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11,700 | 23,235,648 | Albendazole may be of similar effectiveness to metronidazole , may have fewer side effects , and has the advantage of a simplified regimen . | BACKGROUND Giardiasis infection may be asymptomatic , or can cause diarrhoea ( sometimes severe ) , weight loss , malabsorption , and , in children , failure to thrive .
It is usually treated with metronidazole given three times daily for five to 10 days .
OBJECTIVES To evaluate the relative effectiveness of alternative antibiotic regimens for treating adults or children with symptomatic giardiasis . | We examined the therapeutic effects of albendazole compared to metronidazole in 120 patients with giardiasis in Hamdan . Patients were r and omized to receive albendazole ( 400 mg , once daily for 5 days ) or metronidazole ( 250 mg , 3 times a day for 5 days ) . Demographic data of the patients , results of stool examination for Giardia trophozoites before and after treatment , and drug side-effects were recorded . After treatment 6 ( 10.0 % ) of the albendazole group had trophozoites compared with 14 ( 23.3 % ) of metronidazole group ( P < 0.05 ) . Patients in the albendazole group had fewer side-effects while 43.3 % of the metronidazole group experienced a metallic taste and 35.0 % experienced loss of appetite . Albendazole is an easy , safe and effective treatment for giardiasis An open , r and omized study was carried out with 100 children to compare the efficacy and security of albendazole and metronidazole to eradicate Giardia lamblia . We included 100 patients in primary school age with giardiasis confirmed by parasitoscopic test who had not received treatment during the 2 previous months . A complete clinical study was performed . By using an aleatory code , the children were distributed in 2 groups : A and B. The clinical data was corroborated and the following tests were made : cell blood count , blood chemistry , direct and concentrated coproparasitoscopic study . Both groups were given an antiparasite treatment consisting of albendazole for group A or metronidazole for group B. Clinical , parasitological and blood controls were conducted before , during and after the treatment . A therapeutic efficacy of 94 % and 98 % for group A and B , respectively , was found . We concluded that albendazole and metronidazole are equally effective in a 5 days treatment period , but some undesirable effects may occur with metronidazole AIM To investigate the efficacy and tolerability of albendazole and metranidazole treatment in giardiasis . METHODS The open comparative r and omized trial was carried out prospect ively from December 1999 to July 2001 in Duzce City of Turkey . The diagnosis was based on the presence of signs and symptoms compatible with giardiasis including a positive stool examination of giardia cysts or trophozoite . Metranidazole group consisted of 29 patients and was given metranidazole 500 mg , three times a day for 5 d and albendazole group was consisted of 28 patients and was given albendazole 400 mg/d for 5 d. RESULTS There were no significant differences in demographical and therapeutical effects and patient 's compliance between both groups . But side effects were seen more in metranidazole group than in albendazole group . CONCLUSION Albendazole is as effective as metranidazole in adults ' giardiasis . Albendazole has less side effect potentials than metranidazole in the treatment of giardiasis Therapy with metronidazole is the recommended option in giardiasis . However , some clinical trial reports suggest the appearance of drug resistance to explain therapeutic failure . Several investigations have been carried out on the effect of probiotic microorganisms for preventing or treating gastrointestinal diseases , but little is known about their efficacy against protozoal infections . The principal objective of our study was to evaluate the efficacy of Saccharomyces boulardii against Giardia lamblia infections . A double-blind , placebo-controlled study was carried out on adult patients with giardiasis . Group 1 ( 30 patients ) included metronidazole 750 mg 3 times daily along with S. boulardii capsules ( 250 mg b.i.d . orally ) for 10 d while group 2 ( 35 patients ) was treated with metronidazole 750 mg 3 times daily and with empty capsules as placebo for 10 d. Patients were re-examined at 2 and 4 weeks after treatment , and stool examinations were performed . At week 2 , G. lamblia cysts were detected in 6 cases ( 17.1 % ) of group 2 and none in group 1 . At the end of the fourth week , presence of the cysts continued in the same 6 cases in group 2 ( control group ) . These findings indicated that S. boulardii may be effective in treating giardiasis when combined with metronidazole therapy Giardia lamblia is a flagellate protozoan that produces symptoms by infecting the small bowel and biliary tract in the trophozoite form . Diagnosis is currently established by microscopic visualization of the organism in appropriate intestinal contents ( stool , small-bowel contents , or biopsy specimen ) . Adult patients with diarrhea and one or more enteric symptoms may be enrolled in clinical trials of new drugs for the treatment of giardial disease . A r and omized , double-blind , active-concurrent-control design is recommended . Post hoc stratification by age , immune status , chronicity of disease , and ease of establishing diagnosis ( organism load ) may be performed . Microbiological assessment 48 hours to 7 days after the completion of therapy is paramount for determining final outcome Fifty-five patients , 51 males and 4 females heavily infected with Giardia lamblia were treated with a single 2 g dose of tinidazole ( four tablets ) ; 53 were cured . Of 20 other infected patients kept under the same conditions and given four placebo tablets , 18 continued to pass cysts or trophozoites in the stools during the whole 3- to 4-wk follow-up period in hospital . There were no side effects attributed to the drug The efficacy of single-dose ornidazole versus seven days metronidazole in the treatment of giardiasis was tested in a r and omized study of 75 Kibbutzim children in Israel . All the children treated were clinical ly cured , and the parasites disappeared from stool examinations after the first follow-up . By the end of the study ( 21 days after the beginning of treatment ) , all the patients remained free of symptoms , but cysts ofGiardia lamblia were found in the stools of three children from the ornidazole group ( p=0.24 ) . The possibility of treatingGiardia lamblia with ornidazole in a single dose , with results similar to those obtained with a seven-day course of metronidazole , makes this drug a good alternative in the treatment ofGiardia lamblia in children , especially if compliance is not assured One hundred children were entered into a r and omized study to compare the efficacy and safety of furazolidone and metronidazole when given in liquid suspension for treatment of giardiasis . The study was conducted between May 1985 and February 1986 . Dosages were calculated on the basis of body weight , and treatment lasted 10 days . Clinical diagnosis of giardiasis was confirmed by the presence of Giardia cysts in stools . Children were excluded from the study if stool culture was positive for pathogenic bacteria . Eighteen of the 100 children were withdrawn from the study because of noncompliance with the protocol . Of the 82 remaining patients , 37 received furazolidone and 45 metronidazole . No statistically significant differences in efficacy between treatments were found . With the exception of one case of urticaria , which occurred in a patient who received metronidazole , both drugs were well tolerated . In this study , furazolidone and metronidazole were equally safe and effective in treating children with giardiasis A r and omized controlled trial was carried out to study the efficacy of combined albendazole and praziquantel in the treatment of giardiasis in school-age children . Eighty-four children were r and omly allocated to 3 groups : group 1 ( n = 31 ) albendazole 400 mg combined with praziquantel 20 mg/kg ; group 2 ( n = 26 ) albendazole 800 mg as a single dose ; group 3 ( n = 27 ) tinidazole 50 mg/kg as a single dose . The treatment was considered curative when Giardia was not found in two consecutive stool sample s. The parasitological cure rate was 74.2 % for combined single-dose albendazole-praziquantel , 50 % and 92.6 % in the albendazole and tinidazole groups respectively ( p = 0.0023 ) . There was no statistically significant difference between the cure rates of the combined regimen and tinidazole ( p > 0.05 ) . This combined regimen was considered safe , with only minor side-effects being observed . Of the single-dose regimens , tinidazole still achieves the highest parasitological cure rate for giardiasis . The albendazole-praziquantel combined regimen may be an alternative single-dose therapy for giardiasis in children , especially as this combination will eradicate common intestinal protozoa and co-existing helminths . Whether the dosage of this combination treatment should be adjusted for G. intestinalis remains to be established by further study The therapeutic effects of quinacrine ( Atabrine ) and metronidazole ( Flagyl ) were compared in a 3-year prospect i ve study of 160 infants and children ( 86 boys and 74 girls ranging in age from 4.5 months to 13 years ) with giardiasis . The most common symptom was recurrent abdominal pain . In each study group stool examinations were done 5 days , 1 month , and 6 months after treatment . There were no treatment failures with metronidazole , whereas four of those treated with quinacrine had positive stools 5 days after treatment , indicating possible failure . There were no recurrences at 1 month ; after 6 months , however , Giardia infection was found in 13 % of both treatment groups . These recurrences were seen mainly in children from families with other infected members . Considering the low failure rate , the minimal side effects , and the relatively more tolerable flavor , metronidazole seems to be preferrable in the treatment of giardiasis . A dosage of 15 - 25 mg/kg a day for 5 days is recommended The adverse effects and treatment failures to some of the currently recommended drugs for giardia infection have given rise to the need for alternative antigiardial agents . In an open , r and omized parallel group study , the safety and efficacy of albendazole was compared with that of metronidazole for the treatment of giardiasis in children . Sixty two children aged between 2 - 12 years were r and omized to receive either albendazole suspension 400 mg daily for 5 days or metronidazole suspension 7.5 mg/kg thrice daily for 5 days . The mean days required for cure , as evident by absence of cysts and /or trophozoites in the stool specimen , was 3.7 + 1.4 and 4.5 + 1.1 days , respectively for children on albendazole and metronidazole therapy . Six children on metronidazole therapy developed anorexia 2 to 4 days after the treatment . Albendazole proved as effective as metronidazole in the treatment of giardia infection in children with the added advantage of absence of anorexia 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 . The protozoan parasite Giardia lamblia is a major cause of waterborne enteric disease worldwide . Lectins are proteins that bind to carbohydrate ( sugar ) moieties . Potential targets for lectins are found on the surface of most single-celled organisms . Modest concentrations of wheat germ agglutinin ( WGA ) have been shown to inhibit G. lamblia excystation and trophozoite growth in vitro and can reduce cyst passage in mice infected with the closely related protozoan parasite , G. muris . Commercial preparations of wheat germ ( WG ) contain 13 - 53 microg of WGA per gram . We performed a double-masked , placebo-controlled study of dietary supplementation with WG in 63 subjects with giardiasis in Montreal and Lima ( 25 asymptomatic patients passing cysts ; 38 patients with symptoms ) . Asymptomatic subjects received WG ( 2 g , 3 times a day ) or placebo ( cornstarch , 2 g , 3 times a day ) for 10 days , followed by metronidazole ( 250 mg 3 times a day ) for 7 days . Symptomatic subjects received metronidazole ( 250 mg 3 times a day ) plus either WG or placebo for 7 days . Stool specimens were collected every day ( Montreal ) or every other day ( Lima ) for 10 days and on Day 35 for microscopic examination and coproantigen determination . Subjects kept a diary of symptoms for 10 days after recruitment . In asymptomatic subjects , both cyst passage and coproantigen levels were reduced by approximately 50 % in those taking WG compared with the placebo group ( P < 0.01 and P = 0.06 , respectively ) . In symptomatic subjects , cyst passage and coproantigen levels fell precipitously in response to metronidazole therapy , and there were no clinical ly important differences between those receiving supplemental WG or placebo . However , symptoms appear to have resolved more rapidly in the subjects taking WG in addition to metronidazole . The WG supplement was well tolerated in both symptomatic and asymptomatic subjects . These data suggest that components of WG , possibly WGA , either alone or in combination with antiprotozoal agents , can influence the course of human giardiasis The efficacy of albendazole for the treatment of giardiasis has been indicated by previous in-vitro and in-vivo studies . In order to compare the therapeutic efficacy of albendazole and metronidazole , 107 Giardia-positive children ( aged 3 - 15 years ) , diagnosed by three consecutive positive stool examinations , were enrolled in the study . Of these children , 52 were given a single daily dose of albendazole 10 mg/kg for 5 days , and 55 were given metronidazole 20 mg/kg daily in three doses for 7 days . Parasite eradication was achieved in 47 ( 90.4 % ) of 52 children treated with albendazole and 49 ( 89.1 % ) of 55 children treated with metronidazole ( p > 0.05 ) . These results suggest that albendazole is an effective treatment option for childhood giardiasis The adverse effects and treatment failures to some of the currently recommended drugs for giardia infection have given rise to the need for alternative antigiardial agents . In an open , r and omized parallel group study , the safety and efficacy of albendazole was compared with metronidazole for the treatment of giardiasis in children . Sixty four children of age ranging from 2 - 12 years was r and omized to receive either albendazole suspension 400 mg daily for 5 days or metronidazole suspension 400 mg daily for 5 days or metronidazole suspension 7.5 mg/Kg thrice daily for 5 days . The mean days required for cure , as evident by absence of cysts and /or trophozoites in the stool specimen , were 3.7 + /- 1.4 and 4.5 + /- 1.1 days , respectively for children on albendazole and metronidazole therapy . Six children on metronidazole therapy developed anorexia 2 to 4 days after the treatment . Albendazole proved as effective as metronidazole in the treatment of giardia infection in children with the added advantage of the absence of anorexia 50 patients with giardiasis were treated with either metronidazole or tinidazole in r and om order according to a code . 25 patients received 2.0 g metronidazole on 2 consecutive days ; 19 were cured ( 76 % ) ; 7 patients complained of mild side-effects . 25 patients received tinidazole 2.0 g as a single dose , and 22 were cured ( 88 % ) ; 5 patients complained of mild side-effects . The difference between the results of the two regimens was not statistically significant . A 1-week course of metronidazole ( 200 mg 3 times daily ) was successful in 8/9 failures ; 1 patient was finally cured with mepacrine This study describes a prospect i ve , r and omized , clinical trial in patients infected with the protozoa Giardia lamblia . Patients received a 10-day treatment with twice a day doses of either 120,000 U ( USP ) of bacitracin zinc , 120,000 U ( USP ) of bacitracin , 120,000 U ( USP ) of neomycin , or 60,000 U ( USP ) of bacitracin zinc and 60,000 U ( USP ) of neomycin . At the first assessment ( day 11 ) , all 21 subjects ( 100 % ) treated with bacitracin zinc had ceased to show Giardia parasites in their stools compared with 19 ( 95 % ) of 20 receiving bacitracin , 20 ( 90.9 % ) of 22 subjects receiving neomycin , and 17 ( 89.5 % ) of 19 subjects receiving bacitracin zinc plus neomycin . During the two-week follow up period , one ( 5.3 % ) of the 19 subjects examined who received bacitracin zinc experienced a recurrence compared with one ( 6.7 % ) of 15 receiving bacitracin , one ( 5.0 % ) of 20 receiving neomycin , and 0 ( 0 % ) of 14 receiving the combination treatment . Final cure rates of 94.7 % for bacitracin zinc , 87.5 % for bacitracin , 86.4 % for neomycin , and 87.5 % for bacitracin zinc plus neomycin were obtained . No synergistic activity was noted between bacitracin zinc and neomycin . Side effects were generally limited to nausea , abdominal discomfort , and diarrhea in a small number of patients This study was design ed to compare the treatment efficacy of single dose of ornidazole with 5 d treatments of ornidazole and metronidazole in children with giardiasis . 175 children , between 2 and 15 y old , whose stool sample s were found to be positive for Giardia lamblia cysts and /or trophozoites by either saline-Lugol , formalin-ethyl acetate or trichrome staining , were enrolled in the study . Of these children , 105 were treated with a single dose of ornidazole : 35 with 30 mg/kg , 35 with 25 mg/kg and 35 with 20 mg/kg ; 35 were treated with 25 mg/kg per day of ornidazole for 5 d in 2 doses and 35 children were treated with 20 mg/kg per day metronidazole for 7 d in 3 doses . All cases were examined on the 7th , 10th and 14th days after treatment by the same methods ; clinical symptoms were also evaluated . Giardia lamblia was eradicated in 34 of 35 ( 97 % ) , 34 of 35 ( 97 % ) and 33 of 35 ( 94 % ) patients treated with 30 , 25 and 20 mg/kg single doses of ornidazole , respectively . Eradication was achieved in all 35 patients treated with 25 mg/kg per day ornidazole for 5 d and in 31 of 35 ( 89 % ) patients treated with metronidazole . There was no statistically significant difference among doses of ornidazole ( p > 0.05 ) ; however , all ornidazole treatment regimens were significantly more effective than metronidazole treatment ( p < 0.05 ) . No important side-effects were detected in any patients and clinical symptoms disappeared in all . Single-dose ornidazole treatment could be considered as a proper and effective alternative method for the treatment of giardiasis in children Giardiasis and soil-transmitted helminthosis are prevalent in many parts of the world . Application of a single drug for treatment of both giardiasis and soil-transmitted helminthosis is highly desirable . One hundred children of both sexes , ranging from 7 to 12 years old with Giardia intestinalis cysts or trophozoites in their stool sample s , were r and omly separated into two groups of 50 individuals each . Each group received either mebendazole tablets 200 mg thrice daily for 5 days or metronidazole tablet 15 mg/kg/day in three divided doses , for 7 days . The results were evaluated by microscopic examination of stools on two successive occasions : 1 week and 2 weeks after treatment . Each occasion consisted of three stool examination on 3 successive days . The cure rate of mebendazole-treated children was 43 out of 50 ( 86 per cent ) , and for metronidazole it was 45 out of 50 ( 90 per cent ) with no statistical difference between the two groups . No side-effects were observed in the mebendazole-treated group , whereas nausea , anorexia and metallic taste were observed in 4.9 , 6 and 24 per cent of metronidazole-treated children , respectively . In conclusion , the use of mebendazole , which is less toxic with no side-effects , is available and effective on Giardia intestinalis as well as intestinal nematodes , is recommended especially in the areas where giardiasis and intestinal nematodiasis are prevalent and overlap Sixty-three expatriate residents and travellers in Bangladesh , infected with Giardia lamblia , participated in two studies to compare the therapeutic efficacy of tinidazole and metronidazole . In the first trial 33 r and omly selected patients were treated with tinidazole ( 50 mg/kg of body weight to a maximum of 2 g ) or metronidazole ( 60 mg/kg of body weight to a maximum of 2.4 g ) in a single oral dose . Patients were followed for 4 weeks after the end of therapy for the presence of G. lamblia in their stools . Sixteen ( 94 % ) of 17 patients receiving tinidazole were free of G. lamblia during that period , compared to only 9 ( 56 % ) of 16 patients who had received metronidazole ( P less than 0.02 ) . In the second trial patients were r and omly allocated to a treatment schedule of either metronidazole as a single dose on 3 successive days ( 50 mg/kg of body weight to a maximum of 2 g daily ) or tinidazole as a single oral dose ( 50 mg/kg of body weight to a maximum of 2 g ) . All 15 patients treated with tinidazole and 14 ( 93 % ) of 15 patients treated with metronidazole were free of G. lamblia during the 4-week follow-up period . A single oral dose of tinidazole is a highly effective treatment for giardiasis and is equal in efficacy to a 3-day therapy with metronidazole Twenty patients with intestinal giardiasis , already resistant to 3 - 5 previous courses of oral metronidazole , were r and omly distributed into 2 different groups : 10 subjects were given oral albendazole ( 440 mg/two times per day for 7 days ) and 10 were su bmi tted to the association of albendazole ( 400 mg/two times per day for 7 days ) plus metronidazole ( 250 mg/three times per day for 7 days ) . All patients were evaluated both for clinical and parasitological status , immediately before and after therapy and , then , 4 weeks later . Only 3 patients of those treated with albendazole alone , showed a clinical and parasitological remission at the end of therapy , and one of them relapsed 4 weeks later . All patients who underwent albendazolemetronidazole association responded to the therapy and all except one were defined as " cured " 4 weeks later . Our study demonstrates that albendazole alone is not an effective therapeutic alternative for " metronidazole-resistant " giardiasis . The association of metronidazole plus albendazole seems synergic and deserves further studies Enteric infection by Giardia intestinalis is a common cause of diarrhoea world‐wide and a significant cause of morbidity in children A retrospective review of adenoviral infection in pediatric liver transplant recipients was done at Children 's Hospital of Pittsburgh to define its epidemiology and clinical importance . Medical records of patients with adenovirus were review ed and data collected regarding clinical course , microbiologic studies , biopsy results , immunosuppression , concurrent infections , and outcome . Of 484 liver transplant recipients , 49 had 53 episodes of adenoviral infection . The most common sites of adenoviral infection were the liver , lung , and gastrointestinal tract . Serotypes 1 , 2 , and 5 were recovered most often ; type 5 was commonly associated with hepatitis . Invasive adenoviral infection occurred in 20 children , leading to death in 9 . Median time from transplantation until isolation of adenovirus was 25.5 days . This timing suggests either reactivation or donor-associated transmission . Prospect i ve studies using molecular epidemiologic techniques will be helpful in evaluating transmission patterns of adenovirus in this population OBJECTIVES After a large waterborne outbreak of Giardia infection in Bergen , some patients experienced persisting abdominal symptoms despite metronidazole treatment . This study aim ed at investigating possible causes for their symptoms . METHODS Over a 15 month period , 124 referred patients were evaluated in a prospect i ve cohort analysis with a st and ardised investigation including duodenal biopsies and aspirate , blood tests and faecal parasite and calprotectin tests . Recovered subjects were recruited for symptom analysis . RESULTS Persisting Giardia duodenalis infection was found in 40 patients ( 32.3 % ) . Duodenal biopsies showed signs of inflammation in 57 patients ( 47.1 % ) . Microscopic duodenal inflammation was present in 34 ( 87.2 % ) of the Giardia positive and 23 ( 28.0 % ) of the Giardia negative patients . There were significant associations between persistent Giardia positivity , microscopic duodenal inflammation and a positive calprotectin test . Duodenal aspirate and duodenal biopsies performed poorly in diagnosis of persistent giardiasis . CONCLUSIONS In patients with persisting symptoms after metronidazole treated Giardia infection we commonly found chronic Giardia infection and microscopic duodenal inflammation , especially in illness duration less than 7 months . Both these findings subsided over time . Increasingly , investigations could not determine a definite cause for the persistent symptoms . The very long-term post-giardiasis diarrhoea , bloating , nausea and abdominal pain documented here need further study Summary Sixty patients with parasitologically confirmed giardiasis were treated with metronidazole using four different regimens administered to four groups of 15 patients each . A seven-day course of 200 mg thrice daily successfully eliminated the organism in 11 patients . A repetition of the seven-day course after an interval of one week was successful in 14 patients , a single dose of 2400 mg in nine patients , and two 2400 mg doses on successive days in 12 patients . Late relapses , detected more than one month after therapy , were relatively common in the single-dose groups . Side-effects associated with the 2400 mg dosages were frequent but tolerable . ZusammenfassungSechzig Patienten mit parasitologisch bestätigter Lambliasis wurden mit Metronidazol beh and elt , wobei vier verschiedene Dosierungsschemen bei vier Gruppen von je 15 Patienten zur Anwendung kamen . Eine 7tägige Beh and lung mit 200 mg dreimal täglich führte bei 11 Patienten zu erfolgreicher Beseitigung des Parasiten . Eine Wiederholung der 7tägigen Beh and lung nach einwöchigem Intervall führte bei 14 Patienten zum Erfolg . Eine Einzeldosis von 2400 mg bei 9 Patienten sowie zwei Dosen von 2400 mg an zwei aufein and erfolgenden Tagen bei 12 Patienten waren ebenfalls erfolgreich . Spätrezidive , die länger als einen Monat nach der Beh and lung entdeckt wurden , traten in den mit Einzeldosen beh and elten Gruppen relativ oft auf . Die mit den Dosierungen von 2400 mg einhergehenden Nebenwirkungen waren häufig , jedoch erträglich Abstract Background : Albendazole ( ABZ ) is a benzimidazole carbamate compound currently in use for human medical practice against enterobiasis and soil-transmitted helminthiasis ( STH ) ; However , its spectrum of activity is broad and goes beyond these infections . Objective : This study compares the efficacy and safety of ABZ versus metronidazole ( MTZ ) in human giardiasis . Research design and methods : A r and omized , double-blind , clinical trial was carried out at the Centre of Hygiene , Epidemiology and Microbiology in Matanzas City , Cuba . Adult patients with confirmed symptomatic G. duodenalis mono-infection were r and omly assigned to receive either ABZ [ 400 mg daily ( n = 75 ) ] or MTZ [ 250 mg t.i.d . ( n = 75 ) ] , both for 5 days . Follow-up fecal sample s were obtained at 3 , 5 , 7 days after treatment end . Results : The efficacy was similar for both treatment groups : ABZ ( 82.6 % ) and MTZ ( 85.3 % ) ; p > 0.05 . Side-effects including bitter taste , headache , vomiting and dizziness were significantly higher in the MTZ group . Abdominal pain was significantly higher in ABZ group . Conclusion : ABZ was found as effective as MTZ in the treatment of G. duodenalis infections in adult patients from Cuba and could be a useful drug in areas where co-infection with STH infections is common One hundred children suffering from symptomatic giardiasis were treated with either tinidazole or metronidazole in r and om order . Both the drugs were given as a single oral dose calculated on the basis of 50 mg/kg body weight . Parasitological and clinical cure was obtained in 40 ( 80 % ) of 50 patients given tinidazole and in 18(36 % ) of 50 patients given metronidazole . This difference in cure rates was significant ( p less than 0.01 ) . Furthermore , control of diarrhoea and negative stool conversion for G. lamblia were achieved earlier with tinidazole than with metronidazole , the differences being significant ( p less than 0.01 ) from the 8th post-treatment day . Gastro-intestinal side-effects of mild degree occurred in 6 patients on tinidazole and in 2 patients on metronidazole ; they comprised nausea , vomiting , and bitter taste . Neither drug caused any abnormal deviation in blood counts or in biochemical tests of liver and kidney function Between July and October 1987 an outpatient study of 191 children with acute diarrhea was undertaken in two rural communities in Mexico . Through a double-blind r and omization we compared the efficacy of a combination therapy of furazolidone , 7.5 mg/kg/day , plus st and ard oral rehydration therapy ( ORT ) ( 96 patients ) versus a placebo plus ORT ( 95 patients ) , each given for 5 days . Diarrheal stool sample s were collected from all patients before therapy . By means of a two-vial transport media system the sample s were sent to a university laboratory and examined for viral , bacterial , and parasitic organisms . The most commonly isolated organisms were enterotoxigenic Escherichia coli ( 13 % ) and Giardia lamblia ( 13 % ) . Patients who received furazolidone plus ORT showed a greater reduction in duration of diarrhea when compared with those receiving placebo plus ORT ( 63.4 h versus 71.44 h ) . There was also a trend toward shorter duration of diarrhea in patients with Giardia who were treated with furazolidone/ORT compared with Giardia patients in the placebo/ORT group . When fecal leukocytes were present in the stool , the furazolidone/ORT-treated patients had a significantly higher percentage of clinical cures ( 79 % versus 54 % , p = 0.03 ) and an overall shorter duration of diarrhea ( 62.0 h versus 80.6 h , p = 0.055 ) at the end of 5 days of therapy than did the placebo/ORT-treated group The aim of the study was to test new treatment protocol s for giardiasis , which are less toxic , cheaper , and easier to use than the conventional treatment . 