks postpartum , healthy , and fully breastfeeding at the start of treatment . Forty-two mothers elected to use the etonogestrel-releasing implant , Implanon , while 38 chose use of a non-hormone medicated intrauterine device ( IUD ) . One month after implant placement , the dose of etonogestrel ingested by the infants via breast milk was 19.86 ng/kg/day , which decreased to 10.45 ng/kg/day at the end of the study period ( month 4 ) . The volume of breast milk production was not affected by the use of Implanon . There were no significant differences between groups in milk content of total fat , total protein , and lactose . The timing and quantity of supplementary feedings did not differ between the two groups . Growth of the infants was analyzed by treatment and gender . For the girls , no differences between groups were seen for body weight , body length , and head circumference . The same applied to the boys except for a somewhat larger , although not statistically significant , increase in body weight for boys whose mother used Implanon . There was a low incidence of intercurrent illnesses in the infants of both groups . None of the conditions was of a serious nature . From the present study , we conclude that Implanon did not change the volume and composition of breast milk . The low concentration of etonogestrel ingested by the infant was not associated with adverse effects OBJECTIVE : To evaluate lactogenesis after early postpartum insertion of the etonogestrel contraceptive implant . METHODS : Healthy peripartum women with healthy , term newborns who desired the etonogestrel implant for contraception were r and omly assigned to early ( 1–3 days ) or st and ard ( 4–8 weeks ) postpartum insertion . The primary outcomes , time to lactogenesis stage II and lactation failure , were documented by a vali date d measure . The noninferiority margin for the mean difference in time to lactogenesis stage II was defined as 8 additional hours . Secondary data ( device continuation and contraceptive use , breast milk analysis , supplementation rates , side effects , and bleeding patterns ) were collected at periodic intervals for 6 months . RESULTS : Sixty-nine women were enrolled . Thirty-five were r and omly assigned to early insertion and 34 to st and ard insertion . There were no statistically significant differences between the groups in age , race , parity , mode of delivery , use of anesthesia , or prior breastfeeding experience . Early insertion was demonstrated to be noninferior to st and ard insertion in time to lactogenesis stage II ( early : [ mean±st and ard deviation ] 64.3±19.6 hours ; st and ard : 65.2±18.5 hours , mean difference , −1.4 hours , 95 % confidence interval [ CI ] −10.6 to 7.7 hours ) . Early insertion was also demonstrated to be noninferior to st and ard insertion in incidence of lactation failure ( 1/34 [ 3 % ] in the early insertion group , 0/35 [ 0 % ] in the st and ard insertion group [ risk difference , 0.03 , 95 % CI −0.02 to 0.08 ] ) . Use of formula supplementation was not significantly different between the groups . Milk composition at 6 weeks was not significantly different between the groups . CONCLUSION : Breastfeeding outcomes were similar in women who underwent early compared with st and ard postpartum insertion of the etonogestrel implant . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00847587 . LEVEL OF EVIDENCE : OBJECTIVE : To estimate whether 6-month use of the levonorgestrel-releasing intrauterine device ( IUD ) would be higher when insertion occurred within 10 minutes of placental delivery compared with 6–8 weeks postpartum . METHODS : We enrolled pregnant women planning vaginal deliveries and desiring a postpartum levonorgestrel-releasing IUD . Patients were r and omly assigned when admitted in labor to postplacental or delayed IUD insertion . The women followed up in person at 6–8 weeks and 6 months and were contacted by telephone at 3 months . Women were ineligible for a study IUD postenrollment for intrapartum events including infection , hemorrhage , and cesarean delivery ; these women were contacted by phone at 3 and 6 months . Expelled IUDs were replaced per patient preference . RESULTS : Successful IUD placement occurred in 50 of 51 participants ( 98.0 % ) and 46 of 51 participants ( 90.2 % ) in the postplacental and delayed groups , respectively ( P=.2 ) . Expulsion within 6 months occurred in 12 of 50 ( 24.0 % ; 95 % confidence interval [ CI ] , 13.1–38.2 ) and two of 46 ( 4.4 % ; 95 % CI 0.5–14.8 ) participants , respectively ( P=.008 ) . Intrauterine device use at 6 months was 43 of 51 ( 84.3 % ; 95 % CI 71.4–93.0 ) and 39 of 51 ( 76.5 % ; 95 % CI 62.5–87.2 ) , respectively ( P=.32 ) . For ineligible patients , only 11 of 41 ( 26.8 % ) women were using IUDs at 6 months and two ( 4.9 % ) had become pregnant . CONCLUSION : Intrauterine device use 6 months after delivery is similar in women who have postpartum or scheduled delayed IUD placement through a study after replacement of expelled IUDs . Expulsions are significantly higher with postplacental compared with delayed IUD placement . Women asked to follow up with their own health care providers for delayed insertion are significantly less likely to receive an IUD . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00476021 . LEVEL OF EVIDENCE : Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity A study was conducted to determine whether the onset or maintenance of lactation might be influenced by the administration of ovulation-inhibiting drugs for contraceptive purpose s when they were taken : 1 ) before the beginning of the lactation-period ; or 2 ) during the lactation period . The milk yield of 100 mothers who received an ovulation inhibitor ( 2.5 . mg lynestrenol ) from Day 1 postpartum was investigated . In order to exclude psychic factors 50 % of the tablets were placebos of identical appearance . The administration of the ovulation-inhibitor from Day 1 postpartum did not influence the commencement of lactation of the total milk yield in the first 10 days of the child-bed period . No clear influence on the milk yeild was observed during the subsequent observation period of 4 weeks . No differences were observed in another double group of mothers 70 women altogether who received the ovulation-inhibitor or the placebo from Day 10 postpartum BACKGROUND Mirena is a levonorgestrel-releasing intrauterine system ( LNG-IUS ) that provides highly effective and long-acting progestogen-only contraception . OBJECTIVE The objective of this study was to analyze the possible effects of using LNG-20 microg IUS on breast-feeding performance , infant growth and infant development during the first postpartum year as compared with the Copper T380A intrauterine device ( Cu T380A IUD ) . DESIGN This study is a prospect i ve , controlled and r and omized trial . SETTING The study was conducted at the Department of Obstetrics and Gynecology , Assiut University Hospital , Egypt . METHODS Three hundred twenty lactating women asking for initiation of contraception during the early postpartum stage were assigned r and omly into two groups , the LNG-20 microg IUS group ( n=163 ) and the Cu T380A group ( n=157 ) . The insertions were done 6 - 8 weeks postpartum . Each participant was followed up at three monthly intervals after insertion and until the first birthday of her baby . During these visits , the breast-feeding pattern was assessed , certain infant physical growth parameters were measured and a set of infant development tests was performed . RESULTS No pregnancy occurred in both groups . There were no significant differences in the net continuation rates between the two groups ( 89.3 for LNG-IUS vs. 90.9 for Cu T380A ) . The LNG-20 microg IUS group had comparable rates of breast-feeding continuation , complete weaning , full breast-feeding and partial breast-feeding , with the Cu-IUD group . No statistically significant differences were found between groups with regard to all infant physical growth parameters and various infant development tests . CONCLUSION The findings of the current study confirm that the use of LNG-20 microg IUS during the first postpartum year in lactating women provides highly effective and acceptable contraception and does not negatively influence breast-feeding or the growth and development of breast-fed infants 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 A single tablet of either of the three different types of oral contraceptive preparations , viz . " Gynovlar " containing 3000 micrograms norethisterone ( NET ) and 50 micrograms ethinyl estradiol ( EE2 ) or " Ovral " containing 250 micrograms levonorgestrel ( LNG ) and 50 micrograms EE2 , or a daily progestogen only type--"Minipill " containing 30 micrograms of LNG only , were administered to 40 normal lactating women on a r and om basis . The sampling schedule in all the three body fluids , i.e. the maternal sera , breast milk and the infant 's sera , was kept in such a manner that the peak levels of the contraceptive steroids would be expected to be present in these fluids . The results of this study indicate that the transfer ratio of LNG or NET from the maternal sera to her breast milk was approximately 10 % ( 6 - 34 % ) for Gynovlar , 9 % ( 5 - 18 % ) for Ovral and 6 % ( 2 - 34 % ) for Minipill . However , it was interesting to observe that whereas the transfer ratio of NET or LNG from breast milk to infant 's sera was similar for combination pills--8 % ( 3 - 23 % ) for Gynovlar and 12 % ( 3 - 42 % ) for Ovral , it was significantly higher for progestogen only Minipills--38 % ( 13 - 92 % ) for LNG . The precise reason for the higher transfer ratio of LNG from breast milk to infant 's serum in Minipill users can not be explained This study was an open trial where 1994 subjects each received Depo Provera injectable contraceptive every three months for one year and were observed a total of 20,294.3 woman months . At the time of observation , only one accidental pregnancy had occurred giving a use-effectiveness rate of 99.94 % and a cumulative continuation rate of 72.87 % . There were no significant adverse effects on weight and blood pressure . The main side effects were spotting , prolonged bleeding , and amenorrhea and these were also the main reasons of discontinuation . Complaints related to bleeding problems gradually decreased and complaints of amenorrhea increased with continued use . In lactating women , side effects occurrence rate was lower and continuation rate was higher in comparison with non-lactating women . Users did not report any effect on milk secretion . The results of this study confirm that Depo Provera is a very effective contraceptive method . With appropriate counseling and medical support , high acceptability and continuation rate can be achieved . Depo Provera is especially suitable for lactating women and could become a popular contraceptive method for lactating Chinese women Abstract The effect upon lactation of two methods of post-partum contraception was evaluated . An experimental group of 100 healthy young mothers , positively oriented towards breast-feeding , received Chlormadinone diacetate ( Clogestone ) , a C 21 progestogen , 0.6 mg daily in a continuous oral regimen . This group was observed for a total of 1,300 months . A similar group of 173 young women , who received an inert I.U.D. ( Lippes ' D ) was used as control . In this latter group , 100 women were strongly motivated to breast-feed and were encouraged about proper procedures . The remaining 73 were not comparably motivated . Lactation was maintained for the longest period , in the greatest number of mothers in the Clogestone series . The overall lactation performance of women in the I.U.D. series was markedly lower ; motivated mothers were able to breast-feed their infants for longer periods than the disinterested mothers , in whom milk secretion declined rapidly . The C 21 progestogen did not interfere with lactation ; more than 40 % of mothers in this series were able to nurse their children for periods over 12 months . Some factors involved in lactation are discussed This study was design ed to establish a possible influence of estrogen and progestagen on human milk composition . Estrogens have been widely used for inhibition of lactation in nonnursing mothers . They prevent breast engorgement and pain but do not prevent lactogenesis . Subjects were 175 healthy nursing mothers . 66 were treated orally with an estrogen ( ethinylestradiol .3 mg daily in 3 equal doses ) ; 63 were treated orally with a progestagen ( 6-alpha-methyl-17-alpha hydroxyprogesterone acetate 30 mg daily in 3 equal doses ) ; a control group of 46 were treated with a placebo in the same way . Treatment was continued for 5 full days after the women had given birth . Milk yield was not affected . Specimens were analyzed for lactose protein and fat content . A highly significant increase in protein content was observed in the milk of the estrogen-treated mother ( p less than .01 ) . This seems to be explained by a direct pharmacological action on the mammary gl and s. The high doses of ethinyl-estradiol establish a level of estrogenic activity which is nonphysiological during the lactation period . Progesterone had no significant effect A double-blind clinical trial to examine the effects of oral and long-acting injectable contraceptive steroids on milk lipid and its fatty acid content has been done in Szeged , Hungary , and Khon-Kaen , Thail and . In Szeged , a combined and a progestin-only pill did not significantly alter total milk lipid . In Khon-Kaen , treatment with the combined pill was followed by a significant increase in the proportion of milk lipid . In the group treated with the long-acting injectable contraceptive , depot-medroxyprogesterone acetate ( DMPA ) , the milk lipid decreased significantly in the first six weeks in comparison with the control group and the individual pretreatment values . A similar but weaker effect was noticed with the progestin-only pill in Khon-Kaen . Few consistently significant differences were found in the shorter chain fatty acids ( myristic , lauric and palmitic acids ) during treatment . The percentage proportions were increased during the combined pill treatment in Szeged and Khon-Kaen , and reduced in DMPA and progestin-only treatment in Khon-Kaen milks . The possibility that these reflected a response to a milk volume decrease in the combined pill treatment and a reduction in milk lipid synthesis in association with DMPA and the progestin-only pill is discussed . In Khon-Kaen , linoleic acid ( which is not synthesized in the body ) was increased by comparison with the controls , as a percentage proportion of the fatty acids in the progestin-only and DMPA groups . Calculation of the amounts of linoleic acid per litre of milk revealed that there had been a significant decrease of linoleic , eicosadienoic , dihommo-gamma-linolenic , arachidonic , docosatetraenoic acids in the w6 family and alpha-linolenic acid in the w3 family in the first two post-treatment visits ( 3 and 4 ) . This reduction in essential fatty acid output follows the reduction in milk volume . In Khon-Kaen , the combined pill group showed a significant decrease compared with the controls , in the proportions of dihommo-gamma-linolenic acid . The difference in response of the mothers in Khon-Kaen and Szeged is discussed in relation to their different nutritional background A clinical study was design ed to test whether sustained administration of progesterone to nursing mothers could prolong lactation and delay the postpartum recovery of fertility . The hormone was administered by subdermal implantation of six pellets that each contained 100 mg of progesterone . This treatment was administered to 84 fully nursing women on day 30 post partum . Control groups were composed of 130 fully nursing women who received an injectably placebo , and by 125 fully nursing women who received a TCu 200 intrauterine contraceptive device . An exacting list of requirements for admission to and continuation in the study was applied to all groups . No pregnancies occurred in the progesterone-treated group from the second to the sixth postpartum month . This period coincided with the period of elevation plasma progesterone attributable to hormone released from the implants . The cumulative probability of pregnancy in the placebo group was 10.2 per 100 women at the sixth month . Treatment with progesterone did not change the duration of lactation or the rate of child growth , and no adverse effects were recorded . These results warrant further investagation of the use of progesterone as an alternative method to prevent conception in nursing women INTRODUCTION The puerperium is the period of highest risk for thrombosis during a woman 's reproductive life and it is an important time for initiating an effective contraceptive method in order to increase intergestational interval . Thus , the objective of the present study was to evaluated the effects of the etonogestrel (ENG)-releasing contraceptive implant inserted immediately postpartum on maternal hemostasis markers during the first six weeks of delivery . MATERIAL S AND METHODS Forty healthy women aged 18 to 35 years-old were r and omized to receive either the ENG-releasing implant 24 - 48 h after delivery ( implant group ; n=20 ) or nothing ( control group ) until the sixth postpartum week . Blood sample s were collected at 24 - 48 h and at 6 weeks after delivery , and hemostatic variables , including fibrinogen , coagulation factors , protein C , free protein S , antithrombin , α2-antiplasmin , plasminogen activator inhibitor 1 , thrombin-antithrombin complex ( TAT ) , prothrombin fragment (PF)1 + 2 , and D-dimers , as well as normalized activated protein C sensitivity ratio ( nAPCsr ) , thrombin time , activated partial thromboplastin time , and prothrombin time were evaluated . RESULTS Insertion of the ENG-releasing contraceptive implant did not change the physiological reduction in overall coagulation ( TAT and PF1 + 2 ) and fibrinolysis ( D-dimer ) markers , or nAPCsr . Reductions in factors II , VII , X and fibrinogen and increases in factor V were greater in the control than in the implant group . Clotting factors remained within normal limits throughout the study . CONCLUSION The ENG-releasing contraceptive implant inserted immediately postpartum did not have negative effects on physiological variations of the hemostatic system during the first 6 weeks postpartum In response to the concept that a good postpartum program should begin prenatally , this study was design ed to determine whether the provision of expert contraceptive counseling during the antenatal period would have an impact on contraceptive uptake , patterns of contraceptive usage , and pregnancy rates during the first year after childbirth . Over 500 women attending antenatal clinics in each of three centers ( Edinburgh , Scotl and ; Shanghai , People 's Republic of China ; Cape Town , South Africa ) were r and omized to receive expert contraceptive advice ( participants , n = 771 ) or the st and ard advice routinely given in that setting ( controls , n = 866 ) . Follow-up was by postal or interviewer-administered question naires at 16 and 52 weeks after childbirth . There were no significant differences in the prevalence of contraceptive use at one year ( over 79 % in all centers ) between participants and controls . In Edinburgh , participants were more likely to undergo sterilization ( p < 0.01 ) than controls , otherwise there were no differences among Edinburgh , Shanghai , or Cape Town in either the methods of contraception chosen or in the methods used over time . Contraceptive counseling delivered antenatally appeared to have no impact on the pregnancy rate during the first year after childbirth . In Shanghai , over 11 % of women in both groups underwent termination of pregnancy in the year of follow-up . In conclusion , although women in all centers said they found the opportunity to discuss contraception antenatally was useful , it had very little effect on contraceptive use or on subsequent pregnancy rates The study was design ed to test the long-term influence of a low-dose combined oral contraceptive upon lactation and infant growth when treatment was initiated at day 30 postpartum . The contraceptive tested contained ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg . Two control groups were formed by women who received an injectable placebo or a Copper T at day 30 postpartum . Women in the injectable placebo group received non-hormonal contraceptives at day 90 postpartum . An exacting list of requirements for admission and continuation in the study was applied to all groups . The oral contraceptive group had a significantly lower percentage of cases in full nursing from the 4th through the 10th postpartum month when compared to both control groups . The average absolute weight of infants in the oral contraceptive group was significantly lower at several ages when compared to the placebo group but not when compared to the Copper T group . No adverse side effects upon infant 's health were detected . It was concluded that the oral contraceptive tested showed a moderate inhibitory influence upon lactation when treatment was initiated at the beginning of the second postpartum month BACKGROUND The use of breastfeeding as a method of birth spacing occasionally ends in " unplanned pregnancy . " This is due to unexpected expiration of one or more of the lactation amenorrhea method ( LAM ) prerequisites . The current study tests a new concept that the in-advance provision of single packet of progestogen emergency contraception ( EC ) pills during the postpartum LAM counseling may decrease the incidence of unplanned pregnancy during breastfeeding . STUDY DESIGN This was a registered two-armed r and omized controlled trial ( NCT 01111929 ) . Women intending to breastfeed and to postpone pregnancy for 1 year or more were approached . They received adequate postpartum contraceptive counseling . Women intending to use LAM were r and omly assigned to one of two groups . The LAM-only group received the proper LAM counseling and did not receive counseling about EC . The LAM-EC group received counseling for both LAM and EC with in-advance provision of one packet of EC pills . They were advised to use these pills if one of the prerequisites of LAM expires and sexual relation has occurred before the initiation of another regular contraceptive protection . All the participants were advised that they need to use another regular method upon expiration of any of the LAM prerequisites . RESULTS Eligible women were 1158 parturients r and omized into two equal groups . Forty-four percent of the women provided with EC used them . Significantly more women in the LAM-EC group initiated regular contraception within or shortly after the first 6 months postpartum when compared with those in the LAM-only group ( 30.5 % vs. 7.3 % , respectively ; p=.0004 ) . Pregnancy occurred in 5 % of the LAM-only group as compared with 0.8 % in the LAM-EC group ( p=.005 ) . Minimal side effects were reported after EC use . CONCLUSION In-advance provision of EC pills can increase the rate of initiation of regular contraception once one or more of the prerequisites of LAM expire . Consequently , the use of EC pills as a temporary backup of LAM can decrease the incidence of unplanned pregnancy during breastfeeding . The use of progestogen EC pill during lactation is safe and tolerable Breast milk volume and composition and infant growth were measured at three- and four-week intervals , up to six months , in a multicenter r and omized double-blind trial comparing a low-dose combined oral contraceptive ( OC ) with a progestogen-only OC . A nonr and om group using nonhormonal methods was also studied in the three centers : Szeged , Hungary ; Bangkok , Thail and ; and Khon Kaen , Thail and . A fourth group , users of depot-medroxyprogesterone acetate ( DMPA ) was included in the two Thai centers . Altogether , 341 women were recruited into the study . Combined OCs caused a significant decrease in milk output and total energy content as well as widespread changes in milk constituents . In the DMPA group , no significant changes were observed in milk volume , and only minor shifts occurred in milk composition , which varied between centers . No differences were found between the progestogen-only pill and DMPA . No hormonal contraceptive was associated with any significant difference in infant weight or fat fold , nor in the rate of discontinuation for failure to gain weight . This study reiterates the need to avoid combined OCs during the first few weeks or months of lactation . Both norgestrel and DMPA appear to be safe for use in both developing and developed countries , at least when the nutritional status of the mother and infant are adequate , but further research is needed on the safety of these contraceptives in population s with malnutrition Normal postpartum women , who had a spontaneous vaginal delivery of one full-term male infant , free of congenital abnormalities and other diseases , were recruited for this study . Thirteen women received 150 mg depot-medroxy-progesterone acetate ( DMPA ) , intramuscularly on days 42 + 1 and 126 + 1 postpartum . Infants of nine mothers , who did not receive DMPA , served as controls . Blood sample s were collected from treated mothers on days 44 , 47 , 74 , 124 , 128 , and 130 postpartum for medroxyprogesterone acetate ( MPA ) measurements . Four-hour urine collection s were obtained from all 22 infants in the morning on days 38 , 40 , 42 , 44 , 46 , 53 , 60 , 67 , 74 , 88 , 102 , 116 , 122 , 124 , 126 , 128 , 130 , and 137 . Urinary follicle stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , unconjugated testosterone , and unconjugated cortisol were measured by radioimmunoassay , and serum MPA and urinary MPA metabolites were measured by gas chromatography-mass spectrometry ( GC-MS ) . No MPA metabolites could be detected in the urine of the infants from the DMPA-receiving mothers . Hormonal profiles in the urine sample s were not suppressed in comparison with those of the control infants . The present study demonstrates that DMPA , administered to the mother , does not influence the hormonal regulation of the breast-fed normal male infant 451 women who delivered at St. Josephs Hospital Copenhagen from July-September 1966 were given a daily tablet of Norinyl-1 ( norethisterone 1 mg and mestranol .05 mg ) or a placebo from the day after birth until discharge on Day 8 . Lactation was assessed by the patient and the nursing staff . Significantly more women ( p- < .01 ) who were taking Norinyl-1 used supplementary feeding . There was no significant difference in 1 ) infants weight gain between the 2 groups and 2 ) febrile breast engorgement between the 2 groups although it seemed to be slightly lower in the drug group Two multicenter , double-blind , placebo-controlled studies were conducted to evaluate the effectiveness of triphasic norgestimate/ethinyl estradiol ( Ortho Tri-Cyclen ) for the treatment of acne vulgaris . To our knowledge , these studies were the first double-blind , placebo-controlled trials to evaluate the efficacy of an oral contraceptive ( OC ) in the treatment of acne ; in fact , they are probably the first placebo-controlled trials ever completed using modern OC . This article examines the conduct and feasibility of these studies including discussion s on study planning enrollment , maintenance of the blind , continuation rates , and pregnancy prevention . Subjects were between the ages of 15 and 49 years , with moderate acne vulgaris , no contraindications to oral contraceptive use , and were willing to use a nonsteroidal method of birth control during the 6 months of the trial . More than 500 participants were enrolled in 1 year . Discontinuation rates between groups were similar . To explore the reasons for the similar and low discontinuation rates , OC-related side effects were evaluated in comparison to placebo . This analysis revealed that the OC exhibited a side effect profile that was similar , in many cases , to that of placebo . Although pregnancies occurred in the placebo arm , the incidence was consistent with expected failure rates for users of nonsteroidal methods in the general population OBJECTIVE To assess the effect of medroxyprogesterone acetate on lactation when it is given immediately post partum . DESIGN Prospect i ve cohort study with follow-up through 16 weeks post partum . SETTING Urban teaching hospital in Baltimore , Md. PARTICIPANTS Consecutive sample ( N = 95 ) of mothers who were delivered of healthy , term newborns , had home telephones , received either medroxyprogesterone or nonhormonal contraception at discharge , and were currently breast-feeding their newborns . MAIN OUTCOME MEASURES Lactation ( duration and frequency ) and timing of first introduction of formula were measured by weekly telephone interviews . RESULTS Maternal characteristics included the mean + /- SD maternal age ( 24 + /- 5 years ) , race ( 90 % African American ) , history of pregnancy ( 63 % multiparous ) , marital status or relationship ( 50 % married or living with partner ) , and medical assistance ( 81 % of the recipients received aid ) . Women who were receiving medroxyprogesterone ( n = 43 ) were older ( P < .05 ) and were more likely to be married ( P < .05 ) compared with those who were receiving nonhormonal contraception ( n = 52 ) . No other factors that were likely to influence lactation were significantly different . Groups did not differ in the baseline-planned duration of lactation . Follow-up data were obtained on 90 women ( 96 % ) . The groups were comparable in the duration of lactation ( medroxyprogesterone : 98 % , 74 % , 55 % , 47 % , and 42 % were breast-feeding at least once per day at 1 , 4 , 8 , 12 , and 16 weeks , respectively [ median , 10.14 weeks ] , vs nonhormonal contraception : 86 % , 70 % , 47 % , 36 % , and 30 % , respectively [ median , 6.57 weeks ] [ P = .19 ] ) . The percentage of subjects who were exclusively breast-feeding at these times and the timing of formula introduction also did not differ by group . CONCLUSION Medroxyprogesterone , when given to mothers in an urban community immediately after delivery , has no detrimental effect on the duration of lactation , frequency of lactation , and timing of introduction of formula within the first 16 weeks post partum The study was design ed to test the short-term influence of a low-dose combined oral contraceptive upon lactation and infant growth when treatment was initiated at day 30 postpartum . The contraceptive tested contained ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg . Two control groups were formed by women who received either an oral placebo or an injectable placebo at day 30 postpartum . An exacting list of requirements for admission and continuation in the study was applied to all groups . The oral contraceptive group had a lower percentage of cases in exclusive breastfeeding at day 91 postpartum when compared to both control groups . Infants in the oral contraceptive group showed a significantly lower average absolute weight at days 61 and 91 postpartum and a significantly lower average daily weight increase during the first month of treatment when compared to both control groups . It was concluded that the oral contraceptive tested had a negative influence upon lactation and child growth The objective was to compare the efects of Exluton with those of Multiload Cu250 , in an open-label , bi-center , r and omized study in breastfeeding women . Subjbects were r and omized to one of the treatment groups 6 weeks after delivery . Women and their infants returned to the study site monthly and follow-up data regarding qualitative and quantitative characteristics of the breast milk , infant growth and infant and maternal health were obtained . There were no statistically significant differences between groups with regard to : ( 1 ) amount of milk drunk , amount of milk production , and number of daily breastfeedings ; ( 2 ) mean milkl concentrations of nutritional constituents ( except higher milk levels of calcium and magnesiuum with Exluton during the first month ) ; ( 3 ) infant anthropometric paramenters . There were no between-group differences with regard to systolic or diastolic blood pressure . During the study , the mean maternal body weight in the Exluton group was significantly lower than in the multioload Cu250 group . There were no differences between groups with regard to child or maternal health , except a lower incidence of child illness after 6 months in the Exluton group . This study confirms that both Exluton and Multiload Cu250 are acceptable and safe contraceptive methods in breastfeeding women . ResuméL'objectif était de comparer les effets de l'Exluton et ceux du stérilet Multiload Cu250 , lors d'une étude r and omisée , ouverte et menée dans deux centres , portant sur des mères allaitent leurs nouveau-nés . Les sujets ont été répartis au hasard dans un des groupes de traitement 6 semaines aprèrs l'accouchement . Les femmes et leurs enfants revenaient au centre d'étude tous les mois . Lors du suivi , on a enregistré les données concernant les caractéristiques qualitatives et quantitatives du lait maternel , la croissance des enfants et la santé de la mère et de l'enfant . Aucune différence statistiquementt significative entre les deux groupes n'a été relevée en ce qui concenrne : ( 1 ) la quantité de lait absorbée , la quantité de lait produite et le nombre de tétées par jour ; ( 2 ) la teneur moyenne en éléments nutritifs du laif ( sauf des niveaux plus élevés de calcium et de magnésium dans le groupe Exluton durant le premier mois ) ; ( 3 ) les paramètres anthropom'etriques de l'enfant . Aucune différence non plus n'a été constatée entre les groupes du point de vue de la pression sanguine systolique et diastolique . Pendant l'étude , le poids corporel moyen de la mère dans le groupe Exluton était significativement moins important que dans le groupe Multiload Cu250 . S'agissant de la santé de l'enfant et de la mère , aucune différence n'est apparue entre les groupes , à l'exception d'une moindre incidence de maladie chez l'enfant après 6 mois dans le groupe Exluton . Cette étude confirme que l'Exluton et le Multiload Cu250 sont des méthodes contraceptives acceptables et sures pour les femmes qui allaitent leurs enfants . ResumenEl objetiveo fue comparar los efectos de Exluton con los de Multikload Cu250 en un estudio aleatorizado de rótulo abierto y dos centros entre mujeres que amamantaban . Las mujeres fueron seleccionadas al azar para uno de los grupos de tratmaiento a las 6 semanas del parto . Las mujeres y sus bebés regresaron al lugar del estudio mensualmente y se obtuvieron datos de seguimiento relativos a caradcterísticas cualitativas y cuantitativas de la leche demadre , crecimiento de los bebés y salud maternoinfantil . No hubo diferencias estadísticamente significativas entre los grupos con respecto a : ( 1 ) cantidad de leche ingerida , cantidad de leche producida y número de amamantamientos diario ; ( 2 ) concventracionesácteas medias de los elementos nutricionales ( salvo niveles lácteos más altos de calcio y magnesio con Exluton durante el primer mes ) ; ( 3 ) parámetros antropométricos de los bebés . No hubo diferenias entrelos grupos con respecto a presión sanguínea sistólica o diastólica . Durante el estudio , el peso corporal medio de las madres en el grupo de Exluton fue significativamente inferior al del grupo Multiload Cu250 . No hubo diferencias entre los grupos con respecto a la salud de las madres o los bebés , salvo un menor incidencia de enfermedades infantiles después de 6 meses en el grupo de Excluton . Este estudio confirma que tanto Exluton como Multiload Cu250 son métodos anticonceptivos aceptables y seguros en mujeres que Abstract In a double blind study , 40 women delivered by cesarean section were divided into four groups , and were given either placebo , estrogen , progestogen , or a combination of these daily for 14 days , starting on the second day postpartum . The criteria chosen to assess the results ( subjective maternal impressions , milk yield , and changes in babies ' weights ) showed increased milk production in all medicated groups compared to the controls To find out the safety , effectiveness and tolerability of using desogestrel ( 75 microg/day ) , a progesterone only pill on lactating mother , a prospect i ve clinical study was undertaken among 200 lactating women during the period from 1st January 2010 to 13th June 2011 at Gice Clinic , Kalyani , Nadia , West Bengal . The same number of cases were taken as placebo for comparison . Desogestrel was started after six weeks of delivery for six months . Patients were review ed at 8th , 12th , 16th , 24th weeks and one year . The very interesting results were found from the follow-up study that desogestrel ( 75 microg/day ) did not alter the amount and composition of breast milk , pregnancy was not reported as compared to placebo . The drug had good tolerability , less side-effects and did not affect the growth and development of breastfed babies . Due to the safety , good efficacy , tolerability and less side-effects it is concluded that desogestrel ( 75 microg/day ) was well accepted in majority of women ( 97.5 % ) and provided good contraceptive efficacy during the lactating period . This treatment does not have any effect on the growth and development of breastfed baby Objective To evaluate the effects of desogestrel 75μg/day , as a progestogen‐only pill compared with a copper‐bearing intrauterine contraceptive device ( IUCD ) on lactation and to study the safety of both treatments in mothers and children . Transfer of etonogestrel to breast milk was studied in a subgroup of desogestrel users . The children were to be followed up until 2.5 years of age A non-comparative study of a progestin-only oral contraceptive ( POC ) containing 75 micrograms norgestrel was conducted at 22 sites in 14 countries . This study was design ed to evaluate safety , contraceptive efficacy , and the overall acceptability of a POC in breastfeeding women . A total of 4,088 women entered the study over a three-year period and 29,399 woman-months of experience was gathered . Women had follow-up visits at 2 , 6 , and 11 months after admission . Headaches and vaginal discharge were the medical complaints most commonly reported by women , both prior to and after admission . Menstrual problems were reported by 59 % of the women after admission . Of the 3,714 women who returned for at least one follow-up visit , 1,101 ( 29.6 % ) discontinued through month 11 . The 11-month total discontinuation percentage , including those lost to follow-up ( 25.3 % ) was 51.6 % . The most common reason given for discontinuation was a woman 's desire for a change in contraceptive method . Only 4.9 % discontinued pill use for menstrual problems , a percentage far below those generally reported for POCs . Twenty-nine unintended pregnancies occurred through 11 months giving a gross cumulative life table rate of 1.2 per 100 women ( Pearl Index = 1.4 ) . The POC appears to be a safe , effective and acceptable contraceptive option for postpartum breastfeeding women Because of its unique features , the contraceptive effectiveness and tolerance during breast-feeding of 16-methylene-17 alpha-acetoxy-19-nor-4-pregnene-3,20-dione ( elcometrine ) , delivered within a single subdermal capsule of medical grade polydimethylsiloxane , was investigated . Unlike other progestational steroids , elcometrine has no affinity for and rogen and estrogen receptors and is inactive by the oral route . A total of 66 breast-feeding women receiving elcometrine by the subdermal route were enrolled in the study , and 69 women who elected to use Copper-T380 intrauterine devices ( IUD ) served as control subjects . The women and their infants were observed until the end of the first postpartum year . There were no significant differences in growth and development measurements among the infants in the elcometrine and control groups . The percentage of infants continuing to breast-feed at 3 and 6 months was significantly higher in the elcometrine group . There were no significant differences between the concentration of elcometrine in the mother 's blood and milk . At 75 days , blood levels of elcometrine in the infants were near the undetectable and were significantly lower than the levels in maternal blood or milk ( p < 0.01 ) . In 15 of 25 infants , blood levels of elcometrine were at the limit of assay sensitivity or undetectable . Two pregnancies occurred in women using IUD , whereas none occurred in those using implants . There were menstrual bleeding irregularities in both groups . A single elcometrine capsule placed subcutaneously at 6-monthly intervals appears to be an effective method of contraception for lactating women and results in blood concentrations of nursing infants at or near undetectable levels OBJECTIVE To measure infants ' breast milk intake and infant growth when their mothers initiated either combined oral contraceptive ( COC ) , levonorgestrel-releasing intrauterine system , or etonogestrel-releasing implant , or copper intrauterine device ( IUD ) as a reference group . DESIGN Prospect i ve trial . SETTING University-based hospital . PATIENT(S ) On postpartum day 42 , 40 women initiated a contraceptive method according to their choice . INTERVENTION(S ) Deuterium ( D2O ; 0.5 g/kg mother 's weight ) was ingested by mothers on postpartum days 42 , 52 , and 63 as a marker of total body fluid . MAIN OUTCOME MEASURE(S ) Infants ' milk intake from 42 to 63 postpartum days was assessed by measurement of D2O levels in infants ' saliva and infant growth by measuring their body weight , height , and tibia length . Women recorded all infant feed and changes of diapers wet with urine . Breastfeeding continuation was assessed at 6 months postpartum . RESULT ( S ) Infant mean milk intake , mean growth increase , mean number of breastfeeding episodes , daily wet diaper changes , and mean duration of exclusively breastfeeding ( ~5 months ) were similar in the four groups . CONCLUSION ( S ) Use of a COC , the two progestin-only contraceptives , or copper IUD did not affect the amount of infant milk intake and growth up to 9 weeks of age . The incidence of full breastfeeding and breastfeeding continuation was similar with contraceptive hormonal use and no use . CLINICAL TRIALS REGISTRATION NUMBER NCT01388582 The objective of this study was to test the influence of NORPLANT implants upon lactation and infant growth . The results obtained during the first postpartum year are reported . One-hundred women were enrolled in the implant group . The control group was formed by 100 women who received a Copper T IUD . Treatments were administered at day 55 + /- 3 . At admission all subjects were in exclusive breastfeeding with an adequate weight increase of the infant . No significant differences were found between the treated and control groups in the percentage of women in full nursing at different postpartum intervals , except for the 12th month postpartum where a lower percentage of cases from the NORPLANT group was in the full nursing category . No difference was found in the time of weaning . The infants showed a normal weight gain rate in both groups although the girls from the NORPLANT group showed a significantly lower daily weight increase during the 4th month than the girls from the IUD group . No pregnancies were diagnosed . No women asked for implant removal during the first year . No serious side effects related to treatment were detected . Bleeding irregularities were rare during breastfeeding which is in contrast with what occurs in non-nursing women treated with NORPLANT implants . Levonorgestrel concentrations found in milk were variable and individual values ranged from 23 to 311 pg/ml . The dose received by the infant can be estimated around 15 to 18 ng/Kg/day during the first month of treatment when the higher plasma values of levonorgestrel are observed . These levels is conjunction with the clinical observations reported here minimize the potential problems associated with levonorgestrel transference through maternal milk . Nevertheless , long-term studies are required to settle this matter and until more information is available , NORPLANT implant use in lactating women should be limited to cases who require a highly effective contraceptive method and where non-hormonal methods of similar effectiveness are contraindicated or unacceptable This study was a non-r and omized clinical trial which compared the breast-feeding experience of 250 Argentine women taking levonorgestrel 0.03 mg daily ( begun one week after delivery ) with that of 250 women using non-hormonal contraceptives . Weight gain of unsupplemented infants , the most important of the several criteria used to assess breast-feeding performance , was similar for the two contraceptive groups . Levonorgestrel users began supplementary feeding of their infants significantly later than did non-hormonal users ; levonorgestrel users were also somewhat less likely to discontinue breast-feeding during the study period . The two contraceptive groups were similar with regard to several other measures of breast-feeding performance : growth of all infants ( regardless of supplementation ) , patterns of contraceptive discontinuation , mothers ' subjective impressions of breast-milk sufficiency , and comparison of supplementation initiation with previous experience 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 The objective of this study was to evaluate the contraceptive efficacy and clinical performance of a Nestorone subdermal implant ( NES ) in the postpartum period . NES ( n = 100 ) and Copper T intrauterine device ( T-Cu ; n = 100 ) acceptors initiated contraception at 8 weeks postpartum and were followed at monthly intervals during the first year and at 3-month intervals thereafter . Pregnancy rates , breastfeeding performance , infant growth , bleeding pattern , and side effects were assessed . Blood and milk NES concentration were measured . No pregnancy occurred in 2195 and 2145 woman-months of NES implant and T-Cu use , respectively . No effect of NES on lactation and infant growth and no serious adverse events were observed . Lactational amenorrhea was significantly longer in NES users ( 353 + /- 20 days ) than in T-Cu users ( 201 + /- 11 days ) . More NES users ( 55.8 % ) experienced prolonged bleedings than did T-Cu users ( 36.2 % ) . Concentrations of NES in breast milk ranged between 54 - 135 pmol/liter . The Nestorone implant is a highly effective contraceptive , safe for breastfed infants because the steroid is inactive by the oral route In a r and omised controlled trial to determine the optimum time of initiation of Ovrette , a progestin only oral contraceptive among postpartum women , who fully or nearly fully breast-fed their infants in the first six months , no difference was found between group 1 ( initiating at six weeks postpartum ) and group 2 ( initiating the pill at return of menses or 6 months postpartum ) . There were no pregnancies in either group during the 18 month follow-up . There were no significant differences in the continuation rates between the two group Uniplant is a single contraceptive implant intended for one year use . It contains the progestogen nomegestrol acetate . The clinical performance and the effect of its use during the first postpartum year on breastfeeding performance and growth and health of the infants were studied and compared to the findings in a parallel group who used an intrauterine contraceptive device ( IUD ) in a prospect i ve , non-r and omized study . This was carried out in Assiut , Egypt . Two-hundred-forty fully breastfeeding mothers asking for initiation of contraception early postpartum were assigned according to their choices into either nomegestrol subdermal contraceptive implant ( Uniplant ) ( 120 women ) or intrauterine contraceptive device ( CuT 380A ) ( 120 women ) . The mother and infant pairs were followed up at monthly intervals during the first three months and at two-month intervals thereafter up until the first birthday of the baby . No pregnancy occurred in the two groups . Amenorrhea was significantly more prolonged in the Uniplant group than in the IUD group . There were no significant differences in net continuation rates between the two groups ( 88.3 versus 92.4 per 100 women , respectively ) . There were no significant differences between the two groups in the number of breastfeeding episodes , time of weaning , and the cumulative rates of full and partial breastfeeding . There were no significant differences between the two groups in infant weight , weight gain per day , or in infant linear growth . There were no significant differences in the incidence of important health problems affecting the infants of the two groups . However , there were seven infant deaths , six of them were in the Uniplant group . Uniplant subdermal contraceptive implants can be offered as a new contraceptive option suitable for nursing mothers The objective of this paper was to compare the efficacy , acceptability , safety , and bleeding pattern of TCu 380A intrauterine device ( IUD ) and progesterone-releasing vaginal ring used by breastfeeding women . The study population included 97 breastfeeding women using IUD and 100 women using vaginal ring . Of the IUD users , no insertion failure , perforation , or accidental pregnancy occurred in 12 months . There was one IUD expulsion . There were no discontinuations of IUD due to medical reasons other than expulsion . The total discontinuation rate was 2.3 % . In the ring group , no accidental pregnancy occurred . The major reasons for discontinuation were ring use-related problems and vaginal problems . The total discontinuation rate was 65.4 % within 1 year . The frequency of any one complaint among the ring users was higher than that among the IUD users . There were no differences in the proportion of women having no sexual activity and in the weight of their babies between the two groups . Compared with the IUD users , the median number of bleeding/spotting ( B/S ) episodes and B/S days of the vaginal ring users were fewer ; consequently , the mean length of B/S-free interval was longer in all four reference periods ; the mean length of B/S episode and segment were the same ; the occurrence of amenorrhea was more frequent ; in contrast , the proportions of normal bleeding patterns were fewer . The frequencies of prolonged bleeding , frequent bleeding , and infrequent bleeding patterns did not differ between the two groups . The percentage of irregular bleeding was fewer only in the first two reference periods . It is concluded that the TCu 380A IUD and progesterone-releasing vaginal ring used by breastfeeding women are safe and effective . The higher discontinuation rate of the ring users was mainly because of use-related problems . Breastfeeding women with TCu 380A IUD had better tolerance and acceptability . The TCu 380A IUD does not , but the progesterone-releasing vaginal ring does , suppress the recovery of ovarian function . However , once return of menstruation occurred , there were no differences in bleeding patterns between the two contraceptive methods A prospect i ve study was made on the duration of lactation in 406 mothers injected postpartum for contraception with medroxyprogesterone acetate ( DMPA ) , 150 or 250–300 mg , IM , at 3-or 6− month intervals . Breast feedings up to 2 per day were recorded , and findings compared with those from 173 nontreated controls . Eighty percent of the DMPA group were nursing successfully at the sixth month and 42 % at the 12th month postpartum . These figures are significant and compare favorably with the control group . No advantage was found in the administration of DMPA earlier than the second or third month after delivery . Amenorrhea persisted during lactation . No pathologic breast conditions were observed . The eventual mechanism of DMPA in galactopoiesis has yet to be clarified WHO conducted a three-centre study in Hungary and Thail and to evaluate the effects of hormonal contraception on lactation and infant growth . Women choosing oral contraceptives were r and omly assigned to a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel ( N = 86 ) or a progestin-only preparation containing 75 micrograms dl-norgestrel ( N = 85 ) . Identical packaging and treatment schedules allowed double-blind observation . One-hundred- and -eleven women using no contraception or non-hormonal methods acted as controls . In the two Thai centres 59 women using depot-medroxyprogesterone acetate formed an additional comparison group . All subjects were healthy women with normal deliveries , whose infants had normal birth weights and satisfactory growth in the neonatal period . Breast milk volume was determined by pump expression using st and ardized procedures . Information was obtained on nursing frequency and supplementation , infant growth and morbidity . Pretreatment observations at 6 weeks post-partum were used as a baseline , and subjects were followed-up at 9 , 12 , 16 , 20 and 24 weeks post-partum . Women using combined oral contraceptives had a decline in milk volume within 6 weeks of initiating treatment , whereas no significant decrease was observed in the other treatment groups . After 18 weeks of treatment , combined oral contraceptive users experienced a 41.9 % decline in milk volume , compared to 12.0 % with progestin-only minipills and 6.1 % in the non-hormonal controls . The prevalence of complementary feeding and withdrawals due to inadequate milk supply were comparable in the four treatment groups . However , data were not available on the daily amounts of complementary feeds . There were no significant differences in growth of infants between treatment groups . Thus , women may have compensated for declines in milk volume by more supplementary feeding or by more prolonged and intense suckling episodes . We conclude that 30 micrograms estrogen-containing combined oral contraceptives impair milk secretion , but in the selected healthy group of mothers and children studied with the prevailing level of supplementary feeding , this did not adversely affect infant growth Few longitudinal studies are available which relate data on breastfeeding and growth of the last-born child to data on the mother 's subsequent pregnancy . The purpose of the present prospect i ve study from Bhutan was to compare growth rate of children weaned during a subsequent pregnancy , with those of children weaned at the same age , but from non-pregnant mothers . Measurements of weight of 113 children and interviews with their mothers were done monthly through 32 months during the children 's first 3 years of life . The period of overlap between lactation and pregnancy had a median duration of 5 months , and increased with an average of one week for each month reduction in the subsequent birth interval ( P < 0.01 ) . Children who stopped breastfeeding during their mothers ' subsequent pregnancy showed a reduced growth rate during the last months before termination of breastfeeding when compared to children weaned at the same age , but from non-pregnant mothers ( P = 0.04 ) , and when compared to children who continued breastfeeding ( P = 0.06 ) A copper-releasing IUD and levonorgestrel-releasing IUDs releasing 30 micrograms and 10 micrograms levonorgestrel per day were inserted six weeks after delivery in 110 volunteers . During the treatment , events and patterns of bleeding were recorded and plasma levonorgestrel concentrations were measured . The number of events in one year of follow-up was very low , four removals out of 40 in the copper-releasing IUD group and five removals out of 70 in the levonorgestrel-releasing IUD group . Bleeding and spotting was significantly more common after insertion of a levonorgestrel-releasing IUD than a copper-releasing IUD , but it was scanty and well-tolerated . After three months , levonorgestrel-releasing IUD patients had less bleeding and spotting than the copper-releasing IUD patients . No pregnancies occurred during the study period . There were two uterine perforations with a uterine sound at the insertion . In the 30-micrograms per day levonorgestrel-releasing IUD group , initially high plasma levonorgestrel concentrations reached a plateau four weeks after the insertion . In the 10-micrograms per day levonorgestrel-releasing IUD group , the plasma concentrations of levonorgestrel stabilized after the initial two weeks OBJECTIVE : To estimate the effect of progestin-only compared with combined hormonal contraceptive pills on rates of breastfeeding continuation in postpartum women . Secondary outcomes include infant growth parameters , contraceptive method continuation , and patient satisfaction with breastfeeding and contraceptive method . METHODS : Postpartum breastfeeding women who desired oral contraceptives were r and omly assigned to progestin-only and combined hormonal contraceptive pills . At 2 and 8 weeks postpartum , participants completed in-person question naires that assessed breastfeeding continuation and contraceptive use . Infant growth parameters including weight , length , and head circumference were assessed at 8 weeks postpartum . Telephone question naires assessing breastfeeding , contraceptive continuation , and satisfaction were completed at 3–7 weeks and 4 and 6 months . Breastfeeding continuation was compared between groups using Cox proportional hazards regression . Differences in baseline demographic characteristics and in variables between the two intervention groups were compared using & khgr;2 tests , Fisher exact test , or two- sample t tests as appropriate . RESULTS : Breastfeeding continuation rates at 8 weeks ( progestin-only 63.5 % ; combined hormonal 64.1 % ) , contraceptive continuation , and infant growth parameters did not differ between users of progestin-only and combined hormonal contraceptive pills . Infant formula supplementation and maternal perception of inadequate milk supply were associated with decreased rates of breastfeeding in both groups . CONCLUSION : Choice of combined hormonal or progestin-only contraceptive pills administered 2 weeks postpartum did not adversely affect breastfeeding continuation . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01465022 . LEVEL OF EVIDENCE : BACKGROUND The effects of etonogestrel (ETG)-releasing contraceptive implant during the immediate postpartum period on maternal safety are unknown . STUDY DESIGN Forty healthy women exclusively breastfeeding were r and omized to receive either ETG-releasing implant 24 - 48 h after delivery ( n=20 ) or depot medroxyprogesterone acetate ( DMPA group ; n=20 ) at the sixth week postpartum . We measured blood pressure , maternal and neonatal weight , body mass index ( BMI ; kg/m(2 ) ) , waist circumference ( WC ) , complete blood count , C-reactive protein , interleukin-6 , tumor necrosis factor ( TNF-alpha ) , lipid profile , fasting serum glucose and maintenance of exclusive lactation up to the 12th week postpartum . RESULTS Decreases in mean maternal weight , BMI ( kg/m(2 ) ) and WC were significantly greater in the ETG-releasing implant group than in the DMPA group during the first 6 weeks postpartum ( -4.64+/-2.71 kg vs. -2.6+/-2.45 kg mean+/-SD , p=.017 ; -1.77+/-1.06 kg/m(2 ) vs. -0.97+/-0.95 kg/m(2 ) , p=.026 ; -15.3+/-6.72 cm vs. -9.05+/-5.84 cm , p=.003 , respectively ) . In addition , total cholesterol and HDL , were lower in DMPA users , and TNF-alpha and leukocytes were higher in DMPA users compared to in the implant group , between 6 and 12 weeks after delivery . The newborns of implant users showed a trend towards gaining more weight , as compared with the infants of the DMPA mothers during the first 6 weeks of life ( implant group : + 1460.50+/-621.34 g vs. DMPA group : + 1035.0+/-562.43 g , p=.05 ) . The remaining variables , including the duration of exclusive breastfeeding , were similar between the groups . CONCLUSION The insertion of ETG-releasing contraceptive implant during the immediate postpartum period was not associated with deleterious maternal clinical effects or with significant maternal metabolic alterations or decreased infant weight gain BACKGROUND The objective of this study was to assess the effect of timing of postpartum levonorgestrel-releasing intrauterine device ( IUD ) insertion on breast-feeding continuation . STUDY DESIGN Women interested in using a levonorgestrel IUD postpartum were r and omized to immediate postplacental insertion ( postplacental group ) or insertion 6 - 8 weeks after vaginal delivery ( delayed group ) . Duration and exclusivity of breast-feeding were assessed at 6 - 8 weeks , 3 months , and 6 months postpartum . Only women who received an IUD were included in this analysis . RESULTS Breast-feeding was initiated by 32 ( 64 % ) of 50 of women receiving a postplacental IUD and 27 ( 58.7 % ) of 46 of women receiving a delayed IUD ( p=.59 ) . More women in the delayed group compared with the postplacental group continued to breast-feed at 6 - 8 weeks ( 16/46 vs. 15/50 , p=.62 ) , 3 months ( 13/46 vs. 7/50 , p=.13 ) , and 6 months postpartum ( 11/46 vs. 3/50 , p=.02 ) . The results did not differ when only women who initiated breast-feeding or only primiparous women with no prior breast-feeding experience were analyzed . CONCLUSIONS Immediate postplacental insertion of the levonorgestrel IUD is associated with shorter duration of breast-feeding and less exclusive breast-feeding . Further studies on the effects of early initiation of progestin-only methods on women 's lactation experience are needed |
1,779 | 18,801,204 | Anxiety and depression scores were generally lower in the TFCBT groups than in the SC groups .
Conclusion There is evidence for the effectiveness of TFCBT compared to SC in preventing chronic PTSD in patients with an initial ASD diagnosis . | Background Early trauma-focused cognitive-behavioural therapy ( TFCBT ) holds promise as a preventive intervention for people at risk of developing chronic post-traumatic stress disorder ( PTSD ) . | Acute stress disorder ( ASD ) is a precursor of chronic posttraumatic stress disorder ( PTSD ) . Twenty-four participants with ASD following civilian trauma were given 5 sessions of either cognitive-behavioral therapy ( CBT ) or supportive counseling ( SC ) within 2 weeks of their trauma . Fewer participants in CBT ( 8 % ) than in SC ( 83 % ) met criteria for PTSD at posttreatment . There were also fewer cases of PTSD in the CBT condition ( 17 % ) than in the SC condition ( 67 % ) 6 months posttrauma . There were greater statistically and clinical ly significant reductions in intrusive , avoidance , and depressive symptomatology among the CBT participants than among the SC participants . This study represents the 1st demonstration of successful treatment of ASD with CBT and its efficacy in preventing chronic PTSD This research represents the first controlled treatment study of hypnosis and cognitive- behavioral therapy ( CBT ) of acute stress disorder ( ASD ) . Civilian trauma survivors ( N=87 ) who met criteria for ASD were r and omly allocated to 6 sessions of CBT , CBT combined with hypnosis ( CBT-hypnosis ) , or supportive counseling ( SC ) . CBT comprised exposure , cognitive restructuring , and anxiety management . CBT-hypnosis comprised the CBT components with each imaginal exposure preceded by a hypnotic induction and suggestions to engage fully in the exposure . In terms of treatment completers ( n=69 ) , fewer participants in the CBT and CBT-hypnosis groups met criteria for posttraumatic stress disorder at posttreatment and 6-month follow-up than those in the SC group . CBT-hypnosis result ed in greater reduction in reexperiencing symptoms at posttreatment than CBT . These findings suggest that hypnosis may have use in facilitating the treatment effects of CBT for posttraumatic stress Ninety female recent assault survivors who met symptom criteria for posttraumatic stress disorder ( PTSD ) were r and omized to one of three interventions : Brief Cognitive Behavioral Intervention , which focused on processing the traumatic event ( B-CBT ) ; assessment condition ( AC ) ; or supportive counseling ( SC ) . Within 4 weeks of an assault , participants met weekly with a therapist for four 2-hr sessions . Across all interventions , participants reported decreases in PTSD symptoms , depression , and anxiety over time . At postintervention , participants in B-CBT reported greater decreases in self-reported PTSD severity and a trend toward lower anxiety than those in SC . At 3-month follow-up , participants in B-CBT evidence d lower general anxiety than those in SC and a trend toward lower self-reported PTSD severity . At last available follow-up ( on average , 9-months postassault ) , all three interventions were generally similar in outcome . These findings suggest that a trauma-focused intervention aim ed at those with severe PTSD symptoms after an assault can accelerate recovery OBJECTIVE Acute stress disorder permits an early identification of trauma survivors who are at risk of developing chronic posttraumatic stress disorder ( PTSD ) . This study aim ed to prevent PTSD by an early provision of cognitive behavior therapy . Specifically , this study indexed the relative efficacy of prolonged exposure and anxiety management in the treatment of acute stress disorder . METHOD Forty-five civilian trauma survivors with acute stress disorder were given five sessions of 1 ) prolonged exposure ( N = 14 ) , 2 ) a combination of prolonged exposure and anxiety management ( N = 15 ) , or 3 ) supportive counseling ( N = 16 ) within 2 weeks of their trauma . Forty-one trauma survivors were assessed at the 6-month follow-up . RESULTS Fewer patients with prolonged exposure ( 14 % , N = 2 of 14 ) and prolonged exposure plus anxiety management ( 20 % , N = 3 of 15 ) than supportive counseling ( 56 % , N = 9 of 16 ) met the criteria for PTSD after treatment . There were also fewer cases of PTSD in the prolonged exposure group ( 15 % , N = 2 of 13 ) and the prolonged exposure plus anxiety management group ( 23 % , N = 3 of 13 ) than in the supportive counseling group ( 67 % , N = 10 of 15 ) 6 months after the trauma . Chronic PTSD in the supportive counseling condition was characterized by greater avoidance behaviors than in the prolonged exposure condition or the prolonged exposure plus anxiety management condition . CONCLUSIONS These findings suggest that PTSD can be effectively prevented with an early provision of cognitive behavior therapy and that prolonged exposure may be the most critical component in the treatment of acute stress disorder The aim of this study was to index the long-term benefits of early provision of cognitive behavior therapy to trauma survivors with acute stress disorder . Civilian trauma survivors ( n = 80 ) with acute stress disorder were r and omly allocated to either cognitive behavior therapy ( CBT ) or supportive counseling ( SC ) - 69 completed treatment , and 41 were assessed four years post-treatment for post-traumatic stress disorder ( PTSD ) with the Clinician Administered PTSD Scale . Two CBT patients ( 8 % ) and four SC patients ( 25 % ) met PTSD criteria at four-year follow-up . Patients who received CBT reported less intense PTSD symptoms , and particularly less frequent and less avoidance symptoms , than patients who received SC . These findings suggest that early provision of CBT in the initial month after trauma has long-term benefits for people who are at risk of developing PTSD The long-term benefits of cognitive behaviour therapy ( CBT ) for trauma survivors with acute stress disorder were investigated by assessing patients 3 years after treatment . Civilian trauma survivors ( n=87 ) were r and omly allocated to six sessions of CBT , CBT combined with hypnosis , or supportive counselling ( SC ) , 69 completed treatment , and 53 were assessed 2 years post-treatment for post-traumatic stress disorder ( PTSD ) with the Clinician-Administered PTSD Scale . In terms of treatment completers , 2 CBT patients ( 10 % ) , 4 CBT/hypnosis patients ( 22 % ) , and 10 SC patients ( 63 % ) met PTSD criteria at 2-years follow-up . Intent-to-treat analyses indicated that 12 CBT patients ( 36 % ) , 14 CBT/hypnosis patients ( 46 % ) , and 16 SC patients ( 67 % ) met PTSD criteria at 2-year follow-up . Patients who received CBT and CBT/hypnosis reported less re-experiencing and less avoidance symptoms than patients who received SC . These findings point to the long-term benefits of early provision of CBT in the initial month after trauma |
1,780 | 29,534,221 | Dietary intake and behaviors appear to have some influence on oxytocin , with more pronounced effects found with exogenously administered oxytocin | Context Oxytocin plays an important hormonal role in the regulation of feeding and energy intake .
Objective The aims of this review were to 1 ) determine the effects of dietary intake/behaviors on endogenous oxytocin and 2 ) examine the effect of exogenous oxytocin on dietary intake/behaviors . | Background / Objectives : Animal studies and pilot experiments in men indicate that the hypothalamic neuropeptide oxytocin limits food intake , and raise the question of its potential to improve metabolic control in obesity . Subjects/ Methods : We compared the effect of central nervous oxytocin administration ( 24 IU ) via the intranasal route on ingestive behaviour and metabolic function in 18 young obese men with the results in a group of 20 normal-weight men . In double-blind , placebo-controlled experiments , ad libitum food intake from a test buffet was examined in fasted subjects 45 min after oxytocin administration , followed by the assessment of postpr and ial , reward-driven snack intake . Energy expenditure was repeatedly assessed by indirect calorimetry and blood was sample d to determine concentrations of blood glucose and hormones . Results : Oxytocin markedly reduced hunger-driven food intake in the fasted state in obese but not in normal-weight men , and led to a reduction in snack consumption in both groups , whereas energy expenditure remained generally unaffected . Hypothalamic – pituitary – adrenal axis secretion and the postpr and ial rise in plasma glucose were blunted by oxytocin in both groups . Conclusions : Oxytocin exerts an acutely inhibitory impact on food intake that is enhanced rather than decreased in obese compared with normal-weight men . This pattern puts it in contrast to other metabolically active neuropeptides and bodes well for clinical applications of oxytocin in the treatment of metabolic disorders Fragile X syndrome ( FXS ) is a rare inherited genetic disorder causing severe intellectual disability and autistic-like symptoms . Individuals with FXS , males in particular , often exhibit extreme eye gaze avoidance and hyperarousal when they encounter stressful social situations . We investigated whether oxytocin ( OT ) , a hormone with prosocial and anxiolytic effects , could alleviate symptoms of social anxiety in this population . A r and omized double-blind placebo-controlled single-dose trial was performed with intranasal administration of placebo , 24 IU OT and 48 IU OT . Measures of eye gaze frequency , heart rate , respiratory sinus arrhythmia ( RSA ) , heart rate variability ( HRV ) and salivary cortisol were obtained during a structured social challenge conducted 50 min following OT administration . Ten low-functioning males with FXS ( aged 13 - 28 years ) traveled to Stanford for the initial visit : 8 completed the study . Eye gaze frequency improved significantly in response to the 24 IU OT dose and salivary cortisol levels decreased significantly in response to the 48 IU OT dose . There was no effect of OT on heart rate , RSA or HRV although individual plots of the heart rate data suggested that OT increased heart rate in some participants and decreased heart rate in others . These findings suggest that intranasal administration of OT may ameliorate some symptoms of social anxiety in patients with FXS . Further double-blind placebo-controlled studies of OT , conducted in combination with behavioral treatment programs , may be warranted We investigated the effects of intranasal oxytocin ( OXT ) on trust and cooperation in borderline personality disorder ( BPD ) , a disorder marked by interpersonal instability and difficulties with cooperation . Although studies in healthy adults show that intranasal OXT increases trust , individuals with BPD may show an altered response to exogenous OXT because the effects of OXT on trust and pro-social behavior may vary depending on the relationship representations and expectations people possess and /or altered OXT system functioning in BPD . BPD and control participants received intranasal OXT and played a social dilemma game with a partner . Results showed that OXT produced divergent effects in BPD participants , decreasing trust and the likelihood of cooperative responses . Additional analyses focusing on individual differences in attachment anxiety and avoidance across BPD and control participants indicate that these divergent effects were driven by the anxiously attached , rejection-sensitive participants . These data suggest that OXT does not uniformly facilitate trust and pro-social behavior in humans ; indeed , OXT may impede trust and pro-social behavior depending on chronic interpersonal insecurities , and /or possible neurochemical differences in the OXT system . Although popularly dubbed the ' hormone of love ' , these data suggest a more circumspect answer to the question of who will benefit from OXT Background and Aim Social difficulties and problems related to eating behaviour are common features of both anorexia nervosa ( AN ) and bulimia nervosa ( BN ) . The aim of this study was to examine the impact of intranasal oxytocin on consummatory behaviour and emotional recognition in patients with AN and BN in comparison to healthy controls . Material s A total of 102 women , including 35 patients with anorexia nervosa ( AN ) , 34 patients with bulimia nervosa ( BN ) , and 33 healthy university students of comparable age and intelligence , participated in a double-blind , single dose placebo-controlled cross-over study . A single dose of intranasal administration of oxytocin ( 40 IU ) ( or a placebo ) was followed by an emotional recognition task and an apple juice drink . Food intake was then recorded for 24 hours post-test . Results Oxytocin produced no significant change in appetite in the acute or 24 hours free living setting s in healthy controls , whereas there was a decrease in calorie consumption over 24 hours in patients with BN . Oxytocin produced a small increase in emotion recognition sensitivity in healthy controls and in patients with BN , In patients with AN , oxytocin had no effect on emotion recognition sensitivity or on consummatory behaviour . Conclusions The impact of oxytocin on appetite and social cognition varied between people with AN and BN . A single dose of intranasal oxytocin decreased caloric intake over 24 hours in people with BN . People with BN showed enhanced emotional sensitivity under oxytocin condition similar to healthy controls . Those effects of oxytocin were not found in patients with AN . Trial Registration Clinical Trials.gov Rationale Social cognition influences social interactions . Alcohol reportedly facilitates social interactions . However , the acute effects of alcohol on social cognition are relatively poorly studied . Methods We investigated the effects of alcoholic or non-alcoholic beer on emotion recognition , empathy , and sexual arousal using the dynamic face emotion recognition task ( FERT ) , Multifaceted Empathy Test ( MET ) , and Sexual Arousal Task ( SAT ) in a double-blind , r and om-order , cross-over study in 60 healthy social drinkers . We also assessed subjective effects using visual analog scales ( VASs ) , blood alcohol concentrations , and plasma oxytocin levels . Results Alcohol increased VAS ratings of stimulated , happy , talkative , open , and want to be with others . The subjective effects of alcohol were greater in participants with higher trait inhibitedness . Alcohol facilitated the recognition of happy faces on the FERT and enhanced emotional empathy for positive stimuli on the MET , particularly in participants with low trait empathy . Pictures of explicit sexual content were rated as less pleasant than neutral pictures after non-alcoholic beer but not after alcoholic beer . Explicit sexual pictures were rated as more pleasant after alcoholic beer compared with non-alcoholic beer , particularly in women . Alcohol did not alter the levels of circulating oxytocin . Conclusions Alcohol biased emotion recognition toward better decoding of positive emotions and increased emotional concern for positive stimuli . No support was found for a modulatory role of oxytocin . Alcohol also facilitated the viewing of sexual images , consistent with disinhibition , but it did not actually enhance sexual arousal . These effects of alcohol on social cognition likely enhance sociability . Trial registration www . clinical Objective Pre clinical studies indicate that oxytocin is anorexigenic and has beneficial metabolic effects . Oxytocin effects on nutrition and metabolism in humans are not well defined . We hypothesized that oxytocin would reduce caloric intake and appetite , and alter levels of appetite-regulating hormones . We also explored metabolic effects of oxytocin . Methods We performed a r and omized , placebo-controlled crossover study of single-dose intranasal oxytocin ( 24 IU ) in 25 fasting healthy men . After oxytocin/placebo , subjects selected breakfast from a menu , and were given double portions . Caloric content of food consumed was measured . Visual analogue scales were used to assess appetite and blood was drawn for appetite-regulating hormones , insulin , and glucose before and after oxytocin/placebo . Indirect calorimetry assessed resting energy expenditure ( REE ) and substrate utilization . Results Oxytocin reduced caloric intake with a preferential effect on fat intake and increased levels of the anorexigenic hormone cholecystokinin without affecting appetite or other appetite-regulating hormones . There was no effect of oxytocin on REE . Oxytocin result ed in a shift from carbohydrate to fat utilization and improved insulin sensitivity . Conclusions Intranasal oxytocin reduces caloric intake and has beneficial metabolic effects in men without concerning side effects . The efficacy and safety of sustained oxytocin administration in the treatment of obesity warrants investigation OBJECTIVE To find out if cholecystokinin ( CCK ) stimulates the secretion of oxytocin in humans , and if there are any differences in secretion between healthy women and those with normal-transit constipation . DESIGN Prospect i ve open study . SETTING Teaching hospital , Sweden . SUBJECTS 8 healthy female volunteers and 6 women with chronic refractory normal-transit constipation . INTERVENTIONS Subjects were fasted before experiments . On one day they were given emulsified corn oil and another an intravenous injection of 1 Ivy dog unit ( IDU ) CCK/kg body weight . Blood sample s were taken before each experiment at 10 minutes and at the time the experiments started . Blood sample s were also taken after each experiment at 10 , 20 , 30 , 45 , 60 , 90 and 120 minutes . MAIN OUTCOME MEASURES Concentrations of CCK and oxytocin . RESULTS Ingestion of corn oil significantly increased the plasma concentration of CCK in both groups ( healthy women p = 0.03 and constipated women p = 0.008 ) . Injection of CCK also led as expected to hypercholecystokininaemia in both groups ( p = 0.008 and p = 0.03 , respectively ) . The corn oil increased oxytocin secretion in both groups ( p = 0.02 and 0.03 , respectively ) and exogenous CCK increased the secretion still further ( p = 0.008 and 0.03 , respectively ) . CONCLUSIONS Both corn oil and injection of CCK led to an increased CCK concentration in plasma . Oxytocin was secreted in response to endogenous as well as exogenous CCK stimulation . There was no difference between healthy and constipated women in either parameter analysed |
1,781 | 26,342,485 | With respect to total bleeding risk , no significant difference was observed between dabigatran , rivaroxaban , apixaban , and vitamin K antagonists ( VKAs ) by mixed-treatment comparison .
The similar results were seen in the direct comparison .
Conclusions Risks of bleeding with dabigatran , rivaroxaban , apixaban , and VKAs were similar in peri-procedural period of CA for AF | Background Comprehensive comparisons of safety ( measured by bleeding risk ) between multiple novel oral anticoagulants ( NOACs and warfarin ) in the peri-procedural period of catheter ablation ( CA ) for atrial fibrillation ( AF ) are rare . | Background : The novel oral anticoagulants ( NOACs ) are used for stroke prevention in atrial fibrillation ( AF ) , but their safety and efficacy in the periablation period are not well established . Additionally , no st and ard procedure for managing periprocedural and intraprocedural anticoagulation has been established . Objective : To evaluate the frequency of hemorrhagic and thrombotic events as well as periprocedural management strategies of NOACs compared with warfarin as anticoagulation therapy for AF ablation . Methods : This was a retrospective cohort study from a prospect i ve AF ablation registry maintained at a large , academic medical center . Results : A total of 374 cases ( 173 warfarin , 123 dabigatran , 61 rivaroxaban , and 17 apixaban ) were included in the analysis . The overall hemorrhagic/thrombotic event rate was 14.2 % ( major hemorrhage 2.7 % , minor hemorrhage 11.2 % , thrombotic stroke 0.5 % ) . The frequency of minor hemorrhage was significantly higher with warfarin compared with dabigatran ( 15 % vs 5.7 % , P = 0.012 ) . The average heparin dose required to reach the goal activated clotting time ( ACT ) was 5600 units for warfarin , 12 900 units for dabigatran ( P < 0.001 ) , 15 100 units for rivaroxaban ( P < 0.001 ) , and 14 700 units for apixaban ( P < 0.001 ) . The average time in minutes to reach the goal ACT was significantly longer , compared with warfarin , for dabigatran ( 57 vs 28 , P < 0.001 ) , rivaroxaban ( 63 vs 28 , P < 0.001 ) , and apixaban ( 72 vs 28 , P < 0.001 ) . Conclusions : Compared with warfarin , periprocedural anticoagulation with dabigatran result ed in fewer minor hemorrhages and total adverse events after AF ablation . Patients anticoagulated with NOACs required larger doses of heparin and took longer to reach the goal ACT compared with patients anticoagulated with warfarin OBJECTIVES The purpose of this study was to evaluate the feasibility and safety of periprocedural dabigatran during atrial fibrillation ( AF ) ablation . BACKGROUND AF ablation requires optimal periprocedural anticoagulation for minimizing bleeding and thromboembolic complications . The safety and efficacy of dabigatran as a periprocedural anticoagulant for AF ablation are unknown . METHODS We performed a multicenter , observational study from a prospect i ve registry including all consecutive patients undergoing AF ablation in 8 high-volume centers in the United States . All patients receiving dabigatran therapy who underwent AF ablation on periprocedural dabigatran , with the dose held on the morning of the procedure , were matched by age , sex , and type of AF with an equal number of patients undergoing AF ablation with uninterrupted warfarin therapy over the same period . RESULTS A total of 290 patients , including 145 taking periprocedural dabigatran and an equal number of matched patients taking uninterrupted periprocedural warfarin , were included in the study . The mean age was 60 years with 79 % being male and 57 % having paroxysmal AF . Both groups had a similar CHADS(2 ) score , left atrial size , and left ventricular ejection fraction . Three thromboembolic complications ( 2.1 % ) occurred in the dabigatran group compared with none in the warfarin group ( p = 0.25 ) . The dabigatran group had a significantly higher major bleeding rate ( 6 % vs. 1 % ; p = 0.019 ) , total bleeding rate ( 14 % vs. 6 % ; p = 0.031 ) , and composite of bleeding and thromboembolic complications ( 16 % vs. 6 % ; p = 0.009 ) compared with the warfarin group . Dabigatran use was confirmed as an independent predictor of bleeding or thromboembolic complications ( odds ratio : 2.76 , 95 % confidence interval : 1.22 to 6.25 ; p = 0.01 ) on multivariate regression analysis . CONCLUSIONS In patients undergoing AF ablation , periprocedural dabigatran use significantly increases the risk of bleeding or thromboembolic complications compared with uninterrupted warfarin therapy BACKGROUND We aim ed to evaluate the feasibility of an oral direct thrombin inhibitor , dabigatran , as a periprocedural anticoagulant for use with ablation of atrial fibrillation ( AF ) . METHODS Consecutive patients scheduled to undergo an AF ablation were r and omly assigned to receive dabigatran ( n = 45 ) or warfarin ( n = 45 ) to compare their clinical feasibility . Both of those oral anticoagulants were discontinued the day before the ablation and were resumed after confirming hemostasis of the venipuncture site . A bridging therapy with heparin was not used in either of the patient groups . RESULTS Dabigatran was switched to warfarin before the ablation because of dyspepsia in three patients . An occurrence of rebleeding from the venipuncture site was less common in dabigatran-allocated patients than in warfarin-allocated patients ( 20 % vs 44 % ; P = 0.013 ) . The reduction in the D-dimer level after the initiation of oral anticoagulants was greater in the dabigatran-allocated patients than in the warfarin-allocated patients . The time from the initiation of the anticoagulants to the ablation was significantly shorter in the dabigatran-allocated patients than in the warfarin-allocated patients ( 43 ± 7 vs 63 ± 13 days ; P < 0.0001 ) . There was only one fatal periprocedural complication in a patient receiving warfarin , who had a mesenteric arterial thrombosis after the ablation . CONCLUSIONS An anticoagulation strategy with dabigatran may surpass that with warfarin in reducing both the periprocedural risk of minor bleeding and a hypercoagulable state , and the time to ablation in patients undergoing ablation of AF Background and Objectives Two new oral anticoagulants , rivaroxaban and dabigatran , with no need for anticoagulation monitoring , are available for patients with atrial fibrillation ( AF ) . We aim ed to compare their anticoagulant effects and safety when used during the AF ablation periprocedural period . Methods Patients undergoing AF ablation were r and omly assigned to receive rivaroxaban 15 mg once daily ( N = 30 ) or dabigatran 110 mg twice daily ( N = 30 ) . Rivaroxaban was withheld on the morning of the day before the ablation , and dabigatran was discontinued from the evening of the day before the procedure . Both anticoagulants were then resumed after haemostasis of the access site . D-dimer levels were measured just before the ablation , at the end of the ablation , and at 24 h and 48 h after the procedure . Results The baseline D-dimer levels were identical in both groups . However , D-dimer levels increased more markedly following the ablation procedure in patients receiving rivaroxaban than in those receiving dabigatran ( mean ± st and ard deviation from 0.62 ± 0.16 to 1.09 ± 0.38 μg/mL vs from 0.59 ± 0.08 to 0.75 ± 0.17 μg/mL ; p < 0.0001 ) . The rate of rebleeding from the access site was similar in patients receiving rivaroxaban and those receiving dabigatran ( 33 vs 27 % ; p = 0.78 ) . Conclusion As compared with dabigatran , rivaroxaban may increase the risk of hypercoagulability when used during the periprocedural period of AF ablation , suggesting a potential rebound effect of rivaroxaban or a mismatch between its half-life and dose regimen Background Systemic thromboembolism and bleeding remain the two most common and serious complications of catheter ablation of atrial fibrillation . A variety of periprocedure anticoagulation strategies have been proposed to mitigate these risks . Although operators are now routinely administering dabigatran for anticoagulation in this setting , its relative safety and effectiveness compared to warfarin are unknown . Methods and results A total of 202 patients received dabigatran as part of their periprocedural anticoagulation regimen at the time of initial or redo catheter ablation for symptomatic atrial fibrillation . A comparison group of 202 patients treated with warfarin was r and omly selected from patients undergoing atrial fibrillation ( AF ) ablation during the same time period . AF types were paroxysmal in 223 patients , persistent in 158 patients , and longst and ing persistent in 13 patients . Mean age was 60.0 ± 10.5 years , 55 % had a history of hypertension , and mean CHADS-VASc score was 1.7 ± 1.3 . “ Continuous ” warfarin or dabigatran was administered in 80 and 32 % of patients , respectively . Time to first dose of dabigatran post-procedure was 12.2 ± 10.3 h. Two dabigatran and no warfarin-treated patients had systemic thromboembolism ( p = NS ) ; five dabigatran and three warfarin-treated patients had bleeding complications ( p = NS , combined endpoint p = 0.116 ) . One dabigatran patient had severe pericardial bleeding ( 3 L blood loss ) . Conclusions In a retrospective pilot trial comparing the risks of systemic thromboembolism or bleeding complications in patients treated with warfarin or dabigatran anticoagulation , the outcomes were similar . A prospect i ve trial is warranted BACKGROUND Periprocedural anticoagulation using uninterrupted warfarin could reduce the risk of thromboembolic complications of atrial fibrillation ( AF ) ablation . Few studies , however , have evaluated the efficacy and safety of periprocedural dabigatran in AF ablation . METHODS AND RESULTS A total of 211 consecutive patients who underwent AF ablation , including 110 patients who received 110 mg dabigatran twice daily ( group D ) and 101 patients who received dose-adjusted warfarin ( international normalized ratio , 2.0 - 3.0 ; group W ) , were evaluated . Dabigatran was discontinued on the morning of the procedure , and resumed on the next morning . Warfarin was continued throughout the procedure . During the procedure , heparin infusion was maintained to achieve an activated clotting time of > 300s . Postprocedural cerebral magnetic resonance imaging ( MRI ) was performed in 60 patients ( group D , n=31 ; group W , n=29 ) . No periprocedural deaths or symptomatic thromboembolic complications were observed in either group . MRI indicated a silent cerebral infa rct ion in 1 patient in each group . Five patients in group D and 11 in group W had minor bleeding ( P=0.12 ) . Cardiac tamponade occurred in 2 patients in group W , but in none in group D. Total bleeding complications occurred less frequently in group D ( 4.5 % ) than in group W ( 12.9 % ; P<0.05 ) . CONCLUSIONS Dabigatran at a dose of 110 mg twice daily was safe for AF ablation in patients with a relatively low risk of thromboemboli , suggesting that it may become an alternative to warfarin in those patients AIMS Experiences with novel oral anticoagulants ( NOACs ) early after atrial fibrillation ( AF ) catheter ablation are limited and show controversial results . We aim ed to assess the longer-term safety , efficacy , and acceptance of NOACs in a large real-world cohort of patients presenting for AF catheter ablation . METHODS AND RESULTS From July 2010 until June 2012 , 259 patients undergoing AF catheter ablation were prospect ively included . Novel oral anticoagulants were given for at least 3 months post-ablation . Clinical outcome ( stroke , thromboembolic events , major bleeding ) , adverse effects , and drug adherence were assessed at discharge and follow-up . On admission patients were presented with a variety of anticoagulants including 54 patients ( 21 % ) already on NOACs prior ablation . After ablation 38 % of patients received dabigatran 110 mg , 56 % 150 mg , and 6 % received rivaroxaban 20 mg . There were four periprocedural thromboembolic and major bleeding complications ( 1.5 % ) , all in patients without NOACs prior ablation ( two on warfarin and two on heparin ) . During long-term follow-up [ 311 ( 199 ; 418 ) days ] no stroke , systemic embolism , or major haemorrhage could be observed . Uneventful electrical cardioversions and reablation procedures were performed in 27 and 12 patients on dabigatran , respectively . Novel oral anticoagulants were prematurely stopped or switched to another anticoagulant due to side effects or at the preference of the treating general practitioner in 9 and 10 patients , respectively . CONCLUSION In this prospect i ve observational study , anticoagulation with NOACs following AF catheter ablation was safe and effective at long-term follow-up . Fast onset of action makes NOACs especially attractive in patients without effective anticoagulation on admission and in patients following periprocedural complications OBJECTIVES The purpose of this study was to evaluate the feasibility and safety of uninterrupted rivaroxaban therapy during atrial fibrillation ( AF ) ablation . BACKGROUND Optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during and after AF ablation . The safety and efficacy of uninterrupted rivaroxaban therapy as a periprocedural anticoagulant for AF ablation are unknown . METHODS We performed a multicenter , observational , prospect i ve study of a registry of patients undergoing AF ablation in 8 centers in North America . Patients taking uninterrupted periprocedural rivaroxaban were matched by age , sex , and type of AF with an equal number of patients taking uninterrupted warfarin therapy who were undergoing AF ablation during the same period . RESULTS A total of 642 patients were included in the study , with 321 in each group . Mean age was 63 ± 10 years , with 442 ( 69 % ) males and 328 ( 51 % ) patients with paroxysmal AF equally distributed between the 2 groups . Patients in the warfarin group had a slightly higher mean HAS- BLED ( hypertension , abnormal renal/liver function , stroke , bleeding history or predisposition , labile international normalized ratio , elderly , drugs/alcohol concomitantly ) score ( 1.70 ± 1.0 vs. 1.47 ± 0.9 , respectively ; p = 0.032 ) . Bleeding and embolic complications occurred in 47 ( 7.3 % ) and 2 ( 0.3 % ) patients ( both had transient ischemic attacks ) respectively . There were no differences in the number of major bleeding complications ( 5 [ 1.6 % ] vs. 7 [ 1.9 % ] , respectively ; p = 0.772 ) , minor bleeding complications ( 16 [ 5.0 % ] vs. 19 [ 5.9 % ] , respectively ; p = 0.602 ) , or embolic complications ( 1 [ 0.3 % ] vs. 1 [ 0.3 % ] , respectively ; p = 1.0 ) between the rivaroxaban and warfarin groups in the first 30 days . CONCLUSIONS Uninterrupted rivaroxaban therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy Purpose Left atrial catheter ablation for patients with atrial fibrillation ( AF ) requires periprocedural anticoagulation to minimize thromboembolic complications . High rates of major bleeding complications using dabigatran etexilate for periprocedural anticoagulation have been reported , raising concerns regarding its safety during left atrial catheter ablation . We sought to evaluate the safety and efficacy of a dabigatran use strategy versus warfarin , at a single high-volume AF ablation center . Methods We performed a retrospective analysis on consecutive patients undergoing left atrial ablation at V and erbilt Medical Center from January 2011 through August 2012 with a minimum follow-up of 3 months . Patient cohorts were divided into two groups , those utilizing dabigatran etexilate pre- and post-ablation and those undergoing ablation on dose-adjusted warfarin , with or without low-molecular-weight heparin bridging . Dabigatran was held 24–30 h pre-procedure and restarted 4–6 h after hemostasis was achieved . We evaluated all thromboembolic and bleeding complications at 3 months post-ablation . Results A total of 254 patients underwent left atrial catheter ablation for atrial fibrillation or left atrial flutter . Periprocedural anticoagulation utilized dabigatran in 122 patients and warfarin in 135 patients . Three late thromboembolic complications occurred in the dabigatran group ( 2.5 % ) , compared with one ( 0.7 % ) in the warfarin group ( p = 0.28 ) . The dabigatran group had similar minor bleeding ( 2.5 vs. 7.4 % , p = 0.07 ) , major bleeding ( 1.6 vs. 0.7 % , p = 0.51 ) , and composite of bleeding and thromboembolic complications ( 6.6 vs. 8.9 % , p = 0.49 ) when compared to warfarin . There were no acute thromboembolic complications in either group ( < 24 h post-ablation ) . Conclusions In patients undergoing left atrial catheter ablation for AF or left atrial flutter , use of periprocedural dabigatran etexilate provides a safe and effective anticoagulation strategy compared to warfarin . A prospect i ve r and omized study is warranted |
1,782 | 25,031,191 | There are insufficient and biased data that do not allow any firm conclusions to be made about the comparative effectiveness of first-line allogeneic haematopoietic stem cell transplantation of HLA-matched sibling donors and first-line immunosuppressive therapy of patients with acquired severe aplastic anaemia | OBJECTIVES Acquired severe aplastic anaemia is a rare and potentially fatal disease .
The aim of this Cochrane review was to evaluate the effectiveness and adverse events of first-line allogeneic haematopoietic stem cell transplantation of human leucocyte antigen (HLA)-matched sibling donors compared with first-line immunosuppressive therapy .
SETTING Specialised stem cell transplantations units in primary care hospitals . | Severe acquired aplastic anaemia ( SAA ) is a life-threatening disease characterized by pancytopenia and hypoplastic bone marrow . Autologous T lymphocytes are thought to cause bone marrow failure by immune-mediated excessive apoptosis of stem and progenitor cells . The disease is subclassified into a severe ( neutrophil count , > 0.2 x 10(9)/L [ > 200/microL ] ) and a very severe ( < 0.2 x 10(9)/L [ < 200/microL ] ) ( vSAA ) form . We report the results of a prospect i ve multicenter trial with a combined immunosuppressive regimen of cyclosporin A ( CSA ) , anti-thymocyte globulin ( ATG ) and , in cases with neutrophil counts fewer than 0.5 x 10(9)/L ( < 500/microL ) , granulocyte colony-stimulating factor ( G-CSF ) for treatment of SAA in children . Children with vSAA showed a higher rate of complete response than did children with SAA ( 68 % versus 45 % ; P = .009 ) , as well as better survival ( 93 % versus 81 % ; P < .001 ) . Thus , in children with SAA a more severe disease stage at diagnosis indicates a favorable outcome with immunosuppressive therapy BACKGROUND In severe acquired aplastic anemia , hematopoietic failure is the result of immune-mediated destruction of bone marrow stem and progenitor cells . Immunosuppressive therapy with antithymocyte globulin ( ATG ) plus cyclosporine is an effective alternative to stem-cell transplantation and improves blood counts and survival . Although horse ATG is the st and ard therapy , rabbit ATG is more potent in depleting peripheral-blood lymphocytes and is preferred in other clinical circumstances . METHODS From December 2005 through July 2010 , we performed a r and omized trial comparing these two ATG formulations in conventional regimens . Patients were treated at a single facility . The primary outcome was hematologic response at 6 months , as determined by blood counts . The study was design ed to enroll 60 patients each for the rabbit-ATG and horse-ATG groups and was powered to detect a difference of 25 percentage points in the response rate . RESULTS A large , unexpected difference was observed in the rate of hematologic response at 6 months in favor of horse ATG ( 68 % ; 95 % confidence interval [ CI ] , 56 to 80 ) as compared with rabbit ATG ( 37 % ; 95 % CI , 24 to 49 ; P<0.001 ) . Overall survival at 3 years also differed , with a survival rate of 96 % ( 95 % CI , 90 to 100 ) in the horse-ATG group as compared with 76 % ( 95 % CI , 61 to 95 ) in the rabbit-ATG group ( P=0.04 ) when data were censored at the time of stem-cell transplantation , and 94 % ( 95 % CI , 88 to 100 ) as compared with 70 % ( 95 % CI , 56 to 86 ; P=0.008 ) in the respective groups when stem-cell-transplantation events were not censored . CONCLUSIONS In a r and omized study , rabbit ATG was inferior to horse ATG as a first treatment for severe aplastic anemia , as indicated by hematologic response and survival . ( Funded by the Intramural Research Program of the National Institutes of Health ; Clinical Trials.gov number , NCT00260689 . ) Aplastic anemia ( AA ) is a rare , life threatening disease . Allogeneic bone marrow transplantation ( BMT ) offers the only possibility of cure , i. e. life-long remission . The probability of survival after BMT from an HLA-identical sibling has clearly improved over the last years and at present is about 80 % in patients < 16 years . Transplantation from alternative donors , however , faces unsolved immunological problems . For demographic reasons most patients lack a matched sibling donor . For these patients immunosuppressive therapy ( IST ) is the only alternative therapeutic approach . However this treatment has frequently result ed in clonal , i. e. potentially malignant disease . Overall probability of survival here is only 50 % , in severely granulocytopenic patients ( < 0.2 G/l ) even lower . These individuals represent an important subgroup in pediatric AA . Some patients show only partial reconstitution of their hematopoiesis but satisfactory quality of life . Based on the results of prospect i ve studies a protocol for IST in AA using anti-lymphocyte globulin ( ALG ) , cyclosporin A ( CSA ) and G-CSF is presented . For BMT- patients likewise a protocol for conditioning ( ALG , cyclophosphamide ) and GvHD-prophylaxis is suggested . St and ardisation and improvement of supportive therapy is the third important objective of this pilot protocol 58 patients with severe aplastic anemia ( SAA ) were treated and evaluated in a prospect i ve study either by bone marrow transplantation ( BMT ) or by antilymphocyte globulin ( ALG ) . 19 patients were treated with BMT ; 9 are still alive 6 months to 5 years after BMT ( 47 % ) . 39 patients were treated with ALG ; 28 are alive 5 months to 5 years after ALG ( 72 % ) . 24 of these 28 are self-sustaining and in remission . The results show that treatment with ALG is probably superior to treatment with BMT , and also demonstrate that most patients with SAA have a pool of hematopoietic stem cells able to repopulate the marrow after this type of treatment |
1,783 | 16,437,495 | There is insufficient evidence to evaluate the effects of cold for low-back pain , and conflicting evidence for any differences between heat and cold for low-back pain .
There is moderate evidence in a small number of trials that heat wrap therapy provides a small short-term reduction in pain and disability in a population with a mix of acute and sub-acute low-back pain , and that the addition of exercise further reduces pain and improves function .
No conclusions can be drawn about the use of cold for low-back pain .
There is conflicting evidence to determine the differences between heat and cold for low-back pain | BACKGROUND Heat and cold are commonly utilised in the treatment of low-back pain by both health care professionals and people with low-back pain .