48 children who had been diagnosed as having giardiasis in a health-screening program involving 2 schools , were r and omized to receive four different treatment protocol s. The children were split into 4 treatment groups : I , mebendazole 100 mg t.i.d . for 1 day ; II , mebendazole 100 mg t.i.d . for 7 days ; III , metronidazole 15 mg/kg as one dose for 7 days ; and IV , ornidazole 40 mg/kg as a single dose . The results were evaluated by microscopic examination of stools . The responses to the treatments revealed that the effectiveness of ornidazole was 100 % , metronidazole 92.9 % , mebendazole for 7 days 58.3 % , and mebendazole for 1 day 41.7 % . Minor side-effects were seen in only 3 children receiving ornidazole : 1 had urticaria , while the other 2 suffered from vertigo and nausea . The results of this study show that ornidazole as a single dose can be used as an alternative protocol for treating giardiasis . Further studies should be done to determine the safest effective total single dose Metronidazole , tinidazole and ornidazole were compared in patients treated for Entamoeba histolytica or Giardia lamblia intestinal infections . Only patients with three positive stool specimens for trophozoites and /or cysts of E. histolytica or G. lamblia by the merthiolate iodine formaldehyde ( MIFC ) technique were included . Criteria for cure were at least 10 negative stool specimens over 3 weeks after completing therapy . Fifty-three male patients ( aged 9 - 65 years ) had E. histolytica infection . Seventeen received metronidazole ( 1.5 g daily for 10 days ) , 18 tinidazole ( 1.5 g daily for 10 days ) and 18 ornidazole ( 1 g daily for 10 days ) . Metronidazole yielded 88 % , tinidazole 67 % and ornidazole 94 % cure rates . Side reactions were minor . Eighty patients had G. lamblia infection , of whom 20 received metronidazole ( 0.5 g daily for 10 days ) , 30 tinidazole ( single 2 g dose ) and 30 ornidazole ( single 1 g dose ) . Cure rates were 95 % for metronidazole , 90 % for tinidazole and 97 % for ornidazole with no side reactions Forty-five patients with parasitologically confirmed symtomatic giardiasis were treated with tinidazole . A course of 150 mg twice daily for 7 days cured 14 of 19 patients ( 74 % ) , and a single dose of 2,000 mg cured 24 of 26 ( 92 % ) . After the single dose , mild side effects were common including maltase , lassitude , and dizziness . Three probable cases of the so-called " postgiardiac syndrome " were seen . Either dosage of tinidazole initially cleared all stool sample s of Giardia lamblia , and most clinical and parasitological failures were first detected a few weeks after the treatment . This emphazises the significance of long follow-up periods In Honduras , one of the leading causes of morbidity and mortality among children is diarrhoea , but little is known about its aetiology and risk factors . A prospect i ve longitudinal study of 266 children over a 12 month period in 2 rural villages and a marginal barrio revealed attack rates of 7 episodes per child per year among those less than 36 months of age . The most common parasite was Giardia lamblia , found in 61 % of the children and in 29 % of 848 episodes of diarrhoea . Chronic diarrhoea was noted in 46.6 % of the children and 81 % of them were infected with G. lamblia . Multiple infections with 5 - 10 different species of parasites or commensals were common ( 47 % ) ; no parasites or commensals were found in 17 children ( 6.4 % ) . No case of acute amoebic dysentery was diagnosed either clinical ly or parasitologically , although 20 % of the children had cysts of E. histolytica in the stools . Other potential parasitic pathogens identified were Cryptosporidium sp. ( 6.7 % ) , Hymenolepis nana ( 8 % ) , and Strongyloides stercoralis ( 2.6 % ) . Dientamoeba fragilis was found in iron haematoxylin smears for the first time in Honduras . Important risk factors recognized included high faecal contamination of the environment , lack of potable water , education and housing in the midst of poverty . The marginal barrio was more affected than the rural villages . Should these factors not be changed or modified , diarrhoea caused by infectious agents will remain an endemic life-threatening problem A r and omized controlled trial , 113 school children with Giardia intestinalis infection were treated with albendazole or tinidazole . Albendazole 400 mg once a day x 3 days and tinidazole 50 mg/kg single dose were given orally to 62 and 51 children , respectively . Parasitological cure was documented when there were > or = 2 times negative stool examination for G. intestinalis at 1 - 2 weeks after therapy . Thirty-one of 62 ( 50 % ) children treated with albendazole and 49 of 51 ( 96.1 % ) children treated with tinidazole had parasitological cure ( p < 0.001 ) . No major side effects were observed except one case in tinidazole group had severe headache for 30 hours . Albendazole appears to be safe and produced a moderate cure rate for G. intestinalis infection when a 3 day anthelmintic regimen is given One hundred and twenty four children with symptomatic and parasitologically confirmed giardiasis were treated in a comparative trial . The dosage of antigiardia drug was adjusted to the body surface area of the patients from the adult basic dosage as 100 mg of quinacrine t.i.d . for 5 days , 200 mg of metronidazole t.i.d . for 7 days , 2 gm of metronidazole once , 2 gm of tinidazole once or 2 gm of ornidazole once . They were hospitalized for follow-up for 30 days . The parasitological follow-up consisted of daily examination of stool specimens . Reinfections were unlikely . The rates of success were : a 5-day course of quinacrine , cured all of them , 20 patients ; a 7-day course of metronidazole , 12 of 20 ; metronidazole , single dose , 11 of 21 ; tinidazole , single dose , 18 of 21 ; ornidazole , single dose , 21 of 22 ; placebo , none of 20 . After a single dose , 5 patients had transient elevation of transaminases , one patient in each of metronidazole and tinidazole group 3 patients in ornidazole group . A 5-day course of quinacrine gave excellent result but the drug is not widely marketed . Ornidazole or tinidazole were more effective , both of them were recommended as a drug of choice as single dose therapy , however transient increase of transaminases may occur in some cases 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 Summary In r and om order , a single dose of either tinidazole or metronidazole , calculated as 50mg/kg body weight , was given to 100 children with symptomatic giardiasis . Follow-up was done for 16 days and consisted of 4 clinical , parasitological and biochemical assessment s at intervals of 4 days . The actual mean dose of the drugs received by the patients was 55.5mg/kg of tinidazole and 52.0mg/kg of metronidazole . Success , i.e. parasitic clearance and symptomatic relief was achieved in 80 % of patients given tinidazole as opposed to 36 % of patients given metronidazole ( p < 0.01 ) . Moreover , control of diarrhoea and negative stool conversion for G. lamblia occurred earlier with tinidazole than with metronidazole ( p < 0.01 ) . The incidence of gastrointestinal side-effects was 12 % for tinidazole and 4 % for metronidazole . Neither drug caused any abnormality of the blood count , blood urea , urine analysis or liver function tests OBJECTIVE To evaluate the epidemiology of Giardia lamblia infection , investigate factors which might be associated with clinical manifestations and recurrence , and examine the role of copathogens in disease course . METHODS Prospect i ve 4-year cohort study of children born in an urban slum in north-eastern Brazil . RESULTS Of 157 children followed for > or = 3 months , 43 ( 27.4 % ) were infected with Giardia . The organism was identified in 8.8 % of all stool specimens , and although found with similar frequency in non-diarrhoeal ( 7.4 % ) and diarrhoeal stools ( 9.7 % ) , was more common in children with persistent ( 20.6 % ) than acute diarrhoea ( 7.6 % , P=0.002 ) . Recurrent or relapsing infections were common ( 46 % ) . Children with symptomatic infections had significantly lower weight-for-age and height-for-age than asymptomatic children . Copathogens were not associated with disease course . CONCLUSION With its protean clinical manifestations , Giardia may be associated with substantial morbidity amongst children in Brazil A prospect i ve r and omized , double-blind , placebo-controlled study was conducted to assess the efficacy and safety of nitazoxanide in the treatment of diarrhea caused by Giardia intestinalis or Entamoeba histolytica and /or E. dispar in 89 adults and adolescents , 22 of whom were diagnosed with G. intestinalis , 53 with E. histolytica and /or E. dispar , and 14 with both G. intestinalis and E. histolytica and /or E. dispar . The study medication was administered as 1 nitazoxanide 500-mg tablet or a matching placebo twice daily for 3 days . Thirty-eight ( 81 % ) of 47 patients in the nitazoxanide treatment group resolved diarrhea within 7 days ( median , 3 days ) after initiation of treatment , versus 17 ( 40 % ) of 42 in the placebo group ( P=.0002 ) . With its efficacy in treating a broad spectrum of enteric protozoan pathogens , nitazoxanide could play an important role in the management of diarrhea caused by enteric protozoa , reducing morbidity and costs associated with these diarrheal illnesses The substitution of enzyme immunoassay ( EIA ) techniques for microscopy as a screening tool forGiardia lamblia infection was assessed . Paired stool sample s obtained within a ten-day period from 366 patients with persistent diarrhea were examined by microscopy . In addition , two commercially availableGiardia lamblia-specific ElAs were performed . Compared with microscopy , EIA for coproantigen detection was more sensitive , based on examination of either one or two stool sample s. Repeated examinations increased the number of cases detected , more so for microscopy than EIA . The negative predictive values of the two EIAs performed on the first stool sample were 98.7 % and 97.8 % . The results show that EIA for detection of copro-antigens in a single stool sample may be almost as sensitive for identifyingGiardia infection as repeated microscopy on two sequential stool sample Albendazole , a broad spectrum anthelmintic recently shown to be active in vitro against Giardia duodenalis , was given at 4 different dosages and compared with metronidazole in the treatment of children in Bangladesh infected with Giardia . Three stools were collected over 10 d after treatment and examined microscopically . Albendazole was found to be effective : single doses of either 600 mg ( n = 103 ) or 800 mg ( n = 114 ) successfully treated 62 % and 75 % of infections , respectively ; 400 mg given either once a day for 3 d ( n = 116 ) or for 5 d ( n = 115 ) successfully treated 81 % and 95 % of all infections , respectively . Albendazole given daily at 400 mg for 5 d was as effective as metronidazole , which cured 97 % of infections ( n = 230 ) . Albendazole may thus be an alternative treatment for infections with Giardia , while the moderate efficacy of single doses may provide a benefit in addition to its effects on several species of intestinal helminths A r and omised control multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children is reported . One hundred and fifty children of either sex ( age range : 2–10 years ) were r and omised to receive either a single dose of 400 mg of albendazole suspension , or 22.5 mg/kg/day of metronidazole in 3 divided doses for 5 consecutive days . At the end of therapy , majority of children in both treatment groups were symptom free . Two days after completion of therapy , 97 % of children in both treatment groups were giardia free in the stools . Side effects were noted in 3 children in the albendazole group , and in 20 children in the metronidazole group . We conclude that albendazole suspension is as effective as metronidazole in the treatment of giardial infection in children . It is safe and has fewer side effects as compared to metronidazole Furazolidone and quinacrine hydrochloride were compared for efficacy , toxicity , and ease of administration in 45 young children with giardiasis . With the initial course of therapy , the cure rate was 89 % ( 17/19 ) with furazolidone and with quinacrine it was 64 % ( 9/14 ) in children less than 5 years and 92 % ( 11/12 ) in older children . Cure rates for all courses of therapy were 92 % ( 24/26 ) with furazolidone and 53 % ( 9/17 ) and 92 % ( 12/13 ) in the younger and older children , respectively , treated with quinacrine . Quinacrine failure was usually due to severe vomiting . When re-treated with furazolidone , patients were cured . The disadvantages of furazolidone are the large volume of doses and the expense . In this study , furazolidone was more effective and better tolerated than quinacrine for the treatment of giardiasis |
11,701 | 12,144,364 | School-based violence prevention programs may produce reductions in aggressive and violent behaviors in children who already exhibit such behavior . | OBJECTIVE To quantify the effectiveness of school-based violence prevention programs for children identified as at risk for aggressive behavior . | First through fourth grade rs from 22 suburban elementary schools were screened for cross- setting disruptive behavior as eligibility criteria for participation in a longitudinal secondary prevention study aim ed at reducing the risk for serious externalizing behavioral disorders . Three hundred nine subjects participated in either a multicomponent competence enhancement intervention ( MCEI ) or an information/attention control ( IAC ) condition over a 2-year period . Following baseline measurements , initial intervention effects were assessed at the end of intervention Year 1 , at the beginning of intervention Year 2 ( fall of the next school year ) , and at the end of intervention Year 2 . Multi source assessment s were not supportive of the efficacy of the MCEI over the IAC condition . Children in both groups rated themselves as improved over time in terms of increased adaptive skills and decreased school problems and internalizing symptoms . Teacher and parent ratings of externalizing behavior did not yield evidence of positive change , but teachers noted improved problem solving and observers noted a decrease in behavioral interference in both groups over time , possibly as a result of maturation An attributional intervention was design ed to reduce aggressive males ' tendency to attribute hostile intentions to peers following ambiguously caused peer provocations . African-American elementary school boys ( N = 101 ) , aggressive and nonaggressive , were r and omly assigned to the attributional intervention , an attention training program , or a no-treatment control group . Data were collected on subjects ' attributions about hypothetical and laboratory simulations of peer provocation , disciplinary referrals to the school office , and teacher ratings of aggressive behavior . Aggressive subjects in the attributional intervention were less likely to presume hostile intent by peers in hypothetical and laboratory simulations of ambiguous provocation . They were also less likely to endorse hostile retaliation on judgment measures and to engage in verbally hostile behaviors in the laboratory task . Further , intervention subjects were rated as less aggressive by their teachers following the treatment . Both the benefits of attributional change and its limitations in the African-American population are discussed From a school population of normal children third through fifth grade s ) , thirty children initially identified as “ angry”were r and omly assigned to either an affective imagery training group , an attention group , or a control group . The treatment group received three sessions of affective imagery in which they focused on physiological changes and on their thoughts associated with prior emotional experiences . Teachers recorded pre- , post- , and short term follow-up aggressive behaviors for all thirty children . Cognitive perceptions and attributions were recorded at the same three occasions on the Affect Question naire . Results suggested that , as a result of affective imagery training , angry children 's perceptions and cognitions shifted from “ angry ” towards “ sad , ” and there was a concomitant decrease in observed aggressive classroom behavior V and alism is a major problem facing educators and taxpayers alike . The present investigation analyzed how v and alism costs and student disruption were related to the implementation of a training and consultation package design ed to increase the reinforcing ambience of the school . A positive environment , it was posited , would displace previous events that may have set the occasion for v and alism , with cues to promote productive school performance . Eighteen elementary and junior high schools were involved over a 3-year period . Using a delayed treatment control design , treatment was delivered following either 4 or 13 months of baseline . During treatment , teams of school personnel attended training workshops in behavioral strategies for reducing v and alism and disruption by students in school . Each team also met regularly on its campus to plan and implement programs on a schoolwide basis . To demonstrate that reinforcing procedures were actually implemented and accompanied by change in student performance , these variables were periodically probed throughout the study . Project staff also provided consultation . V and alism costs decreased significantly ( p less than .05 ) more in treatment than control schools , with an average reduction of 78.5 % for all project schools . Rates of praise delivered by project teachers and other r and omly selected teachers in the school increased significantly ( p less than .05 ) , and rates of off-task behavior by students decreased significantly ( p less than .05 ) following treatment . The staff development model used in this study appeared to be both feasible and economical |
11,702 | 27,510,314 | The guideline panel continues to recommend that anticipatory nausea and vomiting are best prevented through optimization of acute and delayed phase chemotherapy-induced nausea and vomiting control .
Benzodiazepines and behavioral therapies , in particular progressive muscle relaxation training , systematic desensitization and hypnosis , continue to be recommended for the treatment of anticipatory nausea and vomiting . | Purpose We aim ed to up date the 2011 recommendations for the prevention and treatment of anticipatory nausea and vomiting in children and adults receiving chemotherapy . | PURPOSE AND METHODS Although a high prevalence of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy ( CT ) has been reported , little has been done to develop strategies to prevent these problems . A double-blind , placebo-controlled study was therefore design ed to assess the usefulness of adding low-dose alprazolam ( 0.5 mg to 2 mg per day ) to a psychologic support program including progressive relaxation training design ed to prevent the aforementioned conditions . Fifty-seven women undergoing adjuvant CT for stage II primary breast cancer agreed to participate in the assessment , which was conducted at four time points : before starting CT , 6 weeks after CT , before the fourth CT , and after the fourth CT . The Hospital Anxiety and Depression Scale ( HADS ) , Montgomery and Asberg Depression Rating Scale ( MADRS ) , Hamilton Anxiety Scale ( HAS ) , Revised Symptom Checklist ( SCL-90-R ) , Morrow Assessment of Nausea and Emesis ( MANE ) , and World Health Organization ( WHO ) grading of acute and subacute toxicities were used to compare the alprazolam ( AA ) and placebo ( PA ) arms of the study . RESULTS At the second evaluation , the results showed a higher rate of anticipatory nausea ( 18 % v 0 % ) in the PA compared with the AA arm ( P = .038 ) . These differences were no more significant at each of the further assessment s. Significant differences were found for the intake of hypnotics at each assessment visit , with the rate of hypnotic users being significantly higher in the PA ( 19 % ) compared with the AA ( 0 % ) arm at the fourth assessment ( P < .05 ) . Anxiety and depression scores of self- and observer-report were similar in the two arms . A significant relationship was found between the development of anticipatory nausea and the self-report of anxiety and depression score measured by HADS at baseline . The average HADS total score at baseline was 15.33 ( SD = 6.56 ) for patients who developed anticipatory nausea and 11.23 ( SD = 6.67 ) for other patients . CONCLUSION The adjunct of alprazolam to a psychologic support program delays the occurrence of anticipatory nausea and controls sleeping problems secondary to adjunct CT . Although studies are needed to improve the efficacy reported here , physicians may already consider the use of alprazolam for cancer patients undergoing CT Fifty-four pediatric cancer patients were studied to determine the relative efficacy of two forms of behavioral intervention for reducing chemotherapy-related distress . Following baseline assessment , subjects were r and omly assigned to receive either hypnosis , non-hypnotic distraction/relaxation , or attention placebo ( control ) during the subsequent identical chemotherapy course . Observational and interview measures of anticipatory and postchemotherapy nausea , vomiting , distress , and functional disruption served as outcome data . Results indicated that treatment condition was the single best predictor of change from baseline to intervention , with children in the hypnosis group reporting the greatest reduction of both anticipatory and postchemotherapy symptoms . The cognitive distraction/relaxation intervention appeared to have a maintenance effect in which symptoms did not get much worse or much better , while children in the control group had symptoms that consistently became worse over time . Emetic potential of the chemotherapy and the prophylactic use of antiemetics each appeared to contribute to the overall severity of symptoms . While the efficacy of hypnosis in the management of chemotherapy distress is supported , the complexities of interacting biologic and psychologic factors are highlighted We examine whether overshadowing by salient stimuli is effective in reducing the ability of a certain environment ( the putative conditioned stimulus ) to evoke conditioned nausea in healthy humans that experience nausea-evoking rotation ( as the unconditioned stimulus , US ) in that environment . Twenty-four rotation-susceptible subjects ( 12 males , 12 females ) were r and omly assigned to receive either overshadowing by salient tasting beverages ( OS+ ) , or a control treatment ( a familiar beverage , water ; OS− ) prior to rotation on three consecutive days ( acquisition ) . To control for taste experiences , the alternative beverage was consumed 12 h later in the home environment ( OS+ : water , OS− : salient beverage ) . At Day 4 ( test ) , all subjects drank the familiar beverage ( water ) prior to rotation ( US ) . Rotation was st and ardized as 2 × 1-min rotation/day . Nausea was determined by a 7-item symptom scale measuring symptom number ( SN ) prior to ( anticipatory ) , immediately after , and 15 and 30 min after rotation and by the Nausea Profile ( NP ) question naire immediately after rotation . Cortisol and tumour necrosis factor (TNF)-α in saliva were sample d at the same time-points . SN and cortisol were also measured at home . Overshadowing reduced anticipatory ( conditioned ) SN . Post-rotation nausea ( i.e. the unconditioned response ) measured by the NP decreased within the OS+ group only . Anticipatory cortisol and TNF-α were not affected by overshadowing . Treatment × gender interactions manifested for post-rotation cortisol and TNF-α . Groups did not differ in SN and cortisol at home . Overshadowing is effective in reducing symptoms of anticipatory nausea and rotation-induced unconditioned nausea ; its effect on endocrine and immunological parameters is gender specific . Its application in alleviation of anticipatory nausea in cancer patients is considered The infusion of cytotoxic drugs in cancer patients is often accompanied by posttreatment nausea ( PN ) . In addition , patients complain about nausea prior to an infusion [ i.e. , anticipatory nausea ( AN ) ] . AN is mainly explained by classical conditioning , with the infusion as the unconditioned stimulus ( US ) and with the stimuli signaling the infusion as conditioned stimuli ( CS ) . Despite this conditioning etiology , a specifically derived therapy to attenuate the CS-US contingency is missing . The purpose of this study is to develop and to test an overshadowing procedure for prevention of AN , and also for the modification of PN intensity . Sixteen cancer patients were assigned to one of two groups : Overshadowing+ ( OV+ ) and Overshadowing- ( OV- ) . At the start of all infusions of two consecutive chemotherapy cycles A and B ( acquisition ) , OV+ subjects drank a saliently tasting beverage ( the overshadowing CS ) , whereas group OV- drank water . All patients received water in cycle C ( test ) . Self-reported symptoms and heart rates were recorded . As expected , in cycle C ( test ) , no patient of group OV+ showed AN , whereas two patients of group OV- developed AN . There was a tendency for a reduction of the intensity of PN , in terms of duration and latency after overshadowing , in cycle C : OV+ patients tended to show a shorter duration and a longer latency between end of infusion and PN onset . In OV- , there was a significantly larger heart rate deceleration in both measurement periods , in the anticipatory and the posttreatment measurement period . Data suggest to apply overshadowing for prevention of AN and modification of PN . Physiological markers of conditioned nausea are revealed . After its procedural implementation , the technique can be used in larger sample s now CONTEXT Demographic , personal , clinical , and behavioral factors predicting chemotherapy-induced nausea and vomiting ( CINV ) have been assessed in the past , but inconsistencies exist in the literature , studies have method ological shortcomings , and many risk factors have been examined in cross-sectional studies and univariate analyses . OBJECTIVES To evaluate the predictive power of personal and treatment-related characteristics in the development of CINV , using a large and prospect ively evaluated sample of a heterogeneous group of cancer patients receiving routine chemotherapy . METHODS This was a multicountry , multisite prospect i ve study over three cycles of chemotherapy . Adult patients from eight European countries about to receive highly and moderately emetogenic chemotherapy were recruited . Clinicians completed a case report form at or before the initial chemotherapy treatment , recording patient demographic and baseline clinical characteristics . Participants completed a daily patient diary for six days per chemotherapy cycle describing their CINV experience . Baseline patient data also included a history of nausea/vomiting ( yes/no ) , patient expectation of nausea ( 0 - 100 mm visual analogue scale [ VAS ] ) , prechemotherapy anxiety ( 0 - 100 mm VAS ) , and prechemotherapy nausea ( 0 - 100 mm VAS ) measured during the 24-hour period before chemotherapy initiation . RESULTS There were 991 evaluable patients with complete Cycle 1 data , 888 for Cycle 2 data , and 769 for Cycle 3 data . A complex picture of predictor variables was shown , with different contribution of variables to the acute , delayed , and overall phases of CINV . Key predictor variables included the use of antiemetics inconsistent with international guidelines , younger age , prechemotherapy nausea , and no CINV complete response in an earlier cycle ( all at P < 0.05 ) . Anxiety , history of nausea/vomiting , and expectations of nausea were important predictors for some phases and cycles but not consistently across the CINV pathway . CONCLUSION The results of this study provide clarity for the relative contribution of a set of characteristics in the development of CINV . Following evidence -based clinical antiemetic guidelines is of paramount importance , alongside treating patients with increased risk for CINV more aggressively , which both could lead to more optimal CINV management . These data can assist clinicians in making decisions about the antiemetic management of their patients Purpose Some patients experience nausea and /or vomiting ( NV ) before receipt of chemotherapy . Our objective was to evaluate the impact of prior chemotherapy-induced NV ( CINV ) on the incidence of anticipatory NV in later cycles . Methods This multicenter , prospect i ve non-interventional study enrolled chemotherapy-naïve adults scheduled to receive highly or moderately emetogenic chemotherapy ( HEC/MEC ) for cancer in six Asia Pacific countries , excluding those with emesis within 24 h before cycle 1 chemotherapy . On day 1 before chemotherapy , patients answered four questions regarding emesis in the past 24 h , nausea , expectation of post-chemotherapy nausea , and anxiety in the past 24 h , the latter three scored from 0–10 ( none – maximum ) . Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3 . Results Five hundred ninety-eight patients ( 59 % female ) were evaluable in cycle 2 ( 49 % HEC , 51 % MEC ) . The incidence of anticipatory emesis was low before cycles 2 and 3 ( 1.5–2.3 % ) . The incidence of clinical ly significant anticipatory nausea ( score of ≥3 ) was 4.8 , 7.9 , and 8.3 % before cycles 1 , 2 , and 3 , respectively , with adjusted odds ratio ( OR ) , 3.95 ( 95 % confidence interval ( CI ) , 2.23–7.00 ; p < 0.001 ) for patients with clinical ly significant nausea in prior cycles , compared with none . The adjusted ORs for other anticipatory NV endpoints ranged from 4.54–4.74 for patients with prior CINV . The occurrence of clinical ly significant anxiety in the prior cycle also result ed in a significantly increased likelihood of anticipatory nausea . Conclusions These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles Adequate control of side effects during medical treatment of cancer increases patient compliance and quality of life . Antiemetic drugs are not an effective treatment for the one in three cancer patients on chemotherapy who experience anticipatory nausea and vomiting ( ANV ) ; the behavioral treatment of systematic desensitization has been found effective for ANV when delivered by clinical psychologists . This study examined the effectiveness of systematic desensitization when delivered by medical personnel versus clinical psychologists . Seventy-two consecutive cancer patients with ANV were r and omly assigned to no-treatment control or to systematic desensitization from 5 behaviorally trained clinical psychologists , 6 clinical oncologists , or 10 oncology nurses . The treatment was found effective in reducing anticipatory nausea , anticipatory vomiting , posttreatment nausea , and posttreatment vomiting compared to control patients , with no significant differences in effectiveness found between clinical psychologists and oncology staff . Although medical personnel should not engage patients in psychotherapy or other interventions that can not be completed successfully , they can treat patients effectively with systematic desensitization and should be encouraged to learn and use this and other behavioral intervention techniques to benefit total patient care This study was design ed to determine ( a ) the relationship of coping style to cancer chemotherapy side efects and ( b ) whether coping style moderated the impact of a relaxation intervention on anxiety , depression , and nausea associated with chemotherapy . Forty-eight cancer patients were assigned r and omly to receive either progressive muscle relaxation training before chemotherapy ( experimental group ) or st and ard care ( control group ) . Spearman correlations indicated that a “ blunting ” or distraction-oriented coping style was associated with less anticipatory anxiety , less depression , and less nausea during and after chemotherapy . Spearman correlations also indicated that a “ monitoring ” or information-gathering coping style was associated with more anticipatory anxiety , and more nausea before and during chemotherapy . Although there was a signijicant effect of the relaxation intervention on posttreatment nausea , there were no other between-group differences . The results did suggest , however , that relaxation was efective in reducing anticipatory anxiety among “ blunters , ” but not “ monitors , ” perhaps because relaxation is a distraction strategy and therefore is consistent with a blunting coping style . The effects of coping and relaxation on pretreatment anxiety may have important implication s , because anxiety is a key factor in classic conditioning models of anticipatory nausea and vomiting To study the effectiveness of hypnosis for decreasing antiemetic medication usage and treatment of chemotherapy-related nausea and vomiting in children with cancer , we conducted a prospect i ve , r and omized , and controlled single-blind trial in 20 patients receiving chemotherapy for treatment of cancer . Patients were r and omized to either hypnosis or st and ard treatment . The hypnosis group used hypnosis as primary treatment for nausea and vomiting , using antiemetic medication on a supplemental ( p.r.n . ) basis only , whereas the control group received a st and ardized antiemetic medication regimen . Nausea , vomiting , and p.r.n . antiemetic medication usage were measured during the first two courses of chemotherapy . Anticipatory nausea and vomiting were assessed at 1 to 2 and 4 to 6 months postdiagnosis . Patients in the hypnosis group used less p.r.n antiemetic medication than control subjects during both the first ( p < .04 ) and second course of chemotherapy ( p < .02 ) . The two groups did not differ in severity of nausea and vomiting . The hypnosis group experienced less anticipatory nausea than the control group at 1 to 2 months postdiagnosis ( p < .02 ) . Results suggest self-hypnosis is effective for decreasing antiemetic medication usage and for reducing anticipatory nausea during chemotherapy Aims and Background : In addition to nausea and vomiting following chemotherapy treatment , cancer patients can experience these side effects prior to a treatment session , the so-called anticipatory nausea and vomiting . As various psychological and neurophysiological aspects have been cl aim ed to be implied in its etiopathogenesis , the present paper aims to shortly review the etiological , epidemiological and therapeutical assumptions on the topic , in particular the psychological-behavioral therapies . Patients and Methods : The present study was carried out on 16 consecutive adult cancer patients affected by chemotherapy-induced anticipatory nausea and vomiting who had received at least four treatment cycles . All of them were su bmi tted to induction of relaxation followed by hypnosis . Results : In all subjects anticipatory nausea and vomiting disappeared , and major responses to chemotherapy-induced emesis control were recorded in almost all patients . Conclusions : The experience highlights the potential value of hypnosis in the management of anticipatory nausea and vomiting ; furthermore , the susceptibility to anticipatory nausea and vomiting is discussed under the psychoanalytic point of view Nausea and vomiting are extremely common and most distressing side effects of high-dose cisplatin therapy . Cisplatin induces anticipatory and acute , as well as , delayed emesis . High doses of metoclopramide can effectively decrease the intensity of these symptoms in up to 70 % of cases . Several agents , including dexamethasone and antihistamines have been demonstrated to either increase the efficacy of metoclopramide or decrease the side effects . Lorazepam , a benzodiazepine , has both antiemetic and anxiolytic properties . It can be useful as an adjunct to metoclopramide-based therapy . We conducted a r and omized trial to evaluate the efficacy of lorazepam in managing anticipatory , acute , and delayed emesis induced by high doses of cisplatin . A total of 180 events involving cisplatin administration ( 100 mg/m2 as a 24-hour continuous infusion ) were r and omized to receive metoclopramide along with dexamethasone and clemastine with and without lorazepam . Categorical scales were utilized to document the incidence of nausea and vomiting and side effects related to antiemetic therapy . All episodes are evaluable . Lorazepam significantly reduced the incidence of anticipatory nausea and vomiting ( P < .05 ) as well as acute emesis ( P = .05 ) induced by cisplatin . Delayed emesis was also decreased ; however , it was statistically significant on day 3 only ( P < .05 ) . Side effects were few except for mild sedation and amnesia , which were significantly more common in those receiving lorazepam ( P < .001 ) . We conclude that lorazepam increases the efficacy of metoclopramide against cisplatin-induced anticipatory , acute , and delayed nausea and vomiting . This four-drug regimen may offer one of the best combinations to be utilized in comparative trials against the newly introduced serotonin antagonists The purpose s of this study were to investigate the prevalence of anticipatory nausea ( AN ) , its associated factors , and its impact on quality of life ( QOL ) among ambulatory cancer patients receiving chemotherapy . Patients were r and omly selected to participate in this study , and were asked to complete the Morrow Assessment of Nausea and Emesis scale , the Hospital Anxiety and Depression Scale , the Short‐form Supportive Care Needs Survey question naire , and the European Organization for Research and Treatment of Cancer QLQ‐C30 question naire . Complete data were available for 214 patients . A total of 10.3 % of the patients experienced very mild to severe AN . The presence of AN was significantly associated with most domains of the investigated patients ’ outcome , including psychological distress and perceived needs , with the exception of the health system and information domain of patients ’ needs , and the physical functioning domain of QOL . Anticipatory nausea was also associated with QOL even after adjustments for age , sex , performance status , and psychological distress . The prevalence of AN in ambulatory cancer patients who receive chemotherapy may not be as high as previously reported . However , given its potentially significant impact on relevant outcome , including QOL , AN should not be neglected in current clinical oncology practice . ( Cancer Sci 2010 ; 101 : 2596–2660 The nausea and vomiting experienced by one in four cancer patients in anticipation of chemotherapy is probably a learned response to treatment . To determine whether behavioral approaches for altering learned responses might be useful treatments for these symptoms , we compared the effects of " systematic desensitization " ( a behavioral treatment in which relaxation is learned as a response to situations in which patients have had anticipatory nausea and vomiting ) with those of counseling and of no treatment . Sixty ambulatory cancer patients with anticipatory nausea and vomiting before their third and fourth chemotherapy treatments were r and omized equally to the three groups . Significantly more patients receiving desensitization reported no anticipatory nausea before their fifth and sixth chemotherapy treatments than patients given counseling ( P less than 0.05 ) or no treatment ( P less than 0.01 ) . Desensitized patients also reported significantly less severe anticipatory nausea ( P less than 0.01 ) and vomiting ( P less than 0.05 ) and a shorter duration of anticipatory nausea ( P less than 0.01 ) . We conclude that systematic desensitization appears to have an antiemetic effect in cancer patients who receive chemotherapy , and may be useful in the management of these problems |
11,703 | 29,086,061 | Results Studies show that the IM plays a key role in the metabolism of the substrates studied .