OBJECTIVES To assess the effects of superficial heat and cold therapy for low-back pain in adults . | Study Design . A prospect i ve , r and omized , single ( investigator ) blind , comparative efficacy trial was conducted . Objective . To compare the efficacy of continuous low-level heat wrap therapy ( 40 C , 8 hours/day ) with that of ibuprofen ( 1200 mg/day ) and acetaminophen ( 4000 mg/day ) in subjects with acute nonspecific low back pain . Summary of Background Data . The efficacy of topical heat methods , as compared with oral analgesic treatment of low back pain , has not been established . Methods . Subjects ( n = 371 ) were r and omly assigned to heat wrap ( n = 113 ) , acetaminophen ( n = 113 ) , or ibuprofen ( n = 106 ) for efficacy evaluation , or to oral placebo ( n = 20 ) or unheated back wrap ( n = 19 ) for blinding . Outcome measures included pain relief , muscle stiffness , lateral trunk flexibility , and disability . Efficacy was measured over two treatment days and two follow-up days . Results . Day 1 pain relief for the heat wrap ( mean , 2 ) was higher than for ibuprofen ( mean , 1.51;P = 0.0007 ) or acetaminophen ( mean , 1.32;P = 0.0001 ) . Extended mean pain relief ( Days 3 to 4 ) for the heat wrap ( mean , 2.61 ) also was higher than for ibuprofen ( mean , 1.68;P = 0.0001 ) or acetaminophen ( mean , 1.95;P = 0.0009 ) . Lateral trunk flexibility was improved with the heat wrap ( mean change , 4.28 cm ) during treatment ( P ≤ 0.009 vs acetaminophen [ mean change , 2.93 cm ] , P ≤ 0.001 vs ibuprofen [ mean change , 2.51 cm ] ) . The results were similar on Day 4 . Day 1 reduction in muscle stiffness with the heat wrap ( mean , 16.3 ) was greater than with acetaminophen ( mean , 10.5;P = 0.001 ) . Disability was reduced with the heat wrap ( mean , 4.9 ) , as compared with ibuprofen ( mean , 2.7;P = 0.01 ) and acetaminophen ( mean , 2.9;P = 0.0007 ) , on Day 4 . None of the adverse events were serious . The highest rate ( 10.4 % ) was reported in the ibuprofen group . Conclusion . Continuous low-level heat wrap therapy was superior to both acetaminophen and ibuprofen for treating low back pain Abstract Objective : To assess the association between competing interests and authors ' conclusions in r and omised clinical trials . Design : Epidemiological study of r and omised clinical trials published in the BMJ from January 1997 to June 2001 . Financial competing interests were defined as funding by for profit organisations and other competing interests as personal , academic , or political . Studies : 159 trials from 12 medical specialties . Main outcome measures : Authors ' conclusions defined as interpretation of extent to which overall results favoured experimental intervention . Conclusions appraised on 6 point scale ; higher scores favour experimental intervention . Results : Authors ' conclusions were significantly more positive towards the experimental intervention in trials funded by for profit organisations alone compared with trials without competing interests ( mean difference 0.48 ( SE 0.13 ) , P=0.014 ) , trials funded by both for profit and non-profit organisations ( 0.30 ( SE 0.10 ) , P=0.003 ) , and trials with other competing interests ( 0.45 ( SE 0.13 ) , P=0.006 ) . Other competing interests and funding from both for profit and non-profit organisations were not significantly associated with authors ' conclusions . The association between financial competing interests and authors ' conclusions was not explained by method ological quality , statistical power , type of experimental intervention ( pharmacological or non-pharmacological ) , type of control intervention ( for example , placebo or active drug ) , or medical specialty . Conclusions : Authors ' conclusions in r and omised clinical trials significantly favoured experimental interventions if financial competing interests were declared . Other competing interests were not significantly associated with authors ' conclusions OBJECTIVE To assess the overall effectiveness of spa therapy compared with usual routine drug therapy in chronic low back pain ( LBP ) . METHODS One hundred and twenty-one patients were r and omly allocated to treatment ( n = 59 ) and control ( n = 62 ) groups . In the treatment group , patients underwent routine drug therapy and spa therapy 6 days/week for 3 consecutive weeks in Saint-Nectaire , France . In the control group , patients received routine drug therapy . Effectiveness was assessed based on clinical measures , duration and intensity of pain , Rol and and Morris ' disability question naire , the patient 's overall evaluation of back health , and drug consumption ( analgesic and antiinflammatory ) . Groups were compared using analysis of covariance with repeated measures . RESULTS At 3 weeks , patients in the treatment group had significant improvement in all outcome variables ( p < 0.0001 ) except for the Schober index and analgesic and antiinflammatory drug consumption . At 6 months , improvement was still significant for the same outcome variables ( p < 0.0001 ) , plus a significant reduction in analgesic consumption . CONCLUSION This study suggests both immediate and 6 month effectiveness of spa therapy in chronic LBP . Spa therapy may be beneficial in the management of chronic LBP Three treatments for non-specific lumbar pain -- balneotherapy , underwater traction bath , and underwater massage -- were assessed in a r and omised prospect i ve controlled trial in 158 out patients . Each group was treated for four weeks and patients were review ed at the end of this period and at 12 months after entry to the trial . The prescription of analgesics and the pain score were significantly reduced in all three treated groups , but there was no difference between the three groups . No significant change occurred in spinal motion and the straight leg raising test . After one year only the analgesic consumption was significantly lower than in the control group OBJECTIVE --To compare the effectiveness of manipulative therapy , physiotherapy , treatment by the general practitioner , and placebo therapy in patients with persistent non-specific back and neck complaints . DESIGN --R and omised clinical trial . SETTING -- Primary health care in the Netherl and s. PATIENTS --256 patients with non-specific back and neck complaints of at least six weeks ' duration who had not received physiotherapy or manipulative therapy in the past two years . INTERVENTIONS --At the discretion of the manipulative therapists , physiotherapists , and general practitioners . Physiotherapy consisted of exercises , massage , and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manipulative therapy consisted of manipulation and mobilisation of the spine . Treatment by general practitioners consisted of drugs ( for example , analgesics ) , advice about posture , home exercises , and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 minutes ) and detuned ultrasound ( 10 minutes ) . MAIN OUTCOME MEASURES --Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients . RESULTS --Many patients in the general practitioner and placebo groups received other treatment during follow up . Improvement in the main complaint was larger with manipulative therapy ( 4.5 ) than with physiotherapy ( 3.8 ) after 12 months ' follow up ( difference 0.9 ; 95 % confidence interval 0.1 to 1.7 ) . Manipulative therapy also gave larger improvements in physical functioning ( difference 0.6 ; -0.1 to 1.3 ) . The global perceived effect after six and 12 months ' follow up was similar for both treatments . CONCLUSIONS --Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment . Furthermore , manipulative therapy is slightly better than physiotherapy after 12 months BACKGROUND AND PURPOSE Since the release of acute low back pain management guidelines in 1994 , little was known about the effect of these guidelines on clinical practice . The purpose of this study was to examine physical therapists ' reported management of acute and subacute lumbar impairment . SUBJECTS One in 10 registered physical therapists who were r and omly selected from southern Ontario , Canada , ( n=454 ) and all registered physical therapists from northern Ontario ( n=331 ) were surveyed . METHODS In the question naire , case scenarios covered 3 areas related to the management of lumbar impairment : ( 1 ) physical examination , ( 2 ) treatment and recommendations , and ( 3 ) therapists ' beliefs regarding its management . RESULTS Five hundred sixty-nine question naires were returned ( response rate=72.5 % ) . Only data obtained for therapists ( n=274 ) whose weekly workload included more than 10 % of people with lumbar impairment were used in the analysis . Overall , patient education , exercise , and electrotherapeutic and thermal modalities were the preferred interventions for acute lumbar impairment ( symptom onset of less than 5 weeks ) with or without sciatica , whereas exercise and work modification were preferred for subacute lumbar impairment ( symptom onset of 5 weeks or longer ) . There was a trend of using electrotherapeutic and thermal modalities with uncertain effectiveness . Only 46.3 % of the therapists agreed or strongly agreed that practice guidelines were useful for managing lumbar impairment . DISCUSSION AND CONCLUSION Although the physical therapists surveyed , in general , followed the guidelines in managing acute lumbar impairment , they felt uncertain regarding the value of practice guidelines . Future research should focus on identifying effective treatment approaches and exploring the effectiveness of practice guidelines BACKGROUND CONTEXT Restorative exercise and palliative modalities are frequently used together for the treatment of acute low back pain . However , little is known about the effects of combining these treatments . PURPOSE To evaluate the efficacy of combining continuous low-level heat wrap therapy with directional preference-based exercise on the functional ability of patients with acute low back pain . STUDY DESIGN / SETTING A r and omized controlled trial was conducted at three outpatient medical facilities . PATIENT SAMPLE One hundred individuals ( age 31.2+/-10.6 years ) with low back pain of less than 3 months duration . OUTCOME MEASURES The primary outcome measure was functional ability assessed by the Multidimensional Task Ability Profile question naire . Secondary outcomes were disability assessed by the Rol and -Morris Disability Question naire and pain relief assessed by a 6-point verbal rating scale . METHODS Participants were r and omized to one of four groups : Heat wrap therapy alone ( heat wrap , n=25 ) ; directional preference-based exercise alone ( exercise , n=25 ) ; combination of heat wrap therapy and exercise ( heat+exercise , n=24 ) ; or control ( booklet , n=26 ) . Treatment was administered for five consecutive days and included four visits to the study center over 1 week . RESULTS At 2 days after the conclusion of treatment ( Day 7 ) , functional improvement for heat+exercise was 84 % , 95 % , and 175 % greater than heat wrap , exercise , and booklet , respectively ( p<.05 ) . Seventy-two percent of the subjects in the heat+exercise group demonstrated a return to pre-injury function compared with 20 % , 20 % , and 19 % for heat wrap , exercise , and booklet , respectively ( p<.05 ) . Disability reduction for heat+exercise was 93 % , 139 % , and 400 % greater than heat wrap , exercise , and booklet , respectively ( p<.05 ) . Pain relief for heat+exercise was 70 % and 143 % greater than exercise and booklet , respectively ( p<.05 ) . CONCLUSIONS Combining continuous low-level heat wrap therapy with directional preference-based exercise during the treatment of acute low back pain significantly improves functional outcomes compared with either intervention alone or control . Either intervention alone tends to be more effective than control Ninety-four patients with non-specific lumbar pain referred to hospital rheumatology and orthopaedic clinics participated in a double-blind controlled trial comparing mobilisation and manipulation with placebo physiotherapy . Results were assessed immediately after the tratment course , two months later , and at one year . Many patients showed improvement , but in contrast to a study on general-practitioner patients with nonspecific back pain no definite advantage could be associated with mobilisation and manipulation . The benefits of mobilisation and manipulation for low back pain are probably restricted to hastening recovery in patients likely rapidly to improve spontaneously . Hence patients whose severity and duration of symptoms warrant specialist referral are less likely to benefit from the technique OBJECTIVE To determine whether traditional bone- setting or continuous light exercise therapy could case back pain and improve function better than ordinary physiotherapy . DESIGN Observer-blinded , r and omized clinical trial with a 6-month follow-up . SETTING An outpatient institution for folk medicine research . PATIENTS Of 147 back pain patients recruited from local health centers and by newspaper announcements , 132 were found eligible ( non-retired-no contraindications to manipulation ) and entered . A final 114 ( one dropout ) with back pain for longer than 7 weeks were included in this intent to treat analysis . INTERVENTIONS Bone- setting , guidance for continuous light back movements or physiotherapy for up to ten 1-hour sessions during 6 weeks . MAIN OUTCOME MEASURES Spinal mobility and muscular performance . Back pain assessed by visual analog scales ( VAS ) . RESULTS The physical measures changed only modestly , from one tenth to half of st and ard deviation , while the VAS was halved . The thoracolumbar side-bending , the modified Schober , and the VAS were significantly better improved by bone- setting than by exercise but not better than by physiotherapy . CONCLUSION Neither bone- setting nor exercise differed significantly from physiotherapy , but bone- setting improved lateral and forward bending of the spine and back pain more than did exercise We conducted a pilot study to evaluate a practical exercise program for elderly people with chronic musculo-skeletal pain . Thirty-three subjects ( mean age , 73 years ; 69 % back pain ; 24 % knee pain ; 9 % hip pain ) were r and omly assigned to one of three groups . Group 1 received a 6-week supervised program of walking . Group 2 received a pain education program that included instruction and demonstration of use of heat , cold , massage , relaxation and distraction . Group 3 received usual care . Outcomes including pain , self-reported health and functional status , and performance-based measures of functional status were evaluated at baseline , at two weeks and at eight weeks ( end of study ) . Attendance was 100 % for the education sessions and 93 % for walking sessions . No injuries were sustained . Both intervention groups demonstrated significant improvements in pain ( p<0.05 ) and performance-based measures of functional status ( p<0.05 ) , while the control group had no changes . These data suggest that patient education and fitness walking can improve overall pain management and related functional limitations among elderly people with chronic musculo-skeletal pain BACKGROUND Reporting of pharmaceutical-industry-sponsored r and omised clinical trials often result in biased findings , either due to selective reporting of studies with non-equivalent arms or publication of low- quality papers , wherein unfavourable results are incompletely described . A r and omised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another . Studies in which intervention and control are thought to be non-equivalent violates the uncertainty principle . METHODS We examined the quality of 136 published r and omised trials that focused on one disease category ( multiple myeloma ) and adherence to the uncertainty principle . To evaluate whether the uncertainty principle was upheld , we compared the number of studies favouring experimental treatments over st and ard ones . We analysed data according to the source of funding . FINDINGS Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores ( mean 2.94 [ SD 1.3 ] ; median 3 ) than r and omised trials supported by 95 governmental or other non-profit organisations ( 2.4 [ 0.8 ] ; 2 ; p=0.06 ) . Overall , the uncertainty principle was upheld , with 44 % of r and omised trials favouring st and ard treatments and 56 % innovative treatments ( p=0.17 ) ; mean and median preference evaluation scores were 3.7 ( 1.0 ) and 4 . However , when the analysis was done according to the source of funding , studies funded by non-profit organisations maintained equipoise favouring new therapies over st and ard ones ( 47 % vs 53 % ; p=0.608 ) to a greater extent than r and omised trials supported solely or in part by profit-making organisations ( 74 % vs 26 % ; p=0.004 ) . INTERPRETATION The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle . Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls STUDY DESIGN Prospect i ve , r and omized , crossover design . OBJECTIVES To compare the effectiveness of the Johnson & Johnson Back Plaster , the ABC Warme-Pflaster , and the ThermaCare HeatWrap on skin and paraspinal muscle temperature . Also , to compare the subjects ' heat perception for the 3 products . BACKGROUND Heat therapy is a common treatment for low back pain and disability . There are a number of products on the market that are suggested to relieve low back pain by providing warmth to the back ; however , their effectiveness for increasing tissue temperature compared with heat sensation has not been tested . METHODS AND MEASURES To measure paraspinal muscle temperature , 1 thermocouple monofilament was inserted into the paraspinal muscle 2 cm from the skin surface at the L3 level using a 20-gauge 1.25-in ( 3.15-cm ) sterile catheter . To measure skin interface temperature , 2 thermocouples were placed on the skin at distances of 5 cm and 7 cm from the insertion site . The Isothermex was used to record temperatures to the nearest 0.1 degrees C for 120 minutes . The subjects also rated heat perception using a 10-cm visual analog scale at 0 , 30 , 60 , 90 , and 120 minutes . Analysis of covariance models were used for statistical analysis . RESULTS There was a significant product x time interaction ( F14,231 = 3.77 , P<.0001 ) at the intramuscular site , but there was not a significant product x time interaction ( F14,231 = 1.03 , P = .4228 ) at the skin site . Both the main effects for product ( F2,33 = 41.59 , P<.0001 ) and time ( F3,51 = 19.02 , P<.0001 ) were significant for the visual analog scale data . The ThermaCare HeatWrap produced significant increases in both skin and intramuscular temperatures with less heat sensation . The Johnson & Johnson Back Plaster and the ABC Warme-Pflaster increased temperature at the skin surface and provided the greatest heat sensations , but they did not provide intramuscular heat . CONCLUSIONS The ThermaCare HeatWrap is more effective at increasing temperature at a 2-cm depth with less perceived heat compared to the Johnson & Johnson Back Plaster and the ABC Warme-Pflaster . The latter 2 products provide a sensation of heat but do not actually provide a muscle temperature change at a depth of 2 cm & NA ; It has recently been shown that ice massage of the web between the thumb and index finger produces significantly greater relief of dental pain than a placebo control procedure . These results indicate that ice massage may be comparable to transcutaneous electrical stimulation ( TES ) and acupuncture , and may be mediated by similar neural mechanisms . The purpose of this study was to examine the relative effectiveness of ice massage and TES for the relief of low‐back pain . Patients suffering chronic low‐back pain were treated with both ice massage and TES . The order of treatments was balanced , and changes in the intensity of pain were measured with the McGill Pain Question naire ( MPQ ) . The results show that both methods are equally effective : based on the Pain Rating Index of the MPQ , 67–69 % of patients obtained pain relief greater than 33 % with each method . The results indicate that ice massage is an effective therapeutic tool , and appears to be more effective than TES for some patients . It may also serve as an additional sensory‐modulation method to alternate with TES to overcome adaptation effects . Evidence that cold signals are transmitted to the spinal cord exclusively by A‐delta fibers and not by C fibers suggests that ice massage provides a potential method for differentiating among the multiple feedback systems that mediate analgesia produced by different forms of intense sensory input The efficacy of trigger-point injection therapy In treatment of low-back strain was evaluated in a prospect i ve , r and omized , double-blind study . The patient population consisted of 63 individuals with low-back strain . Patients with this diagnosis had nonradiating low-back pain , normal neurologic examination , absence of tension signs , and lumbosacral roentgenograms interpreted as being within normal limits . They were treated conservatively for 4 weeks before entering the study . Injection therapy was of four different types : lldocaine , lldocaine combined with a steroid , acupuncture , and vapocoolant spray with acupressure . Results indicated that therapy without injected medication ( 63 % improvement rate ) was at least as effective as therapy with drug injection ( 42 % improvement rate ) , at a P value of 0.09 . Trigger-point therapy seems to be a useful adjunct In treatment of low-back strain . The injected substance apparently is not the critical factor , since direct mechanical stimulus to the trigger-point seems to give symptomatic relief equal to that of treatment with various types of injected A study was conducted to compare the relative efficacy of conventional ( heat , pelvic tilt exercises , postural education and lifting instructions ) and manipulation therapy in back pain management . Twenty-five females were in the conventional therapy group ( CTG ) and 26 females in the manipulation therapy group ( MTG ) . Range of motion of total flexion and extension , total side-flexion and total rotation of the lumbar spine and the straight-leg-raising test were used as criteria to determine efficacy of treatment . The results showed that while the mean treatment time for CTG subjects was 160 minutes ( SD = 7.9 ) that for MTG patients was 121.2 ( SD = 10.2 ) with a significant difference p less than 0.001 . There were significant differences between the two groups with regards to post-treatment differences in total flexion and extension p less than 0.01 ; total side flexion p less than 0.05 ; and total rotation p less than 0.05 in favour of the MTG subjects . There was also significant difference in post-treatment straight-leg-raising values between the two groups p less than 0.05 in favour of the MTG group . It was concluded that manipulation therapy as shown by this study was superior to the conventional method in the treatment of the type of patient described We r and omly surveyed 100 specialists in rehabilitation medicine and 100 rheumatologists concerning their perceptions of the value of 11 different physical modalities -- cold , active and passive exercise , interferential current , laser , magnetotherapy , microwave , shortwave diathermy , traction , ultrasound and transcutaneous nerve stimulation in the treatment of seven different musculoskeletal conditions -- acute arthritis , joint contracture , neck pain , back pain , tendinitis , reflex sympathetic dystrophy and frozen shoulder . There were significant differences in the perceived benefits of modalities which varied by modality and condition . Overall , rehabilitation medicine specialists regarded modalities to be helpful more often than rheumatologists ( P < 0.001 ) BACKGROUND AND PURPOSE Clinicians treating patients with low back pain often use exercise to reduce pain and improve function . The aim of this study was to evaluate the effectiveness of trunk extensor endurance training in reducing pain and decreasing disability in subjects with subacute low back pain ( ie , onset of back pain within 7 days to 7 weeks ) . SUBJECTS AND METHODS Patients were r and omly assigned to either an experimental group or a control group . A visual analog scale and the pain rating index ( PRI ) of the McGill Pain Question naire ( MPQ ) were used to obtain baseline measurements of pain . The Rol and Morris Disability Question naire ( RMDQ ) was used to measure disability , and the Sorensen Test was used to measure trunk extensor endurance . Subjects in the experimental group attended exercise sessions 3 times a week for 6 weeks . Subjects in the control group did not do exercises . Both groups were given back care advice and hot packs for 15 minutes , 3 to 5 times per week . Re assessment s were carried out at 3 and 6 weeks . RESULTS There were differences between the 2 groups at 3 weeks in regard to pain intensity during the evaluation session and pain experienced over the preceding 24 hours , the total MPQ PRI , the sensory component of the MPQ PRI , and the RMDQ . At 6 weeks , no differences were found for pain measurements , disability scores , and holding time on the Sorensen Test . CONCLUSION AND DISCUSSION Trunk extensor endurance training reduced pain and improved function at 3 weeks but result ed in no improvement at 6 weeks when compared with the control group . Endurance exercise is considered to expedite the recovery process for patients with an acute episode of low back pain Study Design . A r and omized , controlled trial , test‐retest design , with a 3‐ , 6‐ , and 30‐month postal question naire follow‐up . Objective . To determine the efficacy of a specific exercise intervention in the treatment of patients with chronic low back pain and a radiologic diagnosis of spondylolysis or spondylolisthesis . Summary of Background Data . A recent focus in the physiotherapy management of patients with back pain has been the specific training of muscles surrounding the spine ( deep abdominal muscles and lumbar multifidus ) , considered to provide dynamic stability and fine control to the lumbar spine . In no study have research ers evaluated the efficacy of this intervention in a population with chronic low back pain where the anatomic stability of the spine was compromised . Methods . Forty‐four patients with this condition were assigned r and omly to two treatment groups . The first group underwent a 10‐week specific exercise treatment program involving the specific training of the deep abdominal muscles , with co‐activation of the lumbar multifidus proximal to the pars defects . The activation of these muscles was incorporated into previously aggravating static postures and functional tasks . The control group underwent treatment as directed by their treating practitioner . Results . After intervention , the specific exercise group showed a statistically significant reduction in pain intensity and functional disability levels , which was maintained at a 30‐month follow‐up . The control group showed no significant change in these parameters after intervention or at follow‐up . Summary . A " specific exercise " treatment approach appears more effective than other commonly prescribed conservative treatment programs in patients with chronically symptomatic spondylolysis or spondylolisthesis OBJECTIVE To assess the efficacy of a back school program for patients with a first episode of acute work-related low back pain requiring compensation . DESIGN A r and omized single-blind controlled trial . SETTING A private physiatrics outpatient clinic . PATIENTS The mean duration of low back pain was 15 days . INTERVENTION Eligible patients were r and omized to a st and ard treatment program that included daily physiotherapy ( n = 86 ) or the same program with the addition of back school ( n = 82 ) . The back school program consisted of three 90-minute sessions given by a single trained instructor at 0 , 1 , and 8 weeks . MAIN OUTCOME MEASURES The primary outcomes were the time off work for the presenting episode of back pain and the number and duration of recurrences in the year following the study onset . Secondary outcomes included the level of pain , spinal mobility , active straight-leg raising , and functional disability assessed by the Oswestry and Rol and -Morris scales . RESULTS Those r and omized to the back school group gained significantly more knowledge , based on the multiple choice examination ( p = .0001 ) and performed the exercise program significantly better ( p = .0001 ) than the st and ard care group . There were no differences between the two treatment groups for either of the primary outcomes . The median time to return to work from r and omization was 33 days for both the back school and the st and ard care groups ( p = .48 ) . The number of compensated recurrences of low back pain over 1 year was similar ( back school = 14 , st and ard care = 10 , p = .16 ) , as was the median duration of these episodes ( back school = 25 days , st and ard care = 70 days , p = .21 ) . There were no significant differences favoring the back school group for any of the secondary outcomes at the posttreatment , 6-month , or 12-month assessment s. CONCLUSION A back school intervention in addition to st and ard care result ed in no reduction in the time to return to work or the number or duration of recurrences of low back pain requiring compensation over a period of one year In a r and omized , observer-blind trial , 150 men and women , aged 21 - 64 years , with chronic/subchronic low-back pain , followed one of these three treatment regimens : 1 ) intensive , dynamic back-muscle exercises ; 2 ) conventional physiotherapy , including isometric exercises for the trunk and leg muscles ; and 3 ) placebo-control treatment involving semihot packs and light traction . Eight treatment sessions were given during the course of 4 weeks , each session lasting 1 hour . The short-term effect was evaluated at the end of the treatment period and 1 month later , and the long-term effect at 6 and 12 months . The evaluations included recording of changes in pain level and assessment of overall treatment effect , which were indicated on visual interval scales . Subgroups of patients could be identified according to their treatment responses : physiotherapy was the superior treatment for the male participants , whereas the intensive back exercises appeared to be most efficient for the female participants . Patients with moderate or hard physical occupations tended toward a better response with physiotherapy , whereas intensive back exercises seemed most effective for those with sedentary/light job functions BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions Mobilization and manipulation have been compared with placebo physiotherapy in patients with nonspecific back pain . Studies were conducted on 94 patients seen in general practice and 94 referred to hospital rheumatology and orthopaedic clinics for a specialist opinion . Assessment s were performed immediately after the treatment course , two months later , and at one year . Most patients in both series showed improvements . In the general practitioner series , there was a slight but definite advantage in favor of those receiving mobilization and manipulation immediately after the course of treatment . However , these differences had largely disappeared at three months , and at one year the two groups were identifical . Analysis of the data indicated that clinical improvement correlated with the shorter length of history . No such advantage in favor of mobilization and manipulation was found in the hospital series . It is believed that this is because the hospital patients all had a longer duration of symptoms and a number of other features that were identified as being significantly worse . This study indicates the high rate of spontaneous resolution of low-back pain . In patients likely to improve anyway , mobilization and manipulation may hasten improvements but do not affect the long-term prognosis This study compared the pain-relieving effects of shortwave diathermy and moist heat on trigger points . Patients with trigger points on the neck or back were r and omly assigned one of these treatments . The sensitivity of each trigger point was measured with a pressure algometer before treatment , 5 minutes after treatment , and 30 minutes after treatment . Sensitive trigger points , at which 2000 grams of force or less caused pain , were more responsive to treatment than moderate trigger points ( painful only at 2000 grams or greater force ) . Both treatments were effective in relieving the pain of sensitive trigger points but shortwave diathermy was more effective at decreasing the sensitivity of both sensitive and moderate trigger points ( P > 0.0581 ) . The pressure algometer was shown to be a useful device for objective ly measuring pain and may be useful in selecting the most effective type of treatment for trigger points . J Orthop Sports Phys Ther 1984;5(4):175 - 178 OBJECTIVE To evaluate of the efficacy and safety of 8 hours of continuous , low-level heatwrap therapy administered during sleep . DESIGN Prospect i ve , r and omized , parallel , single-blind ( investigator ) , placebo-controlled , multicenter clinical trial . SETTING Two community-based research facilities . PARTICIPANTS Seventy-six patients , aged 18 to 55 years , with acute , nonspecific low back pain . INTERVENTIONS Subjects were stratified by baseline pain intensity and gender and r and omized to one of the following treatments : evaluation of efficacy ( heatwrap , n=33 ; oral placebo , n=34 ) or blinding ( unheated wrap , n=5 ; oral ibuprofen , n=4 ) . All treatments were administered for 3 consecutive nights with 2 days of follow-up . MAIN OUTCOME MEASURES Primary : morning pain relief ( hour 0 ) on days 2 through 4 ( 0 - 5-point verbal response scale ) . Secondary : mean daytime pain relief score ( days 2 - 4 , hours 0 - 8 ) , mean extended pain relief score ( day 4 , hour 0 ; day 5 , hour 0 ) , muscle stiffness , lateral trunk flexibility , and disability ( Rol and -Morris Disability Question naire ) . RESULTS Heatwrap therapy was significantly better than placebo at hour 0 on days 2 through 4 for mean pain relief ( P=.00005 ) ; at hours 0 through 8 on days 2 through 4 for pain relief ( P<.001 ) ; at hour 0 on day 4 and at hour 0 on day 5 for mean pain relief ( P<.001 ) ; on day 4 in reduction of morning muscle stiffness ( P<.001 ) ; for increased lateral trunk flexibility on day 4 ( P<.002 ) ; and for decreased low back disability on day 4 ( P=.005 ) . Adverse events were mild and infrequent . CONCLUSIONS Overnight use of heatwrap therapy provided effective pain relief throughout the next day , reduced muscle stiffness and disability , and improved trunk flexibility . Positive effects were sustained more than 48 hours after treatments were completed BACKGROUND AND PURPOSE We surveyed physical therapists about their attitudes , beliefs , and treatment preferences in caring for patients with different types of low back pain problems . SUBJECTS AND METHODS Question naires were mailed to all 71 therapists employed by a large health maintenance organization in western Washington and to a r and om sample of 331 other therapists licensed in the state of Washington . RESULTS Responses were received from 293 ( 74 % ) of the therapists surveyed , and 186 of these cl aim ed to be practicing in setting s in which they treat patients who have back pain . Back pain was estimated to account for 45 % of patient visits . The McKenzie method was deemed the most useful approach for managing patients with back pain , and education in body mechanics , stretching , strengthening exercises , and aerobic exercises were among the most common treatment preferences . There were significant variations among therapists in private practice , hospital-operated , and health maintenance organization setting s with respect to treatment preferences , willingness to take advantage of the placebo effect , and mean number of visits for patients with back pain . CONCLUSIONS AND DISCUSSION These variations emphasize the need for more outcomes research to identify the most effective treatment approaches and to guide clinical practice OBJECTIVE To evaluate the efficacy of 8 hours of continuous low-level heatwrap therapy for the treatment of acute nonspecific low back pain ( LBP ) . DESIGN Prospect i ve , r and omized , parallel , single-blind ( investigator ) , placebo-controlled , multicenter clinical trial . SETTING Five community-based research facilities . PARTICIPANTS Two-hundred nineteen subjects , aged 18 to 55 years , with acute nonspecific LBP . INTERVENTION Subjects were stratified by baseline pain intensity and gender and r and omized to one of the following groups : evaluation of efficacy ( heatwrap , n=95 ; oral placebo , n=96 ) and blinding ( oral ibuprofen , n=12 ; unheated back , wrap n=16 ) . All treatments were administered for 3 consecutive days with 2 days of follow-up . MAIN OUTCOME MEASURES Primary : day 1 mean pain relief ( 0- to 5-point verbal response scale ) . Secondary : muscle stiffness ( 101-point numeric rating scale ) , lateral trunk flexibility ( fingertip-floor distance ) , and Rol and -Morris Disability Question naire over 3 days of treatment and 2 days of follow-up . RESULTS Heatwrap therapy was shown to provide significant therapeutic benefits when compared with placebo during both the treatment and follow-up period . On day 1 , the heatwrap group had greater pain relief ( 1.76+/-.10 vs 1.05+/-.11 , P < .001 ) , less muscle stiffness ( 43.1+/-1.21 vs 47.6+/-1.21 , P=.008 ) , and increased flexibility ( 18.6+/-.44 cm vs 16.5+/-.45 cm , P=.001 ) compared with placebo . Disability was also reduced in the heatwrap group ( 5.3 vs 7.4 , P=.0002 ) . Adverse events were mild and infrequent . CONCLUSION Continuous low-level heatwrap therapy was shown to be effective for the treatment of acute , nonspecific LBP OBJECTIVES This study assessed the effectiveness of adding spa therapy to usual drug treatment in chronic low back pain patients . METHODS A total of 224 patients were assigned r and omly to either a treatment ( n=128 ) or a control ( n=96 ) group . Subjects in both groups received usual drug therapy . Those in the treatment group also underwent spa therapy in Vittel , France , for 6 days a week for 3 consecutive weeks . Effectiveness was assessed using a quality -of-life scale ( the Duke Health Profile ) , clinical measures , and the Rol and and Morris disability question naire . Groups were compared using an analysis of variance with repeated measures . RESULTS At both 3 weeks and 3 months , patients in the treatment group exhibited significant improvement in measures of : physical and mental dimensions of quality of life , anxiety , depression , pain duration , pain intensity , and functional disability . CONCLUSION This study suggests that spa therapy is an effective treatment for chronic low back pain patients Study Design . This was a stratified , r and om telephone survey of adults in North Carolina . Objective To determine the prevalance of chronic low back pain and the extent to which treatment is sought for this condition . Summary of Background Data Chronic low back pain is a major problem . Previous studies often have comb ined acute and chronic back pain . Methods Telephone interviews regarding back pain were conducted with 4437 North Caroliona adults during 1992 . Results Chronic back pain affects 3.9 % of the North Carolina population . Thirty-four percent considered themselves permanently disabled and 52 % assessed their overall health as fair or poor . The median number of bed-disability days per year was three . Seventy-three percent saw a health care provider Of those who sought care , 91 % saw a medical doctore , 29 % saw a physical therapist , and 25 % saw a chiropractor , Use of technology was extensive : 37 % received a computed tomography scan , 25 % received a magnetic resonance imaging scan , and 10.4 % underwent surgery . Conclusions Chronic back pain is common , and the level of care-seeking and costs of care among those afflicted are extremely high Study Design . Prospect i ve r and omized blinded trial in a prehospital emergency system . Objectives . To evaluate the effects of external active warming on acute back pain during rescue transport to hospital . Background Data . Acute low back pain is one of the complaints that most often entails a visit to the physician or use of the emergency system . Superficial ( e.g. , hydrocolloid packs ) and deep heating ( e.g. , ultrasound ) can relieve acute low back pain in a clinical setting . Recent data showed significant benefit for patients in pain from minor trauma treated by active warming during emergency transport . Accordingly , we tested the hypothesis that active warming would reduce pain and anxiety in patients with acute low back pain being transported to a hospital . Methods . A total of 100 patients were included in our study . We selected only those suffering from acute pain > 60 mm on a visual analog scale in the lower back . Patients were r and omly assigned to two groups : active warming with a carbon-fiber electric heating blanket ( Group 1 ) versus passive warming with a woolen blanket ( Group 2 ) during transfer to hospital . Results . Pain scores on arrival at the hospital differed significantly between Group 1 and Group 2 ( P < 0.01 ) . In Group 1 , pain reduction from 74.2 ± 8.5 mm VAS to 41.9 ± 18.9 mm VAS ( P < 0.01 ) was noted between departure from the emergency site and arrival at the hospital . Pain scores remained practically unchanged in Group 2 ( 73.3 ± 11.9 mm VAS and 74.1 ± 12.0 mm VAS ) . Conclusions . Active warming reduces acute low back pain during rescue transport BACKGROUND Although chiropractors often use physical modalities with spinal manipulation , evidence that modalities yield additional benefits over spinal manipulation alone is lacking . OBJECTIVE The purpose of the study was to estimate the net effect of physical modalities on low back pain ( LBP ) outcomes among chiropractic patients in a managed-care setting . METHODS Fifty percent of the 681 patients participating in a clinical trial of LBP treatment strategies were r and omized to chiropractic care with physical modalities ( n = 172 ) or without physical modalities ( n = 169 ) . Subjects were followed for 6 months with assessment s at 2 , 4 , and 6 weeks and at 6 months . The primary outcome variables were average and most severe LBP intensity in the past week , assessed with numerical rating scales ( 0 - 10 ) , and low back-related disability , assessed with the 24-item Rol and -Morris Disability Question naire . RESULTS Almost 60 % of the subjects had baseline LBP episodes of more than 3 months ' duration . The 6-month follow-up was 96 % . The adjusted mean differences between groups in improvements in average and most severe pain and disability were clinical ly insignificant at all follow-up assessment s. Clinical ly relevant improvements in average pain and disability were more likely in the modalities group at 2 and 6 weeks , but this apparent advantage disappeared at 6 months . Perceived treatment effectiveness was greater in the modalities group . CONCLUSIONS Physical modalities used by chiropractors in this managed-care organization did not appear to be effective in the treatment of patients with LBP , although a small short-term benefit for some patients can not be ruled out STUDY DESIGN A r and omized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year . OBJECTIVES To study the efficacy of active rehabilitation on pain , self-experienced disability , and lumbar fatigability . SUMMARY OF BACKGROUND DATA Exercises in an outpatient setting are widely used for the treatment of chronic low back pain . The efficacy of the active rehabilitation approach has been documented in r and omized control studies , but these studies have seldom been focused on lumbar fatigability , which is now recognized as a frequent problem among patients with chronic low back pain . METHODS Fifty-nine middle-aged patients ( 37 men and 22 women ) with nonspecific chronic low back pain were r and omly assigned to 12 weeks ' active rehabilitation or to a passive control treatment ( massage , thermal therapy ) . Pain and disability index , low back pain intensity ( visual analog scale , 100 mm ) , and the objective ly assessed lumbar muscle fatigability ( spectral electromyogram , mean power frequency slope [ MPFSLOPE ] ) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits . RESULTS Results of repeated measures multivariate analysis of variance indicated that back pain intensity ( visual analog scale ) and functional disability ( pain and disability index score ) decreased , and lumbar endurance ( MPFSLOPE ) improved significantly more ( P < 0.05 ) in the active rehabilitation group than in the passive control treatment group , when measured at a 1-year follow-up examination . The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year . The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up , but not at the 1-year follow-up . CONCLUSIONS The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment . However , the group difference in lumbar endurance tended to diminish at the 1-year follow-up Study Design . A multicenter , r and omized , single‐blinded controlled trial with 1‐year follow‐up . Objectives . To evaluate the efficiency of progressively grade d medical exercise therapy , conventional physiotherapy , and self‐exercise by walking in patients with chronic low back pain . Summary and Background Data . Varieties of medical exercise therapy and conventional physiotherapy are considered to reduce symptoms , improve function , and decrease sickness absence , but this opinion is controversial . Methods . Patients with chronic low back pain or radicular pain sick‐listed for more than 8 weeks and less than 52 weeks ( Sickness Certificate II ) were included . The treatment lasted 3 months ( 36 treatments ) . Pain intensity , functional ability , patient satisfaction , return to work , number of days on sick leave , and costs were recorded . Results . Of the 208 patients included in this study , 71 were r and omly assigned to medical exercise therapy , 67 to conventional physiotherapy , and 70 to self‐exercise . Thirty‐three ( 15.8 % ) patients dropped out during the treatment period . No difference was observed between the medical exercise therapy and conventional physiotherapy groups , but both were significantly better than self‐exercise group . Patient satisfaction was highest for medical exercise therapy . Return to work rates were equal for all 3 intervention groups at assessment 15 months after therapy was started , with 123 patients were back to work . In terms of costs for days on sick leave , the medical exercise therapy group saved 906,732 Norwegian Kroner ( NOK ) ( $ 122,531.00 ) , and the conventional physiotherapy group saved NOK 1,882,560 ( $ 254,200.00 ) , compared with the self‐exercise group . Conclusions . The efficiency of medical exercise therapy and conventional physiotherapy is shown . Leaving patients with chronic low back pain untampered poses a risk of worsening the disability , result ing in longer periods of sick leave The effect of spa therapy on chronic low back pain ( LBP ) was assessed in a r and omized trial comparing patients undergoing a 3-week therapy programme in a spa resort in France ( n = 50 ) with patients receiving ambulatory care ( n = 52 ) . After 3 weeks , patients in the spa group had significant improvement in their spine mobility and functional score ( Waddell index ) and a reduction in their daily duration of pain , pain intensity and drug consumption . The long-term effect was assessed after 9 months and showed continued reduction in pain and drug consumption , and improvement in spine mobility but no longer in functional score which returned to baseline level . It is concluded that spa therapy has a positive short-term and a moderate long-term effectiveness on chronic LBP BACKGROUND Primary care requests for radiographs of the lumbar spine have come under increasing scrutiny . Guidelines aim ing to reduce unnecessary radiographs by limiting referrals to patients at high risk of serious disease have been widely distributed . Trial evidence suggests that guidelines can reduce radiography referrals . It is not clear whether this reduction has been achieved in routine practice . AIM This study , using routine data , was conducted to measure trends in pnmary care referrals for lumbar spine radiography at two hospitals between 1994 and 1999 . DESIGN OF STUDY Analysis of primary care requests for lumbar spine radiography from computerised records . SETTING Addenbrooke 's Hospital , Cambridge ( 1 July 1994 to 30 June 1999 ) , and Ipswich General Hospital ( 1 July 1995 to 30 June 1999 ) , United Kingdom . METHOD All primary care requests for lumbar radiography were identified electronically from computerised information systems . A r and om sample of 2100 radiography reports were classified according to clinical importance . These classifications were used to examine whether the proportion of radiographs demonstrating potentially more serious findings had increased between 1994 and 1999 . RESULTS There was no evidence that primary care referrals for radiography of the lumbar spine had decreased between 1994 and 1999 at either hospital . General practitioners did not progressively refer more high-risk patients for lumbar radiography . Only a small proportion of patients had important radiographic findings that might warrant specialist referral or specific therapy . CONCLUSION The implementation of diagnostic guidelines offers much to the NHS . However in these two hospitals , the reduction in radiograph utilisation evident in trials was not achieved . Guideline development is a re source intensive process ; distribution must be supported by more effective implementation strategies Eight r and om groups , each of 15 patients with tendomyotic cervical and lumbar syndrome , underwent acupuncture , one group receiving needle acupuncture at the " correct " sites according to Chinese medicine and another receiving placebo needles at the same sites . In a third group , acupuncture needles were applied at sites which were wholly inconsistent with Chinese practice . The remaining 5 groups took part in a single blind trial involving various types of radiation at the correct acupuncture sites , using an apparatus emitting either laser rays , red light , mixed light , infrared or no radiation at all , without interference from the therapist . All the groups showed improvement , but an analysis according to Kruskal and Wallis revealed no significant differences between type and site of treatment In this multicentre intervention study , we compared an integrated group treatment program which combines psychological and education methods into a more active training approach , with the traditional individual approach of physiotherapy and physical procedures for sub-chronic and chronic low back pain . Our 411 patients had a 4-week inpatient treatment : 243 patients in an experimental program and 168 in a traditional program . Outcomes of 283 patients were assessed 3 months and 1 year after entry . The dropout rate was 31.1 % . Both conditions demonstrated favourable initial effects on functional and psychological parameters , but the integrated approach showed better long-term results for work rehabilitation than the traditional approach . The most successful patients ( n = 58 ) were younger and had a higher educational level in comparison to the unsuccessful subgroup ( n = 71 ) . The main conclusion is that an integrated approach promoting self control and behaviour change through educational measures achieves better long-term results than the traditional individual physiotherapy approach |
1,784 | 25,470,303 | There is low- quality evidence to suggest that there is no difference in effectiveness between different types of interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users and that brief interventions are not superior to assessment -only or to treatment as usual . | BACKGROUND Problem alcohol use is common among illicit drug users and is associated with adverse health outcomes .
It is also an important factor contributing to a poor prognosis among drug users with hepatitis C virus ( HCV ) as it impacts on progression to hepatic cirrhosis or opiate overdose in opioid users .
OBJECTIVES To assess the effects of psychosocial interventions for problem alcohol use in illicit drug users ( principally problem drug users of opiates and stimulants ) . | Aims To determine whether the additional interventions to st and ard care are cost-effective in addressing cocaine and alcohol abuse at 4 months ( 4 M ) and 12 months ( 12 M ) from baseline . Method We conducted a cost-effectiveness analysis of a r and omized controlled trial with three arms : ( 1 ) NIDA 's St and ard intervention ( SI ) ; ( 2 ) SI plus a Well Woman Exam ( WWE ) ; and , ( 3 ) SI , WWE , plus four Educational Sessions ( 4ES ) . Results To obtain an additional cocaine abstainer , WWE compared to SI cost $ 7,223 at 4 M and $ 3,611 at 12 M. Per additional alcohol abstainer , WWE compared to SI cost $ 3,611 and $ 7,223 at 4 M and 12 M , respectively . At 12 M , 4ES was dominated ( more costly and less effective ) by WWE for abstinence outcomes . Conclusions To our knowledge , this is the first cost-effectiveness analysis simultaneously examining cocaine and alcohol abuse in women . Depending on primary outcomes sought and priorities of policy makers , peer-delivered interventions can be a cost-effective way to address the needs of this growing , underserved population . Trial Registration Clinical Trials.gov 82 Ss were studied in a comparative evaluation of a behavioral vs supportive treatment for illegal drug use . Behavioral treatment included stimulus control , urge , control , contracting/family support and competing response procedures for an average of 19 sessions . 37 % of Ss in the behavioral condition were drug-free at 2 months , 54 % at 6 months , and 65 % at 12 months vs 20 + /- 6 % for the alternative treatment during all 12 months . The behavioral treatment was more effective across sex , age , educational level , marital status and type of drug ( hard-drugs , cocaine , and marijuana ) . Greater improvement for this condition was also noted on measures of employment/school attendance , family relationships , depression , institutionalization and alcohol use AIMS This study aim ed to determine the relative effectiveness of 12 months of interim methadone ( IM ; supervised methadone with emergency counseling only for the first 4 months of treatment ) , st and ard methadone treatment ( SM ; with routine counseling ) and restored methadone treatment ( RM : routine counseling with smaller case-loads ) . DESIGN A r and omized controlled trial was conducted comparing IM , SM and RM treatment . IM lasted for 4 months , after which participants were transferred to SM . SETTING The study was conducted in two methadone treatment programs in Baltimore , MD , USA . PARTICIPANTS The study included 230 adult methadone patients newly admitted through waiting-lists . MEASUREMENTS We administered the Addiction Severity Index and a supplemental question naire at baseline , 4 and 12 months post- baseline . Measurements included retention in treatment , self-reported days of heroin and cocaine use , criminal behavior and arrests and urine tests for heroin and cocaine metabolites . FINDINGS At 12 months , on an intent-to-treat basis , there were no significant differences in retention in treatment among the IM , SM and RM groups ( 60.6 % , 54.8 % and 37.0 % , respectively ) . Positive urine tests for the three groups declined significantly from baseline ( Ps < 0.001 and 0.003 , for heroin and cocaine metabolites , respectively ) but there were no significant group x time interactions for these measures . At least one arrest was reported by 30.6 % of the sample during the year , but there were no significant between-group effects . CONCLUSIONS Limited availability of drug counseling services should not be a barrier to providing supervised methadone to adults dependent on heroin -- at least for the first 4 months of treatment Introduction While the impacts of illicit drug use on mortality have been well described , the impact of poly-substance that includes alcohol has received less attention . We examined the impact of binge alcohol use on mortality among a cohort of people who inject drugs ( PWID ) in a Canadian setting . Methods Using data derived from a prospect i ve cohort study of PWID in Vancouver , Canada recruited between May 1996 and November 2013 . We ascertained date s and causes of death through a confidential linkage with the provincial registry and examined the impact of binge alcohol use . The primary outcome of interest was all-cause mortality . We used Cox proportional hazard regression to determine factors associated with mortality , including socio-demographic characteristics , drug use patterns and other risk behaviours . Results During the study period , 2550 individuals were followed ( 844 of whom were HIV positive at baseline ) for a median of 75.4 months ( interquartile range 37.9–113.2 ) . Of these , 795 ( 31 % ) participants reported binge alcohol use at some time during the study period . In multivariable analyses , binge alcohol use remained independently associated with all-cause-mortality ( adjusted hazard ratio = 1.41 ; 95 % confidence interval : 1.06–1.88 ) after adjustment for other drug use patterns . Conclusions Binge alcohol use was associated with time to all-cause mortality among PWID in this setting . Since alcohol use is often overlooked as a risk factor for mortality among this population , these findings highlight the continued need to incorporate addiction treatment and public health interventions and policies that address binge alcohol use to reduce alcohol related-harms Interventions for alcohol- and substance-dependent adults with comorbid depressive disorders are needed , but few have been empirically tested . In a r and omized clinical trial of two psychotherapy interventions for these disorders , we examined whether initial focus of treatment was related to retention , substance use , and depression outcomes . Both interventions , integrated cognitive-behavioral therapy ( ICBT ; n = 105 ) and twelve-step facilitation ( n = 92 ) , were delivered in group formats with entry points every 4 weeks at the beginning of three content-distinct modules . Entry module ( i.e. , initial treatment focus ) was not related to percentage days abstinent , proportion of the sample abstinent , or depression symptoms for either intervention . This was true at both 12 and 24 weeks postbaseline . Furthermore , attendance was similar for both treatments , regardless of initial treatment focus , with a single exception in the ICBT condition . Our findings support the use of modular formats with multiple or rotating entry points for psychotherapy group interventions Active injection drug users ( IDUs ) who are also hazardous alcohol users are at particularly high risk for HIV transmission due to sharing of injection equipment . We recruited AUDIT-positive injectors from the Providence , RI needle exchange program for a r and omized clinical trial testing the effect of a brief motivational intervention ( MI ) on frequency of injection-related HIV risk behavior ( IRRB ) . HIV drug risk behavior was measured as the number of days on which subjects reported sharing works using the 30-day Timeline Followback Method . Overall , 109 subjects reported a mean reduction of IRRB days of 9.1 days from baseline to 6-month follow-up ( p < .001 ) . When compared to controls , there was a trend in reduction of IRRB days to zero at follow-up for MI subject ( OR = 2.1 ; 95 % CI = 0.9 - 4.5 ) , and strongly significant reductions in IRRB days across a range of alternative improvement thresholds . Results from this study demonstrate that MI reduces drug-related HIV risk behaviors among active IDUs . As a brief intervention , MI may be a useful adjunct to existing services intended to reduce harm BACKGROUND Few r and omised controlled trials have been aim ed specifically at substance use reduction among people with psychotic disorders . AIMS To investigate whether a 10-session intervention consisting of motivational interviewing and cognitive-behavioural therapy ( CBT ) was more efficacious than routine treatment in reducing substance use and improving symptomatology and general functioning . METHOD A community sample of people with a psychotic disorder and who reported hazardous alcohol , cannabis and /or amphetamine use during the preceding month was recruited . Participants were r and omly allocated to motivational interviewing/CBT ( n = 65 ) or treatment as usual ( n = 65 ) , and were assessed on multiple outcomes at baseline , 15 weeks , 6 months and 12 months . RESULTS There was a short-term improvement in depression and a similar trend with regard to cannabis use among participants who received the motivational interviewing/CBT intervention , together with effects on general functioning at 12 months . There was no differential benefit of the intervention on substance use at 12 months , except for a potentially clinical ly important effect on amphetamine use . CONCLUSIONS The motivational interviewing/CBT intervention was associated with modest improvements Smoking treatment for newly recovering drug and alcohol-dependent smokers in a residential rehabilitation program was examined . The r and omly assigned conditions ( n = 50 each ) were multicomponent smoking treatment ( MST ) , MST plus generalization training of smoking cessation to drug and alcohol cessation ( MST+G ) , or usual care ( UC ) . Fifty participants who declined smoking treatment ( treatment refusers ) also were studied . Both treatment conditions achieved continuous smoking abstinence rates ( MST : 12 % , MST+G : 10 % , at 12-month follow-up ) that were significantly higher than in the UC condition ( 0 % ) . The MST condition had a continuous drug and alcohol abstinence rate that was significantly higher than that of the MST+G condition ( 40 % vs. 20 % at 12-month follow-up ) although neither differed significantly from that of the UC condition ( 33 % ) . These results support the feasibility of smoking treatment for this population and provide information regarding appropriate treatment components OBJECTIVES We compared the effects of 2 interventions on alcohol use , use of a new syringe at last injection , and condom use at last sexual encounter in a community sample of injection drug users . METHODS Between 2003 and 2006 , 851 out-of-treatment injection drug users were recruited in Raleigh , NC , and Durham , NC , through street outreach and were r and omly assigned to either a 6-session educational intervention or a 6-session motivational intervention . Intervention effects were examined at 6 and 12 months after enrollment . RESULTS In multiple logistic regression analyses adjusted for baseline alcohol use and HCV status , participants assigned to the motivational intervention were significantly less likely than were participants in the educational intervention to be drinking at the 6-month follow-up ( odds ratio = 0.67 ; 95 % confidence interval = 0.46 , 0.97 ) . There were no significant between-group differences in use of a new syringe at last injection or condom use at last sexual encounter at either follow-up . CONCLUSIONS Reducing alcohol use among persons with HCV may slow disease progression and provide important health benefits . Additional strategies are needed for slowing HCV disease progression until more effective HCV treatments are available Background Alcohol use is an important issue among problem drug users . Although screening and brief intervention ( SBI ) are effective in reducing problem alcohol use in primary care , no research has examined this issue among problem drug users . Objective The objective of this study is to determine if a complex intervention including SBI for problem alcohol use among problem drug users is feasible and acceptable in practice . This study also aims to evaluate the effectiveness of the intervention in reducing the proportion of patients with problem alcohol use . Methods Psychosocial intervention for alcohol use among problem drug users ( PINTA ) is a pilot feasibility study of a complex intervention comprising SBI for problem alcohol use among problem drug users with cluster r and omization at the level of general practice , integrated qualitative process evaluation , and involving general practice s in two socioeconomically deprived regions . Practice s ( N=16 ) will be eligible to participate if they are registered to prescribe methadone and /or at least 10 patients of the practice are currently receiving addiction treatment . Patient must meet the following inclusion criteria to participate in this study : 18 years of age or older , receiving addiction treatment/care ( eg , methadone ) , or known to be a problem drug user . This study is based on a complex intervention supporting SBI for problem alcohol use among problem drug users ( experimental group ) compared to an “ assessment -only ” control group . Control practice s will be provided with a delayed intervention after follow-up . Primary outcomes of the study are feasibility and acceptability of the intervention to patients and practitioners . Secondary outcome includes the effectiveness of the intervention on care process ( documented rates of SBI ) and outcome ( proportion of patients with problem alcohol use at the follow-up ) . A stratified r and om sampling method will be used to select general practice s based on the level of training for providing addiction-related care and geographical area . In this study , general practitioners and practice staff , research ers , and trainers will not be blinded to treatment , but patients and remote r and omizers will be unaware of the treatment . Results This study is ongoing and a protocol system is being developed for the study . This study may inform future research among the high-risk population of problem drug users by providing initial indications as to whether psychosocial interventions for problem alcohol use are feasible , acceptable , and also effective among problem drug users attending primary care . Conclusions This is the first study to examine the feasibility and acceptability of complex intervention in primary care to enhance alcohol SBI among problem drug users . Results of this study will inform future research among this high-risk population and guide policy and service development locally and internationally Aim To develop and evaluate the comparative effectiveness of behavioural interventions of enhanced prevention counselling ( EPC ) and simple educational counselling ( SEC ) in reducing hepatitis C viral ( HCV ) infection in sero-negative injecting drug users ( IDU ) . Design R and omised controlled trial ( RCT ) of EPC intervention in comparison with simple educational counselling ( SEC ) . Setting SpecialisedDrug services in London and Surrey , United Kingdom . Participants and Measurements Ninety five IDUs were recruited and r and omised to receive EPC ( n = 43 ) or SEC ( n = 52 ) . Subjects were assessed at baseline using the Addiction Severity Index ( ASI ) , the Injecting Risk Question naire ( IRQ ) , and Drug Injecting Confidence Question naire ( DICQ ) . The primary outcome was measured by the rate of sero-conversion at 6 months and 12 months from baseline and by the ASI , IRQ and DICQ at 6 months from baseline . Hepatitis C testing was undertaken by the innovative test of the dried blood spot ( DBS ) test which increased the rate of testing by 4 fold compared to routine blood testing . Findings SeventyEighty two subjects ( 82 % ) out of the 95 recruited were followed up at 6 months and 62 ( 65 % ) were followed up at 12 months . On the primary outcome measure of the rate of seroconversion , 8 out of 62 patients followed-up at twelve months seroconverted , three in the EPC group and five in the SEC group , indicating incidence rates of 9.1 per 100 person years for the EPC group , 17.2 per 100 person years for the SEC group , and 12.9 per 100 person years for the cohort as a whole . Analysis of the secondary outcome measures on alcohol use , risk behaviour , psychological measures , quality of life , showed no significant differences between the EPC and the SEC groups . However , there were significant changes on a number of measures from baseline values indicating positive change for both groups . Conclusion We were not able to prove the efficacy of EPC in comparison with SEC in the prevention of hepatitis C in IDUs . This was related to low recruitment and retention rates of the participants . Moreover there was a low adherence rate to EPC . The study provided the benefits of developing and introducing behavioural interventions of the EPC and SEC and the DBS screening for Hepatitis C. Moreover the main lessons learnt were that piloting of a new intervention is a crucial first step before conducting pragmatic RCTs of psychological interventions in the field of addiction ; that an infrastructure and culture for psychosocial interventions is needed to enable applied research in the service environment , and research funding is needed for enabling the recruitment of dedicated trained therapists for the delivery of these interventions This study compared the efficacy of 2 approaches for the treatment of cocaine dependence among methadone-maintained patients with and without antisocial personality disorder ( ASPD ) . Patients were r and omly assigned to 4 study conditions : cognitive-behavioral treatment ( CBT ) , contingency management ( CM ) , CBT with CM , or methadone maintenance . The Structural Clinical Interview for Mental Disorders-IV was administered to 108 patients to assess ASPD . A 2-way analysis of variance showed that patients with ASPD were more likely to abstain from cocaine use during treatment than patients without ASPD . The strong treatment effect for ASPD patients was primarily due to the CM condition . Regression analyses showed that ASPD remained significantly related to CM treatment responsivity while controlling for other factors Abstract Motivational enhancement therapy ( MET ) is a brief therapy shown to be effective for problem drinkers . Because the response to MET for other addictive disorders is mixed , we assessed the utility of increasing the number of sessions in subjects with methamphetamine ( MA ) dependence . One therapist was trained in a nine-session manual of MET , which was tested over eight weeks in 30 MA-dependent out patients . Adherence to the manual was assessed by two raters , who review ed a r and om sample of 15 audiotaped therapy sessions . Interventions were rated on a seven-point Likert scale for frequency/extensiveness ( l = not at all to ? = extensively ) and skill level ( I = unacceptable to 7 = high level of mastery ) . Ratings of adherence were moderate for frequency/extensiveness ( 4.2 ± 2.2 and 4.3 ± 1.8 ; Mean ± SD ) and high for skill level ( 5.4 ± 0.6 and 5.2 ± 0.4 ) . Subjects attended 7.0 ± 2.5 ( 78 % ) of nine sessions . Self-reported days of methamphetamine use decreased from 841/1793 ( 47 % ) of the 60 days prior to study entry to 448/1458 ( 31 % ) during the study ( p= 0.011 ) . MA-positive urine sample s decreased from 76/118 ( 64 % ) during screening to 93/210 ( 44 % ) during treatment ( p = 0.015 ) . The MET manual was readily learned , and subjects attended a high proportion of therapy sessions with marked reductions in methamphetamine use Many persons seeking opiate treatment present with complex clinical challenges , which may be exacerbated by alcohol misuse . This report details secondary data analyses aggregating treatment-seeking sample s across 10 National Institute on Drug Abuse ( NIDA ) Clinical Trials Network treatment trials to examine alcohol-related characteristics of opiate- primary ( OP ) clients and compare broad pretreatment characteristics of those with and without an alcohol use disorder ( AUD ) . Analysis of this aggregate OP client sample ( n = 1,396 ) indicated that 38 % had comorbid AUD and that a history of alcohol treatment episodes and recent alcohol problems were common . Further , comparisons of OP clients with and without AUD revealed the former were more likely to have had a history of pervasive difficulties in psychosocial functioning . Findings suggest the need for detection of and intervention for alcohol misuse at the outset of opiate treatment and support for the practice of availing medical , psychological , case management , and other support services This study examined factors associated with expressed violence in the 90 days prior to substance abuse ( SA ) treatment among 125 men and 125 women recently enrolled in treatment . Approximately 85 % of the sample reported a significant conflict situation , and over 32 % reported an incident of physical violence . Both general alcohol and cocaine use patterns ( on days not involving significant interpersonal conflict ) , as well as alcohol and cocaine use on the day of the violent incident , were associated with violence severity . Regression analyses revealed that race , education , age , and both general drinking and cocaine use patterns were associated with violence severity for the most severe violent incident reported . Similarly , regression analyses focusing on alcohol and cocaine use on the day of the most severe incident revealed that higher drinking levels , younger age , minority status , and the interaction of alcohol and cocaine use were associated with violence severity . The results provide important information regarding factors associated with expression of violence among men and women in SA treatment , and have implication s regarding the assessment of violence risk factors . Further , the findings suggest that screening and intervention approaches for violence-related problems should be routine in SA treatment , and appear to be especially indicated for patients reporting alcohol consumption , and co-occurring alcohol and cocaine consumption OBJECTIVE A positive association between delay discounting and substance use has been documented ; substance users tend to discount future rewards more than non-users . However , studies detailing the responsiveness of delay discounting to interventions are lacking , and few have examined how any behavioral intervention affects delay discounting and whether these effects moderate changes in substance abuse . This study assesses the effectiveness of a money management intervention , Advisor-Teller Money Manager ( ATM ) , in reducing delay discounting over time and the relationship of these effects to changes in cocaine use . METHOD Ninety psychiatric patients with histories of cocaine and /or alcohol use were r and omly assigned to 36-weeks of ATM treatment or to a minimal-attention control condition . Delay discounting and cocaine use were measured throughout the intervention with a 52-week follow up measure of cocaine use . Analyses were conducted of ( a ) the effect of ATM on slopes of delay discounting and cocaine abstinence and ( b ) the relationship between change in delay discounting and change in cocaine abstinence . RESULTS The ATM intervention was associated with significantly less delay discounting and less cocaine use over time relative to controls . Increases in delay discounting were associated with decreased abstinence from cocaine . CONCLUSIONS ATM treatment decreased delay discounting rates and these effects extended to cocaine use . Concrete conceptualizations of future events , as occur in financial planning , with higher perceived probability may account for higher valuation of future rewards in counseled patients AIMS To estimate the prevalence of ( a ) hazardous and /or harmful drinking , ( b ) alcohol consumption , ( c ) perceived hepatitis C status ( HCV ) in opiate users in treatment and ( d ) assess the influence of perceived HCV status on consumption and attitudes to risk . DESIGN Cross-sectional survey . SETTING A methadone maintenance clinic and a drug treatment centre within a British substance misuse service in London . PARTICIPANTS A r and om sample of 93 opiate users in treatment . MEASUREMENTS Hazardous and /or harmful drinking was assessed using the Alcohol Use Disorders Identification Test ( AUDIT ) . Alcohol consumption was assessed using several indicators . Data on clinical and demographic characteristics , perceived HCV status , change in consumption and attitudes to alcohol consumption were also collected . FINDINGS A third of the sample were identified as AUDIT cases , 17 % drank more than one unit/day and 15 % were drinking above the weekly , recommended units for safe drinking ( 21 for men , 14 for women ) . Perceived HCV positive status was estimated at 70 % . HCV status influenced consumption with fewer HCV positive than HCV negative clients drinking any alcohol in the previous year . Also , more HCV positive clients than HCV negative clients , reduced their consumption after the HCV test result . HCV status had some influence on attitudes to drinking for HCV positive people , although most were aware that abstinence was important for those with HCV positive status . CONCLUSION Perceived HCV positive status has some influence on alcohol consumption . Despite these findings , training on harm reduction advice on alcohol consumption , particularly in HCV positive clients , should be extended . More intense interventions , within drug treatment services , may be required for those drinkers for whom advice is insufficient Individuals ' use of heroin , cocaine , and alcohol during long-term methadone maintenance treatment ( MMT ) was studied . Prospect ively collected data from 103 heroin-addicted individuals who were consecutively admitted for MMT and remained 2 years in treatment were evaluated . The patients were assessed every 6 months with a st and ardized interview . Three longitudinal patterns of drug abuse were identified . A proportion of patients abstained fully from their particular drug use ( 26 % from heroin , 39 % from cocaine , and 19 % from alcohol ) ; a proportion ( 39 % , 32 % , and 47 % , respectively ) switched between periods of abuse and nonuse of these drugs ; and chronic drug users ( 34 % , 28 % , and 33 % , respectively ) continued use , including periods of daily abuse throughout MMT . Different therapeutic interventions may be needed in patients with different longitudinal patterns of additional substance use during MMT AIMS To test motivational interviewing ( MI ) as a brief intervention for reducing alcohol use among needle exchange clients . DESIGN R and omized clinical trial . SETTING Needle exchange program-Providence , Rhode Isl and , USA . PARTICIPANTS Between 2/98 and 10/99 , we recruited 187 AUDIT-positive ( > 8 ) active injection drug users . INTERVENTION Those assigned to a brief motivational intervention ( MI ) condition received two 1-hour therapist sessions following assessment visits , 1 month apart , focusing on alcohol use and HIV risk-taking . MEASUREMENTS Control and MI subjects received identical research assessment s at baseline , 1 and 6 months following study enrollment . At 6 months , study outcomes included days of alcohol use measured using the time-line follow-back method . FINDINGS Study retention was 96.8 % at 6 months . Participants reported an average of 12.0 drinking days at baseline and 8.3 at 6 months . Significant reductions in drinking days were observed in both treatment conditions . We found significant treatment x baseline drinking day interaction effects . Tests for simple main effects were significant for subjects with above median ( > 9 ) baseline drinking day frequency , but not for those with below median baseline drinking frequency . Comparisons on dichotomous outcomes provided supporting evidence of treatment efficacy ; those in MI were over two times more likely than controls to report reductions of 7 days or more ( P < 0.05 ) . CONCLUSIONS This study provides the first direct evidence that brief MI can decrease alcohol use among active injection drug users with drinking problems . Heavier drinkers seem best suited for this intervention , but the optimal intensity of treatments and which components of brief intervention are most effective deserve further study Abstract The Methamphetamine Treatment Project is a multisite trial that compares the effectiveness of eight models of outpatient treatment for methamphetamine dependence to that of the Matrix model . These eight “ treatment-as-usual ” models represent diverse approaches developed in a variety of setting s to serve markedly different population s. The theoretical foundations of these treatments are described as well as the setting s in which they are delivered . To facilitate comparisons , details are presented with respect to frequency of group and individual sessions , duration of treatment , therapist qualifications , and access to ancillary services . The population s served by these programs vary with respect to race and ethnicity . Most programs serve primarily non-Hispanic Caucasians , but some programs serve significant proportions of Hispanics . Asians , Pacific Isl and ers , and Native Americans . Usual route of administration of methamphetamine also varies by site , with snorting , smoking , and injecting each reported as the most common route of administration at one or more sites . The Minnesota model and cognitive-behavioral approaches are most commonly used in these programs , although contingency management and psychodynamic approaches are also represented . The intensive phase of treatment ranges between four and 24 weeks ; the number of hours per week of client contact varies between one and 13 . This trial will provide the opportunity to test the effectiveness of a wide range of treatments currently in use in community setting AIMS The present study sought to replicate and extend a small pilot study conducted by Baker , Boggs & Lewin ( 2001 ) which demonstrated that brief interventions consisting of motivational interviewing and cognitive-behaviour therapy ( CBT ) were feasible and associated with better outcomes compared with a control condition . DESIGN R and omized controlled trial ( RCT ) . SETTING Greater Brisbane Region of Queensl and and Newcastle , NSW , Australia . PARTICIPANTS The study was conducted among 214 regular amphetamine users . MEASUREMENTS Demographic characteristics , past and present alcohol and other drug use and mental health , treatment , amphetamine-related harms and severity of dependence . FINDINGS The main finding of this study was that there was a significant increase in the likelihood of abstinence from amphetamines among those receiving two or more treatment sessions . In addition , the number of treatment sessions attended had a significant short-term beneficial effect on level of depression . There were no intervention effects on any other variables ( HIV risk-taking , crime , social functioning and health ) . Overall , there was a marked reduction in amphetamine use among this sample over time and , apart from abstinence rates and short-term effects on depression level , this was not differential by treatment group . Reduction in amphetamine use was accompanied by significant improvements in stage of change , benzodiazepine use , tobacco smoking , polydrug use , injecting risk-taking behaviour , criminal activity level , and psychiatric distress and depression level . CONCLUSIONS A stepped-care approach is recommended . The first step in providing an effective intervention among many regular amphetamine users , particularly those attending non-treatment setting s , may include provision of : a structured assessment of amphetamine use and related problems ; self-help material ; and regular monitoring of amphetamine use and related harms . Regular amphetamine users who present to treatment setting s could be offered two sessions of CBT , while people with moderate to severe levels of depression may best be offered four sessions of CBT for amphetamine use from the outset , with further treatment for amphetamine use and /or depression depending on response . Pharmacotherapy and /or longer-term psychotherapy may be suitable for non-responders . An RCT of a stepped-care approach among regular amphetamine users is suggested A sample of 296 drug-using inmates in 14 Swedish prisons was r and omized during 2004–2006 into three intervention groups ; Motivational Interviewing delivered by counselors with workshop-only training , or by counselors with workshop training followed by peer group supervision , and controls . Drug and alcohol use was measured by the Addiction Severity Index ( ASI ) at intake and at 10 months after release . Complete data from 114 clients were analyzed by a stepwise regression analysis . All three groups reduced alcohol and drug use . Limitations in the study are discussed and future research is suggested . The study is financed by grants from the Research Committee of the National Prison and Probation Administration Concurrent alcohol dependence ( AD ) among polysubstance abusers has been associated with negative consequences , although it may not necessarily lead to poor treatment outcomes . One of the most efficacious treatments for cocaine abuse is contingency management ( CM ) , but little research has explored the impact of AD on abstinence outcomes , particularly among patients in methadone maintenance . Using data from three trials of CM for cocaine use , we compared baseline characteristics and posttreatment and follow-up cocaine outcomes between methadone-maintained , cocaine-dependent patients ( N = 193 ) with and without concurrent AD , r and omized to st and ard care ( SC ) with or without CM . Patients with and without concurrent AD had similar baseline characteristics , with the exception that AD patients reported more alcohol use . AD patients achieved longer duration s of cocaine abstinence and were more likely to su bmi t a cocaine-negative sample at follow-up than non-AD patients . Patients r and omized to CM achieved better outcomes than those r and omized to SC , but there was no interaction between treatment condition and AD status . These findings suggest that cocaine-using methadone patients with AD achieve greater cocaine abstinence than their non-AD counterparts and should not necessarily be viewed as more difficult to treat Alcohol-dependent patients in inpatient detoxification were r and omized to treatment-as-usual ( TAU ) intervention or brief family treatment ( BFT ) intervention to promote continuing care postdetoxification . BFT consisted of meeting with the patient and an adult family member ( in person or over the phone ) with whom the patient lived to review and recommend potential continuing care plans for the patient . Results showed that BFT patients ( n = 24 ) were significantly more likely than TAU patients ( n = 21 ) to enter a continuing care program after detoxification . This was a medium to large effect size . In the 3 months after detoxification , days using alcohol or drugs ( a ) trended lower for treatment-exposed BFT patients who had an in-person family meeting than for TAU counterparts ( medium effect ) , and ( b ) were significantly lower for patients who entered continuing care regardless of treatment condition ( large effect ) ABSTRACT The purpose of this study is to evaluate the effectiveness of three interventions ( individual motivational interviewing , group motivational interviewing , or nurse-led hepatitis health promotion ) in reducing drug use . A r and omized , controlled trial was conducted with 256 methadone maintained moderate-to-heavy alcohol-using adults attending one of five MM outpatient clinics . Drug use in the overall sample was significantly reduced from baseline to 6-month follow-up , as assessed by a 30-day recall ( p < 0.0001 ) , with a trend apparent for 6-month recall ( p = 0.09 ) . The group and individual programs revealed significant decreases in drug use at the 30-day recall 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 The effectiveness of motivational enhancement therapy ( MET ) in comparison with counseling as usual ( CAU ) for increasing retention and reducing substance use was evaluated in a multisite r and omized clinical trial . Participants were 461 out patients treated by 31 therapists within 1 of 5 outpatient substance abuse programs . There were no retention differences between the 2 brief intervention conditions . Although both 3-session interventions result ed in reductions in substance use during the 4-week therapy phase , MET result ed in sustained reductions during the subsequent 12 weeks whereas CAU was associated with significant increases in substance use over this follow-up period . This finding was complicated by program site main effects and higher level interactions . MET result ed in more sustained substance use reductions than CAU among primary alcohol users , but no difference was found for primary drug users . An independent evaluation of session audiotapes indicated that MET and CAU were highly and comparably discriminable across sites ABSTRACT Background and Objectives : The present study evaluated the effectiveness of a single clinician delivered brief intervention ( BI ) to reduce problem alcohol use and illicit substance use in an opiate-dependent methadone maintained cohort of patients attending for treatment . Methods : Four addiction treatment centers were r and omly assigned to either treatment as usual ( TAU ; control group ) or BI ( intervention group ) . Clinicians screened patients using the alcohol , smoking , and substance involvement screening test ( ASSIST ) screening tool at baseline and again at three-month follow up . Fidelity checks were performed to ensure that training was delivered effectively and uniformly across all study sites . Feasibility of administering a BI within daily practice was assessed through intervention fidelity checks , patient satisfaction question naires and process evaluation . Results : A total of 465 patients were screened ( 66 % of the overall eligible population ) with a total of 433 ( 93 % ) ASSIST positive cases . R and omization was effective , with no differences in the control versus the intervention arms at baseline for key demographic or clinical indicators including substance us . There was a statistically significant difference between global risk score for the intervention ( x = 39.36 , sd = 25.91 ) group and the control group ( x = 45.27 , SD = 27.52 ) at 3-month follow-up ( t(341 ) = −2.07 , p < .05 ) . Conclusions : This trial provides the first evidence that a single clinician delivered BI can result in a reduction in substance use within a methadone maintained opiate-dependent cohort , and this effect is sustained at three month follow up AIM To evaluate outcomes 1 year after cessation of treatment for cocaine- and alcohol-dependent individuals . DESIGN R and omized controlled trial . SETTING Urban substance abuse treatment center . PARTICIPANTS Ninety-six of 122 subjects r and omized to treatment . INTERVENTIONS One of five treatments delivered over 12 weeks . Cognitive-behavioral treatment ( CBT ) plus disulfiram ; Twelve-Step facilitation ( TSF ) plus disulfiram ; clinical management ( CM ) plus disulfiram ; CBT without disulfiram ; TSF without disulfiram . MEASUREMENTS Percentage of days of cocaine and alcohol use during follow-up , verified by urine toxicology screens and breathalyzer tests . RESULTS First , as a group , participants reported significant decreases in frequency of cocaine , but not alcohol , use after the end of treatment . Secondly , the main effects of disulfiram on cocaine and alcohol use were sustained during follow-up . Finally , initiation of abstinence for even brief periods of time within treatment was associated with significantly better outcome during follow-up . CONCLUSIONS These findings support the efficacy of disulfiram with this challenging population and suggest that comparatively brief treatments that facilitate the initiation of abstinence may have long-term benefits Abstract Several theoretical approaches to alcoholism exist . An operant reinforcement approach was used in the present study to develop a new procedure that rearranged community reinforcers such as the job , family and social relations of the alcoholic such that drinking produced a time-out from a high density of reinforcement . The results showed that the alcoholics who received this Community-Reinforcement counseling drank less , worked more , spent more time with their families and out of institutions than did a matched control group of alcoholics who did not receive these procedures . This new approach appears to be an effective method of reducing alcoholism . An analysis in reinforcement terms is presented of the etiology , epidemiology , and treatment of alcoholism BACKGROUND Important questions remain regarding the necessary duration and intensity for methadone treatment to be effective . METHODS As part of a clinical trial of tuberculosis chemoprophylaxis [ Batki , S.L. , Gruber , V.A. , Bradley , J.M. , Bradley , M. , Delucchi , K. , 2002 . A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users . Drug Alcohol Depend . 66 283 - 293 . doi:10.1016/S0376 - 8716(01)00208 - 3 ] , patients with opioid dependence were recruited from an outpatient 21-day methadone detoxification program and were r and omly assigned to one of three treatment conditions : ( 1 ) continuation in 21-day methadone detoxification ; ( 2 ) transfer to 6-month methadone maintenance with only minimal counseling ; or ( 3 ) transfer to 6-month methadone maintenance with st and ard twice monthly counseling and as-needed social work and psychiatric services . Both the 6-month maintenance treatments were followed by 1.5 months of detoxification . Urine drug tests and self-report measures were collected at baseline , months 1 - 6 , and month 8.5 . RESULTS Compared to 21-day methadone detoxification , 6-month methadone maintenance with either minimal or st and ard counseling result ed in fewer opiate positive urine tests and days of self-reported heroin and alcohol use . There was no change in cocaine use or other outcome measures . The increased counseling available in the st and ard counseling condition did not appear to reduce heroin use further than the minimal counseling condition , in contrast to the effect found for more structured counseling in long-term methadone maintenance ( McLellan et al. , 1993 ) . CONCLUSIONS Six months of methadone maintenance , even with minimal counseling , reduces heroin and alcohol use more than 21-day methadone detoxification AIMS To examine the prevalence rate and predictors of alcohol use problems among patients undergoing methadone maintenance treatment ( MMT ) . DESIGN This was a prospect i ve follow-up study . PARTICIPANTS Study population included 438 patients who underwent more than 6 months of MMT . MEASUREMENTS Demographic and clinical characteristics were collected for each patient prior to treatment , and treatment-related variables were collected during treatment process . Hazardous drinking , alcohol abuse , and dependence were measured using a Chinese version of the Alcohol Use Disorders Identification Test ( AUDIT ) and by measuring breath alcohol concentration . FINDINGS The prevalence rates of alcohol use problems , indicated by hazardous drinking are 31.4 % . The protective predictors of alcohol use problems among MMT patients include an attendance rate of more than 90 % ( odds ratio [ OR ] = 0.54 , 95 % confidence interval [ CI ] = 0.30 - 0.97 ) and being older than 36 years ( OR = 0.48 , 95 % CI = 0.27 - 0.86 ) , and alcohol drinking problem at intake of study is a risk factor ( OR = 5.30 , 95 % CI = 2.87 - 9.76 ) . CONCLUSIONS High attendance rate , which is regarded as a component of clinical policy and a key component of therapeutic context , should be incorporated with brief interventions to lower alcohol use problems among MMT patients BACKGROUND Methadone-maintained ( MM ) clients who engage in excessive alcohol use are at high risk for HIV and hepatitis B virus ( HBV ) infection . Nurse-led hepatitis health promotion ( HHP ) may be one strategy to decrease alcohol use in this population . OBJECTIVE To evaluate the impact of nurse-led HHP , delivered by nurses compared to motivational interviewing ( MI ) , delivered by trained therapists in group sessions or one-on-one on reduction of alcohol use . METHODS A three-arm r and omized , controlled trial , conducted with 256 MM adults attending one of five MM outpatient clinics in the Los Angeles area . Within each site , moderate-to-heavy alcohol-using MM participants were r and omized into one of three conditions : ( 1 ) nurse-led hepatitis health promotion group sessions ( n=87 ) ; ( 2 ) MI delivered in group sessions ( MI-group ; n=79 ) , or ( 3 ) MI delivered one-on-one sessions ( MI-single , n=90 ) . RESULTS Self-reported alcohol use was reduced from a median of 90 drinks/month at baseline to 60 drinks/month at 6-month follow-up . A Wilcoxon sign-rank test indicated a significant reduction in alcohol use in the total sample ( p<.05 ) . In multiple logistic regression analysis controlling for alcohol consumption at baseline and other covariates , no differences by condition were found . DISCUSSION As compared to two programs delivered by MI specialists , a culturally-sensitive and easy to implement nurse-led HHP program produced similar reductions in alcohol use over 6 months . Employing nurse-led programs may allow cost savings for treatment programs as well as a greater integration of alcohol reduction counseling along with a more comprehensive focus on general health-related issues than previously conducted AIMS To evaluate disulfiram and three forms of manual guided psychotherapy for individuals with cocaine dependence and concurrent alcohol abuse or dependence . DESIGN R and omized controlled trial . SETTING Urban substance abuse treatment center . PARTICIPANTS One hundred and twenty-two cocaine/alcohol abusers ( 27 % female ; 61 % African-American or Hispanic ) . INTERVENTIONS One of five treatments delivered over 12 weeks : cognitive behavioral treatment ( CBT ) plus disulfiram ; Twelve Step facilitation ( TSF ) plus disulfiram ; clinical management ( CM ) plus disulfiram ; CBT plus no medication ; TSF plus no medication . MEASUREMENTS Duration of continuous abstinence from cocaine or alcohol ; frequency and quantity of cocaine and alcohol use by week , verified by urine toxicology and breathalyzer screens . FINDINGS Disulfiram treatment was associated with significantly better retention in treatment , as well as longer duration of abstinence from alcohol and cocaine use . The two active psychotherapies ( CBT and TSF ) were associated with reduced cocaine use over time compared with supportive psychotherapy ( CM ) . Cocaine and alcohol use were strongly related throughout treatment , particularly for subjects treated with disulfiram . CONCLUSIONS For the large proportion of cocaine-dependent individuals who also abuse alcohol , disulfiram combined with outpatient psychotherapy may be a promising treatment strategy . This study underlines ( a ) the significance of alcohol use among treatment-seeking cocaine abusers , ( b ) the promise of the strategy of treating co-morbid disorders among drug-dependent individuals , and ( c ) the importance of combining psychotherapy and pharmacotherapy in the treatment of drug use disorders Follow-up data ( mean 9 months ) were obtained for 74 subjects who had been treated for a mean of 8 months and 17 sessions in a controlled comparison of Behavioral vs Supportive Counselling for drug abuse . Based on urinalysis , self-report , and family report , all subjects ( 100 % ) were actively using drugs at pre-treatment . During the last month of treatment , 81 % of the Supportive treatment subjects and 44 % of the Behavioral treatment subjects were using drugs at least once . At the follow-up month , drugs were used at least once by 71 % of the Supportive vs 42 % of Behavioral subjects . When drug use was measured in terms of the number of days of use per month , Supportive counselled subjects did not decrease drug use either by the end of treatment or at follow-up ; for Behavioral subjects , drug use decreased by 63 % by the end of treatment and by 73 % at follow-up . Alcohol use , and days worked/or in school showed a similar pattern of greater improvement for the Behavioral treatment being maintained at the follow-up . These results indicate a substantial treatment-specific reduction of drug usage that endures after treatment is discontinued . The present favorable results appear attributable to the inclusion of family/significant others in therapy and the use of reinforcement contingent on urinalysis results 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 AIMS To estimate the relationship between daily alcohol use and HIV seroconversion among people who inject drugs ( PWID ) in a Canadian setting . DESIGN AND SETTING Data from an open prospect i ve cohort study of PWID in Vancouver , Canada , recruited via snowball sampling and street outreach between May 1996 and November 2013 . An interviewer-administered question naire including st and ardized behavioural assessment and HIV antibody testing were conducted semi-annually . Baseline HIV-seronegative participants completing ≥ 1 follow-up visits were eligible for the present analysis . PARTICIPANTS A total of 1683 eligible participants , were followed for a median of 79.8 [ interquartile range ( IQR ) = 33.3 - 119.1 ] months . MEASUREMENTS The primary end-point was time to HIV seroconversion , with the date of HIV seroconversion estimated as the mid-point between the last negative and the first positive antibody test results . The primary explanatory variable was self-reported daily alcohol use in the previous 6 months assessed semiannually . Other covariates considered included demographic , behavioural , social/structural and environmental risk factors for HIV infection among PWID ( e.g. daily cocaine injection , methadone use , etc . ) . FINDINGS Of 1683 PWID , there were 176 HIV seroconversions during follow-up with an incidence density of 1.5 [ 95 % confidence interval ( CI ) = 1.3 - 1.7 ] cases per 100 person-years . At baseline , 339 ( 20.1 % ) consumed alcohol at least daily in the previous 6 months . In multivariable extended Cox regression analyses , daily alcohol use remained associated independently with HIV seroconversion ( adjusted hazard ratio : 1.48 ; 95 % CI = 1.00 - 2.17 ) . CONCLUSIONS Daily alcohol use appears to be an independent risk factor for HIV seroconversion among our cohort of PWID The aim of this study was to compare two short-term treatments for alcohol-related problems . The study was performed at an outpatient clinic for substance misuse , and subjects ( 65 men and 28 women ) were recruited through advertisements in the local newspaper . The subjects were r and omized to either a four-session guided self-change group or a one-session advice group . Alcohol consumption , degree of alcohol dependence , negative consequences of drinking , and health-related quality of life were measured or assessed , respectively , by using the timeline follow-back technique , the Short Alcohol Dependence Data ( SADD ) question naire , The Drinker Inventory of Consequences question naire , and the Nottingham Health Profile question naire . Biological markers for high alcohol consumption [ carbohydrate-deficient transferrin ( CDT ) and gamma-glutamyl transferase ( gamma-GT ) levels ] were analyzed . All assessment s were made at baseline and at 9- and 23-month follow-up periods after treatment . Self-reported alcohol consumption was significantly reduced ( P < .0001 ) in both treatment groups at the 23-month follow-up period , as were measures of alcohol dependence , negative consequences of drinking , and health-related quality of life , whereas no corresponding reduction was found in CDT or gamma-GT values . No statistically significant differences in self-reported alcohol consumption were found between the two groups . Patient satisfaction was significantly higher with the four-session guided self-change treatment than with the one session of advice . This finding seems to indicate that individuals , although suffering from alcohol-related problems of relatively low severity , appreciate more time with a therapist The effect of alcoholism on indices of productive activity was determined in a prospect i ve , r and omized , and controlled study of alcoholism in narcotic addicts undergoing methadone maintenance ( MM ) therapy . Indices of productive activity included : percentage of persons engaged in productive activities ; number of days worked per quarter ; number of arrests per quarter ; number of hospitalizations ; and days of hospitalizations per quarter . Baseline as well as longitudinal data were obtained on operative alcoholics ( OA ) , inactive alcoholics ( IA ) , and nonalcoholics ( NA ) . OA patients were subsequently r and omized to a control group or groups receiving either abstinence-oriented insight group therapy or controlled drinking-oriented behavioral modification group therapy . The retention rate in MM of OA versus NA during the 29-month clinical phase of the study did not differ significantly . Similarly , no significance was reported with respect to any index of productive activity . Indices of productive activity in OA undergoing treatment as compared to those r and omized to the control group also did not reveal any significant differences . The compliance of OA in seeking and maintaining therapy for their alcoholism , however , was sufficiently poor so that any conclusions concerning the effectiveness of therapy on indices of productive activity should be viewed cautiously Objective . To examine whether the addition of counseling , medical care , and psychosocial services improves the efficacy of methadone hydrochloride therapy in the rehabilitation of opiate‐dependent patients . Design . R and om assignment to one of three treatment groups for a 6‐month clinical trial : ( 1 ) minimum methadone services (MMS)—methadone alone ( a minimum of 60 mg/d ) with no other services ; ( 2 ) st and ard methadone services (SMS)—same dose of methadone plus counseling ; or ( 3 ) enhanced methadone services (EMS)—same dose of methadone plus counseling and on‐site medical/psychiatric , employment , and family therapy . Setting . The methadone maintenance program of the Philadelphia ( Pa ) Veterans Affairs Medical Center . Subjects . Ninety‐two male intravenous opiate users in methadone maintenance treatment . Results . While methadone treatment alone ( MMS ) was associated with reductions in opiate use , 69 % of these subjects had to be “ protectively transferred ” from the trial because of unremitting use of opiates or cocaine , or medical/psychiatric emergencies . This was significantly different from the 41 % of SMS subjects and 19 % of EMS subjects who met the criteria . End‐of‐treatment data ( at 24 weeks ) showed minimal improvements among the 10 MMS patients who completed the trial . The SMS group showed significantly more and larger improvements than did the MMS group ; and the EMS group showed significantly better outcomes than did the SMS group . Minimum methadone services subjects who had been “ protectively transferred ” to st and ard care showed significant reductions in opiate and cocaine use within 4 weeks . Conclusions . Methadone alone ( even in substantial doses ) may only be effective for a minority of eligible patients . The addition of basic counseling was associated with major increases in efficacy ; and the addition of on‐site professional services was even more effective R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community A r and omized prospect i ve study of 625 drug addicts on methadone maintenance revealed that 105 ( 17 % ) were active alcoholics , 47 ( 8 % ) were inactive alcoholics , and 473 ( 76 % ) were not alcoholics . The active alcoholics were r and omly assigned to abstinence therapy , controlled drinking with behavior modification , or a control group receiving the usual clinic services . There were no differences between treatment and control groups at baseline and during follow-up of up to 2 1/2 years , and there was no relation between remission and treatment , suggesting that the effectiveness of currently employed specific interventions for alcoholism in active alcoholic addicts maintained on methadone can not be demonstrated Review s the emergence of research on fitting treatment procedures to the unique needs and proclivities of patients . Traditional research on efficacy of psychotherapy focuses on the role of interventions and theoretical br and s , minimizing factors that can not be r and omly assigned . This line of research has not realized its initial and desired promise , perhaps because it fails to incorporate into the study of psychotherapy important and effective treatment variations that are associated with therapist and non-diagnostic patient factors . Contemporary efforts to “ fit ” treatments to patients emphasize the roles of interventions , participant factors , and context ual/relationship factors . For these complex interactions , any of which reflect factors that can not be r and omly assigned , r and omized clinical trials ( RCT ) protocol s are inappropriate as a “ gold st and ard ” . Several studies are presented which illustrate not only the predictive power of incorporating both treatment mediators and moderators into the realm of psychotherapy study , but the value of a multi- method approach to research . Converging studies moreover , provide a way to incorporate matching algorithms into decisions about assigning optimal treatments BACKGROUND Brief motivational intervention ( BMI ) is one of the few effective strategies targeting alcohol consumption , but has not been tested in young men in the community . We evaluated the efficacy of BMI in reducing alcohol use and related problems among binge drinkers and in maintaining low-risk drinking among non-bingers . METHODS A r and om sample of a census of men included during army conscription ( which is m and atory for 20-year-old males in Switzerl and ) was r and omized to receive a single face-to-face BMI session ( N=199 ) or no intervention ( N=219 ) . A six-month follow-up rate was obtained for 88.7 % of the subjects . RESULTS Among binge drinkers , there was 20 % less drinking in the BMI group versus the control group ( incidence rate ratio=0.80 , confidence interval 0.66 - 0.98 , p=0.03 ) ; the BMI group showed a weekly reduction of 1.5 drinks compared to an increase of 0.8 drinks weekly in the control group . Among subjects who experienced one or more alcohol-related consequences over the last 12 months , there was 19 % less drinking in the BMI group compared to the control group ( incidence rate ratio=0.81 , confidence interval 0.67 - 0.97 , p=0.04 ) . Among non-bingers , BMI did not contribute to the maintenance of low-risk drinking . CONCLUSION BMI reduced the alcohol use of binge drinkers , particularly among those who experienced certain alcohol-related adverse consequences . No preventive effect of BMI was observed among non-bingers . BMI is a plausible secondary preventive option for young binge drinkers |
1,785 | 24,683,067 | The investigators found no difference in adverse effects between composite and amalgam restorations .
There is low- quality evidence to suggest that resin composites lead to higher failure rates and risk of secondary caries than amalgam restorations .
This review reinforces the benefit of amalgam restorations and the results are particularly useful in parts of the world where amalgam is still the material of choice to restore posterior teeth with proximal caries . | BACKGROUND Amalgam has been the traditional material for filling cavities in posterior teeth for the last 150 years and , due to its effectiveness and cost , amalgam is still the restorative material of choice in certain parts of the world .
In recent times , however , there have been concerns over the use of amalgam restorations ( fillings ) , relating to the mercury release in the body and the environmental impact following its disposal .
Resin composites have become an esthetic alternative to amalgam restorations and there has been a remarkable improvement of its mechanical properties to restore posterior teeth .
There is need to review new evidence comparing the effectiveness of both restorations .