However , with the exception of studies focusing on fibre and polyphenols , there have been relatively few recent human studies specifically evaluating microbial metabolism .
Nevertheless , it appears that the IM plays a role in energy homeostasis and that protein microbial breakdown and fermentation produced ammonia , amines , phenols and branch chain fatty acids , and a greater diversity in the microbes present .
Few recent studies appear to have evaluated the effect of the IM composition and metabolism per se in relation with digestible dietary carbohydrate or fat in humans .
Intakes of RS and prebiotics altered levels of specific taxa that selectively metabolised specific prebiotic/carbohydrate-type substances and levels of bifidobacteria and lactobacilli were observed to increase .
In the polyphenol-related studies , a large amount of inter-individual variation was observed in the microbial metabolism and absorption of certain polyphenols .
Conclusions The systematic review demonstrates that the IM plays a major role in the breakdown and transformation of the dietary substrates examined .
Current evidence suggests that more detailed knowledge of the metabolic activities and interactions of the IM hold considerable promise in relation with host health | Purpose There is considerable interest in the effects of the intestinal microbiota ( IM ) composition , its activities in relation with the metabolism of dietary substrates and the impact these effects may have in the development and prevention of certain non-communicable diseases .
It is acknowledged that a complex interdependence exists between the IM and the mammalian host and that the IM possesses a far greater diversity of genes and repertoire of metabolic and enzymatic capabilities than their hosts .
However , full knowledge of the metabolic activities and interactions of the IM and the functional redundancy that may exist are lacking .
Thus , the current review aims to assess recent literature relating to the role played by the IM in the absorption and metabolism of key nutrients and non-nutrients .
In controlled human studies , consistent data exist that show a correlation between the intake of fibre and an increase in bifidobacteria and short-chain fatty acids , in particular butyrate , which leads to lower intestinal pH. Dietary polyphenols rely on modification either by host digestive enzymes or those derived from the IM for absorption to occur . | Objective To highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans ( ITF prebiotics ) in obese women . Methods A double blind , placebo controlled , intervention study was performed with 30 obese women treated with ITF prebiotics ( inulin/oligofructose 50/50 mix ; n=15 ) or placebo ( maltodextrin ; n=15 ) for 3 months ( 16 g/day ) . Blood , faeces and urine sampling , oral glucose tolerance test , homeostasis model assessment and impedancemetry were performed before and after treatment . The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA . Plasma and urine metabolic profiles were analysed by 1H-NMR spectroscopy . Results Treatment with ITF prebiotics , but not the placebo , led to an increase in Bifidobacterium and Faecalibacterium prausnitzii ; both bacteria negatively correlated with serum lipopolysaccharide levels . ITF prebiotics also decreased Bacteroides intestinalis , Bacteroides vulgatus and Propionibacterium , an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels . No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses . However , ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and /or diabetes . Conclusions ITF prebiotics selectively changed the gut microbiota composition in obese women , leading to modest changes in host metabolism , as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures Background Recent studies suggest that some of the clinical effectiveness of soy or daidzein , which is a type of isoflavone , may be attributed to a person ’s ability to produce equol from daidzein . Equol , which is a metabolite of one of the major soybean isoflavones called daidzein , is produced in the gastrointestinal tract by certain intestinal microbiota where present . Habitual dietary patterns may alter the intestinal bacterial profile , and influence the metabolism of isoflavones and the production of equol . Fructooligosaccharides ( FOS ) have a prebiotic activity as well as being a dietary fibre . The purpose of the present study was to determine whether FOS supplementation increases equol production in equol producers and stimulates equol production in equol non-producers in Japanese postmenopausal women . Methods A soy challenge was used to assess equol-producer status prior to the start of the study in healthy postmenopausal Japanese women . The study involved 4 separate groups in r and omised crossover design . First , subjects were classified as equol producers ( n = 25 ) or non-producers ( n = 18 ) , and then they were r and omly assigned to the FOS or control group . All subjects received a daily dose of 37 mg isoflavone conjugates in the capsule ( 21 mg aglycone form ) and either FOS ( 5g/day ) or sucrose as control , in a r and omised crossover study design . Equol -production was assessed by testing the serum and urine before and after the 2-week supplementation period . Results The analyses were conducted on 34 subjects completed the study , 21 ( 61.8 % ) were classified as equol producers , and 13 ( 38.2 % ) as non-producers . Significant differences were observed in the interaction effect of time × equol state after 1 week of intervention ( p = 0.006 ) . However there were no effects after 2 weeks of intervention ( p = 0.516 ) . Finally , in both equol producers and non-producers , FOS supplementation did not affect the serum equol concentration or the urinary equol to daidzein concentration ratios . Conclusions We have reported that FOS intervention ( 5 g/day for 2 weeks ) does not significantly modulate the capacity of intestinal microbiota to produce equol in postmenopausal Japanese women , in either equol producers or non-producers in this pilot study . Further larger investigations that explore the roles of specific intestinal microbiota in equol production will enable the establishment of dietary conditions that are required to enhance equol production Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change . Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression . The animal-based diet increased the abundance of bile-tolerant microorganisms ( Alistipes , Bilophila and Bacteroides ) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia , Eubacterium rectale and Ruminococcus bromii ) . Microbial activity mirrored differences between herbivorous and carnivorous mammals , reflecting trade-offs between carbohydrate and protein fermentation . Foodborne microbes from both diets transiently colonized the gut , including bacteria , fungi and even viruses . Finally , increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat , bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease . In concert , these results demonstrate that the gut microbiome can rapidly respond to altered diet , potentially facilitating the diversity of human dietary lifestyles OBJECTIVES : The prebiotic potential of NUTRIOSE ® – a sugar-free , digestion-resistant dextrin — was evaluated in two r and omized , placebo-controlled trials that included 48 and 40 healthy volunteers , respectively . METHODS : In study 1 , the effect on colonic bacteria of NUTRIOSE ® 10 , 15 or 20 g/day administered for 14 days was examined ; in study 2 , gut microbial changes in response to NUTRIOSE ® 8 g/day for 14 days were monitored using real-time polymerase chain reaction analysis . RESULTS : NUTRIOSE ® increased proliferation of Bacteroides and inhibited Clostridum perfringens in both studies , increased β-glucosidase activity ( at 10 and 15 g/day ) and decreased colonic pH ( at 20 g/day ) . The increase in short-chain fatty acid production with NUTRIOSE ® consumption was not statistically significant . There were no indications of gastrointestinal intolerance at any dose . CONCLUSIONS : According to commonly accepted definitions , NUTRIOSE ® is a prebiotic soluble fibre that provides a beneficial effect on colonic ecology while preserving digestive comfort Dietary phytoestrogens , such as isoflavones , are used as food additives to prevent menopause-related disorders . In addition to other factors , their bioavailability strongly depends on the activity of intestinal bacteria but the underlying interactions remain poorly understood . A r and omized , double-blind , placebo-controlled study was undertaken with 39 postmenopausal women to characterize changes in the dominant microbial communities of the intestinal tract after 2 mo of isoflavone supplementation with and without pro- or prebiotic . The diversity and composition of the dominant microbiota were analyzed by temporal temperature-gradient gel electrophoresis ( TTGE ) and fluorescent in situ hybridization . Isoflavones alone stimulated dominant microorganisms of the Clostridium coccoides-Eubacterium rectale cluster , Lactobacillus-Enterococcus group , Faecalibacterium prausnitzii subgroup , and Bifidobacterium genus . The stimulation of the Clostridium coccoides-Eubacterium rectale cluster depended on the women 's equol excretion and was transient , with the exception of a prolonged bifidogenic effect . Lasting changes in the diversity of the dominant species were also observed . The probiotic strain supplied could be detected by TTGE during its passage through the intestinal tract , and ingestion of fructooligosaccharides triggered a marked and specific bifidogenic effect . In conclusion , this is the first human study that shows changes in the diversity and composition of dominant bacterial communities in response to dietary supplementation with hormone-related compounds combined with functional foods BACKGROUND Bacterial intestinal glucosidases exert an important role in isoflavone absorption . Insoluble dietary fibers such as inulin may stimulate the growth of these bacteria in the colon and , hence , stimulate the absorption of these substances in subjects who may need isoflavone supplementation . OBJECTIVE The objective was to assess the influence of inulin on plasma isoflavone concentrations after intake of soybean isoflavones in healthy postmenopausal women . DESIGN Twelve healthy postmenopausal women participated in a r and omized , double-blind , crossover study . They consumed 40 mg of a conjugated form of soybean isoflavones ( 6 mg daidzein and 18 mg genistein as free form ) with or without 3.66 g inulin twice daily in two 21-d experimental phases . Blood sample s were collected 0 , 1 , 2 , 3 , 4 , 6 , 10 , 12 , and 24 h after intake of isoflavones with breakfast and dinner at the end of each 21-d experimental phase . Plasma concentrations of isoflavones were assessed by HPLC with an electrochemical detector . RESULTS Plasma 24-h areas under the curve indicated that the intake of soybean isoflavones with inulin for 21 d was followed by higher plasma concentrations of daidzein and genistein ( 38 % and 91 % , respectively ) compared with the formulation without inulin . Furthermore , the time for the maximum concentration of daidzein and genistein appeared to be lower after the 21-d intake of soybean isoflavones , with or without inulin . However , the time for the maximum concentration of daidzein and genistein after supplementation with the inulin-containing formulation on day 21 was not significantly different from that after supplementation with the formulation without inulin . CONCLUSIONS Inulin may increase the apparent plasma concentrations of the soybean isoflavones daidzein and genistein in postmenopausal women . The higher plasma concentrations of the 2 isoflavones suggests that the absorption of each was facilitated by the presence of inulin Wheat bran extract ( WBE ) is a food- grade soluble fibre preparation that is highly enriched in arabinoxylan oligosaccharides . In this placebo-controlled cross-over human intervention trial , tolerance and effects on colonic protein and carbohydrate fermentation were studied . After a 1-week run-in period , sixty-three healthy adult volunteers consumed 3 , 10 and 0 g WBE/d for 3 weeks in a r and om order , with 2 weeks ' washout between each treatment period . Fasting blood sample s were collected at the end of the run-in period and at the end of each treatment period for analysis of haematological and clinical chemistry parameters . Additionally , subjects collected a stool sample for analysis of microbiota , SCFA and pH. A urine sample , collected over 48 h , was used for analysis of p-cresol and phenol content . Finally , the subjects completed question naires scoring occurrence frequency and distress severity of eighteen gastrointestinal symptoms . Urinary p-cresol excretion was significantly decreased after WBE consumption at 10 g/d . Faecal bifidobacteria levels were significantly increased after daily intake of 10 g WBE . Additionally , WBE intake at 10 g/d increased faecal SCFA concentrations and lowered faecal pH , indicating increased colonic fermentation of WBE into desired metabolites . At 10 g/d , WBE caused a mild increase in flatulence occurrence frequency and distress severity and a tendency for a mild decrease in constipation occurrence frequency . In conclusion , WBE is well tolerated at doses up to 10 g/d in healthy adults volunteers . Intake of 10 g WBE/d exerts beneficial effects on gut health parameters BACKGROUND A major portion of the catechins in green tea is not absorbed in the small intestine . Bacteria in the colon convert nonabsorbed catechins into simpler phenolic compounds , which may also be absorbed . During the production of black tea , most catechins are polymerized to complex molecules called thearubigins . Little is known about the microbial degradation of these complex polyphenols , but hippuric acid has been identified as a major excretion product associated with black tea consumption . OBJECTIVE To investigate whether green tea and black tea have the same metabolic fate in humans . DESIGN Seventeen healthy male volunteers were studied with a r and omized , full-crossover design . Each intervention period lasted 4 d , ie , a 2-d run-in period with a low-polyphenol diet followed by a 2-d treatment period . Volunteers consumed a daily dose of 6 g green tea solids , 6 g black tea solids , or 360 mg caffeine . Intervention periods were separated by a 10-d washout period . Twenty-four-hour urine sample s were collected during the second day of each treatment period . Hippuric acid was analyzed with HPLC-t and em mass spectrometry . RESULTS The mean excretion of urinary hippuric acid during black tea and green tea consumption was 3.75 + /- 0.28 mmol/24 h and 4.22 + /- 0.28 mmol/24 h , respectively ( 95 % CI for the difference : -0.37 to + 1.30 mmol/24 h ) . The hippuric acid excretion during the control treatment was much lower ( 1.89 + /- 0.28 mmol/24 h ; P < 0.0001 , compared with both black tea and green tea ) . CONCLUSION The ingestion of either green tea or black tea results in a major increase in the excretion of hippuric acid into urine To further underst and how diets containing high levels of fibre protect against colorectal cancer , we examined the effects of diets high in nonstarch polysaccharides ( NSP ) or high in NSP plus resistant starch ( RS ) on the composition of the faecal microbial community in 46 healthy adults in a r and omized crossover intervention study . Changes in bacterial population s were examined using denaturing gradient gel electrophoresis ( DGGE ) of 16S rRNA gene fragments . Bacterial profiles demonstrated changes in response to the consumption of both RS and NSP diets [ analysis of similarities ( ANOSIM ) : R=0.341 - 0.507 , P<0.01 ] . A number of different DGGE b and s with increased intensity in response to dietary intervention were attributed to as-yet uncultivated bacteria closely related to Ruminococcus bromii . A real-time PCR assay specific to the R. bromii group was applied to faecal sample s from the dietary study and this group was found to comprise a significant proportion of the total community when individuals consumed their normal diets ( 4.4+/-2.6 % of total 16S rRNA gene abundance ) and numbers increased significantly ( + /-67 % , P<0.05 ) with the RS , but not the NSP , dietary intervention . This study indicates that R. bromii-related bacteria are abundant in humans and may be significant in the fermentation of complex carbohydrates in the large bowel Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction . Laparoscopic sleeve gastrectomy ( LSG ) , a surgical intervention for obesity , is classified as predominantly restrictive procedure . In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects ( n = 5 per group ) demonstrating identical weight loss during a follow-up period of six months . For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics . The energy-reabsorbing potential of the gut microbiota decreased following LSG , indicated by the Bacteroidetes/Firmicutes ratio , but increased during diet . Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups . No alteration of faecal butyrate was observed , but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention . LSG result ed in enhanced faecal excretion of nonesterified fatty acids and bile acids . LSG , but not dietetic restriction , improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype . Moreover , LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation . This trial is registered with Clinical Trials.gov NCT01344525 BACKGROUND Soy isoflavones may lower breast cancer risk through altered hepatic estrogen metabolism , leading to increased urinary excretion ratios of 2-hydroxyestrone ( 20HE1 ) to 16a-hydroxyestrone ( 16alphaOHE1 ) . MATERIAL S AND METHODS Urinary excretion of 20HE1/16alphaOHE1 was measured in 36 healthy , pre-menstrual women before and after ingestion of a soy-protein formula containing 120 mg of isoflavone daily for one month . Since isoflavone absorption and metabolism depends on intestinal bacteria , effects of co-administration of Lactobacillus GG ( 2 x 10(12 ) ) on estrogen ratios and isoflavone excretion were studied . Urinary isoflavone excretion measurements assessed compliance . RESULTS Soy isoflavone ingestion induced quantitative differences in urinary excretion of estrogen metabolites and isoflavones but failed to alter 20HE1/16alphaOHE1 ratios . Co-administration of Lactobacillus GG with soy reduced excretion of total and individual isoflavones by 40 % ( p=0.08 ) , without altering 2OHE1/16alphaOHE1 ratios . CONCLUSION Isoflavone-rich soy protein administration alone , or with probiotic supplement , did not alter urinary excretion of estrogen metabolites in premenopausal women . However , adding concentrated probiotics may alter isoflavone bioavailability OBJECTIVE Prebiotics and probiotics may be able to modify an obesity-associated gut microbiota . The aim of this study was to examine the individual and combined effects of the prebiotic oligofructose ( OFS ) and the probiotic Bifidobacterium animalis subsp . lactis BB-12 ( BB-12 ) on gut microbiota and host metabolism in obese rats . METHODS Adult male , diet-induced obese Sprague Dawley rats were r and omized to : ( 1 ) Control ( C ) ; ( 2 ) 10 % OFS ; ( 3 ) BB-12 ; ( 4 ) OFS + BB-12 for 8 weeks ( n = 9 - 10 rats/group ) . Body composition , glycemia , gut permeability , satiety hormones , cytokines , and gut microbiota were examined . RESULTS Prebiotic , but not probiotic reduced energy intake , weight gain , and fat mass ( P < 0.01 ) . OFS , BB-12 , and the combined OFS + BB-12 improved glycemia ( P < 0.05 ) . Individually , OFS and BB-12 reduced insulin levels ( P < 0.05 ) . Portal GLP-1 was increased with OFS , whereas probiotic increased GLP-2 ( P < 0.05 ) . There was a marked increase in bifidobacteria and lactobacilli ( P < 0.01 ) with OFS that was not observed with probiotic alone . CONCLUSIONS The impact of prebiotic intake on body composition and gut microbiota was of greater magnitude than the probiotic BB-12 . Despite this , an improvement in glucose AUC with both prebiotic or probiotic demonstrates the beneficial role of each of these " biotic " agents in glycemic control The tolerance and prebiotic effect following oral intake by healthy human subjects of arabinoxylan-oligosaccharides ( AXOS ) , produced by partial enzymic hydrolysis of the wheat fibre arabinoxlyan , were studied . A total of twenty healthy subjects participated in the present r and omised , placebo-controlled cross-over study . They consumed 10 g AXOS or placebo per d each for 3 weeks with a 4-week wash-out period in between . Before and immediately after each intake period , blood sample s were taken to measure haematological and clinical chemistry parameters and the subjects completed a question naire about gastrointestinal symptoms . Additionally , urine was collected over 48 h for analysis of p-cresol and phenol content by GC-MS , and faeces were collected over 72 h for analysis of microbiota using real-time PCR . Of the subjects , ten also performed a urine and faeces collection 2 weeks after the start of intake ( during intervention ) . A limited number of tested blood parameters were influenced in a statistically significantly way by either AXOS or placebo intake , but these changes remained within the normal range . Blood lipids remained unchanged . AXOS had no statistically significant effect on the range of gastrointestinal symptoms , except for a mild increase in flatulence . Urinary p-cresol excretion , an indicator of protein fermentation , was significantly decreased after 2 weeks of AXOS intake . The levels of bifidobacteria were significantly increased after 2 and 3 weeks of AXOS intake as well as after 3 weeks of placebo . However , the effect of AXOS on bifidobacteria was more pronounced than that of placebo . In conclusion , AXOS are a well-tolerated prebiotic at the dose of 10 g/d . AXOS intake increases faecal bifidobacteria and reduces urinary p-cresol excretion BACKGROUND Studies in mice indicate that the gut microbiome influences both sides of the energy-balance equation by contributing to nutrient absorption and regulating host genes that affect adiposity . However , it remains uncertain as to what extent gut microbiota are an important regulator of nutrient absorption in humans . OBJECTIVE With the use of a carefully monitored inpatient study cohort , we tested how gut bacterial community structure is affected by altering the nutrient load in lean and obese individuals and whether their microbiota are correlated with the efficiency of dietary energy harvest . DESIGN We investigated dynamic changes of gut microbiota during diets that varied in caloric content ( 2400 compared with 3400 kcal/d ) by pyrosequencing bacterial 16S ribosomal RNA ( rRNA ) genes present in the feces of 12 lean and 9 obese individuals and by measuring ingested and stool calories with the use of bomb calorimetry . RESULTS The alteration of the nutrient load induced rapid changes in the gut microbiota . These changes were directly correlated with stool energy loss in lean individuals such that a 20 % increase in Firmicutes and a corresponding decrease in Bacteroidetes were associated with an increased energy harvest of ≈150 kcal . A high degree of overfeeding in lean individuals was accompanied by a greater fractional decrease in stool energy loss . CONCLUSIONS These results show that the nutrient load is a key variable that can influence the gut ( fecal ) bacterial community structure over short time scales . Furthermore , the observed associations between gut microbes and nutrient absorption indicate a possible role of the human gut microbiota in the regulation of the nutrient harvest . This trial was registered at clinical trials.gov as NCT00414063 |
11,704 | 28,248,961 | Sevelamer , lanthanum , calcium , iron , diet and combinations of active treatments ( calcium or sevelamer or lanthanum and combination of calcium and sevelamer ) result ed in significantly lower serum phosphate as compared to placebo ( moderate to very low quality of evidence ) .
We found no statistically significant differences between active treatment categories in lowering serum phosphate .
Sevelamer , lanthanum and diet result ed in lower serum calcium compared to calcium ( moderate quality evidence for lanthanum and diet ; low quality evidence for Sevelamer ) .
Iron , sevelamer and calcium yielded lower parathyroid hormone levels as compared to lanthanum .
Meta-regression analyses did not yield a statistically significant association between treatment effect and trial duration .
DISCUSSION / CONCLUSIONS We found few differences between treatments in impact on phosphate and differences in parathyroid hormone .
Relative to calcium , sevelamer , lanthanum and diet showed significant reduction in serum calcium from baseline . | BACKGROUND Chronic kidney disease-mineral and bone disorder ( CKD-MBD ) , a complication of chronic kidney disease , has been linked to reduced quality and length of life .
High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents , also known as phosphate binders .