OBJECTIVES To examine the effects of direct composite resin fillings versus amalgam fillings for permanent posterior teeth , primarily on restoration failure . | The split-mouth design is a popular design in oral health research . In the most common split-mouth study , each of two treatments are r and omly assigned to either the right or left halves of the dentition . The attractiveness of the design is that it removes a lot of inter-individual variability from the estimates of the treatment effect . However , already about 20 years ago the pitfalls of the design have been reported in the oral health literature . Yet , many clinicians are not aware of the potential problems with the split-mouth design . Further , it is our experience that most statisticians are not even aware of the existence of this design . Since most of the critical remarks appeared in the oral health literature , we argue that it is necessary to introduce the split-mouth design to a statistical audience , so that both clinicians and statisticians clearly underst and the advantages , limitations , statistical considerations , and implication s of its use in clinical trials and advise them on its use in practice Two formulations of posterior composite resin ( P-30 and Bisfil-P ) were evaluated and compared to a high-copper , dispersed-phase amalgam ( Dispersalloy ) . One hundred twenty-eight restorations were placed in 27 patients so that each patient received at least one of each material . After 3 years of clinical service , all three restorative material s produced clinical ly acceptable restorations , according to US Public Health Service and Leinfelder criteria . The amalgam restorations , however , underwent less wear ( 44 microns ) than did the posterior composite resin restorations ( 60 to 74 microns ) . Stratification of data by type of tooth , class of restoration , and size of restoration produced the same ranking of wear from lowest to highest : Dispersalloy , Bisfil-P , and P-30 . Resin restorations showed 45 % more wear in molars than in premolars , and more wear was associated with moderately sized restorations than with conservative restorations . The surface texture of restorations of composite resin with porous strontium glass filler was nearly as smooth as that of enamel and was significantly smoother than that of the restorations of composite resin with zinc glass filler or of unpolished amalgam Previous studies noted specific changes in urinary porphyrin excretion patterns associated with exposure to mercury ( Hg ) in animals and humans . In our study , urinary porphyrin concentrations were examined in normal children 8–18 years-old from a re analysis of data provided from a r and omized , prospect i ve clinical trial that was design ed to evaluate the potential health consequences of prolonged exposure to Hg from dental amalgam fillings ( the parent study ) . Our analysis examined dose-dependent correlations between increasing Hg exposure from dental amalgams and urinary porphyrins utilizing statistical models with adjustments for the baseline level ( i.e. study year 1 ) of the following variables : urinary Hg , each urinary porphyrin measure , gender , race , and the level of lead ( Pb ) in each subject ’s blood . Significant dose-dependent correlations between cumulative exposure to Hg from dental amalgams and urinary porphyrins associated with Hg body-burden ( pentacarboxyporphyrin , precoproporphyrin , and coproporphyrin ) were observed . Overall , 5–10 % increases in Hg-associated porphyrins for subjects receiving an average number of dental amalgam fillings in comparison to subjects receiving only composite fillings were observed over the 8-year course of the study . In contrast , no significant correlations were observed between cumulative exposure to Hg from dental amalgams and urinary porphyrins not associated with Hg body-burden ( uroporphyrin , heptacarboxyporphyrin , and hexacarboxyporphyrin ) . In conclusion , our study , in contrast to the no-effect results published from the parent study , further establishes the sensitivity and specificity of specific urinary porphyrins as a biomarker for low-level Hg body-burden , and also reveals that dental amalgams are a significant chronic contributor to Hg body-burden In 41 patients class 11 cavities each of the lower jaw were filled with the material s Adaptic , Concise cap , Epoxydent or amalgam . The models made from impressions were systemically measured by a coordinate measuring machine according to a procedure determined by us ( measuring error of this method about 15 micron ) . After one year the following abrasions were found : amalgam 18 micron + /- 58 micron , Adaptic 92 micron + /- 97 micron , Concise Cap 146 micron + /- 75 micron , Epoxydent 38 micron + /- 50 micron . Evaluation of the clinical examination showed that the material s Concise and Epoxydent were significantly inferior as regards border closure than amalgam and Adaptic . We determined further that a large percentage of composite filling showed visible discoloration of the borders ( Adaptic 42 % , Concise 55 % , Epoxydent 80 % ) . Many of the fillings were discolored after a year . Adaptic was highly significantly different with 31.6 % discolored fillings to both other material s ( Concise 79 % , Epoxydent 78.4 % ) Dental amalgams are a commonly used dental restorative material , and amalgams are about 50 % mercury ( Hg ) . In our study , urinary Hg levels was examined in children of age 8–18 years , with and without dental amalgam fillings , from a completed clinical trial ( parent study ) that was design ed to evaluate the potential health consequences of prolonged exposure to Hg from dental amalgam fillings . Our study was design ed to determine whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and urinary Hg levels . Hg exposure depends on the size and number of teeth with dental amalgams . Overall , consistent with the results observed in the parent study , there was a statistically significant dose-dependent correlation between cumulative exposure to Hg from dental amalgams and urinary Hg levels , after covariate adjustment . Further , it was observed that urinary Hg levels increased by 18 % to 52 % among 8 to 18 year old individuals , respectively , with an average exposure to amalgams , in comparison to study subjects with no exposure to amalgams . The results of our study suggest that dental amalgams contribute to ongoing Hg exposure in a dose-dependent fashion Resin-based composite dental restoration material s may release bisphenol-A , an endocrine-disrupting chemical . Using secondary analysis of a r and omized clinical safety trial of amalgam vs. composites , we tested the hypothesis that dental restoration material s affect children ’s growth . Children ( N = 218 boys , N = 256 girls ) aged 6 to 10 yrs at baseline with ≥ 2 decayed posterior teeth were r and omized to amalgam or composites ( bisphenol-A-diglycidyl-dimethacrylate composite for permanent teeth , urethane-dimethacrylate compomer for primary teeth ) for treatment of posterior caries throughout follow-up . Primary outcomes for this analysis were 5-year changes in BMI -for-age z-scores , body fat percentage ( BF% ) , and height velocity ; exploratory analyses ( n = 113 ) examined age at menarche . Results showed no significant differences between treatment assignment and changes in physical development in boys [ ( composites vs. amalgam ) BF% , 4.9 vs. 5.7 , p = 0.49 ; ( BMI -z-score ) 0.13 vs. 0.25 , p = 0.36 ] or girls ( 8.8 vs. 7.7 , p = 0.95 ; 0.36 vs. 0.21 , p = 0.49 ) . Children with more treatment on primary teeth had greater increases in BF% regardless of material type . Girls assigned to composites had lower risk of menarche during follow-up ( hazard ratio = 0.57 , 95 % CI 0.35 - 0.95 ) . Overall , there were no significant differences in physical development over 5 years in children treated with composites or amalgam . Additional studies examining these restoration material s in relation to age at menarche are warranted ( clinical trials.gov number NCT00065988 ) CONTEXT Dental ( silver ) amalgam is a widely used restorative material containing 50 % elemental mercury that emits small amounts of mercury vapor . No r and omized clinical trials have determined whether there are significant health risks associated with this low-level mercury exposure . OBJECTIVE To assess the safety of dental amalgam restorations in children . DESIGN A r and omized clinical trial in which children requiring dental restorative treatment were r and omized to either amalgam for posterior restorations or resin composite instead of amalgam . Enrollment commenced February 1997 , with annual follow-up for 7 years concluding in July 2005 . SETTING AND PARTICIPANTS A total of 507 children in Lisbon , Portugal , aged 8 to 10 years with at least 1 carious lesion on a permanent tooth , no previous exposure to amalgam , urinary mercury level < 10 microg/L , blood lead level < 15 microg/dL , Comprehensive Test of Nonverbal Intelligence IQ > or = 67 , and with no interfering health conditions . INTERVENTION Routine , st and ard-of-care dental treatment , with one group receiving amalgam restorations for posterior lesions ( n = 253 ) and the other group receiving resin composite restorations instead of amalgam ( n = 254 ) . MAIN OUTCOME MEASURES Neurobehavioral assessment s of memory , attention/concentration , and motor/visuomotor domains , as well as nerve conduction velocities . RESULTS During the 7-year trial period , children had a mean of 18.7 tooth surfaces ( median , 16 ) restored in the amalgam group and 21.3 ( median , 18 ) restored in the composite group . Baseline mean creatinine-adjusted urinary mercury levels were 1.8 microg/g in the amalgam group and 1.9 microg/g in the composite group , but during follow-up were 1.0 to 1.5 microg/g higher in the amalgam group than in the composite group ( P<.001 ) . There were no statistically significant differences in measures of memory , attention , visuomotor function , or nerve conduction velocities ( average z scores were very similar , near zero ) for the amalgam and composite groups over all 7 years of follow-up , with no statistically significant differences observed at any time point ( P values from .29 to .91 ) . Starting at 5 years after initial treatment , the need for additional restorative treatment was approximately 50 % higher in the composite group . CONCLUSIONS In this study , children who received dental restorative treatment with amalgam did not , on average , have statistically significant differences in neurobehavioral assessment s or in nerve conduction velocity when compared with children who received resin composite material s without amalgam . These findings , combined with the trend of higher treatment need later among those receiving composite , suggest that amalgam should remain a viable dental restorative option for children . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00066118 A three-year clinical study was completed at the College of Dentistry comparing the overall performance of Class I amalgam restorations with preventive resin restorations ( PRRs ) . Seventy-four PRRs and fifty-two amalgam restorations were placed in the posterior teeth of thirty-eight patients . The PRR was composed of two material s : P-50 ( 3 M Corp. ) , a heavily filled composite resin , and White Sealant ( 3 M Corp. ) , a light-cured sealant . Fast-set Dispersalloy ( Johnson and Johnson Corp. ) was used for the amalgam restorations . The restorations were evaluated at six months , one year , two years and three years . The USPHS/Ryge system was used to evaluate anatomic form , marginal adaptation , marginal discoloration and recurrent caries of both type restorations . A restoration was considered a failure if any part of the restoration was replaced due to secondary caries . There were two failures of PRRs at six months , and four failures at one year . Failures were due to non retention of the sealant of the PRR and possibly related to operator error . The failures were easily repaired and removed from the study . No PRR failed at the two or three year evaluations . No amalgam restoration failed within the three year period The aim of this study was to obtain information on the restorative dental care of adults in Finl and . A r and om sample of private dentists was drawn from the register , and in spring 2000 they were sent a question naire requesting them to record information for each restoration placed during one ordinary working day . A total of 800 dentists were contacted and 548 responded . The dentists reported placement of 3,455 restorations . Of these , 5 % were Class I , 36 % were Class II , 13 % were Class III , 9 % were Class IV , 21 % were Class V , and 16 % were extensive restorations including 4 or more surfaces . Overall , composite resin was the most common restorative material , and it was used in 79 % of the restorations , whereas amalgam was used in 5 % , compomers in 4 % , and glass ionomers ( either conventional or resin‐modified ) in 7 % of cases . In 5 % of the cases , the tooth was restored with indirect restorative methods , using either gold or ceramic material s. Of the treatments , 65 % were replacements of previous restorations . Secondary caries was the most common reason for replacement ( 36 % , 52 % , and 41 % for composite , glass ionomer , and amalgam , respectively ) . Other common reasons were fractures of the tooth or restoration ( 23 % , 11 % , and 22 % for composite , glass ionomer , and amalgam , respectively ) and lost composite restorations ( 16 % ) . The median age of failed restorations was 15 years for amalgam , 6 years for composite , and 7 years for conventional glass ionomer . Although the longevity of tooth coloured restorations was shorter than that of amalgam , comparisons with our previous studies indicate improved survival periods for tooth coloured material A posterior composite resin restorative material was evaluated over a 3-year period by means of a controlled clinical trial . A total of 52 composite resin restorations and 52 amalgam alloy restorations were included in this trial , and were examined with regard to marginal integrity , surface texture , anatomical form and proximal contact with adjacent teeth . There were no significant differences in clinical performance between test and control material s , which both gave good service over the period of evaluation . Only five restorations ( one of amalgam and four of composite resin ) failed during the trial . Plastic replica dies were used to support the clinical examinations of the restorations , and such dies were found to be helpful Background The objective this study was to investigate the influence of clinical conditions , socioeconomic status , home environment , subjective perceptions of parents and schoolchildren about general and oral health on schoolchildren 's oral health-related quality of life ( OHRQoL ) . Methods A sample of 515 schoolchildren , aged 12 years was r and omly selected by conglomerate analysis from public and private schools in the city of Juiz de Fora , Brazil . The schoolchildren were clinical ly examined for presence of caries lesions ( DMFT and dmft index ) , dental trauma , enamel defects , periodontal status ( presence/absence of bleeding ) , dental treatment and orthodontic treatment needs ( DAI ) . The SiC index was calculated . The participants were asked to complete the Brazilian version of Child Perceptions Question naire ( CPQ11 - 14 ) and a question naire about home environment . Questions were asked about the presence of general diseases and children 's self-perception of their general and oral health status . In addition , a question naire was sent to their parents inquiring about their socioeconomic status ( family income , parents ' education level , home ownership ) and perceptions about the general and oral health of their school-aged children . The chi-square test was used for comparisons between proportions . Poisson 's regression was used for multivariate analysis with adjustment for variances . Results Univariate analysis revealed that school type , monthly family income , mother 's education , family structure , number of siblings , use of cigarettes , alcohol and drugs in the family , parents ' perception of oral health of schoolchildren , schoolchildren 's self perception their general and oral health , orthodontic treatment needs were significantly associated with poor OHRQoL ( p < 0.001 ) . After adjusting for potential confounders , variables were included in a Multivariate Poisson regression . It was found that the variables children 's self perception of their oral health status , monthly family income , gender , orthodontic treatment need , mother 's education , number of siblings , and household overcrowding showed a strong negative effect on oral health-related quality of life . Conclusions It was concluded that the clinical , socioeconomic and home environment factors evaluated exerted a negative impact on the oral health-related quality of life of schoolchildren , demonstrating the importance of health managers addressing all these factors when planning oral health promotion interventions for this population BACKGROUND AND OBJECTIVE : Resin-based dental material s may intraorally release their chemical components and bisphenol A. The New Engl and Children ’s Amalgam Trial found that children r and omized to amalgam had better psychosocial outcomes than those assigned to composites for posterior tooth restorations . The objective of this study was to examine whether greater exposure to dental composites is associated with psychosocial problems in children . METHODS : Analysis of treatment-level data from the New Engl and Children ’s Amalgam Trial , a 2-group r and omized safety trial comparing amalgam with the treatment plan of bisphenol A-glycidyl methacrylate (bisGMA)-based composite and urethane dimethacrylate – based polyacid-modified composite ( compomer ) , among 534 children aged 6 to 10 years at baseline . Psychosocial function at follow-up ( n = 434 ) was measured by using the self-reported Behavior Assessment System for Children ( BASC-SR ) and parent-reported Child Behavior Checklist ( CBCL ) . RESULTS : Children with higher cumulative exposure to bisGMA-based composite had poorer follow-up scores on 3 of 4 BASC-SR global scales : Emotional Symptoms ( β = 0.8 , SE = 0.3 , P = .003 ) , Clinical Maladjustment ( β = 0.7 , SE = 0.3 , P = .02 ) , and Personal Adjustment ( β = –0.8 , SE = 0.2 , P = .002 ) . Associations were stronger with posterior-occlusal ( chewing ) surfaces , where degradation of composite was more likely . For CBCL change , associations were not statistically significant . At-risk or clinical ly significant scores were more common among children with greater exposure for CBCL Total Problem Behaviors ( 16.3 % vs 11.2 % , P-trend = .01 ) and numerous BASC-SR syndromes ( eg , ≥13 vs 0 surface-years , Interpersonal Relations 13.7 % vs 4.8 % , P-trend = .01 ) . No associations were found with compomer , nor with amalgam exposure levels among children r and omized to amalgam . CONCLUSIONS : Greater exposure to bisGMA-based dental composite restorations was associated with impaired psychosocial function in children , whereas no adverse psychosocial outcomes were observed with greater urethane dimethacrylate – based compomer or amalgam treatment levels CONTEXT No r and omized trials have been published that address the concern that inhalation of mercury vapor released by amalgam dental restorations causes adverse health effects . OBJECTIVE To compare the neuropsychological and renal function of children whose dental caries were restored using amalgam or mercury-free material s. DESIGN AND SETTING The New Engl and Children 's Amalgam Trial was a 2-group r and omized safety trial involving 5 community health dental clinics in Boston , Mass , and 1 in Farmington , Me , between September 1997 and March 2005 . PARTICIPANTS AND INTERVENTION A total of 534 children aged 6 to 10 years at baseline with no prior amalgam restorations and 2 or more posterior teeth with caries were r and omly assigned to receive dental restoration of baseline and incident caries during a 5-year follow-up period using either amalgam ( n=267 ) or resin composite ( n = 267 ) material s. MAIN OUTCOME MEASURES The primary neuropsychological outcome was 5-year change in full-scale IQ scores . Secondary outcomes included tests of memory and visuomotor ability . Renal glomerular function was measured by creatinine-adjusted albumin in urine . RESULTS Children had a mean of 15 tooth surfaces ( median , 14 ) restored during the 5-year period ( range , 0 - 55 ) . Assignment to the amalgam group was associated with a significantly higher mean urinary mercury level ( 0.9 vs 0.6 microg/g of creatinine at year 5 , P<.001 ) . After adjusting for r and omization stratum and other covariates , no statistically significant differences were found between children in the amalgam and composite groups in 5-year change in full-scale IQ score ( 3.1 vs 2.1 , P = .21 ) . The difference in treatment group change scores was 1.0 ( 95 % confidence interval , -0.6 to 2.5 ) full-scale IQ score point . No statistically significant differences were found for 4-year change in the general memory index ( 8.1 vs 7.2 , P = .34 ) , 4-year change in visuomotor composite ( 3.8 vs 3.7 , P = .93 ) , or year 5 urinary albumin ( median , 7.5 vs 7.4 mg/g of creatinine , P = .61 ) . CONCLUSIONS In this study , there were no statistically significant differences in adverse neuropsychological or renal effects observed over the 5-year period in children whose caries were restored using dental amalgam or composite material s. Although it is possible that very small IQ effects can not be ruled out , these findings suggest that the health effects of amalgam restorations in children need not be the basis of treatment decisions when choosing restorative dental material s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00065988 STATEMENT OF PROBLEM The increasing trend toward esthetics has led to controversy as to the longevity of esthetic restorations and the wisdom of having traditional restorations replaced for esthetic reasons . With the assumption that the way dentists treat their own teeth may be a good indication of the accumulated wisdom of the profession , knowledge of dentists ' own restorative choices may provide guidance in selecting the most appropriate restorations . PURPOSE The purpose of this article was to determine restorative choices of dentists for personal molars and estimate restoration longevity . MATERIAL AND METHODS Information about dentists ' molars was obtained from a Web-based survey design ed to receive dentists ' demographic data and charting of 8 molar teeth with estimated longevity . Approximately 12,000 e-mails asking to access the website were sent to dentists ' addresses r and omly selected from a commercial data base . Nonrespondents received 1 reminder . The responses were statistically analyzed with a chi-square analysis ( alpha=.05 ) . RESULTS Seven hundred fifty-seven valid replies provided information for 6,034 teeth ( 22 % unrestored , 75 % restored , 2 % missing ) . Restorations reported included amalgam ( 36 % ) , gold inlay/onlay ( 13 % ) , complete veneer crown ( CVC ) ( 10 % ) , metal-ceramic crown ( MCC ) ( 8 % ) , and composite ( 7 % ) . Other esthetic options accounted for less than 3 % . Restorations with more than 20 years longevity included amalgam restorations ( 58 % ) , gold inlays/onlays ( 48 % ) and crowns ( 23 % ) . Fifty-six percent of esthetic restorations and 5 % of amalgams were placed in the last 5 years . The following restorations were placed in the last year ( n=186 ) : 38 % esthetic , 29 % crowns ( 18 % MCC ; 11 % CVC ) , and 17 % gold inlay/onlay or amalgam . Significant differences ( P<.001 ) were identified for dentist 's gender , year of graduation and practice location . CONCLUSIONS Most dentists have not replaced traditional metallic restorations with esthetic alternatives . Dentists still choose nonesthetic options for significant numbers of their own restorations BACKGROUND Limited information is available from r and omized clinical trials comparing the longevity of amalgam and resin-based compomer/composite restorations . The authors compared replacement rates of these types of restorations in posterior teeth during the five-year follow-up of the New Engl and Children 's Amalgam Trial . METHODS The authors r and omized children aged 6 to 10 years who had two or more posterior occlusal carious lesions into groups that received amalgam ( n=267 ) or compomer ( primary teeth)/composite ( permanent teeth ) ( n=267 ) restorations and followed them up semiannually . They compared the longevity of restorations placed on all posterior surfaces using r and om effects survival analysis . RESULTS The average+/-st and ard deviation follow-up was 2.8+/-1.4 years for primary tooth restorations and 3.4+/-1.9 years for permanent tooth restorations . In primary teeth , the replacement rate was 5.8 percent of compomers versus 4.0 percent of amalgams ( P=.10 ) , with 3.0 percent versus 0.5 percent ( P=.002 ) , respectively , due to recurrent caries . In permanent teeth , the replacement rate was 14.9 percent of composites versus 10.8 percent of amalgams ( P=.45 ) , and the repair rate was 2.8 percent of composites versus 0.4 percent of amalgams ( P=.02 ) . CONCLUSION Although the overall difference in longevity was not statistically significant , compomer was replaced significantly more frequently owing to recurrent caries , and composite restorations required seven times as many repairs as did amalgam restorations . CLINICAL IMPLICATION S Compomer/composite restorations on posterior tooth surfaces in children may require replacement or repair at higher rates than amalgam restorations , even within five years of placement OBJECTIVES The replacement of an old amalgam Class II restoration is a common treatment and will remain so for decades . In addition to effectiveness , possible adverse health effects and esthetics , the costs of the treatment options will play a role in the choice of material . The aim of this study was to yield information on the relative cost-effectiveness of the use of composite resins and amalgam for the rerestoration of amalgam Class II restorations . METHODS As part of a larger r and omized clinical trial , treatment effectiveness and treatment costs were estimated in 73 composite and amalgam Class II posterior re-restorations . The main treatment outcome was longevity . Secondary outcomes included need of repair and quality of the margin while in situ . Costs were analyzed from the perspective of dentistry , assuming a treatment strategy aim ed at offering ' value for money ' . From this perspective , differential costs were based on personnel costs as approximated by treatment time . RESULTS Replacing an amalgam Class II restoration with amalgam is associated with lower costs than replacing with a composite resin . A sensitivity analysis , considering type of composite , increasing proficiency with the material , and time needed for future removal of material , demonstrated that these differences are fairly robust . The material s performed equally well for the first 5 years after placement with respect to longevity . Differences in secondary outcomes were minor and not all in favor of the same material . CONCLUSIONS It is tentatively concluded that amalgams are more cost-effective than composites for replacing existing Class II amalgam restorations The rates of abrasion of six composite restorative resins , an unfilled resin , a dental amalgam , two experimental formulations of commercially available composites , and two coating material s were determined with use of a two-body abrasion test . The wear of composite restorative resins , coating material s , and a dental amalgam was evaluated by a two-body abrasion test . Commercial composite resins were ranked . The rate of abrasion of the dental amalgam was similar to that of the composites but less than that of a commercial unfilled resin . The coating material s were abraded more rapidly than the composites . An experimental composite resin containing quartz was abraded less rapidly than one containing lithium aluminum silicate and barium aluminum silicate . This study evaluates the wear of composite restorative resins by an abrasion test . Composite restorative resins , an unfilled resin , and a dental amalgam are ranked . Two experimental formulations , one the resin matrix of a composite material and the other the resin matrix and inorganic filler without a silane coupling agent , are compared for each of two commercial composite restorative material s. Finally , the abrasion resistance of two commercial coating ( glazing ) material s is evaluated n a multicentre clinical trial consisting of 12 centres , 232 amalgam and 932 composite Class I and Class II restorations were placed in 447 adult patients . At the 4-year review 76 per cent of patients with 71 per cent of the restorations were retrieved . In 8 centres after 4 years and 4 centres after 5 years a total of 12 amalgam and 92 Occlusin restorations had been replaced , having been considered to have failed . The reasons for failure were classified into three types : Type 1 , related to the restoration ( loss of material , recurrent caries and unacceptable marginal adaptation ) ; Type 2 , related to the restorative process ( pulpal involvement , primary caries , tooth fracture and unacceptable contact ) and Type 3 , caused by external factors . A greater proportion of the restorations of Occlusin were replaced than the restorations of amalgam . For the restorations of Occlusin the reasons for failure were : Type 1 , 59 per cent ; Type 2 , 32 per cent and Type 3 , 9 per cent . Loss of material and recurrent caries accounted for the failure of 35 and 13 restorations of Occlusin respectively . The main Type 2 reasons for failure of the restorations of Occlusin were pulpal involvement ( 16 restorations ) and primary caries ( 9 restorations ) . The overall 4-year survival of Occlusin restorations relative to Type 1 and to Type 1 + Type 2 reasons for failure was 96 per cent and 93 per cent respectively . The centre was found to have a significant influence on the survival rate in both analyses PURPOSE This paper reports the 5-year performance of the restorations of the high-copper content dental amalgam alloys included in the worldwide programme of clinical trials of Occlusin , including unique data on wear . METHODS The methods employed are common to those previously reported for the multi clinical evaluation of Occlusin . Analysis of the data is limited to simple statistical procedures . RESULTS The findings lend support to existing knowledge concerning the favourable performance of restorations of high-copper content dental amalgam alloys , notably in relation to restorations in moderate- to large-sized Class II preparations in permanent molar teeth . Analysis of the data sheds new light on the influences of variables , including type of tooth restored , size and class of restoration and the presence or absence of occlusal contact(s ) on performance . CONCLUSION Conclusions are drawn regarding ways in which protocol s for future evaluations of the type reported should be exp and ed , and , together with suggestions for further work , it is concluded that this paper is a timely reminder of the value of existing dental amalgam alloys BACKGROUND Failure of dental restorations is a major concern in dental practice . Replacement of failed restorations constitutes the majority of operative work . Clinicians should be aware of the longevity of , and likely reasons for the failure of , direct posterior restorations . In a long-term , r and omized clinical trial , the authors compared the longevity of amalgam and composite . SUBJECTS , METHODS AND MATERIAL S : The authors r and omly assigned one-half of the 472 subjects , whose age ranged from 8 through 12 years , to receive amalgam restorations in posterior teeth and the other one-half to receive resin-based composite restorations . Study dentists saw subjects annually to conduct follow-up oral examinations and take bitewing radiographs . Restorations needing replacement were failures . The dentists recorded differential reasons for restoration failure . RESULTS Subjects received a total of 1,748 restorations at baseline , which the authors followed for up to seven years . Overall , 10.1 percent of the baseline restorations failed . The survival rate of the amalgam restorations was 94.4 percent ; that of composite restorations was 85.5 percent . Annual failure rates ranged from 0.16 to 2.83 percent for amalgam restorations and from 0.94 to 9.43 percent for composite restorations . Secondary caries was the main reason for failure in both material s. Risk of secondary caries was 3.5 times greater in the composite group . CONCLUSION Amalgam restorations performed better than did composite restorations . The difference in performance was accentuated in large restorations and in those with more than three surfaces involved . CLINICAL IMPLICATION S Use of amalgam appears to be preferable to use of composites in multisurface restorations of large posterior teeth if longevity is the primary criterion in material selection The management of occlusal caries in permanent molars . A clinical trial comparing a minimal composite restoration with an occlusal amalgam OBJECTIVE The long-term clinical performance of three posterior resin composites and two amalgams was assessed . METHOD AND MATERIAL S Thirty Class II restorations each of P-30 , Occlusin , Clearfil Posterior ( composites ) , New True Dentalloy , and Solila Nova ( amalgams ) were placed . Review s took place at 6 months and at 1 , 2 , 3 , 4 , 5 , and 10 years . At each visit the gingival condition , the contact point status , and the presence of ledges , gaps , or recurrent caries were assessed . The color match , cavosurface marginal stain , general surface stain , tarnish , and corrosion were also scored where applicable . Epoxy resin replicas were used to measure the maximum depth of wear . RESULTS After 10 years , there had been corrosion of both the high- and low-copper amalgams and a slight deterioration in color match of a number of composite restorations . Eighteen ( of 20 ) Occlusin restorations had obvious cavosurface marginal stain , attributed to staining of the unfilled bonding resin layer . Statistical analysis indicated that New True Dentalloy , Solila Nova , and Clearfil-P exhibited significantly less wear than Occlusin and P-30 . None of the restorations examined at the 10-year recall required replacement . CONCLUSION The five material s , placed in a dental school environment , provided adequate clinical service for 10 years Five-year results from four centres of the multicentre clinical trial of the posterior composite Occlusin are reported . Data is presented in respect of 256 restorations of Occlusin and 69 restorations of a conventional lathe cut amalgam . It is concluded that more than 90 per cent of the restorations under investigation should be rated as clinical ly acceptable after five years in clinical service , that the wear resistance of the restorations of Occlusin , as assessed by the clinicians , was similar in preparations of different sizes and to that of the amalgam controls , and that similar clinical results were obtained irrespective of the technique used to achieve moisture isolation Prospect i ve clinical studies comparing the results of different types of restorations of endodontically treated teeth are lacking . This study compared the clinical success rate of endodontically treated premolars restored with fiber posts and direct composite to the restorations of premolars using amalgam . Premolars with Class II carious lesions were selected and r and omly assigned to one of two experimental groups : ( 1 ) restoration with amalgam or ( 2 ) restoration with fiber posts and composite . One hundred and nine teeth were included in Group 1 and 110 in Group 2 . Patients were recalled after 1 , 3 and 5 years . No statistically significant difference was found between the proportion of failed teeth in the two experimental groups . Significant differences were observed between the proportion of root fractures ( p=0.029 ) and caries ( p=0.047 ) , with more root fractures and less caries observed in the teeth restored with amalgam at the five-year recall . Within the limits of this study , it can be concluded that restorations with fiber posts and composite were found to be more effective than amalgam in preventing root fractures but less effective in preventing secondary caries 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 Dental amalgam is a widely used restorative material containing 50 percent elemental mercury that emits mercury vapor . No r and omized clinical trials have determined whether there are adverse immunological effects associated with this low-level mercury exposure in children . The objective of this study was to evaluate a sub population of the participants in the New Engl and Children 's Amalgam Trial for in vitro manifestations of immunotoxic effects of dental amalgam . METHODS The authors conducted a r and omized clinical trial in which children requiring dental restorative treatment were r and omly assigned to receive either amalgam for posterior restorations or resin-based composite restorations . They assessed 66 children , aged 6 to 10 years , for total white blood cell counts , specific lymphocyte ( T-cell and B-cell ) counts and lymphocyte , neutrophil and monocyte responsiveness across a five-year period . Because of the small number of participants , the authors acknowledge that the study is exploratory in nature and has limited statistical power . RESULTS The mean number of tooth surfaces restored during the five-year period was 7.8 for the amalgam group and 10.1 for the composite group . In the amalgam group , there was a slight , but not statistically significant , decline in responsiveness of T cells and monocytes at five to seven days after treatment ; the authors consistently observed no differences at six , 12 or 60 months . CONCLUSIONS The findings of this study confirm that treatment of children with amalgam restorations leads to increased , albeit low-level , exposure to mercury . In this exploratory analysis of immune function , amalgam exposure did not cause overt immune deficits , although small transient effects were observed five to seven days after restoration placement . CLINICAL IMPLICATION S These findings suggest that immunotoxic effects of amalgam restorations are minimal and transient in children and most likely do not need to be of concern to practitioners considering the use of this restorative dental material A clinical trial comparing the efficacy of an occlusal amalgam restoration with a minimal composite restoration and fissure sealant in the management of occlusal caries in young patients has been performed . One hundred and fifty pairs of restorations were placed in 103 patients and assessed during the 5-year follow-up period . Nineteen restorations failed during this period : 11 amalgam and 8 minimal composite . There was some deterioration in anatomical form and marginal integrity of the remaining amalgam restorations . Of the remaining minimal composites , seven suffered clinical ly detectable wear and a further five had some marginal staining . Forty-nine of the minimal composites needed to have repairs to the fissure sealant . The amalgam restorations occupied , on average , 25 % of the occlusal surface of the tooth , compared with 5 % for the minimal composite resin . The results after a 5-year follow-up showed no significant difference in median survival times between the amalgam and the minimal composite |
1,786 | 25,176,576 | For the treatment of locally advanced HNSCC , platinum-based CTRT is associated with a better OS and PFS compared to RT+CET , and this is probably attributed to improved locoregional disease control . | The combinations of radiotherapy ( RT ) plus chemotherapy ( CTRT ) with cisplatin or , alternatively , RT plus cetuximab ( RT+CET ) , are the treatments of choice for locally advanced squamous cell carcinoma of the head and neck ( HNSCC ) .
We performed a systematic review and meta- analysis of published studies reporting the efficacy of these 2 combined modality therapies for the treatment of locoregionally advanced HNSCC . | Background Human papillomavirus (HPV)-related head and neck cancer has been associated with an improved prognosis in patients treated with radiotherapy ( RT ) + /− chemotherapy ( CT ) ; however , RT combined with epidermal growth factor receptor ( EGFR ) inhibitors has not been fully studied in this group of patients . Methods Immunohistochemical expression of p16 and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 108 stage III/IV head and neck cancer patients treated with RT+CT ( 56 ) or RT+EGFR inhibitors ( 52 ) . Disease-free survival ( DFS ) and overall survival ( OS ) were analyzed by the Kaplan-Meier method . Results DNA of HPV16 was found in 12 of 108 tumors ( 11 % ) and p16 positivity in 18 tumors ( 17 % ) , with similar rates in both arms of treatment . After a median follow-up time of 35 months ( range 6–135 ) , p16-positive patients treated with RT+EGFR inhibitors showed improved survival compared with those treated with RT+CT ( 2-year OS 88 % vs. 60 % , HR 0.18 ; 95 % CI 0.04 to 0.88 ; p = 0.01 ; and 2-year DFS 75 % vs. 47 % , HR 0.17 ; 95 % CI 0.03 to 0.8 ; p = 0.01 ) . However , no differences were observed in p16-negative patients ( 2-year OS 56 % vs. 53 % , HR 0.97 ; 95 % CI 0.55 to 1.7 ; p = 0.9 ; and 2-year DFS 43 % vs. 45 % , HR 0.99 ; 95 % CI 0.57 to 1.7 ; p = 0.9 ) . Conclusions This is the first study to show that p16-positive patients may benefit more from RT+EGFR inhibitors than conventional RT+CT . These results are hypothesis-generating and should be confirmed in prospect i ve trials BACKGROUND We conducted a multinational , r and omized study to compare radiotherapy alone with radiotherapy plus cetuximab , a monoclonal antibody against the epidermal growth factor receptor , in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck . METHODS Patients with locoregionally advanced head and neck cancer were r and omly assigned to treatment with high-dose radiotherapy alone ( 213 patients ) or high-dose radiotherapy plus weekly cetuximab ( 211 patients ) at an initial dose of 400 mg per square meter of body-surface area , followed by 250 mg per square meter weekly for the duration of radiotherapy . The primary end point was the duration of control of locoregional disease ; secondary end points were overall survival , progression-free survival , the response rate , and safety . RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone ( hazard ratio for locoregional progression or death , 0.68 ; P=0.005 ) . With a median follow-up of 54.0 months , the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone ( hazard ratio for death , 0.74 ; P=0.03 ) . Radiotherapy plus cetuximab significantly prolonged progression-free survival ( hazard ratio for disease progression or death , 0.70 ; P=0.006 ) . With the exception of acneiform rash and infusion reactions , the incidence of grade 3 or greater toxic effects , including mucositis , did not differ significantly between the two groups . CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck . ( Clinical Trials.gov number , NCT00004227 . BACKGROUND The phase III EXTREME and CRYSTAL studies demonstrated that the addition of cetuximab to chemotherapy significantly improved survival in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck ( SCCHN ) and KRAS wild-type metastatic colorectal cancer ( mCRC ) . In advanced non-small-cell lung cancer ( NSCLC ) , high EGFR expression was identified as a tumour biomarker that can predict survival benefit associated with the addition of cetuximab to first-line chemotherapy . We investigated whether tumour EGFR expression level was predictive of cetuximab benefit in EXTREME and CRYSTAL study patients . METHODS Prospect ively collected tumour immunohistochemistry data were used to generate an EGFR immunohistochemistry score ( scale 1 - 300 ) for patients in the EXTREME and CRYSTAL studies . For each study , the association between tumour immunohistochemistry score and cetuximab benefit was investigated . The EXTREME and CRYSTAL studies are registered with Clinical Trials.gov , numbers NCT00122460 and NCT00154102 , respectively . FINDINGS Tumour EGFR immunohistochemistry data were available for 411 of 442 ( 93 % ) patients from the EXTREME study intention-to-treat ( ITT ) population and 664 of 666 ( 100 % ) patients from the ITT population of the CRYSTAL study with EGFR-expressing , KRAS wild-type disease . The distribution of immunohistochemistry scores was similar between the treatment arms of each study , but differed between studies . A clinical ly relevant benefit for progression-free and overall survival associated with the addition of cetuximab to chemotherapy was seen across the full score range in EXTREME study patients . Similarly , CRYSTAL study patients derived a clinical benefit across the full score range , with no meaningful association between EGFR expression level and benefit . INTERPRETATION The addition of cetuximab to chemotherapy improved survival in the first-line treatment of recurrent/metastatic SCCHN and KRAS wild-type mCRC regardless of tumour EGFR expression level , indicating that in contrast to findings in NSCLC , EGFR expression level is not a clinical ly useful predictive biomarker in these setting 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 . ) BACKGROUND Concomitant chemoradiotherapy ( CT/RT ) is the st and ard treatment of locally advanced squamous cell carcinoma of the head and neck ( SCCHN ) . We evaluated the efficacy of induction docetaxel ( Taxotere ) , cisplatin , and 5-fluorouracil ( TPF ) before CT/RT versus CT/RT alone . PATIENTS AND METHODS Patients with stage III-IVM0 SCCHN , Eastern Cooperative Oncology Group performance status of zero to one , were r and omly assigned to receive CT/RT alone ( arm A : two cycles of cisplatin 20 mg/m(2 ) , days1 - 4 , plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion , during weeks 1 and 6 of radiotherapy ) or three cycles of TPF ( arm B : docetaxel 75 mg/m(2 ) and cisplatin 80 mg/m(2 ) , day 1 , and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion , every 3 weeks ) followed by the same CT/RT . The primary end point was the rate of radiologic complete response ( CR ) at 6 - 8 weeks after the end of CT/RT . RESULTS A total of 101 patients were r and omly allocated to the study ( 51 arm A ; 50 arm B ) . CR rates were 21.2 % ( arm A ) versus 50 % ( arm B ) . Median progression-free survival and overall survival were , respectively , 19.7 and 33.3 months ( arm A ) and 30.4 and 39.6 months ( arm B ) . Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms . CONCLUSION Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility PURPOSE To compare the efficacy and safety of induction chemotherapy ( ICT ) followed by chemoradiotherapy ( CRT ) or bioradiotherapy ( BRT ) for larynx preservation ( LP ) . PATIENTS AND METHODS Previously untreated patients with stage III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT-docetaxel and cisplatin 75 mg/m(2 ) each on day 1 and fluorouracil 750 mg/m(2 ) per day on days 1 through 5 . Poor responders ( < 50 % response ) underwent salvage surgery . Responders ( ≥ 50 % response ) were r and omly assigned to conventional radiotherapy ( RT ; 70 Gy ) with concurrent cisplatin 100 mg/m(2 ) per day on days 1 , 22 , and 43 of RT ( arm A ) or concurrent cetuximab 400 mg/m(2 ) loading dose and 250 mg/m(2 ) per week during RT ( arm B ) . Primary end point was LP at 3 months . Secondary end points were larynx function preservation ( LFP ) and overall survival ( OS ) at 18 months . RESULTS Of the 153 enrolled patients , 116 were r and omly assigned after ICT ( 60 , arm A ; 56 , arm B ) . Overall toxicity of both CRT and BRT was substantial following ICT . However , treatment compliance was higher in the BRT arm . In an intent-to-treat analysis , there was no significant difference in LP at 3 months between arms A and B ( 95 % and 93 % , respectively ) , LFP ( 87 % and 82 % , respectively ) , and OS at 18 months ( 92 % and 89 % , respectively ) . There were fewer local treatment failures in arm A than in arm B ; salvage surgery was feasible in arm B only . CONCLUSION There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone ( French Groupe Oncologie Radiothérapie Tête et Cou [ GORTEC ] 2000 - 01 trial [ Induction CT by Cisplatin , 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma ] ) . The protocol that can best compare with RT alone after ICT is still to be determined BACKGROUND The relative efficacy of the addition of induction chemotherapy to chemoradiotherapy compared with chemoradiotherapy alone for patients with head and neck cancer is unclear . The PARADIGM study is a multicentre open-label phase 3 study comparing the use of docetaxel , cisplatin , and fluorouracil ( TPF ) induction chemotherapy followed by concurrent chemoradiotherapy with cisplatin-based concurrent chemoradiotherapy alone in patients with locally advanced head and neck cancer . METHODS Adult patients with previously untreated , non-metastatic , newly diagnosed head and neck cancer were eligible . Patients were eligible if their tumour was either unresectable or of low surgical curability on the basis of advanced tumour stage ( 3 or 4 ) or regional-node stage ( 2 or 3 , except T1N2 ) , or if they were a c and i date for organ preservation . Patients were r and omly assigned ( in a 1:1 ratio ) to receive either induction chemotherapy with three cycles of TPF followed by concurrent chemoradiotherapy with either docetaxel or carboplatin or concurrent chemoradiotherapy alone with two cycles of bolus cisplatin . A computer-generated r and omisation schedule using minimisation was prepared and the treatment assignment was done central ly at one of the study sites . Patients , study staff , and investigators were not masked to group assignment . Stratification factors were WHO performance status , primary disease site , and stage . The primary endpoint was overall survival . Analysis was by intention to treat . Patient accrual was terminated in December , 2008 , because of slow enrolment . The trial is registered with Clinical Trials.gov , number NCT00095875 . FINDINGS Between Aug 24 , 2004 , and Dec 29 , 2008 , we enrolled 145 patients across 16 sites . After a median follow-up of 49 months ( IQR 39 - 63 ) , 41 patients had died-20 in the induction chemotherapy followed by chemoradiotherapy group and 21 in the chemoradiotherapy alone group . 3-year overall survival was 73 % ( 95 % CI 60 - 82 ) in the induction therapy followed by chemoradiotherapy group and 78 % ( 66 - 86 ) in the chemoradiotherapy alone group ( hazard ratio 1·09 , 95 % CI 0·59 - 2·03 ; p=0·77 ) . More patients had febrile neutropenia in the induction chemotherapy followed by chemoradiotherapy group ( 16 patients ) than in the chemoradiotherapy alone group ( one patient ) . INTERPRETATION Although survival results were good in both groups there was no difference noted between those patients treated with induction chemotherapy followed by chemoradiotherapy and those who received chemoradiotherapy alone . We can not rule out the possibility of a difference in survival going undetected due to early termination of the trial . Clinicians should still use their best judgment , based on the available data , in the decision of how to best treat patients . The addition of induction chemotherapy remains an appropriate approach for advanced disease with high risk for local or distant failure . FUNDING Sanofi-Aventis BACKGROUND Induction chemotherapy with cisplatin plus fluorouracil followed by radiotherapy is the st and ard alternative to total laryngectomy for patients with locally advanced laryngeal cancer . The value of adding chemotherapy to radiotherapy and the optimal timing of chemotherapy are unknown . METHODS We r and omly assigned patients with locally advanced cancer of the larynx to one of three treatments : induction cisplatin plus fluorouracil followed by radiotherapy , radiotherapy with concurrent administration of cisplatin , or radiotherapy alone . The primary end point was preservation of the larynx . RESULTS A total of 547 patients were r and omly assigned to one of the three study groups . The median follow-up period was 3.8 years . At two years , the proportion of patients who had an intact larynx after radiotherapy with concurrent cisplatin ( 88 percent ) differed significantly from the proportions in the groups given induction chemotherapy followed by radiotherapy ( 75 percent , P=0.005 ) or radiotherapy alone ( 70 percent , P<0.001 ) . The rate of locoregional control was also significantly better with radiotherapy and concurrent cisplatin ( 78 percent , vs. 61 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 56 percent with radiotherapy alone ) . Both of the chemotherapy-based regimens suppressed distant metastases and result ed in better disease-free survival than radiotherapy alone . However , overall survival rates were similar in all three groups . The rate of high- grade toxic effects was greater with the chemotherapy-based regimens ( 81 percent with induction cisplatin plus fluorouracil followed by radiotherapy and 82 percent with radiotherapy with concurrent cisplatin , vs. 61 percent with radiotherapy alone ) . The mucosal toxicity of concurrent radiotherapy and cisplatin was nearly twice as frequent as the mucosal toxicity of the other two treatments during radiotherapy . CONCLUSIONS In patients with laryngeal cancer , radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for laryngeal preservation and locoregional control e17030 Background : Concurrent chemoradiation of LAHNC with cetuximab or cisplatin improves survival . The purpose of this study is to compare cetuximab chemoradiation ( ExRT ) with cisplatin chemoradiation ( ChRT ) in patients treated with IMRT . METHODS Between January 2005 and August 2008 , 24 patients with LAHNC were treated with definitive chemoradiation utilizing IMRT . ExRT was reserved for those whose age or comorbidities precluded ChRT . 15 patients were treated with ChRT and 9 patients were treated with ExRT . Patient charts and Tumor Registry data were review ed for acute and late toxicity and for local/regional failure ( LRF ) , distant metastases and death . RESULTS The ExRT cohort was significantly older ( median age 71 vs 58 , p=0.005 ) and had more larynx/hypopharynx primaries ( 44 % vs 27 % ) . The cohorts were otherwise balanced with respect to T- and N-stage . Median follow-up for the ExRT and ChRT cohorts was 11 and 12 months , respectively . Overall treatment time in compliant patients was lower in ExRT patients ( 46 vs 50 days , p=0.05 ) , reflecting increased use of accelerated radiation fractionation ( 66 % vs 40 % ) . See Table for toxicity outcomes . There was a trend toward increased ≥G3 acute mucositis in the ExRT group ( p=0.07 ) . However , there was less weight loss ( p=0.05 ) . There were similar acute epidermitis and hospitalizations for malnutrition/hydration rates and a nonsignificant decrease in prolonged mucosal toxicity . 1 patient developed skin necrosis and another osteoradionecrosis in the ChRT group . 1-year freedom from LRF was 89 % in the ChRT group vs 56 % in the ExRT group ( p=0.07 ) . Overall survival ( OS ) at 1 year was 100 % ( ChRT ) vs 88 % ( ExRT ) . CONCLUSIONS ExRT showed a trend toward worse acute mucosal toxicity but not late toxicity despite increased rates of altered fractionation with a higher daily dose . ExRT was associated with worse LRC and OS . A r and omized study would best compare outcomes and toxicity profiles . Until such analysis , cetuximab should be reserved for patients unable to tolerate ChRT . [ Table : see text ] No significant financial relationships to disclose PURPOSE To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91 - 11 study evaluating the contribution of chemotherapy added to radiation therapy ( RT ) for larynx preservation . PATIENTS AND METHODS Patients with stage III or IV glottic or supraglottic squamous cell cancer were r and omly assigned to induction cisplatin/fluorouracil ( PF ) followed by RT ( control arm ) , concomitant cisplatin/RT , or RT alone . The composite end point of laryngectomy-free survival ( LFS ) was the primary end point . RESULTS Five hundred twenty patients were analyzed . Median follow-up for surviving patients is 10.8 years . Both chemotherapy regimens significantly improved LFS compared with RT alone ( induction chemotherapy v RT alone : hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.59 to 0.95 ; P = .02 ; concomitant chemotherapy v RT alone : HR , 0.78 ; 95 % CI , 0.78 to 0.98 ; P = .03 ) . Overall survival did not differ significantly , although there was a possibility of worse outcome with concomitant relative to induction chemotherapy ( HR , 1.25 ; 95 % CI , 0.98 to 1.61 ; P = .08 ) . Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT ( HR , 0.58 ; 95 % CI , 0.37 to 0.89 ; P = .0050 ) and over RT alone ( P < .001 ) , whereas induction PF followed by RT was not better than treatment with RT alone ( HR , 1.26 ; 95 % CI , 0.88 to 1.82 ; P = .35 ) . No difference in late effects was detected , but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy ( 30.8 % v 20.8 % with induction chemotherapy and 16.9 % with RT alone ) . CONCLUSION These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS . Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone . New strategies that improve organ preservation and function with less morbidity are needed BACKGROUND Previous results from our phase 3 r and omised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck ( LASCCHN ) at 3 years . Here we report the 5-year survival data , and investigate the relation between cetuximab-induced rash and survival . METHODS Patients with LASCCHN of the oropharynx , hypopharynx , or larynx with measurable disease were r and omly allocated in a 1:1 ratio to receive either comprehensive head and neck radiotherapy alone for 6 - 7 weeks or radiotherapy plus weekly doses of cetuximab : 400 mg/m(2 ) initial dose , followed by seven weekly doses at 250 mg/m(2 ) . R and omisation was done with an adaptive minimisation technique to balance assignments across stratification factors of Karnofsky performance score , T stage , N stage , and radiation fractionation . The trial was un-blinded . The primary endpoint was locoregional control , with a secondary endpoint of survival . Following discussion s with the US Food and Drug Administration , the data set was locked , except for queries to the sites about overall survival , before our previous report in 2006 , so that an independent review could be done . Analyses were done on an intention-to-treat basis . Following completion of treatment , patients underwent physical examination and radiographic imaging every 4 months for 2 years , and then every 6 months thereafter . The trial is registered at www . Clinical Trials.gov , number NCT00004227 . FINDINGS Patients were r and omly assigned to receive radiotherapy with ( n=211 ) or without ( n=213 ) cetuximab , and all patients were followed for survival . Up date d median overall survival for patients treated with cetuximab and radiotherapy was 49.0 months ( 95 % CI 32.8 - 69.5 ) versus 29.3 months ( 20.6 - 41.4 ) in the radiotherapy-alone group ( hazard ratio [ HR ] 0.73 , 95 % CI 0.56 - 0.95 ; p=0.018 ) . 5-year overall survival was 45.6 % in the cetuximab-plus-radiotherapy group and 36.4 % in the radiotherapy-alone group . Additionally , for the patients treated with cetuximab , overall survival was significantly improved in those who experienced an acneiform rash of at least grade 2 severity compared with patients with no rash or grade 1 rash ( HR 0.49 , 0.34 - 0.72 ; p=0.002 ) . INTERPRETATION For patients with LASCCHN , cetuximab plus radiotherapy significantly improves overall survival at 5 years compared with radiotherapy alone , confirming cetuximab plus radiotherapy as an important treatment option in this group of patients . Cetuximab-treated patients with prominent cetuximab-induced rash ( grade 2 or above ) have better survival than patients with no or grade 1 rash . FUNDING ImClone Systems , Merck KGaA , and Bristol-Myers Squibb |
1,787 | 10,094,063 | Communication services were present most often in systems integrated with electronic medical records . | In this systematic review , the authors analyze the functionality provided by recent computer-based guideline implementation systems and characterize the effectiveness of the systems . | OBJECTIVE To study the effect of a computerized medical record and other practice factors on the delivery of preventive health care . DESIGN Prospect i ve , controlled trial . SETTING University general internal medicine teaching clinic . PARTICIPANTS Forty-five internal medicine residents and their 4 supervising attending physicians . INTERVENTION The study group used a computerized ambulatory medical record system that included health care maintenance reminders . The control group used a conventional paper record with a health care maintenance flow sheet . MEASUREMENTS AND MAIN RESULTS The computer reminders significantly increased health care maintenance recommendations made to patients for proctosigmoidoscopy , tetanus vaccination , influenza vaccination , and pneumococcal vaccination , but not for fecal occult blood testing , mammography , Pap smears , or serum thyroxine screening in the elderly . First-year residents were nearly twice as successful as third-year residents in overall health care maintenance . Success scores varied markedly depending on which attending physician was supervising the residents . We found a strong interaction among group assignment , supervising attending , and level of training such that the reminders doubled success scores among first-year residents supervised by two of the attending physicians but had little effect on other subgroups . The time of year and the format of the reminder also had important effects for some of the maneuvers . CONCLUSIONS Although computerized medical records markedly improved the performance of prevention maneuvers by committed physicians , many physicians using computer systems failed to make use of the re source . The reasons for this were complex . Future work in this area should carefully control for personal behaviors and focus upon administrative changes that more effectively implement these potentially powerful tools Advance directives name a surrogate decision maker or provide written instructions with the intent of extending patient autonomy with respect to end-of-life decisions [ 1 - 3 ] . Supported on various grounds by the public [ 1 ] , physicians [ 4 ] , ethicists [ 5 ] , and legislators [ 6 ] , advance directives have also been promoted as a way to control the high costs of health care at the end of life [ 7 , 8 ] . Most patients are interested in establishing advance directives , but few actually complete them [ 1 , 9 , 10 ] . In 1990 , the U.S. Congress passed the Patient Self-Determination Act , which requires hospitals to inform admitted patients about their right to record advance directives [ 6 , 11 ] . The Act does not dictate who should initiate these discussion s ( patients , physicians , or an admissions officer , for example ) [ 12 , 13 ] . It is therefore not surprising that the Act has had little effect on the rate of completion of advance directives [ 11 , 13 - 15 ] . Because hospitalized patients are often acutely ill and lose their ability to make decisions [ 3 ] , it may be more appropriate to discuss such issues before hospitalization [ 12 , 16 , 17 ] . Other interventions aim ed at increasing the establishment of advance directives have met with mixed success [ 18 ] . With one exception [ 19 ] , patient education has had little or no effect [ 20 - 24 ] . More effective interventions have trained physicians , social workers , or counselors to discuss advance directives [ 18 , 22 , 25 - 27 ] ; this has led to the conclusion that counseling by a clinician is the best catalyst for the completion of advance directives [ 28 ] . However , little is known about how to educate and motivate clinicians to solicit advance directives [ 28 ] . We [ 29 - 31 ] and others [ 32 ] have previously shown that computer reminders increase physician compliance with practice guidelines . In this study , we tested the hypothesis that reminding primary care physicians to discuss advance directives would stimulate such discussion s and lead to the establishment of more advance directives . Methods Setting and Patients This study was approved by the institutional review board of Indiana University as expedited research with waiver of informed consent from both patients and physicians . It was conducted in the General Medicine Practice [ 31 ] , an academic primary care practice affiliated with an urban public teaching hospital . This practice is staffed by general internal medicine faculty , fellows , and residents . Each resident and fellow attends the General Medicine Practice one half-day per week ; faculty attend one to four half-days per week . Residents always practice with the same attending faculty physicians . All physicians , except for study investigators , were eligible to participate . At the time of this study , the General Medicine Practice comprised four separate practice s with separate waiting areas , clerks , and nurses . Each practice held eight half-day sessions per week . Each session was attended by two faculty members and two or three residents , each of whom provided primary care to assigned panels of patients . Residents were required to briefly discuss each patient with the attending faculty . Fellows served as faculty and were treated as such . Since 1981 , a computerized program has r and omly assigned new physicians to the practice sessions [ 31 ] . New patients have been sequentially assigned to open appointment slots ; this result ed in no important differences in patients or clinical practice among the sessions [ 29 , 33 ] . We included patients who were at risk for acute deterioration ( and therefore might benefit from advance directives ) because of advanced age ( 75 years , the typical threshold for the oldest old ) or because they were 50 years of age or older and had one of the following chronic conditions : cardiac ischemia , heart failure , chronic lung disease , cancer other than nonmelanomatous skin cancer , cerebrovascular disease , renal insufficiency , or cirrhosis . We chose 50 years of age as a cut-off to yield sufficient numbers of patients . A computer program identified eligible patients among those with scheduled appointments at the General Medicine Practice by using problem lists and test results stored in the Regenstrief Medical Record System [ 34 ] . Eligible patients who kept appointments at the General Medicine Practice were approached by research assistants in the waiting room . The research assistants , who were blinded at all times to the patients ' study groups , explained the study to the patients , invited them to participate , and interviewed those who agreed to participate ; patients from nursing homes and prisons and patients who were deaf or did not speak English were excluded . The assistants then administered the Pfeiffer Mental Status Question naire [ 35 ] ; patients whose scores indicated cognitive dysfunction were excluded . The remaining patients provided sociodemographic information and stated whether they had previously discussed or completed advance directives ; patients who had completed advance directives were excluded . Patients also stated their preferences with regard to six treatments in the event of a terminal illness [ 36 ] . Advance Directives Before the study , we created two separate forms for instruction directives and proxy directives ; these forms became the official advance directive documents of the hospital and its outpatient services . The instruction directive allowed patients to indicate whether , in the event of terminal illness and mental incapacity , they wanted or did not want eight types of care : cardiopulmonary resuscitation , mechanical ventilation , surgery , invasive procedures , nutrition and hydration , transfusion of blood or blood products , antibiotics , or noninvasive diagnostic tests . The primary care physician had to sign each completed instruction directive form to indicate that he or she was aware of its contents . The proxy directive design ated both primary and secondary health care representatives . We placed both advance directive forms in a drawer of the desk of each physician in the General Medicine Practice . We also placed the forms in a bin near the door of the staff room along with other forms and requisitions and business reply envelopes for patients who wanted to complete the forms at home . Research assistants entered the data from completed forms into the Regenstrief Medical Record System , where the forms were available for viewing through computer terminals and workstations in all inpatient and outpatient venues [ 34 ] . Before the study , the three physician-investigators presented the basic concepts of advance directives at gr and rounds . They also had face-to-face meetings with each physician in the General Medicine Practice and explained how to complete and process the forms . We encouraged physicians to discuss advance directives with their elderly and debilitated patients and posted flyers in each practice staffing room suggesting that physicians discuss advance directives with patients who had the target study conditions . Study Methods The intent of the r and omization scheme was to expose physicians to the same type of reminder or reminders , or no reminders , during all of their scheduled primary care visits with enrolled patients . At the time of this study , 32 weekly half-day sessions took place on the four General Medicine Practice practice s. Two sessions attended by study investigators were excluded . We r and omly assigned all of the physicians who worked in a particular half-day session to the same reminder category . At the time of r and omization , 16 physicians ( all of whom were faculty members ) practice d in more than 1 session per week ( 14 practice d in 2 sessions and 2 practice d in 3 sessions ) . Therefore , we r and omly assigned the sessions in a stepped manner by first allocating the 16 physicians and all of their associated sessions to four categories : control ( no reminders ) , computer-generated reminders for instruction directives , computer-generated reminders for proxy directives , and computer-generated reminders for both types of directives . We then r and omly assigned the remaining 8 sessions and their physicians to the four categories ( Table 1 ) . Each practice contained sessions in all four categories , which were equally distributed between mornings and afternoons . Table 1 . Results of R and omization All physicians routinely received computer-generated reminders for patients with scheduled visits . They were reminded to give preventive care , note abnormal test results , and avoid drug interactions [ 29 , 34 ] . These reminders appeared at the bottom of computer-generated printed encounter forms [ 34 ] ( Figure 1 ) . Physicians routinely review ed the encounter forms and the practice chart immediately before visiting the patient . As recommended by Litzelman and coworkers [ 37 ] , the advance directive reminders were followed by a choice list ( discussed today , next visit , not applicable , patient too ill , patient refuses to discuss , I disagree with advance directives ) . Instruction directives were called advance directives , and proxies were called health care representatives ( Figure 1 ) . Figure 1 . General Medicine Practice encounter form showing reminders for both types of advance directive . After patients were enrolled , research assistants attempted to interview them in the waiting room after each scheduled appointment to assess whether they had discussed advance directives with their physicians that day . Patients who answered yes were defined as having had an advance directive discussion . During the first scheduled General Medicine Practice visit in the 5-month period between 11 and 16 months after enrollment , a close-out interview was attempted . If no scheduled visit had occurred by 15 months after enrollment , the close-out interview was attempted by telephone . Form completion was defined as having occurred if either completed form was received between study enrollment and 30 days after the final interview ( this made it possible to receive by mail forms that were completed after the close-out BACKGROUND We compared the efficacy of a computer-generated prompt sheet placed on the front of patients ' charts with a patient-carried prompt card to remind physicians to perform selected health maintenance items . METHODS A r and omized prospect i ve single-blind study was performed in private practice offices in rural eastern North Carolina , with 28 family practitioners and nine general internists participating . Twenty-two physicians were r and omized to the computer prompt group and 22 to the card prompt group . Four physicians in the computer group did not complete the study because of computer software problems , and three physicians did not complete the study because their limited staff was unable to enter patient data into the computer . Before the intervention , 20 patient charts ( 10 males and 10 females ) from each physician were audited for the performance of influenza vaccinations , stool for occult blood , pap smears , breast examinations performed by the physicians , and mammograms . One year after the intervention was instituted , chart audits for the above five items were done again on 20 different patient charts for each physician . RESULTS There was a 7 % increase in the performance of influenza vaccinations in the card group ( 17 % vs 24 % ) compared with a 6 % increase in the computer group ( 20 % vs 26 % ) . There was a 5 % decrease in the performance of stool for occult blood in the card group ( 28 % vs 23 % ) compared with a 1 % increase in the computer group ( 30 % vs 31 % ) . There was an 11 % decrease in the performance of pap smears in the card group ( 26 % vs 15 % ) compared with a 3 % increase in the computer group ( 23 % vs 26 % ) . There was a 2 % decrease in the performance of breast examinations by the physician in the card group ( 35 % vs 33 % ) compared with a 3 % increase in the computer group ( 30 % vs 33 % ) . Finally , there was a 3 % increase in the performance of mammograms in the card group ( 22 % vs 25 % ) compared with an 11 % increase in the computer group ( 15 % vs 26 % ) . CONCLUSIONS Our data show a greater increase in performance of health maintenance items in the computer-prompted group . The performance of stool for occult blood , pap smears , breast examinations performed by the physician , and mammograms were increased more in the computer-prompted group than in the card group . However , there was not a statistically significant difference after intervention for any of the audited health maintenance items for either the computer group or the card group . Overall , health maintenance measures were performed in only a minority of appropriate patients Computers are steadily being incorporated in clinical practice . We conducted a nonr and omised , controlled , prospect i ve trial of electronic messages design ed to enhance adherence to clinical practice guidelines . We studied 126 physicians and nurse practitioners who used electronic medical records when caring for 349 patients with HIV infection in a primary care practice . We analysed the response times of clinicians to the situations that triggered alerts and reminders , the number of ambulatory visits , and hospitalisation . The median response times to 303 alerts in the intervention group and 388 alerts in the control group were 11 and 52 days ( p < 0.0001 ) , respectively . The median response time to 432 reminders in the intervention group was 114 days and that for 360 reminders in the control group was over 500 days ( p < 0.0001 ) . There was no effect on visits to the primary care practice . There was , however , a significant increase in the rate of visits outside the primary care practice ( p = 0.02 ) , which is explained by the increased frequency of visits to ophthalmologists . There were no differences in admission rates ( p = 0.47 ) , in admissions for pneumocystosis ( p = 0.09 ) , in visits to the emergency ward ( p = 0.24 ) , or in survival ( p = 0.19 ) . We conclude that the electronic medical record was effective in helping clinicians adhere to practice guidelines PURPOSE Clinical guidelines are design ed to assist in the management of specific diseases ; however , these guidelines are often neglected in the delivery of care . The purpose of this study was to determine whether clinician use of an clinical practice guideline would increase in response to having , at the patient visit , a decision support system based on a practice guideline that generates a customized management protocol for the individual patient using data from the patient 's electronic medical record . SUBJECTS AND METHODS In a 6-month controlled trial at a primary care clinic , 58 primary care clinicians were r and omized to receive either a special encounter form with the computer-generated guideline recommendations or a st and ard encounter form . The effect of computer-generated advice on clinician behavior was measured as rate of compliance with guideline recommendations . Data from 30 clinicians were analyzed ; data from 28 clinicians were excluded because these clinicians did not meet predefined criteria for minimum exposure to diabetic patient care . RESULTS Availability of patient management recommendations generated by the decision support system result ed in a two-fold increase in clinician compliance with care guidelines for diabetes mellitus ( P = 0.01 ) . Median compliance for the group receiving the recommendations was 32.0 % versus 15.6 % for the control group . CONCLUSION Decision support based on a clinical practice guideline is an effective tool for assisting clinicians in the management of diabetic patients . This decision support system provides a model for how a clinical practice guideline can be integrated into the care process by computer to assist clinicians in managing a specific disease through helping them comply with care st and ards . Use of decision support systems based on clinical practice guidelines could ultimately improve the quality of medical care CONTEXT While clinical guidelines are considered an important mechanism to improve the quality of medical care , problems with implementation may limit their effectiveness . Few empirical data exist about the effect of computer-based systems for application of clinical guidelines on quality of care . OBJECTIVE To determine whether real-time presentation of clinical guidelines using an electronic medical record can increase compliance with guidelines . DESIGN Prospect i ve off-on-off , interrupted time series with intent-to-treat analysis . SETTING University hospital emergency department . SUBJECTS Patients were 280 health care workers ( 50 in the baseline control phase , 156 in the intervention phase , and 74 in the postintervention control phase ) who presented for initial treatment of occupational body fluid exposures , including 89 % ( 248/280 ) who sustained punctures and 81 % ( 208/257 ) who were exposed to blood . Physicians included resident physicians and attending physicians working in the emergency department during the study . INTERVENTIONS Implementation of a computer charting system that provides real-time information regarding history and recommendations for laboratory testing , treatment , and disposition based on rules derived from clinical guidelines . MAIN OUTCOME MEASURES Quality of care as determined by essential items documented in the medical record and in aftercare instructions , compliance with testing and treatment guidelines , and total charges and percentage of charges attributable to guideline -endorsed activities . RESULTS Mean percent documentation of 7 essential items regarding patient history in the medical record increased from 57 % during the baseline period to 98 % in the intervention phase ( 42 % increase ; 95 % confidence interval [ CI ] , 34%-49 % ) and 11 items in aftercare instruction increased from 31 % at baseline to 93 % during the intervention phase ( 62 % increase ; 95 % CI , 51%-74 % ) , but both decreased to baseline when the computer system was removed . Percent compliance with 4 laboratory testing guidelines increased from 63 % at baseline to 83 % during the intervention phase ( 20 % increase ; 95 % CI , 9%-31 % ) but decreased to 52 % when the computer system was removed . Compliance with 5 treatment guidelines increased from 83 % at baseline to 96 % during the intervention phase ( 13 % increase ; 95 % CI , 9%-17 % ) and decreased to 84 % following the intervention . Percentage of charges incurred for indicated laboratory tests and treatment increased from 44 % at baseline to 81 % during the intervention phase ( 37 % increase ; 95 % CI , 22%-52 % ) and decreased to 36 % following the intervention . Average total per-patient charges were $ 460 , $ 384 , and $ 373 in each phase , respectively . CONCLUSIONS Use of a computer-based system for clinical guidelines for management of patients with occupational exposure to body fluids improved documentation , compliance with guidelines , and percentage of charges spent on indicated activities , while decreasing overall charges . The parameters returned to baseline when the computer system was removed Computerized reminder systems have been shown to be effective in improving physician compliance with preventive services guidelines . Very little has been published about the use of computerized reminders for preventive care in diabetes . We implemented a computer-generated reminder system for diabetes care guidelines in a r and omized controlled study in the outpatient clinics of 35 internal medicine residents at the University of Utah and Salt Lake Veterans Affairs Hospitals . After a six month study period , compliance with the recommended care significantly improved in both the intervention group that received patient-specific reminders about the guidelines ( 38.0 % at baseline , 54.9 % at follow-up ) and the control group that received a nonspecific report ( 34.6 % at baseline , 51.0 % at follow-up ) . There was no significant difference between the two groups . Both clinic sites showed similar improvement over baseline levels of compliance . Residents who completed encounter forms used by the system showed a significantly greater improvement in compliance than those who did not complete encounter forms ( 19.7 % vs. 7.6 % , p = 0.006 ) . The improvements in guideline compliance were seen in all areas of diabetes preventive care studied , and significant improvements were seen with recommended items from the medical history , physical exam , laboratory testing , referrals , and patient education . The use of encounter forms by the providers significantly improved documented compliance with the guidelines in almost all categories of preventive care . These results suggest that computerized reminder systems improve compliance with recommended care more by facilitating the documentation of clinical findings and the ordering of recommended procedures than by providing the clinician with patient-specific information about guideline compliance status . Further study is needed to underst and the implication s of these findings to the development of future computerized reminder systems for chronic diseases such as diabetes Aims —To assess changes in practice and outcome in acute upper gastrointestinal haemorrhage following the feedback of data , the reemphasis of national guidelines , and specific recommendations following an initial survey . Design —A prospect i ve , multicentre , audit cycle . Forty five hospitals from three health regions participed in two phases of the audit cycle . Patients —Phase I : 2332 patients with acute upper gastrointestinal haemorrhage ; phase II : 1625 patients with upper gastrointestinal haemorrhage . Methods — Patients were evaluated with respect to management ( with reference to the recommendations in the national guidelines ) , mortality , and length of hospital stay . Results —Following the distribution of data from the first phase of the National Audit and the formulation of specific recommendations for improving practice , the proportion of hospitals with local guidelines or protocol s for the management of upper gastrointestinal haemorrhage rose from 71 % ( 32/45 ) to 91 % ( 41/45 ) ; 12 of the 32 hospitals with guidelines during the first phase revised their guidelines following the initial survey . There was a small but significant increase in the proportion of all patients who underwent endoscopy ( from 81 % to 86 % ) , the proportion who underwent endoscopy within 24 hours of admission ( from 50 % to 56 % ) , and the use of central venous pressure monitoring in patients with organ failure requiring blood transfusion or those with profound shock ( from 30 % to 43 % ) . There was , however , no change in the use of high dependency beds or joint medical/surgical management in high risk cases . There was no significant change in crude or risk st and ardised mortality ( 13.4 % in the first phase and 14.4 % in the second phase ) . Conclusions —Although many of the participating hospitals have made efforts to improve practice by producing or updating guidelines or protocol s , there has been only a small demonstrable change in some areas of practice during the National Audit . The failure to detect any improvement in mortality may reflect this lack of change of practice , but may also reflect the fact that a large proportion of the deaths in this unselected study are not preventable ; only a very large study could hope to demonstrate a significant change out of the context of a clinical trial BACKGROUND Physician adherence to established practice st and ards has become an important national issue . Despite the proliferation of formal st and ards of practice , there is little evidence that the mere availability of guidelines results in changes in physician practice s. This paper presents the results of a study of the effectiveness of a computerized monitoring and notification system in increasing physician compliance with treatment guidelines . METHODS This study prospect ively compared medical staff practice s in two one-year periods utilizing a computer system which tabulated noncompliance and provided reminders . RESULTS Overall , there was a statistically-significant decrease in the number of alerts issued in year two compared to year one ; alerts were issued on 15 % vs 29 % of all patients ( P < .001 ) . The average number of alerts per patient decreased to .20 from .41 . CONCLUSIONS The study results indicate that a clinical decision support system such as that described can improve adherence to treatment guidelines We present the implementation of the indications for surgery for three surgical operations -- cholecystectomy , cataract extraction , and knee arthroscopy -- in a medical expert system , called Iliad . This implementation operates in the preauthorization service of IHC Health Plans ( an insurance company in Salt Lake City ) as a basis for reimbursement of services . Patient data collection forms , derived from Iliad knowledge base , were used by 13 participating surgeons to document the objective patient observations that justify the surgery and , then were faxed to IHC where a trained nurse input the data in Iliad . Iliad 's decisions and reports on any deviations from guidelines are communicated back to the care provider . The study evaluates the impact of the computerized implementation on process , as measured by a question naire , and on outcome as measured by rate of approvals , documentation level , rate of requests , and average cost . The prospect i ve implementation of the computerized guidelines has performed reliably , has been perceived as a preferred alternative to the old preauthorization system , and , most importantly , has enhanced significantly the level of documentation permitting evaluation and determination of appropriateness before surgery In a one-year r and omized controlled trial , we assessed the effectiveness of a computerized mammography reminder system as a component of a program to increase the use of screening mammography in three health care organizations serving inner-city women in Detroit , Michigan ( two sites of a health department , one HMO site , and two sites of a private hospital ) . Four thous and four hundred and one women older than 40 who had visited a study site in the preceding year were r and omly assigned to one of two treatment groups . Limited intervention ( LI ) included physician and staff breast cancer control education , facilitated mammography appointment scheduling procedures , and elimination of out-of-pocket patient cost for mammography ( at three of five sites ) . Full intervention ( FI ) included all components of limited intervention plus an additional series of " cues-to-action . " These included a mammography reminder form inserted in the medical record of women who were due to have mammography , intended to increase physician referral for mammography appointments , and patient reminders intended to increase completion of mammography among referred women . During the one-year intervention period 2,725 r and omized women visited a study site . The 6-month mammography appointment rates among FI women vary from 38 % to 65 % and the FI rate exceeds the LI rate at each site with differences from 13 % ( 95 % Cl , 6 to 20 ) to 29 % ( 21 to 38 ) . The annual completed mammography rate among FI women extends from 43 % to 64 % and exceeds the LI rate at each site by 12 % ( 5 to 19 ) to 25 % ( 16 to 34 ) . After age-adjustment , the mammography intervention effect sizes among the five sites were not significantly different . The average increase in FI compared to LI was 18 % . The computerized reminder system is effective in increasing the use of mammography in each of the study institutions and the major effect is on physician referral for mammography OBJECTIVES The authors conducted a r and omized controlled trial to evaluate the sustained effectiveness of a computerized reminder system in promoting mammography during a second year of continuing intervention at three primary care practice s of a Health Department and a health maintenance organization in Detroit , Michigan . METHODS Out-of-pocket mammography cost was eliminated for all participants ( limited intervention ) . Computer-generated reminders promoting physician referral for mammography were placed in the medical records of women due for mammography 1 month in advance of their due date ( full intervention ) . RESULTS Among 1,225 year 2 visitors , mammography rates were 44 % for full intervention versus 28 % for limited intervention at the health department ( adjusted odds ratio [ OR ] for effect of full intervention 1.84 ; 95 % confidence interval [ CI ] : 1.40 - 2.40 ) and 45 % for full versus 46 % for limited at the health maintenance organization ( adjusted OR 1.06 ; 95 % CI 0.80 - 1.42 ) . These second year results contrasted with those observed for year 1 , during which a significant effect of full intervention was demonstrated for both organizations . After controlling for patient characteristics and site , the effect sizes of full intervention were reduced significantly in the second year compared with the first year ( P = 0.05 ) . CONCLUSIONS The effect of computerized mammography reminders can be sustained in a second year of continued intervention , but individual practice sites and organizations vary in their responsiveness to the intervention . Strategies to promote periodic and repetitive procedure use must identify and address time-varying barriers to their effectiveness OBJECTIVES To study determinants and adverse outcomes ( mortality and rehospitalization ) of beta-blocker underuse in elderly patients with myocardial infa rct ion ; and whether the relative risks ( RRs ) of survival associated with beta-blocker use were comparable to those reported in the large r and omized controlled trials ( RCTs ) . SETTING New Jersey Medicare population . DESIGN Retrospective cohort design using linked Medicare and drug cl aims data from 1987 to 1992 . PATIENTS Statewide cohort of 5332 elderly 30-day acute myocardial infa rct ion ( AMI ) survivors with prescription drug coverage , of whom 3737 were eligible for beta-blockers . MAIN OUTCOME MEASURES beta-Blocker and calcium channel blocker use in the first 90 days after discharge and mortality rates and cardiac hospital readmissions over the 2-year period after discharge , controlling for sociodemographic and baseline risk variables . RESULTS Only 21 % of eligible patients received beta-blocker therapy ; this rate remained unchanged from 1987 to 1991 . Patients were almost 3 times more likely to receive a new prescription for a calcium channel blocker than for a new beta-blocker after their AMIs . Advanced age and calcium channel blocker use predicted underuse of beta-blockers . Controlling for other predictors of survival , the mortality rate among beta-blocker recipients was 43 % less than that for nonrecipients ( RR=0.57 ; 95 % confidence interval [ CI ] , 0.47 - 0.69 ) . Effects on mortality were substantial in all age strata ( 65 - 74 years , 75 - 84 years , and > or = 85 years ) and consistent with the results for elderly subgroups of 2 large RCTs . beta-Blocker recipients were rehospitalized 22 % less often than nonrecipients ( RR=0.78 ; 95 % CI , 0.67 - 0.90 ) . Use of a calcium channel blocker instead of a beta-blocker was associated with a doubled risk of death ( RR= 1.98 ; 95 % CI , 1.44 - 2.72 ) , not because calcium channel blockers had a demonstrable adverse effect , but because they were substitutes for beta-blockers . CONCLUSIONS beta-Blockers are underused in elderly AMI survivors , leading to measurable adverse outcomes . These data suggest that the survival benefits of beta-blockade after an AMI may extend to eligible patients older than 75 years , a group that has been excluded from RCTs Objective To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic . Design A r and omized trial . Setting The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System , Seattle Division . Patients / Participants Clinic providers were r and omized to a control group ( n=35 ) or intervention group ( n=36 ) . We targeted the providers of patients being treated for hypertension with calcium channel blockers , a class of drug not recommended for initial therapy . InterventionAn automated computer query identified eligible patients and their providers . A guideline reminder was placed in the charts of patients of intervention providers ; the charts of patients of control providers received no reminder . Measurements and main results During the 5-month study period , 346 patients were seen by the 36 primary care providers ( staff physicians , nurse practitioners , residents , and fellows ) in the intervention group , and 373 patients were seen by the 35 providers in the control group . Intervention providers changed 39 patients ( 11.3 % ) to other medications during the study period , compared with 1 patient ( < 1.0 % ) of control providers ( p<.0001 ) . For patients whose therapy was unchanged , providers noted angina in 23.1 % , indications other than those for hypertension in 9.5 % , intolerable adverse effects with first-line therapy in 13.9 % , and inadequte control with first-line therapy in 13.9 % . Of those patients without provider-indicated contraindications , 23.6 % were switched from calcium channel blockers to first-line agents during the intervention period . Conclusions The use of a computerized , clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general , and decreased the use of calcium channel blockers for the treatment of hypertension in particular |
1,788 | 28,007,033 | Conclusions Even though effects were small , our results provide indications that intraoperative suggestions can have the potential to reduce the need for medication and enhance recovery . | Background General anesthesia does not block central nervous processing of auditive information .
Therefore , positive suggestions even given during surgery might have the potential to encourage well-being and recovery of patients .
Aim of this review was to summarize the evidence on the efficacy of therapeutic suggestions under general anesthesia in adults undergoing surgery compared to an attention control ( i.e. white noise ) . | There have been cl aims that the postoperative course of patients may be improved by presentation during general anesthesia of therapeutic suggestions which predict a rapid and comfortable postoperative recovery . This study evaluated the effectiveness of such therapeutic suggestions under double-blind and r and omized conditions . A tape recording predicting a smooth recovery during a short postoperative stay without pain , nausea , or vomiting was played during anesthesia to about half the patients ( N = 109 ) , while the remaining , control patients were played a blank tape instead ( N = 100 ) . The patients were primarily undergoing operations on the fallopian tubes , total abdominal hysterectomy , vertical b and ing gastroplasty , cholecystectomy , and ovarian cystectomy or myomectomy . The anesthesia methods consisted of either isoflurane with 70 % nitrous oxide in oxygen to produce end-tidal concentrations of 1.0 , 1.3 , or 1.5 MAC ; or 70 % nitrous oxide in oxygen combined with high or low doses of opioids . Assessment s of the efficacy of the therapeutic suggestions in the recovery room and throughout the postoperative hospital stay included : the frequency of administration of analgesic and antiemetic drugs ; opioid doses ; the incidence of fever ; nausea , retching , and vomiting ; other gastrointestinal and urinary symptoms ; ratings of pain ; ratings of anxiety ; global ratings of the patients ' physical and psychological recoveries by the patients and their nurses ; and length of postoperative hospital stay . There were no meaningful , significant differences in postoperative recovery of patients receiving therapeutic suggestions and controls . These negative results were not likely to be due to insensitivity of the assessment s of recovery , as they showed meaningful interrelations among themselves and numerous differences in recovery following different types of surgery . Widespread utilization of therapeutic suggestions as a routine operating room procedure seems premature in the absence of adequate replication of previously published positive studies In a double‐blind r and omised study , we investigated the influence of positive intra‐operative suggestions , presented to anaesthetised patients undergoing total abdominal hysterectomy , on postoperative pain , nausea and vomiting . One hundred and forty patients were r and omly allocated to listen to one of four tapes containing either white noise or positive suggestions . The positive suggestions related to pain , postoperative nausea and vomiting , or both . We found that the positive intra‐operative suggestions had no beneficial effects in reducing postoperative pain or nausea scores , nor was the consumption of morphine or anti‐emetics reduced Background A high incidence of intraoperative awareness during cardiac surgery has been reported . Midlatency auditory evoked potentials ( MLAEP ) have been used recently as an indicator of awareness . In the current study , memory for information presented during anesthesia was investigated using MLAEP as one experimental indicator in 45 patients scheduled for elective cardiac surgery . Methods In all patients general anesthesia was maintained using high-dosage fentanyl ( 1.2 mg · h−1 ) . In addition , the patients of group 1 ( n = 10 ) received flunitrazepam ( 1.2 mg · h−1 ) , the patients of group 2 ( n = 10 ) isoflurane ( 0.6–1.2 vol% ) , and the patients of group 3 ( n = 10 ) propofol ( 4–8 mg · kg−1 . h−1 ) . Group 4 ( n = 15 ) served as a control , and those patients were assigned r and omly to one of the anesthetic regimes . After sternotomy and before cardiopulmonary bypass , an audiotape , which included an implicit memory task , was presented to the patients of groups 1–3 . Auditory evoked potentials were recorded while the patients were awake and during general anesthesia immediately before and after the audiotape presentation . Latencies of the brain stem peak V and the early cortical potentials Na and Pa were measured . Results Three to 5 days postoperatively no patient had a clear explicit memory of intraoperative events . However , there were statistically significant differences in the incidence of implicit recall among the groups . Five patients in the flunitrazepam-fentanyl group , 1 patient in the isoflurane-fentanyl group , 1 patient in the propofol-fentanyl group , and no patient in the control group showed an implicit memory of the intraoperative tape message . In the awake state , MLAEP showed high peak-to-peak amplitudes and a periodic waveform . In the patients with implicit memory postoperatively , MLAEP continued to show this pattern during general anesthesia . The early cortical potentials Na and Pa did not increase in latency or decrease in amplitude before or after the audiotape presentation . In contrast , in the patients without implicit memory , MLAEP waveform was severely attenuated or abolished . Na and Pa showed marked increases in latencies and decreases in amplitudes or were completely suppressed . In 9 patients , including all patients ( 7 of 9 ) with implicit memory , Pa latency increased less than 12 ms , and 21 of 23 patients without implicit memory showed a Pa latency increase of greater than 12 ms during anesthesia and the audiotape presentation . Therefore , the Pa latency increase of greater or less than 12 ms may provide sensitivity of 100 % and specificity of 77 % in distinguishing patients with implicit memory from patients without implicit memory postoperatively . Conclusions When the early cortical potentials of MLAEP are preserved during general anesthesia , auditory information may be processed and remembered postoperatively by an implicit memory task Ninety-one patients undergoing biliary tract surgery were r and omly assigned to one of three treatment groups in which different sounds were administered , by means of earphones , in a double-blind design . The effects of the administration of positive suggestions , noise or operating theatre sounds on the postoperative course were studied . Results showed that exposure to positive suggestions during general anaesthesia , as compared with noise or operating theatre sounds , protected patients older than 55 yr against prolonged postoperative stay in hospital The clinical value of therapeutic suggestions during general anaesthesia was assessed in a double-blind r and omised placebo-controlled study . 39 unselected patients were allocated to suggestion ( n = 19 ) or control ( n = 20 ) groups who were played either recorded therapeutic suggestions or a blank tape , respectively , during hysterectomy . The patients in the suggestion group spent significantly less time in hospital after surgery , suffered from a significantly shorter period of pyrexia , and were generally rated by nurses as having made a better than expected recovery . Patients in the suggestion group , unlike those in the control group , guessed accurately that they had been played an instruction tape To determine if improved postoperative recovery in surgical in patients receiving intraoperative therapeutic suggestions are applicable in an outpatient population , 70 consenting , unpremedicated adults undergoing elective outpatient hernia repair under general anaesthesia were allocated r and omly to either a therapeutic tape ( TT ) or a comparison tape ( CT ) group . A st and ardized general anaesthetic technique was used with propofol , fentanyl or alfentanil , isoflurane and nitrous oxide in oxygen . Pain , and nausea and vomiting were assessed after operation at 30 , 60 and 90 min and at 2 , 6 and 24 h. The presence of other side effects , such as headache and muscular discomfort , in addition to recall of tape contents , were also evaluated after operation . Absorption ability was measured before operation . The groups were similar in patient characteristics , preoperative , surgical and anaesthetic characteristics , and level of absorption . There were no differences in pain ratings or need for analgesics administered at any time after operation . Nausea/vomiting was experienced significantly fewer times by patients in group TT compared with group CT over the first 90 min ( group CT 15 % , group TT 4 % ; P < 0.02 ) , but not over the last three assessment times ( group CT 10 % , group TT 14 % ; P < 0.25 ) . The therapeutic tape group experienced fewer side effects over the entire postoperative assessment period ( P = 0.03 ) , in particular less headaches ( P = 0.03 ) and less muscular discomfort ( P < 0.02 ) . Use of intraoperative therapeutic suggestions could present mildly significant postoperative benefits in out patients Background : The authors studied whether playing a taped cognitive-behavior message during and immediately following bariatric surgery will improve performance of a postoperative regimen design ed to enhance recovery . Methods : The double-blinded placebo-controlled study consisted of 27 morbidly obese bariatric surgical patients r and omly assigned to listen to either a blank ( Controls ) or a positive therapeutic message audiotape ( Tape ) . A Postoperative Regimen Checklist ( PRC ) quantified different parts of the postoperative recovery regimen . Results : The data showed that patients in the Tape group , compared to the Controls : 1 ) achieved better scores at most PRC assessment points ( p<0.05 ) , 2 ) required less encouragement to perform tasks ( p<0.05 ) , and 3 ) were discharged from the hospital a mean of 1.6 days earlier . Conclusions : A taped cognitive-behavioral message , played to patients repetitively during and immediately following bariatric surgery , is effective in enhancing postoperative compliance and reducing in-patient length of stay In a double-blind , r and omized study , we have examined the influence of positive therapeutic suggestions , presented to anaesthetized patients undergoing total abdominal hysterectomy , on postoperative morbidity and duration of hospital stay . Seventy-five patients were allocated r and omly to be exposed to one of three tapes containing positive therapeutic suggestions , a modified history of the Queen 's Medical Centre , or no message . We found that neither therapeutic suggestions nor the presence of a voice during anaesthesia improved postoperative outcome or reduced duration of hospital stay after total abdominal hysterectomy Purpose : This study was design ed to determine whether music or music in combination with therapeutic suggestions in the intra‐operative period under general anaesthesia could improve the recovery of hysterectomy patients In a double-blind study , 33 patients ( herniorraphy , cholecystectomy and orthopaedic ) were r and omly assigned to either suggestion or control groups . Under known clinical levels of nitrous oxide and enflurane or halothane anaesthesia , suggestion patients were exposed to statements of the importance of touching their ear during a postoperative interview . Compared with controls , suggestion patients did touch their ear ( tetrachoric correlation 0.61 , P less than 0.001 ) and they did so more frequently ( Mann-Whitney U test , P less than 0.02 ) . All suggestion patients were completely amnesic for the intraoperative spoken suggestion , despite inquiries which included hypnotic regression to the operation Background : The authors previously demonstrated memory function during apparently adequate general anesthesia in trauma patients . Hypnotic state fluctuations , stress , and variable amnesic qualities of commonly used anesthetics could account for this effect . Methods : The authors replicated the trauma investigation in 90 elective surgical patients to enable anesthetic titration to a bispectral index value of 50–55 during auditory presentation of word stimuli . Patients were r and omly assigned to maintenance with propofol ( n = 48 ) or isoflurane ( n = 42 ) . Before surgery , state anxiety and trait anxiety were assessed using self-report measures . Postoperative memory assessment relied on the process dissociation procedure using a word stem completion task . Results : There were no differences between groups for relevant demographic , preoperative , or supplemental drug variables . Ninety-eight percent of words were presented within a bispectral index range of 40–60 , with values averaging 48.8 ( SD = 5.7 ) during word presentation . Neither the process dissociation procedure nor st and ard measures of conscious recall and recognition memory showed evidence of explicit or implicit memory . Preoperative stress levels did not correlate with postoperative memory test scores in either study group . Conclusions : In contrast to the results of their previous study , the authors found no evidence of memory function with close control of hypnotic state . This suggests that hypnotic state fluctuations are important to memory activation under anesthesia . Other variables may contribute to preserved memory function as well . Propofol and isoflurane block memory equally well during adequate anesthesia A double-blind , r and omized study was conducted to examine the effect of different types of therapeutic suggestions , administered during general anaesthesia , on post-operative course . Eighty-two patients undergoing cholecystectomy were intra-operatively exposed to either affirmative and non-affirmative suggestions , affirmative or non-affirmative suggestions separately , or some irrelevant text . Patients who had received both affirmative and non-affirmative suggestions spent less time in hospital than patients in the other three groups . No significant differences were demonstrated for subjective well-being measured on the third and sixth days In a double-blind , r and omized study , patients undergoing cholecystectomy were administered one of four different sounds during general anaesthesia : positive suggestions , nonsense suggestions , seaside sounds or sounds from the operating theatre . The effect of these sounds on the postoperative course was examined to assess intraoperative auditory registration . No differences were found between the four groups in postoperative variables Thirty‐two ASA I or II women undergoing abdominal hysterectomy were r and omly allocated to four groups to determine what type , if any , of recorded intraoperative message they would receive . Groups I and II heard a neutral recording with no verbal content . Group III heard an experimental recording with a positive suggestion for a rapid recovery . Group IV had a self‐prepared message . The tapes were played during general anesthesia when anesthetic depth was judged to be stable and adequate by vital signs , end‐tidal anesthetic concentration and EEG compressed spectral array . No patient reported any recall of intraoperative messages when interviewed on the day after surgery . Chart review showed no difference in days of hospitalization , dose of analgesics required , time to beginning oral intake , or the amount of wound drainage ( P<0.05 ) . We conclude that no awareness can be observed directly by recall or indirectly by response to suggestion given under stable and adequate general anesthesia The effect of therapeutic suggestion ‐ implicit processing during balanced anaesthesia was studied in 70 female patients scheduled for elective breast surgery . The patients were r and omly allocated to listen to a message with reassuring information focused on minimising postoperative nausea and vomiting , or just a blank tape during surgery . Occurrence of nausea and vomiting was studied during the postoperative period . No patient recalled any explicit memories during the peroperative period . No major differences were observed in the number of patients who experienced nausea or vomiting during the 24 hour observation period . The patients exposed to positive suggestion did , however , have a lower frequency of recall for nausea and vomiting compared to those just listening to the blank tape . We did not observe any major effect of peroperative suggestion for postoperative nausea and vomiting . However , we can not rule out some implicit processing during balanced anaesthesia This study was design ed to confirm the effect of therapeutic intraoperative auditory suggestion on recovery from anesthesia , to establish the effect of preoperative suggestion , and to assess implicit memory for intraoperative information using an indirect memory task . Sixty consenting unpremedicated patients scheduled for elective gynecologic surgery were r and omly divided into three equal groups : Group 1 received a tape of therapeutic suggestions preoperatively , and the story of Robinson Crusoe intraoperatively ; Group 2 heard the story of Peter Pan preoperatively and therapeutic suggestions intraoperatively ; Group 3 heard the Crusoe story preoperatively and the Peter Pan story intraoperatively . A st and ardized anesthetic technique was used with fentanyl , propofol , isoflurane , and nitrous oxide . After surgery , all patients received patientcontrolled analgesia ( PCA ) with a st and ardized regimen . In the 24 h postsurgery , morphine use was recorded every 6 h and at 24 h an indirect memory test ( free association ) was used to test for memory of the stories . Anxiety scores were measured before surgery and at 6 and 24 h postsurgery . There were no significant differences between groups for postoperative morphine use , pain or nausea scores , anxiety scores , or days spent in hospital after surgery . Seven of 20 patients who heard the Pan story intraoperatively gave a positive association with the word " Hook , " whereas 2 of 20 who did not hear the story gave such an association . Indirect memory for the Pan story was established using confidence interval ( CI ) analysis . ( The 95 % CI for difference in proportion did not include zero ) . No indirect memory for the Crusoe story could be demonstrated . This study did not confirm previous work which suggested that positive therapeutic auditory suggestions , played intraoperatively , reduced PCA morphine requirements . In contrast , a positive implicit memory effect was found for a story presented intraoperatively . ( Anesth Analg 1996;82:148 - 52 The present study explored the effect of positive intrasurgical suggestion during the anesthetic state on postsurgical pain . One-half of the patients who were undergoing elective cholecystectomy or hysterectomy received strong positive intrasurgical suggestion directed specifically towards reducing pain . The control patients received information about pain without suggestion content . There was no effect on postsurgical pain measured by the McGill Pain Question naire and a visual analogue scale . The lack of effect on postsurgical pain indicates that intrasurgical suggestion does not provide a therapeutic method to achieve pain control Thirty patients scheduled for elective cardiopulmonary bypass surgery were interviewed pre‐operatively and postoperatively to assess changes in their emotional state and re collection s , both aware and unaware , of intra‐operative events . A r and om selection of patients heard a prerecorded audio tape towards the end of bypass after they were rewarmed to 37 ° C . The tape contained suggestions for patients to touch their chin during the postoperative interview , to remember three sentences and to recover quickly . The interviewers were blind to the experimental condition . The experimental group touched their chins significantly more often than the control group ( p = 0.015 ) . Sentence recognition did not reach significance and this may be due to the small numbers and low salience of the stimuli . Seven patients ( 23 % ) recalled intra‐operative events , five with the aid of hypnosis . Three reports ( 10 % ) were corroborated . Pre‐operative medication ( p < 0.01 ) and postoperative anxiety ( p < 0.05 ) were significant predictors of those patients who reported recall The influence of therapeutic intraoperative auditory suggestions on the incidence and severity of emetic episodes was investigated in 50 adults ASA I and II patients undergoing elective abdominal hysterectomy . The patients were r and omly divided into two groups , each consisting of 25 patients . In group I , a blank tape was played and in group II , positive suggestion was played via headphones throughout the anaesthetic period . It was observed that there was statistically significant difference ( P < 0.05 ) between the incidence of vomiting in group I ( 60 % ) and group II ( 36 % ) . The number of vomiting episodes per patient in group I was 3.1 + /- 1.2 as compared to 1.7 + /- 0.6 in group II . This difference was statistically significant . The patients requiring rescue antiemetic was significantly higher ( P < 0.05 ) in group I ( 66.6 % ) as compared to group II ( 22.2 % ) . It is concluded that positive therapeutic suggestion may be considered as an alternative to antiemetic therapy A double-blind r and omized study was performed in 100 patients undergoing thyroidectomy to evaluate the effect of positive therapeutic suggestions made during neurolept-anaesthesia . The classic droperidol-fentanyl-N2O technique was used as these drugs preserve the neurophysiological functions required to process the information in the therapeutic suggestions given during general anaesthesia . Patients in the suggestion group heard positive non-affirmative suggestions during the whole operation . An autoreverse tape player was used . The control group listened to an empty tape . Both groups were comparable with respect to demographic variables , anaesthetic technique , drug dosage , duration of anaesthesia and surgery . Patients in the suggestion group suffered significantly less from post-operative nausea or vomiting ( suggestion : 47.2 % vs. control : 85.7 % ) and required less anti-emetic treatment ( suggestion : 30.6 % vs. control : 68.6 % ) . We conclude that therapeutic suggestions heard during neurolept-anaesthesia are processed and decrease post-operative nausea and vomiting in patients after thyroidectomy |
1,789 | 28,524,909 | FINDINGS : Based on evidence , recommended interventions to reduce chronic cancer pain are celiac plexus block for pain related to pancreatic and abdominal cancers and radiation therapy for bone pain . | BACKGROUND : Pain is a common issue for patients with cancer and can be challenging to manage effectively .
Healthcare professionals need to be knowledgeable about evidence ‐based nonpharmacologic interventions .
OBJECTIVES : This systematic review critically appraises the strength and quality of the empirical evidence for nonpharmacologic interventions in reducing chronic cancer pain . | Abstract Purpose Women with breast cancer may experience symptoms of depression , anxiety , pain , fatigue and sleep disturbances during chemotherapy . However , there are few modalities that address multiple , commonly occurring symptoms that may occur in individuals receiving cancer treatment . Cranial electrical stimulation ( CES ) is a treatment that is FDA cleared for depression , anxiety and insomnia . CES is applied via electrodes placed on the ear that deliver pulsed , low amplitude electrical current to the head . Methods This phase III r and omized , sham-controlled study aim ed to examine the effects of cranial microcurrent stimulation on symptoms of depression , anxiety , pain , fatigue , and sleep disturbances in women receiving chemotherapy for early-stage breast cancer . Patients were r and omly assigned to either an actual or sham device and used the device daily for 1 h. The study was registered at clinical trials.gov , NCT00902330 . Results The sample included N = 167 women with early-stage breast cancer . Symptom severity of depression , anxiety , and fatigue and sleep disturbances were generally mild to moderate . Levels of pain were low . Anxiety was highest prior to the initial chemotherapy and decreased over time . The primary outcome assessment ( symptoms of depression , anxiety , fatigue , pain , sleep disturbances ) revealed no statistically significant differences between the two groups , actual CES vs. sham . Conclusion In this study , women receiving chemotherapy for breast cancer experienced multiple symptoms in the mild to moderate range . Although there is no evidence for the routine use of CES during the chemotherapy period for symptom management in women with breast cancer , further symptom management modalities should be evaluated to mitigate symptoms of depression , anxiety , fatigue , pain and sleep disturbances over the course of chemotherapy BACKGROUND Various interventions , including the superior hypogastric plexus block and ganglion impar block , are commonly used for the treatment of pelvic or perineal pain caused by cancer . The inferior hypogastric plexus block ( performed using a trans-sacral approach under fluoroscopy and using a local anesthetics⁄steroid combination ) for the diagnosis and treatment of chronic pain conditions involving the lower pelvic viscera was first described in 2007 . Neurolysis of the inferior hypogastric plexus may be useful for the treatment of pelvic and perineal pain caused by cancer . OBJECTIVES To assess the feasibility , safety and efficacy of the newly introduced inferior hypogastric plexus block , performed using a trans-sacral approach , for the relief of cancer-related pelvic and perineal pain . METHODS A total of 20 patients with cancer pain in the pelvis and ⁄or perineum were injected with 6 mL to 8 mL of 10 % phenol bilaterally by passing a spinal needle through the sacral foramen to perform the inferior hypogastric block . Pain intensity ( measured using a visual analogue scale ) , sleep score , activity score , psychological score and oral morphine consumption pre- and postprocedure were measured . RESULTS Two of the 20 patients died during the follow-up period and were , therefore , excluded from the study . All patients presented with cancer-related pelvic , perineal or pelviperineal pain . Pain scores were reduced from a mean ( ± SD ) of 7.22±1.31 preprocedurally to 4.06±1.73 one week postprocedurally ( P<0.05 ) . In addition , the mean consumption of morphine ( delivered via 30 mg sustained-release morphine tablets ) was reduced from 106.67±32.90 mg to 61.67±40.48 mg after one week ( P<0.05 ) . No complications or serious side effects were encountered during or after the block . DISCUSSION AND CONCLUSION The approach provides a good alternative technique for the treatment of low pelvic and perineal cancer-related pain . Additional studies are required for evaluation and refinement of the technique using other radiological techniques Background : Pain is 1 of the most common symptoms that a cancer patient would experience . A significant barrier to positive pain management is patients ’ misconceptions regarding analgesics and inadequate use of nonpharmacological strategies as pain relief . Objective : The purpose of this study was to investigate the effectiveness of a pain management program ( PMP ) on pain intensity , use of PRN drugs and nonpharmacological strategies as pain relief , and barriers to managing pain in cancer patients . Methods : The study was conducted in the palliative care and hospice ward of a public hospital in Hong Kong . Patients were r and omized to either an experimental group ( receiving the PMP ) or a control group ( routine care ) . There were 38 hospitalized patients , with 20 ( 13 males and 7 females ) in the experimental group and 18 ( 11 males and 7 females ) in the control group ; mean age was 61.95 years ( experimental group ) to 63.94 years ( control group ) . Results : Upon the completion of PMP , pain scores were significantly reduced in both groups , yet patients in the experimental group showed a significant increase in the use of PRN analgesics and nonpharmacological strategies to relieve pain ( P < .05 ) and significantly reduce barriers to managing their cancer pain ( P < .05 ) compared with the control group . Conclusion : Cancer patients should be empowered with pain management education to gain knowledge and correct misconceptions in managing their cancer pain . Implication s for Practice : Integration of the PMP into routine clinical work may help to improve the st and ard of care for cancer patients . It is recommended to provide pain management education to all cancer patients AIM Checklists may improve management of patients in different setting s. However , no studies have been conducted to investigate the use of this tool to improve inpatient pain control . This study , conducted in Italy , aims to describe the experience , in terms of pain control , of the widespread introduction of a checklist for pain control in oncological patients , according to current Italian legislation . MATERIAL S & METHODS In total , 92 Italian centers were r and omly assigned to the use of the 38Checkpain to monitor pain management or to continue their st and ard practice without the use of this tool . RESULTS The 38Checkpain improved the control of pain compared with centers who did not use this tool . CONCLUSION Overall , the findings of this study suggest that the application of the 38Checkpain may help improve control of pain of hospitalized oncological patients PURPOSE / OBJECTIVES To test the effectiveness of two interventions compared to usual care in decreasing attitudinal barriers to cancer pain management , decreasing pain intensity , and improving functional status and quality of life ( QOL ) . DESIGN R and omized clinical trial . SETTING Six outpatient oncology clinics ( three Veterans Affairs [ VA ] facilities , one county hospital , and one community-based practice in California , and one VA clinic in New Jersey ) Sample : 318 adults with various types of cancer-related pain . METHODS Patients were r and omly assigned to one of three groups : control , st and ardized education , or coaching . Patients in the education and coaching groups viewed a video and received a pamphlet on managing cancer pain . In addition , patients in the coaching group participated in four telephone sessions with an advanced practice nurse interventionist using motivational interviewing techniques to decrease attitudinal barriers to cancer pain management . Question naires were completed at baseline and six weeks after the final telephone calls . Analysis of covariance was used to evaluate for differences in study outcomes among the three groups . MAIN RESEARCH VARIABLES Pain intensity , pain relief , pain interference , attitudinal barriers , functional status , and QOL . FINDINGS Attitudinal barrier scores did not change over time among groups . Patients r and omized to the coaching group reported significant improvement in their ratings of pain-related interference with function , as well as general health , vitality , and mental health . CONCLUSIONS Although additional evaluation is needed , coaching may be a useful strategy to help patients decrease attitudinal barriers toward cancer pain management and to better manage their cancer pain . IMPLICATION S FOR NURSING By using motivational interviewing techniques , advanced practice oncology nurses can help patients develop an appropriate plan of care to decrease pain and other symptoms BACKGROUND Arthralgia is a common and debilitating side-effect experienced by breast cancer patients receiving aromatase inhibitors ( AIs ) and often results in premature drug discontinuation . METHODS We conducted a r and omised controlled trial of electro-acupuncture ( EA ) as compared to waitlist control ( WLC ) and sham acupuncture ( SA ) in postmenopausal women with breast cancer who self-reported arthralgia attributable to AIs . Acupuncturists performed 10 EA/SA treatments over 8 weeks using a manualised protocol with 2 Hz electro-stimulation delivered by a TENS unit . Acupuncturists administered SA using Streitberger ( non-penetrating ) needles at non-traditional acupuncture points without electro-stimulation . The primary end-point was pain severity by Brief Pain Inventory ( BPI ) between EA and WLC at Week 8 ; durability of response at Week 12 and comparison of EA to SA were secondary aims . FINDINGS Of the 67 r and omly assigned patients , mean reduction in pain severity was greater in the EA group than in the WLC group at Week 8 ( -2.2 versus -0.2 , p=0.0004 ) and at Week 12 ( -2.4 versus -0.2 , p<0.0001 ) . Pain-related interference measured by BPI also improved in the EA group compared to the WLC group at both Week 8 ( -2.0 versus 0.2 , p=0.0006 ) and Week 12 ( -2.1 versus -0.1 , p=0.0034 ) . SA produced a magnitude of change in pain severity and pain-related interference at Week 8 ( -2.3 , -1.5 respectively ) and Week 12 ( -1.7 , -1.3 respectively ) similar to that of EA . Participants in both EA and SA groups reported few minor adverse events . INTERPRETATIONS Compared to usual care , EA produced clinical ly important and durable improvement in arthralgia related to AIs in breast cancer patients , and SA had a similar effect . Both EA and SA were safe CONTEXT Integrated interventions with combined elements of body movement and psychotherapy on treatment-related symptoms in cancer patients are relatively scarce . OBJECTIVES The aim of the present study is to investigate the effectiveness of dance movement therapy ( DMT ) on improving treatment-related symptoms in a r and omized controlled trial . METHODS A total of 139 Chinese patients with breast cancer awaiting adjuvant radiotherapy were r and omized to DMT or control group . The intervention included six 1.5-hour DMT sessions provided twice a week over the course of radiotherapy . Self-report measures on perceived stress , anxiety , depression , fatigue , pain , sleep disturbance , and quality of life were completed before and after the three-week program . RESULTS DMT showed significant effects on buffering the deterioration in perceived stress , pain severity , and pain interference ( Cohen d = 0.34 - 0.36 , P < 0.05 ) . No significant intervention effects were found on anxiety , depression , fatigue , sleep disturbance , and quality of life ( Cohen d = 0.01 - 0.20 , P > 0.05 ) . CONCLUSION The short-term DMT program can counter the anticipated worsening of stress and pain in women with breast cancer during radiotherapy The objective of this study was to assess the impact of a Swedish massage intervention on oncology patients ' perceived level of distress . Each patient 's distress level was measured using 4 distinct dimensions : pain , physical discomfort , emotional discomfort , and fatigue . A total of 251 oncology patients volunteered to participate in this nonr and omized single-group pre- and post design study for over a 3-year period at a university hospital setting in southeastern Georgia . The analysis found a statistically significant reduction in patient-reported distress for all 4 measures : pain ( F = 638.208 , P = .000 ) , physical discomfort ( F = 742.575 , P = .000 ) , emotional discomfort ( F = 512.000 , P = .000 ) , and fatigue ( F = 597.976 , P = .000 ) . This reduction in patient distress was observed regardless of gender , age , ethnicity , or cancer type . These results lend support for the inclusion of a complementary massage therapy program for hospitalized oncology patients as a means of enhancing their course of treatment BACKGROUND Pancreatic cancer is often accompanied by severe abdominal or back pain . It 's the first study to evaluate the analgesic effect of electroacupuncture on pancreatic cancer pain . A r and omized controlled trial compared electroacupuncture with control acupuncture using the placebo needle . METHODS Sixty patients with pancreatic cancer pain were r and omly assigned to the electroacupuncture group ( n = 30 ) and the placebo control group ( n = 30 ) . Patients were treated on Jiaji ( Ex-B2 ) points T8-T12 bilaterally for 30 min once a day for 3 days . Pain intensity was assessed with numerical rated scales ( NRS ) before the treatment ( Baseline ) , after 3 treatments , and 2 days follow-up . RESULTS Baseline characteristics were similar in the two groups . After 3 treatment , pain intensity on NRS decreased compared with Baseline ( -1.67 , 95 % confidence interval [ CI ] -1.46 to -1.87 ) in the electroacupuncture group ; there was little change ( -0.13 , 95 % CI 0.08 to -0.35 ) in control group ; the difference between two groups was statistically significant ( P < 0.001 ) . Follow-up also found a significant reduction in pain intensity in the electroacupuncture group compared with the control group ( P < 0.001 ) . CONCLUSIONS Electroacupuncture was an effective treatment for relieving pancreatic cancer pain Pre clinical evidence indicates that gene transfer to the dorsal root ganglion using replication‐defective herpes simplex virus (HSV)‐based vectors can reduce pain‐related behavior in animal models of pain . This clinical trial was carried out to assess the safety and explore the potential efficacy of this approach in humans & NA ; St and ard guidelines for cancer pain treatment routinely recommend training patients to reduce barriers to pain relief , use medications appropriately , and communicate their pain‐related needs . Methods are needed to reduce professional time required while achieving sustained intervention effectiveness . In a multisite , r and omized controlled trial , this study tested a pain training method versus a nutrition control . At six oncology clinics , physicians ( N = 22 ) and nurses ( N = 23 ) enrolled patients ( N = 93 ) who were over 18 years of age , with cancer diagnoses , pain , and a life expectancy of at least 6 months . Pain training and control interventions were matched for material s and method . Patients watched a video followed by about 20 min of manual‐st and ardized training with an oncology nurse focused on review ing the printed material and adapted to individual concerns of patients . A follow‐up phone call after 72 h addressed individualized treatment content and pain communication . Assessment s at baseline , one , three , and 6 months included barriers , the Brief Pain Inventory , opioid use , and physician and nurse ratings of their patients ’ pain . Trained versus control patients reported reduced barriers to pain relief ( P < .001 ) , lower usual pain ( P = .03 ) , and greater opioid use ( P < .001 ) . No pain training patients reported severe pain ( > 6 on a 0–10 scale ) at 1‐month outcomes ( P = .03 ) . Physician and nurse ratings were closer to patients ’ ratings of pain for trained versus nutrition groups ( P = .04 and < .001 , respectively ) . Training efficacy was not modified by patient characteristics . Using video and print material s , with brief individualized training , effectively improved pain management over time for cancer patients of varying diagnostic and demographic groups Palliative care at the end of life involves meeting the physical , psychological , social , and practical needs of patients and caregivers . End of life is defined as a phase of life when a person is living with an illness that will worsen and eventually cause death . It is not limited to the short period of time when the person is moribund ( 1 ) . Good clinical care can prevent or alleviate suffering for many patients at the end of life by assessing symptoms and providing psychological and social support to the patients and their families . The purpose of this guideline is to present the available evidence to improve palliative care at the end of life . This guideline does not address any other setting s of palliative care at the end of life . The target audience for this guideline is all clinicians caring for patients needing end-of-life care . The target patient population is everyone with seriously disabling or symptomatic chronic conditions at the end of life . These recommendations are based on the systematic evidence review in the background paper in this issue by Lorenz and colleagues ( 1 ) , which is based on an Agency for Healthcare Research and Quality ( AHRQ ) evidence report ( 2 ) . End-of-life care has been identified by the Institute of Medicine as one of the priority areas to improve quality of health care ( 3 ) . The Institute of Medicine report identified specific gaps related to end-of-life care , such as pain control in advanced cancer and care for patients with advanced organ failure . High- quality evidence on end-of-life care is limited , and most of the evidence is derived from the literature that focused on patients with cancer ; therefore , this guideline does not address many important aspects of end-of-life care . For example , nutritional support , complementary and alternative therapies , and spiritual care were not part of the review . If an end-of-life intervention is not addressed in this guideline , it does not mean that no benefit is related to that particular intervention , but it indicates that the intervention has not been sufficiently studied to demonstrate efficacy . Some important topics in end-of-life care , such as interpersonal and social interventions , may be especially difficult to study . The American College of Physicians ' End-of-Life Care Consensus Panel has a series of papers related to ethical issues around end-of-life care that can be accessed from its Web site ( www.acponline.org/ethics/papers.htm ) . Methods The literature search for this guideline included studies from MEDLINE and review s of cancer , congestive heart failure , and dementia from the Data base of Abstract of Review s of Effects from January 1990 to November 2005 . Citations from the non systematic literature were taken from the review by the National Consensus Project for Quality Palliative Care ( 4 ) . The review included only English- language publications from the United States , Canada , Western Europe , Australia , and New Zeal and . Details about the methods used for the systematic evidence review may be found in detail in the background paper in this issue ( 1 ) . The objective for this guideline was to answer the following questions : 1 . What are the critical elements for clinicians to address when caring for persons coming to the end of life ? 2 . What do definitions of the end of life suggest about identifying patients who could benefit from palliative approaches ? 3 . What treatment strategies work well for pain , dyspnea , and depression ? 4 . What elements are important in advance care planning for patients coming to the end of life ? 5 . What elements of collaboration and consultation are effective in promoting improved end-of-life care ? 6 . What elements of assessment and support are effective for serving caregivers , including family , when patients are coming to the end of life ? This guideline grade s the evidence and recommendations using the American College of Physicians ' clinical practice guidelines grading system , adopted from the classification developed by the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) workgroup ( Table ) . Table . The American College of Physicians ' Guideline Grading System * Critical Elements for End-of-Life Care There is a wide range of critical elements for patients nearing the end of life , as well as for their caregivers . Preventing and treating pain and other symptoms ; supporting families and caregivers ; ensuring the continuity of care ; ensuring respect for persons and informed decision making ; attending to well-being , including existential and spiritual concerns ; and supporting function and survival duration are general issues that are common for most end-of-life care patients ( 411 ) . Identifying Patients Who Could Benefit from Palliative Approaches The literature review did not identify any evidence -based tools that have been vali date d and shown to predict the optimal timing to initiate palliative care services . Decisions to initiate palliative care at the end of life should be individualized on the basis of patient symptoms and preferences . Treatment Strategies Pain Strong evidence from trials of patients with cancer supports the use of nonsteroidal anti-inflammatory drugs , opioids , bisphosphonates , and radiotherapy or radiopharmaceuticals for pain ( 12 ) . Bisphosphonates are specifically effective for bone pain . However , head-to-head comparisons of specific drugs or reports on delivery strategies are difficult to do because of method ological issues and heterogeneity ( 12 ) . Evidence was insufficient to assess the usefulness of exercise or acupuncture in pain management ( 13 , 14 ) . A meta- analysis that included 43 studies showed that palliative care teams are modestly beneficial in providing care for pain management compared with usual care teams ( effect size , 0.13 SD [ 95 % CI , 0.11 to 0.63 SD ] ) ( 15 ) . Other studies that evaluated quality of life showed no difference ( 16 ) and no effect of palliative care consultation ( in contrast to palliative care teams ) on pain scores ( 17 ) . Dyspnea Evidence from 13 studies shows a valuable effect of morphine for dyspnea in advanced lung disease ( st and ardized mean difference , 0.31 [ CI , 0.50 to 0.13 ] ) ( 18 ) . This is also supported by other studies that show the benefits of morphine for treating dyspnea in advanced lung disease and terminal cancer ( 19 , 20 ) . However , using nebulized opioids compared with oral opioids showed no additional benefit . Also , 1 study showed that dihydrocodeine result ed in a statistically but not clinical ly significant increase in Pco 2 during treatment ( 18 ) . Good- quality evidence shows that long-acting -agonists are beneficial in the treatment of dyspnea in chronic obstructive pulmonary disease ( 21 ) . Twelve studies evaluated various interventions for reducing dyspnea in patients with chronic obstructive pulmonary disease , heart failure , cancer , or all conditions . Evidence was mixed when comparing oxygen therapy with room air . One study showed better oxygen saturation , respiratory effort and rate , and dyspnea with oxygen ( 19 ) . However , Bruera and colleagues ( 20 ) showed no difference in dyspnea and fatigue between oxygen and air after a 6-minute walk test . Studies that evaluated service delivery showed no effect of facilitated patientprovider communication or palliative care consultation for dyspnea treatment ( 16 , 17 , 22 , 23 ) . Depression Good evidence supports the effectiveness of long-term use of tricyclic antidepressants or selective serotonin reuptake inhibitors , as well as psychosocial interventions ( education , cognitive and noncognitive behavioral therapy , informational interventions , and individual and group support ) for treating patients with cancer who have depression ( 12 ) . Gysels and Higginson ( 24 ) identified 15 intervention studies that showed that behavioral interventions were effective in the treatment of depression , whereas 1 complementary medicine intervention was ineffective for depression ( 24 ) . Evidence for using guided imagery and exercise showed mixed results ( 13 , 25 ) . Palliative care for out patients did not have any effect on depression and anxiety , and care coordination showed no effect on depression in patients with cancer near the end of life ( 22 , 23 , 26 , 27 ) . Important Elements for Advance Care Planning Research shows that individuals are more likely to use advance directives in the presence of extensive multicomponent interventions than with limited interventions ( 28 , 29 ) . One study showed that hospice use increased when goal -oriented interviews and decisions between palliative care facilitators and patients were communicated to nursing home physicians ( 30 ) . In addition , another study showed an increase in documented treatment limitations and preference-concordant care for patients served by social workers trained in care planning ( 31 ) . Also , proactive communication from skilled discussants , such as an ethics team , can help reduce utilization of unnecessary services without harming patients or family members ( 32 , 33 ) . In summary , various processes , such as consulting caregivers , enhancing clear communication , eliciting values , and addressing the emotional context , are important elements for comprehensive advance care planning . Clinicians should help patients and families plan in advance for likely or important clinical decisions . Collaboration and Consultation to Improve End-of-Life Care Studies have shown that the following factors improve utilization outcomes and patient-centered outcomes : multidisciplinary teams involving nurses and social services , continuity of care and service coordination , and facilitated communication . A meta- analysis of 29 r and omized , controlled trials done by McAlister and colleagues ( 34 ) showed that follow-up by a multidisciplinary team result ed in decreased hospitalizations due to heart failure . In addition , a multidisciplinary approach also improved patients ' quality of life and functional status ( 34 , 35 ) . Another intervention study showed that coordination between primary physician and Up to 50 % of women receiving aromatase inhibitor ( AI ) complain of AI-associated musculoskeletal symptoms ( AIMS S ) and 15 % discontinue treatment . We conducted a r and omized , sham-controlled trial to evaluate whether acupuncture improves AIMS S and to explore potential mechanisms . Postmenopausal women with early stage breast cancer , experiencing AIMS S were r and omized to eight weekly real or sham acupuncture sessions . We evaluated changes in the Health Assessment Question naire Disability Index ( HAQ-DI ) and pain visual analog scale ( VAS ) following the intervention compared to baseline . Serum estradiol , β-endorphin , and proinflammatory cytokine concentrations were measured pre and post-intervention . We enrolled 51 women of whom 47 were evaluable , including 23 r and omized to real and 24 to sham acupuncture . Baseline characteristics were balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group ( p = 0.047 ) . We did not observe a statistically significant difference in reduction of HAQ-DI ( p = 0.30 ) or VAS ( p = 0.31 ) between the two groups . Following eight weekly treatments , we observed a statistically significant reduction of IL-17 ( p ≤ 0.009 ) in both groups . No significant modulation was seen in estradiol , β-endorphin , or other proinflammatory cytokine concentrations in either group . We did not observe a significant difference in AIMS S changes between real and sham acupuncture . As sham acupuncture used in this study may not be equivalent to placebo , further studies with a non-acupuncture arm may be required to establish whether acupuncture is beneficial for the treatment of AIMS BACKGROUND Celiac plexus neurolysis ( CPN ) is an effective but temporary management tool for pancreatic cancer pain ( PCP ) . Clinical studies have shown the duration of benefit with initial CPN to be apaproximately 3 months . When pain recurs , CPN may be repeated , but the outcomes for repeat CPN are not well established . The objective of this study is to determine the success rate and duration of relief following repeat celiac plexus neurolysis ( rCPN ) for PCP . METHODS Patients who underwent rCPN were identified from a data base and their records review ed . Responses of rCPN were then compared with iCPN for success rates and duration of relief . Success was defined as ≥ 50 % pain relief lasting ≥ 1 month . RESULTS Overall , there were 24 rCPN performed . The success rate decreased from 67 % after initial CPN to 29 % following rCPN ( P = 0.13 ) . The mean duration of pain relief decreased in parallel from 3.4 months ( iCPN ) to 1.6 months ( rCPN ) ( P = 0.03 ) . Among those who had a successful rCPN , 2.9 months elapsed from iCPN to rCPN , with disease progression noted in 29 % . In those who failed rCPN , 7.8 months elapsed , with disease progression apapreciated in 71 % of cases . CONCLUSIONS rCPN does not provide as much pain relief as iCPN . Disease progression as detailed on imaging appears to be a major factor in the limitations of rCPN . Further prospect i ve studies are warranted to confirm these results and investigate the utility of rCPN PURPOSE / OBJECTIVES To evaluate the feasibility of a patient-controlled cognitive-behavioral intervention for pain , fatigue , and sleep disturbance during treatment for advanced cancer and to assess initial efficacy of the intervention . DESIGN One group pre- and post-test design . SETTING Outpatient oncology clinics at a comprehensive cancer center in the midwestern United States . SAMPLE 30 adults with advanced ( recurrent or metastatic ) colorectal , lung , prostate , or gynecologic cancer receiving chemotherapy or radiotherapy . METHODS Participants completed baseline measures ( e.g. , demographics , symptom inventory ) and received education and training to use an MP3 player loaded with 12 cognitive-behavioral strategies ( e.g. , relaxation exercises , guided imagery , nature sound recordings ) . Participants used the strategies as needed for symptom management for two weeks , keeping a log of symptom ratings with each use . Following the two-week intervention , participants completed a second symptom inventory and an evaluation of the intervention . MAIN RESEARCH VARIABLES Feasibility , patient-controlled cognitive-behavioral intervention , pain , fatigue , and sleep disturbance . FINDINGS Thirty of 43 eligible patients ( 73 % ) agreed to participate ; of them , 27 ( 90 % ) completed the study . Most reported that they enjoyed the intervention , had learned useful skills , and perceived improvement in their symptoms . Symptom scores at two weeks did not differ significantly from baseline ; however , significant reductions in pain , fatigue , and sleep disturbance severity were found in ratings made immediately before and after use of a cognitive-behavioral strategy . CONCLUSIONS The patient-controlled cognitive-behavioral intervention appears to be feasible for additional study and could reduce day-to-day severity of co-occurring pain , fatigue , and sleep disturbance . IMPLICATION S FOR NURSING A r and omized , controlled trial is needed to test efficacy of the intervention for co-occurring pain , fatigue , and sleep disturbance . Meanwhile , based on previous efficacy studies , cognitive-behavioral strategies can be recommended for certain individual symptoms CONTEXT Pain and depression are 2 of the most prevalent and treatable cancer-related symptoms , yet they frequently go unrecognized , undertreated , or both . OBJECTIVE To determine whether central ized telephone-based care management coupled with automated symptom monitoring can improve depression and pain in patients with cancer . DESIGN , SETTING , AND PATIENTS R and omized controlled trial conducted in 16 community-based urban and rural oncology practice s involved in the Indiana Cancer Pain and Depression ( INCPAD ) trial . Recruitment occurred from March 2006 through August 2008 and follow-up concluded in August 2009 . The participating patients had depression ( Patient Health Question naire-9 score > or = 10 ) , cancer-related pain ( Brief Pain Inventory [ BPI ] worst pain score > or = 6 ) , or both . INTERVENTION The 202 patients r and omly assigned to receive the intervention and 203 to receive usual care were stratified by symptom type . Patients in the intervention group received central ized telecare management by a nurse-physician specialist team coupled with automated home-based symptom monitoring by interactive voice recording or Internet . MAIN OUTCOME MEASURES Blinded assessment at baseline and at months 1 , 3 , 6 , and 12 for depression ( 20-item Hopkins Symptom Checklist [ HSCL-20 ] ) and pain ( BPI ) severity . RESULTS Of the 405 participants enrolled in the study , 131 had depression only , 96 had pain only , and 178 had both depression and pain . Of the 274 patients with pain , 137 patients in the intervention group had greater improvements in BPI pain severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical pain responder ( > or = 30 % decrease in BPI ) than the 137 patients in the usual-care group ( P < .001 for both ) . Similarly , of the 309 patients with depression , the 154 patients in the intervention group had greater improvements in HSCL-20 depression severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical depression responder ( > or = 50 % decrease in HSCL ) than the 155 patients in the usual care group ( P < .001 for both ) . The st and ardized effect size for between-group differences at 3 and 12 months was 0.67 ( 95 % confidence interval [ CI ] , 0.33 - 1.02 ) and 0.39 ( 95 % CI , 0.01 - 0.77 ) for pain , and 0.42 ( 95 % CI , 0.16 - 0.69 ) and 0.41 ( 95 % CI , 0.08 - 0.72 ) for depression . CONCLUSION Central ized telecare management coupled with automated symptom monitoring result ed in improved pain and depression outcomes in cancer patients receiving care in geographically dispersed urban and rural oncology practice s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00313573 Purpose Previous studies have not defined the role of telemonitoring with educational tools in out patients with advanced cancers . We tested the effectiveness of st and ardized education and telemonitoring for improving pain , distress , anxiety , depression , quality of life ( QoL ) , and performance in out patients with advanced cancers . Methods A total of 108 patients were r and omly assigned to receive pain education alone ( control arm ) or pain education plus telemonitoring ( experimental arm ) . Nursing specialists provided video-assisted educational material in both arms and daily telemonitoring for the first week in the experimental arm . Assessment was performed at baseline and 1 week and included evaluations of pain ( Brief Pain Inventory , BPI ) , distress ( Distress Thermometer , DT ) , anxiety , and depression ( Hospital Anxiety and Depression Scale , HADS ) , QoL ( QLQ-C30 ) , and a Karnofsky score . Results Overall ( n = 108 ) , pain intensity was significantly improved at 1 week , including worst pain ( 7.3 to 5.7 , P < 0.01 ) and average pain ( 4.6 to 3.8 , P < 0.01 ) . Additionally , anxiety ( HADS score ≥ 11 , 75 % to 56 % , P < 0.01 ) , depression ( HADS score ≥ 11 , 73 % to 51 % , P < 0.01 ) , QoL ( fatigue and insomnia ) , and the Karnofsky score ( 32 to 66 , P < 0.01 ) were also significantly improved at 1 week . However , the level of distress did not improve . The telemonitoring plus st and ardized education group showed more significant improvement in portion of pain > 4 on VAS scale ( 35 % vs. 19 % , P = 0.02 ) . Conclusions St and ardized pain education using nursing specialists is an efficient way to improve not only pain itself but also anxiety , depression , performance , and QoL. The addition of telemonitoring helps to improve pain management in the outpatient setting CONTEXT Published literature has not defined the effectiveness of st and ardized educational tools that can be self-administered in the general oncology population with pain . OBJECTIVES We sought to determine if an educational intervention consisting of a video and /or booklet for adults with cancer pain could improve knowledge and attitudes about cancer pain management , pain levels , pain interference , anxiety , quality of life , and analgesic use . METHODS Eligible participants had advanced cancer , a pain score > /=2 of 10 in the last week , English proficiency , an estimated prognosis of more than one month , and were receiving outpatient cancer treatment at participating hospitals . Participants completed baseline assessment s and then were r and omly allocated to receive a booklet , a video , both , or neither , in addition to st and ard care . Outcome measures at two and four weeks included the Barriers Question naire ( BQ ) , Brief Pain Inventory , Global Quality of Life Scale , and Hospital Anxiety and Depression Scale . Adequacy of analgesia and severity of pain were assessed with the Pain Management Index and a daily pain diary . RESULTS One hundred fifty-eight participants were recruited from 21 sites over 42 months . Baseline mean barriers scores were lower than reported in previous Australian studies at 1.33 ( st and ard deviation : 0.92 ) . Mean average pain and worst pain scores improved significantly in patients receiving both the video and booklet by 1.17 ( st and ard error [ SE ] : 0.51 , P=0.02 ) and 1.12 ( SE : 0.57 , P=0.05 ) , respectively , on a 0 - 10 scale . The addiction subscale of the BQ score was improved by 0.44 ( SE : 0.19 ) for participants receiving any part of the intervention ( P=0.03 ) . CONCLUSION Provision of a video and /or booklet for people with cancer pain was a feasible and effective adjunct to the management of cancer pain BACKGROUND We compared the effectiveness and cost of a pain screening and treatment program , with usual care in head and neck cancer patients with significant pain . METHODS Patients were screened for the presence of pain and then r and omly assigned to either an intervention group , consisting of a pain treatment protocol and an education program , or to usual care . Primary outcome was change in the Pain Severity Index ( PSI ) over three months . RESULTS We screened 1074 patients of whom 156 were r and omized to either intervention or usual care . Mean PSI was reduced over three months in both groups , with no significant difference between the two groups . The Pain Management Index ( PMI ) at three months , was significantly improved in the intervention group compared with usual care ( P<0.001 ) , as was Patient Satisfaction ( mean difference in scores was statistically significant : -0.30 [ -0.60 to -0.15 ] ) . All subjects reported clinical ly significant levels of anxiety and depression throughout the study . Treatment costs were significantly higher for intervention ( mean=£400 ) compared with usual care ( £ 200 ) , with a low likelihood of being cost-effective . CONCLUSIONS There was no difference in the Pain Severity Index between the two groups . However there were significant improvements in the intervention group in patient satisfaction and PMI . The pain screening process itself was effective . Sufficient benefit was demonstrated as a result of the intervention to allow continued development of pain treatment pathways , rather than allowing pain treatment to be left to nonformalised ad hoc arrangements CONTEXT Cancer treatment capacity in China is severely limited relative to the enormous size of the population ; and many aspects of treatment , such as opioid protocol s for pain control , are not st and ardized . To improve the quality of drug treatment , clinical pharmacists are taking a more active role in patient care . OBJECTIVES This study compared the effectiveness of opioid treatment between cancer patients receiving interventions from Clinical Pharmacist-Led Guidance Teams ( CPGTs ) and a comparable control group . METHODS This was a prospect i ve , multicenter , double-arm , controlled study conducted in China . Multidisciplinary guidance teams were established and led by clinical pharmacists with expertise in cancer pain therapy . The CPGTs provided pre-therapy consultation and drug education to physicians , monitored prescriptions during treatment , and conducted patient follow-up . The process and outcome parameters of therapy were collected and analyzed with overall statistics and logistic regression . RESULTS A total of 542 patients were enrolled , 269 in the CPGT intervention group ( CPGT group ) and 273 controls . St and ardization of opioid administration was improved significantly in the CPGT group , including more frequent pain evaluation ( P<0.001 ) , more st and ardized dosing titration ( P<0.001 ) , and less frequent meperidine prescriptions ( P<0.001 ) . The pain scores in the CPGT group were significantly improved compared with the control group ( P<0.05 ) . The incidences of gastrointestinal adverse events were significantly lower in the CPGT group ( constipation : P=0.041 ; nausea : P=0.028 ; vomiting : P=0.035 ) , and overall quality of life was improved ( P=0.032 ) . No opioid addiction was encountered in the CPGT group . Risk analysis revealed that patient follow-up by pharmacists and the controlled dosing of opioids were the major factors in improving treatment efficacy . CONCLUSION The CPGTs significantly improved st and ardization , efficiency , and efficacy of cancer pain therapy in China . In a country where clinical pharmacy is still developing , this is a valuable service model that may enhance cancer treatment capacity and efficacy while promoting recognition of the clinical pharmacy profession CONTEXT For patients with cancer-related pain and their physicians , routine oncology visits are an opportunity to adjust the analgesic regimen and secure better pain control . However , treatment intensification occurs haphazardly in practice . OBJECTIVES To estimate the effect of patient-centered tailored education and coaching ( TEC ) on the likelihood of analgesic treatment adjustment during oncology visits , and in turn , the influence of treatment adjustment on subsequent cancer pain control , we studied patients enrolled in a r and omized trial of TEC . METHODS Just before a scheduled oncology visit , 258 patients with at least moderate baseline pain received TEC or control ; just after the same visit , they reported on whether the physician recommended a new pain medicine or a change in dose of an existing medicine . Pain severity and pain-related impairment were measured two , six , and 12 weeks later . RESULTS Patients assigned to TEC were more likely than controls to report a change in the analgesic treatment regimen ( 60 % vs. 36 % , P<0.01 ) ; significant effects persisted after adjustment for baseline pain , study site , and physician ( adjusted odds ratio 2.61 , 95 % confidence interval 1.55 , 4.40 , P<0.01 ) . In a mixed-effects repeated measures regression , analgesic change ( but not TEC itself ) was associated with a sustained decrease in pain severity ( P<0.05 ) . CONCLUSION TEC increases the likelihood of self-reported , physician-directed adjustments in analgesic prescribing , and treatment intensification is associated with better cancer pain outcomes Summary This trial reveals the positive impact of a nursing intervention to improve patients ' self‐management of cancer pain and reduce care transition‐related problems . ABSTRACT Patients ' self‐management skills are affected by their knowledge , activities , and attitudes toward pain management . This trial aim ed to test the Self Care Improvement through Oncology Nursing (SCION)‐PAIN program , a multimodular structured intervention to reduce patients ' barriers to self‐management of cancer pain . Two hundred sixty‐three patients with diagnosed malignancy , pain > 3 days , and average pain ≥ 3/10 participated in a cluster‐r and omized trial on 18 wards in 2 German university hospitals . Patients on the intervention wards received , in addition to st and ard pain treatment , the SCION‐PAIN program consisting of 3 modules : pharmacologic , nonpharmacologic pain management , and discharge management . The intervention was conducted by specially trained cancer nurses and included components of patient education , skills training , and counseling . Starting with admission , patients received booster sessions every third day and one follow‐up telephone counseling session within 2 to 3 days after discharge . Patients in the control group received st and ard care . Primary end point was the group difference in patient‐related barriers to self‐management of cancer pain ( Barriers Question naire – BQ II ) 7 days after discharge . The SCION‐PAIN program result ed in a significant reduction of patient‐related barriers to pain management 1 week after discharge from the hospital : mean difference on BQ II was −0.49 points ( 95 % confidence interval −0.87 points to −0.12 points ; P = 0.02 ) . Furthermore , patients showed improved adherence to pain medication ; odds ratio 8.58 ( 95 % confidence interval 1.66–44.40 ; P = 0.02 ) . A post hoc analysis indicated reduced average and worst pain intensity as well as improved quality of life . This trial reveals the positive impact of a nursing intervention to improve patients ' self‐management of cancer pain Complementary therapies are increasingly used to reduce side effects of cancer treatment , without evidence for their effectiveness . In a r and omized , prospect i ve , 2-period , crossover intervention study , the authors tested the effects of therapeutic massage ( MT ) and healing touch ( HT ) , in comparison to presence alone or st and ard care , in inducing relaxation and reducing symptoms in 230 subjects . MT and HT lowered blood pressure , respiratory rate ( RR ) , and heart rate ( HR ) . MT lowered anxiety and HT lowered fatigue , and both lowered totalmooddisturbance . Pain ratings were lower after MT and HT , with 4-week nonsteroidal antiinflammatory drug use less during MT . There were no effects on nausea . Presence reduced RR and HR but did not differ from st and ard care on any measure of pain , nausea , mood states , anxiety , or fatigue . MT and HT are more effective than presence alone or st and ard care in reducing pain , mood disturbance , and fatigue in patients receiving cancer chemotherapy BACKGROUND No study has so far addressed whether differences do exist in the management of cancer pain between patients receiving usual care by primary specialists and those receiving early palliative/supportive intervention . PATIENTS AND METHODS A multicentre cross-sectional study in 32 Italian Hospitals has included 1450 patients , receiving analgesic therapy for cancer pain : 602 with access to primary specialist alone ( st and ard care , SC ) and 848 with early access to a palliative/supportive care ( ePSC ) team , concomitant with primary oncology care . RESULTS Statistically significant differences in the analgesic drug administration according to care model have been evident : non-opioids were more frequently used in SC ( 9.5 % versus 2 % ; P<0.001 ) , while strong opioids in ePSC group ( 80 % versus 63 % ; P<0.001 ) . The number of patients with severe pain was lower in ePSC compared with SC group ( 31 % versus 17 % ; P<0.001 ) . Results of multivariate analysis have shown that ePSC integrated with primary oncologic care ( relative risk 0.69 ; 95 % confidence interval 0.48 - 0.99 ; P=0.045 ) was an independent factor associated with a 31 % reduced risk of suffering from severe pain . CONCLUSIONS An ePSC team provides the most effective st and ard of analgesic therapy for cancer pain . A r and omized clinical trial is needed to confirm these findings Background Ethanol celiac plexus neurolysis ( ECPN ) has been shown to be effective in reducing cancer-related pain in patients with locally advanced pancreatic and periampullary adenocarcinoma ( PPA ) . This study examined its efficacy in patients undergoing PPA resection . Study Design 485 patients participated in this prospect i ve , r and omized , double blind placebo controlled trial . Patients were stratified by preoperative pain and disease resectability . They received either ECPN ( 50 % ethanol ) or 0.9 % normal saline placebo control . The primary endpoint was short and long-term pain and secondary endpoints included postoperative morbidity , QOL and overall survival . Results Data from 467 patients were analyzed . The primary endpoint , the percentage of PPA patients experiencing a worsening of pain compared to preoperative baseline for resectable patients , was not different between the ethanol and saline groups in either the resectable/pain stratum ( 22 % vs 18 % , RR 1.23 ( 0.34 , 4.46 ) ) , or the resectable/no pain stratum ( 37 % vs 34 % , RR 1.10 ( 0.67 , 1.81 ) ) . On multivariable analysis of resected pancreatic ductal adenocarcinoma ( PDA ) patients , there was a significant reduction in pain in the resectable/pain group , suggesting that surgical resection of the malignancy alone ( independent of ECPN ) decrements pain to a significant degree . Conclusions In this study , we have demonstrated a significant reduction in pain following surgical resection of PPA . However the addition of ECPN did not synergize to result in a further reduction in pain , and in fact its effect may have been masked by surgical resection . Given this , we can not recommend the use of ECPN to mitigate cancer related pain in resectable PPA patients The aim of the present study is to find out the influence of rational-emotive behavior therapy ( REBT ) on pain intensity among cancer patients in India and Iran . The study followed a quasi-experimental , pre-post test , carried out with a sample of 88 cancer patients , aged 21 - 52 years , referred to the Baharat cancer hospital of Mysore in India and Shahidzade hospital of Behbahan in Iran . They were r and omly assigned to the experimental ( n = India 21 ; Iran 22 ) and control ( n = India 22 ; Iran 23 ) groups . Pain was measured with the McGill Pain Question naire- MPQ ( 1975 ) , the intervention by REBT has given to the experimental group for 45 days ( ten sessions ) and at the end of intervention , the pain of patients was again evaluated . Concerning to hypothesis of the study , two independent sample T test and three ways mixed ANOVA is used to analyze the data . Results showed that the experimental group in post test had less pain than the control group , but there were no statistically significant differences between Indian and Iranian patients in pain perception . With respect the outcome of study , it has realized that REBT can be used in hospitals and other psychological clinics to reduce the pain of cancer patients Pain control is the most difficult puzzle in patients with terminal pancreatic cancerous pain . Many methods in clinical practice fail in 20 ~ 50 % of patients . The present study aims to explore the effect of nerve block on patients with end-stage pancreatic cancerous pain . In this study , 100 subjects with end-stage pancreatic cancerous pain were enrolled and r and omly assigned into two groups : 68 in nerve block group ( N ) and 32 in sham group ( S ) . One group was treated with nerve block and the other group with sham procedure as controls . The pain score ( by visual analog scale ( VAS ) ) , pain duration , reduction of other analgesic medications , and quality of life ( with question naire QLQ ) were evaluated before and 3 months after interventions . Comparisons were performed between before and after intervention in nerve block group and sham group . The results indicated that compared with sham group , the subjects in nerve block group had significant reduction with pain score , pain duration , and other analgesic medications , as well as improvement of quality of life ( P < 0.05 , respectively ) . In conclusion , nerve block is an effective method for treating patients with end-stage pancreatic cancerous pain Purpose A pilot study to document changes in symptoms after acupuncture or nurse-led supportive care in patients with incurable cancer . Methods Patients receiving palliative care with estimated survival of at least 3 months were screened with the Edmonton Symptom Assessment System ( ESAS ) . Patients ( n=20 ) with significant symptoms were r and omised to receive weekly acupuncture or nurse-led supportive care for 4 weeks . ESAS scores were obtained before and after each treatment , and weekly for 6 weeks after treatment by telephone . Results 42 of 170 patients screened were eligible . 20 gave consent for recruitment . The compliance rate was 90 % for acupuncture and 80 % for nurse-led supportive care . Total symptom scores were reduced by an average of 22 % after each acupuncture visit and by 14 % after each supportive care visit . Compared with baseline , ESAS scores at the end of the follow-up period were reduced by 19 % for the acupuncture arm and 26 % for nurse-led supportive care . Conclusion Patients appear to benefit from incorporating acupuncture in the treatment of advanced incurable cancer . Acupuncture was well tolerated with no significant or unexpected side effects . Acupuncture had an immediate effect on all symptoms , whereas nurse-led supportive care had a larger impact 6 weeks after the final session . Both interventions appear helpful to this population and warrant further study The purpose of this r and omized controlled study was to investigate the effect of a pain education program ( PEP ) on pain intensity , patients ' satisfaction with pain treatment , and patient-related barriers to pain management among Turkish patients with cancer . The study was conducted in a sample of 40 patients who were hospitalized for cancer and experiencing pain . The patients were equally r and omized to either a PEP or a control group . The data were collected by means of the McGill Pain Question naire , the Numeric Rating Scale , and the Barrier Question naire-Revised . After the completion of the question naires at the first interview , patients in the PEP group received pain education using a pain educational booklet and an explanatory slide program that discussed the booklet 's content with the patients . Patients in the control group received routine clinical care . The question naires were reapplied to the patients in both groups after 2 , 4 , and 8 weeks . Participation in a PEP was associated with decreased pain intensity scores for " present " and " least pain " during weeks 2 , 4 , and 8 ( p < .05 ) . Similarly , there were significant differences between the groups with respect to weeks 2 , 4 , and 8 satisfaction with pain treatment ( p < .05 ) . At the end of second week , the total BQ-r score decreased significantly in the PEP group from 2.12 to 1.29 compared with 2.30 to 2.28 in the control group ( p < .001 ) . The findings suggest that the PEP decreases pain intensity , improves satisfaction with treatment , and decreases barriers about cancer pain management in cancer patients . Incorparation of PEP into the st and ard of care for cancer patients with pain may improve the quality of pain management Objective To evaluate the effects of an 8-week multidimensional physical therapy program , including strengthening exercises and recovery massage , on neck and shoulder pain , pressure hypersensitivity , and the presence of active trigger points ( TrPs ) in breast cancer survivors . Methods In this r and omized controlled clinical trial , 44 breast cancer survivors were r and omly assigned into 2 groups : CUI DATE group who received a multidimensional physical therapy program ; or CONTROL group who received usual care treatment for breast cancer . CUI DATE program consisted of 24 hours of individual physical training ( aerobic , mobility , stretching , and strengthening exercises ) and 12 hours of physical therapy recovery ( stretching , massage ) interventions ( 3 times/wk , 90 min ) . Outcomes included neck and shoulder pain ( visual analog scale , 0 to 100 ) , pressure pain thresholds over the C5-C6 zygapophyseal joints , deltoid muscles , second metacarpal and tibialis anterior muscles , and the presence of active TrPs in shoulder muscles . Outcomes were assessed at baseline and after the 8-week program by a blinded assessor . Results The CUI DATE group showed an estimated improvement for neck pain of –56 mm [ 95 % confidence interval ( CI ) , −71-–40 , P<0.001 ; effect size 2.72 , 1.94 to 3.44 ] and for shoulder/axillary of –56 mm ( 95 % CI , –74-–38 , P<0.001 ; effect size 2.45 , 1.66 to 3.23 ) . Improvements were also noted for pressure pain thresholds levels : C5-C6 zygapophyseal joints ( between-group differences 101 kPa , 95 % CI , 60 - 143 ; effect size 1.68 , 1.00 to 2.35 ; 92 kPa 55 to 129 ; d : 1.98 , 1.18 to 2.77 ) , deltoid muscles ( 98 kPa , 45 to 149 ; d : 1.34 , 0.62 to 2.04 ; 75 kPa 18 to 132 ; d : 1.12 , 0.27 to 1.96 ) , second metacarpal ( 93 kPa , 45 to 134 ; d : 1.30 , 0.63 to 1.86 ; 99 kPa 59 to 139 ; d : 1.60 , 0.96 to 2.24 ) , and tibialis anterior muscles ( 71 kPa , 40 to 144 ; d : 1.16 , 0.65 to 2.34 ; 118 kPa 57 to 178 ; d : 1.17 , 0.56 to 1.77 ) . Finally , patients within the CUI DATE program showed a greater reduction of active muscle TrPs compared with the CONTROL group ( P<0.01 ) . Conclusions An 8-week multidimensional program including strengthening exercises , and massage as major components was effective for improving neck and shoulder pain and reducing widespread pressure hyperalgesia in breast cancer survivors compared with usual care treatment BACKGROUND The technique of alcohol injection during EUS-guided celiac plexus neurolysis ( CPN ) in patients with pancreatic cancer-related pain has not been st and ardized . OBJECTIVE To compare pain relief and safety of alcohol given as 1 versus 2 injections during EUS-guided CPN ( EUS-CPN ) . Secondary outcomes examined were characteristics that predict response and survival . DESIGN Single-blinded , prospect i ve , r and omized , parallel-group study . SETTING Tertiary-care center . PATIENTS This study involved patients with pancreatic cancer-related pain . INTERVENTION EUS-CPN done by injecting 20 mL of 0.75 % bupivacaine and 10 mL 98 % alcohol into 1 or 2 sites at the celiac trunk . Participants were interviewed by telephone at 24 hours and weekly thereafter . MAIN OUTCOME MEASUREMENTS Time until onset of pain relief , duration of pain relief , complications . RESULTS Fifty patients ( mean age 63 years ; 24 men ) were enrolled and r and omized ( 29 in 1-injection , 21 in 2-injections groups ) . Pain relief was observed in 37 ( 74 % ) patients : 20 ( 69 % ) in the 1-injection group and 17 ( 81 % ) in the 2-injection group ( chi-square P = .340 ) . Median onset of pain relief was 1 day for both 1-injection ( range 1 - 28 days ) and 2-injection ( range 1 - 21 days ) groups ( Mann-Whitney P = .943 ) . Median duration of pain relief in the 1-injection and 2-injection groups was 11 weeks and 14 weeks , respectively ( log-rank P = .612 ) . Complete pain relief was observed in 4 ( 8 % ) patients total , 2 in each group . There were no long-term complications . LIMITATIONS Single-blinded study . CONCLUSION There were no differences in onset or duration of pain relief when either 1 or 2 injections were used . There was no difference in safety or survival between the 2 groups Background Breast cancer is the most common cancer in women worldwide , affecting one in eight women . Breast-conserving surgery ( BCS ) has become a well-established alternative to mastectomy in the treatment of breast cancer , providing a less invasive treatment . Just as life expectancy after breast cancer has improved , so has morbidity increased . One of the most relevant and debilitating consequences of oncological breast surgery is postmastectomy pain syndrome ( PMPS ) . Our results published in 2011 on the treatment of PMPS in patients who had undergone mastectomy and radiotherapy and our experience in scar treatment with fat grafts were the theoretical bases for this prospect i ve study . Methods From April 2011 to April 2012 a total of 96 patients , who had undergone lumpectomy and radiation therapy , with the diagnosis of PMPS were considered for fat grafts . We performed autologous fat grafting in 59 patients ( study group ) , whereas 37 patients did not receive any further surgical procedure ( control group ) . Pain assessment was performed using the visual analog scale ( VAS ) before and after treatment in the treated group and in the control group at the first visit and the control visit , with a mean follow-up of 10 months . Results were analyzed using the Wilcoxon rank sum test . Results Four patients were lost to follow-up ( two patients in the control group and two patients in the treated group ) . A significant VAS pain decrease was detected in patients treated with autologous fat grafting ( 3.1 point reduction , p ≤ 0.005 ) . Conclusion Because of the safety , efficacy , and optimal tolerability of the procedure , we believe that fat grafting can be considered useful in treating PMPS in patients who have undergone BCS and radiotherapy . Level of Evidence IIIFor a full description of these Evidence -Based Medicine ratings , please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 OBJECTIVE To compare the effects of resistance and cardiovascular exercise on functional mobility in individuals with advanced cancer . DESIGN Prospect i ve , 2-group pretest-posttest pilot study with r and omization to either resistance or cardiovascular exercise mode . SETTING Comprehensive community cancer center and a hospital-based fitness facility . PARTICIPANTS Volunteer sample of individuals ( N=66 ; 30 men ; 36 women ; mean age , 62y ) with advanced cancer recruited through the cancer center , palliative care service , rehabilitation department , and a local hospice . INTERVENTIONS Ten weeks of individualized resistance or cardiovascular exercise , prescribed and monitored by oncology-trained exercise personnel . MAIN OUTCOME MEASURES Functional mobility was assessed using the Short Physical Performance Battery ( SPPB ) ; self-reported pain and fatigue were assessed secondarily using visual analog scales . Data were analyzed using a split plot 2 × 2 analysis of variance ( α=.05 ) . RESULTS Fifty-two patients ( 78.8 % ) completed the study : 23 ( 67.7 % ) of 34 patients in the resistance arm and 29 ( 90.6 % ) of 32 patients in the cardiovascular arm . No participant withdrew because of study adverse events . Ten-week outcomes ( n=52 ) included a significant increase in SPPB total score ( P<.001 ) , increase in gait speed ( P=.001 ) , and reduction in fatigue ( P=.05 ) . Although cardiovascular exercise participants had a modestly greater improvement in SPPB total score than resistance training participants ( F1,49=4.21 , P=.045 ) , the difference was not confirmed in a subsequent intention-to-treat analysis ( N=66 ) . CONCLUSIONS Individuals with advanced cancer appear to benefit from exercise for improving functional mobility . Neither resistance nor cardiovascular exercise appeared to have a strong differential effect on outcome PURPOSE / OBJECTIVES Through a r and omized clinical trial , to compare patients undergoing an initial course of chemotherapy who report pain and fatigue at baseline and who are receiving conventional care alone with those receiving conventional care plus a nursing intervention on outcomes reported at 20 weeks . SETTING Chemotherapy clinics of two comprehensive and two community cancer centers . METHODS Interviews were conducted at baseline and 10 and 20 weeks . An 18-week , 10-contact nursing intervention utilizing problem-solving approaches to symptom management and improving physical functioning and emotional health was implemented . SAMPLE The sample consisted of 53 patients in the experimental arm and 60 in the control arm who reported pain and fatigue at baseline . VARIABLES Pain and fatigue , numbers of other symptoms , and physical role impact and social-functioning subscales from the Medical Outcomes Study 36 Short Form . FINDINGS Patients who received the intervention reported a significant reduction in the number of symptoms experienced and improved physical and social functioning . Fewer patients in the experimental arm reported both pain and fatigue at 20 weeks . CONCLUSIONS Behavioral interventions targeted to patients with pain and fatigue can reduce symptom burden , improve the quality of the daily life of patients , and demonstrate the " value-added " role of nursing care for patients undergoing chemotherapy . IMPLICATION S FOR NURSING These data support the " value-added " role of nursing interventions for symptom management and improved quality of life during the course of cancer treatment ABSTRACT Neuropathic pain is common among cancer patients and often difficult to treat . This study used Scrambler therapy , a patient-specific electrocutaneous nerve stimulation device , to treat cancer patients with pain . Patients received Scrambler therapy for 10 sessions ( one daily ) over a two-week period . The primary outcome was changed in pain numerical rating scale ( NRS ) at one month ; secondary outcomes were changes in the Brief Pain Inventory and European Organization for Treatment and Cancer QLC-CIPN-20(EORTC CIPN-20 ) , over time . Thirty-nine patients , mean age 56.5 yr , 16 men and 23 women , were treated over an 18-month period for an average of 9.3 days each . The “ now ” pain scores reduced from 6.6 before treatment to 4.5 at 14 days , 4.6 , 4.8 , and 4.6 at 1 , 2 , and 3 months , respectively ( p < 0.001 ) . Clinical ly important and statistically significant improvements were seen in average , least , and worst pain ; BPI interference with life scores , and motor and sensory scales on the EORTC CIPN-20 . No adverse effects were observed . In this single arm trial , Scrambler therapy appeared to relieve cancer-associated chronic neuropathic pain both acutely and chronically , and provided sustained improvements in many indicators of quality of life & NA ; We aim ed to determine the effectiveness of a lay‐administered tailored education and coaching ( TEC ) intervention ( aim ed at reducing pain misconceptions and enhancing self‐efficacy for communicating with physicians ) on cancer pain severity , pain‐related impairment , and quality of life . Cancer patients with baseline “ worst pain ” of ⩾4 on a 0–10 scale or at least moderate functional impairment due to pain were r and omly assigned to TEC or enhanced usual care ( EUC ) during a telephone interview conducted in advance of a planned oncology office visit ( 265 patients r and omized to TEC or EUC ; 258 completed at least one follow‐up ) . Patients completed question naires before and after the visit and were interviewed by telephone at 2 , 6 , and 12 weeks . Mixed effects regressions were used to evaluate the intervention adjusting for patient , practice , and site characteristics . Compared to EUC , TEC was associated with increased pain communication self‐efficacy after the intervention ( P < .001 ) ; both groups showed significant ( P < .0001 ) , similar , reductions in pain misconceptions . At 2 weeks , assignment to TEC was associated with improvement in pain‐related impairment ( −0.25 points on a 5‐point scale , 95 % confidence interval −0.43 to −0.06 , P = .01 ) but not in pain severity ( −0.21 points on an 11‐point scale , −0.60 to 0.17 , P = .27 ) . The improvement in pain‐related impairment was not sustained at 6 and 12 weeks . There were no significant intervention by subgroup interactions ( P > .10 ) . We conclude that TEC , compared with EUC , result ed in improved pain communication self‐efficacy and temporary improvement in pain‐related impairment , but no improvement in pain severity . Compared with control , tailored education and coaching for patients with cancer‐related pain improved communication self‐efficacy and reduced pain‐related impairment in the short term but had no sustained benefits CONTEXT Pain , fatigue , and sleep disturbance commonly co-occur in patients receiving treatment for advanced cancer . OBJECTIVES A pilot r and omized controlled trial was conducted to assess initial efficacy of a patient-controlled cognitive-behavioral ( CB ) intervention for the pain , fatigue , and sleep disturbance symptom cluster . METHODS Eighty-six patients with advanced lung , prostate , colorectal , or gynecologic cancers receiving treatment at a comprehensive cancer center were stratified by recruitment clinics ( chemotherapy and radiation therapy ) and r and omized to intervention or control groups . Forty-three patients were assigned to receive training in and use of up to 12 relaxation , imagery , or distraction exercises delivered via an MP3 player for two weeks during cancer treatment . Forty-three patients were assigned to a waitlist control condition for the same two week period . Outcomes included symptom cluster severity and overall symptom interference with daily life measured at baseline ( Time 1 ) and two weeks later ( Time 2 ) . RESULTS Eight participants dropped out ; 78 completed the study and were analyzed ( 36 intervention and 42 control subjects ) . Participants used the CB strategies an average of 13.65 times ( SD=6.98 ) . Controlling for baseline symptom cluster severity and other relevant covariates , it was found that the symptom cluster severity at Time 2 was lower in the intervention group ( M(Adj)=2.99 , SE=0.29 ) than in the waitlist group ( M(Adj)=3.87 , SE=0.36 ) , F(1 , 65)=3.57 , P=0.032 . Symptom interference with daily life did not differ between groups . No significant adverse events were noted with the CB intervention . CONCLUSION Findings suggest that the CB intervention may be an efficacious approach to treating the pain , fatigue , and sleep disturbance symptom cluster . Future research is planned to confirm efficacy and test mediators and moderators of intervention effects 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 CONTEXT Exercise benefits patients with cancer , but studies of home-based approaches , particularly among those with Stage IV disease , remain small and exploratory . OBJECTIVES To conduct an adequately powered trial of a home-based exercise intervention that can be facilely integrated into established delivery and reimbursement structures . METHODS Sixty-six adults with Stage IV lung or colorectal cancer were r and omized , in an eight-week trial , to usual care or incremental walking and home-based strength training . The exercising participants were instructed during a single physiotherapy visit and subsequently exercised four days or more per week ; training and step-count goals were advanced during bimonthly telephone calls . The primary outcome measure was mobility assessed with the Ambulatory Post Acute Care Basic Mobility Short Form . Secondary outcomes included ratings of pain and sleep quality as well as the ability to perform daily activities ( Ambulatory Post Acute Care Daily Activities Short Form ) , quality of life ( Functional Assessment of Cancer Therapy-General ) , and fatigue ( Functional Assessment of Cancer Therapy-Fatigue ) . RESULTS Three participants dropped out and seven died ( five in the intervention and two in the control group , P=0.28 ) . At Week 8 , the intervention group reported improved mobility ( P=0.01 ) , fatigue ( P=0.02 ) , and sleep quality ( P=0.05 ) compared with the usual care group , but did not differ on the other measures . CONCLUSION A home-based exercise program seems capable of improving the mobility , fatigue , and sleep quality of patients with Stage IV lung and colorectal cancer PURPOSE Celiac plexus neurolysis ( CPN ) is currently used as salvage therapy for morphine-resistant pancreatic cancer pain . Endoscopic ultrasound-guided CPN ( EUS-CPN ) can be performed early , at the time of EUS . We hypothesized that early EUS-CPN would reduce pain and morphine consumption , increase quality of life ( QOL ) , and prolong survival . PATIENTS AND METHODS Patients were eligible if referred for EUS for suspected pancreatic cancer with related pain . If EUS and EUS-guided fine-needle aspiration cytology confirmed inoperable adenocarcinoma , patients were r and omly assigned to early EUS-CPN or conventional pain management . Pain scores ( 7-point Likert scale ) , morphine equivalent consumption , and QOL scores ( Digestive Disease Question naire-15 ) were assessed at 1 and 3 months . RESULTS Five hundred eighty eligible patients were seen between April 2006 and December 2008 . Ninety-six patients were r and omly assigned ( 48 patients per study arm ) . Pain relief was greater in the EUS-CPN group at 1 month and significantly greater at 3 months ( difference in mean percent change in pain score = -28.9 [ 95 % CI , -67.0 to 2.8 ] , P = .09 , and -60.7 [ 95 % CI , -86.6 to -25.5 ] , P = .01 , respectively ) . Morphine consumption was similar in both groups at 1 month ( difference in mean change in morphine consumption = -1.0 [ 95 % CI , -47.7 to 49.2 ] , P = .99 ) , but tended toward lower consumption at 3 months in the neurolysis group ( difference in mean change in morphine consumption = -49.5 [ 95 % CI , -127.5 to 7.0 ] , P = .10 ) . There was no effect on QOL or survival . CONCLUSION Early EUS-CPN reduces pain and may moderate morphine consumption in patients with painful , inoperable pancreatic adenocarcinoma . EUS-CPN can be considered in all such patients at the time of diagnostic and staging EUS PURPOSE / OBJECTIVES To evaluate the effectiveness of a psychoeducational program ( i.e. , PRO-SELF Pain Control Program ) compared to st and ard care in increasing patients ' knowledge regarding cancer pain management . DESIGN R and omized clinical trial . SETTING Seven outpatient setting s in northern California . SAMPLE 174 out patients with cancer and pain from bone metastasis . METHODS Following r and omization into either the PRO-SELF or st and ard care group , patients completed the Pain Experience Scale ( PES ) prior to and at the completion of the intervention . MAIN RESEARCH VARIABLES Total and individual item scores on the PES . FINDINGS Total PES knowledge scores increased significantly in the PRO-SELF group ( 21 % ) compared to the st and ard care group ( 0.5 % ) . Significant improvements in knowledge scores for patients in the PRO-SELF group were found on five of the nine PES items when compared to baseline scores . CONCLUSIONS The PRO-SELF Pain Control Program was an effective approach to increase patients ' knowledge of cancer pain management . IMPLICATION S FOR NURSING The use of a structured paper- and -pencil question naire , such as the PES , as part of a psychoeducational intervention provides an effective foundation for patient education in cancer pain management . Oncology nurses can use patients ' responses to this type of question naire to individualize the teaching and to spend more time on the identified knowledge deficits . This individualized approach to education about pain management may save staff time and improve patient outcomes BACKGROUND Acupuncture is being used for treatment of cancer-related symptoms in numerous setting s , yet empirical evidence supporting the effects of acupuncture in this setting is lacking . Group acupuncture is an economical way to provide acupuncture to patients at a reduced cost . OBJECTIVE In this retrospective study we sought to evaluate the effects of group acupuncture on specific cancer-related symptoms in persons receiving outpatient cancer treatment . METHODS Patients were receiving group acupuncture treatments through an integrative oncology program in a large community oncology practice in west central Florida . A short patient-completed assessment of seven basic cancer-related symptoms using a 0 - 10 numeric rating scale was completed at each acupuncture treatment . Basic demographic information , including age , gender , race/ethnicity , and cancer type was obtained from the medical record . Paired sample t-tests were used to evaluate differences in symptoms before the first treatment and at the fourth treatment . RESULTS Fifty patients completed at least four weekly acupuncture treatments in 2014 . Forty-three of them completed symptom assessment s and were included in this analysis . The mean age of participants was 66.4 years . The majority of patients were white , non-Hispanic , and female . No significant improvement in symptoms were identified at the third treatment . At the time of the fourth group acupuncture , participants reported significantly less pain/numbness and problems with digestion . DISCUSSION The results of this study provide evidence to support the efficacy of group acupuncture for pain , neuropathy , and digestive problems in persons with cancer . A minimum of four weekly treatments may be necessary before improvements are noted . Limitations include a retrospective design , incomplete symptom evaluation , and possible response bias . Future studies of group acupuncture for cancer-related symptoms should utilize a prospect i ve , controlled design , use vali date d measures to thoroughly evaluate targeted symptoms , and include a more racially and ethnically diverse sample More than 85 % of cancer-related pain is pharmacologically controllable , but some patients require interventional treatments . Although audit assessment of these interventions is of importance to clarify the types of patients likely to receive benefits , there have been no multicenter studies in Japan . The primary aims of this study were ( 1 ) to clarify the frequency of neural blockade in certified palliative care units and palliative care teams , ( 2 ) determine the efficacy of interventions , and ( 3 ) explore the predictors of successful or unsuccessful intervention . All patients who received neural blockade were consecutively recruited from seven certified palliative care units and five hospital palliative care teams in Japan . Primary responsible physicians reported pain intensity on the Support Team Assessment Schedule , performance status , communication levels on the Communication Capacity Scale , presence or absence of delirium , opioid consumption , and adverse effects before and one week after the procedure on the basis of retrospective chart review . A total of 162 interventions in 136 patients were obtained , comprising 3.8 % of all patients receiving specialized palliative care services during the study period . Common procedures were epidural nerve block with local anesthetic and /or opioids ( n = 84 ) , neurolytic sympathetic plexus block ( n = 24 ) , and intrathecal nerve block with phenol ( n = 21 ) . There were significant differences in the frequency of neural blockade between palliative care units and palliative care teams ( 3.1 % vs. 4.6 % , respectively , P = 0.018 ) , and between institutions whose leading physicians are anesthesiologists or have other specialties ( 4.8 % vs. 1.5 % , respectively , P < 0.001 ) . Pain intensity measured on the Support Team Assessment Schedule ( 2.9 + /- 0.8 to 1.7 + /- 0.9 , P < 0.001 ) , performance status ( 2.7 + /- 1.0 to 2.4 + /- 1.0 , P < 0.001 ) , and opioid consumption ( 248 + /- 348 to 186 + /- 288 mg morphine equivalent/day , P < 0.001 ) were significantly improved after interventions . There was a tendency toward improvement in the communication level measured on the Communication Capacity Scale . There was no significant improvement in the prevalence of delirium , but six patients ( 32 % ) recovered from delirium after interventions . Adverse effects occurred in 9.2 % , but all were predictable or transient . No fatal complications were reported . Pain intensity was significantly more improved in patients who survived 28 days or longer than others ( P = 0.002 ) . There were no significant correlations of changes in pain intensity with the performance status or previous opioid consumption . In conclusion , neural blockade was performed in 3.8 % of cancer patients who received specialized palliative care services in Japan . Neural blockade could contribute to the improvement of pain intensity , performance service status , and opioid consumption without unpredictable serious side effects Context Some patients nearing death seek pain relief with massage , but little is known about the effectiveness of massage in managing pain in palliative care setting s. Contribution In this r and omized trial in 380 patients with advanced cancer , improvement in pain and mood immediately after treatment was greater with massage than with simple touch . Unfortunately , there were no sustained differences in pain , quality of life , or analgesic use during 3 weeks . Adverse effects were infrequent and similar in both groups . Implication Massage may offer some immediate relief for patients with advanced cancer , but the absence of sustained effects demonstrates the need for more effective strategies to manage pain at the end of life . The Editors Symptom relief is central to end-of-life care ; however , many terminally ill individuals experience serious pain and other physical and emotional symptoms ( 14 ) . Studies examining the efficacy of therapies that may mediate these symptoms deserve the highest priority . The Institute of Medicine and the National Institutes of Health recommend research directed at improving end-of-life care ( 5 , 6 ) . Pain associated with advanced cancer can cause physical and emotional distress , leading to decreased functional ability and quality of life . Massage may interrupt the cycle of distress through the therapist 's intention ( presence , communication , and desire to produce a therapeutic response ) , induction of a relaxation response , increased blood and lymphatic circulation , potentiation of analgesic effects , decreased inflammation and edema , manual release of muscle spasms , increased endogenous endorphin release , and competing sensory stimuli that override pain signals ( 711 ) . Despite theoretical bases supporting the use and growing acceptance of massage therapy , few r and omized clinical trials have assessed its efficacy . Large trials have been difficult to design and carry out ; challenges include frailty of patients with late-stage cancer and reluctance of health care providers to refer patients because of the possibility of r and omization to nonmassage therapy control ( 12 ) . Therapeutic massage can reduce pain and improve symptom distress and quality of life for patients with cancer at the end of life . The purpose of the REST ( Reducing End-of-Life Symptoms with Touch ) study was to evaluate the efficacy of massage compared with an exposure controlling for time , attention , and touch . We hypothesized that massage would decrease pain and explored effects on quality of life , physical and emotional symptom distress , and analgesic medicine use . Methods Design Overview We conducted this prospect i ve , 2-group , r and omized , single-blind trial between November 2003 and October 2006 . After we evaluated patients for inclusion and exclusion criteria , patients provided written informed consent . Then we r and omly assigned patients to a treatment group ( massage ) or control exposure ( simple touch ) . Figure 1 depicts the timing of the study procedures for a hypothetical participant . We collected individual characteristics , disease , pain characteristics , symptom distress , quality of life , functional status ( Karnofsky Performance Scale score ) ( 13 ) , expected helpfulness of massage for pain , and concurrent interventions ( pharmacologic and nonpharmacologic ) at baseline ( within 72 hours of study enrollment ) and at 3 subsequent weekly visits over the 3 to 4 weeks of participation ( sustained outcomes ) . Final data collection occurred approximately 1 week after the final treatment . Data collectors were blinded to treatment assignment . Participants received up to six 30-minute treatments over 2 weeks , with at least 24 hours between treatment sessions . The initial treatment session occurred within 48 hours of baseline data collection . The treatment provider and patient determined the scheduling of treatment sessions . Treatment providers who were not blinded to treatment assignment obtained the immediate outcomes just before and after every treatment session . All participants received routine care in addition to the specified interventions . The Colorado Multiple Institutional Review Board and , where applicable , site-specific institutional review boards approved the study . Figure 1 . Study overview : timing of study procedures . Setting and Participants Study sites included 15 U.S. hospices that are members of the Population -based Palliative Care Research Network ( PoPCRN ) ( 14 ) and the University of Colorado Cancer Center , Aurora , Colorado . Eligible participants were English-speaking adults with advanced cancer ( stage III or IV , all cancer types , any care setting ) who had at least moderate pain ( score 4 on a 0- to 10-point scale ) in the week before enrollment , an anticipated life expectancy of at least 3 weeks , and the ability to consent . Exclusion criteria included receipt of professional massage within 1 month of enrollment , anticoagulant therapy , known platelet count less than 10109 cells/L , or known unstable spine . R and omization and Interventions Verification of eligibility was forwarded by a study coordinator from each study site to the University of Colorado research ers . Two design ated investigators r and omly assigned patients ; assignments were transmitted back to the requesting site . All study personnel other than the on-site study coordinators and these 2 design ated investigators were blinded to the r and omization sequence . An SAS software program ( SAS Institute , Cary , North Carolina ) generated the r and omization sequence by producing a r and omized block design stratified by study site . Block size r and omly varied among 2 , 4 , and 6 so that it was not possible to predict the next assignment . To minimize the likelihood that potential participants would decline enrollment because of reluctance to be r and omly assigned , we offered massage after study completion to those assigned to the control group . Experimental Treatment : Massage Therapy The massage intervention included gentle effleurage , petrissage , and myofascial trigger point release . Effleurage is a smooth , gliding stroke ; petrissage is squeezing , rolling , and kneading the muscles ; and trigger point release provides concentrated finger pressure to painful localized areas in muscles to break cycles of spasm and pain ( 15 ) . Individual therapist judgment dictated the frequency of rhythm , rate , or stroke ; sequence or mix of strokes ; time spent in each stroke ; stroke length ; and body area massaged ( 16 ) . Massage therapists spent 65 % of the time in effleurage and 35 % in petrissage . The most frequently massaged areas of the body were the neck and upper back ( about 80 % of the time ) and arms , h and s , lower legs , and feet ( about 75 % of the time ) . Other areas , such as the chest , abdomen , buttocks , back of the thighs , and forehead were massaged less than 50 % of the time . Therapists appropriately modified massage in persons with skin fragility , postural limitations , edema , osteoporosis , or bone metastasis . Therapists avoided sites of inflammation or infection , hyperesthesias , injury , surgery , ports , catheters , deep venous thrombosis , and tumors . Therapists identified and treated up to 3 myofascial trigger points per session ( located 15 % to 25 % of the time in the neck , upper trapezius , and lower trapezius regions ) . One half of the sessions were provided with the patient supine , 25 % seated , and the remainder split between side-lying and prone positions . Temperature and level of privacy varied with setting . Fewer than 25 % of participants were unclothed during treatments . Massage was performed by licensed massage therapists who had at least 6 months of experience treating patients with advanced cancer or hospice patients and completed a minimum 500-hour program of study in massage from an institution recognized by their state as a vocational school . Control Exposure We design ed the control exposure , simple touch , to control for the time , attention , touch , and healing intent components of the intervention ( 17 ) . The control consisted of placement of both h and s on the participant for 3 minutes at each of the following locations bilaterally : base of neck , shoulder blades , lower back , calves , heels , clavicles , lower arms , h and s , patellae , and feet . Pressure was light and consistent , with no side-to-side h and movement . Control therapy providers interrupted conscious healing intention by silently counting backward from 100 by 7 , reciting nursery rhymes , or planning their day 's activities ( 18 , 19 ) . The control treatments were provided by individuals with no past body or energy work experience . All treatment providers participated in st and ardized h and s-on training , received a study manual and training video , and were evaluated for competency in study procedures . We monitored adherence to study protocol s during twice-yearly site visits . Treatment providers in both groups used Biotone hypoallergenic unscented massage cream ( Biotone , San Diego , California ) . For the purpose s of st and ardization and to mediate the presence of intervening variables , we did not permit music , essential oils , or energy work and instructed treatment providers to limit their communication to providing instructions or responding to therapy-related questions . To minimize variation by treatment provider , 1 primary massage therapist or simple-touch provider per participant at each study site administered study treatments . Outcomes and Follow-up We used face-to-face , interviewer-administered question naires to collect all study data . We measured neuropathic pain at baseline only by the Neuropathy Pain Scale ( 0- to 10-point scale ) , which is sensitive to pain qualities most common to neuropathic pain syndromes ( 20 , 21 ) . Presence of neuropathic pain was defined as a Neuropathy Pain Scale summary score greater than 3 . Primary Outcomes : Immediate and Sustained Change in Pain The immediate effect was measured by the pain intensity scale of the Memorial Pain Assessment Card ( MPAC ) ( 0 to 10 points ; 10 = worst pain ) ( 22 ) . The sustained effect was measured BACKGROUND Endoscopic ultrasound-guided celiac plexus neurolysis ( EUS-CPN ) represents an alternative approach to pain palliation in patients with advanced pancreatic cancer . AIM to evaluate the safety and initial efficacy of EUS-CPN in patients with painful unresectable pancreatic cancer . METHODS Patients with inoperable body-tail pancreatic adenocarcinoma without prior chemotherapy and pain requiring opioid analgesia were included prospect ively in this cohort study in a tertiary medical center . Central EUS-CPN was performed and the brief pain inventory and the Functional Assessment of Cancer Therapy measurement were applied before and 2 weeks after the procedure . RESULTS Thirty-two patients underwent the procedure in one session without complications . Follow-up revealed overall pain relief in 24 patients ( 75 % ) and significant improvement in pain scores . Ratings of pain interfering with general activity , walking , work , mood , enjoyment of life , relations with others , and sleep improved significantly . Physical , functional , and emotional well-being improved significantly , except for acceptance of illness and enjoyment of life . CONCLUSION Central EUS-CPN was an efficient and safe method for palliative pain management in our patients with inoperable pancreatic body-tail adenocarcinoma . The pain alleviation improved the patients ' functional status , sleep , and quality of life , although other variables could also be involved , but acceptance of the illness and enjoyment of life did not change after treatment PURPOSE Colorectal cancer ( CRC ) may have a negative impact on a person 's quality of life . Psycho-educational interventions for patients with CRC are rarely studied . The purpose of this feasibility trial was to evaluate the effect of a psycho-educational programme ( PEP ) on the health-related quality of life ( HRQL ) of patients treated for CRC and anal cancer . METHODS Patients with CRC and anal cancer were r and omly assigned to a PEP ( n = 47 ) or st and ard treatment ( n = 39 ) . The PEP included informative lectures , discussion , and reflection . HRQL was evaluated using the SF-36 at baseline and 1 , 6 , and 12 months after the end of the PEP . RESULTS Patients in the PEP group had significantly better Mental Health scores after 1 month and significantly better Bodily Pain scores after 6 months compared with patients who received st and ard care . CONCLUSION The results of this study indicate that a PEP can have a short-term effect on the mental health and bodily pain of patients treated for CRC and anal cancer when comparing with a control group . The article discusses the method ological difficulties of evaluating an intervention such as this PEP in a clinical setting Few studies have evaluated cognitive‐behavioral interventions as an adjunct treatment for chronic cancer‐related pain . A r and omized clinical trial was performed evaluating the efficacy of 3 brief cognitive‐behavioral techniques : relaxation , distraction , and positive mood interventions BACKGROUND Pain is a major concern for individuals with cancer , particularly older adults who make up the largest segment of individuals with cancer and who have some of the most unique pain challenges . One of the priorities of hospice is to provide a pain-free death , and while outcomes are better in hospice , patients still die with poorly controlled pain . OBJECTIVE This article reports on the results of a Translating Research into Practice intervention design ed to promote the adoption of evidence -based pain practice s for older adults with cancer in community-based hospices . SETTING This Institutional Human Subjects Review Board-approved study was a cluster r and omized controlled trial implemented in 16 Midwestern hospices . METHODS Retrospective medical records from newly admitted patients were used to determine the intervention effect . Additionally , survey and focus group data gathered from hospice staff at the completion of the intervention phase were analyzed . RESULTS Improvement on the Cancer Pain Practice Index , an overall composite outcome measure of evidence -based practice s for the experimental sites , was not significantly greater than control sites . Decrease in patient pain severity from baseline to post-intervention in the experimental group was greater ; however , the result was not statistically significant ( P = 0.1032 ) . CONCLUSIONS Findings indicate a number of factors that may impact implementation of multicomponent interventions , including unique characteristics and culture of the setting , the level of involvement with the change processes , competing priorities and confounding factors , and complexity of the innovation ( practice change ) . Our results suggest that future study is needed on specific factors to target when implementing a community-based hospice intervention , including determining and measuring intervention fidelity prospect ively Narrative medicine is based upon physicians ' awareness of patients ' narration of their suffering , their hopes , and how illness has affected them . It offers a model for improving health outcomes . To determine whether incorporating a narrative approach in patients with cancer decreases pain intensity and improves their global sense of well-being , we performed a r and omized , single-blind controlled trial in adult patients with cancer and average pain intensity levels of at least 5/10 . Two hundred thirty-four patients were r and omized into three groups : ( 1 ) narrative ( n=79 ) , in which patients wrote a story about how cancer affected their lives for at least 20 minutes once a week for three weeks ; ( 2 ) question naire ( n=77 ) , in which patients filled out the McGill Pain Question naire ; and ( 3 ) control ( n=78 ) , in which patients came weekly to medical visits during which they received usual customary care . Patients rated their pain on a 0 - 10 scale and their well-being on a seven-point Likert scale weekly for eight weeks . Two raters independently evaluated the emotional content of the narratives . Pain intensity and sense of well-being were similar in all groups before and after treatment . Subgroup analyses showed that patients whose narratives had high emotional disclosure had significantly less pain and reported higher well-being scores than patients whose narratives were less emotional . Further study is needed to demonstrate whether the implementation of narrative medicine is associated with health benefits in this and other context In inoperable malignancy , pain relief with opioids is often inadequate . Nerve block procedures may improve symptom control . Our aim was to assess celiac plexus block ( CPB ) and thoracoscopic splanchnicectomy ( TS ) in patients receiving appropriate medical management ( MM ) . Methods : Patients with confirmed irresectable malignancy of the pancreas or upper abdominal viscera who required opioid analgesia were r and omized to MM alone , MM+CPB , or MM+TS . R and omization was stratified by treatment centre , tumour type and previous opioid medication . The primary endpoint was pain relief at 2 months . Results : 65 patients ( 58 pancreas cancer ) were r and omized , 18 withdrew or died within 2 months . Effective pain relief was achieved in only one third of subjects at 2 weeks , and just under half at 2 months ( MM : 6/19 and 5/12 evaluable patients ; CPB : 5/14 and 5/9 ; TS 4/14 and 4/11 ) . There were no significant differences between the groups in pain scores or opioid consumption , and there was no correlation between continued use of opioids and effective pain relief . Discussion : Previous r and omized studies have shown small differences in pain scores , but no difference in opioid consumption and quality of life . The absence of any benefit from interventions in the present study questions their value Background : Patients with acute leukemia usually experience pain , fatigue , and sleep disorders , which affect their quality of life . Massage therapy , as a nondrug approach , can be useful in controlling such problems . However , very few studies have been conducted on the effects of massage therapy on the complications of leukemia . Objective : The aim of this study was to examine the effects of slow-stroke back massage ( SSBM ) on the symptom cluster in acute leukemia adult patients undergoing chemotherapy . Methods : In this r and omized controlled trial , 60 patients with acute leukemia were allocated r and omly to either the intervention or control group . The intervention group received SSBM 3 times a week ( every other day for 10 minutes ) for 4 weeks . The pain , fatigue , and sleep disorder intensities were measured using the numeric rating scale . The sleep quality was measured using the Pittsburgh Sleep Quality Index . Statistical tests of & khgr;2 , t test , and the repeated-measure analysis of variance were used for data analysis . Results : Results showed that the SSBM intervention significantly reduced the progressive sleep disorder , pain , fatigue , and improved sleep quality over time . Conclusions : Slow-stroke back massage , as a simple , noninvasive , and cost-effective approach , along with routine nursing care , can be used to improve the symptom cluster of pain , fatigue , and sleep disorders in leukemia patients . Implication s for Practice : Oncology nurses can increase their knowledge regarding this symptom cluster and work to diminish the cluster components by using SSBM in adult leukemia patients PURPOSE OF THE RESEARCH This paper reports findings from a r and omized controlled pilot study evaluating the PRO-SELF Plus Pain Control Program , a U.S.-developed cancer pain self-management intervention , regarding feasibility and effect sizes in a German patient sample . METHODS AND SAMPLE Thirty-nine German oncology out patients were r and omized to intervention ( n = 19 ) and control ( n = 20 ) groups . The intervention group received the PRO-SELF Plus Pain Control Program in 6 visits and 4 phone calls a 10-week period . The control group received st and ard education and care . The intervention employed three key strategies : information provision , skills building , and nurse coaching . Primary outcomes were changes in average and worst pain intensity . Secondary outcomes included changes in pain-related knowledge , opioid intake , and self-efficacy . Data were collected at enrollment , then at 6 , 10 , 14 , and 22 weeks . KEY RESULTS The group-by-time effect showed a statistically significant increase in knowledge ( week 10 : p = 0.04 ; week 22 : p < 0.01 ) . Despite slight reductions in average and worst pain , no statistically significant changes were found for pain , opioid intake , or self-efficacy . CONCLUSIONS This study is the first to evaluate and demonstrate the feasibility of a U.S.-developed cancer pain self-management intervention in a German patient population . Pain self-management related knowledge improved significantly and effect sizes for pain reduction were determined . Findings from this pilot RCT provide the basis for planning a larger RCT . CLINICAL TRIAL REGISTRATION NUMBER NCT00920504 Purpose . Pain control is an ongoing challenge in the oncology setting . Prior to implementing a large r and omized trial at our institution , we investigated the feasibility , safety , and initial efficacy of acupuncture for uncontrolled pain among cancer patients . Hypotheses . Our hypotheses were that the acupuncture treatments provided would be ( a ) feasible , ( b ) safe , and ( c ) a beneficial adjunct to pain management . Study Design . This was a single arm , nonr and omized pragmatic pilot study . Methods . Participants experiencing pain ≥4 on a 0 to 10 numeric rating scale received a maximum of 10 treatments on an individualized basis . Recruitment , attrition , compliance , and adverse events ( AEs ) were assessed . Pain ( Brief Pain Inventory – Short Form ) , quality of life ( MD And erson Symptom Inventory [ MDASI ] ) , and patient satisfaction were assessed at baseline and at the end of treatment . Results . Of 115 patients screened , 52 ( 45 % ) were eligible and agreed to participate . Eleven ( 21 % ) were lost to follow-up , leaving 41 who completed all study procedures . No AEs were reported . Mean pain severity was 6.0 ± 1.3 at baseline and 3.8 ± 2.0 at follow-up ( P < .0001 ) . Pain interference was 6.2 ± 2.3 at baseline and 4.3 ± 2.8 at follow-up ( P < .0011 ) . On the MDASI , the mean symptom severity was 4.6 ± 1.8 at baseline and 3.2 ± 1.9 at follow-up ( P < .0001 ) , and mean symptom interference was 5.8 ± 2.4 at baseline and 4.1 ± 2.9 at follow-up ( P < .002 ) . Prescribed pain medications decreased across the course of the study . Patient satisfaction was high : 87 % reported that their expectations were met “ very well ” or “ extremely well ” ; 90 % said they were likely to participate again ; 95 % said they were likely to recommend acupuncture to others ; and 90 % reported they found the service to be “ useful ” or “ very useful . ” Conclusions . Acupuncture was feasible , safe , and a helpful treatment adjunct for cancer patients experiencing uncontrolled pain in this study . R and omized placebo-controlled trials are needed to confirm these results Background Despite state-of-the-art therapeutic strategies for pain , some types of chronic pain remain difficult to treat . We evaluated the effectiveness of an innovative neuromodulative approach to the treatment of chronic pain using electrical stimulus integrated with pharmacological support . Methods The MC5-A Calmare © is a new device for patient-specific cutaneous electrostimulation which , by “ scrambling ” pain information with “ no pain ” information , aims to reduce the perception of pain intensity . We prospect ively treated 73 patients with cancer- ( 40 ) and non-cancer-related ( 33 ) pain whose pain management was unsatisfactory . The primary objective of the study was to assess efficacy and tolerability of the device . Pain intensity was assessed daily with a Numerical Rating Scale ( NRS ) for the duration of treatment ( 2 weeks ) and then on a weekly basis for the 2 weeks of follow-up . Results Mean pain value at T0 ( pre-treatment value ) was 6.2 [ ±2.5 SD ( st and ard deviation ) ] , 1.6 ( ±2.0 ) ( p < 0.0001 ) at T2 ( after the 10th day of treatment ) , and 2.9 ( ±2.6 ) ( p < 0.0001 ) at T4 ( after the second week of follow-up , i.e. , 1 month after the beginning of treatment ) . Response after the second week of treatment showed a clear reduction in pain for both cancer ( mean absolute delta of the reduction in NRS value = 4.0 ) and non-cancer ( mean delta = 5.2 ) patients . The pain score had decreased by 74 % at T2 . On the basis of pre-established response criteria , there were 78 % of responders at T2 and 81 % at T4 . No side effects were reported . Conclusions Our preliminary results suggest that cutaneous electrostimulation with the MC5-A Calmare © can be hypothesized as part of a multimodality approach to the treatment of chronic pain . Further studies on larger numbers of patients are needed to assess its efficacy , to quantify the effects of inter-operator variability , and to compare results obtained from the active device versus those from a sham machine Background : The undertreatment of cancer pain remains a significant clinical problem . Objective : The aim of this r and omized controlled trial was to evaluate the efficacy of the PRO-SELF Pain Control Program that was modified for Norwegian cancer patients in decreasing pain and increasing opioid intake compared with control care . Interventions / Methods : Oncology out patients with pain from bone metastasis were r and omized into the PRO-SELF ( n = 87 ) or control ( n = 92 ) groups . A nurse visited patients in the PRO-SELF group in their home at weeks 1 , 3 , and 6 and conducted telephone interviews at weeks 2 , 4 , and 5 . Patients in both groups completed a daily diary of pain intensity ratings and analgesic intake . Results : For both groups , significant decreases in pain intensity scores and in hours per day in pain ( both , P < .001 ) were found over the 6 weeks of the study . However , no significant group × time interactions were found for any of the pain measures . In both groups , total dose of opioid taken increased over time . However , no significant group × time interactions were found for changes over time in the total dose , around-the-clock dose , or as-needed dose of opioid analgesics taken . Conclusions : Possible reasons for the lack of efficacy include an inadequate dose of the psychoeducational intervention , inadequate changes in analgesic prescriptions , and /or the impact of attention provided to the control group . Implication s for Practice : Coaching , nursing support , and the use of a pain diary may be important interventions to reduce pain intensity BACKGROUND AND AIMS Pelvic cancer pain is a chronic pain related to the involvement of viscera , neural , and pelvic muscular . The study was carried out to evaluate the efficacy of anterior ultrasound-guided superior hypogastric plexus neurolysis in pelvic cancer pain in gynecological cancer patients . MATERIAL & METHODS The study was conducted after approval of our Institutional Ethics Committee . A total of 50 patients diagnosed with the advanced stage of a gynecological malignancy with severe pelvic pain were enrolled and r and omly divided in two groups ; in Group I , patients were given oral morphine , while in Group II , patients underwent anterior ultrasonography (USG)-guided superior hypogastric neurolysis . Oral morphine was given as rescue analgesia in both the groups . The parameters recorded were pain , functional capacity , global satisfaction score , and adverse effects . RESULTS There was a significant decrease in visual analog scale ( VAS ) score in the both groups , but the decline in VAS scores from baseline in Group II was significantly ( P < 0.05 ) greater . The daily morphine consumption in Group II decreased throughout the study , and more patients in Group II improved in their functional capacity , although it was statistically insignificant . It was observed that global satisfaction scores were better in Group II during the initial first ( P = 0.001 ) week and 1 month ( P = 0.04 ) compared with Group I. CONCLUSION The anterior USG-guided superior hypogastric plexus neurolysis is a useful technique in relieving pelvic pain in gynecological malignancies . However , it requires expertise to perform the block . It also avoids the radiation exposure involved with computed tomography-guided and fluoroscopy-guided superior hypogastric block Arthralgia affects postmenopausal breast cancer survivors ( BCSs ) receiving aromatase inhibitors ( AIs ) . This study aims to establish the feasibility of study ing the impact of yoga on objective functional outcomes , pain , and health-related quality of life ( HR-QOL ) for AI-associated arthralgia ( AIAA ) . Postmenopausal women with stage I to III breast cancer who reported AIAA were enrolled in a single-arm pilot trial . A yoga program was provided twice a week for 8 weeks . The Functional Reach ( FR ) and Sit and Reach ( SR ) were evaluated as primary outcomes . Pain , as measured by the Brief Pain Inventory ( BPI ) , self-reported Patient Specific Functional Scale ( PSFS ) , and Functional Assessment of Cancer Therapy – Breast ( FACT-B ) were secondary outcomes . Paired t tests were used for analysis , and 90 % provided data for assessment at the end of the intervention . Participants experienced significant improvement in balance , as measured by FR , and flexibility , as measured by SR . The PSFS improved from 4.55 to 7.21 , and HR-QOL measured by FACT-B also improved ; both P < .05 . The score for the Pain Severity subscale of the BPI reduced . No adverse events nor development or worsening of lymphedema was observed . In all , 80 % of participants adhered to the home program . Preliminary data suggest that yoga may reduce pain and improve balance and flexibility in BCSs with AIAA . A r and omized controlled trial is needed to establish the definitive efficacy of yoga for objective functional improvement in BCSs related to AIAA PURPOSE Arthralgia occurs in up to 50 % of breast cancer survivors treated with aromatase inhibitors ( AIs ) and is the most common reason for poor AI adherence . We conducted , in 121 breast cancer survivors receiving an AI and reporting arthralgia , a yearlong r and omized trial of the impact of exercise versus usual care on arthralgia severity . PATIENTS AND METHODS Eligibility criteria included receiving an AI for at least 6 months , reporting ≥ 3 of 10 for worst joint pain on the Brief Pain Inventory ( BPI ) , and reporting < 90 minutes per week of aerobic exercise and no strength training . Participants were r and omly assigned to exercise ( 150 minutes per week of aerobic exercise and supervised strength training twice per week ) or usual care . The BPI , Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index , and Disabilities of the Arm , Shoulder and H and ( DASH ) question naire were completed at baseline and at 3 , 6 , 9 , and 12 months . Intervention effects were evaluated using mixed-model repeated measures analysis , with change at 12 months as the primary end point . RESULTS Over 12 months , women r and omly assigned to exercise ( n = 61 ) attended 70 % ( ± st and ard deviation [ SD ] , 28 % ) of resistance training sessions and increased their exercise by 159 ( ± SD , 136 ) minutes per week . Worst joint pain scores decreased by 1.6 points ( 29 % ) at 12 months among women r and omly assigned to exercise versus a 0.2-point increase ( 3 % ) among those receiving usual care ( n = 60 ; P < .001 ) . Pain severity and interference , as well as DASH and WOMAC pain scores , also decreased significantly at 12 months in women r and omly assigned to exercise , compared with increases for those receiving usual care ( all P < .001 ) . CONCLUSION Exercise led to improvement in AI-induced arthralgia in previously inactive breast cancer survivors Summary A pain consultation combined with a pain education program significantly improves pain , daily interference , and patient adherence in oncology out patients compared with st and ard care . ABSTRACT Pain education programs ( PEP ) and pain consultations ( PC ) have been studied to overcome patient‐related and professional‐related barriers in cancer pain management . These interventions were studied separately , not in combination , and half of the studies reported a significant improvement in pain . Moreover , most PEP studies did not mention the adequacy of pain treatment . We studied the effect of PC combined with PEP on pain and interference by pain with daily functioning in comparison to st and ard care ( SC ) . Patients were r and omly assigned to SC ( n = 37 ) or PC‐PEP ( n = 35 ) . PEP consisted of patient‐tailored pain education and weekly monitoring of pain and side effects . We measured overall reduction in pain intensity and daily interference over an 8‐week period as well as adequacy of pain treatment and adherence . The overall reduction in pain intensity and daily interference was significantly greater after r and omization to PC‐PEP than to SC ( average pain 31 % vs 20 % , P = .03 ; current pain 30 % vs 16 % , P = .016 ; interference 20 % vs 2.5 % , P = .01 ) . Adequacy of pain management did not differ between the groups . Patients were more adherent to analgesics after r and omization to PC‐PEP than to SC ( P = .03 ) . In conclusion , PC‐PEP improves pain , daily interference , and patient adherence in oncology out patients |
1,790 | 23,032,363 | All interventions were feasible to implement in a real-life setting , and theoretical evidence was provided for almost all studies .