The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD . | 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 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 Secondary hyperparathyroidism ( SHPTH ) is present in many patients with end-stage renal disease ( ESRD ) and has been linked to uremic bone disease . Parathyroid hormone ( PTH ) levels are affected by calcium , vitamin D , and phosphorus . Recent data suggests that serum magnesium may also modulate PTH levels . Objective The aim of this retrospective study was to investigate the impact of different calcium ( Ca ) and magnesium ( Mg ) concentrations of dialysis solutions on serum Mg and serum PTH levels in peritoneal dialysis ( PD ) patients . Patients and methods Two groups of PD patients -group A ( n = 17 ) on “ st and ard ” Ca and Mg dialysis solution ( SCa – MgD ) ( Ca : 1.62 mmol/l , Mg : 0.75 mmol/l and Lactate 35 mmol/l ) , and group B ( n = 29 ) on “ low ” Ca and Mg dialysis solution ( LCa – MgD ) ( Ca : 1.25 mmol/l , Mg : 0.25 mmol/l and Lactate 40 mmol/l ) , on PD for more than 6 months , were studied . Calcium carbonate ( CaCO3 ) was used as the phosphate ( P ) binder in 87 % ( 40/46 ) of the patients . Biochemical parameters were evaluated every 1–2 months over 6 months and the mean values were computed . Results No significant differences were found between the two groups in all parameters except for serum Mg and PTH . Serum Mg was higher in SCa – MgD group compared to those in the LCa – MgD group ( 1.05 ± 0.19 vs 0.90 ± 0.23 mmol/l , respectively ) and serum PTH was higher in LCa – MgD group compared to those in SCa – MgD group ( 72.3 ± 64.2 vs 31.1 ± 39.0 pmol/l , respectively ) even though serum Ca was not different . There was a statistically significant inverse correlation between serum Mg and PTH levels ( r = −0.357 , p < 0.05 ) . ConclusionS erum Mg is lower and serum PTH higher in patients dialyzed with lower Mg concentration dialysis solution compared to those with higher Mg concentration dialysis solution . Our study confirms previous reports that serum Mg may have a suppressive role on PTH synthesis and /or secretion , and thus may play a role in pathogenesis of adynamic bone disease that often develops in patients on chronic PD with high calcium and high magnesium concentrations 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 Parathyroid hormone ( PTH ) is a cardinal factor in the pathogenesis of bone disease in the dialysis population . The spectrum of renal osteodystrophy has been reported to have changed during the past years , and adynamic bone disease has emerged as the most common bone disorder in these patients . Continuous ambulatory peritoneal dialysis ( CAPD ) is considered a risk factor for the development of this condition , and furthermore , the adynamic bone lesion is associated with a state of relative hypoparathyroidism ( hypo-PTH ) . Calcium , vitamin D , and phosphorus play a key role in the control of parathyroid gl and function in uremic patients . However , magnesium may also be able to modulate PTH secretion in a way similar to calcium . Objective The aims of this study were ( 1 ) to analyze the serum Mg concentration in a large group of CAPD patients , ( 2 ) to study the relationship between serum Mg and PTH levels , and ( 3 ) to investigate whether this relationship is independent of other factors , such as calcium , phosphorus , and calcitriol , that regulate parathyroid function . Patients and Methods We studied 51 stable patients , aged 23 – 77 years , under maintenance CAPD for more than 6 months ( range 8 – 48 months ) . Calcium carbonate was used as a phosphate binder in all patients , and 9 subjects also received aluminum hydroxide . No patient had been previously treated with vitamin D. Biochemical parameters were prospect ively evaluated over 6 months , and the mean values were computed . Results The mean serum Mg was 1.08 ± 0.19 mmol/L , and hypermagnesemia , defined as a Mg level higher than 1.01 mmol/L , was found in 30 patients ( 59 % ) . Thirty-one subjects ( 60 % ) had an intact PTH ( iPTH ) level lower than 120 pg/mL and were diagnosed as having relative hypo-PTH . Except for the values of iPTH and alkaline phosphatase , the only difference between the two groups was the serum Mg concentration , which was significantly higher in patients with hypo-PTH ( 1.16 ± 0.15 mmol/L vs 0.91 ± 0.14 mmol/L ; p < 0.001 ) . Furthermore , iPTH levels were lower in patients with hypermagnesemia than in subjects with normal serum Mg ( 69 ± 49 pg/mL vs 190 ± 89 pg/mL , p < 0.001 ) . There was a significant correlation between serum Mg and PTH levels ( r = –0.70 , p < 0.01 ) . After controlling for the effect of other variables by partial correlation analysis , a significant positive association between P and PTH ( r = 0.25 , p < 0.05 ) , and a negative relationship between Mg and PTH ( r = –0.57 , p < 0.001 ) were evident . A forward stepwise multiple regression analysis showed that only P and Mg predicted PTH values ( multiple r = 0.59 , p < 0.001 ) . Conclusions Hypermagnesemia and hypoparathyroidism are frequent in CAPD patients . There is a significant inverse relationship between serum Mg concentration and iPTH levels . Furthermore , this association is independent of the most important factors regulating parathyroid gl and function ( calcium , phosphorus , and calcitriol ) . These results suggest that hypermagnesemia may have a suppressive effect on PTH synthesis and /or secretion . Therefore , elevated serum Mg levels may play a role in the pathogenesis of adynamic bone disease 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 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 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 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 BACKGROUND Elevations in serum phosphorus are associated with renal decline in animal models and progression of established chronic kidney disease ( CKD ) in human observational studies . We examined whether serum phosphorus levels increase the risk of incident CKD or end-stage renal disease ( ESRD ) in two population -based prospect i ve cohort studies . METHODS Overall , 2269 participants free of CKD [ estimated glomerular filtration rate ( eGFR ) < 60 mL/min/1.73(2 ) ] from the Framingham Heart Study ( FHS ; mean age 42 years ; 53 % women ) and 13,372 participants from the Third National Health and Nutrition Examination Survey ( NHANES III ; mean age 44.3 years , 52 % women ) contributed to the present study . In the FHS , we evaluated the relationship between baseline phosphorus category ( < 2.5 mg/dL , 2.5 - 3.49 mg/dL , 3.5 - 3.99 mg/dL and ≥4 mg/dL ) and incident CKD ( n = 267 ) . In NHANES , we examined the relationship between phosphorus below and above 4 mg/dL in relation to incident ESRD ( n = 65 ) . RESULTS FHS participants in the highest phosphorus category had an increased risk of CKD [ odds ratio 2.14 ; 95 % confidence interval ( CI ) , 1.07 - 4.28 ; P = 0.03 ] in multivariable-adjusted models when compared to the referent group ( 2.5 - 3.49 mg/dL ) . Similarly , NHANES III participants with phosphorus levels ≥4 mg/dL demonstrated an increased risk of incident ESRD compared to those < 4 mg/dL ( relative risk 1.90 ; 95 % CI 1.03 - 3.53 ; P = 0.04 ) . CONCLUSIONS In prospect i ve studies of the general population , serum phosphorus levels in the upper-normal range were associated with a doubling in the risk of developing incident CKD and ESRD Background Coronary calcification in patients with end-stage renal disease ( ESRD ) is associated with an increased risk of cardiovascular outcomes and death from all causes . Previous evidence has been limited by short follow-up periods and inclusion of a heterogeneous cluster of events in the primary analyses . Objective To describe coronary calcification in patients incident to ESRD , and to identify whether calcification predicts vascular events or death . Design Prospect i ve sub study of an inception cohort . Setting Tertiary care haemodialysis centre in Ontario ( St Joseph ’s Healthcare Hamilton ) . Participants Patients starting haemodialysis who were new to ESRD . Measurements At baseline , clinical characterization and spiral computed tomography ( CT ) to score coronary calcification by the Agatston-Janowitz 130 scoring method . A primary outcome composite of adjudicated stroke , myocardial infa rct ion , or death . Methods We followed patients prospect ively to identify the relationship between cardiac calcification and subsequent stroke , myocardial infa rct ion , or death , using Cox regression . Results We recruited 248 patients in 3 centres to our main study , which required only biochemical markers . Of these 164 were at St Joseph ’s healthcare , and eligible to participate in the sub study ; of these , 51 completed CT scanning ( 31 % ) . Median follow up was 26 months ( Q1 , Q3 : 14 , 34 ) . The primary outcome occurred in 16 patients ; 11 in the group above the median and 5 in the group below ( p = 0.086 ) . There were 26 primary outcomes in 16 patients ; 20 ( 77 % ) events in the group above the coronary calcification median and 6 ( 23 % ) in the group below ( p = 0.006 ) . There were 10 deaths ; 8 in the group above the median compared with 2 in the group below ( p = 0.04 ) . The hazard ratios for coronary calcification above , compared with below the median , for the primary outcome composite were 2.5 ( 95 % CI 0.87 , 7.3 ; p = 0.09 ) and 1.7 ( 95 % CI 0.55 , 5.4 ; p = 0.4 ) , unadjusted and adjusted for age , respectively . For death , the hazard ratios were 4.6 ( 95 % CI 0.98 , 21.96 ; p = 0.054 ) and 2.4 ( 95 % CI 0.45 , 12.97 ; p = 0.3 ) respectively . Limitations We were limited by a small sample size and a small number of events . Conclusions Respondent burden is high for additional testing around the initiation of dialysis . High coronary calcification in patients new to ESRD has a tendency to predict cardiovascular outcomes and death , though effects are attenuated when adjusted for age . Abrégé Context eLa calcification de l'artère coronaire chez les patients atteints d’insuffisance rénale terminale ( IRT ) est associée à un risque accru de troubles cardiovasculaires et de mortalité , toutes causes confondues . Les données précédemment recueillies se limitaient à un suivi de courte durée , de même qu’à l ’ inclusion de séries d’accidents non liés lors de l’analyse préliminaire . ObjectifsDécrire la calcification de l'artère coronaire chez les patients atteints d’IRT et déterminer si la calcification de l'artère coronaire peut prédire des accidents vasculaires et la mort . Type d’étudeSous-étude prospect i ve de cohorte selon le mode d'installation . CadreUne unité de soins tertiaires en dialyse , en Ontario ( St Joseph ’s Healthcare Hamilton ) . Participants Des patients qui sont nouvellement atteints d’IRT et qui entament une hémodialyse . MesuresEn début de traitement , une caractérisation clinique et une tomodensitométrie ( TDM ) hélicoïdale qui permettent de mesurer la calcification de l'artère coronaire sur 130 , selon l’échelle d’Agatston-Janowitz . L’indicateur principal des résultats comprend l’AVC , l’infa rct us du myocarde ou la mort . MéthodesNous avons suivi les patients de manière prospect i ve , afin de cibler la relation entre la calcification de l'artère coronaire et l’AVC , l’infa rct us du myocarde ou la mort subséquente , en utilisant la régression de Cox . RésultatsNous avons recruté 248 patients dans trois unités , dans le cadre de l’étude principale , qui ne requérait que des biomarqueurs chimiques . De ces patients , 164 étaient de St Joseph ’s Healthcare , et étaient admissibles à la sous-étude ; 51 avaient effectué une tomographie par ordinateur ( 31 % ) . Le suivi médian s’étendait sur 26 mois ( Q1 , Q3 : 14 , 34 ) . L’indicateur principal a été observé chez 16 patients ; 11 dans le groupe se trouvant au-dessus de la médiane , et 5 dans le groupe inférieur ( p?=?0,086 ) . On a observé 26 indicateurs principaux chez 16 patients ; 20 ( 77 % ) accidents dans le groupe se trouvant au-dessus de la médiane en ce qui a trait à la calcification et 6 ( 23 % ) dans le groupe inférieur ( p?=?0,006 ) . Il y a eu 10 décès ; 8 dans le groupe se trouvant au-dessus de la médiane et 2 dans le groupe inférieur ( p?=?0,04 ) . Les taux de risque de calcification de l'artère coronaire se trouvant au-dessus et sous la médiane , pour les indicateurs principaux , étaient respectivement de 2,5 ( 95 % IC 0,98 ; 21,96 ; p?=?0,054 ) et 2,4 ( 95 % IC 0,45 , 12,97 ; p?=?0,3).Limites de l’étudeNous avons été limités par la taille restreinte de l’échantillon , de même que par le petit nombre d’accidents . Conclusion Le fardeau du répondant repose sur des examens supplémentaires au moment de commencer la dialyse . Un fort taux de calcification de l’artère coronaire chez les patients nouvellement atteints d’IRT tend à prédire des accidents cardiovasculaires et la mort , bien que les effets soient atténués après révision en fonction de l'âge 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 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. 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 Background The relative effectiveness and safety of sevelamer , a mineral-free phosphate binder , for treatment of hyperphosphatemia in children with chronic kidney disease is uncertain . Aim This study was design ed to compare the efficacy and acceptability of sevelamer hydrochloride to calcium acetate as a phosphate binder in pediatric patients with chronic kidney disease . Methods A 12-week open-label trial of sevelamer hydrochloride vs calcium acetate was initiated in 22 patients , aged 2–18 , with CKD stages 3 and 4 . After a 2-week washout of phosphate binders and vitamin D , patients were r and omized to receive sevelamer hydrochloride or calcium acetate . The effect of therapy was adjusted for baseline blood levels of calcium , phosphorus , calcium-phosphate product , alkaline phosphatase , PTH and GFR using ANOVA . The primary end point was the decrease in serum phosphorus levels after 12 weeks of treatment . Results Of the 22 patients enrolled , data of 19 patients were used for analysis . The adjusted mean serum phosphate levels at 12 weeks did not differ significantly between calcium acetate- ( 5.3 mg/dl ) and sevelamer-treated subjects ( 6.1 mg/dl ) ( P adjusted means = 0.6 ) . The adjusted blood level of calcium at 12 weeks was significantly lower in the sevelamer-treated patients ( 8.2 mg/dl ) compared to those treated with calcium acetate ( 9.1 mg/dl ) ( P adjusted means = 0.01 ) . In the sevelamer group , there was a non-significant decrease in serum bicarbonate , whereas the total and LDL cholesterol significantly decreased at 12 weeks ( P = 0.04 ) . Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug . Conclusions Compared to calcium acetate , use of sevelamer in children with chronic kidney disease is associated with similar reduction in serum phosphate levels , lower risk of hypercalcemia , and marked decrease in serum lipid levels 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 / Aim : Dietary phosphate intake and vitamin D receptor activator ( VDRA ) regulate fibroblast growth factor 23 ( FGF23 ) ; iron may modulate FGF23 metabolism . We aim ed to determine whether oral iron supplementation influences serum FGF23 concentration in hemodialysis ( HD ) patients , while excluding the effect of dietary phosphate intake . Methods : This prospect i ve study enrolled 27 maintenance HD patients with iron deficiency and hyperphosphatemia treated with sevelamer-HCl . The phosphate binder was changed from sevelamer-HCl to ferric citrate hydrate ( FCH ) to maintain constant phosphate levels . VDRA , other phosphate binders , and cinacalcet HCl were not changed . Serum intact FGF23 , C-terminal FGF23 ( C-term FGF23 ) , intact parathyroid hormone ( PTH ) , 1,25(OH)2D and other parameters were monitored for 12 weeks . Results : Serum phosphate levels ( 5.89 ± 1.45 mg/dl at baseline , 5.54 ± 1.35 mg/dl at 12 weeks ) and 1,25(OH)2D levels were unchanged . Serum ferritin levels increased from 25.6 ± 24.3 ng/ml at baseline to 55.8 ± 33.5 ng/ml at 12 weeks with FCH administration . Serum intact FGF23 and C-term FGF23 levels significantly decreased at 12 weeks compared with baseline ( 2,000 ( 1,300.0 - 3,471.4 ) to 1,771.4 ( 1,142.9 - 2,342.9 ) pg/ml , p = 0.01 , and 1,608.7 ( 634.8 - 2,308.7 ) to 1,165.2 ( 626.1 - 1,547.8 ) RU/ml , p = 0.007 , respectively ) ; serum intact PTH levels significantly increased ( 96 ( 65 - 125 ) to 173 ( 114 - 283 ) pg/ml , p < 0.001 ) . Conclusions : Oral FCH administration decreased serum intact FGF23 and C-term FGF23 levels and increased intact PTH levels ; phosphate and 1,25(OH)2D levels were unchanged . Oral FCH administration to treat iron deficiency is a possible strategy for reducing serum FGF23 levels independent of phosphate and VDRA 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 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 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 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 Abstract Background : Cardiac valve calcification ( CVC ) and left ventricular ( LV ) alterations are frequent complication in end-stage renal disease ( ESRD ) . We determined the prevalence of CVC and LV hypertrophy ( LVH ) in ESRD patients before renal replacement therapy and 12 months after peritoneal dialysis ( PD ) . Methods : A prospect i ve longitudinal of 50 incident PD patients was studied . Demographic and clinical data were recorded and blood assayed at baseline and after 1-year of follow-up . CVC and LVH were evaluated by M-mode two-dimensional echocardiography . Results : CVC of the mitral and aortic valves and of both valves were noted in 30 , 18 and 10 % of patients , respectively . After 12 months of PD regimen , 20 % patients had aortic , 24 % mitral and 8 % had calcification of both valves . After one year of PD , LVH was 62 and 36 % in patients with and without CVC , respectively ( p < 0.05 ) . Endothelin-1 is an independent predictor of CVC at the baseline , while nitric oxide is inversely an independent predictor at the end of follow-up . Conclusions : CVC is associated with LVH in PD patients . These findings identified a potential role for monitored markers to be incorporated into therapeutic strategies aim ed at detection and treatment of cardiovascular complications and prevention strategies 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 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 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 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 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 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 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 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 |
11,705 | 24,740,211 | Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment .
The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment .
Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period .
The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period .
Plasma nitrate and nitrite levels , and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols .
According to these results , a single oral dose of flavan-3-ols elevates blood pressure and flow transiently , and these effects induce NO production through increased shear stress on endothelial cells | Several systematic review s have reported that flow mediated dilatation ( FMD ) was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols ; however , the mechanisms responsible for this effect are not clear .
In this study , we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo . | Moderate-intensity endurance exercise training improves vascular endothelial vasomotor function ; however , the impact of high-intensity exercise training has been equivocal . Thus , the effect of the physiological stress of the exercise remains poorly understood . Furthermore , enhanced vascular repair mediated by circulating progenitor cells may also be improved . To address whether the physiological stress of exercise training is an important factor contributing to these adaptations , 20 healthy participants trained for 6 weeks . Training involved either moderate ( MSIT ; n= 9 ) or heavy metabolic stress ( HSIT ; n= 11 ) interval exercise training programmes matched for total work and duration of exercise . Before and after training , flow-mediated dilatation , low-flow-mediated constriction and total vessel reactivity were measured at the brachial artery using Doppler ultrasound . Circulating progenitor cells ( CD34 + , CD133 + and CD309/KDR+ ) were measured by flow cytometry ( means ± SD ) . Relative ( MSIT pre- 5.5 ± 3.4 versus post-training 6.6 ± 2.5 % ; HSIT pre- 6.6 ± 4.1 versus post-training 7.0 ± 3.4 % , P= 0.33 ) and normalized ( P= 0.16 ) flow-mediated dilatation did not increase with either training programme . However , low-flow-mediated constriction was greater after training in both groups ( MSIT pre- −0.5 ± 3.2 versus post-training −1.9 ± 3.1 % ; HSIT pre- −1.0 ± 1.7 versus post-training −2.9 ± 3.0 % , P= 0.04 ) and contributed to greater total vessel reactivity ( MSIT pre- 7.4 ± 3.3 versus post-training 10.1 ± 3.7 % ; HSIT pre- 10.9 ± 5.9 versus post-training 12.7 ± 6.2 % , P= 0.01 ) . Peak reactive hyperaemia and the area under the shear rate curve were not different between groups , either before or after training . Although circulating progenitor cell numbers increased following heavy-intensity interval exercise training , variability was great amongst participants [ MSIT pre- 16 ± 18 versus post-training 14 ± 12 cells ( ml whole blood)−1 ; HSIT pre- 8 ± 6 versus post-training 19 ± 23 cells ( ml whole blood)−1 , P= 0.50 ] . Overall , vasoconstrictor function may be augmented by moderate- and heavy-intensity interval exercise training in young adults . However , circulating progenitor cell numbers were not increased , suggesting that these cells are not likely to be upregulated as a result of training OBJECTIVES Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients . BACKGROUND Even in fully medicated diabetic patients , overall prognosis is unfavorable due to deteriorated cardiovascular function . Based on epidemiological data , diets rich in flavanols are associated with a reduced cardiovascular risk . METHODS In a feasibility study with 10 diabetic patients , we assessed vascular function as flow-mediated dilation ( FMD ) of the brachial artery , plasma levels of flavanol metabolites , and tolerability after an acute , single-dose ingestion of cocoa , containing increasing concentrations of flavanols ( 75 , 371 , and 963 mg ) . In a subsequent efficacy study , changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day , thrice-daily dietary intervention with either flavanol-rich cocoa ( 321 mg flavanols per dose ) or a nutrient-matched control ( 25 mg flavanols per dose ) . Both studies were undertaken in a r and omized , double-masked fashion . Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites , respectively . RESULTS A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD ( at 2 h : from 3.7 + /- 0.2 % to 5.5 + /- 0.4 % , p < 0.001 ) . A 30-day , thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30 % ( p < 0.0001 ) , while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study . Treatment was well tolerated without evidence of tachyphylaxia . Endothelium-independent responses , blood pressure , heart rate , and glycemic control were unaffected . CONCLUSIONS Diets rich in flavanols reverse vascular dysfunction in diabetes , highlighting therapeutic potentials in cardiovascular disease An inverse relation exists between intake of flavonoid-rich foods , such as cocoa , and cardiovascular-related mortality . Favorable effects of flavonoids on the endothelium may underlie these associations . We performed a r and omized , double-blind , placebo-controlled study to test the hypothesis that acute cocoa ingestion dose dependently increases endothelium-dependent vasodilation , as measured by an increase in brachial artery flow-mediated dilation ( FMD ) , in healthy older adults . Measurements were obtained before ( preingestion ) and after ( 1- and 2-h postingestion ) ingestion of 0 ( placebo ) , 2 , 5 , 13 , and 26 g of cocoa in 23 adults ( 63 ± 2 yr old , mean ± SE ) . Changes in brachial artery FMD 1- and 2-h postingestion compared with preingestion were used to determine the effects of cocoa . FMD was unchanged 1 ( Δ-0.3 ± 0.2%)- and 2-h ( Δ0.1 ± 0.1 % ) after placebo ( 0 g cocoa ) . In contrast , FMD increased both 1-h postingestion ( 2 g cocoa Δ0.0 ± 0.2 % , 5 g cocoa Δ0.8 ± 0.3 % , 13 g cocoa Δ1.0 ± 0.3 % , and 26 g cocoa Δ1.6 ± 0.3 % : P < 0.05 compared with placebo for 5 , 13 , and 26 g cocoa ) and 2-h postingestion ( 2 g cocoa Δ0.5 ± 0.3 % , 5 g cocoa Δ1.0 ± 0.3 % , 13 g cocoa Δ1.4 ± 0.2 % , and 26 g cocoa Δ2.5 ± 0.4 % : P < 0.05 compared with placebo for 5 , 13 , and 26 g cocoa ) on the other study days . A serum marker of cocoa ingestion ( total epicatechin ) correlated with increased FMD 1- and 2-h postingestion ( r = 0.44 - 0.48 ; both P < 0.05 ) . Collectively , these results indicate that acute cocoa ingestion dose dependently increases brachial artery FMD in healthy older humans . These responses may help to explain associations between flavonoid intake and cardiovascular-related mortality in humans |
11,706 | 23,872,953 | Epidemiologic studies have shown that , overall , the habitual consumption of a diet high in saturated fat , well-done meats , and calcium is associated with an increased risk for advanced prostate cancer .
An inconsistent association was observed for intake of total meat , fruits , and vegetables .
Although most case-control studies suggest that intake of these nutrients or foods significantly alters advanced prostate cancer risk , cohort studies yielded mixed results .
No apparent effect of fish and zinc intake on advanced prostate cancer was found in most epidemiologic studies .
Epidemiologic studies conducted to date have revealed that some dietary factors modulate the risk for advanced prostate cancer .
If these findings are confirmed by more adequately powered epidemiologic studies , especially prospect i ve cohort studies that measure the nutrients and their biochemical indicators , the risk of advanced prostate cancer , which is fatal and thus clinical ly significant , may be reduced by dietary modification or chemoprevention | Prostate cancer is the second most common cancer among men worldwide .
Although some nutrients have been linked to the development of total prostate cancer , it remains unclear whether these nutrients modulate the risk of its clinical ly significant form - advanced tumor .