All except one self-management interventions were equally effective to or better than the control option .
The self-management articles document substantial benefits for patients , and partly also for health professionals and the health care system .
Supporting self-management seems to be especially promising , but consultation support also shows encouraging results | Objective To assess the method ological quality of the RCTs , and summarize effects and benefits from the method ologically best studies . | OBJECTIVE . Injury risk , depressive symptoms , and substance use are the leading causes of adolescent morbidity and death . The goal of this r and omized , controlled trial was to determine whether computerized screening with real-time printing of results for pediatricians increased the identification of these adolescent behavioral concerns . METHODS . A total of 878 primary care patients 11 to 20 years of age participated in computerized behavioral screening ( the Health eTouch system ) in waiting rooms of 9 urban clinics . These clinics all served predominantly low-income patients . The clinics were r and omly assigned to have pediatricians receive screening results either just before face-to-face encounters with patients ( immediate- results condition ) or 2 to 3 business days later ( delayed- results condition ) . RESULTS . Fifty-nine percent of Health eTouch respondents had positive results for ≥1 of the following behavioral concerns : injury risk behaviors , significant depressive symptoms , or substance use . Sixty-eight percent of youths in the immediate- results condition who screened positive were identified as having a problem by their pediatrician . This was significantly higher than the recognition rate of 52 % for youths in the delayed- results condition . CONCLUSION . Immediate provision of an adolescent 's self-report of behavioral concerns to a pediatrician increased recognition of those problems , compared with the delayed provision of results Background Asthma is a chronic lung disease in which recurrent asthma symptoms create a substantial burden to individuals and their families . At the same time the economic burden associated with asthma is considerable . Methods The cost-effectiveness study was part of a single centre prospect i ve r and omised controlled trial comparing a nurse-led telemonitoring programme to usual care in a population of asthmatic out patients . The study included 109 asthmatic out patients ( 56 children ; 53 adults ) . The duration of follow-up was 12 months , and measurements were performed at baseline , 4 , 8 , and 12 months . Patients were asked to transfer their monitor data at least twice daily and by judging the received data and following a stepwise intervention protocol a nurse was able to act as the main caregiver in the intervention group . In both groups the EQ-5D and the SF-6D were used to obtain estimates of health state utilities . One year health care costs , patient and family costs , and productivity losses were calculated . The mean incremental costs were weighted against the mean incremental effect in terms of QALY . Results The study population generally represented mild to moderate asthmatics . No significant differences were found between the groups with regard to the generic quality of life . Overall , the mean health care costs per patient were higher in the intervention group than in the control group . The intervention costs mainly caused the cost difference between the groups . The intervention costs the society € 31,035/QALY gained with regard to adults and with regard to children € 59,071/QALY gained . Conclusion If the outcome is measured by generic quality of life the nurse-led telemonitoring programme is of limited cost-effectiveness in the study population . From the societal perspective the probability of the programme being cost-effective compared to regular care was 85 % at a ceiling ratio of € 80,000/QALY gained among the adults and 68 % among the children . A decrease in the price of the asthma monitor will substantial increase the probability of the programme to be cost-effective . Trial registration Number : OBJECTIVE ( 1 ) To evaluate preliminary effects of a computerized support system on congruence between patients ' reported symptoms and preferences and those addressed in the patient consultation and ( 2 ) to investigate the system 's ease of use , time requirements , and patient satisfaction . DESIGN Fifty-two patients were r and omly assigned to intervention or control conditions . MEASUREMENTS Cancer patients scheduled for an outpatient visit used the system on a tablet computer to report their symptoms and preferences prior to their consultation . This information was processed , printed , and provided to the patient and clinician in the subsequent consultation in the experimental group but not in the control group . RESULTS While patients in both groups were equivalent at baseline in symptom characteristics , there was significantly greater congruence between patients ' reported symptoms and those addressed by their clinicians in the experimental group . The system scored high on ease of use . There were no significant group differences in patient satisfaction . CONCLUSION This study provided beginning evidence that eliciting patients ' symptoms and preferences and providing clinicians with this information prior to consultation can be an effective and feasible strategy to improve patient-centered care A r and omized , controlled trial was conducted to assess the effectiveness of Blue Angel for Asthma Kids , an Internet-based interactive asthma educational and monitoring program , used in the management of asthmatic children . One hundred sixty-four ( n = 164 ) pediatric patients with persistent asthma were enrolled and r and omized into two study groups for a 12-week controlled trial . The intervention group had 88 participants who were taught to monitor their peak expiratory flows ( PEF ) and asthma symptoms daily on the Internet . They also received an interactive response consisting of a self-management plan from the Blue Angel monitoring program . The control group had 76 participants who received a traditional asthma care plan consisting of a written asthma diary supplemented with instructions for self-management . Disease control was assessed by weekly averaged PEF values , symptom scores , and asthma control tests . Adherence measures were assessed by therapeutic and diagnostic monitoring . Outcome was assessed by examining quality of life and retention of asthma knowledge . The data were analyzed by comparing results before and after the trial . At the end of trial , the intervention group decreased nighttime ( -0.08 + /- 0.33 vs. 0.00 + /- 0.20 , p = 0.028 ) and daytime symptoms ( -0.08 + /- 0.33 vs. 0.01 + /- 0.18 , p = 0.009 ) ; improved morning ( 241.9 + /- 81.4 vs. 223.1 + /- 55.5 , p = 0.017 ) and night PEF ( 255.6 + /- 86.7 vs. 232.5 + /- 55.3 , p = 0.010 ) ; increased adherence rates ( p < 0.05 ) ; improved well-controlled rates ( 70.4 % vs. 55.3 % , p < 0.05 ) ; improved knowledge regarding self-management ( 93.2 % vs. 70.3 % , p < 0.05 ) ; and improved quality of life ( 6.5 + /- 0.5 vs. 4.3 + /- 1.2 on a 7-point scale , p < 0.05 ) when compared with conventional management . The Internet-based asthma telemonitoring program increases selfmanagement skills , improves asthma outcomes , and appears to be an effective and well-accepted technology for the care of children with asthma and their caregivers Heart failure ( HF ) is the leading cause of rehospitalization in older adults . The purpose of this pilot study was to examine whether telemonitoring by an advanced practice nurse reduced subsequent hospital readmissions , emergency department visits , costs , and risk of hospital readmission for patients with HF . One hundred two patient/caregiver dyads were r and omized into 2 groups postdischarge ; 84 dyads completed the study . Hospital readmissions , emergency department visits , costs , and days to readmission were abstract ed from medical records . Participants were interviewed soon after discharge and 3 months later about effects of telemonitoring on depressive symptoms , quality of life , and caregiver mastery . There were no significant differences due to telemonitoring for any outcomes . Caregiver mastery , informal social support , and electronic home monitoring were not significant predictors for risk of hospital readmission . Further studies should address the interaction between the advanced practice nurse and follow-up intervention with telemonitoring of patients with HF to better target those who are most likely to benefit Objective To determine the feasibility and efficacy of a six-month , cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation . Methods Participants who completed a two-week run-in were r and omly assigned to either MOBILE-Coached ( n = 9 ) or MOBILE-Self-Monitored ( n = 8) . All participants met with a nurse to develop an individualized exercise plan , were issued a pedometer and exercise booklet , and instructed to continue to log their daily exercise and symptoms . MOBILE-Coached also received weekly reinforcement text messages on their cell phones ; reports of worsening symptoms were automatically flagged for follow-up . Usability and satisfaction were assessed . Participants completed incremental cycle and six minute walk ( 6MW ) tests , wore an activity monitor for 14 days , and reported their health-related quality of life ( HRQL ) at baseline , three , and six months . Results The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18 % predicted . Participants reported that logging their exercise and symptoms ( FEV1 ) of 40 ± was easy and that keeping track of their exercise helped them remain active . There were no differences between groups over time in maximal workload , 6MW distance , or HRQL ( p > 0.05 ) ; however , MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months ( p = 0.04 ) . Conclusions We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring . The latter finding needs to be interpreted with caution since this was a purely exploratory study . Trial registration Clinical Trials.gov ( NCT00373932 ) Internet-delivered psychological treatment of major depression has been investigated in several trials , but the role of personalized treatment is less investigated . Studies suggest that guidance is important and that automated computerized programmes without therapist support are less effective . Individualized e-mail therapy for depression has not been studied in a controlled trial . Eighty-eight individuals with major depression were r and omized to two different forms of Internet-delivered cognitive behaviour therapy ( CBT ) , or to a waiting-list control group . One form of Internet treatment consisted of guided self-help , with weekly modules and homework assignments . St and ard CBT components were presented and brief support was provided during the treatment . The other group received e-mail therapy , which was tailored and did not use the self-help texts i.e. , all e-mails were written for the unique patient . Both treatments lasted for 8 weeks . In the guided self-help 93 % completed ( 27/29 ) and in the e-mail therapy 96 % ( 29/30 ) completed the posttreatment assessment . Results showed significant symptom reductions in both treatment groups with moderate to large effect sizes . At posttreatment 34.5 % of the guided self-help group and 30 % of the e-mail therapy group reached the criteria of high-end-state functioning ( Beck Depression Inventory score below 9 ) . At six-month follow-up the corresponding figures were 47.4 % and 43.3 % . Overall , the difference between guided self-help and e-mail therapy was small , but in favour of the latter . These findings indicate that both guided self-help and individualized e-mail therapy can be effective BACKGROUND : Interactive Health Communication Applications ( IHCAs ) are computer-based , usually web-based health information packages for patients that combine information with at least one of social support , decision support , or behaviour change support . These are innovations in health care and their effects on health are uncertain . OBJECTIVES : To assess the effects of IHCAs for people with chronic disease . SEARCH STRATEGY : We design ed a four-part search strategy . First , we search ed electronic bibliographic data bases for published work ; second , we search ed the grey literature and third , we search ed for ongoing and recently completed clinical trials in the appropriate data bases . Finally , research ers of included studies were contacted , and reference lists from relevant primary and review articles were followed up . As IHCAs require relatively new technology , the search commenced at 1990 where possible . SELECTION CRITERIA : R and omised controlled trials ( RCTs ) of Interactive Health Communication Applications for adults and children with chronic disease . DATA COLLECTION AND ANALYSIS : One review er screened abstract s. Two review ers screened all c and i date studies to determine eligibility , apply quality criteria , and extract data from included studies . Authors of included RCTs were contacted for missing data . Results of RCTs were pooled using a r and om effects model and st and ardised mean differences ( SMDs ) were calculated to provide net effect sizes . MAIN RESULTS : We screened 24,757 unique citations and retrieved 958 papers for further assessment , yielding 28 RCTs involving 4042 participants . One of these had an inadequate method of concealment of allocation , and sensitivity analyses were performed to determine the effects of including or excluding these data in the meta-analyses . Results in the abstract are from the meta-analyses excluding data from this study .IHCAs were found to have a positive effect on knowledge ( SMD 0.49 ; 95 % confidence interval ( CI ) 0.14 to 0.84 ) and on social support ( SMD 0.47 ; 95 % CI 0.28 to 0.66 ) . IHCAs were found to have no effect on self-efficacy ( SMD 0.15 ; 95 % CI -0.13 to 0.43 ) or behavioural outcomes ( SMD -0.09 ; 95 % CI -0.49 to 0.32 ) . IHCAs had a negative effect on clinical outcomes ( SMD -0.32 ; 95 % CI -0.63 to -0.02 ) . REVIEW ERS ' CONCLUSIONS : The number and range of IHCAs is increasing rapidly ; however there is a shortage of high quality evaluative data . Consumers who wish to increase their knowledge or social support amongst people with a similar problem may find an IHCA helpful . However , consumers whose primary aim is to achieve optimal clinical outcomes should not use an IHCA at present . Further research is needed to determine the reason for this negative effect on clinical outcomes , whether an optimal IHCA can achieve behaviour change and improved health outcomes , and if so , what are the essential features of such an IHCA , and the extent to which they differ according to patient group or condition Cardiovascular disease is the leading cause of morbidity and mortality in the USA . Disease management programs , while successful , are intensive and expensive . Follow-up is often inadequate , incomplete , and inconsistent . To address these problems , we developed an Internet- Telemedicine system . Patients send/receive data to/from their care provider via the Internet . The system optimizes function and minimizes cost ( all hardware is off the shelf and FDA approved ) . We are currently using this Telemedicine system in a prospect i ve , r and omized clinical trial , to reduce CVD risk in medically underserved population s. Over an 8-month time interval , we found very high rates of usage of the Telemedicine system ( 92 % ) . This rate of self-monitoring greatly exceeded the self-monitoring rate in controls ( 48 % ) . The patient-entered Telemedicine blood pressure values were similar to the meter recorded values and to the office values PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial Objectives To evaluate the impact of a mobile phone-based , remote monitoring , advanced symptom management system ( ASyMS © ) on the incidence , severity and distress of six chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) in patients with lung , breast or colorectal cancer . Design A two group ( intervention and control ) by five time points ( baseline , pre-cycle 2 , pre-cycle 3 , pre-cycle 4 and pre-cycle 5 ) r and omised controlled trial . Setting Seven clinical sites in the UK ; five specialist cancer centres and two local district hospitals . Participants One hundred and twelve people with breast , lung or colorectal cancer receiving outpatient chemotherapy . Interventions A mobile phone-based , remote monitoring , advanced symptom management system (ASyMS © ).Main outcome measures Chemotherapy-related morbidity of six common chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) . Results There were significantly higher reports of fatigue in the control group compared to the intervention group ( odds ratio = 2.29 , 95%CI = 1.04 to 5.05 , P = 0.040 ) and reports of h and –foot syndrome were on average lower in the control group ( odds ratio control/intervention = 0.39 , 95%CI = 0.17 to 0.92 , P = 0.031 ) . Conclusion The study demonstrates that ASyMS © can support the management of symptoms in patients with lung , breast and colorectal cancer receiving chemotherapy 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 The evaluation in real-life setting s of services for the follow-up and control of hypertensive patients is a complex intervention , which still needs analysis of the roles , tasks , and re sources involved in the basic items : patient , healthcare professional , and the interaction between the two . To evaluate the impact of patient-general practitioner ( GP ) short-messages-based interaction , isolated from other items , on the degree of hypertension control in the follow-up of medium-to-low-risk patients in primary care , a r and omized controlled trial has been performed : 38 GPs enrolled 285 hypertensive patients who recorded the results of self-blood-pressure ( BP ) monitoring , heart rate , and body weight , and completed an optional question naire in an identical manner over a six-month period . The telemedicine group ( TmG ) sent the data to a telemedicine-based system that enabled patient-GP interaction ; the control group ( CG ) recorded the data on paper and could only deliver it to their GP personally in the routine visits . In the TmG , the results were better , but not significantly so , for : 1 ) degree of hypertension control , in terms of the percentage of uncontrolled hypertensives at the final visit ( TmG versus CG : 31.7 % versus 35.6 % ; p = 0.47 ) ; 2 ) reduction in hypertension during follow-up , comparing measurements ( performed by a professional ) at the initial and final visits of systolic BP ( 15.5 versus 11.9 ; p = 0.13 ) and diastolic BP ( 9.6 versus 4.4 ; p = 0.40 ) ; and 3 ) adherence to the protocol within compliance levels of interest in a real-life follow-up service : Gt50 % ( 84.8 % versus 73.3 % ) and Gt25 % ( 92.4.8 % versus 75.4 % ) ( p = 0.053 ) . Other factors such as average values of self-measured systolic BP , diastolic BP and heart rate , acceptability of the protocol , and median number of consultations and hospital admissions were similar in both groups . Outcomes show that , taken alone , the patient-GP short-messages-based interaction has very little impact on the degree of hypertension control in patients with this profile . In complex interventions , to discriminate the impact of each of its components in isolation will enable us to design an efficient follow-up service , little dem and ing in terms of healthcare professional dedication , and optimized in other basic aspects Electronic health records ( EHRs ) and EHR-connected patient portals offer patient-provider collaboration tools for visit-based care . During a r and omized controlled trial , primary care patients completed pre-visit electronic journals ( eJournals ) containing EHR-based medication , allergies , and diabetes ( study arm 1 ) or health maintenance , personal history , and family history ( study arm 2 ) topics to share with their provider . Assessment with surveys and usage data showed that among 2027 patients invited to complete an eJournal , 70.3 % su bmi tted one and 71.1 % of su bmi tters had one opened by their provider . Surveyed patients reported they felt more prepared for the visit ( 55.9 % ) and their provider had more accurate information about them ( 58.0 % ) . More arm 1 versus arm 2 providers reported that eJournals were visit-time neutral ( 100 % vs 53 % ; p<0.013 ) , helpful to patients in visit preparation ( 66 % vs 20 % ; p=0.082 ) , and would recommend them to colleagues ( 78 % vs 22 % ; p=0.0143 ) . eJournal integration into practice warrants further study Internet-based self-help for social phobia with minimal therapist support via email have shown efficacy in several controlled trials by independent research teams . The role and necessity of therapist guidance is , however , still largely unclear . The present study compared the benefits of a 10-week web-based unguided self-help treatment for social phobia with the same intervention complemented with minimal , although weekly , therapist support via email . Further , a third treatment arm was included , in which the level of support was flexibly stepped up , from no support to email or telephone contact , on dem and of the participants . Eighty-one individuals meeting diagnostic criteria for social phobia were r and omly assigned to one of the three conditions . Primary outcome measures were self-report measures of symptoms of social phobia . Secondary outcome measures included symptoms of depression , interpersonal problems , and general symptomatology . Measures were taken at baseline , post-treatment , and at 6-month follow-up . Data from a telephone-administered diagnostic interview conducted at post-treatment were also included . Results showed significant symptom reductions in all three treatment groups with large effect sizes for primary social phobia measures ( Cohen 's d=1.47 ) and for secondary outcome measures ( d=1.16 ) . No substantial and significant between-groups effects were found on any of the measures ( Cohen 's d=00-.36 ) . Moreover , no difference between the three conditions was found regarding diagnosis-free status , clinical ly significant change , dropout rates , or adherence measures such as lessons or exercises completed . These findings indicate that Internet-delivered treatment for social phobia is a promising treatment option , whether no support is provided or with two different types of therapist guidance OBJECTIVE To examine the effects of a computer-assisted , interactive tailored patient assessment ( ITPA ) tool in oncology practice on : documented patient care , symptom distress , and patients ' need for symptom management support during treatment and rehabilitation . DESIGN AND METHODS For this repeated measures clinical trial at a university hospital in Norway , 145 patients starting treatment for leukemia or lymphoma were r and omly assigned to either an intervention ( n=75 ) or control group ( n=70 ) . Both groups used the ITPA for symptom assessment s prior to inpatient and outpatient visits for up to one year . The assessment summary , which displayed patients ' self-reported symptoms , problems , and distress in rank-order of the patient 's need for support , was provided to physicians and nurses in the intervention group only but not in the control group . RESULTS Significantly more symptoms were addressed in the intervention group patient charts versus those of the control group . Symptom distress in the intervention group decreased significantly over time in 11 ( 58 % ) of 19 symptom/problem categories versus 2 ( 10 % ) for the control group . Need for symptom management support over time also decreased significantly more for the intervention group than the control group in 13 ( 68 % ) symptom categories . CONCLUSION This is the first study to show that an ITPA used in an interdisciplinary oncology practice can significantly improve patient-centered care and patient outcomes , including reduced symptom distress and reduced need for symptom management support Background Internet administered cognitive behaviour therapy ( CBT ) is a promising new way to deliver psychological treatment , but its effectiveness in regular care setting s and in relation to more traditional CBT group treatment has not yet been determined . The primary aim of this study was to compare the effectiveness of Internet- and group administered CBT for panic disorder ( with or without agoraphobia ) in a r and omised trial within a regular psychiatric care setting . The second aim of the study was to establish the cost-effectiveness of these interventions . Methods Patients referred for treatment by their physician , or self-referred , were telephone-screened by a psychiatric nurse . Patients fulfilling screening criteria underwent an in-person structured clinical interview carried out by a psychiatrist . A total of 113 consecutive patients were then r and omly assigned to 10 weeks of either guided Internet delivered CBT ( n = 53 ) or group CBT ( n = 60 ) . After treatment , and at a 6-month follow-up , patients were again assessed by the psychiatrist , blind to treatment condition . Results Immediately after r and omization 9 patients dropped out , leaving 104 patients who started treatment . Patients in both treatment conditions showed significant improvement on the main outcome measure , the Panic Disorder Severity Scale ( PDSS ) after treatment . For the Internet treatment the within-group effect size ( pre-post ) on the PDSS was Cohen 's d = 1.73 , and for the group treatment it was d = 1.63 . Between group effect sizes were low and treatment effects were maintained at 6-months follow-up . We found no statistically significant differences between the two treatment conditions using a mixed models approach to account for missing data . Group CBT utilised considerably more therapist time than did Internet CBT . Defining effect as proportion of PDSS responders , the cost-effectiveness analysis concerning therapist time showed that Internet treatment had superior cost-effectiveness ratios in relation to group treatment both at post-treatment and follow-up . Conclusions This study provides support for the effectiveness of Internet CBT in a psychiatric setting for patients with panic disorder , and suggests that it is equally effective as the more widely used group administered CBT in reducing panic- and agoraphobic symptoms , as well as being more cost effective with respect to therapist time . Trial registration Clinical Trials.gov Background People with chronic obstructive pulmonary disease ( COPD ) continue to experience dyspnea with activities of daily living ( ADL ) despite optimal medical management . Information and communication technologies may facilitate collaborative symptom management and could potentially increase the reach of such interventions to those who are unable to attend face-to-face pulmonary rehabilitation or self-management programs . Objective The purpose of this r and omized study was to test the efficacy of two 6-month dyspnea self-management programs , Internet-based ( eDSMP ) and face-to-face ( fDSMP ) , on dyspnea with ADL in people living with COPD . Methods We r and omly assigned 50 participants with moderate to severe COPD who were current Internet users to either the eDSMP ( n = 26 ) or fDSMP ( n = 24 ) group . The content of the two programs was similar , focusing on education , skills training , and ongoing support for dyspnea self-management , including independent exercise . The only difference was the mode ( Internet/personal digital assistant [ PDA ] or face-to-face ) in which the education sessions , reinforcement contacts , and peer interactions took place . Participants returned to one of two academic clinical sites for evaluation at 3 and 6 months . The primary outcome of dyspnea with ADL was measured with the Chronic Respiratory Question naire . Secondary outcomes of exercise behavior , exercise performance , COPD exacerbations , and mediators , such as self-efficacy and social support , were also measured . A satisfaction survey was administered and a semistructured exit interview was conducted at the final visit . Results The study was stopped early due to multiple technical challenges with the eDSMP , but follow-up was completed on all enrolled participants . Data were available for 39 participants who completed the study ( female : 44 % ; age : 69.5 ± 8.5 years ; percent predicted forced expiratory volume in 1 s : 49.6 ± 17.0 % ) . The fDSMP and eDSMP showed similar clinical ly meaningful changes in dyspnea with ADL from baseline to 3 months ( fDSMP : + 3.3 points ; eDSMP : + 3.5 points ) and sustained these improvements at 6 months ( fDSMP : + 4.0 points ; eDSMP : + 2.5 points ; time effects P < .001 ; group by time P = .51 ) . Self-reported endurance exercise time ( P = .001 ) , physical functioning ( P = .04 ) , and self-efficacy for managing dyspnea ( P = .02 ) also showed positive improvements over time in both groups with no significant differences with respect to program modality . Participants who completed the study reported favorable satisfaction with the programs . Conclusions Although there were numerous technical challenges with the eDSMP , both dyspnea self-management programs were effective in reducing dyspnea with ADL in the short term . Our findings will need to be confirmed in a larger r and omized trial with more mature Web and personal digital assistant tools , use of a control group , and longer follow-up . Trial registration clinical trials.gov NCT00102401 , We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 OBJECTIVE To establish the rate of and reasons for cancellations of surgery on the scheduled day in an Australian hospital . DESIGN Prospect i ve survey . SETTING Major metropolitan tertiary hospital , 13 May to 15 November 2002 . MAIN OUTCOME MEASURES Proportion of operations cancelled on the day of surgery , obtained each day from the operating theatre list and a separate list of additions and cancellations compiled on the day ; reasons for cancellations from the cancellation list , extended or confirmed , as necessary , by question ing of bookings and ward staff , or members of the surgical team ; estimated and actual duration of each operation and patient information from hospital clinical records . RESULTS 7913 theatre sessions were scheduled by 133 surgeons in the study period ; 941 of these ( 11.9 % ) were cancelled on the day , including 724 of 5472 ( 13.2 % ) elective procedures on working weekdays . Main reasons for cancellation were : no theatre time due to over-run of previous surgery ( 18.7 % ) ; no postoperative bed ( 18.1 % ) ; cancelled by patient ( 17.5 % ) ; and change in patient clinical status ( 17.1 % ) . Procedural reasons ( including patient not ready , no surgeon , list error , administrative cause , and communication failure ) totalled 21.0 % . Ear , nose and throat surgery experienced the most cancellations ( 19.6 % ) , followed by cardiothoracic surgery ( 15.8 % ) . CONCLUSIONS There were five major reasons of similar magnitude for on-the-day surgery cancellations . We estimated that 60 % of cancellations of elective procedures were potentially avoidable . Change of one factor leading to cancellation ( eg , provision of more postoperative beds ) is not likely to lead to improvement unless the other major factors are also tackled OBJECTIVE To determine if a patient-centered , computer-assisted diabetes care intervention increased perceived autonomy support , perceived competence ( from self-determination theory ) , and if these constructs mediated the effect of the intervention on ADA/NCQA recommended diabetes care outcomes . DESIGN A r and omized controlled trial of 866 adult type 2 diabetes patients in heterogeneous primary care setting s in Colorado . MAIN OUTCOME MEASURES Perceived autonomy support , perceived competence , patient satisfaction , glycemic control ( HbA1c ) , ratio of total to HDL cholesterol , diabetes distress , and depressive symptoms . RESULTS The computer-assisted intervention increased patient perception of autonomy support relative to a computer-based control condition ( p = .05 ) . Change in perceived competence partially mediated the effects of increased autonomy support on the change in lipids , diabetes distress , and depressive symptoms . The construct of autonomy support was found to be separate from that of patient satisfaction . CONCLUSIONS A patient-centered , computer-assisted intervention was effective in improving diabetes self-management outcomes , in part , because it increased patients ' perception that their autonomy was supported which changed perceived competence . These findings support the self-determination model for health behavior change and the chronic care model and support the further study of the use of these technologies to motivate patients to improve their health outcomes OBJECTIVE To assess the quality of r and omization from reports of trials in a sample of specialist journals , and to compare those results with a similar assessment from a sample of general medical journals . DESIGN Evaluation of all 206 reports of parallel-group r and omized trials published in the 1990 and 1991 volumes of four journals of obstetrics and gynecology and of 81 reports of trials published during 1987 in four general medical journals . RESULTS Of the reports published in the specialist and in the general medical journals , only 32 % and 48 % , respectively , reported having used an adequate method to generate r and om numbers ; only 23 % and 26 % , respectively , contained information showing that steps had been taken to conceal assignment until the point of treatment allocation ; and merely 9 % and 15 % , respectively , described adequate methods of both sequence generation and allocation concealment . In those reports of trials that had apparently used unrestricted r and omization , the differences in sample sizes between treatment and control groups were much smaller than would be expected by chance , and that feature was more marked in the specialist journals . In reports of trials in which hypothesis tests had been used to compare baseline characteristics , only 2 % of tests reported in specialist journals and 4 % of tests reported in general journals were statistically significant , lower than the expected rate of 5 % . CONCLUSIONS Generating unbiased comparison groups requires proper r and omization , yet the reports in these specialist and general journals usually provided inadequate or unacceptable information . Additional analyses suggest that nonr and om manipulation of comparison groups and selective reporting of baseline comparisons may have occurred BACKGROUND Asthma is an important cause of morbidity , absence from school , and use of health services among children . Computer-based educational programs can be design ed to enhance children 's self-management skills and to reduce adverse outcomes . OBJECTIVE To assess the effectiveness of an interactive device programmed for the management of pediatric asthma . DESIGN A r and omized controlled trial ( 66 participants were in the intervention group and 68 were in the control group ) . SETTING Interventions conducted at home and in an outpatient hospital clinic . PARTICIPANTS Inner-city children aged 8 to 16 years diagnosed as having asthma by a physician . INTERVENTION An asthma self-management and education program , the Health Buddy , design ed to enable children to assess and monitor their asthma symptoms and quality of life and to transmit this information to health care providers ( physicians , nurses , or other case managers ) through a secure Web site . Control group participants used an asthma diary . MAIN OUTCOME MEASURES Any limitation in activity was the primary outcome . Secondary outcomes included perceived asthma symptoms , absence from school , any peak flow reading in the yellow or red zone , and use of health services . RESULTS After adjusting for covariates , the odds of having any limitation in activity during the 90-day trial were significantly ( P = .03 ) lower for children r and omized to the Health Buddy . The intervention group also was significantly ( P = .01 ) less likely to report peak flow readings in the yellow or red zone or to make urgent calls to the hospital ( P = .05 ) . Self-care behaviors , which were important correlates of asthma outcomes , also improved far more for the intervention group . CONCLUSION Compared with the asthma diary , monitoring asthma symptoms and functional status with the Health Buddy increases self-management skills and improves asthma outcomes UNLABELLED This study evaluated the ability of end-of-day ( EOD ) ratings to accurately reflect momentary ( EMA ) ratings on 10 widely used pain and fatigue items . Rheumatology patients ( n = 105 ) completed > or=5 r and omly scheduled EMA assessment s of each item per day as well as EOD ratings . Correlations were high between EOD and EMA ratings of the 5 pain items ( r = .90 to .92 ) and somewhat lower for the 5 fatigue/energy items ( r = .71 to .86 ) . To examine the ability of EOD ratings to represent 1 week of EMA ratings , 7 EOD ratings were averaged and correlated with EMA ( r > or= .95 for pain items , r = .88 to .95 for fatigue/energy items ) . Further , averaging only 3 to 5 EOD ratings achieved very high correlations with 1 week of EMA ratings . Within-subject correlations of EOD with mean daily EMA across 7 days confirmed patients ' ability to provide daily ratings that accurately reflect their day-to-day variation in symptom levels . These EOD results were compared to traditional recall ratings collected in the same protocol . It was concluded ( 1 ) that EOD ratings were a better representation of EMA than were recall ratings , and ( 2 ) that EOD ratings across a reporting period can replace EMA for studies targeting average levels of pain or fatigue . PERSPECTIVE This study in chronic pain patients demonstrated that end-of-day ratings of pain are highly accurate representations of average levels of pain experience across a day ; ratings of fatigue were somewhat less accurate , though still at a level that would be valid We conducted a six-month r and omised controlled trial of home telemonitoring for patients with chronic obstructive pulmonary disease ( COPD ) . A total of 40 stable patients with moderate to severe COPD who had completed pulmonary rehabilitation took part . They were r and omised to receive st and ard care ( controls ) or st and ard care plus home telemonitoring ( intervention ) . During the monitoring period , patients in the telemonitoring group recorded their symptoms and physical observations twice daily . The data were transmitted automatically at night via the home telephone line . Nurses could access the data through a website and receive alerting email messages if certain conditions were detected . The patients completed the St George 's Respiratory Question naire , Hospital Anxiety and Depression and the EuroQoL EQ-5D quality of life scores before and after pulmonary rehabilitation , and then periodically during the trial . There were significant and clinical ly important improvements in the scores immediately following pulmonary rehabilitation , but thereafter there were no differences in quality of life scores between the groups at any time , or consistently within either group over time . The study showed that telemonitoring was safe but , despite being well used , it was not associated with changes in quality of life in patients who had stable COPD BACKGROUND Experience from other fields of internal medicine shows that Internet-based technology can be used to monitor various diseases . The new technology h and les complex calculation programs easily , and it is a unique way of communicating . These advantages might be used in optimizing the treatment for asthmatic subjects because undertreatment is a common problem found in European asthmatic subjects . OBJECTIVE We sought to investigate the outcome of monitoring and treatment using a physician-managed online interactive asthma monitoring tool and to assess whether the outcome differs from that of monitoring and treatment in an outpatient respiratory clinic or in primary care . METHODS Three hundred asthmatic subjects were r and omized to 3 parallel groups in a 6-month prospect i ve study : ( 1 ) Internet-based monitoring ( n = 100 ) ; ( 2 ) specialist monitoring ( n = 100 ) ; and ( 3 ) general practitioner ( GP ) monitoring ( n = 100 ) . All the patients were examined on entry into the study and after 6 months of treatment . RESULTS The treatment and monitoring with the Internet-based management tool lead to significantly better improvement in the Internet group than in the other 2 groups regarding asthma symptoms ( Internet vs specialist : odds ratio of 2.64 , P = .002 ; Internet vs GP : odds ratio of 3.26 ; P < .001 ) , quality of life ( Internet vs specialist : odds ratio of 2.21 , P = .03 ; Internet vs GP : odds ratio of 2.10 , P = .04 ) , lung function ( Internet vs specialist : odds ratio of 3.26 , P = .002 ; Internet vs GP : odds ratio of 4.86 , P < .001 ) , and airway responsiveness ( Internet vs GP : odds ratio of 3.06 , P = .02 ) . CONCLUSION When physicians and patients used an interactive Internet-based asthma monitoring tool , better asthma control was achieved BACKGROUND Nearly half of the Norwegian population cl aim that they would like to use the internet to communicate with their general practitioner . A web-based system complying with Norway 's strict statutory requirements for the processing of personal data was developed and tested in an effort to assess the implication s of this mode of communication . MATERIAL AND METHOD The system was tested for one year in a group practice with six doctors . 200 patients were recruited and r and omized into intervention and control groups . Data was collected through question naires , interviews and system logs . RESULTS The 48 patients who used the system sent on average 3.3 messages , the six doctors sent between nine and 65 messages each . Traditional inquiries ( visits , telephones ) to the doctor averaged 3.2 and 4.5 for the intervention and control group respectively . 41 % of the messages were inquiries about health issues , 22 % were about renewals of prescriptions and sick leave notes , while 13 % were requests for an appointment . Patients and doctors were both positive to this mode of communication . Patients who did not use the service said that they expected to use it in the future . INTERPRETATION Electronic communication appears to replace some consultations and telephone inquiries . The study gives reason to expect that communication between patients and general practitioners over the internet will be more important in the future OBJECTIVE There is a well-documented gap between diabetes care guidelines and the services received by patients in most health care setting s. This report presents 12-month follow-up results from a computer-assisted , patient-centered intervention to improve the level of recommended services patients received from a variety of primary care setting s. RESEARCH DESIGN AND METHODS A total of 886 patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program . Physicians were stratified and r and omized to intervention or control conditions and evaluated on two primary outcomes : number of recommended laboratory screenings and recommended patient-centered care activities completed from the National Committee on Quality Assurance/American Diabetes Association Provider Recognition Program ( PRP ) . Secondary outcomes were evaluated using the Problem Areas in Diabetes 2 quality of life scale , lipid and HbA1c levels , and the Patient Health Question naire-9 depression scale . RESULTS The program was well implemented and significantly improved both the number of laboratory assays and patient-centered aspects of diabetes care patients received compared with those in the control condition . There was overall improvement on secondary outcomes of lipids , HbA1c , quality of life , and depression scores ; between-condition differences were not significant . CONCLUSIONS Staff in small , mixed-payer primary care offices can consistently implement a patient-centered intervention to improve PRP measures of quality of diabetes care . Alternative explanations for why these process improvements did not lead to improved outcomes , and suggested directions for future research are discussed The present study investigates the efficacy of an Internet-based cognitive-behavioral therapy program for bereaved people suffering complicated grief . The program combines established methods of psychotherapy with new technology– therapists and patients communicated exclusively by e-mail . Bereaved individuals diagnosed with complicated grief ( n = 55 ) were r and omly assigned to either the treatment group or a waiting list control condition . The 5-week intervention consisted of three modules : ( 1 ) exposure to bereavement cues ; ( 2 ) cognitive re appraisal ; and ( 3 ) integration and restoration . The Impact of Event Scale ( IES ) , a failure to adapt scale , and the depression and anxiety subscales of the Brief Symptom Inventory ( BSI ) were used to assess treatment outcomes . Participants in the treatment group ( n = 26 ) improved significantly relative to participants in the waiting condition on symptoms of intrusion , avoidance , maladaptive behavior , and general psychopathology , and showed a large treatment effect . Follow-up results show that this improvement was maintained after 3 months BACKGROUND AND AIM Electronic patient-provider communication promises to improve efficiency and effectiveness of clinical care . This study aims to explore whether a secure web-based messaging system is an effective way of providing patient care in general practice s. METHOD We conducted a r and omised controlled trail and recruited 200 patients from the waiting area in one primary clinic in Norway . Participants were r and omised to either the intervention group , which received access to a secure messaging system , or the control group receiving st and ard care without such access . Primary outcome measures were number of online consultations , telephone consultations and office visits in the two groups . Data were derived from patient records and collected 1 year prior to ( baseline ) , and 1 year after the intervention . RESULTS Forty-six percent of the patients who were given access to the messaging system ( n=99 ) used the online communication system on at least one occasion ( ranging from 1 to 17 messages per patient per year ) . A total of 147 electronic messages were sent to six general practitioners during a 1-year trial period . Eleven percent of the messages were to schedule an appointment . In 10 % of the messages , the GP was unable to respond adequately and recommended an office visit . The reduction in office visits over time was greater for the intervention group than for the control group ( P=0.034 ) . There was however no significant difference in the number of telephone consultations between the groups during the study ( P=0.258 ) . CONCLUSION The use of a secure electronic messaging system reduced the number of office visits at the general practice , but not phone consultations We have evaluated the feasibility of using the mobile phone short message service ( SMS ) for symptom monitoring in patients with asthma . All consecutive patients admitted to hospital for asthma during an 11-month period were considered for enrolment ( n = 497 ) . Those meeting the inclusion criteria were r and omized into a control ( n = 60 ) and intervention group ( n = 60 ) . Patients in the intervention group received SMS messages according to a structured workflow , while patients in the control group had no SMS support . In the intervention group , the mean response rate to the messages was 82 % . There was an improvement in the Asthma Control Test ( ACT ) scores in 36 subjects in the intervention group compared to 28 subjects in the control group . There were reductions in the number of nebulizations in 54 subjects in the control group compared to 50 subjects in the intervention group , and reductions in emergency department visits in 57 subjects in the control group compared to 51 subjects in the intervention group . However , none of these differences were significant . There was no reduction in admission rates in either group ( P = 0.5 ) . The service was accepted by most patients , but its long-term effectiveness on the management of asthma remains to be determined Background : Efforts to enhance patient-physician communication may improve management of underdiagnosed chronic conditions . Patient internet portals offer an efficient venue for coaching patients to discuss chronic conditions with their primary care physicians ( PCP ) . Objectives : We sought to test the effectiveness of an internet portal-based coaching intervention to promote patient-PCP discussion about chronic conditions . Research Design : We conducted a r and omized trial of a nurse coach intervention conducted entirely through a patient internet-portal . Subjects : Two hundred forty-one patients who were registered portal users with scheduled PCP appointments were screened through the portal for 3 target conditions , depression , chronic pain , mobility difficulty , and r and omized to intervention and control groups . Measures : One-week and 3-month patient surveys assessed visit experiences , target conditions , and quality of life ; chart abstract ions assessed diagnosis and management during PCP visit . Results : Similar high percentages of intervention ( 85 % ) and control ( 80 % ) participants reported discussing their screened condition during their PCP visit . More intervention than control patients reported their PCP gave them specific advice about their health ( 94 % vs. 84 % ; P = 0.03 ) and referred them to a specialist ( 51 % vs. 28 % ; P = 0.002 ) . Intervention participants reported somewhat higher satisfaction than controls ( P = 0.07 ) . Results showed no differences in detection or management of screened conditions , symptom ratings , and quality of life between groups . Conclusions : Internet portal-based coaching produced some possible benefits in care for chronic conditions but without significantly changing patient outcomes . Limited sample sizes may have contributed to insignificant findings . Further research should explore ways internet portals may improve patient outcomes in primary care . Clinical Trials.gov registration NCT00130416 OBJECTIVE . The goal was to determine whether home asthma telemonitoring with store- and -forward technology improved outcomes , compared with in-person , office-based visits . METHODS . A total of 120 patients , 6 to 17 years of age , with persistent asthma were assigned r and omly to the office-based or virtual group . The 2 groups followed the same ambulatory clinical pathway for 12 months . Office-based group patients received traditional in-person education and case management . Virtual group patients received computers , Internet connections , and in-home , Internet-based case management and received education through the study Web site . Disease control outcome measures included quality of life , utilization of services , and symptom control . RESULTS . A total of 120 volunteers ( 45 female ) were enrolled . The groups were clinical ly comparable ( office-based : 22 female/38 male ; mean age : 9.0 ± 3.0 years ; virtual : 23 female/37 male ; mean age : 10.2 ± 3.1 years ) . Virtual patients had higher metered-dose inhaler with valved holding chamber technique scores than did the office-based group at 52 weeks ( 94 % vs 89 % ) , had greater adherence to daily asthma symptom diary su bmi ssion ( 35.4 % vs 20.8 % ) , had less participant time ( 636 vs 713 patient-months ) , and were older . Caregivers in both groups perceived an increase in quality of life and an increase in asthma knowledge scores from baseline . There were no other differences in therapeutic or disease control outcome measures . CONCLUSIONS . Virtual group patients achieved excellent asthma therapeutic and disease control outcomes . Compared with those who received st and ardized office-based care , they were more adherent to diary su bmi ssion and had better inhaler scores at 52 weeks . Store- and -forward telemedicine technology and case management provide additional tools to assist in the management of children with persistent asthma ABSTRACT Aim . To see if home telemonitors reduce healthcare use in those with optimized chronic obstructive pulmonary disease ( COPD ) . Methods . We r and omized 40 stable patients with moderate to severe COPD , who had completed at least 12 sessions of outpatient pulmonary rehabilitation ( PR ) , to receive st and ard care ( Controls ) for 52 weeks or st and ard care plus Docobo HealthHUB monitors at home for 26 weeks followed by 26 weeks st and ard care ( Tm Group ) . During the monitoring period , the Tm Group completed symptoms and physical observations twice daily which were stored and then uploaded at 2 am through a freephone l and line . Nurses could access the data through a secure web site and received alerting e-mails if certain combinations of data occurred . Results . There were fewer primary care contacts for chest problems ( p < 0.03 ) in the Tm group , but no differences between the groups in emergency room visits , hospital admissions , days in hospital or contacts to the specialist COPD community nurse team , during the monitoring period . After the monitors were removed , there were no differences between the groups for any of the health care contacts ( p > 0.20 throughout ) . Conclusion . In stable , optimized COPD patients who have already completed PR , telemonitoring in addition to best care , reduces primary care chest contacts but not hospital or specialist team utilization RATIONALE , AIMS AND OBJECTIVES The aim of the study was to evaluate the effects on , and the relationship between , asthma symptoms , asthma-specific quality of life and medical consumption of a nurse-led telemonitoring intervention compared with regular care in asthma in the Netherl and s. METHODS One hundred and nine asthmatic out patients ( 56 children ; 53 adults ) were r and omly assigned to the treatment arms ( 12-month follow-up ) . The control group received regular outpatient care , while the intervention group used an asthma monitor with modem at home with an asthma nurse as the main caregiver . Clinical asthma symptoms and medical consumption were measured by using diaries . Asthma-specific quality of life was measured by the ( Paediatric ) Asthma Quality of Life Question naire . RESULTS The study population generally represented mild to moderate asthmatics . The results show improvement in follow-up , but no statistically significant difference between the groups was observed . Moderate to high correlations were found within the outcome parameters , but the most remarkable was the low and statistically significant correlation between asthma-specific quality of life ( daily functioning ) and the self-reported beta-2 agonists . CONCLUSION Overall , the telemonitoring programme evaluated in this study did not significantly decrease asthma symptoms or medical consumption , or improve asthma-specific quality of life . The results showed that a telemonitoring programme on its own is not a guarantee of success . The patients ' perception of asthma-specific quality of life ( daily functioning ) should be a key element in asthma telemonitoring programmes Background There has been relatively little research on the role of web-based support for self-care in the management of minor , acute symptoms , in contrast to the wealth of recent research into Internet interventions to support self-management of long-term conditions . Objective This study was design ed as an evaluation of the usage and effects of the “ Internet Doctor ” website providing tailored advice on self-management of minor respiratory symptoms ( eg , cough , sore throat , fever , runny nose ) , in preparation for a definitive trial of clinical effectiveness . The first aim was to evaluate the effects of using the Internet Doctor webpages on patient enablement and use of health services , to test whether the tailored , theory-based advice provided by the Internet Doctor was superior to providing a static webpage providing the best existing patient information ( the control condition ) . The second aim was to gain an underst and ing of the processes that might mediate any change in intentions to consult the doctor , by comparing changes in relevant beliefs and illness perceptions in the intervention and control groups , and by analyzing usage of the Internet Doctor webpages and predictors of intention change . Methods Participants ( N = 714 ) completed baseline measures of beliefs about their symptoms and self-care online , and were then automatically r and omized to the Internet Doctor or control group . These measures were completed again by 332 participants after 48 hours . Four weeks later , 214 participants completed measures of enablement and health service use . Results The Internet Doctor result ed in higher levels of satisfaction than the control information ( mean 6.58 and 5.86 , respectively ; P = .002 ) and result ed in higher levels of enablement a month later ( median 3 and 2 , respectively ; P = .03 ) . Underst and ing of illness improved in the 48 hours following use of the Internet Doctor webpages , whereas it did not improve in the control group ( mean change from baseline 0.21 and -0.06 , respectively , P = .05 ) . Decline in intentions to consult the doctor between baseline and follow-up was predicted by age ( beta = .10 , P= .003 ) , believing before accessing the website that consultation was necessary for recovery ( beta = .19 , P < .001 ) , poor underst and ing of illness ( beta = .11 , P = .004 ) , emotional reactions to illness ( beta = .15 , P < .001 ) , and use of the Diagnostic section of the Internet Doctor website ( beta = .09 , P = .007 ) . Conclusions Our findings provide initial evidence that tailored web-based advice could help patients self-manage minor symptoms to a greater extent . These findings constitute a sound foundation and rationale for future research . In particular , our study provides the evidence required to justify carrying out much larger trials in representative population sample s comparing tailored web-based advice with routine care , to obtain a definitive evaluation of the impact on self-management and health service use PURPOSE To examine the effects on process of care and patient well-being , of the regular collection and use of health-related quality -of-life ( HRQL ) data in oncology practice . PATIENTS AND METHODS In a prospect i ve study with repeated measures involving 28 oncologists , 286 cancer patients were r and omly assigned to either the intervention group ( regular completion of European Organization for Research and Treatment of Cancer-Core Quality of Life Question naire version 3.0 , and Hospital Anxiety and Depression Scale on touch-screen computers in clinic and feedback of results to physicians ) ; attention-control group ( completion of question naires , but no feedback ) ; or control group ( no HRQL measurement in clinic before encounters ) . Primary outcomes were patient HRQL over time , measured by the Functional Assessment of Cancer Therapy-General question naire , physician-patient communication , and clinical management , measured by content analysis of tape-recorded encounters . Analysis employed mixed-effects modeling and multiple regression . RESULTS Patients in the intervention and attention-control groups had better HRQL than the control group ( P = .006 and P = .01 , respectively ) , but the intervention and attention-control groups were not significantly different ( P = .80 ) . A positive effect on emotional well-being was associated with feedback of data ( P = .008 ) , but not with instrument completion ( P = .12 ) . A larger proportion of intervention patients showed clinical ly meaningful improvement in HRQL . More frequent discussion of chronic nonspecific symptoms ( P = .03 ) was found in the intervention group , without prolonging encounters . There was no detectable effect on patient management ( P = .60 ) . In the intervention patients , HRQL improvement was associated with explicit use of HRQL data ( P = .016 ) , discussion of pain , and role function ( P = .046 ) . CONCLUSION Routine assessment of cancer patients ' HRQL had an impact on physician-patient communication and result ed in benefits for some patients , who had better HRQL and emotional functioning The adherence and disease-control outcomes associated with the use of an Internet-based store- and -forward video home telehealth system to manage asthma in children were studied . Pediatric patients with persistent asthma were provided with home computers and Internet access and monitored biweekly over the Internet . All patients were seen in the pediatric clinic at 0 , 2 , 6 , 12 , and 24 weeks . Half of the patients received asthma education in person and half via an interactive Web site . Adherence measures were assessed by therapeutic and diagnostic monitoring . Therapeutic monitoring included digital videos of patients using their controller medication inhaler . Diagnostic monitoring included an asthma symptom diary and a video of peak flow meter use . Videos were su bmi tted electronically twice a week by using in-home telemonitoring with store- and -forward technology . Feedback was provided electronically to each patient . Disease control was assessed by examining quality of life , utilization of services , rescue-therapy use , symptom control , satisfaction with home telemonitoring , and retention of asthma knowledge . Patients were r and omly assigned to an asthma education group ( Internet versus office ) , and the data were analyzed by comparing results for study days 0 - 90 and 91 - 180 . Ten children participated . A total of 321 videos of inhaler use and 309 videos of peak flow meter use were su bmi tted . Inhaler technique scores improved significantly in the second study period . Su bmi ssion of diagnostic monitoring videos and asthma diary entries decreased significantly . Peak flow values as a percentage of personal best values increased significantly . Overall , there was no change in quality of life reported by patients . However , the caregivers in the virtual-education group reported an increase in the patients ' quality -of-life survey scores . Emergency department visits and hospital admissions for asthma were avoided . Rescue therapy was infrequent . A high rate of satisfaction with home telemonitoring was reported . Internet-based , store- and -forward video assessment of children 's use of asthma medications and monitoring tools in their homes appeared effective and well accepted R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community Context Patient self-management is an essential component of asthma care , and the Internet is a medium to potentially support patients in self-management . Contribution This r and omized trial compared Internet-based asthma self-management with usual care and found modest improvements in asthma control and lung function with the Internet intervention , but found no reduction in exacerbations and changes in asthma-related quality of life that were less than clinical ly significant at 12 months . Implication Although Internet-based self management can improve some asthma outcomes , the improvements were small and the program did not reduce the number of exacerbations . The Editors Asthma is a chronic disorder of the airways that is characterized by recurring respiratory symptoms , variable airflow obstruction , airway hyperresponsiveness , and underlying inflammation ( 1 , 2 ) . Recent clinical guidelines for the management of asthma distinguish 4 essential components of asthma care : assessment and monitoring , patient education , control of environmental and comorbid factors that affect asthma , and drug treatment . With appropriate medical care , well-informed and empowered patients can control their asthma and live full , active lives ( 1 , 2 ) . However , despite the availability of monitoring tools and effective therapy , asthma control is suboptimal in many patients worldwide , and long-term management falls far short of the goals set in the guidelines ( 3 ) . Self-monitoring , education , and specific medical care are important aspects in improving the lives of patients with asthma ( 1 , 2 ) . However , many patients with mild or moderate persistent asthma do not attend checkups regularly or visit their physician with symptoms of the disease ( 4 ) . In addition , in practice , both patients and their health care providers are reluctant to use written self-management plans ( 5 ) . Internet technology is increasingly seen as an appealing tool to support self-management for patients with chronic disease in remote and underserved population s ( 68 ) . However , to date , studies on Internet-based asthma self-management show only short-term improvements in asthma control , lung function , and quality of life ( 911 ) . Long-term studies on the effect of Internet-based self-management , including all its essential features , are not available . Therefore , we developed a guided self-management tool for adult patients with asthma that included Internet-based home monitoring and treatment advice ( action plan ) , online education , and remote Web communication with a specialized asthma nurse . The goal of our study was to assess the long-term clinical effectiveness of Internet-based self-management education compared with usual physician-provided care alone . Methods Design Overview We conducted a 12-month , multicenter , nonblinded , r and omized , controlled trial . We r and omly assigned patients to Internet-based self-management ( Internet group ) as an adjunct to usual care or to usual physician-provided care alone ( usual care group ) . The Internet-based self-management program included weekly asthma control monitoring and treatment advice , online and group education , and remote Web communications with a specialized asthma nurse . The intervention continued for 12 months after enrollment . The Medical Ethics Committee of the Leiden University Medical Center , Leiden , the Netherl and s , approved the study . Setting and Participants We recruited patients from 37 general practice s ( 69 general practitioners ) in the Leiden and The Hague area and the Outpatient Clinic of the Department of Pulmonology at the Leiden University Medical Center from September 2005 to September 2006 . Inclusion criteria were physician-diagnosed asthma coded according to the International Classification of Primary Care in the electronic medical record ( 12 ) , age 18 to 50 years , prescription of inhaled corticosteroids for at least 3 months in the previous year , no serious comorbid conditions that interfered with asthma treatment , access to the Internet at home , and mastery of the Dutch language . We excluded patients who were receiving maintenance oral glucocorticosteroid treatment . On the basis of diagnosis , age , prescribed asthma medication , and comorbid conditions , we sent eligible patients an invitation letter followed by 1 reminder letter after 2 to 4 weeks if they did not respond to the first . We continued this process until a total of 200 patients had entered the study ( September 2006 ) . All participants gave written consent . R and omization and Intervention In a 2-week baseline period before r and omization , we collected data on patient demographic characteristics , asthma-related quality of life , symptom control , lung function , and medication level . We provided basic education about core information on asthma , action of medications , and inhaler technique instructions to all patients . We trained all participants to measure FEV1 daily with a h and -held electronic spirometer ( PiKo-1 , Ferraris Respiratory , Hertford , United Kingdom ) and to report the highest value of 3 measurements in the morning before taking medication ( 2 , 13 ) . They were shown how to report these values on a personal page on a secure Web application by using a login password ( or how to report by mobile telephone text message ) . Patients were also asked to report their nighttime and daytime asthma symptom scores on this Internet page or by text message . We asked all participants to complete the Asthma Control Question naire on their personal Internet page each week ( 14 ) . We did not give any patients feedback about lung function or asthma control . After the 2-week baseline period , we r and omly assigned participants to either the Internet group or the usual care group . We stratified according to care provider ( primary vs. subspecialty care ) and asthma control at baseline ( 15 ) . We r and omly assigned patients to the 2 groups ( 1:1 ratio ) by using a computer-generated , permuted-block scheme . Allocation took place by computer after collection of the baseline data , ensuring concealment of allocation . The Internet-based self-management program consisted of the 4 principal components of asthma self-management and was accessed through the specially design ed Web site , which allowed monitoring through the Web site ( or text message on a mobile telephone ) , use of an Internet-based treatment plan , online education , and Web communications with a specialized asthma nurse ( 16 ) . Patients monitored their asthma weekly by completing an electronic version of the Asthma Control Question naire on the Web site and instantly received feedback on the current state of their asthma control along with advice on how to adjust their treatment according to a predefined algorithm and treatment plan ( Table 1 and Appendix Figures 1 , 2 , 3 , 4 , and 5 ) . Depending on the scores su bmi tted , patients received 4 types of self-treatment advice . When 4 consecutive Asthma Control Question naire scores were 0.5 or less , patients were advised to decrease treatment according to treatment plan . When 2 consecutive scores were greater than 0.5 but less than 1.0 , patients were advised to increase treatment according to treatment plan . When 1 score was 1.0 or more but less than 1.5 , patients were advised to immediately increase treatment according to treatment plan . Finally , when 1 score was 1.5 or more , patients were advised to immediately increase treatment and contact the asthma nurse . Table 1 . Treatment Plan Appendix Figure 1 . Algorithm based on consecutive ACQ scores to adjust medical treatment . * ACQ = Asthma Control Question naire . At entry of the algorithm , the evaluation period is bypassed . The evaluation period starts after treatment was stepped up . The optimal control period starts after 1 ACQ score 0.5 and ends after 1 ACQ score > 0.5 . Appendix Figure 2 . Screen shot of daily lung function and symptom monitoring . Appendix Figure 3 . Screen shot of feedback on daily lung function and symptom monitoring . Appendix Figure 4 . Screen shot of weekly Asthma Control Question naire monitoring . Appendix Figure 5 . Screen shot of feedback on Asthma Control Question naire , treatment advice according to personalized treatment plan , and results of past 6 months . We advised no medication changes during the 4 weeks after treatment was stepped up ( evaluation period ) . In addition to weekly assessment s , patients could optionally report daily symptoms and lung function and were able to contact our asthma nurse though the Web or by telephone . Thus , any acute deterioration warranting a visit to the general practitioner or hospital could be detected ( Appendix Figures 2 and 3 ) . We aim ed to empower patients to use the Internet-based self-management tool and to develop a patientprovider partnership in asthma care ( 2 ) . Self-management education consisted of both Web-based and face-to-face , group-based education . Web-based education included asthma information , news , frequently asked questions , and interactive communication with a respiratory nurse specialist . We scheduled 2 group-based education sessions , which lasted 45 to 60 minutes , for patients in the Internet-based self-management group within 6 weeks after entering the trial . Both sessions included exploration of a patient 's interests and previous knowledge ( negotiating an agenda and patient-centered education ) , personalized feedback , and empowerment of self-management ( self-efficacy and implementing a plan for change ) ( 2 , 17 ) . The first educational session also included pathophysiology of asthma , information on the Web-based action plan , and information and review of inhalation technique . The second educational session gave information about the mechanisms and side effects of medication and explained trigger avoidance . Patients in the usual care group received asthma care according to the Dutch general practice guidelines on asthma management in adults , which recommend a medical review and treatment adjustment every 2 to 4 weeks in unstable asthma and medical review once or twice Cancellation of scheduled surgery is undesirable for patients and an inefficient use of re sources . We prospect ively collected data for 52 consecutive months in a public general hospital to estimate the prevalence and causes . The overall cancellation rate was 6.5 % ( 2559 of 39 115 scheduled operations ) . Cancellation by broad category was for ‘ medical reasons ’ in 50 % , ‘ patient‐related factors ’ in 23 % , and due to ‘ administrative/logistic problems ’ in 25 % . The commonest specific causes within these categories were respectively : infections/fever ( 18 % ) , patient did not attend ( 20 % ) and lack of theatre time ( 23 % ) . This data will help direct re sources to target prevention of cancellations as a result of these main problems |
1,791 | 23,933,855 | In conclusion , r and omized studies in humans suggest that statin therapy mobilizes EPCs into the circulation . | Numerous clinical trials have demonstrated early reductions in cardiovascular events occurring independently of the lipid-lowering effects of statins .
These pleiotropic effects have been attributed to antiinflammatory properties , to atherosclerotic plaque stabilization , and more recently to mobilization of endothelial progenitor cells ( EPCs ) .
Our aim was to evaluate the evidence supporting statin-induced EPC mobilization in humans .
We , therefore , performed a computerized literature search and systematic review of r and omized trials to determine the effect of statin therapy and statin dosing on circulating EPC numbers . | BACKGROUND Intensive statin therapy can lower the risk of recurrence of major cardiac events in patients with acute coronary syndromes . This could be related to the ability of statins to increase levels of Endothelial Progenitor Cells ( EPCs ) , which were demonstrated to be favorably associated with a better prognosis and post-infa rct ion left ventricular remodeling in patients with ischemic heart disease . AIM OF THE STUDY First , to evaluate , in a r and omized clinical trial , the effect of an intensive vs a st and ard treatment with statins on EPC mobilization in patients undergoing a successful primary or rescue percutaneous coronary intervention ; secondary , to evaluate whether left ventricular remodeling could be influenced by statin therapy through EPC mobilization . METHODS Forty ST-segment elevation myocardial infa rct ion ( STEMI ) patients undergoing a successful primary or rescue PCI were r and omized to receive atorvastatin 80 mg immediately after the admission ( Intensive Treatment , IT ) or atorvastatin 20 mg from the day of the discharge ( St and ard Treatment , ST ) . CD34+/KDR+ EPC count by flow cytometry and left ventricular function by 2-D Echo were measured on admission , at discharge and at 4 months follow up . RESULTS We found that EPC count was similar in the two groups of patients both on admission and at discharge . At follow up , however , EPC count was higher in patients r and omized to IT compared to patients r and omized to ST ( 7.59+/-7.30 vs 3.04+/-3.93 , p=0.04 ) . However , LV volumes , ejection fraction and wall motion score index were similar in both groups . CONCLUSIONS An intensive statin treatment after primary or rescue PCI is associated with a higher EPC count at follow up as compared to st and ard treatment . This beneficial effect did not translate in an improvement of LV function Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p < 0.00001 ) , and the respective probabilities of escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p < 0.00001 ) in the risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients CONTEXT Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome , but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events . OBJECTIVE To determine whether treatment with atorvastatin , 80 mg/d , initiated 24 to 96 hours after an acute coronary syndrome , reduces death and nonfatal ischemic events . DESIGN AND SETTING A r and omized , double-blind trial conducted from May 1997 to September 1999 , with follow-up through 16 weeks at 122 clinical centers in Europe , North America , South Africa , and Australasia . PATIENTS A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infa rct ion . INTERVENTIONS Patients were stratified by center and r and omly assigned to receive treatment with atorvastatin ( 80 mg/d ) or matching placebo between 24 and 96 hours after hospital admission . MAIN OUTCOME MEASURES Primary end point event defined as death , nonfatal acute myocardial infa rct ion , cardiac arrest with resuscitation , or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization . RESULTS A primary end point event occurred in 228 patients ( 14.8 % ) in the atorvastatin group and 269 patients ( 17.4 % ) in the placebo group ( relative risk [ RR ] , 0.84 ; 95 % confidence interval [ CI ] , 0.70 - 1.00 ; P = .048 ) . There were no significant differences in risk of death , nonfatal myocardial infa rct ion , or cardiac arrest between the atorvastatin group and the placebo group , although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization ( 6.2 % vs 8.4 % ; RR , 0.74 ; 95 % CI , 0.57 - 0.95 ; P = .02 ) . Likewise , there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures , worsening heart failure , or worsening angina , although there were fewer strokes in the atorvastatin group than in the placebo group ( 12 vs 24 events ; P = .045 ) . In the atorvastatin group , mean low-density lipoprotein cholesterol level declined from 124 mg/dL ( 3.2 mmol/L ) to 72 mg/dL ( 1.9 mmol/L ) . Abnormal liver transaminases ( > 3 times upper limit of normal ) were more common in the atorvastatin group than in the placebo group ( 2.5 % vs 0.6 % ; P<.001 ) . CONCLUSION For patients with acute coronary syndrome , lipid-lowering therapy with atorvastatin , 80 mg/d , reduces recurrent ischemic events in the first 16 weeks , mostly recurrent symptomatic ischemia requiring rehospitalization Objectives We investigated the effects of short-term use of atorvastatin on CD34+/VEGF-R2+/CD133+/CD45- endothelial progenitor cell ( EPC ) count after on-pump coronary artery bypass surgery ( CABG ) . Methods Between Feb-2010 and May-2010 , we r and omly assigned , in a placebo-controlled , double-blind study , 60 consecutive patients who underwent isolated , first-time CABG to receive either 14-day atorvastatin ( 40 mg/day ) or placebo preoperatively . Urgent CABG and recent myocardial infa rct ion were excluded . EPCs were quantified ( cells/μl ) by flow cytometric phenotyping obtained from venous blood sample s collected preoperatively ( T1 ) , 6-hours ( T2 ) , and on the 5th day postoperatively ( T3 ) . Levels of markers of inflammation and serum cardiac troponin I were also measured preoperatively and daily until day-5 after surgery . Results There were no differences in baseline risk factors including cholesterol profiles , and EuroSCORES between the groups . The composite primary end-point , favored statin group with higher amount of circulating , early EPC count ( cells/μl ) at all time points compared with placebo ( T1 , 2.30 ± 0.02 versus 1.58 ± 0.03 , p < 0.001 ; T2 , 5.00 ± 0.06 versus 2.19 ± 0.06 , p < 0.001 ; T3 , 3.03 ± 0.08 versus 1.78 ± 0.02 , p < 0.001 ) . Postoperative hsCRP rise were inversely correlated with EPC count , and were significantly lower in the statin group ( T1 , 0.8 ± 0.1 versus 2.2 ± 1.5 , p < 0.001 ; T2 , 72.9 ± 3.2 versus 96.0 ± 3.6 , p < 0.001 ; T3 , 4.3 ± 1.2 versus 11.4 ± 4.1 , p < 0.001 ) . Furthermore , the incidence of postoperative atrial fibrillation was significantly lower in the statin group compared to placebo ( 3.3 % versus 23 % , p = 0.02 ) . Conclusions Short-term atorvastatin use increases circulating early EPCs both pre- and post-operatively and is associated with better preservation of sinus rhythm and reduced hsCRP levels . ( Clinical Trials.gov number , NCT01096875 BACKGROUND Smoking is a major cardiovascular risk factor , leading to endothelial dysfunction . The present study investigated the hypothesis that pitavastatin , an HMG-CoA reductase inhibitor , may improve endothelial function in chronic smokers via its antioxidant properties . METHODS AND RESULTS The 30 male chronic smokers who exhibited mild hypercholesterolemia at the time of physical check-up were enrolled and r and omized to the pitavastatin group ( 2 mg/day , n=15 ) or the untreated control group ( n=15 ) . Before and after the 4-week treatment period , endothelium-dependent flow-mediated dilation ( FMD ) and endothelium-independent dilation by glyceryl trinitrate ( GTD ) were examined , and the FMD/GTD ratio was calculated . The pitavastatin group showed a significant restoration of endothelial function ( percent change in FMD : + 49.6 % vs + 1.4 % ; percent change in FMD/GTD ratio : + 26.6 % vs 4.5 % , P<0.05 respectively ) , and a significant reduction in oxidative stress levels ( malondialdehyde-low-density lipoprotein-cholesterol : 16.6 % vs + 7.5 % ; free radical activity : 1.8 % vs + 9.7 % , P<0.05 respectively ) compared with the control group . Pitavastatin had no effect on the number of circulating CD34(+)CD133(+ ) progenitor cells , endothelial progenitor cells , or the MMP-2 , MMP-9 and VEGF levels . In vitro oxidative stress monitoring assay revealed that pitavastatin protected endothelial cells against oxidative stress . CONCLUSIONS Pitavastatin restores endothelial function , even in chronic smokers , possibly through its antioxidative properties . ( Circ J 2010 ; 74 : 195 - 202 ) Background —Endothelial nitric oxide ( eNO ) bioavailability is severely reduced after myocardial infa rct ion ( MI ) and in heart failure . Statins enhance eNO availability by both increasing eNO production and reducing NO inactivation . We therefore studied the effect of statin treatment on eNO availability after MI and tested its role for endothelial progenitor cell mobilization , myocardial neovascularization , left ventricular ( LV ) dysfunction , remodeling , and survival after MI . Methods and Results —Wild-type ( WT ) and eNO synthase (eNOS)−/− mice with extensive anterior MI were r and omized to treatment with vehicle ( V ) or atorvastatin ( Ator , 50 mg/kg QD by gavage ) for 4 weeks starting on day 1 after MI . Ator markedly improved endothelium-dependent , NO-mediated vasorelaxation ; mobilization of endothelial progenitor cells ; and myocardial neovascularization of the infa rct border in WT mice after MI while having no effect in eNOS−/− mice . LV dysfunction and interstitial fibrosis were markedly attenuated by Ator in WT mice , whereas no effect was observed in eNOS−/− mice after MI . Importantly , Ator significantly increased the survival rate during 4 weeks after MI in WT mice ( Ator versus V , 80 % versus 46 % ; P<0.01 , n=75 ) but not in eNOS−/− mice ( 43 % versus 48 % ; NS , n=42 ) . Conclusions —These findings suggest that increased eNO availability is required for statin-induced improvement of endothelial progenitor cell mobilization , myocardial neovascularization , LV dysfunction , interstitial fibrosis , and survival after MI . eNO bioavailability after MI likely represents an important therapeutic target in heart failure after MI and mediates beneficial effects of statin treatment after MI Background —Statins may exert important pleiotropic effects , ie , improve endothelial function , independently of their impact on LDL cholesterol . In humans , however , pleiotropic effects of statins have never been unequivocally demonstrated because prolonged statin treatment always results in reduced LDL cholesterol levels . We therefore tested the hypothesis that similar reductions in LDL cholesterol with simvastatin and ezetimibe , a novel cholesterol absorption inhibitor , result in different effects on endothelial function . Methods and Results —Twenty patients with chronic heart failure were r and omized to 4 weeks of simvastatin ( 10 mg/d ) or ezetimibe ( 10 mg/d ) treatment . Flow-dependent dilation ( FDD ) of the radial artery was determined by high-resolution ultrasound before and after intra-arterial vitamin C to determine the portion of FDD inhibited by radicals ( ΔFDD-VC ) . Activity of extracellular superoxide dismutase , a major vascular antioxidant enzyme system , was determined after release from the endothelium by a heparin bolus injection . Endothelial progenitor cells were analyzed with an in vitro assay . Simvastatin and ezetimibe treatment reduced LDL cholesterol to a similar extent ( 15.6 % versus 15.4 % ; P = NS ) , whereas changes in mevalonate , the product of HMG-CoA-reductase , differed between groups ( Δmevalonate-simvastatin , −1.04±0.62 versus Δmevalonate-ezetimibe , 1.79±0.94 ng/mL ; P<0.05 between groups ) . Importantly , FDD was markedly improved after simvastatin ( 10.5±0.6 % versus 5.1±0.7 % ; P<0.01 ) but not after ezetimibe treatment ( 5.6±0.5 % versus 5.8±0.6 % ; P = NS ) . ΔFDD-VC was substantially reduced after simvastatin but not after ezetimibe treatment . Extracellular superoxide dismutase activity was increased by > 100 % ( P<0.05 ) after simvastatin but not ezetimibe treatment . Simvastatin treatment increased the number of functionally active endothelial progenitor cells , whereas ezetimibe had no effect . Conclusions —Four weeks of simvastatin treatment improves endothelial function independently of LDL cholesterol lowering , at least in part by reducing oxidant stress . Simvastatin may thereby exert important pleiotropic effects in humans Objectives Recent clinical trials suggest an LDL-independent superiority of intensive statin therapy in reducing target vessel revascularization and peri-procedural myocardial infa rct ions in patients who undergo percutaneous coronary interventions ( PCI ) . While animal studies demonstrate that statins mobilize endothelial progenitor cells ( EPCs ) which can enhance arterial repair and attenuate neointimal formation , the precise explanation for the clinical PCI benefits of high dose statin therapy remain elusive . Thus we serially assessed patients undergoing PCI to test the hypothesis that high dose Atorvastatin therapy initiated prior to PCI mobilizes EPCs that may be capable of enhancing arterial repair . Methods and Results Statin naïve male patients undergoing angiography for stent placement were r and omized to st and ard therapy without Atorvastatin ( n = 10 ) or treatment with Atorvastatin 80 mg ( n = 10 ) beginning three days prior to stent implantation . EPCs were defined by flow cytometry ( e.g. , surface marker profile of CD45dim/34+/133+/117 + ) . As well , we also enumerated cultured angiogenic cells ( CACs ) by st and ard in vitro culture assay . While EPC levels did not fluctuate over time for the patients free of Atorvastatin , there was a 3.5-fold increase in EPC levels with high dose Atorvastatin beginning within 3 days of the first dose ( and immediately pre-PCI ) which persisted at 4 and 24 hours post-PCI ( p<0.05 ) . There was a similar rise in CAC levels as assessed by in vitro culture . CACs cultured in the presence of Atorvastatin failed to show augmented survival or VEGF secretion but displayed a 2-fold increase in adhesion to stent struts ( p<0.05 ) . Conclusions High dose Atorvastatin therapy pre-PCI improves EPC number and CAC number and function in humans which may in part explain the benefit in clinical outcomes seen in patients undergoing coronary interventions Background —Therapeutic neovascularization may constitute an important strategy to salvage tissue from critical ischemia . Circulating bone marrow – derived endothelial progenitor cells ( EPCs ) were shown to augment the neovascularization of ischemic tissue . In addition to lipid-lowering activity , hydroxymethyl glutaryl coenzyme A reductase inhibitors ( statins ) reportedly promote the neovascularization of ischemic tissue in normocholesterolemic animals . Methods and Results —Fifteen patients with angiographically documented stable coronary artery disease ( CAD ) were prospect ively treated with 40 mg of atorvastatin per day for 4 weeks . Before and weekly after the initiation of statin therapy , EPCs were isolated from peripheral blood and counted . In addition , the number of hematopoietic precursor cells positive for CD34 , CD133 , and CD34/kinase insert domain receptor was analyzed . Statin treatment of patients with stable CAD was associated with an ≈1.5-fold increase in the number of circulating EPCs by 1 week after initiation of treatment ; this was followed by sustained increased levels to ≈3-fold throughout the 4-week study period . Moreover , the number of CD34/kinase insert domain receptor – positive hematopoietic progenitor cells was significantly augmented after 4 weeks of therapy . Atorvastatin treatment increased the further functional activity of EPCs , as assessed by their migratory capacity . Conclusion —The results of the present study define a novel mechanism of action of statin treatment in patients with stable CAD : the augmentation of circulating EPCs with enhanced functional activity . Given the well-established role of EPCs of participating in repair after ischemic injury , stimulation of EPCs by statins may contribute to the clinical benefit of statin therapy in patients with CAD Endothelial progenitor cells ( EPCs ) are a subtype of hematopoietic stem cells , which contribute to the repair of injured endothelium . Treatment with atorvastatin has been shown to increase EPC count in patients with coronary artery disease . Therefore , we investigated whether atorvastatin augments the number of EPCs after cardiopulmonary bypass ( CPB ) surgery . We conducted a r and omized double-blind , placebo-controlled , 2-way crossover trial in 50 patients undergoing elective coronary surgery . Patients received either 3-week treatment with atorvastatin or placebo . EPCs were quantitated by flow cytometric phenotyping on blood sample s. Levels of interleukin , IL-6 and IL-8 ; tumor necrosis factor α ; SDF-1α ; granulocyte colony-stimulating factor ; and vascular endothelial growth factor were determined at recruitment , preoperatively , post-CPB , and 6 , 12 , and 24 hours postoperatively . The atorvastatin group showed a significantly higher amount of EPCs both pre- and postoperatively compared with the placebo , with a > 4-fold increase compared with the baseline values . CPB induced an increase in all cytokines , but the levels of proinflammatory cytokines were significantly lower in the atorvastatin group ( P < 0.05 ) . Statin did not affect levels of SDF-1α , granulocyte colony-stimulating factor , and vascular endothelial growth factor . However , no correlation was found between plasma levels of any cytokine and number of EPCs , with the exception of SDF-1α . Pretreatment with atorvastatin significantly increases the amount of EPCs after CPB , by a mechanism independent of plasma levels of cytokines and cholesterol OBJECTIVE Endothelial progenitor cells ( EPCs ) contribute to the maintenance of endothelial integrity and function . We investigated the effects of rosuvastatin and allopurinol on the number of EPCs in patients with heart failure and aim ed to provide insight into the molecular inflammatory and oxidative mechanisms that could be responsible for the alterations in EPC levels after treatment . METHODS Sixty patients with systolic heart failure were r and omized to receive rosuvastatin 10mg/d , allopurinol 300mg/d or placebo and followed up for 1 month . The number of CD34(+)/KDR(+ ) and CD34(+)/CD133(+)/KDR(+ ) EPCs in blood was evaluated by flow cytometry . Endothelial function was assessed by brachial artery flow-mediated dilation . Levels of markers of inflammation and oxidative stress were also determined . RESULTS Circulating EPCs were significantly increased after rosuvastatin treatment ( from 230 ( 170 - 380 ) and 10 ( 8 - 24 ) to 390 ( 230 - 520 ) and 19 ( 8 - 33 ) cells/10(6 ) lymphomonocytes , respectively , p=0.004 and p=0.008 ) , whereas they remained unchanged in the other groups . The increase in EPC levels was not associated with the changes in the levels of the measured inflammatory and oxidative markers . CONCLUSION Short-term treatment with rosuvastatin , but not allopurinol , significantly increases the number of circulating EPCs in patients with heart failure providing further insights into its role in these individuals . The impact of rosuvastatin on EPCs is not mediated by changes in inflammatory and oxidative status Objective To investigate the impacts of Xuezhikang ( 血脂康 , XZK ) or pravastatin combined with antihypertensive drugs on circulating endothelial progenitor cells ( CEPCs ) in essential hypertensive ( EH ) patients . Methods Eighty-eight EH patients were enrolled into the study and r and omly assigned to the antihypertensive drug treatment group ( ATH group , 29 cases ) , the pravastatin treatment group ( PRA group , 29 cases ) and the Xuezhikang treatment group ( XZK group , 30 cases ) . Patients in the 3 groups were treated with routine antihypertensive drugs . In addition , pravastatin and Xuezhikang were given to the patients in the PRA group and XZK group , respectively . After an eight-week treatment , CEPCs were counted using a laser scanning confocal microscope , and their proliferation function was evaluated by the MTT colorimetric assay and the adherent cell number was counted to estimate the adhesion function . Results After the treatment , CEPCs in the PRA group ( 116.60±5.70 ) and XZK group ( 114.40±6.55 ) was significantly higher than that in the ATH group ( 88.00±6.32 , P<0.01 ) . CEPCs proliferation capability and the adhesion function in the PRA group ( 0.406±0.016 , 33.60±4.26 ) and XZK group ( 0.415±0.018 , 34.30±3.77 ) were obviously superior to those in the ATH group ( 0.333±0.021 , P<0.01 ; 23.30±3.19 , P<0.01 ) . No significant difference was found between the pravastatin group and the XZK group . Conclusions Combined use of XZK or pravastatin with the anti-hypertensive therapy could increase the CEPCs number and improve their function in EH patients with the blood pressure controlled by antihypertensive drugs , leading to benefits independent of pressure-lowering effects BACKGROUND Pilot studies suggest that intracoronary transplantation of progenitor cells derived from bone marrow ( BMC ) or circulating blood ( CPC ) may improve left ventricular function after acute myocardial infa rct ion . The effects of cell transplantation in patients with healed myocardial infa rct ion are unknown . METHODS After an initial pilot trial involving 17 patients , we r and omly assigned , in a controlled crossover study , 75 patients with stable ischemic heart disease who had had a myocardial infa rct ion at least 3 months previously to receive either no cell infusion ( 23 patients ) or infusion of CPC ( 24 patients ) or BMC ( 28 patients ) into the patent coronary artery supplying the most dyskinetic left ventricular area . The patients in the control group were subsequently r and omly assigned to receive CPC or BMC , and the patients who initially received BMC or CPC crossed over to receive CPC or BMC , respectively , at 3 months ' follow-up . RESULTS The absolute change in left ventricular ejection fraction was significantly greater among patients receiving BMC ( + 2.9 percentage points ) than among those receiving CPC ( -0.4 percentage point , P=0.003 ) or no infusion ( -1.2 percentage points , P<0.001 ) . The increase in global cardiac function was related to significantly enhanced regional contractility in the area targeted by intracoronary infusion of BMC . The crossover phase of the study revealed that intracoronary infusion of BMC was associated with a significant increase in global and regional left ventricular function , regardless of whether patients crossed over from control to BMC or from CPC to BMC . CONCLUSIONS Intracoronary infusion of progenitor cells is safe and feasible in patients with healed myocardial infa rct ion . Transplantation of BMC is associated with moderate but significant improvement in the left ventricular ejection fraction after 3 months |
1,792 | 23,611,141 | Conclusion : The current literature provides clinical trial evidence that non-pharmacologic interventions can delay progression of functional impairment or disability among community-dwelling dementia patients . | Objectives : Older adults with dementia experience progressive functional decline , which contributes to caregiver burden and nursing home placement .
The goal of this systematic review was to determine if any non-pharmacologic interventions have delayed functional decline among community-dwelling dementia patients . | OBJECTIVE To determine the effectiveness of community based occupational therapy on daily functioning of patients with dementia and the sense of competence of their care givers . DESIGN Single blind r and omised controlled trial . Assessors were blinded for treatment allocation . SETTING Memory clinic and day clinic of a geriatrics department and participants ' homes . PARTICIPANTS 135 patients aged > or = 65 with mild to moderate dementia living in the community and their primary care givers . INTERVENTIONS 10 sessions of occupational therapy over five weeks , including cognitive and behavioural interventions , to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision . MAIN OUTCOME MEASURES Patients ' daily functioning assessed with the assessment of motor and process skills ( AMPS ) and the performance scale of the interview of deterioration in daily activities in dementia ( IDDD ) . Care giver burden assessed with the sense of competence question naire ( SCQ ) . Participants were evaluated at baseline , six weeks , and three months . RESULTS Scores improved significantly relative to baseline in patients and care givers in the intervention group compared with the controls ( differences were 1.5 ( 95 % confidence interval 1.3 to 1.7 ) for the process scale ; -11.7 ( -13.6 to -9.7 ) for the performance scale ; and ( 11.0 ; 9.2 to 12.8 ) for the competence scale ) . This improvement was still significant at three months . The number needed to treat to reach a clinical ly relevant improvement in motor and process skills score was 1.3 ( 1.2 to 1.4 ) at six weeks . Effect sizes were 2.5 , 2.3 , and 1.2 , respectively , at six weeks and 2.7 , 2.4 , and 0.8 , respectively , at 12 weeks . CONCLUSIONS Occupational therapy improved patients ' daily functioning and reduced the burden on the care giver , despite the patients ' limited learning ability . Effects were still present at 12 weeks , which justifies implementation of this intervention . TRIAL REGISTRATION Clinical Trials NCT00295152 [ Clinical Trials.gov ] CONTEXT Optimal treatment to postpone functional decline in patients with dementia is not established . OBJECTIVE To test a nonpharmacologic intervention realigning environmental dem and s with patient capabilities . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve 2-group r and omized trial ( Care of Persons with Dementia in their Environments [ COPE ] ) involving patients with dementia and family caregivers ( community-living dyads ) recruited from March 2006 through June 2008 in Pennsylvania . INTERVENTIONS Up to 12 home or telephone contacts over 4 months by health professionals who assessed patient capabilities and deficits ; obtained blood and urine sample s ; and trained families in home safety , simplifying tasks , and stress reduction . Control group caregivers received 3 telephone calls and educational material s. MAIN OUTCOME MEASURES Functional dependence , quality of life , frequency of agitated behaviors , and engagement for patients and well-being , confidence using activities , and perceived benefits for caregivers at 4 months . RESULTS Of 284 dyads screened , 270 ( 95 % ) were eligible and 237 ( 88 % ) r and omized . Data were collected from 209 dyads ( 88 % ) at 4 months and 173 ( 73 % ) at 9 months . At 4 months , compared with controls , COPE patients had less functional dependence ( adjusted mean difference , 0.24 ; 95 % CI , 0.03 - 0.44 ; P = .02 ; Cohen d = 0.21 ) and less dependence in instrumental activities of daily living ( adjusted mean difference , 0.32 ; 95 % CI , 0.09 - 0.55 ; P = .007 ; Cohen d = 0.43 ) , measured by a 15-item scale modeled after the Functional Independence Measure ; COPE patients also had improved engagement ( adjusted mean difference , 0.12 ; 95 % CI , 0.07 - 0.22 ; P = .03 ; Cohen d = 0.26 ) , measured by a 5-item scale . COPE caregivers improved in their well-being ( adjusted mean difference in Perceived Change Index , 0.22 ; 95 % CI , 0.08 - 0.36 ; P = .002 ; Cohen d = 0.30 ) and confidence using activities ( adjusted mean difference , 0.81 ; 95 % CI , 0.30 - 1.32 ; P = .002 ; Cohen d = 0.54 ) , measured by a 5-item scale . By 4 months , 64 COPE dyads ( 62.7 % ) vs 48 control group dyads ( 44.9 % ) eliminated 1 or more caregiver-identified problems ( chi(2/1 ) = 6.72 , P = . 01 ) . CONCLUSION Among community-living dyads , a nonpharmacologic biobehavioral environmental intervention compared with control result ed in better outcomes for COPE dyads at 4 months . Although no group differences were observed at 9 months for patients , COPE caregivers perceived greater benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00259454 Background Agitation in Alzheimer ’s disease ( AD ) is common and associated with poor patient life- quality and carer distress . The best evidence -based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality . There are no memantine trials in clinical ly significant agitation but post-hoc analyses in other population s found reduced agitation . We tested the primary hypothesis , memantine is superior to placebo for clinical ly significant agitation , in patients with moderate-to-severe AD . Methods and Findings We recruited 153 participants with AD and clinical ly significant agitation from care-homes or hospitals for a double-blind r and omised-controlled trial and 149 people started the trial of memantine versus placebo . The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory ( CMAI ) . Secondary outcomes were : 12 weeks CMAI ; 6 and 12 weeks Neuropsychiatric symptoms ( NPI ) , Clinical Global Impression Change ( CGI-C ) , St and ardised Mini Mental State Examination , Severe Impairment Battery . Using a mixed effects model we found no significant differences in the primary outcome , 6 weeks CMAI , between memantine and placebo ( memantine lower −3.0 ; −8.3 to 2.2 , p = 0.26 ) ; or 12 weeks CMAI ; or CGI-C or adverse events at 6 or 12 weeks . NPI mean difference favoured memantine at weeks 6 ( −6.9 ; −12.2 to −1.6 ; p = 0.012 ) and 12 ( −9.6 ; −15.0 to −4.3 p = 0.0005 ) . Memantine was significantly better than placebo for cognition . The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD . Conclusions Memantine did not improve significant agitation in people with in moderate-to-severe AD . Future studies are urgently needed to test other pharmacological c and i date s in this group and memantine for neuropsychiatric symptoms . Trial Registration Clinical Trials.gov NCT00371059 Trial Registration International St and ard R and omised Controlled Trial PURPOSE OF STUDY The authors determined short-term effects of a home environmental intervention on self-efficacy and upset in caregivers and daily function of dementia patients . They also determined if treatment effect varied by caregiver gender , race , and relationship to patient . DESIGN AND METHODS Families ( N = 171 ) of dementia patients were r and omized to intervention or usual care control group . The intervention involved 5 90-min home visits by occupational therapists who provided education and physical and social environmental modifications . RESULTS Compared with controls , intervention caregivers reported fewer declines in patients ' instrumental activities of daily living ( p = .030 ) and less decline in self-care and fewer behavior problems in patients at 3 months post-test . Also , intervention spouses reported reduced upset ( p = .049 ) , women reported enhanced self-efficacy in managing behaviors ( p = .038 ) , and women ( p = .049 ) and minorities ( p = .037 ) reported enhanced self-efficacy in managing functional dependency . IMPLICATION S The environmental program appears to have a modest effect on dementia patients ' IADL dependence . Also , among certain subgroups of caregivers the program improves self-efficacy and reduces upset in specific areas of caregiving BACKGROUND Second-generation ( atypical ) antipsychotic drugs are widely used to treat psychosis , aggression , and agitation in patients with Alzheimer 's disease , but their benefits are uncertain and concerns about safety have emerged . We assessed the effectiveness of atypical antipsychotic drugs in out patients with Alzheimer 's disease . METHODS In this 42-site , double-blind , placebo-controlled trial , 421 out patients with Alzheimer 's disease and psychosis , aggression , or agitation were r and omly assigned to receive olanzapine ( mean dose , 5.5 mg per day ) , quetiapine ( mean dose , 56.5 mg per day ) , risperidone ( mean dose , 1.0 mg per day ) , or placebo . Doses were adjusted as needed , and patients were followed for up to 36 weeks . The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change ( CGIC ) scale at 12 weeks . RESULTS There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason : olanzapine ( median , 8.1 weeks ) , quetiapine ( median , 5.3 weeks ) , risperidone ( median , 7.4 weeks ) , and placebo ( median , 8.0 weeks ) ( P=0.52 ) . The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine ( 22.1 weeks ) and risperidone ( 26.7 weeks ) as compared with quetiapine ( 9.1 weeks ) and placebo ( 9.0 weeks ) ( P=0.002 ) . The time to the discontinuation of treatment due to adverse events or intolerability favored placebo . Overall , 24 % of patients who received olanzapine , 16 % of patients who received quetiapine , 18 % of patients who received risperidone , and 5 % of patients who received placebo discontinued their assigned treatment owing to intolerability ( P=0.009 ) . No significant differences were noted among the groups with regard to improvement on the CGIC scale . Improvement was observed in 32 % of patients assigned to olanzapine , 26 % of patients assigned to quetiapine , 29 % of patients assigned to risperidone , and 21 % of patients assigned to placebo ( P=0.22 ) . CONCLUSIONS Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis , aggression , or agitation in patients with Alzheimer 's disease . ( Clinical Trials.gov number , NCT00015548 [ Clinical Trials.gov ] . ) CONTEXT Most older adults with dementia will be cared for by primary care physicians , but the primary care practice environment presents important challenges to providing quality care . OBJECTIVE To test the effectiveness of a collaborative care model to improve the quality of care for patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS Controlled clinical trial of 153 older adults with Alzheimer disease and their caregivers who were r and omized by physician to receive collaborative care management ( n = 84 ) or augmented usual care ( n = 69 ) at primary care practice s within 2 US university-affiliated health care systems from January 2002 through August 2004 . Eligible patients ( identified via screening or medical record ) met diagnostic criteria for Alzheimer disease and had a self-identified caregiver . INTERVENTION Intervention patients received 1 year of care management by an interdisciplinary team led by an advanced practice nurse working with the patient 's family caregiver and integrated within primary care . The team used st and ard protocol s to initiate treatment and identify , monitor , and treat behavioral and psychological symptoms of dementia , stressing nonpharmacological management . MAIN OUTCOME MEASURES Neuropsychiatric Inventory ( NPI ) administered at baseline and at 6 , 12 , and 18 months . Secondary outcomes included the Cornell Scale for Depression in Dementia ( CSDD ) , cognition , activities of daily living , re source use , and caregiver 's depression severity . RESULTS Initiated by caregivers ' reports , 89 % of intervention patients triggered at least 1 protocol for behavioral and psychological symptoms of dementia with a mean of 4 per patient from a total of 8 possible protocol s. Intervention patients were more likely to receive cholinesterase inhibitors ( 79.8 % vs 55.1 % ; P = .002 ) and antidepressants ( 45.2 % vs 27.5 % ; P = .03 ) . Intervention patients had significantly fewer behavioral and psychological symptoms of dementia as measured by the total NPI score at 12 months ( mean difference , -5.6 ; P = .01 ) and at 18 months ( mean difference , -5.4 ; P = .01 ) . Intervention caregivers also reported significant improvements in distress as measured by the caregiver NPI at 12 months ; at 18 months , caregivers showed improvement in depression as measured by the Patient Health Question naire-9 . No group differences were found on the CSDD , cognition , activities of daily living , or on rates of hospitalization , nursing home placement , or death . CONCLUSIONS Collaborative care for the treatment of Alzheimer disease result ed in significant improvement in the quality of care and in behavioral and psychological symptoms of dementia among primary care patients and their caregivers . These improvements were achieved without significantly increasing the use of antipsychotics or sedative-hypnotics . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00246896 OBJECTIVE To test whether the Tailored Activity Program ( TAP ) reduces dementia-related neuropsychiatric behaviors , promotes activity engagement , and enhances caregiver well-being . DESIGN Prospect i ve , two-group ( treatment , wait-list control ) , r and omized , controlled pilot study with 4 months as main trial endpoint . At 4 months , controls received the TAP intervention and were reassessed 4 months later . SETTING Patients ' homes . PARTICIPANTS Sixty dementia patients and family caregivers . INTERVENTION The eight-session occupational therapy intervention involved neuropsychological and functional testing , selection , and customization of activities to match capabilities identified in testing , and instruction to caregivers in use of activities . MEASUREMENTS Behavioral occurrences , activity engagement , and quality of life in dementia patients ; objective and subjective burden and skill enhancement in caregivers . RESULTS At 4 months , compared with controls , intervention caregivers reported reduced frequency of problem behaviors , and specifically for shadowing and repetitive question ing , and greater activity engagement including the ability to keep busy . Fewer intervention caregivers reported agitation or argumentation . Caregiver benefits included fewer hours doing things and being on duty , greater mastery , self-efficacy , and skill enhancement . Wait-list control participants following intervention showed similar benefits for reductions in behavioral frequency and caregiver hours doing things for the patient and mastery . Caregivers with depressed symptoms derived treatment benefits similar to nondepressed caregivers . CONCLUSIONS Tailoring activities to the capabilities of dementia patients and training families in activity use result ed in clinical ly relevant benefits for patients and caregivers . Treatment minimized trigger behaviors for nursing home placement and reduced objective caregiver burden . Noteworthy is that depressed caregivers effectively engaged in and benefited from the intervention In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVES Dementia is a rapidly growing public health problem in low and middle income countries . There is an urgent need , in the absence of formal services , to develop interventions design ed to improve the lives of people with dementia , and their families . This study tests the effectiveness of the 10/66 caregiver intervention among people with dementia , and their carers . DESIGN A single blind parallel group r and omized controlled trial ( IS RCT N41039907 ) . SETTING Moscow . PARTICIPANTS Sixty family caregivers of people aged 65 and over with dementia were r and omized to receive the intervention and medical care as usual ( n = 30 ) or medical care as usual only ( n = 30 ) . Caregiver and person with dementia outcomes were assessed at baseline and after 6 months . INTERVENTION The caregiver education and training intervention was delivered over five , weekly , half-hour sessions and was made up of three modules : ( i ) assessment ( one session ) ; ( ii ) basic education about dementia ( two sessions ) ; and ( iii ) training regarding specific problem behaviors ( two sessions ) . MEASUREMENTS Dementia was diagnosed using DSM-IV criteria . Caregiver : Zarit Carer Burden Interview ; carer psychological distress ( SRQ 20 ) ; and carer Quality of Life ( WHOQOL-BREF ) . Person with dementia : Behavioural and Psychological symptoms ( NPI-Q ) ; quality of life ( DEMQOL ) . RESULTS Caregivers in the intervention group reported large and statistically significant net improvements at 6-month follow-up in burden compared to controls . No group differences were found on caregiver psychological distress and patient and caregiver quality of life . CONCLUSIONS The low-level intervention seems to be as , if not more , effective than similar interventions applied in high income countries OBJECTIVES To estimate the magnitude of small meaningful and substantial individual change in physical performance measures and evaluate their responsiveness . DESIGN Secondary data analyses using distribution- and anchor-based methods to determine meaningful change . SETTING Secondary analysis of data from an observational study and clinical trials of community-dwelling older people and subacute stroke survivors . PARTICIPANTS Older adults with mobility disabilities in a strength training trial ( n=100 ) , subacute stroke survivors in an intervention trial ( n=100 ) , and a prospect i ve cohort of community-dwelling older people ( n=492 ) . MEASUREMENTS Gait speed , Short Physical Performance Battery ( SPPB ) , 6-minute-walk distance ( 6MWD ) , and self-reported mobility . RESULTS Most small meaningful change estimates ranged from 0.04 to 0.06 m/s for gait speed , 0.27 to 0.55 points for SPPB , and 19 to 22 m for 6MWD . Most substantial change estimates ranged from 0.08 to 0.14 m/s for gait speed , 0.99 to 1.34 points for SPPB , and 47 to 49 m for 6MWD . Based on responsiveness indices , per-group sample sizes for clinical trials ranged from 13 to 42 for substantial change and 71 to 161 for small meaningful change . CONCLUSION Best initial estimates of small meaningful change are near 0.05 m/s for gait speed , 0.5 points for SPPB , and 20 m for 6MWD and of substantial change are near 0.10 m/s for gait speed , 1.0 point for SPPB , and 50 m for 6MWD . For clinical use , substantial change in these measures and small change in gait speed and 6MWD , but not SPPB , are detectable . For research use , these measures yield feasible sample sizes for detecting meaningful change PURPOSE OF THE STUDY To identify risk factors for early nursing home placement ( NHP ) in Alzheimer 's disease ( AD ) , focusing on the impact of longitudinal change in cognition , activities of daily living ( ADL ) , service utilization , and cholinesterase inhibitor treatment ( ChEI ) . DESIGN AND METHODS In an open , 3-year , prospect i ve , multicenter study in a routine clinical setting , 880 AD patients were treated with either donepezil , rivastigmine , or galantamine . At baseline and every 6 months , they were assessed with several rating scales including Mini-Mental State Examination , Instrumental Activities of Daily Living scale ( IADL ) , and Physical Self-Maintenance scale . Moreover , the dose of ChEI , the amount of weekly assistance ( home help service and adult day care ) , and the date of NHP were recorded . Cox regression models were constructed to predict the risk of NHP . RESULTS During the study , 206 patients ( 23 % ) were admitted to nursing homes . Factors that precipitated institutionalization were lower cognitive and functional abilities at baseline , faster rate of decline in IADLs , female gender , solitary living , and a lower mean dose of ChEI . The men living alone and patients with a substantial increase in adult day care also demonstrated shorter time to NHP . IMPLICATION S The rate of functional but not cognitive decline was a strong risk factor for NHP . The results could be used to identify the care recipients that might risk early NHP to ensure that these individuals receive a sufficient level of assistance . Furthermore , higher doses of ChEI might postpone institutionalization in AD This study was an attempt to improve the quality of the relationship between dementia caregivers and their loved ones by decreasing the gap between caregivers ' expectations and patients ' actual functional abilities and by teaching supportive skills . Although a group of 49 caregiver-patient dyads were recruited , the outcome measures of only those dyads ( 47 ) that completed the week seven session were used for analysis . Half of the dyads were r and omized to an intervention group and the other half to a waiting list . The intervention group ( N = 24 ) completed a four-session caregiver training program in which caregivers first watched investigators administering to their loved ones the Texas Functional Living Scale and later progressed to helping their loved ones by appropriate cueing to perform the tasks involved . Comparisons were made between baseline scores , scores at seven weeks , and scores at the end of 17 weeks on the congruence between caregiver estimates and patients ' actual performance on the Independent Living Scale and measures of cognition , function , preillness quality of relationship , caregiver mood , feeling of self-efficacy , and several other measures . We were not able to increase the congruence between caregiver estimates and patients ' actual performance and found no change in any other measure . We did find the expected relationship between depression and caregiver sense of self-efficacy OBJECTIVES To test the effects of an intervention that helps families manage distressing behaviors in family members with dementia . DESIGN Two-group r and omized trial . SETTING In home . PARTICIPANTS Two hundred seventy-two caregivers and people with dementia . INTERVENTION Up to 11 home and telephone contacts over 16 weeks by health professionals who identified potential triggers of patient behaviors , including communication and environmental factors and patient undiagnosed medical conditions ( by obtaining blood and urine sample s ) and trained caregivers in strategies to modify triggers and reduce their upset . Between 16 and 24 weeks , three telephone contacts reinforced strategy use . MEASUREMENTS Primary outcomes were frequency of targeted problem behavior and caregiver upset with and confidence managing it at 16 weeks . Secondary outcomes were caregiver well-being and management skills at 16 and 24 weeks and caregiver perceived benefits . Prevalence of medical conditions for intervention patients were also examined . RESULTS At 16 weeks , 67.5 % of intervention caregivers reported improvement in targeted problem behavior , compared with 45.8 % of caregivers in a no-treatment control group ( P=.002 ) , and reduced upset with ( P=.03 ) and enhanced confidence managing ( P=.01 ) the behavior . Additionally , intervention caregivers reported less upset with all problem behaviors ( P=.001 ) , less negative communication ( P=.02 ) , less burden ( P=.05 ) , and better well-being ( P=.001 ) than controls . Fewer intervention caregivers had depressive symptoms ( 53.0 % ) than control group caregivers ( 67.8 % , P=.02 ) . Similar caregiver outcomes occurred at 24 weeks . Intervention caregivers perceived more study benefits ( P<.05 ) , including ability to keep family members home , than controls . Blood and urine sample s of intervention patients with dementia showed that 40 ( 34.1 % ) had undiagnosed illnesses requiring physician follow-up . CONCLUSION Targeting behaviors up setting to caregivers and modifying potential triggers improves symptomatology in people with dementia and caregiver well-being and skills To address the need for nonpharmacologic approaches to managing difficult behaviors in patients with dementia , a repeated measures design was used to test the effectiveness of educational and behavioral intervention on behavioral and functional outcomes in home-dwelling patients with dementia and their caregivers ' knowledge of dementia . Baseline and 6-month postintervention data were collected for 108 subjects ( 54 caregiver/patient pairs ) following r and om assignment to an intervention or comparison group . Findings included increases in caregiver knowledge in two treatment groups and patient self-care ability in one treatment group and ratings of the most effective behavioral interventions by caregivers BACKGROUND Cure of dementia is not possible , but quality of life of patients and caregivers can be improved . Our aim is to investigate effects of community occupational therapy on dementia patients ' and caregivers ' quality of life , mood , and health status and caregivers ' sense of control over life . METHODS Community-dwelling patients aged 65 years or older , with mild-to-moderate dementia , and their informal caregivers ( n = 135 couples of patients with their caregivers ) were r and omly assigned to 10 sessions of occupational therapy over 5 weeks or no intervention . Cognitive and behavioral interventions were used to train patients in the use of aids to compensate for cognitive decline and caregivers in coping behaviors and supervision . Outcomes , measured at baseline , 6 weeks , and 12 weeks , were patients ' and caregivers ' quality of life ( Dementia Quality of Life Instrument , Dqol ) , patients ' mood ( Cornell Scale for Depression , CSD ) , caregivers ' mood ( Center for Epidemiologic Studies Depression Scale , CES-D ) , patients ' and caregivers ' health status ( General Health Question naire , GHQ-12 ) , and caregivers ' sense of control over life ( Mastery Scale ) . RESULTS Improvement on patients ' Dqol overall ( 0.8 ; 95 % confidence interval [ CI ] , 0.6-.1 , effect size 1.3 ) and caregivers ' Dqol overall ( 0.7 ; 95 % CI , 0.5-.9 , effect size 1.2 ) was significantly better in the intervention group as compared to controls . Scores on other outcome measures also improved significantly . This improvement was still significant at 12 weeks . CONCLUSION Community occupational therapy should be advocated both for dementia patients and their caregivers , because it improves their mood , quality of life , and health status and caregivers ' sense of control over life . Effects were still present at follow-up OBJECTIVES To determine whether a specific , st and ardized training regimen can improve muscle strength and physical functioning in people with dementia . DESIGN Double-blinded , r and omized , controlled trial with 3-month intervention and 3-month follow-up period in 2006 to 2009 . SETTING Outpatient geriatric rehabilitation . PARTICIPANTS Individuals with confirmed mild to moderate dementia , no severe somatic or psychological disease , and ability to walk 10 m. Most participants were still living independently with or without supportive care . INTERVENTION Supervised , progressive resistance and functional group training for 3 months specifically developed for people with dementia ( intervention , n = 62 ) compared with a low-intensity motor placebo activity ( control , n = 60 ) . MEASUREMENTS Primary outcome measures were one-repetition maximum in a leg press device for maximal strength and duration of the five-chair-st and test for functional performance . Secondary outcome measures were assessed for a number of established parameters for maximal strength , physical function , and physical activity . RESULTS Training significantly improved both primary outcomes ( percentage change from baseline : maximal strength , intervention group ( IG ) : + 51.5 ± 41.5 kg vs control group ( CG ) : -1.0 ± 28.9 kg , P < .001 ; functional performance , IG : -25.9 ± 15.1 seconds vs CG : + 11.3 ± 60.4 seconds , P < .001 ) . Secondary analysis confirmed effects for all strength and functional parameters . Training gains were partly sustained during follow-up . Low baseline performance on motor tasks but not cognitive impairment predicted positive training response . Physical activity increased significantly during the intervention ( P < .001 ) . CONCLUSION The intensive , dementia-adjusted training was feasible and substantially improved motor performance in frail , older people with dementia and may represent a model for structured rehabilitation or outpatient training OBJECTIVE To determine the feasibility and efficacy of a home-based exercise intervention program to improve the functional performance of patients with Alzheimer 's Disease ( AD ) . METHODS Twenty-seven home-dwelling patients with AD were r and omized to either an exercise intervention program delivered by their caregivers or a home safety assessment control . Measures of functional performance ( primary ) , cognition , neuropsychiatric symptoms , quality of life and caregiver burden ( secondary ) were obtained at baseline and at 6 and 12 weeks following r and omization . For each outcome measure , intent-to-treat analyses using linear r and om effects models were performed . Feasibility and adverse events were also assessed . RESULTS Adherence to the exercise program was good . On the primary outcomes ( functional performance ) patients in the exercise group demonstrated a trend for improved performance on measures of h and function and lower extremity strength . On secondary outcome measures , trends toward worse depression and lower quality of life ratings were noted . CONCLUSIONS The physical exercise intervention developed for the study , delivered by caregivers to home-dwelling patients with AD , was feasible and was associated with a trend for improved functional performance in this group of frail patients . Given the limited efficacy to date of pharmacotherapies for AD , further study of exercise intervention , in a variety of care setting , is warranted Objectives : ( 1 ) To examine the feasibility of group physical activity in a day-care routine . ( 2 ) To assess the impact of this programme on functional fitness . Design : Ten-week observational period , followed by 12 weeks of intervention in r and omized controlled design , followed by 12 weeks of intervention only . Setting : A day-care centre for demented older individuals . Participants : Twenty-nine demented ( Mini-Mental State Exam score 13.3 ± 5.83 ) day-care attendees , mean ± SD age 76.9 ± 6.72 . Intervention : Group physical activity vs. social activity , followed by increased-intensity physical activity for both groups . Measurements : Performance rate ( PR ) in physical activity sessions , Timed Get Up and Go ( TGUG ) , Sit-to-St and ( STS ) and Functional Reach ( FR ) . Results : Approximately 60 % of the participants performed almost all movements or repetitions in both intervention phases . No improvements were observed following the first phase of physical activity . A reduction of 3.2 seconds ( ±1.2 SE ) was noted in the time needed to perform the TGUG following the increased-intensity physical activity . Conclusion : A carefully tailored group physical activity , conducted twice weekly with a group of 12—15 participants in a medium size room , and led by a physical activity teacher assisted by a staff aide , is feasible . Although physical activity performed mainly while sitting is ineffective , it can be effective to a meaningful degree when performed while st and ing or walking OBJECTIVES To investigate the effectiveness of an exercise program in improving ability to perform activities of daily living ( ADLs ) , physical performance , and nutritional status and decreasing behavioral disturbance and depression in patients with Alzheimer 's disease ( AD ) . DESIGN R and omized , controlled trial . SETTING Five nursing homes . PARTICIPANTS One hundred thirty-four ambulatory patients with mild to severe AD . INTERVENTION Collective exercise program ( 1 hour , twice weekly of walk , strength , balance , and flexibility training ) or routine medical care for 12 months . MEASUREMENTS ADLs were assessed using the Katz Index of ADLs . Physical performance was evaluated using 6-meter walking speed , the get-up- and -go test , and the one-leg-balance test . Behavioral disturbance , depression , and nutritional status were evaluated using the Neuropsychiatric Inventory , the Montgomery and Asberg Depression Rating Scale , and the Mini-Nutritional Assessment . For each outcome measure , the mean change from baseline to 12 months was calculated using intention-to-treat analysis . RESULTS ADL mean change from baseline score for exercise program patients showed a slower decline than in patients receiving routine medical care ( 12-month mean treatment differences : ADL=0.39 , P=.02 ) . A significant difference between the groups in favor of the exercise program was observed for 6-meter walking speed at 12 months . No effect was observed for behavioral disturbance , depression , or nutritional assessment scores . In the intervention group , adherence to the program sessions in exploratory analysis predicted change in ability to perform ADLs . No adverse effects of exercise occurred . CONCLUSION A simple exercise program , 1 hour twice a week , led to significantly slower decline in ADL score in patients with AD living in a nursing home than routine medical care BACKGROUND Few studies evaluate whether short-term intervention effects are maintained over time for families caring for persons with dementia . This article examines whether treatment effects found at 6 months following active treatment were sustained at 12 months for 127 family caregivers who participated in an occupational therapy intervention tested as part of the National Institutes of Health Re sources for Enhancing Alzheimer 's Caregiver Health ( REACH ) initiative . METHODS A r and omized two-group design was implemented with three assessment points : baseline , 6 months , and 12 months . Caregivers were r and omly assigned to a usual care control group or intervention that consisted of six occupational therapy sessions to help families modify the environment to support daily function of the person with dementia and reduce caregiver burden . Following 6-month active treatment , a maintenance phase consisted of one home and three brief telephone sessions to reinforce strategy use and obtain closure . Non-inferiority statistical analysis was used to evaluate whether intervention caregivers maintained treatment benefits from 6 to 12 months in comparison to controls . RESULTS For the sample of 127 at 6 months , caregivers in intervention reported improved skills ( p = .028 ) , less need for help providing assistance ( p = .043 ) , and fewer behavioral occurrences ( p = .019 ) compared to caregivers in control . At 12 months , caregiver affect improved ( p = .033 ) , and there was a trend for maintenance of skills and reduced behavioral occurrences , but not for other outcome measures . CONCLUSION An in-home skills training program helps sustain caregiver affect for those enrolled for more than 1 year . More frequent professional contact and ongoing skills training may be necessary to maintain other clinical ly important outcomes such as reduced upset with behaviors The objective was to assess the effect of a structured intervention on caregiver stress and the institutionalization rate of patients with dementia and problem behaviors . Caregivers contacting the Federazione Alzheimer Italia ( AI ) to receive help , advice , or information in relation to problem behaviors of out patients were enrolled . Eligible caregiver-patient dyads were r and omized to receive either a structured intervention or the counseling AI usually provides ( control group ) . After basal assessment , families were reassessed at 6 and 12 months . Problem behavior ( particularly agitation ) was the only variable significantly correlated ( P = 0.006 ) with the baseline caregivers ’ stress score . Thirty-nine families completed the 12-month follow-up ; the mean problem behavior score was significantly lower in the intervention than the control group ( p < 0.03 ) ; the time needed for care of the patient increased by 0.5 ± 9.7 hours/day in the control group and decreased by 0.3 ± 4.1 in the intervention group ( p = 0.4 , Wilcoxon test ) . The main determinant of institutionalization seemed to be the level of caregiver stress ( p = 0.03 ) . In patients of the intervention group , there was a significant reduction in the frequency of delusions . This pilot study suggests that caregiver stress is relieved by a structured intervention . The number of families lost to follow-up , the relatively short duration of the study , and the ceiling effect due to the severity of the clinical characteristics of patients probably all partly dilute the observed findings Assisted walking and walking combined with conversation were compared to a conversation-only intervention in nursing home residents with Alzheimer disease . Sixty-five subjects r and omly assigned to treatment group were tested at baseline and end of treatment . Subjects ' mean Mini-Mental State Examination score was 10.83 ; mean age was 87 . Treatment was given for 30 minutes three times a week for 16 weeks . Subjects in the assisted walking group declined 20.9 % in functional mobility ; the conversation group declined 18.8 % . The combined walking and conversation treatment group declined only 2.5 % . These differences in outcome were significant and appear to have been affected by differences in treatment fidelity . Subjects in the conversation treatment group completed 90 % of intended treatment compared with 75 % in the combined group and only 57 % in the assisted walking group . Failure to treat was due to subject refusal and physical illness . The conversation component of the combined walking and conversation treatment intervention appears to have improved compliance with the intervention , thereby improving treatment outcome . Results indicate that assisted walking with conversation can contribute to maintenance of functional mobility in institutionalized population s with Alzheimer disease . Staff assigned to this task should be prepared to use effective communication strategies to gain acceptance of the intervention PURPOSE We examine 6-month effects of the Environmental Skill-Building Program on caregiver well-being and care recipient functioning and whether effects vary by caregiver gender , race ( White or non-White ) , and relationship ( spouse or nonspouse ) . DESIGN AND METHODS We enrolled 255 family caregivers of community-residing persons with Alzheimer 's disease or related disorders , of whom 190 participated in a follow-up interview . Caregivers were r and omized to a usual care control group or intervention group that received five home contacts and one telephone contact by occupational therapists , who provided education , problem-solving training , and adaptive equipment . Baseline and 6-month follow-up included self-report measures of caregiver objective and subjective burden , caregiver well-being , and care recipient problem behaviors and physical function . RESULTS Compared with controls ( n = 101 ) , intervention caregivers ( n = 89 ) reported less upset with memory-related behaviors , less need for assistance from others , and better affect . Intervention spouses reported less upset with disruptive behaviors ; men reported spending less time in daily oversight ; and women reported less need for help from others , better affect , and enhanced management ability , overall well-being , and mastery relative to control group counterparts . Statistically significant treatment differences were not found for hours helping with instrumental activities of daily living , upset with providing assistance with instrumental activities of daily living and activities of daily living , perceived change in somatic symptoms , White versus non-White caregivers , or care recipient outcomes . IMPLICATION S The Environmental Skill-Building Program reduces burden and enhances caregiver well-being in select domains and has added benefit for women and spouses Objective To test the effectiveness of a comprehensive specific care plan in decreasing the rate of functional decline in patients with mild to moderate Alzheimer ’s disease compared with usual care in memory clinics . Design Cluster r and omised trial . Setting 50 memory clinics in France . Participants Patients with Alzheimer ’s disease ( mini-mental state examination score 12 - 26 ) . 1131 patients were included : 574 from 26 clinics in the intervention group , and 557 from 24 clinics in the usual care ( control ) group . Memory clinics were the unit of r and omisation . Intervention The intervention included a comprehensive st and ardised twice yearly consultation for patients and their caregivers , with st and ardised guidelines for the management of problems identified during the assessment . Main outcome measures The primary outcome measure was change on the Alzheimer ’s Disease Cooperative Study -activities of daily living scale assessed at 12 and 24 months . Secondary outcome measures were the rate of admission to institutional care and mortality . Results At two years the assessment was completed by 58.4 % ( n=335 ) of patients in the intervention group and 61.6 % ( n=343 ) in the control group . The rate of functional decline at two years did not differ between the groups . The annual rate of change on the Alzheimer ’s Disease Cooperative Study -activities of daily living was estimated at −5.73 ( 95 % confidence interval −6.89 to −4.57 ) in the intervention group and −5.96 ( −7.05 to −4.86 ) in the control group ( P=0.78 ) . Conclusion A comprehensive specific care plan in memory clinics had no additional positive effect on functional decline in patients with mild to moderate Alzheimer ’s disease . Future research should aim to determine the effects of more direct involvement of general practitioners . Trial registration Clinical Trials.gov NCT00480220 CONTEXT Exercise training for patients with Alzheimer disease combined with teaching caregivers how to manage behavioral problems may help decrease the frailty and behavioral impairment that are often prevalent in patients with Alzheimer disease . OBJECTIVE To determine whether a home-based exercise program combined with caregiver training in behavioral management techniques would reduce functional dependence and delay institutionalization among patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 153 community-dwelling patients meeting National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer Disease and Related Disorders Association criteria for Alzheimer disease , conducted between June 1994 and April 1999 . INTERVENTIONS Patient-caregiver dyads were r and omly assigned to the combined exercise and caregiver training program , Reducing Disability in Alzheimer Disease ( RDAD ) , or to routine medical care ( RMC ) . The RDAD program was conducted in the patients ' home over 3 months . MAIN OUTCOME MEASURES Physical health and function ( 36-item Short-Form Health Survey 's [ SF-36 ] physical functioning and physical role functioning subscales and Sickness Impact Profile 's Mobility subscale ) , and affective status ( Hamilton Depression Rating Scale and Cornell Depression Scale for Depression in Dementia ) . RESULTS At 3 months , in comparison with the routine care patients , more patients in the RDAD group exercised at least 60 min/wk ( odds ratio [ OR ] , 2.82 ; 95 % confidence interval [ CI ] , 1.25 - 6.39 ; P = .01 ) and had fewer days of restricted activity ( OR , 3.10 ; 95 % CI , 1.08 - 8.95 ; P<.001 ) . Patients in the RDAD group also had improved scores for physical role functioning compared with worse scores for patients in the RMC group ( mean difference , 19.29 ; 95 % CI , 8.75 - 29.83 ; P<.001 ) . Patients in the RDAD group had improved Cornell Depression Scale for Depression in Dementia scores while the patients in the RMC group had worse scores ( mean difference , -1.03 ; 95 % CI , -0.17 to -1.91 ; P = .02 ) . At 2 years , the RDAD patients continued to have better physical role functioning scores than the RMC patients ( mean difference , 10.89 ; 95 % CI , 3.62 - 18.16 ; P = .003 ) and showed a trend ( 19 % vs 50 % ) for less institutionalization due to behavioral disturbance . For patients with higher depression scores at baseline , those in the RDAD group improved significantly more at 3 months on the Hamilton Depression Rating Scale ( mean difference , 2.21 ; 95 % CI , 0.22 - 4.20 ; P = .04 ) and maintained that improvement at 24 months ( mean difference , 2.14 ; 95 % CI , 0.14 - 4.17 ; P = .04 ) . CONCLUSION Exercise training combined with teaching caregivers behavioral management techniques improved physical health and depression in patients with Alzheimer disease Dementia population worldwide is considerable in elderly people . Exercise regulates the brain function , but the mechanism by which it does so is unknown . The effect of regular exercise on cognitive function and exercise capacity in senile dementia patients was investigated . Thirty female patients with senile dementia who participated in the study were divided into two groups : the exercise group ( EG , n = 15 ) and the control group ( CG , n = 15 ) . The exercise group completed a regular exercise program , and their cognitive function , activities of daily living and exercise capacity levels were evaluated at baseline , 6 months and after 12 months . Subjects exercised 30 - 60 minutes per day , 2 - 3 times per week for 12 months . Mini-mental state examination ( MMSE ) ( pre : 14.53 + /- 5.34 , post : 17.47 + /- 6.90 ) and ADL ( pre : 14.40 + /- 5.32 , post : 17.53 + /- 5.46 ) scores were significantly enhanced in the exercise group with senile dementia , compared to those in the control group . Exercise capacities such as cardiopulmonary function ( pre : 128.47 + /- 55.43 , post : 184.40 + /- 41.16 ) , muscle strength ( pre : 10.07 + /- 3.61 , post : 13.7 + /- 3.90 ) , muscular endurance ( pre : 8.13 + /- 4.45 , post : 12.13 + /- 5.14 ) , flexibility ( - 1.53 + /- .30 , post : 2.20 + /- .70 , balance ( pre : 1.73 + /- .28 , post : 1.20 + /- .77 ) , and agility ( pre : 21.80 + /- 3.24 , post : 10.87 + /- 2.99 ) also increased in the exercise group . Our findings showed that regular exercise can enhance cognitive and functional activity scores in dementia patients , suggesting that senile dementia may improve by participating in a regular exercise program Background : Deficits in attention-related cognitive performance measured as dual-task performance represent early markers of dementia and are associated with motor deficits and increased risk of falling . The purpose of this study was to examine the effect of a specific dual-task training in patients with mild to moderate dementia . Methods : Sixty-one geriatric patients with confirmed dementia took part in a 12-week r and omized , controlled trial . Subjects in the intervention group ( IG ) underwent dual-task – based exercise training . The control group ( CG ) performed unspecific low-intensity exercise . Motor performance ( gait speed , cadence , stride length , stride time , single support ) and cognitive performance ( serial 2 forward calculation [ S2 ] , serial 3 backward calculation [ S3 ] ) were examined as single and dual tasks . Decrease in performance during dual tasks compared to single task expressed as motor , cognitive , and combined motor/cognitive dual-task cost ( DTC ) was calculated before and after intervention . Primary outcome was defined as DTC for gait speed under complex S3 conditions . Results : Specific training significantly improved dual-task performance under complex S3 conditions compared to the CG ( reduction of DTC : gait speed 21.7 % IG , 2.6 % CG , p < 0.001 ; other gait variables : 8.7 % to 41.1 % IG , −0.9 % to 8.1 % CG , p ≤ 0.001 to 0.056 ; combined motor/cognitive : 20.6 % IG , 2.2 % CG , p = 0.026 ) . No significant effects were found under less challenging dual-task S2 conditions or for cognitive dual-task S3 performance . Conclusions : The specific exercise program was effective to improve dual-task performance in patients with dementia . Classification of evidence : This study provides Class II evidence that specific dual-task training improves dual-task performance during walking under complex S3 conditions in geriatric patients with mild to moderate dementia BACKGROUND Depression and antidepressant use are common in Alzheimer disease ( AD ) , but the effect of antidepressant treatment for depression on longer term outcomes is unknown . The authors report the Week-24 outcomes of patients who participated in a 12-week efficacy study of sertraline for depression of AD . METHODS One hundred thirty-one participants ( sertraline = 67 , placebo = 64 ) with mild-moderate AD and depression participated in the study . Patients who showed improvement on the modified Alzheimer 's Disease Cooperative Study Clinical Global Impression-Change ( mADCS-CGIC ) after 12 weeks of r and omized treatment with sertraline or placebo continued double-blinded treatment for an additional 12 weeks . Depression response and remission at 24 weeks were based on mADCS-CGIC score and change in Cornell Scale for Depression in Dementia ( CSDD ) score . Secondary outcome measures included time to remission , nonmood neuropsychiatric symptoms , global cognition , function , and quality of life . RESULTS One hundred seventeen ( 89.3 % ) participants completed all study assessment s and 74 ( 56.5 % ; sertraline = 38 , placebo = 36 ) completed all 24 weeks on r and omized treatment . By 24 weeks , there were no between-group differences in depression response ( sertraline = 44.8 % , placebo = 35.9 % ; odds ratio [ 95 % CI ] = 1.23 [ 0.64 - 2.35 ] ) , change in CSDD score ( median difference = 0.6 [ 95 % CI : -2.26 to 3.46 ] , chi2 [ df = 2 ] = 1.03 ) , remission rates ( sertraline = 32.8 % , placebo = 21.8 % ; odds ratio [ 95 % CI ] = 1.61 [ 0.70 - 3.68 ] ) , or secondary outcomes . Common selective serotonin reuptake inhibitor-associated adverse events , specifically diarrhea , dizziness , and dry mouth , and pulmonary serious adverse events were more frequent in sertraline-r and omized patients than in placebo subjects . CONCLUSIONS Sertraline treatment is not associated with delayed improvement between 12 and 24 weeks of treatment and may not be indicated for the treatment of depression of AD |
1,793 | 22,071,851 | Due to the sub-optimal quality of the trials and statistically non-significant results , it is not possible to draw any conclusions for treatment . | BACKGROUND Chronic Obstructive Pulmonary Disease ( COPD ) is characterised by inflammation of the airways and destruction of pulmonary tissue with post bronchodilator FEV1/FVC of < 0.70 ( forced expiratory volume in one second/forced vital capacity ) .
Evidence indicates an increased prevalence of anxiety disorders in patients with chronic obstructive pulmonary disease ( COPD ) , as compared with the general population and persons suffering from many other chronic illnesses .
Anxiety in people with COPD has been shown to increase disability and impair functional status , result ing in an overall reduction in quality of life .
As such , pharmacological interventions are commonly used to treat anxiety disorders in patients with COPD .
OBJECTIVES To assess the effect of pharmacological interventions on anxiety disorders in people with COPD , in terms of improvement of anxiety symptoms , quality of life , exercise tolerance , reduction in length of hospital stay and FEV1 . | BACKGROUND Although the underlying pathology is initially confined to the lungs , the associated emotional responses to chronic obstructive pulmonary disease ( COPD ) contribute greatly to the result ing morbidity . The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms . METHODS We conducted a 12-week , r and omized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Question naire ( CRQ ) , an evaluative COPD -specific quality -of-life question naire , was the primary outcome . RESULTS 23 patients were r and omized and 15 completed the trial ( 8 on Paroxetine ; 7 on placebo ) . In the per- protocol analysis , we observed statistically and clinical ly significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ : emotional function ( adjusted mean difference : 1.1 ; 95 % confidence interval [ CI ] : 0.0 - 2.2 ) and mastery ( difference : 1.1 ; CI : 0.4 - 1.8 ) . Dyspnea and fatigue improved , but to an extent that did not reach statistical significance . In the intention-to-treat analysis , none of the differences in CRQ scores was significant . Paroxetine was not associated to any worsening of respiratory symptoms . CONCLUSIONS The results of this small r and omized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present . This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD Chronic obstructive pulmonary disease ( COPD ) affects over 16 million people in the United States and is a major cause of disability and death worldwide . Its prevalence and mortality are increasing disproportionately among the elderly , women , African-Americans , persons of lower socioeconomic status , and the population s of developing countries in which tobacco is aggressively marketed . In contrast to other major chronic diseases such as heart disease and cancer , medical treatments for COPD have not made decisive inroads into its morbidity or death rates over the last 20 years , result ing in continuing efforts to reduce disability in patients with established disease . Depression is a source of increased disability in COPD , and , as in other chronically ill patient population s , is often unrecognized and untreated in the primary and specialty care sectors . Nearly half of all patients experience some depressive symptoms and at least one-fifth have had one or more major depressive episodes , frequently of long duration . Evidence from r and omized controlled trials supports the thesis that patients with mild depression improve with multidisciplinary rehabilitation , whereas patients with major depression may require specific pharmacotherapy to achieve significant improvement in mood disorder and day-to-day function . In addition to its impact on disability , depression may contribute indirectly to the etiology and progression of COPD through its relationship to addictive smoking . Mood disorder in adolescence and early adulthood contributes to early smoking and failure to quit , even after the onset of respiratory disease in later life . Patients with a history of major depression are more likely to fail in smoking cessation programs and to develop a major depressive episode when they do stop . This relationship calls for psychiatrically informed intervention models to improve long-term abstinence rates . The functional impairments associated with COPD are themselves potential promoters of depressive morbidity and chronicity , acting through complex causal pathways . Progressive hypoxia due to respiratory insufficiency leads to structural brain changes and neurocognitive deficits that impair day-to-day function and reduce adaptive potential ; and oxygen therapy , as now practice d , offers minimal neurocognitive and mood benefits to most patients . Limited data from studies of experimental hypoxia in animals suggest that relatively mild lack of oxygen impairs the function and plasticity of critical neurotransmitter systems implicated in both cognition and mood , although current practice st and ards withhold oxygen therapy until late in the course of disease when the damaging effects of hypoxia on the brain have become well established . Neuropsychiatric approaches to the prevention , delay , and treatment of brain dysfunction should be a primary objective of research to improve patient outcomes . A comprehensive relational model that links pulmonary disease , hypoxia , neurocognitive impairment , and structural brain disease with depression provides a useful framework for the design of such studies . The near-term research agenda should include three components : ( 1 ) practical methods for improving physician and patient recognition of depression and neurocognitive impairment as targets for intervention ; ( 2 ) additional trials of st and ard antidepressant treatment approaches for both major and minor depression ; and ( 3 ) tests of the hypothesis that late-onset depression in patients with COPD is a marker for the presence of neurocognitive deficits and structural brain changes . The long-range research agenda must aim at preventive interventions design ed to forestall brain deterioration . Controlled clinical trials of supplemental oxygen in patients with mild hypoxia and minimal cognitive deficits are needed to determine whether early treatment can reverse or moderate decline , reduce the incidence and chronicity of depression , and improve response to antidepressant treatment . Novel neuroprotective therapies such as antioxidant supplementation and modulation of monoaminergic neurotransmission , coupled with overall improvements in long-term respiratory disease management that minimize episodes of increased systemic oxidative stress , should be considered for multisite trials design ed to define optimal treatment and prevention Buspirone is an anxiolytic agent that appears to have no sedative effects . The aim of this study was to assess the effects of buspirone on breathlessness and exercise tolerance in patients with chronic airway obstruction . Sixteen patients , age 56.9 + /- 17.0 ; forced expiratory volume in 1 s ( FEV1 ) 1.15 + /- 0.42 l ; FEV1/forced vital capacity ( FVC ) 50.7 + /- 15.0 % ; PaCO2 42.2 + /- 5.5 mm Hg ; and PaO2 57.6 + /- 10 mm Hg , underwent a 6-min walking test , an incremental cycle ergometer test , an incremental treadmill walking test with self- assessment of dyspnea on Borg 's scale during exercise and an assessment of respiratory drive ( P 0.1 ) , timing [ inspiration time (TI)/total breathing time ( Ttot ) ] , PaO2 , PaCO2 , FVC , FEV1 , following oral administration for 14 days of placebo or buspirone ( 20 mg daily ) in a double-blind , cross-over r and omized way . We also used the symptom check list-90-R for the assessment of subjective complaints and symptomatic behavior . A significant improvement in anxiety , depression and obsessive symptoms and complaints was noted after buspirone treatment . The P 0.1 , TI/Ttot , arterial blood gases and respiratory mechanics did not change after drug treatment . There was an improvement in exercise tolerance and in the sensation of dyspnea during the buspirone period . Thus , as given in this study , oral buspirone has therapeutic potential in the treatment of dyspnea in patients with chronic lung disease Over the ensuing seven months she had three more clinical relapses , each accompanied by reappearance in the stools of either the organism or its cytotoxin , or both . Each improvement after vancomycin ( eight to 14-daycourses ) was accompanied by disappearance of the organism . At one point she was given cholestyramine , but she was unable to tolerate it . Her illness was punctuated by malnutrition and episodes of heart failure . She was given no other antibiotics . After the sixth relapse maintenance treatment with oral vancomycin 125 mg eight-hourly was begun . With this regimen diarrhoea was controlled and stools over the next 10 weeks remained negative for C difficile and its cytotoxin . There was no adverse reaction to vancomycin throughout Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients , detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate . The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression . Thirty patients completed a 12-week , r and omized controlled trial of nortriptyline . Nortriptyline was clearly superior to placebo for treatment of depression . Nortriptyline treatment was accompanied by marked improvements in anxiety , certain respiratory symptoms , overall physical comfort , and day-to-day function ; placebo effects were negligible . Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment . These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients There is controversy as to whether effects on mood play a role in mediating the response to corticosteroids in chronic obstructive pulmonary disease ( COPD ) . If alterations in mood are important , it is conceivable that psychotropic drugs such as mianserin might produce similar responses to prednisolone in patients with COPD .Twelve patients age 62.5 y , with FEV1 29 % of predicted and < 15 % reversibility to salbutamol completed a r and omised , double-blind crossover study . After an initial three week placebo run-in period patients received three weeks of prednisolone 40 mg daily or mianserin 60–90 mg daily with an intervening three week placebo washout period . Full respiratory function tests , bicycle ergometry and 6 minute walks were performed before and after the run-in and at the end of each period . Psychological and functional assessment s were also made at each visit . Prednisolone significantly increased FVC , maximum ventilation ( VEmax ) and maximum heart rate ( HRmax ) compared with placebo , with mean for the difference of 0.251 , 2.561 · min−1 and 12 beats · min−1 respectively . FVC , maximum oxygen uptake ( VO2max ) and HRmax were also significantly increased with prednisolone compared with mianserin . Anxiety scores were significantly lower with prednisolone compared with placebo . In contrast , mianserin had no significant effects on lung function , exercise or psychological parameters compared with placebo . The improvements in ventilation , exercise and anxiety scores following treatment with prednisolone were not reproduced by mianserin , suggesting that the effects of prednisolone in COPD are unlikely to be due to alterations in mood The objective of this study was to determine if buspirone would alleviate anxiety and improve exercise tolerance of anxious patients with chronic airflow obstruction ( CAO ) . Eleven male patients with mild to moderate anxiety and CAO completed this study comparing buspirone , 10 to 20 mg given three times a day , with placebo . Patients were evaluated with State Trait Anxiety Inventory , spirometry , 12-min walk , incremental exercise on a cycle ergometer to symptom limitation and measurement of dyspnea with a modified Borg scale at exercise levels and the end of each 2 min on 12-min walk . There were no significant differences in anxiety scores , work load , maximum oxygen consumption per minute , maximum expired volume per minute , PETCO2 , PETO2 , 12-min walking distance or dyspnea scores after 6 weeks of buspirone or placebo therapy . We conclude that administration of buspirone has no significant effect on anxiety levels , exercise capabilities or PETO2 or PETCO2 in patients with CAO and mild anxiety The aim of this study was to determine whether treating concomitant depression improves quality of life and exercise tolerance in COPD patients . Out- patients with moderate to severe , stable COPD completed Hospital Anxiety-Depression ( HAD ) and General Health question naires . A psychiatrist interviewed those with high scores . In a r and omised , double-blind fashion , 28 depressed COPD patients took a selective serotonin re-uptake inhibitor , Paroxetine 20 mg daily , or matched placebo for 6 weeks . Subsequently , all patients took un-blinded Paroxetine for 3 months . From these question naires , 35 % of 135 patients had significant depression , but this was confirmed by psychiatric interview in only 21 % . Throughout the study , there were no changes in laboratory lung function nor in home peak flow . Six weeks ' treatment produced no significant differences between placebo and treatment group in either depression , quality of life scores or 6-minute walking distances , although overall improvements in depression , correlated with increases in walking distance . Three months of un-blinded treatment , significantly improved depression scores ( self-complete HAD , Beck 's Depression and psychiatrist-completed Montgomery-Asberg scores ) , walking distances ( 369 to 427 m , p = 0.0003 ) and St. George 's Respiratory Question naire Total Scores ( 65 to 58 , p = 0.033 ) . Although self-complete question naires over-diagnose depression , the condition is nevertheless common in patients with moderately severe COPD . Six weeks of antidepressants is insufficient to improve either depression , quality of life or exercise tolerance . However , our study suggests that a longer course of treatment may be effective and that improvements in depression are associated with improvements in exercise tolerance . A larger , double blind study with a longer treatment period is indicated During each of two six-week treatment periods , 12 depressed out patients with chronic obstructive pulmonary disease received increasing doses of doxepin hydrochloride or a placebo as tolerated . The mean maximal doses of doxepin hydrochloride and placebo were 105 and 128 mg , respectively . Three of the 12 patients dropped out because of doxepin 's side effects . The depression and anxiety scores at the end of the treatment periods were virtually identical and not significantly different from baseline scores . Changes in the 12-minute walking distance were more closely correlated with changes in the depression and anxiety scores than with changes in the forced expiratory volume in 1 s or forced vital capacity . Thus , doxepin is ineffective in treating depressed patients with chronic obstructive pulmonary disease ; improvements in the 12-minute walking distance were closely correlated with improvements in the depression or anxiety scores |
1,794 | 26,590,198 | The positive deviance approach was most frequently applied within North America , in secondary care , and to address healthcare-associated infections .
Research predominantly identified positive deviants and generated hypotheses about how they succeeded .
Applications of positive deviance typically lacked staff and /or patient involvement , and the methods used often required extensive re sources . | BACKGROUND The positive deviance approach focuses on those who demonstrate exceptional performance , despite facing the same constraints as others . '
Positive deviants ' are identified and hypotheses about how they succeed are generated .
These hypotheses are tested and then disseminated within the wider community .
The positive deviance approach is being increasingly applied within healthcare organisations , although limited guidance exists and different methods , of varying quality , are used .
This paper systematic ally review s healthcare applications of the positive deviance approach to explore how positive deviance is defined , the quality of existing applications and the methods used within them , including the extent to which staff and patients are involved . | OBJECTIVE To evaluate the effectiveness of a positive deviance strategy for the improvement of h and hygiene compliance in 2 adult step-down units . DESIGN A 9-month , controlled trial comparing the effect of positive deviance on compliance with h and hygiene . SETTING Two 20-bed step-down units at a tertiary care private hospital . METHODS The first phase of our study was a 3-month baseline period ( from April to June 2008 ) in which h and hygiene episodes were counted by use of electronic h and washing counters . From July to September 2008 ( ie , the second phase ) , a positive deviance strategy was implemented in the east unit ; the west unit was the control unit . During the period from October to December 2008 ( ie , the third phase ) , positive deviance was applied in both units . RESULTS During the first phase , there was no statistically significant difference between the 2 step-down units in the number of episodes of h and hygiene per 1,000 patient-days or in the incidence density of healthcare-associated infections ( HAIs ) per 1,000 patient-days . During the second phase , there were 62,000 h and hygiene episodes per 1,000 patient-days in the east unit and 33,570 h and hygiene episodes per 1,000 patient-days in the west unit ( P < .01 ) . The incidence density of HAIs per 1,000 patient-days was 6.5 in the east unit and 12.7 in the west unit ( p = .04 ) . During the third phase , there was no statistically significant difference in h and hygiene episodes per 1,000 patient-days ( P = .16 ) or in incidence density of HAIs per 1,000 patient-days . CONCLUSION A positive deviance strategy yielded a significant improvement in h and hygiene , which was associated with a decrease in the overall incidence of HAIs UNLABELLED RATIONALE , AIMS & OBJECTIVE : Tools for the assessment of the quality of research studies tend to be specific to a particular research design ( e.g. r and omized controlled trials , or qualitative interviews ) . This makes it difficult to assess the quality of a body of research that addresses the same or a similar research question but using different approaches . The aim of this paper is to describe the development and preliminary evaluation of a quality assessment tool that can be applied to a method ologically diverse set of research articles . METHODS The 16-item quality assessment tool ( QATSDD ) was assessed to determine its reliability and validity when used by health services research ers in the disciplines of psychology , sociology and nursing . Qualitative feedback was also gathered from mixed- methods health research ers regarding the comprehension , content , perceived value and usability of the tool . RESULTS Reference to existing widely used quality assessment tools and experts in systematic review confirmed that the components of the tool represented the construct of ' good research technique ' being assessed . Face validity was subsequently established through feedback from a sample of nine health research ers . Inter-rater reliability was established through substantial agreement between three review ers when applying the tool to a set of three research papers ( κ = 71.5 % ) , and good to substantial agreement between their scores at time 1 and after a 6-week interval at time 2 confirmed test-retest reliability . CONCLUSIONS The QATSDD shows good reliability and validity for use in the quality assessment of a diversity of studies , and may be an extremely useful tool for review ers to st and ardize and increase the rigour of their assessment s in review s of the published papers which include qualitative and quantitative work BACKGROUND Family planning programmes in developing countries need a better underst and ing of nurse-patient communication in order to improve the quality of counselling . OBJECTIVES To identify factors in the clinic and in the community that enable nurses and patients to communicate effectively with one another . DESIGN The study explored the personal experiences of nurses and patients who communicate especially effectively during family planning consultations ( so-called " positive deviants " ) . SETTING Sixty-four r and omly selected public clinics located in East Java , Indonesia . PARTICIPANTS Seven positive deviant nurses and 32 positive deviant patients were identified from among 64 nurses and 768 patients who participated in an earlier patient coaching study . Flooding prevented 5 patients from participating in the study , reducing their number to 27 . METHODS Investigators conducted : ( 1 ) a content analysis of qualitative data collected by structured in-depth interviews and focus-group discussion s ( FGDs ) with positive deviant nurses and patients , and ( 2 ) analyses of variance ( ANOVA ) of quantitative data on clinic , nurse , and patient characteristics . RESULTS Positive deviant nurses identified four factors , listed in rough order of importance , that helped them communicate effectively : independent study to strengthen their knowledge and skills ; communication aids ; feedback from colleagues ; and motivation stemming from a desire to help people , patients ' appreciation , husb and 's support , and increased income . Positive deviant patients identified five enabling factors : motivation due to their need for a service ; confidence in their own communication skills ; positive feedback from nurses ; belief in patients ' right and responsibility to communicate with nurses ; and communication aids . CONCLUSIONS Insights from positive deviant nurses and patients suggest that efforts to improve nurse-patient communication should go beyond conventional communication skills training . Managers should consider a mix of clinic-based interventions ( such as peer feedback , communication aids , and better management of patient flow ) and community-based interventions ( such as patient education and mass media ) UNLABELLED Improvement of chronic disease management in primary care entails monitoring indicators of quality over time and across patients and practice s. Informatics tools are needed , yet implementing them remains challenging . OBJECTIVE To identify critical success factors enabling the translation of clinical and operational knowledge about effective and efficient chronic care management into primary care practice . DESIGN A prospect i ve case study of positive deviants using key informant interviews , process observation , and document review . SETTING A chronic disease management ( CDM ) collaborative of primary care physicians with documented improvement in adherence to clinical practice guidelines using a web-based patient registry system with CDM guideline -based flow sheet . PARTICIPANTS Thirty community-based physician participants using predominantly paper records , plus a project management team including the physician lead , project manager , evaluator and support team . ANALYSIS A critical success factor ( CSF ) analysis of necessary and sufficient pathways to the translation of knowledge into clinical practice . RESULTS A web-based CDM ' toolkit ' was found to be a direct CSF that allowed this group of physicians to improve their practice by tracking patient care processes using evidence -based clinical practice guideline -based flow sheets . Moreover , the information and communication technology ' factor ' was sufficient for success only as part of a set of seven direct CSF components including : health delivery system enhancements , organizational partnerships , funding mechanisms , project management , practice models , and formal knowledge translation practice s. Indirect factors that orchestrated success through the direct factor components were also identified . A central insight of this analysis is that a comprehensive quality improvement model was the CSF that drew this set of factors into a functional framework for successful knowledge translation . CONCLUSIONS In complex primary care setting s environment where physicians have low adoption rates of electronic tools to support the care of patients with chronic conditions , successful implementation may require a set of interrelated system and technology factors |
1,795 | 27,367,726 | RESULTS Eight r and omized controlled studies met the inclusion criteria , and their subsequent analysis revealed that improvements in psychological and social outcomes do occur during short- and long-term weight loss programmes , but that low-carbohydrate diets have no greater effect on psychosocial outcomes when compared to diets of different macronutrient composition at either short- or long-term follow-up ( one-year ) .
The short- and long-term improvements in psychosocial outcomes seen in patients undergoing weight-loss treatment appear to be independent of the macronutrient composition of their diet | BACKGROUND Little is known about the relative psychosocial effects of carbohydrate reduction in comparison to other weight-loss diets in subjects receiving treatment for obesity/overweight .
We , therefore , set out to conduct a systematic review of the psychosocial outcomes of such patients , treated by means of either a low-carbohydrate diet or an isocaloric diet of other macronutrient composition . | BACKGROUND / OBJECTIVE Very low-carbohydrate , high-fat ( LC ) diets are used for type 2 diabetes ( T2DM ) management , but their effects on psychological health remain largely unknown . This study examined the long-term effects of an LC diet on psychological health . METHODS One hundred and fifteen obese adults [ age : 58.5 ± 7.1 years ; body mass index : 34.6 ± 4.3 kg m(-2 ) ; HbA1c : 7.3 ± 1.1 % ] with T2DM were r and omized to consume either an energy-restricted ( ~6 to 7 MJ ) , planned isocaloric LC or high-carbohydrate , low-fat ( HC ) diet , combined with a supervised exercise programme ( 3 days week(-1 ) ) for 1 year . Body weight , psychological mood state and well-being [ Profile of Mood States ( POMS ) , Beck Depression Inventory ( BDI ) and Spielberger State Anxiety Inventory ( SAI ) ] and diabetes-specific emotional distress [ Problem Areas in Diabetes ( PAID ) Question naire ] and quality of life [ QoL Diabetes-39 ( D-39 ) ] were assessed . RESULTS Overall weight loss was 9.5 ± 0.5 kg ( mean ± SE ) , with no difference between groups ( P = 0.91 time × diet ) . Significant improvements occurred in BDI , POMS ( total mood disturbance and the six subscales of anger-hostility , confusion-bewilderment , depression-dejection , fatigue-inertia , vigour-activity and tension-anxiety ) , PAID ( total score ) and the D-39 dimensions of diabetes control , anxiety and worry , sexual functioning and energy and mobility , P < 0.05 time . SAI and the D-39 dimension of social burden remained unchanged ( P ≥ 0.08 time ) . Diet composition had no effect on the responses for the outcomes assessed ( P ≥ 0.22 time × diet ) . CONCLUSION In obese adults with T2DM , both diets achieved substantial weight loss and comparable improvements in QoL , mood state and affect . These results suggest that either an LC or HC diet within a lifestyle modification programme that includes exercise training improves psychological well-being OBJECTIVE To investigate the effects of weight loss diets on mood , food cravings , and other self-reported symptoms . RESEARCH METHODS AND PROCEDURES Mood and other symptoms were evaluated by participant self-report using the Atkins Health Indicator Test ( AHIT ) in individuals undergoing weight loss following either a low-carbohydrate , ketogenic diet ( LCKD ) or a low-fat diet ( LFD ) . Participants were 119 overweight community volunteers r and omized to an LCKD or an LFD . An additional 51 participants who had completed an earlier trial contributed data for the psychometric analyses but were not included in the prospect i ve analyses . Self-reported symptom levels on seven scales factor-analytically derived from the AHIT ( negative affect , fatigue , somatic symptoms , physical effects of hunger , insomnia , hunger , and stomach problems ) were acquired during 12 visits . RESULTS After adjusting for the change in BMI over the course of the trial , participants experienced significant improvements in most symptoms regardless of diet . Diet group x visit interactions were observed for negative affect [ F(9,803 ) = 2.30 , p = 0.015 ] and hunger [ F(9,803 ) = 3.62 , p < 0.0002 ] . Examination of means indicated that the LCKD group reported less negative affect and hunger , compared with the LFD group . DISCUSSION Regardless of diet , participants experienced significant improvement in a broad range of symptoms . Symptoms of negative affect and hunger improved to a greater degree in patients following an LCKD compared with those following an LFD . Whether these symptom changes explain the greater short-term weight loss generally experienced by LCKD followers deserves further research Objective To compare the effects of isocaloric , energy-restricted very low-carbohydrate ketogenic ( VLCK ) and low-fat ( LF ) diets on weight loss , body composition , trunk fat mass , and resting energy expenditure ( REE ) in overweight/obese men and women . Design R and omized , balanced , two diet period clinical intervention study . Subjects were prescribed two energy-restricted ( -500 kcal/day ) diets : a VLCK diet with a goal to decrease carbohydrate levels below 10 % of energy and induce ketosis and a LF diet with a goal similar to national recommendations ( % carbohydrate : fat : protein = ~60:25:15%).Subjects15 healthy , overweight/obese men ( mean ± s.e.m . : age 33.2 ± 2.9 y , body mass 109.1 ± 4.6 kg , body mass index 34.1 ± 1.1 kg/m2 ) and 13 premenopausal women ( age 34.0 ± 2.4 y , body mass 76.3 ± 3.6 kg , body mass index 29.6 ± 1.1 kg/m2 ) . Measurements Weight loss , body composition , trunk fat ( by dual-energy X-ray absorptiometry ) , and resting energy expenditure ( REE ) were determined at baseline and after each diet intervention . Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person . Results Actual nutrient intakes from food records during the VLCK ( % carbohydrate : fat : protein = ~9:63:28 % ) and the LF ( ~58:22:20 % ) were significantly different . Dietary energy was restricted , but was slightly higher during the VLCK ( 1855 kcal/day ) compared to the LF ( 1562 kcal/day ) diet for men . Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss , total fat loss , and trunk fat loss for men ( despite significantly greater energy intake ) . The majority of women also responded more favorably to the VLCK diet , especially in terms of trunk fat loss . The greater reduction in trunk fat was not merely due to the greater total fat loss , because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women . Absolute REE ( kcal/day ) was decreased with both diets as expected , but REE expressed relative to body mass ( kcal/kg ) , was better maintained on the VLCK diet for men only . Individual responses clearly show the majority of men and women experience greater weight and fat loss on a VLCK than a LF diet . Conclusion This study shows a clear benefit of a VLCK over LF diet for short-term body weight and fat loss , especially in men . A preferential loss of fat in the trunk region with a VLCK diet is novel and potentially clinical ly significant but requires further validation . These data provide additional support for the concept of metabolic advantage with diets representing extremes in macronutrient distribution BACKGROUND The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed . METHODS We r and omly assigned 132 severely obese subjects ( including 77 blacks and 23 women ) with a mean body-mass index of 43 and a high prevalence of diabetes ( 39 percent ) or the metabolic syndrome ( 43 percent ) to a carbohydrate-restricted ( low-carbohydrate ) diet or a calorie- and fat-restricted ( low-fat ) diet . RESULTS Seventy-nine subjects completed the six-month study . An analysis including all subjects , with the last observation carried forward for those who dropped out , showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet ( mean [ + /-SD ] , -5.8+/-8.6 kg vs. -1.9+/-4.2 kg ; P=0.002 ) and had greater decreases in triglyceride levels ( mean , -20+/-43 percent vs. -4+/-31 percent ; P=0.001 ) , irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications . Insulin sensitivity , measured only in subjects without diabetes , also improved more among subjects on the low-carbohydrate diet ( 6+/-9 percent vs. -3+/-8 percent , P=0.01 ) . The amount of weight lost ( P<0.001 ) and assignment to the low-carbohydrate diet ( P=0.01 ) were independent predictors of improvement in triglyceride levels and insulin sensitivity . CONCLUSIONS Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet , with a relative improvement in insulin sensitivity and triglyceride levels , even after adjustment for the amount of weight lost . This finding should be interpreted with caution , given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study . Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed BACKGROUND In the United States , obesity is a major clinical and public health problem causing diabetes , dyslipidemia , and hypertension , as well as increasing cardiovascular and total mortality . Dietary restrictions of calories and saturated fat are beneficial . However , it remains unclear whether replacement of saturated fat with carbohydrates ( as in the US National Cholesterol Education Program [ NCEP ] diet ) or protein and monounsaturated fat ( as in our isocaloric modified low-carbohydrate [ MLC ] diet , which is lower in total carbohydrates but higher in protein , monounsaturated fat , and complex carbohydrates ) is optimal . METHODS We r and omized 60 participants ( 29 women and 31 men ) to the NCEP or the MLC diet and evaluated them every 2 weeks for 12 weeks . They were aged 28 to 71 years ( mean age , 44 years in the NCEP and 46 years in the MLC group ) . A total of 36 % of participants from the NCEP group and 35 % from the MLC group had a body mass index ( calculated as weight in kilograms divided by the square of height in meters ) greater than 27 . The primary end point was weight loss , and secondary end points were blood lipid levels and waist-to-hip ratio . RESULTS Weight loss was significantly greater in the MLC ( 13.6 lb ) than in the NCEP group ( 7.5 lb ) , a difference of 6.1 lb ( P = .02 ) . There were no significant differences between the groups for total , low density , and high-density lipoprotein cholesterol , triglycerides , or the proportion of small , dense low-density lipoprotein particles . There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group . Waist-to-hip ratio was not significantly reduced between the groups ( P = .27 ) , but it significantly decreased within the MLC group ( P = .009 ) . CONCLUSIONS Compared with the NCEP diet , the MLC diet , which is lower in total carbohydrates but higher in complex carbohydrates , protein , and monounsaturated fat , caused significantly greater weight loss over 12 weeks . There were no significant differences between the groups in blood lipid levels , but favorable changes were observed within the MLC diet group OBJECTIVE We examined the effects of an intensive lifestyle intervention ( ILI ) , compared with a diabetes support and education ( DSE ) control intervention , on long-term changes in depression symptoms , antidepressant medication ( ADM ) use , and health-related quality of life ( HRQoL ) in overweight/obese individuals with type 2 diabetes . RESEARCH DESIGN AND METHODS Look AHEAD was a multisite r and omized controlled trial of 5,145 overweight/obese participants assigned to ILI ( design ed to produce weight loss ) or DSE and followed for a median of 9.6 years . The Beck Depression Inventory ( BDI ) was administered at baseline , annually at years 1–4 , and again at year 8 . Mean BDI scores and incidence of BDI scores ≥10 , indicative of likely mild or greater depression , were examined . Annually through year 10 , participants reported their ADM use and completed the Medical Outcomes Study Short Form 36 ( SF-36 ) question naire , which yields physical component summary ( PCS ) and mental component summary ( MCS ) scores . RESULTS ILI significantly reduced the incidence of mild or greater depression symptoms ( BDI scores ≥10 ) compared with DSE ( hazard ratio [ HR ] = 0.85 ; 95 % CI 0.75–0.97 ; P = 0.0145 ) . Although SF-36 PCS scores worsened over time in both groups , ILI participants reported better physical function than DSE throughout the first 8 years ( all P values < 0.01 ) . There were no significant differences between treatment arms in the proportion of participants who used ADMs or in SF-36 MCS scores . CONCLUSIONS ILI for overweight/obese patients with type 2 diabetes may reduce the risk of developing clinical ly significant symptoms of depression and preserve physical HRQoL. These findings should be considered when evaluating the potential benefits of ILIs This study investigated the acceptability of two very-low-calorie diets in 16 moderately overweight persons participating in a weight reduction program . Subjects were prescribed a 1000 - 1200 kcal balanced diet the first month and asked to complete appetite and mood scales on a weekly basis . They were then r and omly assigned to either a protein-sparing-modified fast ( PSMF ) or a protein-formula-liquid diet , each of which provided about 400 kcal daily . Analysis of the appetite data showed that PSMF subjects reported significantly less hunger and preoccupation with eating than did liquid diet subjects during 2 of the 4 weeks on a very-low-calorie diet . Subjects in both conditions reported significant reductions in anxiety . Results are discussed in terms of possible advantages of PSMF After a baseline period of free-feeding , 20 obese out patients alternated between four 2-wk periods of minimal-carbohydrate diet ( 800 kcal ; 58 % protein and 42 % fat by weight ) and of a carbohydrate-supplemented diet ( 1,000 kcal ; 42 % protein , 30 % fat , and 28 % carbohydrate ) . In a comparison of psychological adjustment during the baseline and low-calorie diets , the initial 2 wk of dieting was associated with a decrease in appetite and elevation of psychological well-being , regardless of the composition of the diet . Thereafter , appetite and mood approached basal levels . Further changes in these psychological reactions to dieting did not vary with the type of diet . There was no support for the idea that a minimal-carbohydrate , protein-supplemented fast decreases appetite and elevates mood more in comparison with a similar diet containing enough carbohydrate to minimize ketosis BACKGROUND Low-carbohydrate diets are often used to promote weight loss , but their effects on psychological function are largely unknown . OBJECTIVE We compared the effects of a low-carbohydrate , high-fat ( LCHF ) diet with a conventional high-carbohydrate , low-fat ( HCLF ) diet on mood and cognitive function . DESIGN Ninety-three overweight or obese participants [ x + /- SEM age : 50.2 + /- 0.8 y ; body mass index ( in kg/m2 ) : 33.6 + /- 0.4 ] were r and omly assigned to an energy-restricted ( approximately 6 - 7 MJ , 30 % deficit ) , planned isocaloric LCHF diet or an HCLF diet for 8 wk . Body weight and psychological well-being were measured by using the Profile of Mood States , Beck Depression Inventory , and Spielberger State Anxiety Inventory instruments at baseline and fortnightly . Cognitive functioning ( working memory and speed of processing ) was assessed at baseline and week 8 . RESULTS The LCHF diet result ed in significantly greater weight loss than did the HCLF diet ( 7.8 + /- 0.4 and 6.4 + /- 0.4 kg , respectively ; P = 0.04 ) . Both groups showed improvements in psychological well-being ( P < 0.01 for time ) , with the greatest effect occurring during the first 2 wk , but there was no significant difference between groups . There were no significant between-group differences in working memory ( P = 0.68 ) , but there was a significant time x diet interaction for speed of processing ( P = 0.04 ) , so that this measure improved less in the LCHF than in the HCLF diet group . CONCLUSIONS Both dietary patterns significantly reduced body weight and were associated with improvements in mood . There was some evidence for a smaller improvement in cognitive functioning with the LCHF diet with respect to speed of processing , but further studies are required to determine the replicability of this finding After a weight-maintaining diet base-line , obese female in patients were provided with either a carbohydrate-restricted diet ( 827 kcal ; 35 % protein , 64 % fat , 1 % carbohydrate ) or a carbohydrate-containing diet ( 827 kcal ; 35 % protein , 36 % fat , 29 % carbohydrate ) for 6 wk . When compared with the psychological adjustment during the base-line diet , there was a temporary increase in appetite and a tendency toward dysphoric moods and attitudes during the 1st wk of both treatment diets . After adaptation to the treatment diets , appetite and other psychological states were similar to those during the pretreatment weight-maintaining diet . There was no support for the idea that a carbohydrate-free protein-supplemented fast decreases appetite and elevates mood in comparison with an isocaloric carbohydrate-containing diet . Thus , suppression of appetite alone does not appear to be sufficient reason in itself for using diets of this type BACKGROUND Ad libitum , low-carbohydrate diets decrease caloric intake and cause weight loss . It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake . OBJECTIVE We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake . DESIGN Appetite , caloric intake , body weight , and fat mass were measured in 19 subjects placed sequentially on the following diets : a weight-maintaining diet ( 15 % protein , 35 % fat , and 50 % carbohydrate ) for 2 wk , an isocaloric diet ( 30 % protein , 20 % fat , and 50 % carbohydrate ) for 2 wk , and an ad libitum diet ( 30 % protein , 20 % fat , and 50 % carbohydrate ) for 12 wk . Blood was sample d frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve ( AUC ) for insulin , leptin , and ghrelin . RESULTS Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC . Mean ( + /-SE ) spontaneous energy intake decreased by 441 + /- 63 kcal/d , body weight decreased by 4.9 + /- 0.5 kg , and fat mass decreased by 3.7 + /- 0.4 kg with the ad libitum , high-protein diet , despite a significantly decreased leptin AUC and increased ghrelin AUC . CONCLUSIONS An increase in dietary protein from 15 % to 30 % of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss . This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets The purpose of this study was to conduct an assessment of binge eating severity among obese persons . Two question naires were developed . A 16-item Binge Eating Scale was constructed describing both behavioral manifestations ( e.g. , eating large amounts of food ) and feeling/cognitions surrounding a binge episode ( e.g. , guilt , fear of being unable to stop eating ) . An 11-item Cognitive Factors Scale was developed measure two cognitive phenomena thought to be related to binge eating : the tendency to set unrealistic st and ards for a diet ( e.g. , eliminating " favorite foods " ) and low efficacy expectations for sustaining a diet . The results showed that the Binge Eating Scale successfully discriminated among persons judged by trained interviewers to have either no , moderate or severe binge eating problems . Significant correlation between the scales were obtained such that severe bingers tended to set up diets which were unrealistically strict while reporting low efficacy expectations to sustain a diet . The discussion highlighted the differences among obese persons on binge eating severity and emphasized the role of cognitions in the relapse of self control of eating Overweight and obese men and women ( 24 - 61 yr of age ) were recruited into a r and omized trial to compare the effects of a low-fat ( LF ) vs. a low-carbohydrate ( LC ) diet on weight loss . Thirty-one subjects completed all 10 wk of the diet intervention ( retention , 78 % ) . Subjects on the LF diet consumed an average of 17.8 % of energy from fat , compared with their habitual intake of 36.4 % , and had a result ing energy restriction of 2540 kJ/d . Subjects on the LC diet consumed an average of 15.4 % carbohydrate , compared with habitual intakes of about 50 % carbohydrate , and had a result ing energy restriction of 3195 kJ/d . Both groups of subjects had significant weight loss over the 10 wk of diet intervention and nearly identical improvements in body weight and fat mass . LF subjects lost an average of 6.8 kg and had a decrease in body mass index of 2.2 kg/m2 , compared with a loss of 7.0 kg and decrease in body mass index of 2.1 kg/m2 in the LC subjects . The LF group better preserved lean body mass when compared with the LC group ; however , only the LC group had a significant decrease in circulating insulin concentrations . Group results indicated that the diets were equally effective in reducing systolic blood pressure by about 10 mm Hg and diastolic pressure by 5 mm Hg and decreasing plasminogen activator inhibitor-1 bioactivity . Blood beta-hydroxybutyrate concentrations were increased in the LC only , at the 2- and 4-wk time points . These data suggest that energy restriction achieved by a very LC diet is equally effective as a LF diet strategy for weight loss and decreasing body fat in overweight and obese adults BACKGROUND Little is known about the comparative effect of weight-loss diets on metabolic profiles during dieting . OBJECTIVE The purpose of this study was to compare the effect of a low-carbohydrate diet ( < or = 20 g/d ) with a high-carbohydrate diet ( 55 % of total energy intake ) on fasting and hourly metabolic variables during active weight loss . DESIGN Healthy , obese adults ( n = 32 ; 22 women , 10 men ) were r and omly assigned to receive either a carbohydrate-restricted diet [ High Fat ; mean + /- SD body mass index ( BMI ; in kg/m(2 ) ) : 35.8 + /- 2.9 ] or a calorie-restricted , low-fat diet ( High Carb ; BMI : 36.7 + /- 4.6 ) for 6 wk . A 24-h in-patient feeding study was performed at baseline and after 6 wk . Glucose , insulin , free fatty acids ( FFAs ) , and triglycerides were measured hourly during meals , at regimented times . Remnant lipoprotein cholesterol was measured every 4 h. RESULTS Patients lost a similar amount of weight in both groups ( P = 0.57 ) . There was an absence of any diet treatment effect between groups on fasting triglycerides or on remnant lipoprotein cholesterol , which was the main outcome . Fasting insulin decreased ( P = 0.03 ) , and both fasting ( P = 0.040 ) and 24-h FFAs ( P < 0.0001 ) increased within the High Fat group . Twenty-four-hour insulin decreased ( P < 0.05 for both groups ) . Fasting LDL cholesterol decreased in the High Carb group only ( P = 0.003 ) . In both groups , the differences in fasting and 24-h FFAs at 6 wk were significantly correlated with the change in LDL cholesterol ( fasting FFA : r = 0.41 , P = 0.02 ; 24-h FFA : r = 0.52 , P = 0.002 ) . CONCLUSIONS Weight loss was similar between diets , but only the high-fat diet increased LDL-cholesterol concentrations . This effect was related to the lack of suppression of both fasting and 24-h FFAs Objective Very-low-calorie diets have been shown to produce dramatic improvements in glycemic control in obese subjects with non-insulin-dependent ( type II ) diabetes . There have been no studies of the psychological responses of diabetic subjects to these diets . Research Design and Methods This study examined changes in hunger , depression , and anxiety in 33 obese type II diabetic subjects who were r and omly assigned to behavior modification programs that used either a balanced diet of 4185–6277 J∕day ( 1000–1500 cal∕day ) throughout or included an 8-wk period of a very-low-calorie diet ( 1674 J∕day or 400 cal∕day of lean meat , fish , or fowl ) . Subjects completed the Beck Depression Inventory , the Spielberger State Anxiety Question naire , and self-report measures of hunger frequently throughout the 20-wk program . Results Both groups experienced significant improvements in depressive symptomatology , anxiety , and lessening of hunger during the course of the program , with no significant differences observed between the balanced diet and the very-low-calorie diet groups . Conclusions Very-low-calorie diets , used in the context of a behavioral weight-control program , result in reductions in hunger and improvements in mood state comparable to those observed on more moderate weight-loss regimens OBJECTIVE : To study the effect on weight loss in obese subjects by replacement of carbohydrate by protein in ad libitum consumed fat-reduced diets . DESIGN : R and omized dietary intervention study over six months comparing two ad libitum fat reduced diets ( 30 % of total energy ) strictly controlled in composition : High-carbohydrate ( HC , protein 12 % of total energy ) or high-protein ( HP , protein 25 % of total energy ) . SETTING AND PARTICIPANTS : Subjects were 65 healthy , overweight and obese subjects ( 50 women , 15 men , aged 18–55 y ) r and omly assigned to HC ( n=25 ) , HP ( n=25 ) or a control group ( C , n=15 ) . All food was provided by self- selection in a shop at the department , and compliance to the diet composition was evaluated by urinary nitrogen excretion . MAIN OUTCOME MEASURE : Change in body weight , body composition and blood lipids . RESULTS : More than 90 % completed the trial . Weight loss after six months was 5.1 kg in the HC group and 8.9 kg in the HP group ( difference 3.7 kg , 95 % confidence interval (CI)(1.3–6.2 kg ) P<0.001 ) , and fat loss was 4.3 kg and 7.6 kg , respectively ( difference 3.3 kg ( 1.1–5.5 kg ) P<0.0001 ) , whereas no changes occurred in the control group . More subjects lost > 10 kg in the HP group ( 35 % ) than in the HC group ( 9 % ) . The HP diet only decreased fasting plasma triglycerides and free fatty acids significantly . CONCLUSIONS : Replacement of some dietary carbohydrate by protein in an ad libitum fat-reduced diet , improves weight loss and increases the proportion of subjects achieving a clinical ly relevant weight loss . More freedom to choose between protein-rich and complex carbohydrate-rich foods may allow obese subjects to choose more lean meat and dairy products , and hence improve adherence to low-fat diets in weight reduction programs The impact of a low-carbohydrate/high-protein diet compared with a high-carbohydrate/low-fat diet on ratings of hunger and cognitive eating restraint were examined . Overweight premenopausal women consumed a low-carbohydrate/high-protein ( n=13 ) or high-carbohydrate/low-fat diet ( n=15 ) for 6 weeks . Fasting body weight ( BW ) was measured and the Eating Inventory was completed at baseline , weeks 1 to 4 , and week 6 . All women experienced a reduction in BW ( P<.01 ) , although relative BW loss was greater in the low-carbohydrate/high-protein vs high-carbohydrate/low-fat group at week 6 ( P<.05 ) . Based on Eating Inventory scores , self-rated hunger decreased ( P<.03 ) in women in the low-carbohydrate/high-protein but not in the high-carbohydrate/low-fat group from baseline to week 6 . In both groups , self-rated cognitive eating restraint increased ( P<.01 ) from baseline to week 1 and remained constant to week 6 . Both diet groups reported increased cognitive eating restraint , facilitating short-term weight loss ; however , the decrease in hunger perception in the low-carbohydrate/high-protein group may have contributed to a greater percentage of BW loss Context Low-carbohydrate weight reduction diets are popular despite a dearth of data on long-term efficacy and adverse effects . Contribution Community-dwelling hyperlipidemic persons were r and omly assigned to either a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet for 24 weeks . Compared to the low-fat group , patients in the low-carbohydrate group lost more weight , had a greater decrease in triglyceride levels , and had higher high-density lipoprotein cholesterol levels . Levels of low-density lipoprotein cholesterol remained stable in both groups . Side effects were more common in the low-cholesterol group but were generally mild . Caution s While the study suggests the efficacy and relative safety of the low-cholesterol diet , the high dropout rate , self-directed adherence to the diet , and relatively short observation period challenge the generalizability of the findings . The Editors As the prevalence of obesity has increased over the past 20 years ( 1 ) , the difficulties faced by overweight patients and their health care practitioners have become apparent . Fewer than 25 % of Americans who attempt to lose weight actually reduce caloric intake and increase exercise as currently recommended ( 2 ) . Persons who successfully lose weight have difficulty maintaining their weight loss ( 3 ) . Therefore , it is not surprising that consumers spend $ 33 billion yearly on weight loss products and services in search of effective therapies ( 2 ) . Because many weight loss interventions are unproven and untested , practitioners often lack information with which to recommend a certain therapy or to monitor a patient once a therapy is chosen . One approach to weight loss that has gained recognition in the face of modest supportive scientific evidence is the low-carbohydrate diet . A popular version of this diet recommends extreme restriction of carbohydrate intake to less than 20 g/d initially ( 4 ) . This level of carbohydrate restriction can induce serum and urinary ketones and weight loss ( 5 , 6 ) . However , until recently , available data on low-carbohydrate diets came from small studies of short duration , most of which were uncontrolled ( 5 , 7 - 10 ) . We examined body weight , body composition , serum lipid levels , and adverse effects over 24 weeks in hyperlipidemic persons who were r and omly assigned to follow a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet commonly used to induce weight loss and decrease serum lipid levels . Methods Participants Generally healthy persons were recruited from the community . Inclusion criteria were age 18 to 65 years , body mass index of 30 to 60 kg/m2 , desire to lose weight , elevated lipid levels ( total cholesterol level > 5.17 mmol/L [ > 200 mg/dL ] , low-density lipoprotein [ LDL ] cholesterol level > 3.36 mmol/L [ > 130 mg/dL ] , or triglyceride level > 2.26 mmol/L [ 200 mg/dL ] ) , and no serious medical condition . Exclusion criteria were use of any prescription medication in the previous 2 months ( except for oral contraceptives , estrogen therapy , and stable thyroid medication ) , pregnancy or breastfeeding , use of any weight loss diet or diet pills in the previous 6 months , and baseline ketonuria . All participants provided written informed consent , and the institutional review board of Duke University Health System approved the study . Participants received no monetary incentive . Interventions By using a computer-generated simple r and omization list , participants were allocated to receive the low-carbohydrate diet or low-fat diet . The intervention for both groups included group meetings , diet instruction , and an exercise recommendation . Group meetings took place at an outpatient research clinic twice monthly for 3 months , then monthly for 3 months . These meetings typically lasted 1 hour and consisted of diet instruction , supportive counseling , question naires , and biomedical measurements . During the study , participants selected their own menus and prepared or bought their own meals according to the guidelines presented to them . Participants were encouraged to exercise for 30 minutes at least 3 times weekly , but no formal exercise program or incentives were provided . Low-Carbohydrate Diet Using a popular diet book published by a lay press and additional h and outs , trained research staff instructed participants to restrict intake of carbohydrates to less than 20 g/d ( 4 ) . Participants were permitted unlimited amounts of animal foods ( meat , fowl , fish , and shellfish ) , unlimited eggs , 4 oz of hard cheese , 2 cups of salad vegetables ( such as lettuce , spinach , or celery ) , and 1 cup of low-carbohydrate vegetables ( such as broccoli , cauliflower , or squash ) daily . Participants were encouraged to drink 6 to 8 glasses of water daily . When participants were halfway to their goal body weight ( determined at the week 10 visit with assistance from research personnel ) , they were advised to add approximately 5 g of carbohydrates to their daily intake each week until they reached a level at which body weight was maintained . To simulate the practice of the study sponsor , the low-carbohydrate diet group also received daily nutritional supplements ( multivitamin , essential oils , diet formulation , and chromium picolinate ; for a list of the composition of these supplements , see the Appendix ) ( 6 ) . Low-Fat Diet Using a commonly available booklet and additional h and outs , a registered dietitian instructed participants in a diet consisting of less than 30 % of daily energy intake from fat , less than 10 % of daily energy intake from saturated fat , and less than 300 mg of cholesterol daily ( 11 , 12 ) . The recommended energy intake was 2.1 to 4.2 MJ ( 500 to 1000 kcal ) less than the participant 's calculated energy intake for weight maintenance ( body weight in pounds 10 ) ( 13 ) . Primary Outcome Measure Body weight and body mass index were the primary outcome measures . At each visit , participants were weighed on the same calibrated scale while wearing lightweight clothing and no shoes . Body mass index was calculated as body weight in kilograms divided by height in meters squared . Secondary Outcome Measures Adherence Adherence to the diet was measured by self-report , food records , and , for the low-carbohydrate diet group , urinary ketone assessment . Diet Composition All participants completed a 24-hour recall of food intake at baseline and take-home food records ( 5 consecutive days , including a weekend ) that were collected at each meeting during the study . Participants were instructed on how to document food intake and were given h and outs with examples of how to complete the records . A sample of participants ( 13 in the low-carbohydrate diet group and 7 in the low-fat diet group ) who completed the study was selected for food record analysis by the research staff on the basis of adequacy of detail in their records . A registered dietitian analyzed the food records by using a nutrition software program ( Nutritionist Five , version 1.6 [ First Data Bank , Inc. , San Bruno , California ] ) . Ketonuria Restriction of dietary intake of carbohydrates to less than 40 g/d typically results in ketonuria that is detectable by dipstick analysis , which can be used to monitor adherence to the low-carbohydrate diet ( 14 , 15 ) . At each return visit , participants provided a fresh urine specimen for analysis . The following semi-quantitative scale was used to categorize ketone content : none , trace ( up to 0.9 mmol/L [ 5 mg/dL ] ) , small ( 0.9 to 6.9 mmol/L [ 5 to 40 mg/dL ] ) , moderate ( 6.9 to 13.8 mmol/L [ 40 to 80 mg/dL ] ) , large80 ( 13.8 to 27.5 mmol/L [ 80 to 160 mg/dL ] ) , and large160 ( > 27.5 mmol/L [ > 160 mg/dL ] ) . Body Composition Body composition was estimated by using bioelectric impedance ( model TBF-300A [ Tanita Corp. , Arlington Heights , Illinois ] ) at approximately the same time of day ( afternoon or evening ) at each return visit . In a subset of 33 participants , the percentage of body fat as measured by bioelectric impedance had excellent correlation with the percentage as measured by dual-energy x-ray absorptiometry ( r = 0.93 [ 95 % CI , 0.87 to 0.97 ] ) . Vital Signs Blood pressure and pulse rate were measured in the nondominant arm by using an automated digital cuff ( model HEM-725C [ Omron Corp. , Vernon Hills , Illinois ] ) after the participant had been sitting for 3 minutes . Two measurements were taken at each visit and averaged for the analysis . Serum Lipids and Lipoproteins Serum specimens for lipid measurement were obtained in the morning after at least 8 hours of fasting at the screening visit and at 8 , 16 , and 24 weeks . Other Metabolic Effects Serum tests for sodium , potassium , chloride , urea nitrogen , creatinine , calcium , phosphorus , total protein , albumin , uric acid , total bilirubin , alanine aminotransferase , aspartate aminotransferase , alkaline phosphatase , thyroid-stimulating hormone , iron , hemoglobin , leukocyte count , and platelet count were obtained at the screening visit and at 8 , 16 , and 24 weeks . The glomerular filtration rate was estimated by using an equation that included age ; sex ; race ; and serum levels of albumin , creatinine , and urea nitrogen ( Modification of Diet in Renal Disease Study equation ) ( 16 ) . Adverse Effects At all return visits , participants completed an open-ended question naire on side effects . At the 20- and 24-week visits , participants completed a checklist of the side effects that were most often mentioned during the study . Statistical Analysis Analyses were performed by using S-PLUS software , version 6.1 ( Insightful Corp. , Seattle , Washington ) , or SAS software , version 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) . For categorical outcomes , groups were compared by using the chi-square test or Fisher exact test , as appropriate . For all primary and secondary continuous outcomes , linear mixed-effects models ( PROC MIXED procedure in SAS software ) that included fixed and r and om effects were used to determine expected mean values at each time point and to test hypotheses of group differences . In most body weight and BACKGROUND Despite the popularity of the low-carbohydrate , high-protein , high-fat ( Atkins ) diet , no r and omized , controlled trials have evaluated its efficacy . METHODS We conducted a one-year , multicenter , controlled trial involving 63 obese men and women who were r and omly assigned to either a low-carbohydrate , high-protein , high-fat diet or a low-calorie , high-carbohydrate , low-fat ( conventional ) diet . Professional contact was minimal to replicate the approach used by most dieters . RESULTS Subjects on the low-carbohydrate diet had lost more weight than subjects on the conventional diet at 3 months ( mean [ + /-SD ] , -6.8+/-5.0 vs. -2.7+/-3.7 percent of body weight ; P=0.001 ) and 6 months ( -7.0+/-6.5 vs. -3.2+/-5.6 percent of body weight , P=0.02 ) , but the difference at 12 months was not significant ( -4.4+/-6.7 vs. -2.5+/-6.3 percent of body weight , P=0.26 ) . After three months , no significant differences were found between the groups in total or low-density lipoprotein cholesterol concentrations . The increase in high-density lipoprotein cholesterol concentrations and the decrease in triglyceride concentrations were greater among subjects on the low-carbohydrate diet than among those on the conventional diet throughout most of the study . Both diets significantly decreased diastolic blood pressure and the insulin response to an oral glucose load . CONCLUSIONS The low-carbohydrate diet produced a greater weight loss ( absolute difference , approximately 4 percent ) than did the conventional diet for the first six months , but the differences were not significant at one year . The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease . Adherence was poor and attrition was high in both groups . Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate , high-protein , high-fat diets Background The purpose of this study was to assess the quality of methodology in orthopaedics-related r and omized controlled trials ( RCTs ) published from January 2006 to December 2010 in the top orthopaedic journals based on impact scores from the Thompson ISI citation reports ( 2010 ) . Methods Journals included American Journal of Sports Medicine ; Journal of Orthopaedic Research ; Journal of Bone and Joint Surgery , American ; Spine Journal ; and Osteoarthritis and Cartilage . Each RCT was assessed on ten criteria ( r and omization method , allocation sequence concealment , participant blinding , outcome assessor blinding , outcome measurement , interventionist training , withdrawals , intent to treat analyses , clustering , and baseline characteristics ) as having empirical evidence for biasing treatment effect estimates when not performed properly . Results A total of 232 RCTs met our inclusion criteria . The proportion of RCTs in published journals fell from 6 % in 2006 to 4 % in 2010 . Forty-nine percent of the criteria were fulfilled across these journals , with 42 % of the criteria not being amendable to assessment due to inadequate reporting . The results of our regression revealed that a more recent publication year was significantly associated with more fulfilled criteria ( β = 0.171 ; CI = −0.00 to 0.342 ; p = 0.051 ) . Conclusion In summary , very few studies met all ten criteria . Thus , many of these studies likely have biased estimates of treatment effects . In addition , these journals had poor reporting of important method ological aspects We compared the effects of two diets on glycated hemoglobin ( HbA1c ) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes ( HbA1c>6 % ) . We r and omized participants to either a medium carbohydrate , low fat , calorie-restricted , carbohydrate counting diet ( MCCR ) consistent with guidelines from the American Diabetes Association ( n = 18 ) or a very low carbohydrate , high fat , non calorie-restricted diet whose goal was to induce nutritional ketosis ( LCK , n = 16 ) . We excluded participants receiving insulin ; 74 % were taking oral diabetes medications . Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance . At 3 months , mean HbA1c level was unchanged from baseline in the MCCR diet group , while it decreased 0.6 % in the LCK group ; there was a significant between group difference in HbA1c change favoring the LCK group ( −0.6 % , 95 % CI , −1.1 % to −0.03 % , p = 0.04 ) . Forty-four percent of the LCK group discontinued one or more diabetes medications , compared to 11 % of the MCCR group ( p = 0.03 ) ; 31 % discontinued sulfonylureas in the LCK group , compared to 5 % in the MCCR group ( p = 0.05 ) . The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group ( p = 0.09 ) . Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications . This clinical trial was registered with Clinical Trials.gov , number NCT01713764 Objective Dietary carbohydrate is the major determinant of postpr and ial glucose levels , and several clinical studies have shown that low-carbohydrate diets improve glycemic control . In this study , we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus . Research design and methods Eighty-four community volunteers with obesity and type 2 diabetes were r and omized to either a low-carbohydrate , ketogenic diet ( < 20 g of carbohydrate daily ; LCKD ) or a low-glycemic , reduced-calorie diet ( 500 kcal/day deficit from weight maintenance diet ; LGID ) . Both groups received group meetings , nutritional supplementation , and an exercise recommendation . The main outcome was glycemic control , measured by hemoglobin A1c . Results Forty-nine ( 58.3 % ) participants completed the study . Both interventions led to improvements in hemoglobin A1c , fasting glucose , fasting insulin , and weight loss . The LCKD group had greater improvements in hemoglobin A1c ( -1.5 % vs. -0.5 % , p = 0.03 ) , body weight ( -11.1 kg vs. -6.9 kg , p = 0.008 ) , and high density lipoprotein cholesterol ( + 5.6 mg/dL vs. 0 mg/dL , p < 0.001 ) compared to the LGID group . Diabetes medications were reduced or eliminated in 95.2 % of LCKD vs. 62 % of LGID participants ( p < 0.01 ) . Conclusion Dietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes . The diet lower in carbohydrate led to greater improvements in glycemic control , and more frequent medication reduction/elimination than the low glycemic index diet . Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes Objective : Very low-carbohydrate diets are widely used for weight loss yet few controlled studies have determined how these diets impact cardiovascular risk factors compared to more traditional low-fat weight loss diets . The primary purpose of this study was to compare a very low-carbohydrate and a low-fat diet on fasting blood lipids , LDL subclasses , postpr and ial lipemia , and insulin resistance in overweight and obese women . Methods : Thirteen normolipidemic , moderately overweight ( body fat > 30 % ) women were prescribed two hypocaloric ( −500 kcal/day ) diets for 4 week periods , a very low-carbohydrate ( < 10 % carbohydrate ) and a low-fat ( < 30 % fat ) diet . The diets were consumed in a balanced and r and omized fashion . Two fasting blood draws were performed on separate days and an oral fat tolerance test was performed at baseline , after the very low-carbohydrate diet , and after the low-fat diet . Results : Compared to corresponding values after the very low-carbohydrate diet , fasting total cholesterol , LDL-C , and HDL-C were significantly ( p ≤ 0.05 ) lower , whereas fasting glucose , insulin , and insulin resistance ( calculated using the homeostatic model assessment ) were significantly higher after the low-fat diet . Both diets significantly decreased postpr and ial lipemia and result ed in similar nonsignificant changes in the total cholesterol/HDL-C ratio , fasting triacylglycerols , oxidized LDL , and LDL subclass distribution . Conclusions : Compared to a low-fat weight loss diet , a short-term very low-carbohydrate diet did not lower LDL-C but did prevent the decline in HDL-C and result ed in improved insulin sensitivity in overweight and obese , but otherwise healthy women . Small decreases in body mass improved postpr and ial lipemia , and therefore cardiovascular risk , independent of diet composition Untested alternative weight loss diets , such as very low carbohydrate diets , have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors . Therefore , we design ed a r and omized , controlled trial to determine the effects of a very low carbohydrate diet on body composition and cardiovascular risk factors . Subjects were r and omized to 6 months of either an ad libitum very low carbohydrate diet or a calorie-restricted diet with 30 % of the calories as fat . Anthropometric and metabolic measures were assessed at baseline , 3 months , and 6 months . Fifty-three healthy , obese female volunteers ( mean body mass index , 33.6 + /- 0.3 kg/m(2 ) ) were r and omized ; 42 ( 79 % ) completed the trial . Women on both diets reduced calorie consumption by comparable amounts at 3 and 6 months . The very low carbohydrate diet group lost more weight ( 8.5 + /- 1.0 vs. 3.9 + /- 1.0 kg ; P < 0.001 ) and more body fat ( 4.8 + /- 0.67 vs. 2.0 + /- 0.75 kg ; P < 0.01 ) than the low fat diet group . Mean levels of blood pressure , lipids , fasting glucose , and insulin were within normal ranges in both groups at baseline . Although all of these parameters improved over the course of the study , there were no differences observed between the two diet groups at 3 or 6 months . beta- Hydroxybutyrate increased significantly in the very low carbohydrate group at 3 months ( P = 0.001 ) . Based on these data , a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and , over 6 months , is not associated with deleterious effects on important cardiovascular risk factors in healthy women This study examined a new method of providing brief , individual lifestyle modification to obese individuals treated by pharmacotherapy . Twenty-six women with a mean ( + /- SD ) age of 47.0 + /- 7.2 years , weight of 97.6 + /- 13.0 kg , and body mass index of 36.5 + /- 5.0 kg/m2 were prescribed 60 mg/d of fenfluramine and 15 mg/d of phentermine for one year . In addition , half of the women were r and omly assigned to traditional group behavior modification , conducted by a nutritionist , which included 32 75-minute sessions during the year . The other half were provided lifestyle modification by a physician during 10 15 - 20 minute structured visits . All participants received identical treatment manuals and comparable assignments for behavior change . At the end of one year , patients in the physician group achieved the same highly successful weight losses as those treated by group behavior modification ( 13.9 + /- 9.6 kg vs. 15.4 + /- 7.9 kg , respectively ) . Treatment was associated with highly significant improvements in lipids and lipoproteins , as well as in mood and several measures of appetite . Weight loss the first four weeks , as well as patient completion of daily food records during the first 18 weeks , correlated positively with weight loss at weeks 18 , 26 , and 52 . Results of this study await replication using larger sample s but strongly suggest that effective lifestyle modification can be provided during brief , structured physician visits . The findings are discussed in terms of their implication s for the treatment of obesity in primary care practice This study compared the weight losses of 49 obese women r and omly assigned to a 52-week behavioral program combined with either moderate or severe caloric restriction . Subjects in the balanced deficit diet ( BDD ) condition were prescribed a 1,200-kcal/day diet throughout treatment , and those in the very-low-calorie diet ( VLCD ) condition were given a 420-kcal/day liquid diet for 16 weeks and a 1,200-kcal/day diet thereafter . The VLCD subjects lost significantly more weight than the BDD subjects at all periods through Week 26 , at which time mean losses were 21.45 and 11.86 kg , respectively . VLCD subjects , however , regained weight during the next 26 weeks of weekly therapy and during a 26-week weight maintenance program that provided biweekly meetings . Mean weight losses at the end of the maintenance program were 10.94 and 12.18 kg , respectively . Reports of binge eating declined in both groups , and no relationship was observed between binge eating and weight loss or attrition BACKGROUND Very low-carbohydrate ( LC ) diets are often used to promote weight loss , but the long-term effects on psychological function remain unknown . METHODS A total of 106 overweight and obese participants ( mean [ SE ] age , 50.0 [ 0.8 ] years ; mean [ SE ] body mass index [ calculated as weight in kilograms divided by height in meters squared ] , 33.7 [ 0.4 ] ) were r and omly assigned either to an energy-restricted ( approximately 1433 - 1672 kcal [ to convert to kilojoules , multiply by 4.186 ] ) , planned isocaloric , very low-carbohydrate , high-fat ( LC ) diet or to a high-carbohydrate , low-fat ( LF ) diet for 1 year . Changes in body weight , psychological mood and well-being ( Profile of Mood States , Beck Depression Inventory , and Spielberger State Anxiety Inventory scores ) , and cognitive functioning ( working memory and speed of processing ) were assessed . RESULTS By 1 year , the overall mean ( SE ) weight loss was 13.7 ( 1.8 ) kg , with no significant difference between groups ( P = .26 ) . Over the course of the study , there were significant time x diet interactions for Spielberger State Anxiety Inventory , Beck Depression Inventory , and Profile of Mood States scores for total mood disturbance , anger-hostility , confusion-bewilderment , and depression-dejection ( P < .05 ) as a result of greater improvements in these psychological mood states for the LF diet compared with the LC diet . Working memory improved by 1 year ( P < .001 for time ) , but speed of processing remained largely unchanged , with no effect of diet composition on either cognitive domain . CONCLUSIONS Over 1 year , there was a favorable effect of an energy-restricted LF diet compared with an isocaloric LC diet on mood state and affect in overweight and obese individuals . Both diets had similar effects on working memory and speed of processing . Trial Registration anzctr.org.au Identifier : 12606000203550 OBJECTIVES To compare the effects of a low-carbohydrate ( LC ) diet with those of a low-fat ( LF ) diet on weight loss and serum lipids in overweight adolescents . DESIGN A r and omized , controlled 12-week trial . SETTING Atherosclerosis prevention referral center . METHODS R and om , nonblinded assignment of participants referred for weight management . The study group ( LC ) ( n = 16 ) was instructed to consume < 20 g of carbohydrate per day for 2 weeks , then < 40 g/day for 10 weeks , and to eat LC foods according to hunger . The control group ( LF ) ( n = 14 ) was instructed to consume < 30 % of energy from fat . Diet composition and weight were monitored and recorded every 2 weeks . Serum lipid profiles were obtained at the start of the study and after 12 weeks . RESULTS The LC group lost more weight ( mean , 9.9 + /- 9.3 kg vs 4.1 + /- 4.9 kg , P < .05 ) and had improvement in non-HDL cholesterol levels ( P < .05 ) . There was improvement in LDL cholesterol levels ( P < .05 ) in the LF group but not in the LC group . There were no adverse effects on the lipid profiles of participants in either group . CONCLUSIONS The LC diet appears to be an effective method for short-term weight loss in overweight adolescents and does not harm the lipid profile OBJECTIVE This study sought to examine the effects of a 3-month programme of dietary advice to restrict carbohydrate intake compared with reduced-portion , low-fat advice in obese subjects with poorly controlled Type 2 diabetes . RESEARCH DESIGN AND METHODS One hundred and two patients with Type 2 diabetes were recruited across three centres and r and omly allocated to receive group education and individual dietary advice . Weight , glycaemic control , lipids and blood pressure were assessed at baseline and 3 months . Dietary quality was assessed at the end of study . RESULTS Weight loss was greater in the low-carbohydrate ( LC ) group ( -3.55 + /- 0.63 , mean + /- sem ) vs. -0.92 + /- 0.40 kg , P = 0.001 ) and cholesterol : high-density lipoprotein ( HDL ) ratio improved ( -0.48 + /- 0.11 vs. -0.10 + /- 0.10 , P = 0.01 ) . However , relative saturated fat intake was greater ( 13.9 + /- 0.71 vs. 11.0 + /- 0.47 % of dietary intake , P < 0.001 ) , although absolute intakes were moderate . CONCLUSIONS Carbohydrate restriction was an effective method of achieving short-term weight loss compared with st and ard advice , but this was at the expense of an increase in relative saturated fat intake OBJECTIVE To evaluate the efficacy and safety of a carbohydrate restricted versus a low fat diet on weight loss , metabolic markers , body composition , and cardiac function tests in severely obese adolescents . STUDY DESIGN Subjects were r and omly assigned to 1 of 2 diets : a high protein , low carbohydrate ( 20 g/d ) diet ( high protein , low carbohydrate , HPLC ) or low fat ( 30 % of calories ) regimen for 13 weeks ; close monitoring was maintained to evaluate safety . After the intervention , no clinical contact was made until follow-up measurements were obtained at 24 and 36 weeks from baseline . The primary outcome was change in body mass index Z-score for age and sex ( BMI -Z ) at 13 , 24 , and 36 weeks . RESULTS Forty-six subjects ( 24 HPLC , 22 in low fat ) initiated and 33 subjects completed the intervention ; follow-up data were available on approximately half of the subjects . Significant reduction in ( BMI -Z ) was achieved in both groups during intervention and was significantly greater for the HPLC group ( P = .03 ) . Both groups maintained significant BMI -Z reduction at follow-up ; changes were not significantly different between groups . Loss of lean body mass was not spared in the HPLC group . No serious adverse effects were observed related to metabolic profiles , cardiac function , or subjective complaints . CONCLUSIONS The HPLC diet is a safe and effective option for medically supervised weight loss in severely obese adolescents Comparaison apres traitement et au bout d'un an des effets sur la perte de poids chez des femmes obeses de protocol es de traitement : a ) comportant uniquement un regime hypocalorique ; b ) joignant a ce dernier une therapie comportementale ; c ) comprenant uniquement la therapie comportementale . A long terme c'est le traitement associe le plus This study compared the psychological effects of a low-protein high-carbohydrate ( LPHC ) diet and a high-protein low-carbohydrate ( HPLC ) diet in women with polycystic ovary syndrome ( PCOS ) . Twenty-five overweight women with PCOS were matched for age , weight , and whether they were trying to conceive . They were r and omly allocated to the LPHC or HPLC diet for 16 weeks . All participants attended a weekly exercise , group support and educational program . The Hospital Anxiety and Depression Scale and the Rosenberg Self Esteem Scale were administered at the beginning and end of the study . The HPLC diet was associated with significant reduction in depression and improvement in self-esteem . There was no change in any psychological measures for the LPHC group . There was no difference in weight loss between the groups . Due to enhanced feelings of well-being , it is possible that HPLC diets may be associated with better compliance and hence be more successful in the long term treatment of obesity BACKGROUND Low-carbohydrate diets are effective for weight reduction in people without diabetes , but there is limited evidence for people with Type 2 diabetes . Aims To assess the impact of a low-carbohydrate diet on body weight , glycated haemoglobin ( HbA(1c ) ) , ketone and lipid levels in diabetic and non-diabetic subjects . METHODS Thirteen Type 2 diabetic subjects ( on diet or metformin ) and 13 non-diabetic subjects were r and omly allocated to either a low-carbohydrate diet ( < or = 40 g carbohydrate/day ) or a healthy-eating diet following Diabetes UK nutritional recommendations and were seen monthly for 3 months . Subjects ( 25 % male ) were ( mean + /- sd ) age 52 + /- 9 years , weight 96.3 + /- 16.6 kg , body mass index 35.1 kg/m(2 ) , HbA(1c ) 6.6 + /- 1.1 % , total cholesterol 5.1 + /- 1.1 mmol/l , high-density lipoprotein cholesterol 1.3 + /- 0.4 mmol/l , low-density lipoprotein cholesterol 3.1 + /- 0.9 mmol/l , triglycerides ( geometric mean ) 1.55 ( 1.10 , 2.35 ) mmol/l and ketones range 0.0 - 0.2 mmol/l . RESULTS Analysis was by intention to treat with last observation carried forward . Twenty-two of the participants ( 85 % ) completed the study . Weight loss was greater ( 6.9 vs. 2.1 kg , P = 0.003 ) in the low-carbohydrate group , with no difference in changes in HbA(1c ) , ketone or lipid levels . CONCLUSIONS The diet was equally effective in those with and without diabetes OBJECTIVE Conflicting evidence exists as to weight loss produced by diets with different carbohydrate/protein ratio . The aim was to compare the long-term effects of high-protein vs. high-carbohydrate diet ( HPD , HCD ) , combined with cognitive behavior therapy ( CBT ) . DESIGN AND METHODS In a r and omized trial , 88 obese participants ( mean age , 46.7 ; mean BMI , 45.6 kg m(-2 ) ) were enrolled in a 3-week inpatient and 48-week outpatient treatment , with continuous CBT during the study period . All subjects consumed a restricted diet ( 1,200 kcal day(-1 ) for women , 1,500 for men ; 20 % energy from fat , < 10 % saturated fat ) . HPD derived 34 % energy from proteins , 46 % from carbohydrates ; HCD 17 % from proteins , 64 % from carbohydrates . The primary outcome was 1-year percent weight loss . Secondary outcomes were attrition rates and changes in cardiovascular risk factors and psychological profile . RESULTS Attrition rates were similar between groups ( 25.6 % ) . In the intention-to-treat analysis , weight loss averaged 15.0 % in HPD and 13.3 % in HCD at 1 year , without any difference throughout the study period . Both diets produced a similar improvement in secondary outcomes . CONCLUSIONS The relative carbohydrate and protein content of the diet , when combined with intensive CBT , does not significantly affect attrition rate , weight loss and psychosocial outcome in patients with severe obesity |
1,796 | 24,433,563 | There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk .
There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk , but there was evidence to recommend avoiding cow 's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months .
Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk .
There was very little evidence about strategies for preventing food allergy in older children or adults . | BACKGROUND Food allergies can have serious physical , social , and financial consequences .
This systematic review examined ways to prevent the development of food allergy in children and adults . | A total of 105 “ high‐risk ” infants born in 1988 were studied prospect ively from birth to 18 months of age . The infants were recommended breastfeeding and /or hypoallergenic formula ( Nutramigen or Profylac ) combined with avoidance of solid foods during the first 6 months of life . All mothers had unrestricted diet . Avoidance of daily exposure to tobacco smoke , furred pets and dust‐collecting material s in the bedroom were advised . This prevention group was compared with a control group consisting of 54 identically defined “ high‐risk ” infants born in 1985 in the same area . All infants had either severe single atopic predisposition combined with cord blood IgE ≥ 0.5 KU/1 or biparental atopic predisposition . The control group had unrestricted diet and was not advised about environmental factors . Apart from the prevention programme and year of birth the prevention group and the control group were comparable . The parents were highly motivated and compliance was good . The rate of participation was 97 % , and 85 % followed the dietary measures strictly . The cumulative prevalence of atopic symptoms was significantly lower at 18 months in the prevention group ( 32 % ) , as compared with the control group ( 74 % ) ( p<0.01 ) , due to reduced prevalence of recurrent wheezing ( 13 % , versus 37 % ; p<0.01 ) , atopic dermatitis ( 14 % versus 31 % ; p<0.01 ) , vomiting/diarrhoea ( 5 % versus 20 % ; p<0.01 ) and infantile colic ( 9 % versus 24 % ; p<0.01 ) . The cumulative prevalence of food allergy was significantly lower in the prevention group ( 6 % versus 17 % ; p<0.05 ) . In both high‐risk groups daily exposure to tobacco smoke increased the risk of recurrent wheezing significantly ( p<0.01 ) . The main difference between the prevention group and the control group was the diet . Thus , feeding with breastmilk and /or hypoallergenic formula combined with avoidance of solid foods until the age of 6 months appeared to reduce the cumulative prevalence of atopic symptoms during the first 18 months of life We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids ( ω-3 LCPUFA ) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life . Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω-3 PUFAs and the frequency and severity of infant allergic disease . 145 pregnant women , at risk of having an allergic infant , were r and omized to daily supplementation with 1.6 g eicosapentaenoic acid ( EPA ) and 1.1 g docosahexaenoic acid ( DHA ) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding . Clinical examinations , skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed . No difference in the prevalence of allergic symptoms was found between the intervention groups . The cumulative incidence of IgE-associated disease was lower in the ω-3-supplemented group ( 6/54 , 13 % ) compared with the placebo group ( 19/62 , 30 % , p=0.01 ) . Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease ( p=0.01 - 0.05 ) in a dose-dependent manner . Higher maternal and infant proportions of DHA and EPA were found if the infants presented none , when compared with multiple allergic symptoms , ( p<0.05 ) regardless of sensitization . In summary , the ω-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease , but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age . Furthermore , high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype BACKGROUND Partially hydrolyzed whey formula ( pHWF ) has been recommended for infants with a family history of allergic disease at the cessation of exclusive breast-feeding to promote oral tolerance and prevent allergic diseases . OBJECTIVE To determine whether feeding infants pHWF reduces their risk of allergic disease . METHODS A single-blind ( participant ) r and omized controlled trial was conducted to compare allergic outcomes between infants fed a conventional cow 's milk formula , a pHWF , or a soy formula . Before birth , 620 infants with a family history of allergic disease were recruited and r and omized to receive the allocated formula at cessation of breast-feeding . Skin prick tests to 6 common allergens ( milk , egg , peanut , dust mite , rye grass , and cat d and er ) were performed at 6 , 12 , and 24 months . The primary outcome was development of allergic manifestations ( eczema and food reactions ) measured 18 times in the first 2 years of life . RESULTS Follow-up was complete for 93 % ( 575/620 ) at 2 years and 80 % ( 495/620 ) at 6 or 7 years of age . There was no evidence that infants allocated to the pHWF ( odds ratio , 1.21 ; 95 % CI , 0.81 - 1.80 ) or the soy formula ( odds ratio , 1.26 ; 95 % CI , 0.84 - 1.88 ) were at a lower risk of allergic manifestations in infancy compared with conventional formula . There was also no evidence of reduced risk of skin prick test reactivity or childhood allergic disease . CONCLUSION Despite current dietary guidelines , we found no evidence to support recommending the use of pHWF at weaning for the prevention of allergic disease in high-risk infants BACKGROUND Maternal diet during pregnancy might be one of the factors that influences fetal immune responses associated with childhood allergy . OBJECTIVE We analyzed the association between maternal diet during the last 4 wk of pregnancy and allergic sensitization and eczema in the offspring at 2 y of age . DESIGN Data from 2641 children at 2 y of age were analyzed within a German prospect i ve birth cohort study ( LISA ) . Maternal diet during the last 4 wk of pregnancy was assessed with a semiquantitative food-frequency question naire , which was administered shortly after childbirth . RESULTS High maternal intake of margarine [ adjusted odds ratio ( aOR ) : 1 . 49 ; 95 % CI : 1.08 , 2.04 ] and vegetable oils ( aOR : 1.48 ; 95 % CI : 1.14 , 1.91 ) during the last 4 wk of pregnancy was positively associated and high maternal fish intake ( aOR : 0.75 ; 95 % CI : 0.57 , 0.98 ) was inversely associated with eczema during the first 2 y in the offspring . High celery ( aOR : 1.85 ; 95 % CI : 1.18 , 2.89 ) and citrus fruit ( aOR : 1.73 ; 95 % CI : 1.18 , 2.53 ) intakes increased the risk of sensitization against food allergens . In turn , sensitization against inhalant allergens was positively related to a high maternal intake of deep-frying vegetable fat ( aOR : 1.61 ; 95 % CI : 1.02 , 2.54 ) , raw sweet pepper ( aOR : 2.16 ; 95 % CI : 1.20 , 3.90 ) , and citrus fruit ( aOR : 1.72 ; 95 % CI : 1.02 , 2.92 ) . CONCLUSIONS We suggest that the intake of allergenic foods and foods rich in n-6 polyunsaturated fatty acids during pregnancy may increase and foods rich in n-3 polyunsaturated fatty acids may decrease the risk of allergic diseases in the offspring BACKGROUND Early feeding with cow 's milk ( CM ) may increase the risk of cow 's milk allergy ( CMA ) . OBJECTIVE We sought to examine prospect ively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula . METHODS We studied 6209 unselected healthy , full-term infants , of whom 5385 ( 87 % ) required supplementary milk while in the hospital . The infants were r and omly assigned to receive CM formula ( 1789 infants ) , pasteurized human milk ( 1859 infants ) , or whey hydrolysate formula ( 1737 infants ) . The comparison group ( 824 infants ) was composed of infants who were exclusively breast-fed . The infants were followed for 18 to 34 months for symptoms suggestive of CMA . The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet . RESULTS The cumulative incidence of CMA in the infants fed CM was 2.4 % compared with 1.7 % in the pasteurized human milk group ( odds ratio [ OR ] , 0.70 ; 95 % confidence interval [ CI ] , 0 . 44 - 1.12 ) and 1.5 % in the whey hydrolysate group ( OR , 0.61 ; 95 % CI , 0 . 38 - 1.00 ) . In the comparison group , CMA developed in 2.1 % of the infants . Among the infants who required supplementary feeding at hospital , both exposure to CM while in the hospital ( OR , 1.54 ; 95 % CI , 1.04 - 2.30 ; P = .03 ) and obvious parental atopy ( OR , 2.32 ; 95 % CI , 1.53 - 3.52 ; P < .001 ) increased the risk of CMA . CONCLUSIONS Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements , but exclusive breast-feeding does not eliminate the risk The aim of this study was to assess the preventive effect of exclusive breast-feeding and early solid food avoidance on atopic dermatitis ( AD ) in infancy . This study is part of a dietary clinical trial in a prospect i ve cohort of healthy term newborns at risk of atopy . It was recommended to breast-feed for at least 4 months and to avoid solid food in the same time-period . Eight hundred and sixty-five infants exclusively breast-fed , and 256 infants partially or exclusively formula-fed , were followed-up until the end of the first year following birth . AD and sensitization to milk and egg were considered as study end-points . The 1-year incidence of AD was compared between the two study groups . Adjusted odds ratios ( OR ) with 95 % confidence intervals ( CI ) were calculated by multiple logistic regression . The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given . In the breast-fed group , the adjusted OR for AD was 0.47 ( 95 % CI 0.30 - 0.74 ) . The strongest risk factor was the occurrence of AD in the subject 's core family . The risk of infants with AD to be sensitized to milk was four times higher , and to egg eight times higher , than in infants without AD . Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence . We conclude that in infants at atopic risk , exclusive breast-feeding for at least 4 months is effective in preventing AD in the first year of life This prospect i ve , long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy . Infants were r and omly assigned to receive either the hydrolysate formula ( n = 92 ) or an adapted cow milk formula ( n = 85 ) alone or with breast-feeding for 4 months . The groups did not differ in family allergy history scores or cord blood IgE levels . After 4 months , total IgE levels and allergic reactions did not differ significantly between groups , although the hydrolysate group had a lower prevalence of eczema . At 12 months of age , neither IgE levels nor allergic reactions were significantly different . At 2 years of age , however , 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group ; the differences were significant for eczema ( p < 0.001 ) but not for asthma . At 4 years of age , allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group ; the difference was significant only for eczema ( p < 0.01 ) . These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma In a prospect i ve study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk , a casein hydrolysate ( Nutramigen ) or a new ultrafiltrated whey hydrolysate ( Profylac ) on the development of cow milk protein allergy/intolerance ( CMPA/CMPI ) was assessed and compared . All the infants had biparental or severe single atopic predisposition , the latter combined with cord blood IgE > or = 0.5 kU/L. At birth all infants were r and omized to Nutramigen or Profylac , which was used when breastfeeding was insufficient or not possible during the first 6 months of life . During the same period this regimen was combined with avoidance of solid foods and cow milk protein . All mothers had unrestricted diets and were encouraged to do breastfeeding only . Moreover , avoidance of daily exposure to tobacco smoking , furred pets and dust-collecting material s in the bedroom was advised . The infants were followed prospect ively from birth to 18 months of age . All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI . A total of 154 ( 97 % ) were followed up and 141 followed the diet strictly . Eighty-eight ( 62 % ) of the infants were breastfed for at least 6 months , 20 ( 14 % ) were breastfed exclusively , 59 and 62 had varying amounts of Nutramigen or Profylac respectively . CMPA/CMPI was diagnosed in 1/20 , 1/59 and 3/62 in the breastfed , the Nutramigen and Profylac groups respectively , but 1 of the latter also had Nutramigen . None of the infants showed reactions against Nutramigen or Profylac . In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies . In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life . Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora . We assessed the effect on atopic disease of Lactobacillus GG ( which is safe at an early age and effective in treatment of allergic inflammation and food allergy ) . METHODS In a double-blind , r and omised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative ( or partner ) with atopic eczema , allergic rhinitis , or asthma , and postnatally for 6 months to their infants . Chronic recurring atopic eczema , which is the main sign of atopic disease in the first years of life , was the primary endpoint . FINDINGS Atopic eczema was diagnosed in 46 of 132 ( 35 % ) children aged 2 years . Asthma was diagnosed in six of these children and allergic rhinitis in one . The frequency of atopic eczema in the probiotic group was half that of the placebo group ( 15/64 [ 23 % ] vs 31/68 [ 46 % ] ; relative risk 0.51 [ 95 % CI 0.32 - 0.84 ] ) . The number needed to treat was 4.5 ( 95 % CI 2.6 - 15.6 ) . INTERPRETATIONS Lactobacillus GG was effective in prevention of early atopic disease in children at high risk . Thus , gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics , for prevention of atopic disease The allergy preventive effect of extensively ( N ) and partially ( PH ) hydrolysed cows ’ milk formulas compared with a regular formula ( RM ) was assessed in 155 infants with a family history of allergy . No cows ’ milk was given during the first nine months of life and no egg and fish up to 12 months of age . Breast feeding mothers avoided the same foods . At weaning the infants were r and omised to one of the formula groups . The cumulative incidence of atopic symptoms at 18 months was 51 , 64 , and 84 % in the N , PH , and RM groups , respectively . From 6 to 18 months there were significantly less cumulative atopic symptoms in the N group compared with the RM group , and significantly less than the PH group up to 6 ( N = 25 % ; PH = 46 % ) and 9 months ( N = 34 % , PH = 58 % ) . At 9 months significantly fewer infants in the N group ( 10 % ) than in the PH group ( 33 % ) had a positive skin prick test to eggs . The findings support an allergy preventive effect of an extensively hydrolysed formula , but not of a partially hydrolysed formula , during the first 18 months of life of high risk infants BACKGROUND : Docosahexaenoic acid ( DHA ) has been associated with downregulation of inflammatory responses . OBJECTIVE : To report the effect of DHA supplementation on long-term atopic and respiratory outcomes in preterm infants . METHODS : This study is a multicenter , r and omized controlled trial comparing the outcomes for preterm infants <33 weeks ' gestation who consumed expressed breast milk from mothers taking either tuna oil ( high-DHA diet ) or soy oil ( st and ard-DHA ) capsules . Data collected included incidence of bronchopulmonary dysplasia ( BPD ) and parental reporting of atopic conditions over the first 18 months of life . RESULTS : Six hundred fifty-seven infants were enrolled ( 322 to high-DHA diet , 335 to st and ard ) , and 93.5 % completed the 18-month follow-up . There was a reduction in BPD in boys ( relative risk [ RR ] : 0.67 [ 95 % confidence interval ( CI ) : 0.47–0.96 ] ; P = .03 ) and in all infants with a birth weight of < 1250 g ( RR : 0.75 [ 95 % CI : 0.57–0.98 ] ; P = .04 ) . There was no effect on duration of respiratory support , admission length , or home oxygen requirement . There was a reduction in reported hay fever in all infants in the high-DHA group at either 12 or 18 months ( RR : 0.41 [ 95 % CI : 0.18–0.91 ] ; P = .03 ) and at either 12 or 18 months in boys ( RR : 0.15 [ 0.03–0.64 ] ; P = .01 ) . There was no effect on asthma , eczema , or food allergy . CONCLUSIONS : DHA supplementation for infants of <33 weeks ' gestation reduced the incidence of BPD in boys and in all infants with a birth weight of < 1250 g and reduced the incidence of reported hay fever in boys at either 12 or 18 months Forty‐eight children with a biparental history of atopic disease were followed from birth to 4 years of age . One group was fed soy and the other cow 's milk from weaning to 9 months of age . Two‐thirds of the children developed symptoms of atopic disease with no significant difference between the groups . No difference was found in the serum immunoglobulins ( IgE antibodies , IgA , IgG and IgM ) during the observation period . The soy fed children showed transiently lower levels of IgG antibodies to cow 's milk but higher levels of IgG antibodies to soy protein . Six children showed cow 's milk intolerance and a further five had symptoms possibly related to the use of cow 's milk . Withholding cow 's milk during the first 9 months did not reduce the incidence of symptoms of cow 's milk intolerance from birth to 4 years of age . Thus , no benefit was found from replacing cows ' milk with soy . A prolonged breast feeding seems most rational for infants at risk of developing atopic disease , even if the present study did not show evidence of a prophylactic effect of breast milk against the development of atopic disease ABSTRACT A prospect i ve case‐control study is presented to assess an allergy prevention programme in children up to 36 months of age . Infants born at three maternity hospitals were followed from birth : 279 infants with high atopic risk ( intervention group ) were compared with 80 infants with similar atopic risk but no intervention ( non‐intervention group ) . The intervention programme included dietary measures ( exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet ) and environmental measures ( avoidance of parental smoking in the presence of the babies , day care > 2 years of life ) . Mothers in this group who had insufficient breast milk were r and omly assigned to one of two coded formulas : either a hydrolysed milk formula ( Nidina HA , Nestlé ) or a conventional adapted formula ( Nan , Nestlé ) . Other environmental measures remained the same as for the breastfeeding mothers . The non‐intervention group were either breastfed or received the usual Italian milk feeding and weaning diet , without environmental advice . The main outcome measures were anthropometric measurements and allergic disease manifestations . Normal anthropometric data were observed both in the intervention group and in the nonintervention group . The incidence of allergic manifestations was much lower in the intervention group than in the nonintervention group at 1 year ( 11.5 versus 54.4 % , respectively ) and at 2 years ( 14.9 versus 65.6 % ) and 3 years ( 20.6 versus 74.1 % ) . Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non‐intervention group from birth up to the second year of life , while urticaria and gastrointestinal disorders were only present in the non‐intervention group in the first year of life . Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non‐intervention group . Relapse of the same allergic symptom was less in the intervention group ( 13.0 % ) than in the non‐intervention group ( 36.9 % ) . In comparison to the non‐intervention group , there were fewer intervention group cases with two or more different allergic symptoms ( 8.7 versus 32.6 % ) , and they were more likely to avoid steroid treatment ( 0 versus 10.8 % ) and hospital admission ( 0 versus 6.5 % ) . Babies in the non‐intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group . In the intervention group the breastfed infants had the lowest incidence of allergic symptoms , followed by the infants fed the hydrolysed formula ( ns ) . Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants , although less than their counterparts in the non‐intervention group . Of the affected subjects in the intervention group , 80.4 % were RAST and /or Prick positive to food or inhalant allergens . Total serum IgE values detected at birth in the intervention group were not predictive , but at 1 and 2 years of age , IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy . In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups . Of the various factors tested in the non‐intervention group , the following were the most important in the pathogenesis of allergic symptoms : ( i ) formula implementation begun in the first week of life ; ( ii ) early weaning ( < 4 months ) ; ( iii ) feeding beef ( < 6 months ) ; ( iv ) early introduction of cow 's milk ( < 6 months ) ; and ( v ) parental smoking in the presence of the babies and early day care admission ( < 2 years of life ) . All the preventive measures used in this study ( exclusive breastfeeding and /or hydrolysed milk feeding , delayed and selective introduction of solid foods , and environmental advice ) were effective at the third year of follow‐up , greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions Background The European Academy of Allergy and Clinical Immunology is developing guidelines about how to prevent and manage food allergy . As part of the guidelines development process , a systematic review is planned to examine published research about the prevention of food allergy . This systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology , prevention , diagnosis and clinical management , and impact on quality of life , which will be used to inform clinical recommendations . The aim of this systematic review will be to assess the effectiveness of approaches for the primary prevention of food allergy . Methods Seven bibliographic data bases will be search ed from their inception to September 30 , 2012 for systematic review s , r and omized controlled trials , quasi-r and omized controlled trials , controlled clinical trials , controlled before- and -after studies , interrupted time series and cohort studies . Cohort studies will be included due to an inability to r and omize with interventions such as breastfeeding . Studies that focused on the development of either food sensitization ( a proxy measure ) or food allergy will also be eligible for inclusion . Studies will be critically appraised using the Critical Appraisal Skills Program and Cochrane Risk of Bias tools , as appropriate . Discussion There is a lack of rigorous evidence to support recommendations about how to prevent the development of food allergy . It would appear that it is important to see the prevention of food allergy in the context of individual , family and wider factors that may influence its development . There is much left to learn about preventing food allergy , and this is a priority given the high societal and healthcare costs involved . This systematic review will help to further this learning Aims : To determine the effect of brief early exposure to cows ' milk on the expression of atopy during the first five years of life . Methods : Follow up analysis of a double blind , placebo controlled , r and omised feeding intervention trial ( BOKAAL study ) . Subjects were 1108 children from 1533 initially r and omised breast fed neonates in the Netherl and s. Atopic disease and prevalence of allergic symptoms at age 1 , 2 , and 5 , and specific IgE at age 1 and 5 were determined . Results : Atopic disease in the first year was found in 10.0 % ( cows ' milk ) versus 9.3 % ( placebo ) of the children , with a relative risk ( RR ) of 1.07 . No differences were found in the second year either . At age 5 , atopic disease was found in 26.3 % ( cows ' milk ) versus 25.0 % ( placebo ) , RR 1.05 . There was no difference in the prevalence of allergic symptoms . Specific IgE to cows ' milk ( RAST positive 2 + or more ) was 5.8 % ( cows ' milk ) versus 4.1 % ( placebo ) at age 1 ( RR 1.43 ) , and 5.3 % versus 3.0 % at age 5 ( RR 1.77 ) . There was no difference in sensitisation to other common allergens between the two groups . Conclusion : Early , brief exposure to cows ' milk in breast fed children is not associated with atopic disease or allergic symptoms up to age 5 The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas , in infants with a high risk for development of allergic disease . High-risk infants from four Danish centres were included in the period from June 1994 to July 1995 . Five-hundred and ninety-five high-risk infants were identified . High-risk infants were defined as having biparental atopy , or a single atopic first-degree relative combined with cord blood immunoglobulin E ( IgE ) > or = 0.3 kU/l . At birth all infants were r and omized to one of three different blinded formulas . All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively . If breast-feeding was insufficient , one of the three formulas , according to r and omization , was given during the first 4 months . It was recommended not to introduce cow 's milk , cow 's milk products . and solid foods until the age of 4 months . After the age of 4 months a normal unrestricted diet and conventional cow 's milk-based formula were given when needed . All infants were followed-up prospect ively with interview and physical examination at the age of 6 , 12 , and 18 months , and if any possible atopic symptoms were reported . If food allergy was suspected , controlled elimination/challenge procedures were performed in a hospital setting . Of 550 infants included in the study , 514 were seen at all visits and 36 were excluded owing to noncompliance . Of 478 infants who completed the study , 232 were exclusively breast-fed , 79 received an extensively hydrolyzed casein formula ( Nutramigen ) , 82 an extensively hydrolyzed whey formula ( Profylac ) , and 85 a partially hydrolyzed whey formula ( Nan HA ) , during the first 4 months of life . These four groups were identical in regard to atopic predisposition , cord blood IgE , birthplace , and gender . Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes , whereas the three formula groups were identical concerning environmental factors . The frequency of breast-feeding was high ; only eight ( 2 % ) children were not breast-fed at all . The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods . No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms . The cumulative incidence of parental-reported cow 's milk allergy was significantly higher in children fed partially hydrolyzed formula ( Nan HA ) compared with extensively hydrolyzed formula ( Nutramigen or Profylac ) at 12 and 18 months ( NanHA , 7.1 % ; Nutramigen , 2.5 % ; Profylac , 0 % ; p=0.033 ) . The cumulative incidence of confirmed cow 's milk allergy was 1.3 % ( three of 232 ) in exclusively breast-fed infants , 0.6 % ( one of 161 ) in infants fed extensively hydrolyzed formula ( Nutramigen or Profylac ) , and 4.7%(four of 85 ) in infants fed partially hydrolyzed formula ( Nan HA ) . Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow 's milk allergy , 0.6 % vs. 4.7 % ( p=0.05 ) , but because of the small number of cases the results should be interpreted with caution . Compared with other similar studies the frequency ofatopic symptoms was low , even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months BACKGROUND Early vitamin supplementation is given routinely to infants in many countries , but it is unclear whether this affects the risk of allergic diseases . OBJECTIVES We sought to study the association between early-life supplementation of vitamins A and D in water-soluble form or in peanut oil and allergic diseases up to 4 years of age . METHODS A prospect i ve birth cohort of 4089 newborn infants was followed for 4 years using parental question naires repeatedly to collect information on exposure and health . At 4 years , the response rate was 90 % , and allergen-specific IgE levels to food and airborne allergens were measured in 2614 of the participating children . RESULTS Vitamins A and D were given to 98 % of the children in infancy , and vitamins based in peanut oil dominated ( 90 % ) . Children supplemented with vitamins A and D in water-soluble form during the first year of life had an almost 2-fold increased risk of asthma ( adjusted odds ratio [ OD ] , 2.18 ; 95 % CI , 1.45 - 3.28 ) , food hypersensitivity ( adjusted OR , 1.89 ; 95 % CI , 1.33 - 2.65 ) , and sensitization to common food and airborne allergens ( adjusted OR , 1.88 ; 95 % CI , 1.34 - 2.64 ) at age 4 years compared with those receiving vitamins in peanut oil . No increased risk of IgE antibodies to peanut was seen in children receiving vitamins in peanut oil . CONCLUSION Supplementation of vitamins A and D in water-soluble form seems to increase the risk of allergic disease up to the age of 4 years compared with supplementation with the same vitamins given in peanut oil . CLINICAL IMPLICATION S Vitamins A and D in oil does not seem to increase the risk of allergic disease during childhood Objective To determine whether dietary n-3 long chain polyunsaturated fatty acid ( LCPUFA ) supplementation of pregnant women with a fetus at high risk of allergic disease reduces immunoglobulin E associated eczema or food allergy at 1 year of age . Design Follow-up of infants at high hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome ( DOMInO ) r and omised controlled trial . Setting Adelaide , South Australia . Participants 706 infants at high hereditary risk of developing allergic disease whose mothers were participating in the DOMInO trial . Interventions The intervention group ( n=368 ) was r and omly allocated to receive fish oil capsules ( providing 900 mg of n-3 LCPUFA daily ) from 21 weeks ’ gestation until birth ; the control group ( n=338 ) received matched vegetable oil capsules without n-3 LCPUFA . Main outcome measure Immunoglobulin E associated allergic disease ( eczema or food allergy with sensitisation ) at 1 year of age . Results No differences were seen in the overall percentage of infants with immunoglobulin E associated allergic disease between the n-3 LCPUFA and control groups ( 32/368 ( 9 % ) v 43/338 ( 13 % ) ; unadjusted relative risk 0.68 , 95 % confidence interval 0.43 to 1.05 , P=0.08 ; adjusted relative risk 0.70 , 0.45 to 1.09 , P=0.12 ) , although the percentage of infants diagnosed as having atopic eczema ( that is , eczema with associated sensitisation ) was lower in the n-3 LCPUFA group ( 26/368 ( 7 % ) v 39/338 ( 12 % ) ; unadjusted relative risk 0.61 , 0.38 to 0.98 , P=0.04 ; adjusted relative risk 0.64 , 0.40 to 1.02 , P=0.06 ) . Fewer infants were sensitised to egg in the n-3 LCPUFA group ( 34/368 ( 9 % ) v 52/338 ( 15 % ) ; unadjusted relative risk 0.61 , 0.40 to 0.91 , P=0.02 ; adjusted relative risk 0.62 , 0.41 to 0.93 , P=0.02 ) , but no difference between groups in immunoglobulin E associated food allergy was seen . Conclusion n-3 LCPUFA supplementation in pregnancy did not reduce the overall incidence of immunoglobulin E associated allergies in the first year of life , although atopic eczema and egg sensitisation were lower . Longer term follow-up is needed to determine if supplementation has an effect on respiratory allergic diseases and aeroallergen sensitisation in childhood . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12610000735055 ( DOMInO trial : ACTRN12605000569606 ) BACKGROUND The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated . OBJECTIVE We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow 's milk formula ( CMF ) in a r and omized , double-blind trial . METHODS Between 1995 and 1998 , 2252 newborns with atopic heredity were r and omly assigned at birth to receive one of 4 blinded formulas : partially or extensively hydrolyzed whey formula , extensively hydrolyzed casein formula , or CMF as milk substitute for the first 4 months when breast-feeding was insufficient . The cohort was followed from birth until 6 years of age with yearly question naires . Outcomes were physician-diagnosed allergic diseases ( atopic dermatitis , food allergy , allergic urticaria , asthma , and hay fever/allergic rhinitis ) . Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis . RESULTS In the intent-to-treat analysis the relative risk of a physician 's diagnosis of allergic manifestation ( AM ) compared with CMF was 0.82 ( 95 % CI , 0.70 - 0.96 ) for partially hydrolyzed whey formula , 0.90 ( 95 % CI , 0.78 - 1.04 ) for extensively hydrolyzed whey formula , and 0.80 ( 95 % CI , 0.69 - 0.93 ) for extensively hydrolyzed casein formula . The corresponding figures for atopic eczema were 0.79 ( 95 % CI , 0.64 - 0.97 ) , 0.92 ( 95 % CI , 0.76 - 1.11 ) , and 0.71 ( 95 % CI , 0.58 - 0.88 ) , respectively . In the per- protocol analysis all effects were stronger and significant . No significant effect on other AMs was found . CONCLUSION The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age Infants born to atopic parents have been found to be at high risk of allergy development . The present study investigated the effect of a maternal milk-free diet during late pregnancy and lactation on the immune response and allergy incidence in at-risk and control infants . Atopic mothers were r and omly allocated into an intervention group ( n 12 ) or an unrestricted-diet group ( n14 ) and compared with non-atopic mothers following an unrestricted diet ( n 12 ) . The intervention involved a maternal milk-free diet during late pregnancy and lactation . Infants were followed up for 18 months postnatally . A significant fall in maternal serum beta-lactoglobulin (beta-Lg)-immunoglobulin G ( IgG ) antibody levels ( P < 0.05 ) was observed after a 7-week milk-exclusion diet . In maternal and cord serum sample s the levels of beta-Lg-IgG and alpha-casein-IgG antibodies were significantly correlated ( r 0.89 , P < 0.0001 and r 0.71 , P < 0.001 respectively ) . Higher levels of beta-Lg-IgG ( P < 0.05 ) were observed in the cord serum sample s compared with paired maternal serum sample s. Single-blind allergy assessment by a paediatrician at 12 and 18 months showed that the infants born in the non-atopic group had a significantly lower allergy incidence compared with the infants born in the atopic group following an unrestricted diet ( P < 0.008 and P < 0.02 respectively ) . The allergy incidence in the infants born in the atopic diet group was significantly lower compared with that of the atopic group following an unrestricted diet ( P < 0.04 ) . It was observed that the atopic nature of the parents significantly affected the allergy incidence in their children . A trend towards a beneficial effect of a maternal milk-free diet during late pregnancy and lactation was also observed in infants born to atopic parents Background / Objectives : To determine the impact of a not hydrolyzed fermented infant formula containing heat-killed Bifidobacterium breve C50 and Streptococcus thermophilus 065 ( HKBBST ) on the incidence of allergy-like events during the first 2 years of life in children at high risk of atopy . Subjects/ Methods : This multicenter , r and omized , double-blind , controlled study included infants at high risk of atopy . Infants used HKBBST or a st and ard infant formula ( SIF ) since birth until 1 year of age , and were followed at 4 , 12 and 24 months after birth . Skin prick tests ( SPTs ) for six foods and six aeroallergens were systematic ally performed and adverse events ( AEs ) were recorded . In case of potentially allergic AE ( PAAE ) , allergy could be further tested by SPT , patch tests and quantification of specific IgEs . If cow 's milk allergy ( CMA ) was suspected , an oral challenge could also be performed . Results : The study included 129 children , 63 were r and omized to SIF , 66 to HKBBST . The use of HKBBST milk did not alter the proportion of CMA but decreased the proportion of positive SPT to cow 's milk ( 1.7 vs 12.5 % , P=0.03 ) , and the incidence of digestive ( 39 vs 63 % , P=0.01 ) and respiratory potentially allergic AEs ( 7 vs 21 % , P=0.03 ) at 12 months , and that of respiratory PAAEs at 24 months ( 13 vs 35 % , P=0.01 ) . Conclusions : HKBBST decreased the incidence of PAAEs in children with family history of atopy , during the first months of life and after the formula was stopped . Oral tolerance to cow 's milk in infants at high risk of atopy may therefore be improved using not hydrolyzed fermented formulae The 209 mothers to be , enrolled in a r and omized , prospect i ve , allergy-prevention study from allergy-prone families , totally abstained from cow 's milk and egg from gestational week 28 to delivery . This article presents the development of allergic disease at 5 years of age in their children , compared with the development of allergic disease in the children of the control mothers who took normal food throughout pregnancy . The prevalence of allergic disease could be evaluated in 198 children ( 95 % ) . Allergic disease was monitored with question naires , skin prick testing , serum-IgE determinations , and physical examination . Eczema , allergic rhinoconjunctivitis , and asthma was equally common in the groups . Persistent food intolerance to egg was significantly more common in children of the mothers receiving the diet . This long-term follow-up confirms our previous findings that maternal elimination diet during late pregnancy does not prevent the development of allergic disease in the genetically predisposed child ABSTRACT . A cohort of 1749 newborns in the municipality of Odense were followed prospect ively for the development of cow 's milk allergy ( CMA ) during their first year of life . Altogether 39 fulfilled the criteria for CMA ( 2.2 % ) . Out of the 39 infants , 17 developed symptoms of CMA during breast‐feeding , in all cases before the age of 3 months . Nine of these were solely breast‐fed at the time of diagnosis , giving a one year incidence of CMA in exclusively breastfed infants of 0.5 % ( 9/1 749 ) in a study population with a frequency of exclusive breast‐feeding of 52 % at 3 months of age . None of the infants had signs of CMA in the neonatal period . Review of records from the newborn nursery revealed that all 9 infants had been exposed to cow 's milk formula in amounts corresponding to approximately 0.4‐3.0 g of Beta‐lactoglobulin ( BLG ) during the first three days of life . Human milk sample s were analyzed by enzyme‐linked immunosorbent assay ( ELISA ) for the content of bovine BLG . Detectable amounts ( 0.5–45 ng/ml ) were found in 3/9 sample s of human milk against which the infants reacted clinical ly . Analysis of the size distribution by high pressure liquid gel permeation chromatography in combination with ELISA indicated a molecular weight of BLG corresponding to that of monomeric BLG ( 18 kD ) . Possibly early inadvertent and occasional exposure to cow 's milk proteins may initiate sensitization in predisposed neonates . Subsequent exposure to minute amounts of bovine milk proteins in human milk may act as booster doses eliciting allergic reactions BACKGROUND Early life allergen exposure may increase the risk of childhood allergy , but the protective effect of reduction in allergen exposure remains uncertain . OBJECTIVE To evaluate the effect of reduction in food and house dust mite ( HDM ) allergen exposure in infancy in preventing asthma and allergy . METHODS Infants , at higher risk because of family predisposition , were recruited prenatally and r and omized to prophylactic ( n = 58 ) and control ( n = 62 ) groups . Prophylactic group infants were either breast-fed with mother on a low allergen diet or given an extensively hydrolyzed formula . Exposure to HDM was reduced by the use of an acaricide and mattress covers . The control group followed st and ard advice . Development of allergic diseases and sensitization to common allergens ( atopy ) was assessed blindly at ages 1 , 2 , 4 , and 8 years in all 120 children . RESULTS Repeated measurement analysis , adjusted for all relevant confounding variables , confirmed a preventive effect on asthma : adjusted odds ratio ( OR ) , 0.24 ; 95 % CI , 0.09 - 0.66 ; P = .005 ; atopic dermatitis , OR , 0.23 ; CI , 0.08 - 0.64 ; P = .005 ; rhinitis , OR , 0.42 ; CI , 0.19 - 0.92 ; P = .03 ; and atopy , OR , 0.13 ; CI , 0.05 - 0.32 ; P < .001 . The protective effect was primarily observed in the subgroup of children with persistent disease ( symptoms at all visits ) and in those with evidence of allergic sensitization . CONCLUSION Allergic diseases can be reduced , for at least the first 8 years of life , by combined food and HDM allergen avoidance in infancy . CLINICAL IMPLICATION S Strict food and HDM allergen avoidance should be considered for prevention of allergy in high-risk infants To determine whether a cow 's milk-based human milk fortifier ( HMF ) added to mother 's milk while breastfeeding or a cow 's milk-based preterm formula compared to exclusively mother 's milk after hospital discharge , increases the incidence of developing allergic diseases among very preterm infants ( VPI ) during the first year of life . Of a cohort of 324 VPI ( gestational age 24 - 32 wk ) , the exclusively breastfed VPI were shortly before discharge r and omized to breastfeeding without fortification or supplementing with a fortifier . Those not breastfed were fed a preterm formula . The intervention period was from discharge until 4 months corrected age ( CA ) . Follow-up was performed at 4 and 12 months CA including specific IgE to a panel of allergens at 4 months CA . The incidence during and prevalence at 12 months CA of recurrent wheezing ( RW ) was 39.2 % and 32.7 % , while atopic dermatitis ( AD ) was 18.0 % and 12.1 % , respectively . Predisposition to allergic disease increased the risk of developing AD ( p=0.04 ) [ OR 2.6 ( 95 % CI 1.0 - 6.4 ) ] and the risk of developing RW ( p=0.02 ) [ OR 2.7 ( 95 % CI 1.2 - 6.3 ) ] . Boys had an increased risk of developing RW ( p=0.003 ) [ OR 3.1 ( 95 % CI 1.5 - 6.5 ) ] . No difference was found between nutrition groups . None developed food allergy . Compared to exclusively breastfed , VPI supplemented with HMF or fed exclusively a preterm formula for 4 months did not have an increased risk of developing allergic diseases during the first year of life Several studies have demonstrated that dietary and environmental manipulations in the first months of life have a protective effect on the development of allergic diseases in babies " at risk " of atopy . We have prospect ively followed up 174 " high risk " infants who underwent dietary and environmental manipulations , such as exclusive breast-feeding for the first 6 months of life , supplemented if necessary with soy-protein formula ( Isomil , Abbott ) , delayed weaning beyond the 6th month of life , and rigorous environmental manipulations for the elimination of house-dust mite and passive smoking . The low prevalence of atopic disease ( 10 % ) and the trivial course of the allergic manifestations in this " at risk " population confirm the effectiveness of this preventive program . Moreover , this study demonstrates that the incidence of atopic dermatitis peaks at 6 months , and decreases until it disappears . Food allergy appears only at 6 months and may disappear later . The incidence of asthma peaks at 6 and 36 months and decreases at low levels in the intervals . Allergic rhinitis develops not sooner than 36 months BACKGROUND Despite the current World Health Organization recommendation that infants be exclusively breastfed for 6 mo , this practice remains unusual in both developed and developing countries . OBJECTIVE The objective was to compare health and development outcomes at age 6.5 y in children who were exclusively breastfed for 3 mo ( EBF3 ) or for 6 mo ( EBF6 ) ; in the EBF3 group , the children continued partial breastfeeding for > or = 6 mo . DESIGN This was a prospect i ve cohort study nested within a large , cluster-r and omized trial of a breastfeeding promotion intervention in the Republic of Belarus . Outcomes compared at 6.5 y included anthropometric measurements , systolic and diastolic blood pressure , intelligence quotient , teachers ' ratings of academic performance , parent- and teacher-rated behavior , atopic symptoms , allergen skin-prick tests , and dental caries . All statistical analyses were adjusted for cluster- and individual-level covariates and for clustering of outcomes within the clinics at which the children were examined . RESULTS The 2427 EBF3 and 524 EBF6 children who were followed up represented 84.7 % and 89.4 % , respectively , of those followed for the first year of life . The only significant differences observed between the 2 groups were in mean body mass index , triceps skinfold thickness , and hip circumference , all of which were higher in the EBF6 group . CONCLUSIONS We observed no demonstrable beneficial or adverse long-term effects on child health of exclusive breastfeeding for 6 mo . Higher adiposity measures in the EBF6 group probably reflect reverse causality rather than a causal effect of prolonged exclusive breastfeeding . Established benefits appear to be limited to the period of exclusive breastfeeding At the age of 5 years , the prevalence of atopic manifestations was analysed in 58 formula-fed “ at risk ” infants because of a history of atopic disease in at least two first degree relatives . Infants were r and omly assigned to receive either a partial whey-hydrolysate formula ( n : 28 ) or a regular cow 's milk formula ( n : 30 ) during the first 6 months of life ; thereafter , feeding was unrestricted . Only non-breastfed infants were included . The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease . At 6 months , the prevalence of cow 's milk protein ( CMP ) sensitivity was significantly decreased in the hydrolysate group ( 7 % versus 43%;P : 0.002 ) . At the age of 12 ( 21 % versus 53%;P : 0.029 ) , 36 ( 25 % versus 57%;P : 0.018 ) and 60 months ( 29 % versus 60%;P : 0.016 ) there was still a significant difference in the number of atopic manifestations , if calculated cumulatively . There was no difference between the groups if only the new cases after the age of 6 months were considered . Eczema was less frequent in the whey-hydrolysate group , but only during the 1st year of life , suggesting a decreased prevalence of CMP sensitivity . During the first 6 months , diarrhoea of non-infectious origin occurred in 8/30 infants ( 27 % ) of the adapted formula group , and in no infant in the hydrolysate group . “ Colic as single manifestation ” was considered of “ allergic ” origin in 1/28 infants in the hydrolysate group , and in 4/30 infants in the adapted formula group . If gastro-intestinal symptoms such as “ diarrhoea and colic as single manifestation ” are not considered , the number of infants with CMP sensitivity remains only significant for the first 6 months ( P : 0.004 ) . At 12 , 36 and 60 months , differences are not significant ( 0.106 , 0.116 and 0.07 , respectively ) . The results of this study support the hypothesis that allergy prevention is antigen specific . Conclusion If mother 's milk is not available and other studies confirm these results , there might be an indication for partial hydrolysates in infants with a family history of atopy , since these formulae reduce the incidence of CMP sensitivity In a previously published prospect i ve study , we followed the development of allergic symptoms in term infants with a slightly reduced birthweight ( − 1 SD to − 2 SD ) . These children received , according to local routing early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia . Of 216 infants 207 were observed for allergic symptoms up to 18 months of age . One group ( F ) received cow milk formula during the first days of life before the mother 's breastmilk production started and was then breastfed ; the other ( B ) was not given any formula before normal breastfeeding started . Unexpectedly , we found fewer allergic symptoms , in particular allergic skin problems , in the group fed cow milk , the difference being concentrated to children with a family fistory of allergic symptoms . At 5 Years of age 183 of the 207 children have been reinvestigated . Mild symptoms of allergy ( suspected and obvious ) were found in 22 % ( F ) and 27 % ( B ) respectively(NS ) . Moderate and severe symptoms of allergy ( obvious ) were found in 4.2 % ( F ) and 4.5 % ( B ) . In the subgroup with a double family history of allergic symptoms , 28 % ( 7/25 , F ) and 59 % ( 10/17 , B ) had symptoms of allergy ( p<0.05 ) . This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included , 1.4 % ( F ) and 53%(B ) respectively ( p < 0.05 ) . Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms . This difference was mainly caused by a reduced incidence of mild symptoms , some of which might not be true allergic symptoms . The incidence of moderate to severe disease was not affected , which can possibly be due to the relatively small number of children , expecially in the high risk group . Thus feeding with a high allergenic load during the first days of life seems , in the long run , to be ineffective in inhibiting the development of Significant ( moderate and severe ) atopic disease Several studies have demonstrated that early intervention may modulate the natural course of atopic disease . Our objective was to prevent sensitization to house-dust mite and food allergens , as well as the development of atopic symptoms during infancy , by the combination of an educational package and the use of mite allergen-impermeable mattress encasings . A multicentre European , population -based , r and omized , controlled study of children at increased atopic risk [ Study on the Prevention of Allergy in Children in Europe ( SPACE ) ] was performed in five countries ( Austria , Germany , Greece , the UK , and Lithuania ) , and included three cohorts - schoolchildren , toddlers , and newborns . We report on the newborn cohort . A total of 696 newborns were included from Austria , the UK , and Germany . Inclusion criteria were : a positive history of parental allergy ; and a positive skin-prick test or specific immunoglobulin E ( IgE ) ( IgE > or = 1.43 kU/L ) against at least one out of a panel of common aeroallergens in one or both parents . At 1 year of age , the overall sensitization rate against the tested allergens [ dust-mite allergens : Dermatophagoides pteronyssinus and Dermatophagoides farinae ( Der p and Der f ) ] and food allergens ( egg , milk ) in the prophylactic group was 6.21 % vs. 10.67 % in the control group . The prevalence of sensitization against Der p was 1.86 % in the prophylactic group vs. 5 % in the control group . In conclusion , we were able to demonstrate , in a group of newborns at risk for atopic diseases , that the sensitization rate to a panel of aero- and food allergens could be effectively decreased through the use of impermeable mattress encasings and the implementation of easy-to-perform preventive measures Of 5,500 newborn infants whose family histories were screened , 900 were found to have anamnestic risk . Cord-blood IgE was evaluable in 4,677 of these newborns , of which 394 had levels > or = 1 IU/mL ; 84 infants had both anamnestic risk and elevated cord-blood IgE levels . Parents of infants with anamnestic risk were informed of their child 's risk of atopy . Additionally , for 391 infants at two of the three participating hospitals , a preventive diet was prescribed that recommended breastfeeding for the first 6 months of life , with maternal diet restricted to no more than 200 dL of cow milk per day , no more than one egg per week , and no tomato , fish , shellfish , nuts , or foods allergenic to the mother . Only soy formula was recommended , and introduction of solid foods was also carefully prescribed . Furthermore , doctors recommended against exposure to tobacco smoke , animal allergens , and early entrance into daycare . Evaluable infants whose parents complied with the prescribed diet were found to have a lower incidence of atopy during the first year of life ( 13.3 % , n = 158 ) than infants whose parents had ignored the prescribed diet ( 54.7 % , n = 86 ) or infants whose parents were offered no dietary recommendations ( 28.9 % , n = 218 ) . Differences between the compliant group and the two groups with unrestricted diets were significant , indicating that this prescribed diet may protect against or delay onset of food allergies during the first year of life BACKGROUND The literature regarding the association between breast-feeding and atopic diseases has been contradictory . OBJECTIVE We have assessed the relationship between breast-feeding and atopic disorders in a cohort followed into middle age . METHODS The Tasmanian Asthma Study is a population -based prospect i ve cohort study that has followed participants from the age of 7 to 44 years . Exclusive breast-feeding in the first 3 months of life was examined as a risk factor for atopic diseases by using multiple logistic regression and generalized estimating equation analyses . RESULTS At age 7 years , exclusively breast-fed children with a maternal history of atopy had a marginally lesser risk of current asthma than those not exclusively breast-fed ( odds ratio [ OR ] , 0.8 ; 95 % CI , 0.6 - 1.0 ) . However , after age 7 years , the risk reversed , and exclusively breast-fed children had an increased risk of current asthma at 14 ( OR , 1.46 ; 95 % CI , 1.02 - 2.07 ) , 32 ( OR , 1.84 ; 95 % CI , 1.06 - 3.3 ) , and 44 ( OR , 1.57 ; 95 % CI , 1.15 - 2.14 ) years . Exclusively breast-fed children also had a reduced risk of food allergy at age 7 years but an increased risk of food allergy ( OR , 1.26 ; 95 % CI , 1.1 - 1.5 ) and allergic rhinitis ( OR , 1.2 ; 95 % CI , 1.0 - 1.3 ) at 44 years . CONCLUSION Exclusively breast-fed babies with a maternal history of atopy were less likely to develop asthma before the age of 7 years , but more likely to develop asthma after the age of 7 years . CLINICAL IMPLICATION S The current recommendation to breast-feed high-risk infants for protection against early wheezing illness can be confirmed . However , the recommendation should be reconsidered for protection against allergic asthma and atopy in the longer term BACKGROUND There is growing interest in the potential role of anti-inflammatory n-3 polyunsaturated fatty acids ( n-3 PUFAs ) in the prevention of allergic disease . OBJECTIVE We sought to determine whether maternal dietary supplementation with n-3 PUFAs during pregnancy could modify immune responses in infants . METHODS In a r and omized , controlled trial 98 atopic , pregnant women received fish oil ( 3.7 g n-3 PUFAs per day ) or placebo from 20 weeks ' gestation until delivery . Neonatal PUFA levels and immunologic response to allergens were measured at birth . RESULTS Eighty-three women completed the study . Fish oil supplementation ( n = 40 ) achieved significantly higher proportions of n-3 PUFAs in neonatal erythrocyte membranes ( mean + /- SD , 17.75 % + /- 1.85 % as a percentage of total fatty acids ) compared with the control group ( n = 43 , 13.69 % + /- 1.22 % , P < .001 ) . All neonatal cytokine ( IL-5 , IL-13 , IL-10 , and IFN-gamma ) responses ( to all allergens ) tended to be lower in the fish oil group ( statistically significant only for IL-10 in response to cat ) . Although this study was not design ed to examine clinical effects , we noted that infants in the fish oil group were 3 times less likely to have a positive skin prick test to egg at 1 year of age ( odds ratio , 0.34 ; 95 % confidence interval , 0.11 to 1.02 ; P = .055 ) . Although there was no difference in the frequency of atopic dermatitis at 1 year of age , infants in the fish oil group also had significantly less severe disease ( odds ratio , 0.09 ; 95 % confidence interval , 0.01 to 0.94 ; P = .045 ) . CONCLUSIONS These data suggest a potential reduction in subsequent infant allergy after maternal PUFA supplementation . More detailed follow-up studies are required in larger cohorts to establish the robustness of these findings and to ascertain their significance in relation to longer-term modification of allergic disease in children Dietary n-3 polyunsaturated fatty acids ( PUFA ) may represent a mode of allergy prevention . Cord blood ( CB ) CD34 + hemopoietic progenitors are altered in infants at risk of atopy . We therefore studied the effects of dietary n-3 PUFA supplementation during pregnancy on numbers and function of progenitors in neonates at high risk of atopy . In a double-blind study , atopic , pregnant women were r and omized to receive fish oil capsules or placebo from 20 wk gestation until delivery . At birth , CB CD34 + cells were isolated and analyzed by flow cytometry for expression of cytokine ( IL-5Rα , IL-3Rα , granulocyte/macrophage colony-stimulating factor Rα ) or chemokine ( CXCR4 and CCR3 ) receptors . CB cells were also cultured in methylcellulose assays for eosinophil/basophil colony-forming cells . At age 1 y , infants were clinical ly assessed for atopic symptoms and skin tests . Percentages of CB CD34 + cell numbers were higher after n-3 PUFA than placebo . Co-expression of cytokine or chemokine receptors on CD34 cells was not altered by n-3 PUFA supplementation . However , there were significantly more IL-5-responsive CB eosinophil/basophil colony forming units ( Eo/B-CFU ) in the fish oil , compared with the control , group . Overall , there was a positive association between CD34 + cells and IL-5-responsive Eo/B-CFU in CB and 1 y clinical outcomes , including atopic dermatitis and wheeze . Dietary n-3 PUFA supplementation during pregnancy in atopic mothers alters infant cord blood hemopoietic progenitor phenotype . This may have an impact on development of atopic disease BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later . Allergic children have a different fecal microflora , with less lactobacilli and bifidobacteria . Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation . OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies . METHODS In a double-blinded , placebo-controlled study we r and omized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture ( 2 lactobacilli , bifidobacteria , and propionibacteria ) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months . Infants also received a prebiotic galacto-oligosaccharide or placebo . At 5 years , we evaluated the cumulative incidence of allergic diseases ( eczema , food allergy , allergic rhinitis , and asthma ) and IgE sensitization . RESULTS Of the 1018 intent-to-treat infants , 891 ( 88 % ) attended the 5-year visit . Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar : 52.6 % versus 54.9 % and 29.5 % versus 26.6 % , respectively , and 41.3 % in both . No significant difference appeared in frequencies of eczema ( 39.3 % vs 43.3 % ) , atopic eczema ( 24.0 % vs 25.1 % ) , allergic rhinitis ( 20.7 % vs 19.1 % ) , or asthma ( 13.0 % vs 14.1 % ) between groups . However , less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics ( 24.3 % vs 40.5 % ; odds ratio , 0.47 ; 95 % CI , 0.23 % to 0.96 % ; P = .035 ) . CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children . It conferred protection only to cesarean-delivered children |
1,797 | 18,646,094 | There was no clear effect of pharmacological therapy on the prevention of depression or other endpoints .
A significant improvement in mood and the prevention of depression was evident for psychotherapy , but the treatment effects were small .
A small but significant effect of psychotherapy on improving mood and preventing depression was identified . | BACKGROUND Depression is an important consequence of stroke that impacts on recovery yet often is not detected or is inadequately treated .