Therefore , this study sought to perform a systematic review of the literature on this topic . | We prospect ively investigated the associations between dietary patterns and risk of prostate cancer in the Health Professionals Follow-up Study . Between 1986 and 2000 , 3,002 incident prostate cancer cases were identified in our cohort . Using factor analysis , two major dietary patterns were identified , a prudent and a western dietary pattern . Dietary patterns were not appreciably associated with risk of total prostate cancer . For the highest versus the lowest quintiles , the multivariable relative risk ( RR ) for the prudent pattern was 0.94 [ 95 % confidence interval ( CI ) , 0.83 - 1.06 ] , and for the western pattern , the multivariable RR was 1.03 ( 95 % CI , 0.92 - 1.17 ) . Neither were these associated with risk of advanced prostate cancer [ highest versus lowest quintile , prudent pattern ( RR , 1.01 ; 95 % CI , 0.68 - 1.49 ) ; western pattern ( RR , 1.13 ; 95 % CI , 0.77 - 1.67 ) ] . Higher western pattern scores were suggestively associated with a greater risk of advanced prostate cancer among older men [ highest versus lowest quintile ( RR , 1.35 ; 95 % CI , 0.97 - 1.90 ) ] , but not after adding processed meat to the model [ highest versus lowest quintile ( RR , 1.11 ; 95 % CI , 0.75 - 1.65 ) ] . We did not find any evidence for a protective association between prudent pattern and risk of prostate cancer . The lack of association between a western dietary pattern as identified by factor analysis in our cohort and prostate cancer risk suggests that dietary risk factors for prostate cancer are likely to differ from those for other conditions , such as cardiovascular disease and type 2 diabetes , that have been associated with a western dietary pattern in this cohort . ( Cancer Epidemiol Biomarkers Prev 2006;15(1):167–71 BACKGROUND Multivitamin supplements are used by millions of Americans because of their potential health benefits , but the relationship between multivitamin use and prostate cancer is unclear . METHODS We prospect ively investigated the association between multivitamin use and risk of prostate cancer ( localized , advanced , and fatal ) in 295,344 men enrolled in the National Institutes of Health (NIH)-AARP Diet and Health Study who were cancer free at enrollment in 1995 and 1996 . During 5 years of follow-up , 10,241 participants were diagnosed with incident prostate cancer , including 8765 localized and 1476 advanced cancers . In a separate mortality analysis with 6 years of follow-up , 179 cases of fatal prostate cancer were ascertained . Multivitamin use was assessed at baseline as part of a self-administered , mailed food-frequency question naire . Relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were calculated by use of Cox proportional hazards regression , adjusted for established or suspected prostate cancer risk factors . RESULTS No association was observed between multivitamin use and risk of localized prostate cancer . However , we found an increased risk of advanced and fatal prostate cancers ( RR = 1.32 , 95 % CI = 1.04 to 1.67 and RR = 1.98 , 95 % CI = 1.07 to 3.66 , respectively ) among men reporting excessive use of multivitamins ( more than seven times per week ) when compared with never users . The incidence rates per 100,000 person-years for advanced and fatal prostate cancers for those who took a multivitamin more than seven times per week were 143.8 and 18.9 , respectively , compared with 113.4 and 11.4 in never users . The positive associations with excessive multivitamin use were strongest in men with a family history of prostate cancer or who took individual micronutrient supplements , including selenium , beta-carotene , or zinc . CONCLUSION These results suggest that regular multivitamin use is not associated with the risk of early or localized prostate cancer . The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation BACKGROUND Anticarcinogenic activities of vitamin K have been observed in various cancer cell lines , including prostate cancer cells . Epidemiologic studies linking dietary intake of vitamin K with the development of prostate cancer have not yet been conducted . OBJECTIVE We evaluated the association between dietary intake of phylloquinone ( vitamin K1 ) and menaquinones ( vitamin K2 ) and total and advanced prostate cancer in the Heidelberg cohort of the European Prospect i ve Investigation into Cancer and Nutrition . DESIGN At baseline , habitual dietary intake was assessed by means of a food-frequency question naire . Dietary intake of phylloquinone and menaquinones ( MK-4 - 14 ) was estimated by using previously published HPLC-based food-content data . Multivariate-adjusted relative risks of total and advanced prostate cancer in relation to intakes of phylloquinone and menaquinones were calculated in 11 319 men by means of Cox proportional hazards regression . RESULTS During a mean follow-up time of 8.6 y , 268 incident cases of prostate cancer , including 113 advanced cases , were identified . We observed a nonsignificant inverse association between total prostate cancer and total menaquinone intake [ multivariate relative risk ( highest compared with lowest quartile ) : 0.65 ; 95 % CI : 0.39 , 1.06 ] . The association was stronger for advanced prostate cancer ( 0.37 ; 0.16 , 0.88 ; P for trend = 0.03 ) . Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat . Phylloquinone intake was unrelated to prostate cancer incidence ( 1.02 ; 0.70 , 1.48 ) . CONCLUSIONS Our results suggest an inverse association between the intake of menaquinones , but not that of phylloquinone , and prostate cancer . Further studies of dietary vitamin K and prostate cancer are warranted 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 The incidence of prostate cancer is much lower in Asian than Western population s. Given that environmental factors such as dietary habits may play a major role in the causation of prostate cancer and the high consumption of green tea in Asian population s , this low incidence may be partly due to the effects of green tea . The JPHC Study ( Japan Public Health Center-based Prospect i ve Study ) was established in 1990 for cohort I and in 1993 for cohort II . The subjects were 49,920 men aged 40 - 69 years who completed a question naire that included their green tea consumption habit at baseline and were followed until the end of 2004 . During this time , 404 men were newly diagnosed with prostate cancer , of whom 114 had advanced cases , 271 were localized , and 19 were of an undetermined stage . Green tea was not associated with localized prostate cancer . However , consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer . The multivariate relative risk was 0.52 ( 95 % confidence interval : 0.28 , 0.96 ) for men drinking 5 or more cups/day compared with less than 1 cup/day ( p(trend ) = 0.01 ) . Green tea may be associated with a decreased risk of advanced prostate cancer Phytanic acid is a saturated fatty acid found predominantly in red meat and dairy products and may contribute to increases in prostate cancer risk that are observed with higher intakes of these foods . We constructed a novel summary measure of phytanic acid intake and prospect ively examined its association with prostate cancer risk in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study --a cohort of Finnish male smokers aged 50 - 69 years . Diet was assessed at baseline in 27,111 participants using a vali date d 276-item dietary question naire . Since phytanic acid is not currently included in food composition tables , we used the published phytanic acid content of 151 major food items to estimate total daily intake . During up to 21 years of follow-up , a total of 1,929 incident prostate cancer cases ( including 438 advanced cases ) were identified . Higher phytanic acid intake , though unrelated to the risk of localized disease [ relative risks ( RR ) and 95 % confidence intervals ( CI ) for increasing quartiles of intake = 1.00 ( ref ) , 0.83 ( 0.68 - 1.01 ) , 0.76 ( 0.62 - 0.94 ) and 0.91 ( 0.74 - 1.13 ) ; p trend = 0.23 ] , was associated with increased risks of advanced prostate cancer [ RR and 95 % CI = 1.00 ( ref ) , 1.43 ( 1.09 - 1.89 ) , 1.31 ( 0.99 - 1.75 ) and 1.38 ( 1.02 - 1.89 ) ; p trend = 0.06 ] . This association appeared to be driven predominantly by phytanic acid obtained from dairy products ( particularly butter ) . Our study indicates that phytanic acid may contribute to previously observed associations between high-fat animal foods ( particularly dairy products ) and prostate cancer risk , although some caution is warranted as it may be acting as a surrogate marker of dairy fat Supplemental vitamin E ( α-tocopherol ) has been linked to lower prostate cancer incidence in one r and omized trial and several , although not all , observational studies . The evidence regarding dietary intake of individual vitamin E isoforms and prostate cancer is limited and inconclusive , however . We prospect ively examined the relations of supplemental vitamin E and dietary intakes of α- , β- , γ- , and δ- tocopherols to prostate cancer risk among 295,344 men , ages 50 to 71 years and cancer-free at enrollment in 1995 to 1996 , in the NIH-AARP Diet and Health Study . At baseline , participants completed a question naire that captured information on diet , supplement use , and other factors . Proportional hazards models were used to estimate relative risks ( RR ) and 95 % confidence intervals ( 95 % CI ) of prostate cancer . During 5 years of follow-up , 10,241 incident prostate cancers were identified . Supplemental vitamin E intake was not related to prostate cancer risk ( for > 0 - 99 , 100 - 199 , 200 - 399 , 400 - 799 , and ≥800 IU/d versus never use : RR , 0.97 , 0.89 , 1.03 , 0.99 , and 0.97 ( 95 % CI , 0.87 - 1.07 ) respectively ; Ptrend = 0.90 ) . However , dietary γ-tocopherol , the most commonly consumed form of vitamin E in the United States , was significantly inversely related to the risk of advanced prostate cancer ( for highest versus lowest quintile : RR , 0.68 ; 95 % CI , 0.56 - 0.84 ; Ptrend = 0.001 ) . These results suggest that supplemental vitamin E does not protect against prostate cancer , but that increased consumption of γ-tocopherol from foods is associated with a reduced risk of clinical ly relevant disease . The potential benefit of γ-tocopherol for prostate cancer prevention deserves further attention . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1128–35 High-temperature cooked meat contains heterocyclic amines , including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP ) , and polycyclic aromatic hydrocarbons , such as benzo(a)pyrene ( BaP ) . In rodents , a high intake of PhIP induces prostate tumors . We prospect ively investigated the association between meat and meat mutagens , specifically PhIP , and prostate cancer risk in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . Diet was assessed using a 137-item food frequency question naire and a detailed meat-cooking question naire linked to a data base for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline ( MeIQx ) , 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline ( DiMeIQx ) , and PhIP . During follow-up , we ascertained a total of 1,338 prostate cancer cases among 29,361 men ; of these , 868 were incident cases ( diagnosed after the first year of follow-up ) and 520 were advanced cases ( stage III or IV or a Gleason score of > or = 7 ) . Total , red , or white meat intake was not associated with prostate cancer risk . More than 10 g/d of very well done meat , compared with no consumption , was associated with a 1.4-fold increased risk of prostate cancer [ 95 % confidence interval ( 95 % CI ) , 1.05 - 1.92 ] and a 1.7-fold increased risk ( 95 % CI , 1.19 - 2.40 ) of incident disease . Although there was no association with MeIQx and DiMeIQx , the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer ( 95 % CI , 1.01 - 1.48 ) and a 1.3-fold increased risk of incident disease ( 95 % CI , 1.01 - 1.61 ) . In conclusion , very well done meat was positively associated with prostate cancer risk . In addition , this study lends epidemiologic support to the animal studies , which have implicated PhIP as a prostate carcinogen Laboratory and clinical data indicate an antitumor effect of 1,25(OH)2 vitamin D ( 1,25(OH)2D ) on prostate cancer . High calcium intake suppresses formation of 1,25(OH)2D from 25(OH)D , thereby decreasing the 1,25(OH)2D level . Ingestion of fructose reduces plasma phosphate transiently , and hypophosphatemia stimulates 1,25(OH)2D production . We thus conducted a prospect i ve study among 47,781 men of the Health Professionals Follow-Up Study free of cancer in 1986 to examine whether calcium and fructose intake influenced risk of prostate cancer . Between 1986 and 1994 , 1369 non-stage A1 and 423 advanced ( extraprostatic ) cases of prostate cancer were diagnosed . Higher consumption of calcium was related to advanced prostate cancer [ multivariate relative risk ( RR ) , 2.97 ; 95 % confidence interval ( CI ) , 1.61 - 5.50 for intakes > or = 2000 mg/day versus < 500 mg/day ; P , trend , 0.002 ] and metastatic prostate cancer ( RR , 4.57 ; CI , 1.88 - 11.1 ; P , trend , < 0.001 ) . Calcium from food sources and from supplements independently increased risk . High fructose intake was related to a lower risk of advanced prostate cancer ( multivariate RR , 0.51 ; CI , 0.33 - 0.80 , for intakes > 70 versus < or = 40 g/day ; P , trend , 0.007 ) . Fruit intake was inversely associated with risk of advanced prostate cancer ( RR , 0.63 ; 95 % CI , 0.43 - 0.93 ; for > 5 versus < or = 1 serving per day ) , and this association was accounted for by fructose intake . Non-fruit sources of fructose similarly predicted lower risk of advanced prostate cancer . A moderate positive association between energy-adjusted fat intake and advanced prostate cancer was attenuated and no longer statistically significant when controlled for calcium and fructose . Our findings provide indirect evidence for a protective influence of high 1,25(OH)2D levels on prostate cancer and support increased fruit consumption and avoidance of high calcium intake to reduce the risk of advanced prostate cancer BACKGROUND Prostate cancer is a disease with a complex etiology . Oxidative stress has been implicated in its pathogenesis ; however , few prospect i ve studies have investigated the association between an oxidative stress/balance score and risk of prostate cancer . METHODS We investigated associations between an oxidative balance score , calculated as the summation of individual scores obtained from five pro-oxidative and eight anti-oxidative exposures , as well as each individual constituent of the score and risks of prostate cancer overall , and by clinical characteristics , in a case-cohort study ( 661 cases and 1864 subcohort ) nested within the Canadian Study of Diet , Lifestyle , and Health cohort . Men in the lowest quintiles of each pro-oxidant exposure received a score of four ( the highest score ) , while those in the highest quintile received a score of zero ( the lowest score ) . In contrast , scoring for all anti-oxidants was performed in the opposite way . Total oxidative balance score was calculated by summating all individual scores of pro- and anti-oxidative variables , with higher values indicating a higher antioxidant status . RESULTS The average oxidative balance score was similar between prostate cancer cases and men in the subcohort : 25.2 and 25.3 , respectively . There was no association between oxidative balance score and overall risk of prostate cancer with hazard ratios ( HRs ) of 1.00 , 1.02 , 1.03 , 0.97 and 1.01 for increasing quintiles of the score ( p-trend=0.71 ) . There were also no associations for non-advanced or advanced disease , or when analysis was restricted to incident cases that arose after two years of follow-up ( n=508 ) . In general constituents of the score were not associated with prostate cancer , except for red meat intake ( HR=1.44 ; 95%CI 1.06 - 1.95 comparing Q5 vs. Q1 ) and lycopene ( HRs of 0.7 - 0.8 for increasing quintiles ) . CONCLUSION Our findings do not support an association between oxidative balance score and risks of overall prostate cancer or advanced disease Meats cooked at high temperatures , such as pan-frying or grilling , are a source of carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons . We prospect ively examined the association between meat types , meat cooking methods , meat doneness , and meat mutagens and the risk for prostate cancer in the Agricultural Health Study . We estimated relative risks and 95 % confidence intervals ( 95 % CI ) for prostate cancer using Cox proportional hazards regression using age as the underlying time metric and adjusting for state of residence , race , smoking status , and family history of prostate cancer . During 197,017 person-years of follow-up , we observed 668 incident prostate cancer cases ( 613 of these were diagnosed after the first year of follow-up and 140 were advanced cases ) among 23,080 men with complete dietary data . We found no association between meat type or specific cooking method and prostate cancer risk . However , intake of well or very well done total meat was associated with a 1.26-fold increased risk of incident prostate cancer ( 95 % CI , 1.02 - 1.54 ) and a 1.97-fold increased risk of advanced disease ( 95 % CI , 1.26 - 3.08 ) when the highest tertile was compared with the lowest . Risks for the two heterocyclic amines 2-amino-3,4,8-trimethylimidazo-[4,5-f]quinoxaline and 2-amino-3,8-dimethylimidazo-[4,5-b]quinoxaline were of borderline significance for incident disease [ 1.24 ( 95 % CI , 0.96 - 1.59 ) and 1.20 ( 95 % CI , 0.93 - 1.55 ) , respectively ] when the highest quintile was compared with the lowest . In conclusion , well and very well done meat was associated with an increased risk for prostate cancer in this cohort . ( Cancer Epidemiol Biomarkers Prev 2008;17(1):80–7 Red and processed meat may increase risk of advanced prostate cancer . Data on postdiagnostic diet and prostate cancer are sparse , but postdiagnostic intake of poultry with skin and eggs may increase risk of disease progression . Therefore , we prospect ively examined total , unprocessed , and processed red meat , poultry , and eggs in relation to risk of lethal prostate cancer ( e.g. , men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up ) among 27 , 607 men followed from 1994 to 2008 . We also conducted a case-only survival analysis to examine postdiagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with nonmetastatic prostate cancer during follow-up . In the incidence analysis , we observed 199 events during 306,715 person-years . Men who consumed 2.5 or more eggs per week had an 81 % increased risk of lethal prostate cancer compared with men who consumed less than 0.5 eggs per week ( HR : 1.81 ; 95 % CI : 1.13–2.89 ; Ptrend : 0.01 ) . In the case-only survival analysis , we observed 123 events during 19,354 person-years . There were suggestive , but not statistically significant , positive associations between postdiagnostic poultry ( HR ≥ 3.5 vs. < 1.5 servings per week : 1.69 ; 95 % CI : 0.96–2.99 ; Ptrend : 0.07 ) and postdiagnostic processed red meat ( HR ≥ 3 vs. < 0.5 servings per week : 1.45 ; 95 % CI : 0.73–2.87 ; Ptrend : 0.08 ) and risk of progression of localized prostate cancer to lethal disease . In conclusion , consumption of eggs may increase risk of developing a lethal form of prostate cancer among healthy men . Cancer Prev Res ; 4(12 ) ; 2110–21 . © 2011 AACR Higher intakes of calcium and dairy products , a major source of dietary calcium , are reported to increase the risk of prostate cancer , potentially due to reductions in circulating vitamin D with increasing calcium intake . We prospect ively examined the association of dairy product and calcium intake with prostate cancer risk in 29,509 men , including 1,910 cases , in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . We also evaluated the relation of calcium intake with serum 25-hydroxy-vitamin D [ 25(OH)D ] and 1,25-dihydroxy-vitamin D [ 1,25(OH)2D ] , in a Prostate , Lung , Colorectal , and Ovarian Trial sub study ( n = 275 ) . Dietary intake was assessed using a food frequency question naire . Baseline serum 1,25(OH)2D was determined by RIA . Greater intake of dairy products , particularly low-fat dairy products , was weakly associated with increased risk of prostate cancer [ relative risk ( RR ) , 1.12 ; 95 % confidence intervals ( CI ) , 0.97 - 1.30 ; P trend = 0.06 for > 2.75 versus ≤0.98 servings of total dairy/day ; 1.23 ( 1.07 - 1.41 ) for low-fat dairy ] . Greater dietary calcium intake was associated with increased risk of prostate cancer ( RR , 1.34 ; 95 % CI , 0.93 - 1.94 ; P trend = 0.02 for > 2,000 versus < 1,000 mg/day ) , but greater supplementary calcium intake was not associated with the risk . Associations of dairy product and dietary calcium intake were evident for nonaggressive disease ( RR , 1.20 ; 95 % CI , 0.99 - 1.46 ; P trend = 0.01 for dairy products ; 1.64 , 1.04 - 2.57 ; P trend = 0.002 for dietary calcium ) , but not aggressive disease ( RR , 1.02 ; 95 % CI , 0.81 - 1.28 for dairy products ; 0.94 , 0.49 - 1.80 for dietary calcium ) . Calcium intake was not associated with serum 25-hydroxy-vitamin D and 1,25(OH)2D concentration . In this large prospect i ve study in a prostate cancer screening trial , greater dietary intake of calcium and dairy products , particularly low-fat types , may be modestly associated with increased risks for nonaggressive prostate cancer , but was unrelated to aggressive disease . Furthermore , we found no relationship between calcium intake and circulating vitamin D. ( Cancer Epidemiol Biomarkers Prev 2007;16(12):2623–30 Laboratory and animal studies suggest a beneficial effect of zinc on prostate cancer . We evaluated the association between dietary and supplemental zinc and prostate cancer within the VITamins And Lifestyle ( VITAL ) cohort , a study specifically design ed to evaluate the impact of dietary supplements and cancer risk . Of 35,242 men who completed the baseline dietary and supplemental question naire , 832 men developed invasive prostate cancers between October 2000 and December 2004 . Ten-year average intake of supplemental zinc was not associated with a reduced prostate cancer risk overall ( adjusted hazard ratio ( HR ) = 0.82 ( 95 % confidence interval ( CI ) 0.58–1.14 ) for > 15mg/day vs. nonuse , P for trend = 0.44 ) ; however , risk of advanced prostate cancer ( regionally invasive or distant metastatic , n = 123 ) decreased with greater intake of supplemental zinc ( adjusted HR = 0.34 , 95 % CI = 0.13–1.09 for 10-yr average intake > 15 mg/day vs. nonuse , P for trend = 0.04 ) . Dietary zinc was not associated with prostate cancer . In this prospect i ve cohort , long-term supplemental zinc intake was associated with reduced risk of clinical ly relevant advanced disease . This study had limited ability to study early-stage disease because detection of early-stage disease is highly related to having a PSA test , and information on PSA was only available at baseline . Because few other epidemiologic studies have investigated the association between zinc and prostate cancer , and these have not yielded consistent findings , further research is needed Although dietary risk factors may differ between localized and advanced prostate cancer , data on associations between the consumption of fruits and vegetables and risk of localized and advanced cancers are limited . We examined associations between fruit and vegetable consumption and risk of prostate cancer in a Japanese population . During 1995–1998 , a vali date d food frequency question naire was administered to 43,475 men aged 45–74 yr . During 321,061 person-years of follow-up until the end of 2004 , 339 cases of prostate cancer were identified . Consumption of fruits or total vegetables was not associated with a decreased risk of total prostate cancer , with corresponding multivariate hazard ratios of the highest vs. lowest quartiles of 1.09 ( 95 % CI = 0.77–1.53 ; trend P = 0.39 ) for fruits and 1.33 ( 95 % CI = 0.93–1.91 ; trend P = 0.52 ) for total vegetables . Also , no association was observed for intake of either fruits or vegetables ( total or any subtype ) with localized or advanced prostate cancer . This prospect i ve cohort study suggests that consumption of fruits or vegetables may not be associated with the risk of either localized or advanced prostate cancer in Japanese men . However , the possibility of confounding by detection bias on the risk of localized cancer could not be totally ruled out α-Tocopherol supplementation ( 50 mg daily for 5 - 8 years ) reduced prostate cancer incidence by 32 % in the α-Tocopherol , β-Carotene Cancer Prevention Study . We investigated whether serum α-tocopherol or intake of vitamin E ( eight tocopherols and tocotrienols ) was associated with prostate cancer risk with up to 19 years of follow-up in the α-Tocopherol , β-Carotene Cancer Prevention Study cohort . Of the 29,133 Finnish male smokers , ages 50 to 69 years recruited into the study , 1,732 were diagnosed with incident prostate cancer between 1985 and 2004 . Baseline serum α-tocopherol was measured by high-performance liquid chromatography and the components of vitamin E intake were estimated based on a 276-item food frequency question naire and food chemistry analyses . Proportional hazard models were used to determine multivariate-adjusted relative risks ( RR ) and 95 % confidence intervals ( 95 % CI ) . Higher serum α-tocopherol was associated with reduced risk of prostate cancer ( RR , 0.80 ; 95 % CI , 0.66 - 0.96 for highest versus lowest quintile ; Ptrend = 0.03 ) and was strongly and inversely related to the risk of developing advanced disease ( RR , 0.56 ; 95 % CI , 0.36 - 0.85 ; Ptrend = 0.002 ) . The inverse serum α-tocopherol-prostate cancer association was greater among those who were supplemented with either α-tocopherol or β-carotene during the trial . There were no associations between prostate cancer and the individual dietary tocopherols and tocotrienols . In summary , higher prediagnostic serum concentrations of α-tocopherol , but not dietary vitamin E , was associated with lower risk of developing prostate cancer , particularly advanced prostate cancer . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1253–9 Lycopene bioavailability from a single dose of fresh tomatoes or tomato paste ( 23 mg lycopene ) ingested together with 15 g corn oil was compared by analyzing carotenoid concentrations in the chylomicron fraction . The lycopene isomer pattern was the same in both fresh tomatoes and tomato paste . The triacylglycerol response in chylomicrons was not significantly different after both treatments . Ingestion of tomato paste was found to yield 2.5-fold higher total and all-trans-lycopene peak concentrations ( P < 0.05 and P < 0.005 , respectively ) and 3.8-fold higher area under the curve ( AUC ) responses ( P < 0.001 ) than ingestion of fresh tomatoes . The same was calculated for lycopene cis-isomers , but only the AUC response for the cis-isomers was significantly higher after ingestion of tomato paste ( P < 0.005 ) . No difference was observed in the alpha- and beta-carotene response . Thus , in humans , the bioavailability of lycopene is greater from tomato paste than from fresh tomatoes |
11,707 | 27,261,419 | Depressive symptoms and older age were associated with less vigorous PA in meta-regression analyses .
Our data confirm that people with schizophrenia engage in significantly less moderate and vigorous PA versus controls . | OBJECTIVE Physical activity ( PA ) improves health outcomes in people with schizophrenia .
It is unclear how much PA people with schizophrenia undertake and what influences PA participation .
We conducted a meta- analysis to investigate PA levels and predictors in people with schizophrenia . | Background Patients with schizophrenia have lower longevity than the general population as a consequence of a combination of risk factors connected to the disease , lifestyle and the use of medications , which are related to weight gain . Methods A multicentric , r and omized , controlled-trial was conducted to test the efficacy of a 12-week group Lifestyle Wellness Program ( LWP ) . The program consists of a one-hour weekly session to discuss topics like dietary choices , lifestyle , physical activity and self-esteem with patients and their relatives . Patients were r and omized into two groups : st and ard care ( SC ) and st and ard care plus intervention ( LWP ) . Primary outcome was defined as the weight and body mass index ( BMI ) . Results 160 patients participated in the study ( 81 in the intervention group and 79 in the SC group ) . On an intent to treat analysis , after three months the patients in the intervention group presented a decrease of 0.48 kg ( CI 95 % -0.65 to 1.13 ) while the st and ard care group showed an increase of 0.48 kg ( CI 95 % 0.13 to 0.83 ; p=0.055 ) . At six-month follow-up , there was a significant weight decrease of −1.15 kg , ( CI 95 % -2.11 to 0.19 ) in the intervention group compared to a weight increase in the st and ard care group ( + 0.5 kg , CI 95 % -0.42–1.42 , p=0.017 ) . Conclusion In conclusion , this was a multicentric r and omized clinical trial with a lifestyle intervention for individuals with schizophrenia , where the intervention group maintained weight and presented a tendency to decrease weight after 6 months . It is reasonable to suppose that lifestyle interventions may be important long-term strategies to avoid the tendency of these individuals to increase weight . Clinical trials.gov The study objective was to evaluate the feasibility of a telephone delivered intervention consisting of motivational interviewing and cognitive behavioural strategies aim ed at improving diet and physical activity in people diagnosed with psychotic disorders . Twenty participants diagnosed with a non-acute psychotic disorder were recruited . The intervention consisted of eight telephone delivered sessions targeting fruit and vegetable ( F&V ) consumption and leisure screen time , as well as smoking and alcohol use ( as appropriate ) . F&V frequency and variety , and overall diet quality ( measured by the Australian Recommended Food Score , ARFS ) , leisure screen time , overall sitting and walking time , smoking , alcohol consumption , mood , quality of life , and global functioning were examined before and 4-weeks post-treatment . Nineteen participants ( 95 % ) completed all intervention sessions , and 17 ( 85 % ) completed follow-up assessment s. Significant increases from baseline to post-treatment were seen in ARFS fruit , vegetable and overall diet quality scores , quality of life and global functioning . Significant reductions in leisure screen time and overall sitting time were also seen . Results indicated that a telephone delivered intervention targeting key cardiovascular disease risk behaviours appears to be feasible and relatively effective in the short-term for people diagnosed with psychosis . A r and omized controlled trial is warranted to replicate and extend these findings The objective of this multicenter r and omised clinical trial was to examine the effect of exercise versus occupational therapy on mental and physical health in schizophrenia patients BACKGROUND The aim of this r and omized clinical trial follow-up at three months was to evaluate the effectiveness of an educational intervention with a focus on diet and physical activity ( PA ) to change the amount of PA , body mass index ( BMI ) and the waist circumference ( WC ) in patients with severe mental illness . METHODS We recruited 332 out patients with severe mental disorders undergoing treatment with antipsychotic medication from Mental Healthcare Centers of Barcelona . They were r and omly assigned to an intervention or a control group . The patients in the intervention group participated in a group PA and diet educational program . The blinded measurements at 0 and 3 months were : the level of PA ( IPAQ question naire ) , BMI , WC , blood pressure , dietary habits ( PREDIMED question naire ) , quality of life ( SF-36 question naire ) and laboratory parameters ( cholesterol , triglycerides , glucose ) . RESULTS The average age was 46.7 years and 55 % were males . Schizophrenia had been diagnosed in 67.1 % of them . At 3 months , the average weekly walking METs rose significantly in the IG 266.05 METs ( 95%CI : 16.86 to 515.25 ; P=0.036 ) . The total MET average also rose although not significantly : 191.38 METs ( 95%CI : 1.38 to 381.38 ; P=0.086 ) . However , the BMI decreased significantly more in the CG , by 0.26kg/m(2 ) ( 95%CI : 0.02 to 0.51 ; P=0.038 ) , than in the IG . There were no significant differences in the WC . CONCLUSIONS The short-term results suggest that the intervention increases the level of PA , but does not improve physical or laboratory parameters . TRIAL REGISTRATION Clinical trials.gov NCT01729650 ( effectiveness of a physical activity and diet program in patients with psychotic disorder [ CAPiCOR ] ) BACKGROUND People with psychosis often experience weight gain , which places them at risk of cardiovascular disease , diabetes , and early death . OBJECTIVE To determine the uptake , adherence , and clinical effectiveness of a healthy living intervention design ed to reduce weight gain . METHOD An exploratory r and omized controlled trial , comparing the intervention with treatment as usual ( TAU ) in 2 early intervention services for psychosis in Engl and . DSM-IV classification was the diagnostic criteria used to assign the psychiatric diagnoses . The primary outcome was change in body mass index ( BMI ) from baseline to 12-month follow-up . The study was conducted between February 2009 and October 2012 . RESULTS 105 service users , with a BMI of ≥ 25 ( ≥ 24 in South Asians ) , were r and omized to intervention ( n = 54 ) or TAU ( n = 51 ) after stratification by recent commencement of antipsychotic medication . Ninety-three service users ( 89 % ) were followed up at 12 months . Between-group difference in change in BMI was not significant ( effect size = 0.11 ) . The effect of the intervention was larger ( effect size = 0.54 , not significant ) in 15 intervention ( 28 % ) and 10 TAU ( 20 % ) participants who were taking olanzapine or clozapine at r and omization . CONCLUSIONS The healthy living intervention did not show a significant difference in BMI reduction compared to the TAU group . TRIAL REGISTRATION www.is rct n.org identifier : IS RCT N22581937 Ninety seven out patients with schizophrenia spectrum disorders ( SSDs ) were r and omly assigned to the Walk , Address Sensations , Learn About Exercise , Cue Exercise Behavior for SSDs ( WALC-S ) , a motivational intervention design ed to increase exercise in SSDs ( n = 48 ) , or a time and attention control group ( TAC , n = 49 ) . WALC-S and TAC groups met weekly for 4 weeks before a 16 week walking program was offered to all subjects . We compared the exercise attendance , persistence and compliance of the groups during the walking program . WALC-S recipients attended more walking groups , for more weeks and walked more minutes than those receiving TAC . Percent of WALC-S or TAC groups attended was significantly correlated with overall attendance ( r = 0.38 , P = 0.001 ) and persistence ( r = −.29 , P = 0.01 ) , as well as number of minutes walked . This study is among the first to examine interventions design ed to enhance exercise motivation in SSDs AIM Initiating antipsychotic medication frequently induces rapid , clinical ly significant weight gain . We aim ed to evaluate the effectiveness of a lifestyle and life skills intervention , delivered within 4 weeks of antipsychotic medication initiation , in attenuating weight gain in youth aged 14 - 25 years with first-episode psychosis ( FEP ) . METHODS We undertook a prospect i ve , controlled study in two early psychosis community services . Intervention participants ( n = 16 ) received a 12-week individualized intervention delivered by specialist clinical staff ( nurse , dietician and exercise physiologist ) and youth peer wellness coaches , in addition to st and ard care . A comparison group was recruited from a similar service and received st and ard care ( n = 12 ) . RESULTS The intervention group experienced significantly less weight gain at 12 weeks compared to st and ard care ( 1.8 kg , 95 % CI -0.4 to 2.8 vs. 7.8 kg , 4.8 - 10.7 , P < 0.001 ) . Thirteen per cent ( 2/16 ) of the intervention group experienced clinical ly significant weight gain ( greater than 7 % of baseline weight ) , while 75 % ( 9/12 ) of the st and ard care group experienced this level of weight gain . Similar positive effects of the intervention were observed for waist circumference . CONCLUSIONS A lifestyle and life skills intervention delivered as part of st and ard care attenuated antipsychotic-induced weight gain in young people with FEP . The intervention was acceptable to the young people referred to the service . Such interventions may prevent the seeding of future disease risk and in the long-term help reduce the life expectancy gap for people living with serious mental illness PURPOSE We tested the feasibility and preliminary efficacy of a lifestyle intervention for middle-aged and older patients with schizophrenia and type-2 diabetes mellitus , using a r and omized pre-test , post-test control group design . METHOD Individuals with a diagnosis of schizophrenia or schizoaffective disorder over the age of 40 were r and omly assigned to 24-week Diabetes Awareness and Rehabilitation Training ( DART ; n=32 ) groups or Usual Care plus Information ( UCI ; n=32 ) comparison groups . Participants were recruited from board- and -care facilities and day treatment programs . Fifty-seven patients completed baseline and 6-month assessment s consisting of an interview , measures of body mass index , blood pressure , fasting blood chemistry , and accelerometry . A mixed-model analysis of variance was used to analyze the data . RESULTS A significant group x time interaction was found for body weight , with patients in the DART group losing a mean of 5 lb and those in the UCI gaining a mean 6 lb . Significant group x time interactions were also found for triglycerides , diabetes knowledge , diabetes self-efficacy , and self-reported physical activity , but not for fasting plasma glucose or glycosylated hemoglobin . CONCLUSIONS Group-based lifestyle interventions are feasible and produce positive health changes in middle-aged and older patients with schizophrenia and diabetes mellitus |
11,708 | 27,362,975 | We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life .
However , there were few results only based on subgroups of the trial population s. None of the trials reported substantial effects regarding weight gain or any other adverse events .
Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes . | BACKGROUND Short-acting insulin analogue use for people with diabetes is still controversial , as reflected in many scientific debates .
OBJECTIVES To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes . | BACKGROUND AND AIM While lispro insulin has been reported to lower postpr and ial blood glucose concentrations , less consistent effects have been shown for glycosylated hemoglobin ( HbA1c ) levels . Aim of this study was to determine whether pre-meal association of NPH , an intermediate-acting insulin , with lispro improves overall glycemic control in type 1 diabetic patients . METHODS AND RESULTS Eighty-five type 1 diabetic patients were studied in a multicenter r and omized comparative ( human regular vs lispro insulin ) crossover ( 3-month ) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary . The number of injections was kept constant : 42 % and 58 % of patients injected insulin 3 and 4 times per day , respectively . Fasting and prepr and ial blood glucose levels were similar , while postpr and ial levels improved after lispro compared to human regular insulin ( breakfast : 8.28 + /- 2.39 vs 9.28 + /- 2.72 mmol/l ; lunch : 8.33 + /- 2.67 vs 9.06 + /- 2.67 mmol/l , dinner : 8.06 + /- 2.72 vs 9.28 + /- 2.44 mmol/l , ANOVA : p = 0.003 ) . HbA1c also improved after lispro : 8.1 + /- 0.9 vs 8.3 + /- 0.8 % , p < 0.05 . The rate of hypoglycemia was similar . Patients showed better acceptance of lispro treatment ( p < 0.001 ) . CONCLUSIONS Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia . This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long OBJECTIVE Insulin administered by jet injectors is dispensed over a larger subcutaneous area than insulin injected with a syringe , which may facilitate a more rapid absorption . This study compared the pharmacologic profile of administration of insulin aspart by jet injection to that by conventional insulin pen . RESEARCH DESIGN AND METHODS Euglycemic glucose clamp tests were performed in 18 healthy volunteers after subcutaneous administration of 0.2 units/kg body wt of aspart , either administered by jet injection or by conventional pen , using a r and omized , double-blind , double-dummy , cross over study design . Pharmacodynamic and pharmacokinetic profiles were derived from the glucose infusion rate ( GIR ) needed to maintain euglycemia and from plasma insulin levels , respectively . RESULTS The time to maximal GIR was significantly shorter when insulin was injected with the jet injector compared with conventional pen administration ( 51 ± 3 vs. 105 ± 11 min , P < 0.0001 ) . The time to peak insulin concentration was similarly reduced ( 31 ± 3 vs. 64 ± 6 min , P < 0.0001 ) and peak insulin concentrations were increased ( 108 ± 13 vs. 79 ± 7 mU/L , P = 0.01 ) when insulin was injected by jet injection compared with conventional pen injection . Jet injector insulin administration reduced the time to 50 % glucose disposal by ∼40 min ( P < 0.0001 ) . There were no differences in maximal GIR , total insulin absorption , or total insulin action between the two devices . CONCLUSIONS Administration of insulin aspart by jet injection enhances insulin absorption and reduces the duration of glucose-lowering action . This profile resembles more closely the pattern of endogenous insulin secretion and may help to achieve better meal insulin coverage and correction of postpr and ial glucose excursions OBJECTIVE To evaluate the progression of retinopathy during pregnancy and postpartum in ( insulin-dependent ) women with type 1 diabetes treated with insulin lispro or with regular human insulin . RESEARCH DESIGN AND METHODS A prospect i ve open study of 69 pregnant women with diabetes was performed . A total of 36 of the women were treated with insulin lispro ( lispro group ) and 33 were treated with conventional short-acting human insulin ( regular insulin group ) . The retinopathy level was estimated by color fundus photography every trimester and postpartum . Glycemic control during pregnancy , hypoglycemia ( blood glucose level <3 mmol/l ) in 24-h glucose profile , blood pressure , and proteinuria were registered . RESULTS HbA(1c ) values were similar at baseline in the first trimester but thereafter were lower in the lispro group than in the regular insulin group throughout pregnancy ( P = 0.022 , repeated- measures ANOVA ) . The number of hypoglycemic episodes did not differ between the treatment groups . In multivariable logistic regression analysis with retinopathy severity ( Diabetes Control and Complications Trial level ) in the third trimester as the dependent variable , only nulliparity qualified as a predictor in the model [ Exp(B ) = 4.0 , 95 % CI 1.1 - 13.7 , P = 0.030 ] . Factors such as duration of diabetes , type of insulin used , mean HbA(1c ) level throughout pregnancy , blood pressure ( systolic or diastolic ) , preeclampsia in the current pregnancy , smoking , or prepregnancy planning did not explain the retinopathy progression . CONCLUSIONS Insulin lispro improves glycemic control during diabetic pregnancy compared with regular insulin with no adverse impact on progression of diabetic retinopathy INTRODUCTION Insulin glulisine ( glulisine ) was evaluated versus regular human insulin ( RHI ) in Type 2 diabetes ( T2DM ) patients . METHODS Patients previously on > 6 months ' continuous insulin treatment aged > or=18 years in a r and omized , multinational , controlled , open-label , parallel group , 26-week study received twice-daily NPH insulin and either glulisine ( 0 - 15 min before breakfast and dinner ; n=448 ) or RHI ( 30 - 45 min before breakfast and dinner ; n=442 ) at least twice daily . RESULTS Mean baseline characteristics were similar between groups . There were no differences in baseline to endpoint HbA(1c ) reductions ( glulisine : -0.32 % ; RHI : -0.35 % ; p=0.5726 ) , and the non-inferiority of glulisine versus RHI was demonstrated ( difference in adjusted mean change 0.03 % ; 95 % CI : -0.07 , 0.13 ) . Postpr and ially , glulisine lowered plasma glucose significantly more versus RHI at 2h ( 14.14 mmol/L versus 15.28 mmol/L ; p=0.0025 ) and excursions at 1h ( 3.99 versus 4.59 ; p=0.0151 ) and 2h ( 4.87 versus 6.03 ; p=0.0002 ) . No between-group differences occurred in the frequencies and monthly rates of all symptomatic hypoglycaemia ; nocturnal hypoglycaemia from Month 4 to treatment end was less frequent with glulisine versus RHI ( 9.1 % versus 14.5 % ; p=0.029 ) . CONCLUSION Glulisine was non-inferior to RHI in reducing HbA(1c ) in T2DM . Glulisine demonstrated superior postpr and ial glucose control and was associated with fewer nocturnal hypoglycaemic episodes , indicating clinical benefits Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Today , insulin analogs are used in millions of diabetic patients . Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time-course of the effect . Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin . However , these changes can also modify the molecular and biological effects of the analogs . The rapid-acting insulin analogs , lispro , aspart , and glulisine , have a rapid onset and shorter duration of action . The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile . Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation . A major question is whether analogs have an increased mitogenic activity in respect to insulin . These lig and s can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor , stimulation of the IGF-1 receptor ( IGF-1R ) , prevalent activation of the extracellular-signaling-regulated kinase ( ERK ) rather than the protein kinase B ( PKB/AKT ) intracellular post-receptor pathways . Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin . In contrast , long-acting analogs behave differently . Although not all data are homogeneous , both glargine and detemir have been found to have a decreased binding to receptors for insulin but an increased binding to IGF-1R , a prevalent activation of the ERK pathway , and an increased mitogenic effect in respect to insulin . Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs ( specifically glargine ) may increase the relative risk for cancer . Results are controversial and method ologically weak . Therefore prospect i ve clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin analogs Summary The objective of this study was to identify possible risk factors of severe hypoglycaemia ( SH ) in a prospect i ve population based study of adult Type I ( insulin-dependent ) diabetic patients . A representative sample of 684 patients ( 41 % women , mean ± SD age 36 ± 11 , diabetes duration 18 ± 11 years ) , living in the district of Northrhine ( 9.5 million inhabitants ) , Germany , were examined in their homes using a mobile ambulance . A comprehensive baseline assessment of possible predictors of SH included sociodemographic and disease related variables , hypoglycaemia awareness , diabetes management , and attitudes and behavioural aspects as expressed by the patients . After a mean of 19 ± 6 months 669 ( 98 % ) patients were interviewed about events of SH since the baseline examination . Using the multiple Cox proportional hazards model , five risk factors of SH were identified : SH during the preceding year [ hazard ratio ( HR ) 2.7 , 95 % confidence intervals ( CI ) 1.8–4.2 ] , any history of SH ( HR 1.9 , CI 1.1–3.4 ) , C-peptide negativity ( HR 4.0 , CI 1.2–12.7 ) , social status ( HR 0.8 for a difference of 5 units for a value range of 0–24 , CI 0.6–0.9 ) , and patients ' determination to reach normoglycaemia ( HR 0.7 for a difference of 1 unit for a value range of 1–6 , CI 0.5–0.9 ) , indicating that the lower the social status and the higher the patients ' determination to reach normoglycaemia , the higher the risk of SH . After eliminating the history of hypoglycaemia from the model , impaired hypoglycaemia awareness and patients ' inappropriate denial of SH as their particular problem became additional significant risk factors of SH . In conclusion , in this population based study of adult Type I diabetic patients , C-peptide negativity , a previous event of SH , patients ' determination to reach normoglycaemia and social class were risk factors of SH . [ Diabetologia ( 1998 ) 41 : 1274–1282 Aims /hypothesisThe aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy , using either the soluble long-acting basal insulin analogue , insulin detemir , in combination with the rapid-acting analogue , insulin aspart , or NPH insulin in combination with mealtime regular human insulin . Methods In this 18-week , 1:1 r and omised , open-labelled , parallel trial , 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively . Results Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin ( HbA1c : 7.88 % vs 8.11 % ; mean difference : −0.22 % point [ 95 % CI : −0.34 to −0.10 ] ; p<0.001 ) . Self-measured 8-point plasma glucose profiles differed between the groups ( p<0.001 ) , with lower postpr and ial plasma glucose levels in the insulin detemir/insulin aspart group . Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( SD : 2.88 vs 3.12 mmol/l ; p<0.001 ) . Risk of overall and nocturnal hypoglycaemia ( 23.00–06.00 hours ) was , respectively , 21 % ( p=0.036 ) and 55 % ( p<0.001 ) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group . Body weight ( adjusted for baseline and change in HbA1c ) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( p<0.001 ) . Conclusions /interpretationBasal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin . The low variability and more physiological action profiles generated with these insulin analogues result ed in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase Insulin lispro is an insulin analogue that has the advantages of being fast-acting , convenient , and less likely to lead to hypoglycaemic episodes . Previous studies have proven its value in treating both Type 1 and Type 2 diabetes both alone and in combination with different treatment regimens.1,2 However , diabetes is heterogeneous and differs in etiology and clinical characteristics in different ethnic groups . Even with the same insulin treatment , different diets will produce different glycaemic profiles . Diet patterns differ between different ethnic groups . Traditional oriental foods are characterized by a higher proportion of carbohydrates and a lower proportion of fat compared to Caucasian diets . To date , there has been no study on the use of insulin lispro in Chinese diabetic patients . Whether the Chinese dietary pattern will affect the efficacy of insulin lispro treatment remains unknown . Therefore , we conducted this trial to assess the efficacy of insulin lispro treatment in Chinese patients Lispro ( LP ) and regular human ( HR ) insulins were compared in Type 1 diabetic ( T1DM ) patients on either a Mediterranean diet or normal diet . Twelve T1DM patients were recruited and r and omized into two groups of 6 , groups A and B. They were treated in different sequences ( in 3-month intervals for 1 year ) . Group A : LP insulin and normal diet , LP insulin and Mediterranean diet , regular insulin and Mediterranean diet , regular insulin and normal diet . Group B : regular insulin and normal diet , regular insulin and Mediterranean diet , LP insulin and Mediterranean diet , LP insulin and normal diet . Each patient was treated with rapid acting insulin , either LP insulin or HR insulin , before each main meal and a dose of slow acting insulin at bedtime . Every 15 days the glycemic control , the incidence and frequency of hypoglycemic episodes , and any adverse events were evaluated . Every 3 months , hematology and a chemistry panel , pre- and post-pr and ial glycemic and insulinemic profiles were evaluated in all patients . HbA1c levels significantly decreased in LP patients on normal diet , post-pr and ial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards , 15-min post-pr and ial insulin levels higher in LP- than in HR-treated patients , and hypoglycemic episodes were significantly less in LP- than in HR-treated patients . LP insulin , irrespective of the type of diet , results in more effective glycemic control , significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet AIMS To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen . METHODS In this 32-week , five-centre , two-way cross-over study , people with Type 1 diabetes ( n = 56 , baseline HbA1c 8.0 + /- 0.8 % ) were r and omized to evening insulin glargine + mealtime insulin lispro or to NPH insulin ( once- or twice-daily ) + mealtime unmodified human insulin . Each 16-week period concluded with a 24-h inpatient plasma glucose profile . RESULTS HbA1c was lower with glargine + lispro than with NPH + human insulin [ 7.5 vs. 8.0 % , difference -0.5 ( 95 % CI -0.7 , -0.3 ) % , P < 0.001 ] . This was confirmed by an 8 % lower 24-h plasma glucose area under the curve ( AUC ) ( 187 vs. 203 mmol l(-1 ) h(-1 ) , P = 0.037 ) , a 24 % reduction in plasma glucose AUC > 7.0 mmol/l1 ( 47 vs. 62 mmol l(-1 ) h(-1 ) , P = 0.017 ) and a 15 % lower post-pr and ial plasma glucose AUC ( 75 vs. 88 mmol l(-1 ) h(-1 ) , P = 0.002 ) . There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l . Monthly rate of nocturnal hypoglycaemia was reduced by 44 % with glargine + lispro ( 0.66 vs. 1.18 episodes/month , P < 0.001 ) . CONCLUSIONS Compared with NPH insulin + unmodified human insulin , the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinical ly significant degree , together with a reduction in nocturnal hypoglycaemia 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 aim of the study was to compare lispro ( LP ) and Insuman(R ) ( I ) insulin in continuous subcutaneous insulin infusion ( CSII ) therapy with respect to blood glucose control as expressed by the st and ard deviation of blood glucose ( SD(BG ) ) and HbA(1c ) and to monitor the well-being ( WBQ ) and treatment satisfaction ( DTSQ ) parameters during such treatment . Forty-one IDDM patients who had used CSII for at least 6 months participated in an open-label , r and omized , cross-over , multicenter study for 4 months ( 2 months LP and 2 months I or vice versa ) . Boluses with LP were given 5 min before each meal and with I 30 min before each meal . During LP administration compared with I , the SD(BG ) of all blood glucose values ( 3.6 mmol/l vs. 3.9 mmol/l , p=0.012 ) , as well as the SD(BG ) of the postpr and ial , blood glucose values ( 3.6 mmol/l vs. 4.0 mmol/l , p=0.006 ) , were significantly reduced . The HbA(1c ) was significantly lower during LP administration ( 7.4 % vs. 7.6 % , p=0.047 ) . The incidence of hypoglycemic events per 30 days ( capillary blood glucose<3.0 mmol/l and /or symptoms ) did not significantly differ between LP and I ( 9.7 vs. 8.0 per month , p=0.23 ) . The total amount of daily insulin was slightly but significantly lower with LP , compared to I ( 38.0 IU vs. 40.3 IU , p=0.004 ) . There was no treatment effects of LP compared to I concerning WBQ and DTSQ . It is concluded that in CSII therapy LP is superior to I with respect to the stability of blood glucose control , a lower HbA(1c ) , a less insulin requirement without increasing the frequency of hypoglycemia The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms . The insulin analogue insulin lispro has a weak self-association and a fast absorption rate . We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus . A 12-month study was performed in 336 patients with insulin-dependent diabetes mellitus ( IDDM ) and 295 patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . The patients were r and omized to inject either regular human insulin 30 to 45 minutes before eating , or insulin lispro immediately before each meal , in addition to basal insulin . The postpr and ial rise in serum glucose was lower in patients receiving insulin lispro than in those receiving regular human insulin therapy . At end point the increment was significantly lower at 1 hour ( 35 % ) and at 2 hours ( 64 % ) after the meal in IDDM patients ; in NIDDM patients , the increment was nonsignificantly lower at 1 hour ( 19 % ) and significantly lower at 2 hours ( 48 % ) . IDDM patients receiving insulin lispro achieved significantly lower glycated hemoglobin ( HbA1c ) levels in patients receiving regular human insulin ( 8.1 % vs 8.3 % ) . In NIDDM patients , HbA1c levels decreased equally in both treatment groups . Due to its fast absorption rate , insulin lispro improves postpr and ial control in diabetes . Insulin lispro can be considered one step toward optimal insulin therapy and improved patient convenience AIMS To compare quality of life ( QoL ) and treatment satisfaction in patients with Type 1 diabetes receiving the rapid-acting insulin analogue , insulin aspart ( IAsp ) , with that in patients receiving soluble human insulin ( HI ) . METHODS In this 6-month , multinational , r and omized , open-label trial , 424 patients from German-speaking countries were subjected to psychometric assessment before and after r and omization ( ratio 2 : 1 ) to basal-bolus treatment with either IAsp ( n = 283 ) or HI ( n = 141 ) . Patients on HI were advised to keep an injection-meal interval of 30 min , whereas patients on IAsp were advised to inject immediately before meals . Treatment satisfaction and diabetes-related QoL were assessed using vali date d instruments to measure the domains of patients ' individual treatment goals , physical complaints , worries about the future , social relations , leisure time flexibility , daily hassles , diet restrictions , burdens and fear of hypoglycaemia , blood glucose fluctuations , self-efficacy , and fear of insulin analogues . RESULTS After 6 months , IAsp was associated with significantly greater improvement in treatment satisfaction than HI in two different scales ( P < 0.01 ) , and in QoL with respect to diet restrictions ( P < 0.01 ) . Improved satisfaction was mainly due to increased dietary and leisure time flexibility ( P < 0.0001 ) . Twenty-three percent of the IAsp group vs. 14 % of the HI group achieved small but important improvements of total QoL ( between-group difference , P < 0.06 ) . The number needed to treat ( NNT ) with IAsp for an important increase in QoL was calculated to be 10 . Regression analyses of potential predictors of improvement in QoL highlighted patients intensely striving for physical strength ( P < 0.01 ; NNT = 7 ) and patients feeling less protected against hypoglycaemia ( P < 0.005 ; NNT = 8) as being the most likely to benefit from IAsp . CONCLUSIONS Under these study conditions , IAsp improved treatment satisfaction and quality of life regarding diet restrictions when compared with human insulin . The ' numbers needed to treat ' for important quality of life benefits indicate that the effect of IAsp in this regard is not trivial Aim : It has been found that non‐fasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes . The main aim of treatment of type 2 diabetic patients is to control plasma glucose and HbA1c levels . In this study , we aim ed to assess the effects of three different insulin regimens ( group I : lispro insulin + NPH insulin , group II : lispro insulin + metformin and group III : regular insulin + NPH insulin ) on overall glycaemic control and metabolic parameters in type 2 diabetic patients with secondary oral anti‐diabetic drug failure OBJECTIVE Patients with diabetes and insulin therapy with human insulin were usually instructed to use an interval of 20–30 min between the injection and meal . We examined the necessity of the injection-to-meal interval ( IMI ) in patients with type 2 diabetes mellitus ( T2DM ) and flexible insulin therapy with human insulin . RESEARCH DESIGN AND METHODS In this r and omized , open crossover trial , 100 patients with T2DM ( 47 % men , mean age = 66.7 years ) were r and omized to the IMI first group ( phase 1 , IMI 20 min ; phase 2 , no IMI ) or IMI last group ( phase 1 , no IMI ; phase 2 , IMI 20 min ) . The main outcome measures were HbA1c , blood glucose profile , incidence of hypoglycemia , quality of life , treatment satisfaction , and patient preference . RESULTS Forty-nine patients were r and omized to the IMI first group and 51 patients to the IMI last group . Omitting the IMI only slightly increases HbA1c ( average intraindividual difference = 0.08 % [ 95 % CI 0.01–0.15 ] ) . Since the difference is not clinical ly relevant , a therapy without IMI is noninferior to its application ( P < 0.001 ) . In the secondary outcomes , the incidence of mild hypoglycemia also did not differ between no IMI and IMI significantly ( mean of differences = −0.10 , P = 0.493 ) . No difference in the blood glucose profile of both groups was found . Treatment satisfaction increased markedly , by 8.08 , if IMI was omitted ( P < 0.001 ) . The total score of the quality of life measure did not show differences between applying an IMI or not . Insulin therapy without IMI was preferred by 86.5 % of patients ( P < 0.001 ) . CONCLUSIONS An IMI for patients with T2DM and prepr and ial insulin therapy is not necessary OBJECTIVE The antibody responses to a novel rapid-acting insulin analog , insulin aspart ( IAsp ) , and their potential clinical correlates were studied with a specifically developed method in 2,420 people with diabetes treated for up to 1 year with prepr and ial subcutaneous injections of IAsp . RESEARCH DESIGN AND METHODS Circulating insulin antibodies were analyzed by radioimmunoassay with (125)I insulin or IAsp tracers and polyethylene glycol precipitation . Four multinational , open , parallel group studies were conducted in Europe and North America , with a total of 1,534 people with diabetes exposed to IAsp and 886 people exposed to human insulin ( HI ) as meal-related insulin for 6 - 12 months . RESULTS Insulin antibodies specific to HI or IAsp were absent in a majority of patients throughout the 6- to 12-month study periods . A majority of the patients ( 64 - 68 % ) had antibodies cross-reacting between HI and IAsp when entering the studies , with baseline levels ( means + /- SD of percent bound/total ) of 16.6 + /- 16.3 % in study 1 and 10.3 + /- 14.0 % in study 4 . In all four studies , cross-reactive antibodies increased in patients exposed to IAsp , with a maximum at 3 months , and thereafter there was a decline toward baseline levels at 9 - 12 months ( levels at 3 and 12 months : 22.3 + /- 19.7 and 16.8 + /- 16.5 % in study 1 and 21.5 + /- 21.9 and 16.9 + /- 17.4 % in study 4 ) . Antibody levels showed similar changes in people with type 1 and type 2 diabetes , and there was no consistent relationship between antibody formation and glycemic control or between antibody formation and safety in terms of adverse events . CONCLUSIONS Treatment with IAsp is associated with an increase in cross-reactive insulin antibodies , with a subsequent fall toward baseline values , without any indication of clinical relevance because no effect on efficacy or safety could be identified Background : Insulin analogues may be associated with fewer episodes of hypoglycemia than conventional insulins . However , they are costly alternatives . We compared the cost-effectiveness of insulin analogues and conventional insulins used to treat type 1 and type 2 diabetes mellitus in adults . Methods : We conducted a cost-effectiveness evaluation of insulin analogues versus conventional insulins using the Center for Outcomes Research Diabetes Model . We compared rapid-acting analogues ( insulin aspart and insulin lispro ) with regular human insulin , and long-acting analogues ( insulin glargine and insulin detemir ) with neutral protamine Hagedorn insulin . We derived clinical information for the comparisons from meta-analyses of r and omized controlled trials . We obtained cost and utility estimates from published sources . We performed sensitivity analyses to test the robustness of our results . Results : For type 1 diabetes , insulin aspart was more effective and less costly than regular human insulin . Insulin lispro was associated with an incremental cost of Can$28 996 per quality -adjusted life-year . The incremental cost per quality -adjusted life-year was Can$87 932 for insulin glargine and Can$387 729 for insulin detemir , compared with neutral protamine Hagedorn insulin . For type 2 diabetes , insulin aspart was associated with an incremental cost of Can$22 488 per quality -adjusted life-year compared with regular human insulin . For insulin lispro , the incremental cost was Can$130 865 . Compared with neutral protamine Hagedorn insulin , insulin detemir was less effective and more costly . Insulin glargine was associated with an incremental cost of Can$642 994 per quality -adjusted life-year . The model was sensitive to changes in the effect size of hemoglobin A1c and to decrements applied to utility scores when fear of hypoglycemia was included as a factor . Interpretation : The cost-effectiveness of insulin analogues depends on the type of insulin analogue and whether the patient receiving the treatment has type 1 or type 2 diabetes . With the exception of rapid-acting insulin analogues in type 1 diabetes , routine use of insulin analogues , especially long-acting analogues in type 2 diabetes , is unlikely to represent an efficient use of finite health care re sources OBJECTIVE To compare the safety and efficacy of insulin aspart ( IAsp ) , buffered regular insulin ( BR ) , and insulin lispro administered by continuous subcutaneous insulin infusion ( CSII ) in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS After completing a 4-week run-in period with BR , 146 adult patients with type 1 diabetes ( with pretrial CSII experience ) were r and omly assigned ( 2:2:1 ) to CSII treatment with IAsp , BR , or lispro for 16 weeks in a multicenter , open-label , r and omized , parallel-group study . Bolus insulin doses were administered 30 min before meals ( BR ) or immediately before meals ( IAsp or lispro ) . RESULTS Treatment groups had similar baseline HbA(1c ) ( 7.3 % + /- 0.7 for IAsp , 7.5 % + /- 0.8 for BR , and 7.3 % + /- 0.7 for lispro ) . After 16 weeks of treatment , HbA1c values were relatively unchanged from baseline , and the mean changes in baseline HbA1c values were not significantly different between the three groups ( 0.00 + /- 0.51 , 0.15 + /- 0.63 , and 0.18 + /- 0.84 for the IAsp , BR , and lispro groups , respectively ) . The rates of hypoglycemic episodes ( blood glucose < 50 mg/dl ) per patient per month were similar ( 3.7 , 4.8 , and 4.4 for the IAsp , BR , and lispro groups , respectively ) . Clogs/blockages in pumps or infusion sets were infrequent ; most subjects ( 76 , 83 , and 75 % in the IAsp , BR , and lispro groups , respectively ) had < or = 1 clog or blockage per 4 weeks during the trial . CONCLUSIONS Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps OBJECTIVE Insulin glulisine is a novel analog of human insulin design ed for use as a rapid-acting insulin . This study compared the safety and efficacy of glulisine with regular human insulin ( RHI ) in combination with NPH insulin . RESEARCH DESIGN AND METHODS In total , 876 relatively well-controlled patients with type 2 diabetes ( mean HbA1c 7.55 % ) were r and omized and treated with glulisine/NPH ( n = 435 ) or RHI/NPH ( n = 441 ) for up to 26 weeks in this r and omized , multicenter , multinational , open-label , parallel-group study . Subjects were allowed to continue the same dose of pre study regimens of oral antidiabetic agent ( OAD ) therapy ( unless hypoglycemia necessitated a dose change ) . RESULTS A slightly greater reduction from baseline to end point of HbA1c was seen in the glulisine group versus RHI ( -0.46 vs. -0.30 % with RHI ; P = 0.0029 ) . Also , at end point , lower postbreakfast ( 156 vs. 162 mg/dl [ 8.66 vs. 9.02 mmol/l ] ; P < 0.05 ) and postdinner ( 154 vs. 163 mg/dl [ 8.54 vs. 9.05 mmol/l ] ; P < 0.05 ) blood glucose levels were noted . Symptomatic hypoglycemia ( overall , nocturnal , and severe ) and weight gain were comparable between the two treatment groups . There were no between-group differences in baseline-to-end point changes in insulin dose . CONCLUSIONS Twice-daily glulisine associated with NPH can provide small improvements in glycemic control compared with RHI in patients with type 2 diabetes who are already relatively well controlled on insulin alone or insulin plus OADs . The clinical relevance of such a difference remains to be established OBJECTIVE To determine the effect of treatment with insulin aspart compared with NPH insulin , together with metformin/placebo and rosiglitazone/placebo . The hypothesis was that combined correction of major pathogenetic defects in type 2 diabetes would result in optimal glycemic control . RESEARCH DESIGN AND METHODS This study was a 2-year investigator-driven r and omized partly placebo-controlled multicenter trial in 371 patients with type 2 diabetes on at least oral antiglycemic treatment . Patients were assigned to one of eight treatment groups in a factorial design with insulin aspart at mealtimes versus NPH insulin once daily at bedtime , metformin twice daily versus placebo , and rosiglitazone twice daily versus placebo . The main outcome measurement was change in A1C . RESULTS A1C decreased more in patients treated with insulin aspart compared with NPH ( −0.41 ± 0.10 % , P < 0.001 ) . Metformin decreased A1C compared with placebo ( −0.60 ± 0.10 % , P < 0.001 ) , as did rosiglitazone ( −0.55 ± 0.10 % , P < 0.001 ) . Triple therapy ( rosiglitazone , metformin , and any insulin ) result ed in a greater reduction in A1C than rosiglitazone plus insulin ( −0.50 ± 0.14 % , P < 0.001 ) and metformin plus insulin ( −0.45 ± 0.14 % , P < 0.001 ) . Aspart was associated with a higher increase in body weight ( 1.6 ± 0.6 kg , P < 0.01 ) and higher