OBJECTIVES To determine if pharmaceutical or psychological interventions can prevent depression and improve physical and psychological outcomes in patients with stroke . | Background and Purpose — Integrated care pathways ( ICP ) may not reduce disability , institutionalization , or duration of hospitalization compared with conventional multidisciplinary team ( MDT ) care in organized stroke rehabilitation . Their potential to improve patient heath status or satisfaction with care is not known . Methods — A comparison of quality of life , caregiver strain , and patient/caregiver satisfaction at 6 months after stroke was undertaken in 152 stroke patients r and omized to receive ICP or MDT care . Differences in processes of care were recorded with the use of a predefined schedule . Multivariate analyses were undertaken to identify the effect of age , sex , stroke severity , functional status , mood , and use of care pathway on quality of life score . Results — The 2 groups were comparable for baseline characteristics of age , sex , stroke severity , and initial disability . MDT care was characterized by greater emphasis on return of higher function and caregiver needs compared with ICP . EuroQol Visual Analogue Scale ( EQ-VAS ) scores were higher in the MDT group ( median , 72 versus 63;P < 0.005 ) , who also had higher scores for EuroQol dimension of social functioning ( P = 0.014 ) . Higher EQ-VAS scores were independently related to MDT care ( P = 0.04 ) , Rankin score ( P = 0.01 ) , and psychological function ( P < 0.0001 ) but not to age , sex , or stroke severity . There were no significant differences in patient or caregiver satisfaction between the 2 setting s. Conclusions — Better quality of life in patients receiving conventional MDT care may be attributable to improved social functioning and greater attention to higher function and caregiver needs during rehabilitation BACKGROUND AND PURPOSE We report the findings of a r and omized controlled trial to determine the effectiveness of a multidisciplinary Stroke Education Program ( SEP ) for patients and their informal carers . METHODS Two hundred four patients admitted with acute stroke and their 176 informal carers were r and omized to receive an invitation to the SEP or to receive conventional stroke unit care . The SEP consisted of one 1-hour small group educational session for in patients followed by six 1-hour sessions after discharge . The primary outcome measure was patient- and carer-perceived health status ( SF-36 ) at 6 months after stroke . Knowledge of stroke , satisfaction with services , emotional outcome , disability , and h and icap and were secondary outcome measures . RESULTS Only 51 of 108 ( 47 % ) surviving patients r and omized to the SEP completed the program , as did 20 of 93 ( 22 % ) informal carers of surviving patients . Perceived health status ( Short Form 36 [ SF-36 ] health survey ) scores were similar for SEP patients and controls . Informal carers in the control group scored better on the social functioning component of the SF-36 than the SEP group ( P=0.04 ) . Patients and informal carers in the SEP group scored higher on the stroke knowledge scale than controls ( patients , P=0.02 ; carers , P=0 . 01 ) . Patients in the SEP group were more satisfied with the information that they had received about stroke ( P=0.004 ) . There were no differences in emotional or functional outcomes between groups . CONCLUSIONS Although the SEP improved patient and informal carer knowledge about stroke and patient satisfaction with some components of stroke services , this was not associated with an improvement in their perceived health status . Indeed , the social functioning of informal carers r and omized to the SEP was less than in the control group The impact of clinical ly diagnosed depression on recovery in activities of daily living over a 2-year follow-up was examined in a prospect i ve study of 63 stroke patients . Although impairment in activities of daily living , neurologic diagnoses and findings , lesion location and volume as measured on computed tomographic scan , demographic variables , cognitive impairment , and social functioning were comparable between depressed ( n = 25 ) and nondepressed ( n = 38 ) patients during their acute hospitalization , the two groups had different patterns of recovery in activities of daily living . At 2 years after suffering a stroke , patients with an in-hospital diagnosis of depression ( either major or minor depression ) were significantly more impaired in both physical activities and language functioning than were non-depressed patients . Among patients with major depression , this disparity in the recovery profile was present even after the depression had remitted . This study emphasizes the need for early recognition and treatment of poststroke depression BACKGROUND Attention is currently focused on family care of stroke survivors , but the effectiveness of support services is unclear . We did a single-blind , r and omised , controlled trial to assess the impact of family support on stroke patients and their carers . METHODS Patients with acute stroke admitted to hospitals in Oxford , UK , were assigned family support or normal care within 6 weeks of stroke . After 6 months , we assessed , for carers , knowledge about stroke , Frenchay activities index , general health question naire-28 scores , caregiver strain index , Dartmouth co-op charts , short form 36 ( SF-36 ) , and satisfaction scores , and , for patients , knowledge about stroke and use of services , Barthel index , Rivermead mobility index , Frenchay activities index , London h and icap scale , hospital anxiety and depression scales , Dartmouth co-op charts , and satisfaction . FINDINGS 323 patients and 267 carers were followed up . Carers in the intervention group had significantly better Frenchay activities indices ( p=0.03 ) , SF-36 scores ( energy p=0.02 , mental health p=0.004 , pain p=0.03 , physical function p=0.025 , and general health perception p=0.02 ) , quality of life on the Dartmouth co-op chart ( p=0.01 ) , and satisfaction with underst and ing of stroke ( 82 vs 71 % , p=0.04 ) than those in the control group . Patients ' knowledge about stroke , disability , h and icap , quality of life , and satisfaction with services and underst and ing of stroke did not differ between groups . Fewer patients in the intervention group than in the control group saw a physiotherapist after discharge ( 44 vs 56 % , p=0.04 ) , but use of other services was similar . INTERPRETATION Family support significantly increased social activities and improved quality of life for carers , with no significant effects on patients Background and Purpose — The efficacy and safety of the selective serotonin reuptake inhibitor fluoxetine have rarely been studied in the treatment of poststroke emotional disturbances . Methods — Stroke patients ( 152 ) who had poststroke depression ( PSD ) , emotional incontinence ( PSEI ) , or anger proneness ( PSAP ) were studied . PSD was evaluated by Beck Depression Inventory and Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , PSEI by Kim ’s criteria , and PSAP was assessed by Spielberger Trait Anger Scale . Subjects were r and omly given either fluoxetine 20 mg/day ( n=76 ) or placebo ( n=76 ) for 3 months . Follow-up evaluations were done 1 , 3 , and 6 months after the beginning of the treatment . The primary outcome measurement was the scores of emotional disturbances at each follow-up assessment . The secondary outcome measurements were the percentage changes of the scores and the subjective responses of the patients . Results — Although patients in the fluoxetine group more often dropped out because of adverse effects , fluoxetine administration was generally safe . Fluoxetine significantly improved PSEI and PSAP , whereas no definitive improvement of PSD was found . Improvement of PSAP was noted even at 3 months after the discontinuation of the treatment . Conclusions — Fluoxetine is efficacious in the treatment of PSEI and PSAP . Its effect on PSD is not solidly confirmed Background and Purpose — The purpose of this study was to determine whether motivational interviewing , a patient-centered counseling technique , can benefit patients ' mood 3 months after stroke . Methods — A single-center , open , r and omized , controlled trial was conducted at a single hospital with a stroke unit . Subjects consisted of 411 consecutive patients on the stroke register who were over 18 years of age and who did not have severe cognitive and communication problems that would prevent them from taking part in an interview ; were not known to be moving out of the area after discharge ; and were not already receiving psychiatric or clinical psychology intervention . All patients received usual stroke care . Patients in the intervention group received 4 individual , weekly sessions of motivational interviewing with a trained therapist in addition to usual stroke care . The primary outcome was the proportion of patients with normal mood at 3 months poststroke measured by the 28-item General Health Question naire ( normal , < 5 ; low ≥5 ) using a mailed question naire . Results — Eighty-one of 207 ( 39.1 % ) patients in the control group and 100 of 204 ( 49.0 % ) patients in the intervention group had normal mood at follow up . A significant benefit of motivational interviewing over usual stroke care ( OR : 1.60 , 95 % CI : 1.04 to 2.46 , P=0.03 ) was found . Conclusion — Our results suggest motivational interviewing leads to an improvement in patients ' mood 3 months after stroke Background : The involvement of five specialist nurses in providing a stroke support service was evaluated quantitatively in a recent r and omized controlled trial . This complementary study used qualitative methods to evaluate trial outcomes more comprehensively . Aims : To identify whether the nurses ' intervention may have influenced the process of stroke recovery . Method : A purpose fully selected sub sample of 30 patients and 15 care-givers were interviewed within 1 - 3 months of their final quantitative assessment ( 12 months after recruitment to the r and omized trial ) . Fifteen of the patients and eight of the care-givers had received visits from a specialist nurse . A semi- structured interview was design ed to include questions on perceptions of the recovery process and evaluation of services received . Results : Some differences were evident between the accounts of control and intervention group subjects . The less tangible aspects of nurses ' interventions - concern , attention , empathy and interest , when combined with sound professional knowledge , had identifiable value to the patients and care-givers . It appeared that the nurses had employed considerable sensitivity and skill in identifying and responding to particular needs at appropriate times . Conclusion : The qualitative evaluation offers a different picture to the quantitative results of the r and omized controlled trial . In general , the findings of the qualitative study are more positive and encouraging than the quantitative results . The majority of patients and care-givers in the intervention group believed that they had benefited from the specialist nurse 's visits Purpose : To evaluate the feasibility and effectiveness of early supported discharge ( ESD ) following acute stroke . Method : An ESD scheme was compared to conventional rehabilitation in a r and omized controlled trial . All patients admitted with acute stroke were considered for inclusion . Eighty-eight ( 20.2 % ) were found to be eligible and 82 were r and omized either to early supported discharge ( n=42 ) or conventional rehabilitation ( n=40 ) . The primary outcome measure was the Nottingham Extended Activities of Daily Living Scale . The General Health Question naire , the Montgomery Aasberg Depression Rating Scale , mortality , placement and patient and carer satisfaction served as secondary outcome measures . Results : Median length of stay was reduced from 31 days in the conventional hospital rehabilitation group to 22 days in the early supported discharge group ( p=0.09 ) . No differences were found regarding primary outcome . The General Health Question naire score showed a significant difference in favour of the early supported discharge group at three months ( 19.5/24 , p = 0.02 ) , but not at six . At six months , the proportion of patients being dead or in institution showed a trend of being higher in the conventional rehabilitation group ( OR 3.8 , 95 % CI 0.8 - 23 ) . Conclusions : Early supported discharge after stroke is feasible and it is possible that it has benefits compared with conventional rehabilitation Background and Purpose — There is inconclusive evidence of the effectiveness of the Stroke Family Support Organiser ( FSO ) service . We report the results from a r and omized controlled trial of the service . Methods — Stroke patients admitted to hospital and their informal caregivers were r and omly allocated to receive the FSO service ( n=126 ) or st and ard care ( n=124 ) . Outcome assessment s were undertaken 4 and 9 months after recruitment with the General Health Question naire 12 , Carer Strain Index , Barthel Index , Extended Activities of Daily Living scale , and a specially design ed question naire to determine knowledge of stroke and satisfaction with services . Results — There were no significant differences between groups in patients ’ mood and independence in personal or instrumental activities of daily living or caregivers ’ mood , strain , or independence . Patients in the intervention group were significantly more knowledgeable about whom to contact for stroke information , reducing the risk of stroke , practical help , community services , and emotional support . Patients in the intervention group were also significantly more satisfied with the stroke information received . Caregivers in the intervention group were significantly more knowledgeable about whom to contact for information on stroke , reducing the risk of stroke , community services , and emotional support . Caregivers in the intervention group were also significantly more satisfied with stroke information . Conclusions — The FSO service had no significant effect on mood , independence in activities of daily living , or reduction in caregiver strain , but it did increase knowledge of stroke and satisfaction with that knowledge . The results may not be representative of all FSO services , and the sample was small relative to the heterogeneity of the participants . However , results suggest that the policies and training procedures of FSOs need to be evaluated to ensure that a cost-effective service is being provided to stroke patients and their caregivers BACKGROUND AND PURPOSE Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion . Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy . We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial . METHODS Patients with major ( n=33 ) or minor ( n=14 ) depression participated in a double-blind treatment study with nortriptyline or placebo . They were examined for change in depressive mood , measured by the Hamilton Rating Scale for Depression ( HAM-D ) , and change in cognitive impairment , assessed by the Mini-Mental State Examination ( MMSE ) , after treatment with nortriptyline or placebo . Cognitive treatment response , as measured by the MMSE , was compared between patients whose depression did and did not respond to treatment . RESULTS Patients whose poststroke depression remitted ( predominantly associated with nortriptyline treatment ) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit ( predominantly associated with placebo treatment ) . CONCLUSIONS Our findings support the contention that poststroke major depression leads to a " dementia of depression . " Prior studies failed to show an effect of treatment because the effect size was too small . Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke We investigated the efficacy of amitriptyline in seven patients with pathological laughing caused by cerebrovascular diseases . In a double-blind placebo-controlled cross-over trial comparing amitriptyline with placebo , 5 of these 7 patients were judged to have shown improvement with amitriptyline , and 1 patient improved with placebo . This difference was statistically significant . No significant side effect of amitriptyline was observed . There was no significant change between amitriptyline and placebo in both self-rating depression scale and minimental state test score . These results suggested that amitriptyline was useful in treating pathological laughing OBJECTIVES ( 1 ) To test whether early prophylactic antidepressive treatment by mianserin is able to prevent poststroke depression , and ( 2 ) to discover whether mianserin as an antidepressant has any beneficial influence on the outcome of ischaemic stroke . METHODS A r and omised , double blind , placebo controlled study involved 100 consecutive patients under 71 years old admitted to hospital for an acute ischaemic stroke ; they were enrolled to receive 60 mg/day mianserin or placebo for 1 year . They were examined on admission , and at 2 , 6 , 12 , and 18 months with depression , stroke , and functional outcome scales . RESULTS According to DSM-III-R , the prevalence of major depression was 6 % at the initial stage , 11 % at 1 year , and 16 % at 18 months . At no time point did prevalences differ between the treatment groups , nor were differences found in depression scales , although at 2 months a greater improvement from initial assessment on the Hamilton depression scale was evident in patients on mianserin ( p=0.05 ) . Some beneficial changes on the Hamilton depression scale and Beck depression inventory were found in patients older than 56 ( median age ) and in men treated with mianserin , but not in other subgroups . Mianserin treatment did not affect stroke outcome as measured by neurological status , nor did it have any influence on functional outcome as measured by Rankin scale or Barthel index . CONCLUSION It was not possible to show that early initiation of antidepressant therapy can prevent poststroke depression , because the prevalence of poststroke depression remained low even in patients on placebo . In this stroke population with a low rate of depressive patients , antidepressive medical treatment failed to affect stroke outcome BACKGROUND Community physiotherapy is often prescribed for stroke patients with long-term mobility problems . We aim ed to assess the effectiveness of this treatment in patients who had mobility problems 1 year after stroke . METHODS We screened 359 patients older than 50 years for a single-masked , r and omised controlled trial to assess the effects of community physiotherapy . Assessment s were made at baseline , 3 , 6 , and 9 months in 170 eligible patients assigned treatment or no intervention . The primary outcome measure was mobility measured by the Rivermead mobility index . Secondary outcome measures were gait speed , number of falls , daily activity ( Barthel index scores ) , social activity ( Frenchay activities index ) , hospital anxiety and depression scale , and emotional stress of carers ( general health question naire 28 ) . Analyses were by intention to treat . FINDINGS Follow-up was available for 146 patients ( 86 % ) . Changes in scores on the Rivermead mobility index ( score range 0 - 15 ) differed significantly between treatment and control groups at 3 months ( p=0.018 ) , but only by a median of 1 point ( 95 % CI 0 - 1 ) , with an interpolated value of 0.55 ( 0.08 - 1.04 ) . Gait speed was 2.6 m/min ( 0.30 - 4.95 ) higher in the treatment group at 3 months . Neither treatment effect persisted at 6-months ' and 9-months ' follow-up . Treatment had no effect on patients ' daily activity , social activity , anxiety , depression , and number of falls , or on emotional stress of carers . INTERPRETATION Community physiotherapy treatment for patients with mobility problems 1 year after stroke leads to significant , but clinical ly small , improvements in mobility and gait speed that are not sustained after treatment ends The survivors to two years , of a population -based stroke incidence study , were r and omly allocated to treatment or control groups in a trial of the effectiveness of a client-centred social work service . After twelve months , no difference was discernible in the use of health or community re sources by the 110 treated subjects or the 103 controls ; no significant difference was present in activity-independence scores . Of the 31 deaths that occurred , 11 were in treatment subjects and 20 in control . The mortality difference was most evident in those subjects not institutionalised at the beginning of the study ; overall the difference was significant at the 7 % level . It is suggested that the social work service had little effectiveness in altering health re source usage but may have been a therapeutic agent in its own right Background and Purpose — This prospect i ve study was design ed to examine the course , associates , and predictors of depressive symptoms during the first 18 months after stroke . Methods — A total of 100 patients were followed up for 18 months after stroke . Depressive symptoms were assessed at 2 weeks and 2 , 6 , 12 , and 18 months after stroke with the Beck Depression Inventory and the Hamilton Rating Scale for Depression , and diagnoses were performed using criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders , Third Edition-Revised . Stroke severity was assessed with the Sc and inavian Stroke Scale and cognitive functions with a comprehensive neuropsychological battery . Patients participated in a r and omized clinical trial of antidepressive medication . Results — In all , 54 % of patients felt at least mildly depressive at some time during the follow-up ; 46 % of those who were depressive during the first 2 months were also depressive at 12 and /or 18 months . Only 12 % of patients were depressive for the first time at 12 or 18 months . The male sex was associated with a more negative change in depressive symptoms during the follow-up . Older age was associated with depressive symptoms during the first 2 months , stroke severity from 6 to 12 months , and the male sex at 18 months . Depressive symptoms were unrelated to the lesion location . Conclusions — Depressive symptoms are frequent and they often have a chronic course . Depression is associated with stroke severity and functional impairment , and with the male sex at 18 months . Attention should be focused on the long-term prognosis of mood disturbances and adaptation Objectives : To describe in detail the nature of the specialist nurse interventions ; to increase underst and ing of the principal problems facing stroke patients and their care-givers in the first year following stroke and to demonstrate how these problems may change over time ; and to investigate the value of qualitative research method ologies within the context of a r and omized trial . Methods : Specialist nurses providing support in the year following stroke were asked to maintain comprehensive written records of their involvement with all patients and care-givers participating in a r and omized controlled trial . Qualitative methods were used to examine the problems faced by stroke patients and their care-givers , and the actions taken by nurses in response . Results : Specialist nurses commenced 120 records . As 19 patients died or left the area during the year-long interventions , we obtained 101 complete records . The problems encountered by stroke patients and their care-givers were numerous , diverse , complex and changed over time . Initially , practical difficulties were noted ; over time , these were accompanied by growing numbers of psychological needs . The nurses responded by providing information , advice , support and monitoring using a flexible , individualized approach . The nurses also collaborated or liaised with 17 other professional groups and provided direct support to care-givers . Conclusion : The need for many stroke patients and their care-givers to be professionally supported during the stages of stroke adjustment , for at least the first year and probably beyond , was emphasized by this study We assessed the prevalence and associations of symptoms of insomnia in patients with acute ischemic stroke , and evaluated whether mianserin as a sedative antidepressant is beneficial in the treatment of poststroke insomnia . One hundred consecutively hospitalized patients were r and omized to receive 60 mg/day of mianserin ( n = 51 ) or placebo for 1 year in a double-blind trial with a 6-month follow-up after the therapy . Symptoms of insomnia were assessed with the three insomnia-related items of the Hamilton Depression Scale ; patients were defined as insomniacs if any of these items was positive . Complaints of insomnia occurred in 68 % of patients on admission , and in 49 % at 18 months , and they were as frequent in all subgroups of patients . From 2 months , symptoms of insomnia were associated independently with depression . Living alone before stroke ( at 0 and 2 months ) and age ( at 12 months ) were other independent predictors of insomnia . The rate of recovery as evaluated by the insomnia score was more rapid in patients on mianserin than in those on placebo . At 2 months , the scores were significantly different favoring mianserin treatment ( 1.3 vs. 0.8 , p = 0.02 ) . We conclude that insomnia is a common complaint after ischemic stroke . Mianserin had a beneficial influence on the recovery from symptoms of insomnia , even though the intensity of poststroke depression was low Background and Purpose : Pharmacotherapy aim ed at stroke rehabilitation through direct central nervous effects may be assumed to work in a similar way for language recovery and sensory-motor recovery . Some data suggest that antidepressant drugs could be beneficial also for functional improvement . This prompted us to investigate whether regression from aphasia after acute stroke could be enhanced by antidepressive drug therapy . Methods : We r and omised 90 acute stroke patients with aphasia to either 600 mg moclobemide or placebo daily for 6 months , within 3 weeks of the onset of stroke . Aphasia was assessed prior to treatment and at 6 months , using Reinvang ’s ‘ Grunntest for afasi ’ and the Amsterdam-Nijmegen-Everyday- Language -Test ( ANELT ) . Result : The degree of aphasia decreased significantly at 6 months , with no difference between the moclobemide- and the placebo-treated groups . Multivariate regression analysis including treatment group , activities of daily living , aetiology of stroke , ANELT , and Reinvang ’s coefficient at baseline , and neurological deficit confirmed these results . In all , 13 in the moclobemide and 10 in the placebo group stopped taking the study medication . No further change was found in the 56 aphasic patients followed up for another 6 months with no medication . Conclusions : Compared to placebo , treatment with moclobemide for 6 months did not enhance the regression of aphasia following an acute stroke Background and Purpose — Poststroke depression is a prevalent and disabling disorder , yet evidence regarding the effectiveness of treating poststroke depression is inconclusive . Our objective was to determine the effectiveness of the Activate-Initiate-Monitor care management program for the treatment of poststroke depression . Methods — We conducted a prospect i ve , r and omized , outcome -blinded trial in 188 ischemic stroke survivors identified at the time of admission to one of 4 Indianapolis hospitals . Depression screening and enrollment occurred between 1 and 2 months poststroke . The Activate-Initiate-Monitor intervention was a care management program that included Activation of the patient to recognize depression symptoms and accept treatment , Initiation of an antidepressant medication , and Monitoring and adjusting treatment . Usual care subjects received nondepression-related education and were prescribed antidepressants at the discretion of their provider . The primary outcome measure was depression response , defined as a Hamilton Depression Inventory score < 8 ( remission ) or a decrease from baseline of at least 50 % at 12 weeks . Results — Intervention and usual care groups did not differ on any key baseline measures . Both depression response ( 51 % versus 30 % , P=0.005 ) and remission ( 39 % versus 23 % , P=0.01 ) were more likely in the Activate-Initiate-Monitor intervention than in the usual care group . This difference in depression scores was present by 6 weeks and persisted through the 12-week assessment . Serious adverse events did not differ between the 2 groups . Conclusion — The Activate-Initiate-Monitor care management model is significantly more effective than usual care in improving depression outcomes in patients with poststroke depression The effectiveness of ongoing rehabilitation services for postacute stroke survivors is poorly documented . We design ed a r and omized control , single-blinded study to demonstrate the effectiveness of intensive outpatient therapy . The treatment intervention consisted of 1 hr each of physical and occupational therapy , four times per week , for 12 wk ; therapy focused on neuromuscular facilitation and functional tasks . All subjects were screened before the therapies and after 3 mo and 9 mo . Forty-nine stroke survivors , who were at least l yr ( mean , 2.9 yr ) poststroke , were r and omized with two treated patients to each control ( no treatment supplied ) . All patients had received inpatient rehabilitation at the time of their acute stroke , but no patient had any ongoing therapy within the last 6 mo . The outcome measures included the Functional Independence Measure ( FIM ) , Brunnstrom stages of motor recovery , timed mobility tasks , and the Jebson h and evaluation . We also evaluated the level of depression , self-esteem , and socialization . The treated patients demonstrated an improvement of 6.6 points over the 3 mo of therapy compared with only 1.5 points in the control group in the FIM motor score transformed using Rasch analysis . The change from time 0 to 3 mo was significant in the treated group but not in the controls . Treated patients maintained their gains at the 9-mo follow-up , and controls lost ground . The treated group improved in terms of socialization and self-esteem as evidence d by a lower Sickness Impact Profile , whereas the controls tended to get worse . There was a trend toward less depression , but this did not reach a P = 0.05 level of significance . This study demonstrates that significant functional gains can still be attained in the postacute stroke survivor , despite prior inpatient rehabilitation services OBJECTIVE The existence of anxiety disorders plays an important role in the prognosis and associated impairment among patients with poststroke depression . The authors examined the efficacy of nortriptyline treatment for patients with comorbid generalized anxiety disorder ( GAD ) and depression after stroke . METHODS Data from three studies were merged to provide 27 patients with comorbid GAD and depression , who participated in double-blind treatment studies comparing nortriptyline ( N=13 ) and placebo ( N=14 ) . Severity of anxiety was measured with the Hamilton Rating Scale for Anxiety ( Ham-A ) , and severity of depression was measured with the Hamilton Rating Scale for Depression ( Ham-D ) . Activities of daily living were assessed by use of the Johns Hopkins Functioning Inventory ( JHFI ) . RESULTS There were no significant differences between the nortriptyline and placebo groups in demographic characteristics , stroke type , and neurological findings . Patients receiving nortriptyline treatment showed significantly greater improvement on the Ham-A , Ham-D , and JHFI than patients receiving placebo . The anxiety symptoms showed earlier improvement than depressive symptoms in patients treated with nortriptyline . CONCLUSIONS These findings suggest that poststroke GAD comorbid with poststroke depression may be effectively treated with nortriptyline , and data indicate the need for a trial specifically design ed to examine treatment of anxiety disorder OBJECTIVE This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke . METHOD A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind r and omized study comparing nortriptyline , fluoxetine , and placebo over 12 weeks of treatment . The majority of patients were recruited from a rehabilitation hospital in Des Moines , Iowa , but other enrollment sites were also used . Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression . Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks . Response to treatment of depression for individual patients was defined as a greater-than-50 % reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression . Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial , compared with patients treated with placebo , on measures of impairment in activities of daily living and levels of cognitive and social functioning . RESULTS Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression , in improving anxiety symptoms , and in improving recovery of activities of daily living as measured by the Functional Independence Measure . There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients . Fluoxetine in increasing doses of 10 - 40 mg/day led to an average weight loss of 15 . 1 pounds ( 8 % of initial body weight ) over 12 weeks of treatment that was not seen with nortriptyline or placebo . CONCLUSIONS Given the doses of medication used in this study , nortriptyline was superior to fluoxetine in the treatment of poststroke depression . Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients , alternative measurement scales , or the optimal time of treatment BACKGROUND AND PURPOSE Organized acute stroke treatment reduces mortality , functional deficits , and the need of institutionalization after stroke . It is largely unknown whether the effects of treatment are due to early or subacute efforts . The aim of this r and omized , controlled study was to test the hypothesis that rehabilitation of stroke patients in the subacute phase in a hospital rehabilitation unit is beneficial in reducing death and dependency and increasing health-related quality of life . METHODS 251 patients initially treated in the hospital were r and omized to subacute rehabilitation in a hospital rehabilitation unit ( n = 127 ) or to the health services in the municipality ( n = 124 ) and were followed up for 7 months . RESULTS The combined outcome of patients being dead or dependent ( Barthel Index score of < 75 ) was 23 % in the hospital group and 38 % in the municipality group ( P=.01 ) . Seven-month survival rates were 90.6 % and 83.9 % ( P=.11 ) , respectively . Dependency in activities of daily living was 12.6 % in the hospital group and 25.0 % in the municipality group ( P=.07 ) . Patients with a BI score of < 50 before rehabilitation had significantly better outcome in the hospital rehabilitation unit , with fewer patients becoming dependent ( P=.005 ) and patients having higher Sc and inavian Stroke Scale ( P=.026 ) and BI scores ( P=.005 ) . No significant differences in health-related quality of life were found . Many patients treated in the municipalities ( 30 % ) did not receive any organized rehabilitation in this study . CONCLUSIONS Subacute rehabilitation of stroke patients in a hospital-based rehabilitation unit improves outcome . Patients with moderate or severe stroke appear to benefit most Objective : To assess the effectiveness of community-based rehabilitation for stroke patients who were not admitted to hospital in South London . Design : R and omized controlled trial . Setting : Patients ' homes in South London . Subjects : Stroke patients not admitted to hospital after a stroke . Intervention : Rehabilitation at home by rehabilitation team for up to three months or usual care . Main outcome measures : The primary outcome measure was the Barthel score . Secondary measures included the Motricity Index , Rivermead ADL , Hospital Anxiety and Depression score and Nottingham Health Profile . Results : Forty-three patients who remained at home were r and omized to rehabilitation team ( 23 ) or ‘ usual ’ care ( 20 ) . The mean number of physiotherapy sessions was three ( range 1–14 ) for the rehabilitation team group and two for the usual care group . Patients ( with a deficit ) in the rehabilitation arm of the trial were more likely to receive occupational , physical and speech therapy than those in the control arm ( p = 0.03 , 0.01 and 0.008 , respectively ) . For those patients actually receiving therapy , there was no evidence that the amount received differed between the groups . However , the number of patients in each of these comparisons was very small . The outcome for patients in the rehabilitation team arm of the trial was nonsignificantly higher ( 0.05 < p < 0.2 ) than for those in the control arm for the areas of Nottingham Health Profile , anxiety , depression , caregiver strain and the proportion of patients living at home . Based on the data observed here , a trial with approximately 150 patients in each arm would be needed to have adequate power to detect a 33 % difference between intervention and control groups in these outcomes . Conclusion : Community therapy support for patients not admitted to hospital is feasible but to determine whether it is cost- or clinical ly effective would require trials of adequate size BACKGROUND AND OBJECTIVE Poststroke depression is one of the most frequent complications of stroke , affecting approximately 20 % to 40 % of all patients . In spite of the importance of this neuropsychiatric disorder , little attention has been given to the prevention of poststroke depression . The purpose of this study was to examine whether prophylactic treatment with the antidepressant mirtazapine in patients with acute stroke given from day 1 after the incidence prevents poststroke depression . METHOD Patients with ischemic stroke received either 30 mg mirtazapine or no antidepressant medication from day 1 after the stroke in an open , r and omized study design . Data were collected from August 2001 to December 2002 . Seventy patients were enrolled in the study and were reexamined on days 7 , 44 , 90 , 180 , 270 , and 360 using neurologic , functional , and depression rating scales . Those poststroke patients who developed depression ( DSM-IV criteria ) but had been r and omly assigned to the nontreatment group were given the antidepressant mirtazapine after the diagnosis of depression had been established . RESULTS Forty percent ( 14/35 ) of the nontreated patients and only 5.7 % ( 2/35 ) of the patients who were treated with mirtazapine developed poststroke depression . Altogether , 16 patients developed poststroke depression , 15 of whom remitted after initiation of treatment with mirtazapine . CONCLUSION Mirtazapine significantly reduced the rate of poststroke depression in patients with acute stroke . The study also demonstrated that this antidepressant was highly effective in treating poststroke depression The incidence of depression following a hemispheric stroke ranges from 25 to 60 % . The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known . We studied subjects both with and without evidence of depression , as indicated by any one of three criteria : ( i ) Clinical diagnosis of depression , ( ii ) Abnormal Zung-depression score . ( iii ) Abnormal dexamethasone suppression test ( DST ) . Patients in a stroke rehabilitation program ( 22 ) were r and omized to receive either placebo or 300 mg/day trazodone-HCl , beginning 30 days after the stroke . Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living ( ADL ) scores , with antidepressant therapy , as compared to patients receiving placebo . An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone , i.e. , in post-stroke depression such a treatment seems to be beneficial BACKGROUND AND PURPOSE Integrated Care Pathway ( ICP ) is an organized , goal -defined , and time-managed plan that has the potential of facilitating timely interdisciplinary coordination , improving discharge planning , and reducing length of hospital stay . METHODS An ICP for stroke rehabilitation based on evidence of best practice , professional st and ards , and existing infrastructure was developed . Its effectiveness was tested in 152 stroke patients undergoing rehabilitation who were r and omized to receive ICP care coordinated by an experienced nurse ( n=76 ) or conventional multidisciplinary care ( n=76 ) . RESULTS The age , sex , premorbid functional ability , and stroke characteristics of the 2 groups were comparable . There were no differences in mortality rates ( 10 [ 13 % ] versus 6 [ 8 % ] ) , institutionalization ( 10 [ 13 % ] versus 16 [ 21 % ] ) , or length of hospital stay ( 50+/-19 versus 45+/-23 days ) between patients receiving ICP or multidisciplinary care . Patients receiving conventional multidisciplinary care improved significantly faster between 4 and 12 weeks ( median change in Barthel Activities of Daily Living Index 6 versus 2 ; P<0.01 ) and had higher Quality of Life scores at 12 weeks ( 65 versus 59 ; P=0.07 ) and 6 months ( 72 versus 63 ; P<0.005 ) . There were no significant differences in the mean duration of physiotherapy ( 42.8+/-41.2 versus 39.4+/-36.4 hours ) or occupational therapy ( 8.5+/-7.5 versus 8.0+/-7.5 hours ) received between the 2 groups . CONCLUSIONS ICP management offered no benefit over conventional multidisciplinary care on a stroke rehabilitation unit . Functional recovery was faster and Quality of Life outcomes better in patients receiving conventional multidisciplinary care The authors have investigated whether treatment of sleep apnoea with nasal continuous positive airway pressure ( nCPAP ) improves depressive symptoms , personal activities of daily living ( ADL ) , cognitive functioning and delirium in patients that have suffered a stroke . Sixty-three patients consecutively admitted to a stroke rehabilitation unit 2 - 4 weeks after a stroke , with an apnoea/hypopnoea index > or = 15 , were r and omized to either nCPAP treatment ( n=33 ) or a control group ( n=30 ) . Four patients dropped out after r and omization . Both groups were assessed at baseline and after 7 and 28 nights using the Montgomery-Asberg Depression Rating Scale ( MADRS ) , Barthel-ADL index , and the Mini-Mental State Examination ( MMSE ) scale . Compared to the control group , depressive symptoms ( MADRS total score ) improved in patients r and omized to nCPAP treatment ( p=0.004 ) . No significant treatment effect was found with regard to delirium , MMSE or Barthel-ADL index . Delirium and low cognitive level ( MMSE score ) explained poor compliance with nCPAP . Depressive symptoms are reduced through nasal continuous positive airway pressure treatment in patients with severe stroke and sleep apnoea . Compliance with nasal continuous positive airway pressure treatment is a problem in stroke patients , especially when delirium and severe cognitive impairment occur This article describes a 3-year study testing the efficacy of a system of home-based , case-managed care for stroke survivors returning to the community following inpatient poststroke rehabilitation . The Stroke Transition after Inpatient Rehabilitation ( STAIR ) study was a r and omized , controlled trial of a postdischarge management strategy carried out in a group of 55 stroke patients , aged 65 or older , who did not have serious residual cognitive or language impairments and returned to the community following inpatient rehabilitation with the assistance of a primary caregiver . The program was shown to facilitate improvement in the general social activity level of the patients in the experimental group at 6 months compared to the control , and there was a trend for this effect to persist at 1 year . Strong relationships were identified between residual disability , social activity level , patients ' perceptions of efficacy , and caregiver stress Current stroke rehabilitation tends to focus on the bio-medical course of disability , often responding to psychological and social issues only when they have been implicated in crises . Although this situation is costly , little evidence exists in relation to how psychological and social outcomes can be facilitated or how psychosocial decline can be prevented . In the area of adjustment following traumatic injury , there has been some suggestion that rehabilitation should focus on the expansion of re sources , skills and self-efficacy as this will enable individuals to cope more effectively with their medical condition and circumstances . The current study was a longitudinal r and omised controlled trial involving 100 people with stroke , 58 of whom were r and omly allocated to an intervention based on the notion of psychosocial skill expansion . All were patients of a major hospital in Queensl and , Australia . An existing self-management intervention ( The Chronic Disease Self-Management Course , Lorig et al. , 2001 ) was used to operationalise the concept of psychosocial skill expansion . The control group reported declines in functioning during the first year following stroke in the areas of family roles , activities of daily living , self-care and work productivity , that were not reported by the intervention group . Although the groups had reached similar levels by one year post-stroke , this intervention may have a protective function , presumably by improving capacity to manage the functional requirements of daily life . However , the intervention did not appear to have its impact through self-efficacy , as was expected , and failed to influence outcomes such as mood or social participation . Nevertheless , the intervention warrants further investigation , given that it appears to improve rehabilitation outcomes , at least in the short-term Poststroke depression has been associated with impaired recovery of activities of daily living ( ADL ) during the first 2 years after stroke . This study examined the effect of remission of poststroke depression on recovery in ADL in a double-blind r and omized treatment study . Based on a semistructured psychiatric exam and DSM-IV diagnostic criteria , a consecutive series of 23 patients who met criteria for major depression ( N = 16 ) or minor depression ( N = 7 ) were selected and r and omly assigned to either active treatment ( nortriptyline ) or placebo . Functional physical ( i.e. , ADL ) impairment was assessed using the Johns Hopkins Functioning Inventory ( JHFI ) . Patients whose depressive disorder remitted at follow-up had significantly greater recovery in ADL functions compared with patients whose depression did not remit . There were no differences in demographic variables , lesion characteristics , and neurological symptoms between the two groups , which would explain the significantly greater improvement among the remitted patients . Because both major and minor depression patients who remitted showed greater improvement in ADL than nonremitted patients some of whom were treated with active and some with placebo medication , nonpharmacotherapeutic mechanisms related to recovery from depression appear to mediate this enhanced recovery Twenty-seven in patients participating in a stroke rehabilitation program were r and omized to receive either placebo or trazodone hydrochloride ( Desyrel ) beginning a mean ( + /- SEM ) of 44 + /- 4 days after stroke . The target dosage was 200 mg/d . Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend toward greater improvement in Barthel activities of daily living ( ADL ) scores with trazodone than with placebo . An abnormal dexamethasone suppression test result was associated with significant improvement in the Barthel ADL scores of patients receiving trazodone ( 38 + /- 6 vs 20 + /- 6 for placebo ) . Patients with stroke and evidence of depression are therefore likely to benefit from treatment with trazodone We report an investigation to identify patient factors which influence social outcome measured by the Frenchay Activities Index at 12 months after a disabling stroke . Using data from a previous r and omised trial a logistic regression model identified gait speed , prestroke Frenchay Activities Index , the Abbreviated Mental Test score , sensory neglect , chronic obstructive airways disease and left hemiplegia as significantly associated with 12-month social outcome scores . The model correctly predicted the social outcome for 78 % of the study population and , when tested on a second data set , correctly predicted 76 % of cases . These patient factors provide insight into social activity recovery after stroke and could be considered as stratification factors in future community stroke r and omised trials OBJECTIVE Poststroke depression has been shown to increase mortality for more than 5 years after the stroke . The authors assessed whether antidepressant treatment would reduce poststroke mortality over 9 years of follow-up . METHOD A total of 104 patients were r and omly assigned to receive a 12-week double-blind course of nortriptyline , fluoxetine , or placebo early in the recovery period after a stroke . Mortality data were obtained for all 104 patients 9 years after initiation of the study . Demographic and clinical measurements were collected at 3 , 6 , 9 , 12 , 18 , and 24 months after the stroke . Survival data were analyzed by using the Kaplan-Meier method . RESULTS Of the 104 patients , 50 ( 48.1 % ) had died by the time of the 9-year follow-up . Of 53 patients who were given full-dose antidepressants , 36 ( 67.9 % ) were alive at follow-up , compared with only 10 ( 35.7 % ) of 28 placebo-treated patients , a significant difference . Logistic regression analysis showed that the beneficial effect of antidepressants remained significant both in patients who were depressed and in those who were nondepressed at enrollment , after the effects of other factors associated with mortality ( i.e. , age , coexisting diabetes mellitus , and chronic relapsing depression ) were controlled . There were no intergroup differences in severity of stroke , impairment in cognitive functioning and activities of daily living impairment , and other medications received . CONCLUSIONS Treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months poststroke significantly increased the survival of both depressed and nondepressed patients . This finding suggests that the pathophysiological processes determining the increased mortality risk associated with poststroke depression last longer than the depression itself and can be modified by antidepressants 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 & NA ; A double‐blind , 3‐phase , cross‐over , placebo‐controlled trial of the pain‐relieving effect of amitriptyline and carbamazepine was carried out in 15 patients with central post‐stroke pain ( CPSP ) but without signs of depression . Treatment was given , in r and omized order , for periods of 4 weeks , separated by 1 week wash‐out . The final doses were 75 and 800 mg/day , respectively , for amitriptyline and carbamazepine . The treatment effects were assessed by daily ratings of pain intensity on a 10‐step verbal scale and at the end of each treatment period by a global rating of the analgesic effect on a 5‐step verbal scale . For the assessment of depression the Comprehensive Psychopathological Rating Scale ( CPRS ) was used . Amitriptyline produced a statistically significant reduction of pain when compared to placebo . According to the global rating , 10 of the 15 patients were responders to this drug . The effect could already be noticed during the second treatment week and it appeared to be correlated to the plasma concentration , since the median total ami‐ and nortriptyline concentrations were 497 and 247 nmol/1 , respectively , for responders and non‐responders . The early onset , together with the fact that the patients were not depressed , nor did they obtain reduced scores on ratings of depressive symptoms and signs , provides strong support for the conclusion that the pain relief was not caused by an antidepressive effect . Five of the 14 patients treated with carbamazepine reported some pain relief , but the effect did not reach statistical significance when compared to placebo . No correlation was found between effect and plasma concentration . In general , the patients tolerated the planned final dose of amitriptyline well . No final dose reduction was necessary . Carbamazepine caused more side effects and the final dose had to be reduced in 4 patients . However , only 1 patient had to be taken off medication , on day 25 , due to drug interaction This study examined the effect of antidepressants in preventing depression after stroke . Nondepressed poststroke patients ( N = 48 ) were r and omly assigned to receive nortriptyline , fluoxetine , or placebo for 3 months by using double-blind methodology and were followed-up for 21 months by using a naturalistic design . During the treatment period , one minor depression developed in the nortriptyline group ( n = 13 at 3 months ) , one minor depression developed in the fluoxetine group ( n = 13 ) , and five minor depressions developed in the placebo group ( n = 15;p < .05 ) . When treatment was discontinued , nortriptyline-treated patients were more likely to develop depression and had significantly more severe depressive symptoms during the next 6 months compared with patients in the other two groups . Both nortriptyline and fluoxetine appeared to be efficacious in preventing depression after stroke . However , nortriptyline produced an increased vulnerability to depression for more than 6 months after it was discontinued . This finding suggests the need to extend prophylactic treatment and monitor patients carefully after the discontinuation of nortriptyline Objectives : To evaluate the effectiveness of an education programme for patients and carers recovering from stroke . Design : R and omized controlled trial . Subjects and setting : One hundred and seventy patients admitted to a stroke rehabilitation unit and 97 carers of these patients . Interventions : The intervention group received a specifically design ed stroke information manual and were invited to attend education meetings every two weeks with members of their multidisciplinary team . The control group received usual practice . Measures : Primary outcome was knowledge of stroke and stroke services . Secondary outcomes were h and icap ( London H and icap Scale ) , physical function ( Barthel Index ) , social function ( Frenchay Activities Index ) , mood ( Hospital Anxiety and Depression Scale ) and satisfaction ( Pound Scale ) . Carer mood was measured by the General Health Question naire-28 . Results : There was no statistical evidence for a treatment effect on knowledge but there were trends that favoured the intervention . The education programme was associated with a significantly greater reduction in patient anxiety score at both three months ( p=0.034 ) and six months ( p=0.021 ) and consequently fewer ‘ cases ’ ( Hospital Anxiety and Depression Scale anxiety subscale score ≥ 11 ) . There were no other significant statistical differences between the patient or carer groups for other outcomes , although there were trends in favour of the education programme . Conclusion : An education programme delivered within a stroke unit did not result in improved knowledge about stroke and stroke services but there was a significant reduction in patient anxiety at six months post stroke onset The purpose of this study was to determine the efficacy of occupational therapy intervention related to the leisure activities of stroke survivors . Forty discharged stroke patients were r and omly assigned to an experimental group , which received occupational therapy intervention related to leisure activities , or to a control group . An independent evaluator assessed the patients ' involvement in activities and satisfaction with that involvement on three separate occasions . The results showed no statistically significant differences between the experimental and control groups in activity involvement or satisfaction with that involvement . There are likely two reasons for these findings . First , the intervention was limited in scope ( i.e. , only five therapist visits ) , and second , many environmental factors strongly influence activity participation and satisfaction OBJECTIVE To examine , in a post hoc analysis of an antidepressant treatment trial , correlates of irritability and aggression after stroke and changes in irritability scores associated with antidepressant treatment . DESIGN Aggressive patients ( n=23 ) were compared with nonaggressive patients ( n=69 ) on numerous measures of psychopathology , poststroke impairment , and neuroimaging findings . SETTING All patients were hospitalized at the time of the initial evaluation for acute stroke or for rehabilitation therapy . PARTICIPANTS Ninety-two patients from the Iowa City Stroke Study were classified as aggressive or nonaggressive , based on symptoms elicited by the Present State Examination ( PSE ) and from family or caretaker reports . INTERVENTION All patients were r and omized to receive nortriptyline , fluoxetine , or placebo using a double-blind methodology . MAIN OUTCOME MEASURE The change in aggression score as elicited by the PSE at the beginning and the end of a 12-week treatment trial . RESULTS Twenty-five percent ( 23/92 ) of patients reported irritability or aggression . Irritable and aggressive patients had higher total PSE scores , Hamilton Depression Rating Scale scores , Hamilton Anxiety Rating Scale ( HAMA ) scores , and lower Mini-Mental State Examination scores . They also had lesions that were more proximal to the frontal pole . Stepwise regression analysis showed that HAMA scores and proximity of lesion to the frontal pole were significant independent predictors of irritability . Among irritable and aggressive patients with depression who responded to antidepressants , there was a significantly greater reduction in irritability after treatment , compared with patients whose depression did not lessen with treatment . CONCLUSIONS Several factors , such as severity of impairment , other psychopathology , and neurobiologic factors , appear to contribute to irritable and aggressive behavior in stroke patients . If depression accompanies aggression , the results of this small study suggest that successful treatment of depression may reduce aggressive behavior BACKGROUND AND PURPOSE Shared care initiatives , albeit commonly utilised in managing other chronic conditions have not been implemented in the area of stroke in Australia . The aims of this project were to adopt a shared care approach for stroke survivors comparing an experimental " shared-care " group with a " treatment-as-usual " control group in reference to the normalization or reversal of vascular risk factors and the detection and management of post-stroke depression . METHODS A r and omised controlled experimental research design was implemented with participants r and omized to an intervention or control group and followed over a 12-month period . The treatment group consisted of a r and omly selected group of patients , discharged from an acute stroke unit and transferred into the shared care model . Risk factors for stroke and depression were compared between the two groups . RESULTS Of 97 patients originally included in the study , 17 dropped out . At 12 months , 80 patients remained for analysis ( 35 in the intervention group and 45 in the control group ) . The findings demonstrated positive trends for patients within the intervention group that were not found within the control group . The percentage of intervention patients reaching target systolic blood pressure ( sBP ) of 140 mmHg after 12 months tended to be greater than in the control group ( p=0.11 , NS ) . In the intervention group , at 12 months , the total cholesterol greater than 5.18 mmol/L was 12.5 % compared to 58.8 % at discharge . In contrast this trend was not so distinct in the control group ( 57.7 % to 42.9 % ) . The percentage of patients reaching target ( recommended ) total cholesterol of 5.18 mmol/L was significantly greater in the shared care patients intervention group relative to the control group ( p=0.02 ) . The average number of walks per week was also significantly greater in intervention group compared to the control group ( p=0.048 ) . Moreover , 45 % of the control group screened as depressed compared with 20 % of the intervention group at 12 months ( p=0.06 ) . CONCLUSIONS This study demonstrates that major risk factors for recurrent stroke and vascular disease in general are better managed with the shared care model than with usual post-discharge care . The significantly reduced depression as found on the screening PHQ9 at 12 months indicated that the intervention was beneficial not only in the detection of depression but also treatment Objectives : To assess the impact of information packs on patients with stroke and their carers , and to pilot some of the methodology for a trial of a Family Support Organiser ( FSO ) . Subjects : Seventy-one patients admitted to Oxford hospitals with acute stroke during February – July 1995 , and 49 informal carers of these patients . Design : R and omized controlled trial . Intervention group received an information pack containing various Stroke Association publications one month after their stroke , or at discharge from hospital , whichever was sooner . Control group received nothing . Follow-up was by interview at the place of residence of the patients six months after their stroke . Measures : Outcome measures assessed knowledge about stroke ; satisfaction with information received ; patient behaviour in terms of access to community services and benefits ; and health status and quality of life . Results : Patients and carers in the intervention group tended to know more about stroke , but these differences were not significant once adjusted for age . Patients in the intervention group ( but not carers ) tended to be more satisfied with the information that they had received , but the differences were not significant . There were no differences with regard to any aspects of quality of life in patients in the intervention group , though carers in the intervention group were found to have significantly better mental health ( p = 0.04 ) . Conclusions : While the study was too small to generate firm conclusions , information leaflets may lead to improved knowledge about stroke several months after they have been distributed . This finding is worth following up with larger studies . The stroke knowledge question naire that was piloted in this trial seems to be able to detect differences between groups Client characteristics associated with outcome of group counseling were identified in a sample of physically disabled persons using st and ardized self report inventories . Thirty-eight subjects were tested before and after an 8 week treatment interval for signs of emotional disorder , inactivity , and social problems related to being severely disabled . Treatment consisted of group conference phone calls using self determined task assignments as a focus for discussion . Change in report of life satisfaction was predicted reliably from pretest data . Loneliness accounted for 73 % of the variance in posttreatment life satisfaction scores . Other significant predictors included signs of depression , alcohol use , and constructs related to social support . Using regression analysis , persons with adjustment problems could be identified and prognosis for treatment predicted with acceptable reliability OBJECTIVES To examine the effect of exercise on depressive symptoms and the effect of baseline depressive symptoms on the benefits from exercise in stroke survivors who have completed acute rehabilitation . DESIGN Planned secondary analysis of the data from a 9-month r and omized , controlled trial . SETTING Participant homes . PARTICIPANTS One hundred stroke survivors who had completed acute rehabilitation . INTERVENTION A progressive , structured , 3-month physical exercise program . MEASUREMENTS Demographics , stroke characteristics , impairments , functional limitations , the Geriatric Depression Scale , the Stroke Impact Scale , and the Medical Outcomes Study 36-Item Short Form . RESULTS Baseline rates of depressive symptoms and other stroke sequelae were similar between the two arms . Ninety-three participants were assessed immediately after the intervention ( 3 months after enrollment ) , and 80 were assessed 9 months after enrollment . Six ( 14 % ) of the exercise group and 16 ( 35.6 % ) of the usual-care group had depressive symptoms at 3 months ( P = .03 ) . At 9 months , three ( 7.5 % ) of the exercisers had significant depressive symptoms compared with 10 ( 25 % ) who received usual care ( P = .07 ) . Participants with and without baseline depressive symptoms had equivalent treatment-related gains in impairments and functional limitations , but only participants with depressive symptoms had improved quality of life . CONCLUSION Exercise may help reduce poststroke depressive symptoms . Depressive symptoms do not limit gains in physical function due to exercise . Exercise may contribute to improved quality of life in those with poststroke depressive symptoms Objective : To evaluate a day service for people aged 18–55 years who had a stroke . Design : A r and omized cross-over study design was used , r and omly allocating individuals to attend the service for six months followed by a period of no attendance for six months . Setting : A day service pilot project was launched in Cardiff in July 1995 for people who were aged between 18 and 55 years and had a stroke . It met one day a week . Subjects : Twenty-six participants were recruited to the study between June 1998 and February 2000 . Their mean age was 48 years ( SD = 7 ) . Interventions : The service aim ed to offer participants the opportunity to identify and pursue meaningful and realistic opportunities within the community . A range of activities occurred at the service including creative activities and social outings . Main outcome measures : The Barthel ADL Index , Extended ADL Scale , Nottingham Leisure Question naire , Short Form 36 , the Hospital Anxiety and Depression Scale , the Canadian Occupational Performance Measure , the Role Checklist and the Semantic Differential Self Concept Scale were used to assess the outcomes from the service . Results : Attending the service increased occupational performance and satisfaction with performance but there was no evidence that depression and anxiety were reduced or that quality of life and self-concept were improved . Conclusion : Although there were some gains from attending the service there were also many unmet needs . Further research is required to continue to identify how best to meet the needs of individuals post stroke under retirement age The purpose of this r and omized controlled trial ( RCT ) was to determine the effectiveness of problem-solving counselling or phone-call support provided by nurses to out patients not well adjusted to chronic illness . Subjects ( N = 293 ) completed measures at baseline and after the six-month period of intervention for psychosocial variables including coping behaviours , purpose in life , and psychosocial adjustment to illness . Subjects receiving phone-call support from nurses demonstrated less psychological distress . Results also suggest that problem-solving counselling improves psychosocial adjustment to chronic illness for out patients who live alone , infrequently use problem-solving coping skills , or frequently use avoidance coping methods . As well , out patients with a low purpose in life who show infrequent use of problem-solving coping skills appear to benefit most from problem-solving counselling provided by nurses . On the other h and , those not well adjusted who frequently use problem-solving coping seem to be served more effectively by phone-call support Abstract Objective : To assess the clinical effectiveness of an early discharge policy for patients with stroke by using a community based rehabilitation team . Design : R and omised controlled trial to compare conventional care with an early discharge policy . Setting : Two teaching hospitals in inner London . Subjects : 331 medically stable patients with stroke ( mean age 71 ) who lived alone and were able to transfer independently or who lived with a resident carer and were able to transfer with help . Interventions : 167 patients received specialist community rehabilitation for up to 3 months after r and omisation . 164 patients continued with conventional hospital and community care . Main outcome measures : Barthel score at 12 months . Secondary outcomes measured impairment with motoricity index , minimental state examination , and Frenchay aphasia screening test ; disability with the Rivermead activity of daily living scales , hospital anxiety and depression scale , and 5 m walk ; h and icap with the Nottingham health profile ; carer stress with caregiver strain index and patient and carer satisfaction . The main process measure was length of stay after r and omisation . Results : One year after r and omisation no significant differences in clinical outcomes were found apart from increased satisfaction with hospital care in the community therapy group . Length of stay after r and omisation in the community therapy group was significantly reduced ( 12 v 18 days ; P<0.0001 ) . Patients with impairments were more likely to receive treatment in the community therapy group . Conclusions : Early discharge with specialist community rehabilitation after stroke is feasible , as clinical ly effective as conventional care , and acceptable to patients . Considerable reductions in use of hospital beds are achievable . Key messages Early discharge from hospital after stroke with specialist rehabilitation at home is feasible without an increase in readmission rates or stress to carers This r and omised controlled trial shows this method to be as effective as conventional care when assessed with a range of measures of impairment , disability , h and icap , carer stress , and patient and carer satisfaction at 1 year Significant reductions in bed usage can be achieved by the provision of a community rehabilitation team with no significant increase in rehabilitation In a 6-week study the efficacy of combined treatment of imipramine plus mianserin was compared to combined treatment of desipramine plus mianserin in patients with post-stroke depression . Patients were required to have a minimum baseline total score of 15 on the 17-item Hamilton Depression Scale ( HAMD ) . The Melancholia Scale ( MES ) was also used to measure severity of depressive states to show that somatic symptoms had little influence on the evaluation of depression . Out of 120 stroke patients screened , 20 patients fulfilled the inclusion criteria . The doses of the drugs were flexible , using side-effects as a guide during treatment . Both intention to treat analysis and efficacy data ( excluding patients who had dropped out during the first 2 weeks of treatment ) showed that imipramine ( mean dose 75 mg daily ) plus mianserin ( mean dose 25 mg daily ) was superior to desipramine ( mean dose 66 mg daily ) plus mianserin ( 27 mg daily ) . The MES was found to be more sensitive than the HAMD for measuring change in depressive states during treatment . The assessment of side-effects using the UKU scale showed good tolerance in general . The only difference between the two treatment groups was seen in micturition disturbances , where the imipramine treated patients had most complaints after 14 days of treatment , but the symptoms disappeared despite continuous treatment OBJECTIVE --To determine whether the intervention of a physiotherapist improved mobility in patients seen more than one year after stroke . DESIGN --R and omised crossover trial comparing two groups offered intervention by a physiotherapist , one immediately after entry into the trial and the other after a delay of three months . The intervention consisted of identifying problems and offering advice and help to solve the problems . SETTING -- Patients ' homes in Oxfordshire . SUBJECTS-- Patients who had reduced mobility due to a stroke more than one year before entry ; 60 were recruited from a community stroke register and 34 in other ways . MAIN OUTCOME MEASURES --St and ard measures of mobility including gait speed , functional ambulation categories , the Nottingham extended activities of daily living index , and individual items from the Barthel activities of daily living index and the Frenchay activities index . Measures of manual dexterity , depression , and anxiety were used as controls . RESULTS --94 patients entered the trial and 49 were r and omised to immediate and 45 to delayed physiotherapy ; 89 were compared at the crossover point . At r and omisation the two groups were comparable . At three months the group given early therapy showed an improvement in gait speed whereas the untreated group had declined ( differences of -3.9 v 6.4 s to walk 10 m ; p less than 0.01 ) ; between three and six months the group given delayed therapy showed improvement and the previously treated group declined ( differences of 6.5 v -3.9 s to walk 10 m ; p less than 0.01 ) . A 9 % ( 95 % confidence interval 0 % to 18 % ) decrease in time taken to walk 10 m was associated with treatment and a 12 % ( 2 % to 19 % ) increase when patients were untreated . Other measures did not change significantly . CONCLUSION --Intervention of an experienced physiotherapist late after stroke specifically improves mobility , albeit by a small amount , but the effects do not seem to be maintained , perhaps because there is an underlying decline in mobility in these patients . Gait speed offers a simple and sensitive measure of outcome BACKGROUND AND PURPOSE In animal models of brain injury , administration of numerous pharmaceuticals is reported to facilitate functional recovery . However , only drugs that increase the release of norepinephrine have been shown to promote recovery when administered late ( days to weeks ) after injury . To determine whether these findings were applicable to humans , we administered the norepinephrine stimulant dextroamphetamine , paired with physical therapy , to hemiplegic stroke patients . METHODS Ten hemiplegic patients who suffered an acute ischemic infa rct ion were entered between days 16 and 30 after onset and r and omly assigned to receive either 10 mg of dextroamphetamine or a placebo orally every fourth day for 10 sessions paired with physical therapy . The Fugl-Meyer Motor Scale was used at baseline , within each session , and for 12 months after onset as the dependent measure . Confounding medications such as alpha-adrenergic antagonists or agonists were excluded in all subjects . RESULTS Although there were no differences between the groups at baseline ( P = .599 ) , there was a significant ( P = .047 ) difference between the groups when the drug had been discontinued for 1 week and at the 12-month follow-up visit ( P = .047 ) . CONCLUSIONS Administration of dextroamphetamine paired with physical therapy increased the rate and extent of motor recovery in a small group of hemiplegic stroke patients . These data support and extend previous findings of the facilitatory aspects of certain types of drugs on recovery from brain injury . The use of neuromodulation may allow the nervous system to adapt previously unused or alternative pathways to relevant external input The purpose of this study was to determine if social support intervention would improve the support experienced by stroke survivors and if improvement would result in better psychosocial outcome . Subjects were drawn from a community-based sample that had received rehabilitation services in the hospital and at home . The study was a r and omized trial ( n = 48 experimental group , n = 40 control group ) , and measures were taken at entry into the study , immediately after intervention ( or , at a comparable time for the control group ) , and again 3 months later . No significant differences were found between groups either on social support measures or psychosocial outcomes . Secondary analyses showed that significant changes in support had been experienced within the sample as a whole in relation to the subjects ' gender , living situation , marital status , and employment status . Findings are discussed in terms of method ologic and programmatic concerns , and recommendations are made for further research with this potentially valuable intervention This pilot study sought to determine if the use of Life Review Therapy would result in lower levels of depression and higher degrees of life satisfaction in individuals with right hemisphere cerebral vascular accidents ( CVAs ) . Fourteen subjects in a southern rehabilitation center were r and omly assigned to either an experimental or control group . The experimental group received three one-hour sessions of Life Review Therapy and the control group viewed three one-hour sessions of neutral video with a follow-up discussion . Following the third session of each group , subjects were administered the Zung Scale for Depression and the Life Satisfaction Index — Form Z. A one-way ANOVA revealed a significantly lower level of depression ( p < .01 ) and a significantly higher degree of life satisfaction ( p < .01 ) in the Life Review Therapy group 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 Abstract Objective : To evaluate whether specialist nurse visits enhance the social integration and perceived health of patients with stroke or alleviate stress in carers in longer term stroke care . Design : Stratified r and omised controlled trial ; both groups assessed at time of recruitment and at 3 , 6 , and 12 months . Setting : Patients with disability related to new stroke who lived in their own homes in the Bradford Metropolitan District . Subjects : 240 patients aged 60 years or over , r and omly allocated to control group ( n = 120 ) or intervention group ( n = 120 ) . Intervention : Visits by specialist outreach nurses over 12 months to provide information , advice , and support ; minimum of six visits during the first six months . The control group received no visits . Main outcome measures : The Barthel index ( functional ability ) , the Frenchay activities index ( social activity ) , the Nottingham health profile ( perceived health status ) . Stress among carers was indicated by the general health question naire-28 ( 28 items ) . The nurses recorded their interventions in trial diaries . Results : There were no significant differences in perceived health , social activities , or stress among carers between the treatment and control groups at any of the assessment s points . A subgroup of mildly disabled patients with stroke ( Barthel index 15 - 19 ) had an improved social outcome at six months ( Frenchay activities index , median difference 3 ( 95 % confidence interval 0 to 6 ; P = 0.03 ) ) and for the full 12 months of follow up ( analysis of covariance P = 0.01 ) compared with the control group . Conclusions : The specialist nurse intervention result ed in a small improvement in social activities only for the mildly disabled patients . No proved strategy yet exists that can be recommended to address the psychosocial difficulties of patients with stroke and their families . Key messages This r and omised controlled trial using specialist nurses in an intervention strategy found that no significant differences were seen at one year follow up between the two groups of patients in wellbeing or social activities and no reduction in stress among carers A significant but small increase in social activities was reported by a subgroup of mildly disabled patients with stroke No proved strategy yet exists to address the psychosocial difficulties of patients with stroke and their BACKGROUND AND PURPOSE Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients , and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals . We carried out a prospect i ve , r and omized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management . METHODS One hundred twenty elderly patients with acute stroke were r and omized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team . Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential . Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital . Family or community support was arranged when necessary for both treatment groups . On recruitment , patient demographics , medical history , clinical features related to stroke , and functional ability as measured by the Barthel Index were noted . Subjects were review ed at 3 and 6 months to assess functional level , hospital and outpatient services received , general well-being , mood , and level of satisfaction . Costs of treatment of the two groups were also compared . RESULTS Functional improvement ( Barthel Index score ) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months ( P = .03 ) . There were also fewer outpatient visits among the day hospital patients at 6 months ( P = .03 ) . No significant difference was found in costs between the two treatment groups . CONCLUSIONS Compared with conventional medical management , care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost A recent r and omized controlled trial evaluated the effects of specialist nurses providing information , advice and support to caregivers and patients at home during the first year after a stroke . Reported here are the results of a complementary study which used qualitative methods to examine the experience of patients and caregivers during the year of recovery after a stroke . We used semi-structured interviews with a purposively selected sample of 30 patients and 15 caregivers at the end of a r and omized controlled trial ( 13 - 16 months post-stroke ) . Patients and caregivers provided vivid descriptions of the recovery process . Recovery was perceived in terms of the degree of congruence patients identified between their lives before , and after , stroke . Patients therefore had individual and personal yardsticks for measuring their recovery . In conclusion , further research and interventions must consider the diverse , complex , dynamic and highly personal character of stroke recovery . Traditional outcome measures are too simplistic to capture patients ' and caregivers ' experiences . There do not appear to be single or simple solutions to the problems of facilitating psycho-social adjustment OBJECTIVE --Comparison of day hospital attendance and home physiotherapy for stroke patients leaving hospital to determine which service produces greater functional and social improvement for the patient , reduces emotional stress for the care giver , and lessens the need for community support . DESIGN --Stratified , r and omised trial of stroke patients attending day hospital two days a week or receiving home treatment from a community physiotherapist . The six month assessment results are reported in this paper . SUBJECTS-- Patients over 60 years old resident within the Bradford metropolitan district discharged home after a new stroke with residual disability . SETTING --Four day hospitals in two health authorities and domiciliary work undertaken by experienced community physiotherapists . MAIN OUTCOME MEASURES --Barthel index , functional ambulatory categories , Motor Club assessment , Frenchay activities index , and Nottingham health profile were used . Carers ' stress was indicated by the general health question naire . Treatment given and community care provided were recorded . RESULTS --Of 124 patients recruited , 108 were available for re assessment at six months . Both treatment groups had significantly improved in functional abilities between discharge and six months . The improvements were significantly greater for patients treated at home ( Mann-Whitney test ; Barthel index , median difference 2 ( 95 % confidence interval 0 to 3 ) p = 0.01 ; Motor Club assessment , median difference 2 ( 1 to 5 ) , p = 0.01 ) . The home treated patients received less treatment ( median difference 16 ( 11 to 21 ) treatments , p less than 0.001 ) . More than a third of patients in both groups showed depressed mood , and a quarter of care givers were emotionally distressed . CONCLUSIONS --Home physiotherapy seems to be slightly more effective and more re source efficient than day hospital attendance and should be the preferred rehabilitation method for aftercare of stroke patients . New strategies are needed to address psychosocial function for both patients and care givers BACKGROUND AND PURPOSE In animals , drugs that increase brain amine concentrations influence the rate and degree of recovery from cortical lesions . It is therefore conceivable that antidepressants may influence outcome after ischemic brain injury in humans . We evaluated the effects of the norepinephrine reuptake blocker maprotiline and the serotonin reuptake blocker fluoxetine on the motor/functional capacities of poststroke patients undergoing physical therapy . METHODS Fifty-two severely disabled hemiplegic subjects were r and omly assigned to three treatment groups ; during 3 months of physical therapy , patients were treated with placebo , maprotiline ( 150 mg/d ) , or fluoxetine ( 20 mg/d ) . Before and at the end of the observation period , we assessed activities of daily living by the Barthel Index , degree of neurological deficit by a neurological scale for hemiplegic subjects , and depressive symptomatology by the Hamilton Depression Rating Scale . RESULTS The diverse treatments ameliorated walking and activities of daily living capacities to different extents . The greatest improvements were observed in the fluoxetine-treated group and the lowest in the maprotiline-treated group . Furthermore , fluoxetine yielded a significantly larger number of patients with good recovery compared with maprotiline or placebo . These effects of the drugs were not related to their efficacy in treating depressive symptoms . CONCLUSIONS Fluoxetine may facilitate or , alternatively , maprotiline may hinder recovery in poststroke patients undergoing rehabilitation . The effects of fluoxetine as an adjunct to physical therapy warrant further investigation , since treatment with fluoxetine may result in a better functional outcome from stroke than physical therapy alone Objective : Selegiline ( L-deprenyl ) is a selective monoamine oxidase B ( MAO- B ) inhibitor used in the treatment of Parkinson 's disease . In addition , it is thought to rescue neurons with a loss of target-derived trophic support . Several mechanisms have been proposed to explain these phenomena , such as the production of neurotrophic actions through astrocyte activation , reduction of free radical production , or the pres ence of antiapoptotic properties . The aim of this study was to investigate whether the systemic administration of selegiline facilitates recovery after a cerebral infa rct ion in humans . Methods : This phase II study was r and omized , double-blind , and placebo con trolled . Selegiline , 5 mg , or matched placebo was given twice a day for 3 months . The drug therapy was started within 48 h after a hemispheric infa rct ion in the territory of middle cerebral artery . There were 24 patients recruited . Twenty patients were followed up to 3 months or until their death , and they represent the efficacy analysis group . The primary efficacy parameters were Sc and inavian Stroke Scale ( SSS ) , Barthel Index ( BI ) , and Fugl-Meyer Scale ( FMS ) . Secondary parameters were Zung Self-Rating Depres sion Scale ( ZDS ) and 15-Dimensional Measure of Health Related Quality of Life test ( 15-D ) . Results : SSS improved statistically significantly from the baseline when com pared with placebo ( p = 0.019 ) . The results were parallel among the other two pri mary efficacy variables ( BI and FMS ) , showing a positive trend for selegiline , although they did not reach statistical significance . Similarly , in the analysis of the secondary efficacy variables , both the 15-D test and ZDS supported this positive trend in favor of selegiline , although no statistically significant differences between groups were found ( p = 0.06 in 15-D test ) . Conclusions : Selegiline seems to be beneficial after a cere bral infa rct ion . This benefit may be due to the enhancement of the recovery process . Key Words : Cerebrovascular disorders — Stroke — Selegiline — L-deprenyl — Recovery of function OBJECTIVE To determine the efficacy and safety of methylpheni date in acute stroke rehabilitation . DESIGN A prospect i ve , r and omized , double-blind , placebo-controlled study . PATIENTS AND SETTING Twenty-one stroke patients consecutively admitted to a community-based rehabilitation unit . INTERVENTION Three-week treatment of methylpheni date ( or placebo ) in conjunction with physical therapy . Methylpheni date was started at 5 mg and increased gradually to 30 mg ( 15 mg at 8:00AM and 15 mg at 12:00 noon ) , and discontinued before discharge . MAIN OUTCOME MEASURES Mood measures included the Hamilton Depression Rating Scale ( HAM-D ) and Zung Self-Rating Depression Scale ( ZDS ) . Cognitive status was evaluated using the Mini-Mental State Exam ( MMSE ) . Motor functioning was assessed using the Fugl-Meyer Scale ( FMS ) and a modified version of the Functional Independence Measure ( M-FIM ) . All measures were administered pretreatment and weekly thereafter . Side effects were measured after each increase in dosage and weekly . RESULTS Patients receiving methylpheni date treatment scored lower on the HAM-D ( F(1,18)=5.714 , p=.028 ) , lower on the ZDS ( F(1,18)=4.206 , p=.055 ) , higher on the M-FIM ( F(1,18)=5.374 , p=.032 ) , and higher on the FMS ( F(1,9)=4.060 , p=.075 ) than patients receiving placebo . CONCLUSION Methylpheni date appears to be a safe and effective intervention in early poststroke rehabilitation that may expedite recovery OBJECTIVE This study was undertaken to test the reliability and validity of the Pathological Laughter and Crying Scale and the effectiveness of nortriptyline treatment for patients with emotional lability following stroke . METHOD Eighty-two patients with ischemic brain injury-54 who had been hospitalized with acute stroke and 28 others who requested treatment for pathological laughing and crying -- were given st and ardized psychiatric and neurological assessment s and then administered the Pathological Laughter and Crying Scale . The 54 acute stroke patients were used to evaluate the Pathological Laughter and Crying Scale , and the 28 patients with pathological emotional display were r and omly assigned to nortriptyline treatment or placebo in a 6-week double-blind trial to assess the efficacy of a tricyclic antidepressant in treatment of this disorder . RESULTS The interrater reliability on the Pathological Laughter and Crying Scale for a subgroup of 15 patients was 0.93 , and the test-retest reliability of the scale was excellent . After 4 and 6 weeks of treatment , scores on the Pathological Laughter and Crying Scale showed significantly greater improvement in the 14 patients given nortriptyline than in the 14 given placebo . Although almost one-half of these patients also had major depression , the improvement in emotional lability was independent of depression status . In addition , response to treatment was not significantly affected by lesion location or time since stroke . CONCLUSIONS The severity of symptoms in pathological emotional display can be reliably quantified with the Pathological Laughter and Crying Scale , and treatment with nortriptyline can effectively ameliorate this emotional disorder OBJECTIVE To assess whether a selective serotonin reuptake inhibitor is effective in the treatment of stroke-associated lability of mood . METHODS Twenty-eight non-depressed patients suffering from post-stroke lability of mood took part in an 8-week double-blind r and omized placebo-controlled trial of a selective serotonin reuptake inhibitor ( 50 mg sertraline per day ) . RESULTS There were statistically significant improvements in a global rating of emotionalism and a specific benefit on tearfulness . The results are discussed in the light of proposed serontonergic mechanisms for emotional lability following stroke . CONCLUSIONS 50 mg of sertraline per day may be an effective and well-tolerated treatment for stroke-associated lability of mood in the absence of depression . This is supportive evidence for the serontonergic hypothesis of lability of mood following stroke Abstract Objective : To examine the effect of contact with a stroke family care worker on the physical , social , and psychological status of stroke patients and their carers . Design : R and omised controlled trial with broad entry criteria and blinded outcome assessment six months after r and omisation . Setting : A well organised stroke service in an Edinburgh teaching hospital Subjects : 417 patients with an acute stroke in the previous 30 days r and omly allocated to be contacted by a stroke family care worker ( 210 ) or to receive st and ard care ( 207 ) . The patients represented 67 % of all stroke patients assessed at the hospital during the study period . Main outcome measures : Patient completed Barthel index , Frenchay activities index , general health question naire , hospital anxiety and depression scale , social adjustment scale , mental adjustment to stroke scale , and patient satisfaction question naire ; carer completed Frenchay activities index , general health question naire , hospital anxiety and depression scale , social adjustment scale , caregiving hassles scale , and carer satisfaction question naire . Results : The groups were balanced for all important baseline variables . There were no significant differences in physical outcomes in patients or carers , though patients in the treatment group were possibly more helpless , less well adjusted socially , and more depressed , whereas carers in the treatment group were possibly less hassled and anxious . However , both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care , in particular those related to communication and support . Conclusions : The introduction of a stroke family care worker improved patients ' and their carers ' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients ' physical wellbeing . Key messages A stroke family care worker in the context of a well organised hospital based stroke service has no definite beneficial effect on the physical , social , or psychological outcome of patients or their carers A stroke family care worker may reduce carers ' hassles and anxiety but render patients more helpless , less well socially adjusted , and more depressed A stroke family care worker may improve patients ' and their carers ' satisfaction with those aspects of stroke services relating to communication and support Purchasers of health care need to decide the value they and their patients place on satisfaction with health The authors tested the effect of sertraline in the prevention of poststroke depression . After experiencing an acute ischemic stroke , nondepressed patients ( N=137 ) were r and omly assigned to 12 months of double-blind treatment with either sertraline ( N=70 ) or placebo ( N=67 ) . Kaplan-Meier analysis showed sertraline to have significantly superior prophylactic efficacy compared with placebo . Two definitions of clinical depression were used : total score > 18 on the HAM-D(17 ) and score > or=9 on the HAM-D(6 ) . Approximately 10 % of the sertraline-treated group developed depression according to either definition , whereas 30 % developed depression in the placebo group . On the HAM-D(6 ) the superiority of sertraline to placebo was demonstrated already after 6 weeks of therapy . Treatment was well tolerated ; patients treated with sertraline experienced significantly fewer adverse events Twenty-eight elderly in patients suffering from major depressive episodes ( diagnosed according to DSM III ) received r and omly , on a double-blind basis , amitriptyline ( 75 mg/die ) or fluoxetine ( 20 mg/die ) for five weeks . There were four drop-outs in the amitriptyline group and two drop-outs in the fluoxetine group . Both groups showed a significant amelioration at the end point for Hamilton Rating Scale of Depression scores compared to the baseline value . Anticholinergic side-effects were significantly more severe in the amitriptyline group . Weight gain was detected only in patients receiving amitriptyline OBJECTIVE We design ed this study to determine whether the daily treatment of nondepressed acute stroke patients with sertraline reduced the incidence of depression at follow-up . METHOD 111 patients with recent stroke ( < 2 weeks ; International Classification of Diseases , Tenth Revision criteria ) were r and omly assigned to treatment with placebo ( N = 56 ) and sertraline ( N = 55 , 50 mg once daily ) in this double-blind , placebo-controlled 24-week clinical trial . Subjects were recruited from the 2 largest teaching hospitals of Western Australia between June 2002 and June 2004 . The primary endpoint of interest was development of clinical ly significant depressive symptoms as assessed by a Hospital Anxiety and Depression Scale-depression subscale score of 8 or above , or as diagnosed by the treating physician during 24 weeks . RESULTS There was no significant difference in the incidence of depressive symptoms during 24 weeks of treatment ( 16.7 % [ 8/48 ] sertraline vs. 21.6 % [ 11/51 ] placebo , rate ratio = 0.8 , 95 % CI = 0.3 to 2.1 , p = .590 ) . The trial medication was discontinued by 51.8 % ( 29/56 ) of patients assigned placebo and 47.3 % ( 26/55 ) assigned sertraline ( p = .634 ) , most often because of perceived side effects or because the treating physician introduced an antidepressant medication . CONCLUSIONS Twenty-four-week treatment with 50 mg of sertraline once daily initiated within 2 weeks of onset of acute stroke is not a significantly more effective strategy to prevent 6-month depression than usual care plus placebo among nondepressed stroke patients . New pharmacologic and nonpharmacologic strategies need to be developed to reduce the health and financial burden associated with depression after stroke |
1,798 | 24,951,319 | Compared to controls , reductions were identified in the operated hip in sagittal range of motion , peak extension , sagittal power generation , abduction moment and external rotation moment .
During stair ascent , these reductions did not become more apparent , although deficits in hip kinetics in all three planes were found .
Walking speed and step length were reduced compared to controls at longer-term follow-up , but not at short-term follow-up .
INTERPRETATION The hip abduction moment deficit was present both in level walking and in stair ascent in total hip arthroplasty patients compared to controls .
Reduced sagittal hip power generation and external rotation moment were also found , of which the clinical relevance remains to be established . | BACKGROUND Differences in the performance of gait and gait-related activities of daily living are known to persist after total hip arthroplasty compared to healthy controls , but the specific underlying deficits ( spatiotemporal , kinematics and kinetics ) are not completely understood .
This review aim ed to map the differences between patients and controls , and between the operated and non-operated limbs during various activities of daily living . | OBJECTIVE To study the hip muscle strength and cross sectional area ( CSA ) in men with hip osteoarthritis ( OA ) compared to age and sex matched healthy controls . METHODS Based on the American College of Rheumatology criteria regarding classification of hip OA , 27 men ( aged 47 - 64 yrs ) with unilateral or bilateral hip OA and 30 age matched r and omly selected healthy male controls were studied . The maximal isometric hip abductor , adductor , flexor , and extensor strength ( Nm ) at 0 degree of hip flexion in the supine position was determined with a dynamometer . The isokinetic hip flexion and extension strength ( peak torque , Nm ) was determined using angular velocities of 60 degrees /s and 120 degrees /s . The subjective severity of hip pain was rated by visual analog scale prior to the muscle strength test . CSA of the pelvic and thigh muscles was measured from magnetic resonance images . RESULTS The reliability of intraclass correlation coefficients for repeated measures of muscle strength varied from 0.70 to 0.94 in controls and from 0.84 to 0.98 in subjects with OA . Hip isometric adductor and abductor strength was 25 % and 31 % lower ( p < 0.001 ) in OA subjects than in controls , respectively . The hip isometric and isokinetic flexion strength was 18 - 22 % lower ( p < 0.01 ) in OA subjects than in controls , but extension strength did not differ between groups . In OA subjects , the hip flexion and extension isometric and isokinetic strength values were 13 - 22 % lower ( p < 0.05 ) on the more deteriorated side compared to the better side . CSA of the pelvic and thigh muscles did not differ between the groups . However , in OA subjects , the CSA of the pelvic and thigh muscles was 6 - 13 % less ( p < 0.05 to < 0.001 ) on the more severely affected hip compared to the better hip . CONCLUSION Men with hip OA have significantly lower abduction , adduction , and flexion muscle strength than controls . The decrease of muscle size and hip pain may contribute to the decrease of muscle strength in hip OA . Other possible underlying causes of the muscle weakness need to be studied OBJECTIVE To compare treadmill training with partial body-weight support ( TT-BWS ) and conventional physical therapy ( PT ) in ambulatory patients with hip arthroplasty . DESIGN R and omized controlled trial . SETTING Rehabilitation center . PARTICIPANTS Eighty patients with a fully loadable implant who could walk independently with crutches after unilateral total hip arthroplasty were r and omized to receive either TT-BWS ( treatment group ) or conventional PT ( controls ) , for 10 working days . INTERVENTIONS Each patient received 45 minutes of individualized PT , either treadmill training plus PT in the experimental or PT alone in the control group . MAIN OUTCOME MEASURES The Harris score , recorded by blind assessors , served as the primary outcome measure . Secondary outcome measures were the hip extension deficit , gait velocity , gait symmetry , affected hip abductor power ; hip abductor amplitude of electromyographic activation ; and the interval from surgery to ab and oning crutches . RESULTS At the end of training , the treatment group 's Harris score was 13.6 points higher ( P<.0001 ) than the control group 's score . Further , hip extension deficit was 6.8 degrees less ( P<.0001 ) , gait symmetry was 10 % greater ( P=.001 ) , affected hip abductor was stronger ( Medical Research Council grade s 4.24 vs 3.73 ; P<.0001 ) , and the amplitude of gluteus medius activity was 41.5 % greater ( P=.001 ) than those measures for controls . Gait velocity did not differ in the 2 groups . These significant differences in favor of the treatment group persisted at 3 and 12 months . The treatment group ab and oned crutches sooner than the control group ( 3 vs 8wk ) . In the treatment group , 39 patients finished treatment , 35 appeared at 3 , and 26 at 12 months for follow-up . In the control group , the corresponding numbers were 40 , 35 , and 24 patients , respectively . CONCLUSION TT-BWS is more effective than conventional PT at restoring symmetrical independent walking after hip replacement AIM Benefits of less damage of soft tissues and muscles in minimally invasive hip replacement lead to expectations of better results in gait rehabilitation . The aim of the study is to evaluate post-operative walking ability in terms of different surgical approaches . METHOD 16 patients underwent a minimally invasive total hip replacement ( MIS group ) and 16 other patients got a THA using a transgluteal approach ( st and ard group ) . Differences in functional indices of ground reaction forces and symmetry indices were measured one day pre-operatively as well as 8 , 14 and 28 weeks post-operatively . The results were compared between the surgical approaches and to an age-matched healthy control group . RESULTS There are significantly reduced pain symptoms and a higher functional ability in both surgical groups 8 weeks post-operatively . There are no differences in gait parameters between the surgical groups after 28 weeks . Trends in gait velocity , temporal parameters and in functional indices of ground reaction forces show advantages for the minimally invasive group 8 and 14 weeks post-operatively . Patients do not reach the age-matched control group . CONCLUSION Obviously the immediate post-operative advantages of minimally invasive hip replacement provide better chances for gait rehabilitation compared to the transgluteal approach . Due to the complexity of the problem clinical and gait analysis studies should be linked more closely This study examined the effect of the surgical approach used in total hip arthroplasty ( THA ) on gait mechanics six months following surgery . Quantitative gait analysis was performed on 29 subjects : 10 anterolateral ( A-L ) and 10 posterolateral ( P-L ) THA patients and nine able-bodied , velocity-matched subjects . Discriminant function analysis was used to determine the distinction of the groups with respect to sagittal plane hip range of motion , index of symmetry , trunk inclination , pelvic drop , hip abduction , and foot progression angles . The A-L group had the largest trunk inclination ( 3.0+/-2.4 degrees ) and the smallest hip range of motion ( 34.0+/-7.4 degrees ) . Both THA groups demonstrated greater asymmetry as expressed by the smaller symmetry index ( 0.97+/-0.04 for A-L and 0.98+/-0.05 for the P-L ) than the able-bodied group ( 0.99+/-0.01 ) . The classification procedure correctly classified 89 % of the control group cases , 90 % of the A-L cases , and 50 % of the P-L cases . These results support the conclusion that six months following surgery , the gait of the majority ( 85 % ) of THA patients has not returned to normal . The A-L patients displayed distinct gait patterns , while a small percentage ( 30 % ) of the P-L patients demonstrated normal gait . While these differences are statistically significant , the clinical significance is unknown and linked to the duration that they persist OBJECTIVE To compare gait patterns in patients with total hip arthroplasty ( THA ) and surface hip arthroplasty . DESIGN Observational study . SETTING Outpatient biomechanical laboratory . PARTICIPANTS Two groups of 10 surface hip arthroplasty and THA patients and 10 control subjects participated in the study ( N=30 ) . The patients were volunteers recruited from a larger r and omized study . INTERVENTIONS Not applicable . MAIN OUTCOMES MEASURES Gait patterns , hip abductor muscle strength , clinical outcomes , and radiographic analyses were compared between groups . RESULTS In the sagittal plane , the THA group showed a larger flexor moment and larger mechanical work in H2S and K3S power bursts compared with surface hip arthroplasty and control subjects . In the frontal plane , both THA and surface hip arthroplasty patients had smaller hip abductor muscles energy generation ( H3F ) than the control group . No difference was found for the hip abductor muscles strength . CONCLUSIONS In the THA group , the larger energy absorption in H2S and K3S would be a cost-effective mechanical adaptation to increase stability . The surface hip arthroplasty characteristics could allow the return to a more normative gait pattern compared with THA . The modification in the frontal plane in surface hip arthroplasty and THA would be related to the hip abductor muscles strength The hip-rating question naire was developed for the assessment of the outcome of total hip replacement . The purpose of this study was to evaluate its reproducibility , validity , and responsiveness . The question naire uses a 100-point scale in which equal weight is given to the domains of global or over-all impact of arthritis , pain , walking , and function . Ninety-eight patients were enrolled in the prospect i ve study and have been followed for at least three months ; sixty-two patients have been followed for six months ; and forty-two patients have been followed for one year . Reproducibility was tested with the use of the kappa statistic in fifty patients whose condition was stable clinical ly , and it was found to be good or excellent both for individual questions and for the total score . The validity of the question naire was assessed by comparison with the scores from a six-minute walking-distance test and arthritis impact-measurement scales . The result of the six-minute walking-distance test correlated with the patient 's response concerning walking distance on the hip-rating question naire . The score for pain from the hip-rating question naire correlated well with the score for pain from the arthritis impact-measurement scales , and the total score from the hip-rating question naire correlated well with the total score from the arthritis impact-measurement scales . The score on the hip-rating question naire was responsive to the change in the clinical condition of the patient , as indicated by a favorable index of responsiveness . The results of the question naire were sensitive enough to demonstrate differences among treatment groups with relatively small sample sizes . This question naire has the characteristics of a useful instrument for assessment of outcomes , such as that after an operation OBJECTIVE To quantify gait impairments in women with pregnancy-related pain in the pelvis which persisted post-partum . Design . Nine patients and nine healthy subjects were studied during treadmill walking at different velocities . BACKGROUND Walking problems in patients with pregnancy-related pain in the pelvis have been known to exist for a long time . To date , no quantitative gait studies have been conducted in this population . METHODS Maximum attainable walking velocity was determined , amplitudes of pelvic and thoracic rotations were calculated , and spectral analysis was used to assess the harmonicity of these rotations . Coordination between pelvic and thoracic rotations was characterized as mean relative Fourier phase and weighted coherence . RESULTS Maximum attainable walking velocity was highly variable between patients , but on average significantly lower than in healthy controls . Moreover , patients had a significantly lower mean relative Fourier phase ( again , highly variable ) and higher weighted coherence . The other parameters did not differ significantly between groups . CONCLUSIONS Coordination between pelvic and thoracic rotations in the transverse plane was affected in patients with pregnancy-related pain in the pelvis . Individual patients may apply different strategies during walking to cope with the underlying problems . RELEVANCE Pregnancy-related pain in the pelvis is poorly understood . Patients with this condition are known to have problems with locomotion . The present study reveals that gait coordination is altered . Theoretically , this underlines the importance of analysing coordination in pathological movement . Clinical ly , better underst and ing the gait problems of women with pregnancy-related pain in the pelvis may contribute to more appropriate treatments Purpose sPost arthroplasty gait analysis has up till now been performed on subjects walking slowly on flat ground rather than challenging them at faster speeds or walking uphill . We therefore asked : ( 1 ) Is there a measurable difference in the performance of hip resurfacing arthroplasty ( HRA ) and total hip arthroplasty ( THA ) limbs at patients ’ self-determined fastest walking speeds and steepest inclines ? and ( 2 ) Is there a relationship between the observed differences between the gait of HRA and THA implanted limbs and patient walking speeds and inclines . Methods In an ethically approved study we recruited patients with bilateral hip arthroplasties : one HRA and one THA . Nine subjects were assessed using an instrumented treadmill at a range of speeds and inclines by a blinded observer . The ground reaction forces of subjects were recorded and an age , sex and BMI matched control group was used for comparison . Results Increasing walking speed correlated strongly with between leg differences in weight acceptance ( r = 0.9 , p = 0.000 ) and push-off force ( r = 0.79 , p = 0.002 ) . HRA implanted limbs accepted significantly more weight at top walking speeds ( 1208 N ± 320 versus 1279 N ± 370 , p = 0.026 ) and pushed off with greater force when walking uphill ( 818 N ± 163 versus 855 ± 166 , p = 0.012 ) . HRA limbs more closely approximated to the gait of the normal control group . Conclusions Arthroplasty implants do have an impact on the gait characteristics of patients . Differences in gait are more likely to be evident when assessment is made at fast speeds and walking uphill . This study suggests that HRA may enable a more normal gait Although treatments for osteoarthritis of the knee are often directed at relieving pain , pain may cause patients to alter how they perform activities to decrease the loads on the joints . The knee-adduction moment is a major determinant of the load distribution between the medial and lateral plateaus . Therefore , the interrelationship between pain and the external knee-adduction moment during walking may be especially important for underst and ing mechanical factors related to the progression of medial tibiofemoral osteoarthritis . Fifty-three subjects with symptomatic radiographic evidence of osteoarthritis of the knee were studied . These subjects were a subset of those enrolled in a double-blind study in which gait analysis and radiographic and clinical evaluations were performed after a 2-week washout of anti-inflammatory and analgesic treatment . The subjects then took a nonsteroidal anti-inflammatory drug , acetaminophen , or placebo for 2 weeks , and the gait and clinical evaluations were repeated . The change in the peak external adduction moment between the two evaluations was inversely correlated with the change in pain ( R = 0.48 , p < 0.001 ) and was significantly different between those whose pain increased ( n = 7 ) , decreased ( n = 18 ) , or remained unchanged ( n = 28 ) ( p = 0.009 ) . Those with increased pain had a significant decrease in the peak external adduction ( p = 0.005 ) and flexion moments ( p = 0.023 ) . In contrast , the subjects with decreased pain tended to have an increase in the peak external adduction moment ( p = 0.095 ) and had a significant increase in the peak external extension moment ( p = 0.017 ) . The subjects whose pain was unchanged had no significant change in the peak external adduction ( p = 0.757 ) , flexion ( p = 0.234 ) , or extension ( p = 0.465 ) moments . Thus , decreases in pain among patients with medial tibiofemoral osteoarthritis were related to increased loading of the degenerative portion of the joints . Additional long-term prospect i ve studies are needed to determine whether increased loading during walking actually results in accelerated progression of the disease Patients with st and ard total hip arthroplasties may have reduced hip abduction and extension moments when compared with normal nonosteoarthritic hips . In comparison , patients after resurfacing total hip arthroplasty appear to have a near-normal gait . The authors evaluated temporal-spatial parameters , hip kinematics , and kinetics in hip resurfacing patients compared with patients with unilateral osteoarthritic hips and unilateral st and ard total hip arthroplasties . Patients with resurfacing walked faster ( average 1.26 m/s ) and were comparable with normals . There were no significant differences in hip abductor and extensor moments of patients with resurfacing compared with patients in the st and ard hip arthroplasty group . This study showed more normal hip kinematics and functionality in resurfacing hip arthroplasty , which may be due to the large femoral head OBJECTIVES The purpose s of this study were : ( 1 ) to identify the primary ( hip ) and secondary ( neighboring joints ) impairments during gait in subjects with a total hip arthroplasty total hip arthroplasty , ( 2 ) to determine which impairments persist when controlling for gait speed and ( 3 ) to study the relationships between primary and secondary impairments in order to describe the locomotor strategies used by these patients . DESIGN . This cross-sectional study compared the gait patterns of women with a total hip arthroplasty to those of healthy women . BACKGROUND . Several studies have reported residual hip impairments in the sagittal plane during gait after a total hip arthroplasty . There is , however , a substantial lack of knowledge in regard to the changes at the neighboring joints and in the other planes of movement . METHODS . Subjects have been examined during a gait laboratory testing session including the simultaneous recording of three-dimensional kinematics and ground reaction forces on one side , and bilateral activation of six lower limb muscles . RESULTS . A significant decrease of 20 % in the hip extensor moment of force during the early stance phase was correlated ( R(2)=43 % ) with a significant decrease of 14 % in gait speed . Moreover , a significant decrease of 59 % in the range of hip extension at the end of the stance phase was observed together with secondary impairments such as a significant increase in the anterior pelvic rotation , in knee flexion and in ankle dorsiflexion . Lastly , a significant increase in ipsilateral bending of the trunk during the single limb support on the operated limb was concomitant with a significant decrease in the hip abductor moment of force . CONCLUSIONS . The decrease in gait speed and the persistence of abnormal gait patterns one year after the total hip arthroplasty were associated respectively with a decrease in the hip extensor moment of force and with a decrease in the range of hip extension ( sagittal plane ) or in the hip abductor moment of force ( frontal plane ) . Relevance The data provided in this paper may serve as guidelines to establish rehabilitation programs design ed to restore optimal locomotor function Better functional outcome is believed by some to occur after hip resurfacing ( HR ) than conventional 28-mm total hip arthroplasty ( THA ) in young and active patients with hip osteoarthritis . However , the postulated superior outcome of HR over THA may simply be the result of a bias in patient selection or the use of a larger femoral head . We therefore asked whether HR would demonstrate superior functional outcome when compared with a THA with a large-diameter femoral head in a r and omized , double-blind study . Gait speed and postural balance evaluations , functional tests , and clinical data were analyzed preoperatively and at 3 , 6 , and 12 months after surgery . Gait speed was used as the primary outcome measure . Forty-eight patients were r and omized in the study and a third group of 14 healthy subjects served as controls . The gait speed and postural balance evaluations , the performance at most functional tests , and clinical scores were similar in HR and large-head THA groups at each followup period . The operated patients reached most control group values at 3 months postoperatively . By these measures , HR did not provide better clinical function over large-head THA.Level of Evidence : Level I , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence Minimally invasive ( MI ) total hip replacement ( THR ) supposedly provides improved ambulation in the immediate post-operative period . This study used a prospect i ve blinded design to analyse early post-operative walking ability using gait analysis . Seventeen patients were available for full analysis with nine having had the MI technique and eight having the st and ard incision ( SI ) technique . Patients were blinded as to the incision used , as were all physiotherapists and assessors . Differences in temporal-spatial variables and joint kinematics measured 1 day pre-operatively , 2 days post-operatively and 42 days ( 6 weeks ) post-operatively were compared between groups . There was no significant difference in velocity , step length of the affected or unaffected leg , stride length or stance phase duration between the MI and SI groups between any of the timepoints tested . There was no significant improvement in the gait kinematics of the MI group compared to the SI group either 2 days post-operatively or 6 weeks post-operatively . Contrary to previous studies , there was no improvement in early post-operative gait for those patients who received THR using the minimally invasive technique While total hip arthroplasty ( THA ) provides pain relief and restores mobility , gait anomalies persist even years after surgery . A muscle sparing surgical approach could result in better postoperative gait mechanics . Our purpose was to compare both the anterior muscle sparing approach and the direct lateral approach ( LAT ) to a matched control group by using three-dimensional motion analysis while performing stair ascent and descent tasks . Lower-limb kinematics and kinetics were recorded for 20 patients that had an anterior approach ( ANT ) , 20 that had a LAT , and 20 age- and weight-matched control participants . Patients were assessed on average 10 months after surgery . Compared to the control group , during stair ascent , the anterior group had reduced peak hip extension , peak hip flexion moment , and peak hip power . The lateral group had reduced peak hip abduction , hip frontal plane range of motion , and peak hip internal rotation . In stair descent , the anterior group had reduced peak hip flexion , peak hip abduction moment and internal rotation , as well as peak hip power . The lateral group had reduced peak hip flexion , peak knee extension moment , and peak hip power . Therefore , gait anomalies persist after THA for both approaches , which could be due to other factors such as preoperative gait adaptations UNLABELLED While others have reported short-term comparisons between various minimally invasive surgical ( MIS ) approaches to total hip arthroplasty ( THA ) and their conventional analogues , longer-term data is lacking , as is information indicating whether MIS approaches to THA provide a biomechanically complete recovery . Furthermore , different MIS approaches have not been compared . Our approaches of interest were a one-incision modified Watson-Jones , and a two-incision approach . HYPOTHESES ( 1 ) There are significant differences in gait recovery patterns between the two surgical groups and ( 2 ) THA subjects have significant differences in function one year after surgery compared to control subjects . To test these hypotheses , THA c and i date s ( n=26 ) were r and omized to receive one of these MIS approaches and evaluated preoperatively , and postoperatively at 3 weeks , and at 3 , 6 and 12 months . Evaluations included three-dimensional gait analysis and 24-hour step-counts . The same data were obtained from 25 control subjects . Recovery time-course was assessed using repeated measures ANOVA . T-tests were used to compare controls with the pooled group of THA subjects . We found no differences between the two THA surgical groups regarding the time-course of recovery ( p≥0.591 ) . Although recovery was statistically complete by 3 months postoperatively for all variables , there were significant differences from controls at 12 months . Most notably , the external hip adduction moment , which reflects hip abductor function , was more than one st and ard deviation below normal ( p<0.001 ) . THA subject inactivity could not explain the gait differences , since one year after surgery daily step counts were not significantly different from controls ( p=0.346 ) . More work is necessary to determine ways to improve biomechanical outcomes for today 's patients with high expectations for function and implant longevity BACKGROUND AND PURPOSE Low bone mass of the proximal femur is a risk factor for hip fractures . Exercise has been shown to reduce bone loss in older individuals ; however , the exercises most likely to influence bone mass of the proximal femur have not been identified . Net moments of force at the hip provide an indication of the mechanical load on the proximal femur . The purpose of this study was to examine various exercises to determine which exercises result in the greatest magnitude and rate of change in moments of force at the hip in older individuals . SUBJECTS AND METHODS Walking and exercise patterns were analyzed for 30 subjects ( 17 men , 13 women ) who were 55 years of age or older ( X = 65.4 , SD = 6.02 , range = 55 - 75 ) and who had no identified musculoskeletal or neurological impairment . Kinematic and kinetic data were obtained with an optoelectronic system and a force platform . Results . Of the exercises investigated , only ascending stairs generated peak moments higher than those obtained during level walking and only in the transverse plane . Most of the exercises generated moments and rate of change in moments with magnitudes similar to or lower than those obtained during gait . CONCLUSION AND DISCUSSION Level walking and exercises that generated moments with magnitudes comparable to or higher than those obtained during gait could be combined in an exercise program design ed to maintain or increase bone mass at the hip Objective : To investigate the correlation between objective and subjective evaluation of patients with total hip replacement . Design : Prospect i ve preliminary trial comparing the Western Ontario and McMaster University question naire ( WOMAC ) and gait analysis preoperatively and three months postoperatively . Setting : A German academic orthopaedic centre specializing in total hip replacement surgery . Subjects : Seventeen patients ( median age 70 years ) with hip osteoarthritis . Intervention : All patients had had a primary unilateral total hip replacement . Main measures : WOMAC question naire to assess self-perceived health status and gait analysis to determine objective gait parameters . Results : Performance of walking as well as subjective judgement of health status improved following surgery ( gait speed P = 0.0222 ; stride length P = 0.038 ; stance phase ratio P = 0.0466 ; WOMAC P < 0.0001 ) . However , the correlation between gait parameters and WOMAC was poor ( r = -0.27 or less ) . Correlation between changes of walking parameters and WOMAC was bad to good ( r = 0.01 to r = -0.72 ) . Conclusion : The WOMAC question naire might not reflect walking performance . The addition of gait analysis is recommended to gain objective information about the quality of gait The purpose of this study was to evaluate whether preoperative gait adaptations persist one year after THR in the same set of subjects . The hypothesis tested was that hip dynamic range of motion and peak external moments during walking return to normal after THR . Hip kinematics and kinetics were measured for 28 subjects before and one year after THR and compared to those of 25 subjects with radiographically normal hips . All THR subjects improved clinical ly after surgery with Harris hip scores improving from 33 - 85 ( average 53 ) to 61 - 100 ( average 95 ) ( sign test p<0.001 ) . Preoperatively dynamic hip range of motion ( ROM ) , and all peak external moments were reduced compared to normal ( Mann-Whitney p < or = 0.040 ) . Improvement was seen in the ROM and all but the frontal plane , and external rotation peak moments ( Friedman p < or = 0.023 ) . The preoperative and postoperative values of the ROM , and peak flexion , abduction and external rotation moments were all significantly correlated ( Spearman p<0.020 ) indicating a possible learned effect from before THR surgery . Postoperative THR subjects continued to have a significantly lower than normal ROM , and peak adduction and peak internal rotation moments ( Mann-Whitney p < or = 0.003 ) . Despite good to excellent clinical functional outcome , gait in THR patients does not return to normal by one year after surgery . Aggressive muscle strengthening is currently not emphasized after THR surgery . Some THR patients may benefit from more intensive rehabilitation before and after surgery The effect of total hip replacement on the health-related quality of life of patients who have osteoarthrosis was examined as part of a r and omized , controlled trial comparing femoral head prostheses that were inserted with or without cement . One hundred and eighty-eight patients were followed for three months : 179 of them , for six months ; 156 , for one year ; and ninety , for two years . The health-related quality of life was assessed with use of the Harris hip score , the Merle d'Aubigné hip score , the Sickness Impact Profile , the Western Ontario and McMaster University ( WOMAC ) Osteoarthritis Index , the McMaster -- Toronto Arthritis ( MACTAR ) Patient Preference Disability Question naire , and the time trade-off technique as a measure of utility . Patients also took the six-minute-walk test . The mean age of the patients in the study was sixty-four years ( range , forty to seventy-five years ) ; ninety-seven patients ( 53 per cent ) were men and ninety-four ( 50 per cent ) had a prosthesis inserted with cement . Only three of 188 patients refused to return for quality -of-life assessment s. There was significant improvement in all health-related quality -of-life measures and in the six-minute-walk test after the operation ( p < 0.01 for all items , except for the work dimension of the Sickness Impact Profile at three months [ p = 0.07 ] ) . Most of the improvement had occurred by three months postoperatively . ( ABSTRACT TRUNCATED AT 250 WORDS After hip arthroplasty , many patients continue to exhibit abnormal gait patterns . The purpose of this study was to compare the vertical ground reaction forces of a group of 27 individuals who have undergone hip arthroplasty with a group of 35 normal control subjects . Specific force measures were determined from vertical ground reaction forces collected on a treadmill instrumented with two force plates . Symmetry indices were calculated on both groups of subjects . First and second peak forces , loading rate , impulse , and stance time were significantly less , while time to first peak force was significantly greater on the affected leg of the hip arthroplasty subjects when compared to their unaffected leg , or to the control group . The hip arthroplasty group showed greater asymmetry of ground reaction forces than the control group did . Bilateral asymmetric limb loading persists well after unilateral hip replacement surgery . Ground reaction force measures have been shown to be an effective means of quantifying the antalgic gait of hip arthroplasty patients |
1,799 | 31,733,044 | Conclusion This study evaluated the survival impact of HPV infection in LSCC patients .
The OS of the HPV‐positive group was better than that of the HPV‐negative group in terms of short‐term survival . | Abstract Objective To evaluate the association of human papilloma virus ( HPV ) infection with prognosis , specifically overall survival ( OS ) and disease‐free survival ( DFS ) , in laryngeal squamous cell carcinoma ( LSCC ) patients . | BACKGROUND Oropharyngeal squamous-cell carcinomas caused by human papillomavirus ( HPV ) are associated with favorable survival , but the independent prognostic significance of tumor HPV status remains unknown . METHODS We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a r and omized trial comparing accelerated-fractionation radiotherapy ( with acceleration by means of concomitant boost radiotherapy ) with st and ard-fractionation radiotherapy , each combined with cisplatin therapy , in patients with squamous-cell carcinoma of the head and neck . Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer . RESULTS The median follow-up period was 4.8 years . The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving st and ard-fractionation radiotherapy ( 70.3 % vs. 64.3 % ; P=0.18 ; hazard ratio for death with accelerated-fractionation radiotherapy , 0.90 ; 95 % confidence interval [ CI ] , 0.72 to 1.13 ) , as were the rates of high- grade acute and late toxic events . A total of 63.8 % of patients with oropharyngeal cancer ( 206 of 323 ) had HPV-positive tumors ; these patients had better 3-year rates of overall survival ( 82.4 % , vs. 57.1 % among patients with HPV-negative tumors ; P<0.001 by the log-rank test ) and , after adjustment for age , race , tumor and nodal stage , tobacco exposure , and treatment assignment , had a 58 % reduction in the risk of death ( hazard ratio , 0.42 ; 95 % CI , 0.27 to 0.66 ) . The risk of death significantly increased with each additional pack-year of tobacco smoking . Using recursive-partitioning analysis , we classified our patients as having a low , intermediate , or high risk of death on the basis of four factors : HPV status , pack-years of tobacco smoking , tumor stage , and nodal stage . CONCLUSIONS Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer . ( Clinical Trials.gov number , NCT00047008 . Purpose Treatment of oropharyngeal squamous cell carcinoma ( OPSCC ) is evolving toward risk-based modification of therapeutic intensity , which requires patient-specific estimates of overall survival ( OS ) and progression-free survival ( PFS ) . Methods To develop and vali date nomograms for OS and PFS , we used a derivation cohort of 493 patients with OPSCC with known p16 tumor status ( surrogate of human papillomavirus ) and cigarette smoking history ( pack-years ) r and omly assigned to clinical trials using platinum-based chemoradiotherapy ( NRG Oncology Radiation Therapy Oncology Group [ RTOG ] 0129 and 0522 ) . Nomograms were created from Cox models and internally vali date d by use of bootstrap and cross-validation . Model discrimination was measured by calibration plots and the concordance index . Nomograms were externally vali date d in a cohort of 153 patients with OPSCC r and omly assigned to a third trial , NRG Oncology RTOG 9003 . Results Both models included age , Zubrod performance status , pack-years , education , p16 status , and T and N stage ; the OS model also included anemia and age × pack-years interaction ; and the PFS model also included marital status , weight loss , and p16 × Zubrod interaction . Predictions correlated well with observed 2-year and 5-year outcomes . The uncorrected concordance index was 0.76 ( 95 % CI , 0.72 to 0.80 ) for OS and 0.70 ( 95 % CI , 0.66 to 0.74 ) for PFS , and bias-corrected indices were similar . In the validation set , OS and PFS models were well calibrated , and OS and PFS were significantly different across tertiles of nomogram scores ( log-rank P = .003 ; < .001 ) . Conclusion The vali date d nomograms provided useful prediction of OS and PFS for patients with OPSCC treated with primary radiation-based therapy Purpose The aim of this prospect i ve case series study was to determine the prevalence of HPV-DNA , analyze the E6 mRNA expression , identify intra-type variation in the E6 oncogene in upper aerodigestive tract ( UADT ) squamous cell carcinoma ( SCC ) , and correlate the presence of HPV-DNA with several clinical parameters and outcome . Methods Frozen sample s of UADT-SCC were analyzed for the presence and characterization of HPV-DNA and RNA sequences by means of polymerase chain reaction ( PCR ) , reverse transcriptase-PCR , and direct sequencing of amplified products . Results HPV-DNA sequences were detected in 10 % of the tumors , all of which were typed as HPV-16 . Positivity for HPV-16 E6/E7 mRNA was observed in five of the eight HPV-positive tumors ( 62.5 % ) . The HPV-16 E6 L83V variant was present in five cases . Multivariate analysis identified a history of absence of smoking ( P = 0.009 ) as a predictor of HPV-positive tumor . No significant differences in overall and disease free survival curves were observed between patients with HPV-positive tumors and patients with tumors without detectable HPV-DNA . Conclusion Our findings support the etiological participation of HPV-16 in a subset of UADT-SCCs from patients lacking traditional risk factors . The potential prognostic significance of HPV-16 E6 L83V variant in HPV-16 positive UADT-SCCs should be more extensively investigated PURPOSE Although p16 protein expression , a surrogate marker of oncogenic human papillomavirus ( HPV ) infection , is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma ( OPSCC ) , its prevalence and significance have not been well established in cancer of the oral cavity , hypopharynx , or larynx , collectively referred as non-OPSCC , where HPV infection is less common than in the oropharynx . PATIENTS AND METHODS p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129 , 0234 , and 0522 studies were determined by immunohistochemistry ( IHC ) and in situ hybridization ( ISH ) . Hazard ratios from Cox models were expressed as positive or negative , stratified by trial , and adjusted for clinical characteristics . RESULTS p16 expression was positive in 14.1 % ( 12 of 85 ) , 24.2 % ( 23 of 95 ) , and 19.0 % ( 27 of 142 ) and HPV ISH was positive in 6.5 % ( six of 93 ) , 14.6 % ( 15 of 103 ) , and 6.9 % ( seven of 101 ) of non-OPSCCs from RTOG 0129 , 0234 , and 0522 studies , respectively . Hazard ratios for p16 expression were 0.63 ( 95 % CI , 0.42 to 0.95 ; P = .03 ) and 0.56 ( 95 % CI , 0.35 to 0.89 ; P = .01 ) for progression-free ( PFS ) and overall survival ( OS ) , respectively . Comparing OPSCC and non-OPSCC , patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC , but patients with p16-negative OPSCC and non-OPSCC have similar outcomes . CONCLUSION Similar to results in patients with OPSCC , patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC , and HPV may also have a role in outcome in a subset of non-OPSCC . However , further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting PURPOSE To determine the prognostic importance of p16 and human papillomavirus ( HPV ) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial . PATIENTS AND METHODS Patients with stage III or IV head and neck squamous cell cancer were r and omly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine . In this sub study , analyses were restricted to patients with oropharyngeal cancer . p16 was detected by immunohistochemistry , and HPV was detected by in situ hybridization and polymerase chain reaction . RESULTS Slides were available for p16 assay in 206 of 465 patients , of which 185 were eligible , and p16 and HPV were evaluable in 172 patients . One hundred six ( 57 % ) of 185 were p16-positive , and in patients evaluable for both p16 and HPV , 88 ( 86 % ) of 102 p16-positive patients were also HPV-positive . Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group ( ECOG ) performance status . p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival ( 91 % v 74 % ; hazard ratio [ HR ] , 0.36 ; 95 % CI , 0.17 to 0.74 ; P = .004 ) and failure-free survival ( 87 % v 72 % ; HR , 0.39 ; 95 % CI , 0.20 to 0.74 ; P = .003 ) . p16 was a significant prognostic factor on multivariable analysis ( HR , 0.45 ; 95 % CI , 0.21 to 0.96 ; P = .04 ) . p16-positive patients had lower rates of locoregional failure and deaths due to other causes . There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients ( HR , 0.33 ; 95 % CI , 0.09 to 1.24 ; P = .13 ) . CONCLUSION HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy Background : Following chemo-radiotherapy ( CCRT ) for human papilloma virus positive ( HPV+ ) locally advanced head and neck cancer , patients frequently undergo unnecessary neck dissection ( ND ) and /or repeated biopsies for abnormal PET-CT , which causes significant morbidity . We assessed the role of circulating HPV DNA in identifying ‘ true ’ residual disease . Methods : We prospect ively recruited test ( n=55 ) and validation ( n=33 ) cohorts . HPV status was confirmed by E7 RT-PCR . We developed a novel amplicon-based next generation sequencing assay ( HPV16-detect ) to detect circulating HPV DNA . Circulating HPV DNA levels post-CCRT were correlated to disease response ( PET-CT ) . Results : In pre-CCRT plasma , HPV-detect demonstrated 100 % sensitivity and 93 % specificity , and 90 % sensitivity and 100 % specificity for the test ( 27 HPV+ ) and validation ( 20 HPV+ ) cohorts , respectively . Thirty-six out of 37 patients ( test and validation cohort ) with complete sample s-set had negative HPV-detect at end of treatment . Six patients underwent ND ( 3 ) and repeat primary site biopsies ( 3 ) for positive PET-CT but had no viable tumour . One patient had positive HPV-detect and positive PET-CT and liver biopsy , indicating 100 % agreement for HPV-detect and residual cancer . Conclusions : We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis . HPV DNA post-treatment correlates with clinical response |
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