incidence of mild daytime hypoglycemia ( 4.9 ± 7.5 vs. 1.7 ± 5.4 number/person/year , P < 0.001 ) compared with NPH . CONCLUSIONS Insulin treatment of postpr and ial hyperglycemia results in lower A1C than treatment of fasting hyperglycemia , at the expense of higher body weight and hypoglycemic episodes . However , insulin therapy has to be combined with treatment of both peripheral and liver insulin resistance to normalize blood glucose , and in this case , the insulin regimen is less important OBJECTIVE To compare the blood glucose levels and variability of premixed insulin aspart ( BIAsp 30 ) with human insulin premix ( BHI 30 ) used in a twice a day injection regimen in elderly type 2 diabetes patients . METHODS 52 cases of inadequate glycemia controlled by oral anti-diabetic drugs were r and omly divided into two groups , treated on a twice-daily regimen with BIAsp 30 ( n = 26 ) and BHI 30 ( n = 26 ) respectively . After achieving the target goal , a continuous glucose monitoring system ( CGMS ) was used to compare the blood glucose levels , blood glucose fluctuant coefficient ( BGFC ) , postpr and ial glucose excursion ( PPGE ) , and occurrence of hypoglycemia . RESULTS BIAsp 30 was as effective as BHI 30 in control glycaemia . Detected by CGMS , there was no statistical differences in blood glucose levels among pre-three main meals , post-lunch and the mean blood glucose ( MBG ) ( all P > 0.05 ) . The BGFC levels were significantly lower in the BIAsp 30 group than in the BHI 30 group [ ( 1.69 ± 0.42 ) mmol/L vs. ( 2.07 ± 0.51 ) mmol/L , t = -3.013 , P < 0.01 ] . The blood glucose increment over breakfast , dinner and the percentage of time at hyperglycaemia ( BG > 11.1 mmol/L ) were lower in the BIAsp 30 group than in the BHI 30 group [ ( 2.89 ± 1.32 ) mmol/L vs. ( 3.83 ± 1.18 ) mmol/L , t = -2.705 , P < 0.01 ; ( 2.69 ± 1.37 ) mmol/L vs. ( 3.55 ± 1.40 ) mmol/L , t = -2.232 , P < 0.05 ; ( 6.21 ± 6.04)% vs. ( 10.01 ± 6.80)% , t = -2.132 , P < 0.05 ] . The frequency of hypoglycemia was lower in the BIAsp 30 group than in the BHI 30 group , but there was no statistical difference ( P > 0.05 ) . CONCLUSION Pre-meal injection of BIAsp 30 in a twice-daily regimen could significantly improve the control of postpr and ial glucose level and reduce the overall glucose excursions so as to lower the risk of hypoglycaemia when compared to BHI 30 Previous studies have shown that heating the insulin injection site may accelerate insulin absorption . We investigated the pharmacological profile of insulin administered with InsuPatch , a local skin‐heating device The present prospect i ve one-year r and omized study was conducted to compare soluble human insulin , with a new rapid-acting human insulin analogue , lispro , with respect to postpr and ial glucose excursions , frequency of hypoglycaemic episodes , glucose control , and long-term safety in 39 subjects ( 20 females , 19 males ) with Type 1 diabetes . The duration of diabetes , gender distribution , and age were similar in the two groups . The total number of hypoglycaemic episodes was significantly less ( p < 0.04 , Wilcoxon rank sum test ) in subjects receiving insulin lispro compared with regular human insulin over the 12-month period . The 2-h postpr and ial glucose excursion at 1 year was also significantly less ( p < 0.05 , ANOVA ) in the group treated with insulin lispro . The reductions in the total number of hypoglycaemic episodes and in the postpr and ial glucose excursion with use of insulin lispro may be beneficial for the long-term management of subjects with Type 1 diabetes . However , the greatest benefit identified by the subjects receiving insulin lispro was the greater convenience of the rapid-acting analogue OBJECTIVE To compare the effects of insulin lispro ( LP ) and human regular insulin ( HR ) when given twice daily with NPH insulin on glycemic control ( HbA1c ) , daily blood glucose profiles and rates of hypoglycemia in patients with type 2 diabetes mellitus after failure to respond to sulfonylurea drugs . RESEARCH DESIGN AND METHODS A 5.5-month r and omized , open-label , parallel study of 148 patients receiving either LP ( n = 70 ) or HR ( n = 78 ) . Eight-point blood glucose profiles and HbA1c measurements were collected at baseline , 1.5 , 3.5 and 5.5 months . RESULTS Two-hour post-breakfast and 2-hour post-supper blood glucose levels ( means [ and st and ard errors ] ) were significantly lower for LP than for HR at the end point ( 9.5 [ 0.4 ] mmol/L v. 10.9 [ 0.4 ] mmol/L and 8.4 [ 0.4 ] mmol/L v. 9.7 [ 0.4 ] mmol/L , respectively , p = 0.02 in both cases ) . HbA1c improved from 10.5 % ( 0.2 % ) ( LP ) and 10.3 % ( 0.2 % ) ( HR ) to 8.0 % ( 0.1 % ) . Hypoglycemia rates were similar during the day ; however , there was an overnight trend to reduced rates with LP ( 0.08 [ 0.03 ] episodes/30 d v. 0.16 [ 0.04 ] episodes/30 d , p = 0.057 ) . Quality -of life assessment showed significant improvement ( p < 0.05 ) in the diabetes-related worry scale for LP subjects whereas HR subjects slightly worsened . CONCLUSIONS With traditional twice-daily insulin administration algorithms , LP improves 2-hour postpr and ial glucose levels , quality of life and overnight hypoglycemia rates while delivering an equivalent level of glycemic control ( HbA1c ) compared with HR to insulin-naïve patients with type 2 diabetes who require insulin OBJECTIVE To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia . Research design and methods An open-label , r and omised , 12-month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness . The efficacy of each treatment was evaluated by glycaemic control ( HbA(1c ) ) , eight-point home blood glucose profiles , and the frequency and severity of hypoglycaemic episodes and quality of life . RESULTS Eighteen ( 55 % ) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study . There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin ( 55 vs 84 episodes , p=0.087 ) . This result ed principally from a 47 % lower incidence of nocturnal severe hypoglycaemia with insulin lispro ( 25 vs 47 episodes , p=0.11 ) . The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments ( HbA(1c ) 9.1 % insulin lispro vs 9.3 % regular human insulin ) . CONCLUSIONS In individuals with type 1 diabetes , who have impaired awareness of hypoglycaemia , treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes . Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia , although a larger study is required to confirm these findings AIMS In intensified insulin therapy , the recent development of short-acting insulin analogues with a very rapid onset of action forces a new discussion in terms of the optimal injection-meal interval . This study evaluated pr and ial glycaemia in patients with Type 1 diabetes following the subcutaneous injection of soluble human insulin ( HI ) and the insulin analogue insulin aspart ( IAsp ) at different injection-meal intervals and investigated whether administration of IAsp after the meal might provide satisfactory metabolic control . METHODS In a r and omized , double-blind , double-dummy , four-period crossover study , 20 Type 1 diabetic patients were investigated . Pr and ial insulin was administered 15 min before the start of the meal ( HI(-15min ) ) , immediately before the meal ( HI(0min ) ; IAsp(0min ) ) and 15 min after the start of the meal ( IAsp(+15min ) ) . RESULTS Plasma glucose excursions from baseline levels during the 4 h ( PGexc ) were highest with HI(0min ) ( 17.9 mmol.l(-1).h ; P < 0.05 vs. other treatments ) and were not statistically different for HI(-15min ) , IAsp(0min ) and IAsp(15min ) ( 13.6 , 11.9 and 14.2 mmol.l(-1).h , respectively ) . Maximum concentration of plasma glucose ( PGmax ) was lowest with IAsp(0min ) ( 11.2 mmol/l ; P < 0.05 vs. other treatments ) . PGmax was comparable with HI(-15min ) , HI(0min ) and IAsp(+15min ) ( 13.3 , 14.1 and 13.2 mmol/l , respectively ) . CONCLUSIONS With regard to pr and ial glycaemia IAsp(+15min ) is as effective as HI(-5min ) and superior to HI(0min ) . Thus , post-pr and ial dosing of the insulin analogue IAsp offers an attractive and feasible therapeutic option for well-controlled patients with Type 1 diabetes mellitus Insulin lispro was compared with regular human insulin with respect to glycaemic control in patients with diabetes mellitus on intensive insulin treatment . Sixty-two patients ( 55 type 1 ; 7 type 2 ) from eight study centres in the Czech Republic , Slovenia and the Slovak Republic participated in a 4-month , open-label , r and omized , crossover study . Patients administered insulin lispro immediately before meals or regular human insulin 30 min before meals . A test meal ( 220 - 400 kcal ) , based on local and individual dietary habits and consistent for each patient throughout the study was given at baseline and at the end of each treatment . At each test meal visit HbA1c , fasting blood glucose , 1-hour and 2-hour postpr and ial blood glucose levels were measured . The level of HbA1c ( 7.6 % + /- 1.5 % versus 7.4 % + /- 1.5 % ) , incidence of hypoglycaemia ( 41 - 66 % of patients --versus 39 - 63 % ) and daily insulin dose ( 0.67 + /- 0.11 U/kg versus 0.65 + /- 0.11 U/kg ) did not differ between treatment groups at endpoint ( insulin lispro versus regular human insulin , respectively ) . Mean 2-hour postpr and ial blood glucose excursion for the insulin lispro group ( 0.0 + /- 3.7 mmol/L ) was significantly lower ( p = 0.035 ) when compared with the regular human insulin group ( 1.3 + /- 3.7 mmol/L ) at endpoint . Therapy with insulin lispro was therefore associated with a significant improvement in postpr and ial blood glucose excursion control when compared with regular human insulin , without an increase in rate of hypoglycaemia OBJECTIVE To compare the efficacy and safety of prepr and ial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes . STUDY DESIGN Open r and omised multicentre study . Women were treated with multiple insulin injections aim ing at normoglycaemia . Blood glucose was determined six times daily , HbA(1c ) every 4 weeks . Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21 , 28 and 34 . PARTICIPANTS 33 pregnant women with type 1 DM were r and omised to treatment with lispro insulin ( n=16 ) or regular insulin ( n=17 ) . RESULTS Blood glucose was significantly lower ( P<0.01 ) after breakfast in the lispro group , while there were no significant group differences in glycemic control during the rest of the day . Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia ( blood glucose < 3.0 mmol/l ) was more frequent in the lispro than in the regular group ( 5.5 vs. 3.9 % , respectively ) . HbA(1c ) values at inclusion were 6.5 and 6.6 % in the lispro and regular group respectively . HbA(1c ) values declined during the study period and were similar in both groups . There was no perinatal mortality . Complications during pregnancy , route of delivery and foetal outcome did not differ between the groups . Retinopathy progressed in both groups , one patient in the regular group developed proliferative retinopathy . CONCLUSION The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies A common treatment regimen for patients with either insulin-dependent diabetes mellitus ( IDDM ) or non-insulin-dependent diabetes mellitus ( NIDDM ) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day . It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal . In practice , patients often inject regular human insulin closer to mealtime , causing a higher post-pr and ial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period . Insulin lispro , a rapid-acting insulin analogue , is best injected just before a meal because of its more rapid absorption and shorter duration of action . In 707 r and omized patients , 379 with IDDM and 328 with NIDDM , we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin ( isophane insulin ) on premeal , 2-hour postpr and ial , and bedtime glycemic control . Assessment s were based on the results of a seven-point blood glucose profile , the insulin dose ( by formulation and time of administration ) , the incidence and frequency of hypoglycemic episodes , and the glycated hemoglobin value . Treatment with insulin lispro result ed in lower postpr and ial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin . Overall glycemic control , frequency of hypoglycemic events , and total insulin dose were not different between the two groups . Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves post-pr and ial glycemic control without increasing the risk of hypoglycemia AIM To compare the therapeutic efficacy of the short-acting insulin analogue insulin lispro ( Humalog ) with that of buffered regular human insulin ( Velosulin ) in patients on insulin pump therapy . PATIENTS AND METHODS Sixty-two ( 45 women and 17 men ) young patients with type 1 diabetes using insulin pump therapy were compared while using buffered regular human insulin for a mean + /- s.e.m . of 20.1+/-1.2 months or insulin lispro for a mean + /- s.e.m . of 19.7+/-0.5 months . The initial mean + /- s.e.m . age and duration of diabetes were 29.1+/-0.9 and 17.7+/-0.9 years , respectively . The mean HbA1c values , basal insulin dosages , premeal insulin dosages and number of low blood sugars were recorded during treatment with both insulins . RESULTS Mean + /- s.e.m . HbA1c values were significantly lower ( p < 0.001 ; paired Wilcoxon t-test ) during insulin lispro treatment ( 7.4+/-0.1 % ) as compared to treatment with buffered regular human insulin ( 7.9+/-0.1 % ) . Total units of insulin ( mean + /- s.e.m.)/kg/day was significantly ( p = 0.03 ) lower ( 0.61+/-0.02 ) during the insulin lispro treatment period as compared to the buffered regular human insulin treated period ( 0.65+/-0.03 ) . Total mean + /- s.e.m . ( U/kg/day ) of basal insulin administered per day was higher when patients received insulin lispro treatment ( 0.44+/-0.02 vs. 0.42+/-0.01 for buffered regular human insulin treated period ; p = 0.002 ) . The premeal insulin boluses ( mean + /- s.e.m . ) for the two treatment groups were significantly different with less insulin required for the insulin lispro treatment period for all three meals ( p < 0.001 , t-test ) . The number of mild/moderate and severe hypoglycaemic episodes were similar in the two groups . CONCLUSION We conclude that use of insulin lispro in pump therapy significantly lowers HbA1c values in comparison to therapy with buffered regular human insulin insulin without increasing hypoglycaemic episodes OBJECTIVE To compare long-term glycemic control and safety of using insulin aspart ( IAsp ) with that of regular human insulin ( HI ) . RESEARCH DESIGN AND METHODS This was a multicenter r and omized open-label 6-month study ( 882 subjects ) with a 6-month extension period ( 714 subjects ) that enrolled subjects with type 1 diabetes . Subjects administered IAsp immediately before meals or regular HI 30 min before meals ; basal NPH insulin was taken as a single bedtime dose in the majority of subjects . Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals . RESULTS Mean postpr and ial blood glucose levels ( mg/dl + /- SEM ) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast ( 156 + /- 3.4 vs. 185 + /- 4.7 ) , lunch ( 137 + /- 3.1 vs. 162 + /- 4.1 ) , and dinner ( 153 + /- 3.1 vs. 168 + /- 4.1 ) , when assessed after 6 months of treatment . Mean HbA1c values ( % + /- SEM ) were slightly , but significantly , lower for the IAsp group ( 7.78 % + /- 0.03 ) than for the regular HI group ( 7.93 % + /- 0.05 , P = 0.005 ) at 6 months . Similar postpr and ial blood glucose and HbA1c values were observed at 12 months . Adverse events and overall hypoglycemic episodes were similar for both treatment groups . CONCLUSIONS Postpr and ial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment . The improvement was not obtained at an increased risk of hypoglycemia . HbA1c was slightly , but significantly , lower for IAsp compared with HI at 6 and 12 months OBJECTIVE To establish whether the short-acting insulin analog lispro can be successfully implemented in long-term intensive insulin therapy in type 1 diabetes , and if so , what its effects are on glycemic control and frequency and awareness of hypoglycemia . RESEARCH DESIGN AND METHODS We r and omized 56 type 1 diabetic patients to treatment with either lispro ( n = 28 ) or human regular insulin ( Hum-R ; n = 28 ) as mealtime insulin for 1 year ( open design , parallel groups ) . Lispro was injected at mealtime and Hum-R was given 10 - 40 min before meals ( bedtime NPH was continued on both occasions ) . With lispro , NPH was added at breakfast ( approximately 70/30 ) , lunch ( approximately 60/40 ) , and supper ( approximately 80/20 ) ( mixing percentage of lispro/NPH ) to optimize premeal and bedtime blood glucose . RESULTS Total daily insulin units were no different in the two treatment groups , but with lispro approximately 30 % less short-acting insulin at meals and approximately 30 % more NPH was needed versus Hum-R ( P < 0.05 ) . The bedtime NPH dosage was no different . With lispro + NPH , the mean daily blood glucose was lower than with Hum-R ( 8.0 + /- 0.1 vs. 8.8 + /- 0.1 mmol/l ; P < 0.05 ) , HbA1c was lower ( 6.34 + /- 0.10 vs. 6.71 + /- 0.11 % , mean value over 1 year ; P < 0.002 ) , and hypoglycemia ( blood glucose < or = 3.8 mmol/l ) was less frequent ( 7.4 + /- 0.5 vs. 11.5 + /- 0.7 episodes/patient-month ) and tended to occur more within 90 min after meals than in the postabsorptive state ( P < 0.05 vs. Hum-R ) . After 1 year , plasma adrenaline and symptom responses to experimental , stepped hypoglycemia improved with lispro and were closer to the responses of 12 nondiabetic control subjects versus Hum-R both in terms of thresholds and magnitude ( P < 0.05 ) . CONCLUSIONS We concluded that mealtime injection of lispro + NPH improves the 24-h blood glucose and the percentage HbA1c as compared with Hum-R. The improvement can be maintained long term . Intensive therapy with lispro + NPH results in less frequent hypoglycemia and better awareness and counterregulation of hypoglycemia BACKGROUND Pregnancy outcome in diabetic women is strictly related to glycemic control during pregnancy . The aim of our study was to compare pregnancy outcome between patients subjected to intensive insulin therapy using regular human insulin and those treated with insulin lispro ( Humalog ) . MATERIAL / METHODS Group A ( n=25 ) was treated with Humalog , and the control group B ( n=46 ) with regular human insulin . Mean age , duration of diabetes , presence of chronic diabetic complications ( according to the White classification ) parity , and BMI did not differ between groups . RESULTS The mean HbA1c concentrations in groups A and B were respectively : 7.8+/-1.4 % vs. 7.5+/-1.5 % in the first trimester , 6.4+/-0.8 % vs. 6.5+/-1.6 % in the second , and 6.7+/-0.7 % vs. 6.3+/-1.2 % in the third ( no significant differences ) . The duration of pregnancy was 36.4+/-3.9 weeks in group A and 37.1+/-1.9 weeks in group B , while the mean neonatal birth weight was 3467+/-790 and 3367+/-666 g , respectively . Neither the frequency of preterm labor and cesarean section nor the frequency of fetal macrosomia and hypoglycemia differed between groups . There was only one malformed infant in the human insulin-treated group , and no statistical difference in the rate of spontaneous abortion between groups . Also , there were no differences in the frequencies of occurrence of hypertension ( essential and pregnancy induced ) and urinary tract infections . CONCLUSIONS The course of pregnancy and perinatal outcome is comparable in intensively treated diabetic women regardless of the short-acting insulin used . Humalog appears to be a safe alternative to human insulin in the treatment of diabetes during pregnancy UNLABELLED Absorption rates of phosphate buffered insulin analogs aspart and lispro prevail over regular human insulin . However , insulin aspart has not been widely used . The aim of this open controlled clinical study is to compare the metabolic effects of insulin aspart and phosphate buffered insulin when both are used in insulin pumps according to the identical algorithms . METHODS Twenty one persons aged 39.9 + /- 2.89 ( mean + /- SE ) years ( y ) with type 1 diabetes mellitus duration of 17.9 + /- 2.21 y treated by an insulin pump for 4.3 + /- 0.53 y ( at least 3 months ) , educated in self monitoring , entered the study . Mean plasma glucose , rates of hypo- and hyperglycaemias from the glucometer memory and other data from the first 256 + /- 19.97 days period with regular human insulin ( check-up 1 and 2 ) and consequent 364 + /- 8.78 days long period with insulin aspart ( check-up 3 and 4 ) were compared ( paired t-test ) . Replacement of human regular insulin with insulin aspart after two check-ups was the only change in the treatment of diabetes . No special therapeutic education or training was made during the study . RESULTS In persons with type 1 diabetes treated by an insulin pump with insulin aspart , despite the lower daily dose of insulin aspart vs human regular insulin , the HbA1c decreased ; the frequency of hypo- and hyperglycaemias and the BMI did not change . CONCLUSIONS Insulin analog aspart appears to be more effective for continuous subcutaneous insulin infusion than regular human insulin Insulin lispro [ Lys ( B28 ) , Pro ( B29 ) human insulin ] is a rapidly absorbed analog that has diminished tendency to self-associate . In four open-label , 1-year-long international r and omized trials , we contrasted the immunogenicity of insulin lispro versus regular human insulin ( RHI ) in patients previously treated with insulin who had IDDM or NIDDM . Using a self-blank subtraction assay , we assessed sera for the presence of insulin-specific antibodies ( ISA ) , insulin lispro-specific antibodies ( LSA ) , and cross-reactive antibodies ( CRA ) . Basal insulin needs were provided either with human ultralente ( UL ) or NPH insulins . After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH , 50 % of patients were r and omly assigned to begin insulin lispro or continue on RHI . At baseline , few pretreated patients had LSA ( 0–4 % ) and ∼ 10 % had ISA , whereas 41–45 % of patients with IDDM and 23–27 % of patients with NIDDM had CRA ( IDDM vs. NIDDM , P < 0.001 ) . Within studies , no significant differences were noted over time in ISA , LSA , or CRA attributable to the type of short-acting insulin . When data were pooled , inconsistent changes were noted in ISA and LSA ( LSA were greater in NIDDM vs. IDDM at baseline , P = 0.001 , and ISA were greater in IDDM vs. NIDDM at 6 months , P = 0.007 ) . Significant levels of CRA were more common in IDDM at all times ( P < 0.001 , P = 0.022 , and P = 0.002 at baseline , 6 months , and 12 months , respectively ) . For patients receiving insulin lispro , no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study ( became positive , remained positive , became negative , or remained negative ) . IDDM patients were more likely to develop or maintain CRA levels ( P = 0.008 vs. NIDDM ) , whereas antibody levels were comparable among positive individuals . No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients OBJECTIVE For intensified insulin therapy of type 1 diabetes , bolus injection of regular human insulin 30–15 min before a meal is currently recommended . This r and omized study is aim ed to determine whether insulin lispro ( LIS ) , a new insulin analog with a rapid onset of action , can provide comparable blood glucose ( BG ) control by injection after the meal . RESEARCH DESIGN AND METHODS Eighteen type 1 diabetic subjects injected regular insulin ( REG ) at 40 , 20 , or 0 min before or LIS at 20 or 0 min before or 15 min after the start of a st and ardized test meal . BG excursions and area under the curve of BG excursions ( AUC ) at the six visits were compared by analysis of variance . Hypoglycemic events ( BG ≤2.78 mmol/1 ) were evaluated in relation to the achieved postpr and ial BG control . RESULTS Mean AUC values were 2.00 , 2.55 , and 3.33 mmol · h · 1−1 for REG given 40 , 20 , and 0 min before the test meal , respectively , and −2.19 , −2.15 , and 1.98 mmol · h · 1−1 for LIS given 20 and 0 min before and 15 min after the start of the test meal , respectively . LIS injected 20 min ( −20 ) or immediately ( 0 ) before the meal was significantly more effective in controlling postpr and ial BG excursion ( P < 0.001 ) than any REG treatment . Postpr and ial injection of LIS ( 15 ) did not compromise postpr and ial BG control and result ed in less hypoglycemia . REG −40 and LIS −20 were associated with early hypoglycemia , but other hypoglycemic events were equally distributed among groups . CONCLUSIONS The optimal time for bolus insulin injection was 20 min before the meal for REG and immediately before the meal for LIS . LIS injected immediately after a st and ard meal provided postpr and ial BG control at least as good as REG injected from 40 to 0 min before the meal . Postpr and ial injection of LIS is an attractive new therapeutic option Insulin aspart has been shown , in medium-term studies , to achieve reductions in HbA(1c ) without increasing the risk of major hypoglycaemia compared with pre-meal human insulin . The aim of the present 3-year study was to evaluate the long-term safety and efficacy of insulin aspart in people with type 1 diabetes . This was a 30-month extension of a multinational , multicentre , open-label , parallel-group study of 753 people with type 1 diabetes , originally r and omly allocated to treatment with insulin aspart or unmodified human insulin before meals , with NPH insulin as basal insulin . Main outcomes measures were hypoglycaemia ( major or minor ) , adverse events and HbA(1c ) . As insulin aspart became commercially available in some countries before the end of the trial , analyses of HbA(1c ) used 30-month data to maintain statistical power . The relative risk estimate of major hypoglycaemia was similar between treatment groups ( relative risk [ RR ] 1.00 [ 95 % CI 0.72 , 1.39 ] ) . The risk of having a minor hypoglycaemic episode was higher with insulin aspart than with human soluble insulin ( RR 1.24 [ 1.09 , 1.39 ] p=0.024 ) . Insulin aspart was significantly superior to human insulin with respect to overall glycaemic control , with a baseline-adjusted HbA(1c ) difference of -0.16 ( -0.32 , -0.01)% ( p=0.035 ) . Insulin aspart was well tolerated and effective during long-term treatment . The HbA(1c ) advantage was maintained with insulin aspart without any adverse impact on the rate of major hypoglycaemia AIMS To compare the efficacy of insulin aspart , a rapid-acting insulin analogue , with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus . METHODS Prospect i ve , multi-centre , r and omized , open-labelled , parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1,070 adult subjects with Type 1 diabetes . Study patients were r and omized 2:1 to insulin aspart or unmodified human insulin before main meals , with NPH-insulin as basal insulin . Main outcome measures were blood glucose control as assessed by HbA1c , eight-point self-monitored blood glucose profiles , insulin dose , quality of life , hypoglycaemia , and adverse events . RESULTS After 6 months , insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 ( 95 % confidence interval 0.03 - 0.22 ) % Hb , P < 0.02 . Eight-point blood glucose profiles showed lower post-pr and ial glucose levels ( mean baseline-adjusted -0.6 to -1.2 mmol/l , P < 0.01 ) after all main meals , but higher pre-pr and ial glucose levels before breakfast and dinner ( 0.7 - 0.8 mmol/l , P < 0.01 ) with insulin aspart . Satisfaction with treatment was significantly better in patients treated with insulin aspart ( WHO Diabetes Treatment Satisfaction Question naire ( DTSQ ) baseline-adjusted difference 2.3 ( 1.2 - 3.3 ) points , P < 0.001 ) . The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 ( 0.59 - 1.18 , NS ) . Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart ( 1.3 vs. 3.4 % of patients , P < 0.05 ) , as were late post-pr and ial ( 4 - 6 h ) events ( 1.8 vs. 5.0 % of patients , P < 0.005 ) . CONCLUSIONS These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control , hypoglycaemia , and quality of life , in people with Type 1 diabetes mellitus OBJECTIVE Several studies have suggested that use of the short-acting insulin analog , insulin lispro , in multiple injection therapy may reduce the risk of hypoglycemia in comparison with regular insulin . This effect might be more pronounced in well-controlled patients , since intensive treatment of IDDM increases the rate of severe hypoglycemic events . This study evaluated the effects of insulin lispro on glycemic control and hypoglycemia rates in well-controlled IDDM patients . RESEARCH DESIGN AND METHODS This was an open , r and omized , 6-month crossover study of 199 IDDM patients . Glycemic control was evaluated by HbA1c , home blood glucose measurements , and rate and timing of hypoglycemic events . At the end of the study , patients completed an evaluation form regarding therapy-related quality of life . RESULTS HbA1c remained constant at ∼ 7.3 % throughout the study . Meal-related glucose excursions were significantly lower with insulin lispro compared with regular insulin ( mean −0.8 ± 1.7 vs. 1.1 ± 1.6 mmol/l , P < 0.001 ) , as was the within-day variability ( M value 27.7 ± 19.7 vs. 30.2 ± 23.1 , P = 0.007 ) . The incidence of severe hypoglycemic events ( 58 vs. 36 , P = 0.037 ) including coma ( 16 vs. 3 , P = 0.004 ) was significantly lower with insulin lispro than with regular insulin . Patients felt that insulin lispro increased flexibility and freedom of lifestyle . CONCLUSIONS In well-controlled IDDM patients , insulin lispro is associated with a lower risk of severe hypoglycemia and coma Quality of life was assessed in a multicentre r and om cross-over study ( UK-Benelux ) of 189 well-controlled IDDM patients undergoing treatment with lispro insulin analog ( Lilly ) . Lispro offered several advantages over regular insulin for intensive diabetes treatment . Patients were more satisfied , felt more flexible in their lifestyle ( no delayed meals due to injections , need for fewer snacks ) , reported a decrease in hypoglycaemic episodes , and considered their glycaemic control as better during the lispro period . Seventy-four percent of patients elected to continue treatment with lispro . A study of different injection times related to meals provided better knowledge of postpr and ial blood glucose excursions after lispro and showed that the optimal time for lispro injection was just before the meal , which was very convenient for the patients . Another study showed that lispro analogue , because of its pharmacokinetic properties , can reduce dietary restrictions in well-controlled IDDM patients on intensified insulin treatment BACKGROUND Insulin analogues have been developed to reduce the risk of hypoglycaemia in patients with diabetes who require insulin-based treatment , but their effect on this endpoint in patients with type 1 diabetes complicated by recurrent severe hypoglycaemia is unknown . We compared the occurrence of severe hypoglycaemic episodes in such patients during treatment with insulin analogues or human insulin . METHODS In this investigator-initiated , prospect i ve , r and omised , open-label , blinded-endpoint crossover trial at seven medical centres in Denmark , we recruited patients ( aged ≥18 years ) with type 1 diabetes ( diagnosed for > 5 years ) who had reported two or more episodes of severe hypoglycaemia in the preceding year . Patients were r and omly assigned ( 1:1 ) using computer-generated site-specific r and omisation lists in blocks of four to treatment with basal-bolus therapy with either analogue insulin ( detemir and aspart ) or human insulin ( human neutral protamine Hagedorn and human regular ) in a balanced crossover design . A 1-year plus 1-year treatment period was specified , consisting of two 3-month run-in periods , each followed by a 9-month maintenance period . The primary endpoint was the number of vali date d episodes of severe hypoglycaemia ( defined by need for treatment assistance from others ) reported during the maintenance periods , analysed by intention to treat . The study is registered with Clinical Trials.gov , number NCT00346996 . FINDINGS Between May 9 , 2007 , and Oct 30 , 2009 , 159 patients were r and omly assigned . 18 patients discontinued during the first run-in period , leaving 141 patients in the intention-to-treat population . 136 severe hypoglycaemic episodes were reported during treatment with human insulin and 105 episodes were reported during treatment with insulin analogues , result ing in an absolute rate reduction of 0.51 episodes ( 95 % CI 0.19 - 0.84 ) per patient-year with insulin analogues . This result corresponds to a relative rate reduction of 29 % ( 95 % CI 11 - 48 ; p=0.010 ) . INTERPRETATION Treatment with insulin detemir and aspart in patients with type 1 diabetes and recurrent severe hypoglycaemia result ed in a clinical ly significant reduced rate of severe hypoglycaemia compared with human insulin . Patients with the greatest chance of benefitting from improved insulin therapy should be offered treatment with insulin analogues and be included in future trials of new insulins . FUNDING Novo Nordisk Aims This r and omized , multi‐centre , double‐blind , stratified , two period , cross‐over trial was undertaken to assess the pharmacokinetics and pharmacodynamics of insulin aspart injected immediately before compared with regular human insulin injected 30 min before a Mediterranean‐style meal in 37 ( 23 M , 14 F ) patients with Type 2 diabetes Summary The aim of these studies was to compare the pharmacokinetics , pharmacodynamics , counterregulatory hormone and symptom responses , as well as cognitive function during hypoglycaemia induced by s. c. injection of 0.15 IU/kg of regular human insulin ( HI ) and the monomeric insulin analogue [ Lys(B28),Pro ( B29 ) ] ( MI ) in insulin-dependent-diabetic ( IDDM ) subjects . In these studies glucose was infused whenever needed to prevent decreases in plasma glucose below 3 mmol/l . After MI , plasma insulin increased earlier to a peak ( 60 vs 90 min ) which was greater than after HI ( 294±24 vs 255±24 pmol/l ) , and plasma glucose decreased earlier to a 3 mmol/l plateau ( 60 vs 120 min ) ( p<0.05 ) . The amount of glucose infused to prevent plasma glucose falling below 3 mmol/l was ∼three times greater after MI than HI ( 293±26 vs 90±25 μmol · kg−1 · 60–375 min−1 , p<0.05 ) . After MI , hepatic glucose production was more suppressed ( 0.7±1 vs 5.9±0.54 μmol · kg−1 · min−1 ) and glucose utilization was less suppressed than after HI ( 11.6±0.65 vs 9.1±0.11μmol · kg−1 · min−1 ) ( p<0.05 ) . Similarly , plasma NEFA , glycerol , and β-OH-butyrate were more suppressed after MI than HI ( p<0.05 ) , whereas plasma lactate increased only after MI , but not after HI . Responses of counterregulatory hormones , symptoms and deterioration in cognitive function during plasma glucose plateau of 3 mmol/l were superimposable after MI and HI ( p = NS ) . Post-hypoglycaemia hyperglycaemia was greater after MI than HI ( at 480 min 12.1±1 vs 11±1 mmol/l ) because of greater hepatic glucose production during insulin waning which occurred at least 135 min earlier with MI as compared to HI ( p<0.05 ) . It is concluded that counterregulatory hormones , symptoms and deterioration in cognitive function during hypoglycaemia respond similarly after MI and HI . The biological effect of MI appears greater than that of HI for at least 4 h after the s.c . injection and appears as a good c and i date for achieving optimal post-pr and ial glucose control in IDDM BACKGROUND : In this study , we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 ( BIAsp30 ) with that of biphasic human insulin 30 ( BHI30 ) over a period of 24 months in patients with type 2 diabetes . METHODS : Patients with type 2 diabetes ( n=125 ) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a r and omized , controlled , multinational trial . RESULTS : No significant difference was found in mean HbA(1c ) after 24 months [ BIAsp30 , 8.35+/-0.20 % ; BHI30 8.13+/-0.16 % ; adjusted mean difference ( BIAsp30-BHI30 ) 0.03 ( 90 % CI -0.29 to 0.34)% , P=0.89 ] . The proportion of patients experiencing major hypoglycaemia was also similar during the first year ( BIAsp30 , 5 % ; BHI30 , 8 % ; P=0.72 ) , but it was significantly lower with BIAsp30 than with BHI30 during the second year ( BIAsp30 , 0 % ; BHI30 , 10 % ; P=0.04 ) . The proportion experiencing minor hypoglycaemia was not significantly different . No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months ( BIAsp30 , 4.87+/-1.92 % ; BHI30 ; 1.00+/-1.66 % ; P=0.13 ) . Body weight change was 0.05+/-0.81 kg in the BIAsp30 group and 2.00+/-0.69 kg in the BHI30 group ( P=0.07 ) . CONCLUSIONS : Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA(1c ) levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes OBJECTIVE Insulin aspart is a novel rapid-acting insulin analog . This study was performed to compare the postpr and ial serum glucose control after administration of insulin aspart with that of unmodified human insulin . RESEARCH DESIGN AND METHODS The trial was a double-blind double-dummy injection three-way cross-over study in 22 subjects with type 1 diabetes . Insulin aspart was injected subcutaneously immediately before the meal , and human insulin was injected subcutaneously 30 min before the meal or immediately before the meal . RESULTS The postpr and ial glucose control as assessed by the excursion of serum glucose was superior with insulin aspart as compared with that with human insulin injected immediately before or 30 min before a meal ( 891 + /- 521 vs. 1,311 + /- 512 vs. 1,106 + /- 571 mmol.l-1.min-1 , P < 0.0001 and P < 0.02 ) . This was accompanied by a significantly lower glucose maximum concentration [ Cmax(SG ) ] for insulin aspart than for human insulin injected immediately before the meal ( 13.5 + /- 3.5 vs. 16.4 + /- 3.4 mmol/l , P < 0.001 ) . Insulin aspart was , on average , absorbed twice as fast as human insulin , with median time to insulin aspart Cmax(ins ) on the order of 40 min , and the maximum concentration was approximately twice as high for insulin aspart . The relative bioavailability of the insulins indicated a similar extent of absorption . Insulin aspart was well tolerated . CONCLUSIONS This study demonstrates the ability of insulin aspart to improve postpr and ial glucose control when compared with human insulin BACKGROUND Subcutaneous absorption is accelerated by the monomeric conformation of insulin Aspart , which provides good glycemic control with a lower risk of hypoglycemia and less body weight increase . In the present study we investigated the efficacy and safety of a rapid-acting human insulin analogue ( insulin Aspart ) delivered with continuous subcutaneous insulin infusion ( CSII ) into Chinese diabetic patients . METHODS A total of 21 patients with type 1 or type 2 diabetes were recruited for the 2-way cross-over , open-labeled trial , and then r and omized to Group A ( n = 10 , treated with insulin Aspart ) or Group B ( n = 11 , treated with Novolin R ) . Insulin Aspart and Novolin R were administered by CSII . Capillary glucose concentrations were measured at 8 time points , pre-pr and ial and postpr and ial , bedtime ( 10 pm ) , midnight ( 2 am ) every day during the treatment . RESULTS The average capillary glucose profiles for the day were much better controlled in Group A than in Group B ( P < 0.01 ) . The blood glucose levels were particularly better controlled in Group A than in Group B at pre-breakfast ( ( 6.72 + /- 1.24 ) mmol/L vs ( 7.84 + /- 1.58 ) mmol/L , P = 0.014 ) , post-breakfast ( ( 8.96 + /- 2.41 ) mmol/L vs ( 11.70 + /- 3.11 ) mmol/L , P = 0.0028 ) , post-supper ( ( 8.15 + /- 2.10 ) mmol/L vs ( 10.07 + /- 2.36 ) mmol/L , P = 0.008 ) , bed time ( ( 7.73 + /- 1.72 ) mmol/L vs ( 9.39 + /- 2.05 ) mmol/L , P = 0.007 ) and midnight ( ( 6.32 + /- 1.16 ) mmol/L vs ( 7.48 + /- 1.36 ) mmol/L , P = 0.0049 ) . There was no significant difference in the frequency of hypoglycemic episodes between the two groups . CONCLUSION Insulin Aspart results in better control of blood glucose levels than regular human insulin ( Novolin R ) in diabetic patients during delivery by CSII OBJECTIVE Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin . Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion ( CSII ) treatment were assessed in an open r and omized crossover trial comparing insulin lispro and regular human insulin , both applied with insulin pumps . RESEARCH DESIGN AND METHODS A total of 113 type 1 patients ( 60 male , 53 female , age [ mean + /- SD ] 37 + /- 12 years , duration of diabetes 19 + /- 9 years ) participated in this open , r and omized crossover study . Both insulins were applied for 4 months each with the appropriate intervals between the pr and ial insulin bolus and the meal ( human insulin : 30 min ; lispro : 0 min ) . Observation parameters were HbA1c , daily and postpr and ial blood glucose profiles , adverse events , rate of hypoglycemic and hyperglycemic events , number of catheter obstructions , and treatment satisfaction as assessed with an international vali date d question naire . RESULTS The patients were well controlled with a mean HBA1c of 7.24 + /- 1.0 % at baseline . HbA1c decreased in both treatment periods , but it was better during insulin lispro treatment ( insulin lispro : 6.8 + /- 0.9 % , regular human insulin : 6.9 + /- 1.0 % , Friedman 's rank-sum test : P < 0.02 ) . In addition , the 1-h and 2-h postpr and ial rises in blood glucose were significantly lower ( P < 0.001 for each meal ) with insulin lispro , result ing in smoother daily glucose profiles as compared with regular human insulin . No significant differences were reported for the rate of hypoglycemia ( mean + /- SD [ median ] : insulin lispro 12.4 + /- 13.9 [ 8 ] , regular human insulin 11.0 + /- 11.2 [ 8 ] ) , for the rate of catheter obstructions ( 42 events in each treatment arm ) , and for the number and type of adverse events . No severe case of ketoacidosis was seen during insulin lispro treatment , whereas one case was reported during therapy with regular human insulin . Treatment satisfaction was better when patients were treated with insulin lispro . CONCLUSIONS Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment . Its safety profile does not differ from that of regular human insulin The present study aim ed at investigating the influence of the time interval between injection of regular insulin and meal ingestion on postpr and ial glucose changes and overall blood glucose control in patients with type 1 diabetes on intensive insulin therapy . Fifteen C-peptide negative subjects were su bmi tted , in a r and omized order , to two 6-week treatment periods in which regular insulin was injected either 5 minutes or 30 minutes before each of the three main meals , in combination with a bedtime NPH insulin injection . The changes in plasma glucose excursions following a breakfast test ( Cmax , Tmax , Cmin , Tmin , AUC0 - 240 min ) were similar in the two experimental protocol s. Furthermore , no significant changes were observed in daily insulin dosages nor in glucose profiles obtained using home blood glucose monitoring . Only a tendency to a greater 90-minutes postpr and ial increase in blood glucose levels was observed when regular insulin was injected 5 minutes rather than 30 minutes before meal . Glycated haemoglobin levels were similar after each treatment period ( 7.6 + /- 0.2 % versus 7.5 + /- 0.2 % ; NS ) and no differences in the incidence or severity of hypoglycaemic episodes were noticed between the two insulin schemes . In conclusion , in type 1 diabetic patients who are rather well controlled with a basal-bolus insulin scheme , the injection of regular insulin 30 minutes before each main meal provides no significant advantage as compared to the injection of regular insulin 5 minutes before meal A total of 166 patients ( 102 type 1 , 64 type 2 ) were r and omised to insulin lispro ( LP ) combined with insulin lispro protamine suspension ( NPL ) , an intermediate-acting formulation of LP , or to regular human insulin ( HR ) combined with human NPH insulin ( NPH ) in this open-label , parallel study . Insulin doses were similar at endpoint . Blood glucose ( BG ) measurements ( before and two hours after meals , bedtime , 3 a.m.)(mmol/l ) were lower with LP/NPL two hours after breakfast ( 8.84 + /- 0.32 vs 10.29 + /- 0.41 , p < 0.001 ) , before lunch ( 6.21 + /- 0.20 vs 7.10 + /- 0.31 , p = 0.016 ) , two hours after the evening meal ( 10.18 + /- 0.36 vs 7.86 + /- 0.28 , p < 0.0.001 ) , and at bedtime ( 7.85 + /- 0.28 vs 9.43 + /- 0.40 , p = 001 ) . HbA1c was lower for LP/NPL at endpoint ( 7.54 + /- 0.11 % vs 7.92 + /- 0.10 % , p = 0.019 ) . There was no difference in hypoglycaemia or insulin antibody levels . LP/NPL result ed in better glycaemic control than HR/NPH without increasing the risk of hypoglycaemia Intensive insulin management improves glycemic control and lowers the risks of long-term microvascular complications ( 1 ) . Several new insulin analogs ( 2 ) are in use to improve glycemic control in type 1 diabetes . Glargine in particular is a “ basal insulin ” ( 3 ) and found to be relatively peakless . Glargine is thought to provide glucose profiles similar to insulin pumps ( 4 ) . Although some clinical studies suggest that glargine lasts 24 h in children with diabetes ( 5 ) , to date there have been no formal pharmacokinetic and pharmacodynamic data to make that cl aim in the pediatric population . In fact , clinical observations in pediatric type 1 diabetes suggest that glargine action may be < 24 h. This would entail twice-daily glargine dosing and short-acting insulin analogs ( SAIs ) , such as lispro and aspart , given separately three to four times per day , result ing in improved glycemic control but compromising compliance and increasing complexity of management ( 6 ) . In this study , we tested the hypothesis that mixing glargine with SAIs and dividing the dose of glargine into twice- versus once-daily dosing would not adversely affect glycemic control as assessed by a continuous glucose monitoring system ( CGMS ) . The protocol was approved by the institutional review board of the Baylor College of Medicine , and consent was obtained before each study . Subjects were recruited from Texas Children ’s Hospital Diabetes Care Center , Houston , Texas . Subjects had type 1 diabetes for at least 1 year with no other chronic illness and were on Aim : To identify factors associated with nocturnal hypoglycaemia in patients with type 2 diabetes who were new ( < 2 months therapy ) to insulin therapy Insulin lispro is a human insulin analog that dissociates more rapidly than human regular insulin after subcutaneous injection , result ing in higher insulin levels at an earlier point in time and a shorter duration of action . The aim of the study was to evaluate if this pharmacokinetic difference would translate into better postpr and ial and overall control in 30 IDDM patients ( age , 35.1 ± 1.5 years ; male-female ratio , 17:13 ; BMI , 24.8 ± 0.5 kg/m2 ; HbA1c , 8.03 ± 0.13 % at baseline ) treated with continuous subcutaneous insulin infusion ( CSII ; Disetronic H-TRON V100 ) in a double-blind crossover clinical study . Patients were r and omized to insulin lispro or human regular insulin for 3 months before crossing over to the other insulin for another 3 months . All meal boluses were given immediately before breakfast , lunch , and supper . An eight-point blood glucose profile was measured once weekly , and HbA1c levels were measured monthly . At the end of the 3-month treatment period , HbA1c levels were significantly lower with insulin lispro , compared with human regular insulin : 7.66 ± 0.13 vs. 8.00 ± 0.16 % ( P = 0.0041 ) . While prepr and ial , bedtime , and 2:00 A.M. values for blood glucose were not significantly different , 1-h postpr and ial blood glucose was significantly improved after breakfast , lunch , and dinner with insulin lispro , compared with human regular insulin : 8.35 vs. 9.79 mmol/l ( P = 0.006 ) , 7.58 vs. 8.74 mmol/l ( P = 0.049 ) , and 7.85 vs. 9.01 mmol/l ( P = 0.03 ) . The incidence of hypoglycemia per 30 days ( blood glucose levels , < 3.0 mmol/l ) was 8.4 ± 1.3 before r and omization , decreasing to 6.0 ± 0.9 for insulin lispro and to 7.6 ± 1.3 for regular insulin during the last month of the study . Two patients in each group reported insulin precipitation . We conclude that insulin lispro improves glycemic control in CSII without increasing the risk of hypoglycemia Aims /hypothesisWe determined the impact of insulin pump therapy on long-term glycaemic control , BMI , rate of severe hypoglycaemia and diabetic ketoacidosis ( DKA ) in children . Methods Patients on pump therapy at a single paediatric tertiary hospital were matched to patients treated by injections on the basis of age , duration of diabetes and HbA1c at the time of pump start . HbA1c , anthropometric data , episodes of severe hypoglycaemia and rates of hospitalisation for DKA were collected prospect ively . Results A total of 345 patients on pump therapy were matched to controls on injections . The mean age , duration of diabetes at pump start and length of follow-up were 11.4 ( ± 3.5 ) , 4.1 ( ± 3.0 ) and 3.5 ( ± 2.5 ) years , respectively . The mean HbA1c reduction in the pump cohort was 0.6 % ( 6.6 mmol/mol ) . This improved HbA1c remained significant throughout the 7 years of follow-up . Pump therapy reduced severe hypoglycaemia from 14.7 to 7.2 events per 100 patient-years ( p < 0.001 ) . In contrast , severe hypoglycaemia increased in the non-pump cohort over the same period from 6.8 to 10.2 events per 100 patient-years . The rate of hospitalisation for DKA was lower in the pump cohort ( 2.3 vs 4.7 per 100 patient-years , p = 0.003 ) over the 1,160 patient-years of follow-up . Conclusions /interpretationThis is the longest and largest study of insulin pump use in children and demonstrates that pump therapy provides a sustained improvement in glycaemic control , and reductions of severe hypoglycaemia and hospitalisation for DKA compared with a matched cohort using injections Late in 2004 , the German Health Ministry held a conference that aim ed to improve outcomes and cost-benefit relations in the treatment of chronic diseases . The ministry was concerned that the increasing costs of treatment were not accompanied by an improvement in patient relevant outcomes . As a consequence , in 2005 the Joint Federal Committee — the top decision body of the German healthcare system — commissioned the Institute for Quality and Efficiency in Health Care ( IQWiG ) with the assessment of diagnostic and therapeutic interventions in chronic diseases , including diabetes . In this context , the Institute assessed the additional benefit of short and long acting insulin analogues compared with that achieved with human insulin . The methods used by the Joint Federal Committee and IQWiG aim ed to evaluate a direct proof of benefit with regard to patient oriented outcomes or valid surrogate parameters.1 2 They required such parameters to be assessed in appropriate r and omised controlled clinical trials , and non-r and omised observational studies were regarded |
11,709 | 30,302,909 | Technical complications were the main reason for failures .
The 5-year clinical performance of RBFPDs is similar to the performance of conventional fixed partial dentures ( FPDs ) and implant-supported crowns . | null | null |
11,710 | 31,179,059 | Trial sequential analysis of continuous data on blood loss and dichotomous outcomes on transfusion of blood products suggested the benefits of a TEG/ROTEM-guided algorithm .
Conclusions TEG or ROTEM-guided transfusion strategies may reduce blood loss volume and the transfusion rates in adult patients undergoing cardiac surgery | Background Severe bleeding and massive transfusion of blood products may be associated with increased morbidity and mortality of cardiac surgery .
A transfusion algorithm incorporating thromboelastography ( TEG ) or rotational thromboelastometry ( ROTEM ) can help to determine the appropriate time and target for the use of hemostatic blood products , which may thus reduce the quantity of blood loss as well as blood products transfused . | Background Abnormal bleeding after cardiopulmonary bypass ( CPB ) is a common complication of cardiac surgery , with important health and economic consequences . Coagulation test – based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding . Methods The authors performed a r and omized prospect i ve trial comparing allogeneic transfusion practice s in 92 adult patients with abnormal bleeding after CPB . Patients with abnormal bleeding were r and omized to one of two groups : a control group following individual anesthesiologist ’s transfusion practice s and a protocol group using a transfusion algorithm guided by coagulation tests . Results Among 836 eligible patients having all types of elective cardiac surgery requiring CPB , 92 patients developed abnormal bleeding after CPB ( incidence , 11 % ) . The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB ( median , 0 units ; range , 0–7 units ) than the control group ( median , 3 units ; range , 0–10 units ) ( P = 0.0002 ) . The median number of platelet units transfused in the operating room after CPB was 4 ( range , 0–12 ) in the algorithm group compared with 6 ( range , 0–18 ) in the control group ( P = 0.0001 ) . Intensive care unit ( ICU ) mediastinal blood loss was significantly less in the algorithm group . Multivariate analysis demonstrated that transfusion algorithm use result ed in reduced ICU blood loss . The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding ( 11.8%vs . 0%;P = 0.032 ) . Conclusions Use of a coagulation test – based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss BACKGROUND Using algorithms based on point of care coagulation tests can decrease blood loss and blood component transfusion after cardiac surgery . We wished to test the hypothesis that a management algorithm based on near-patient tests would reduce blood loss and blood component use after routine coronary artery surgery with cardiopulmonary bypass when compared with an algorithm based on routine laboratory assays or with clinical judgement . METHODS Patients ( n=102 ) undergoing elective coronary artery surgery with cardiac bypass were r and omized into two groups . In the point of care group , the management algorithm was based on information provided by three devices , the Hepcon , thromboelastography and the PFA-100 platelet function analyser . Management in the laboratory test group depended on rapidly available laboratory clotting tests and transfusion of haemostatic blood components only if specific criteria were met . Blood loss and transfusion was compared between these two groups and with a retrospective case-control group ( n=108 ) , in which management of bleeding had been according to the clinician 's discretion . RESULTS All three groups had similar median blood losses . The transfusion of packed red blood cells ( PRBCs ) and blood components was greater in the clinician discretion group ( P<0.05 ) but there was no difference in the transfusion of PRBCs and blood components between the two algorithm-guided groups . CONCLUSION Following algorithms based on point of care tests or on structured clinical practice with st and ard laboratory tests does not decrease blood loss , but reduces the transfusion of PRBCs and blood components after routine cardiac surgery , when compared with clinician discretion . Cardiac surgery services should use transfusion guidelines based on laboratory-guided algorithms , and the possible benefits of point of care testing should be tested against this st and ard We set out to determine if the heparinase-modified thrombelastogram using anticoagulated blood from patients during cardiac surgery could guide treatment with haemostatic components . In 60 patients a simple algorithm predicted a possible 60 - 80 % decrease in the use of haemostatic components . In a second series , 30 patients were allocated to receive components using this intra-operative algorithm and 30 using clinical criteria and laboratory-based tests . Ten patients in the clinical group received a total of 16 units of fresh frozen plasma and nine platelet concentrates compared with five patients transfused with five units of fresh frozen plasma and one platelet concentrate in the algorithm group . Twelve-hour chest tube losses [ algorithm group 470 ( 295 - 820 ) ml , clinical ly managed group 390 ( 240 - 820 ) ml ( median , quartile values ) ] were not different between groups despite the threefold reduction in the use of haemostatic products , showing that intra-operative monitoring of coagulation in the anticoagulated patient can be used to guide treatment OBJECTIVE Aortic surgical procedures requiring hypothermic circulatory arrest are associated with altered hemostasis and increased bleeding . In a r and omized clinical trial , we evaluated effects of thromboelastometrically guided algorithm on transfusion requirements . METHODS Fifty-six consecutive patients ( 25 with acute type A dissection ) undergoing aortic surgery with hypothermic circulatory arrest were enrolled in a r and omized trial during a 6-month period . Patients were r and omly allocated to treatment group ( n = 27 ) with thromboelastometrically guided transfusion algorithm or control group ( n = 29 ) with routine transfusion practice s ( clinical judgment-guided transfusion followed by transfusion according to coagulation test results ) . Primary end point was cumulative allogeneic blood units ( red blood cells , fresh-frozen plasma , and platelets ) transfused . RESULTS Transfusion of allogeneic blood was significantly reduced in the thromboelastometry group : median 9.0 units ( interquartile range , 2.0 - 30.0 units ) versus . 16.0 units ( 9.0 - 23.0 units , P = .02 ) . Most significant decrease was in the use of fresh-frozen plasma ( 3.0 units , 0 - 12.0 units , vs 8.0 units , 4.0 - 18.0 units , P = .005 ) . Postoperative blood loss ( 890 mL/d , 600 - 1250 mL/d vs 950 mL/d , 650 - 1400 mL/d , p = 0.5 ) and rate of surgical re-exploration ( 19 % vs 24 % , P = .7 ) were similar between groups . Thromboelastometrically guided algorithm significantly decreased need for massive perioperative transfusion ( odds ratio , 0.45 ; 95 % confidence interval , 0.2 - 0.9 ; P = .03 ) in multivariable logistic regression analysis . CONCLUSIONS Thromboelastometrically guided transfusion is associated with a decreased use of allogeneic blood units and reduced incidence of massive transfusion in patients undergoing aortic surgery with circulatory arrest BACKGROUND Thromboelastometric evaluation of coagulation might be useful for prediction and management of bleeding after paediatric cardiac surgery . We tested the hypothesis that the use of a thromboelastometry-guided algorithm for blood product management reduces blood loss and transfusion requirements . METHODS We studied 78 patients undergoing paediatric cardiac surgery with cardiopulmonary bypass ( CPB ) for the initial 12 h after operation . Stepwise multiple linear regression was used to develop an algorithm to guide blood product transfusions . Thereafter , we r and omly assigned 100 patients to conventional or algorithm-guided blood product management , and assessed bleeding and red cell transfusion requirements . RESULTS CPB time , post-bypass rotational thromboelastometry ( ROTEM ( ® ) ) EXTEM amplitude at 10 min ( A10 ) , and FIBTEM-A10 were independently associated with chest tube drainage volume during the initial 12 h after operation . Discriminative analysis determined cut-off values of 30 mm for EXTEM-A10 and 5 mm for FIBTEM-A10 , and estimated optimal intraoperative fresh-frozen plasma and platelet concentrate transfusion volumes . Thromboelastometry-guided post-bypass blood product management significantly reduced postoperative bleeding ( 9 vs 16 ml kg(-1 ) , P<0.001 ) and packed red cell transfusion requirement ( 11 vs 23 ml kg(-1 ) , P=0.005 ) at 12 h after surgery , and duration of critical care stay ( 60 vs 71 h , P=0.014 ) . CONCLUSIONS Rotational thromboelastometry-guided early haemostatic intervention by rapid intraoperative correction of EXTEM-A10 and FIBTEM-A10 reduced blood loss and red cell transfusion requirements after CPB , and reduced critical care duration in paediatric cardiac surgical patients . CLINICAL TRIAL REGISTRATION UMIN Clinical Trials Registry UMIN000006832 ( December 4 , 2011 ) UNLABELLED Transfusion therapy after cardiac surgery is empirically guided , partly due to a lack of specific point-of-care hemostasis monitors . In a r and omized , blinded , prospect i ve trial , we studied cardiac surgical patients at moderate to high risk of transfusion . Patients were r and omly assigned to either a thromboelastography (TEG)-guided transfusion algorithm ( n = 53 ) or routine transfusion therapy ( n = 52 ) for intervention after cardiopulmonary bypass . Coagulation tests , TEG variables , mediastinal tube drainage , and transfusions were compared at multiple time points . There were no demographic or hemostatic test result differences between groups , and all patients were given prophylactic antifibrinolytic therapy . Intraoperative transfusion rates did not differ , but there were significantly fewer postoperative and total transfusions in the TEG group . The proportion of patients receiving fresh-frozen plasma ( FFP ) was 4 of 53 in the TEG group compared with 16 of 52 in the control group ( P < 0.002 ) . Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group ( P < 0.05 ) . Patients in the TEG group also received less volume of FFP ( 36 + /- 142 vs 217 + /- 463 mL ; P < 0.04 ) . Mediastinal tube drainage was not statistically different 6 , 12 , or 24 h postoperatively . Point-of-care coagulation monitoring using TEG result ed in fewer transfusions in the postoperative period . We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy . These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery . IMPLICATION S Transfusion of allogeneic blood products is common during complex cardiac surgical procedures . In a prospect i ve , r and omized trial , we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing , and found the algorithm to be effective in reducing transfusion requirements BACKGROUND Allogenic blood transfusion may affect clinical outcomes negatively . Up to 20 % of blood transfusions in the United States are associated with cardiac surgery and so strategies to conserve usage are of importance . This study compares administration according to physician 's choice based on laboratory coagulation tests with application of a strict protocol based on the thromboelastograph ( TEG ) . METHODS Sixty-nine patients presenting for cardiac surgery were r and omised to either study or control groups . In the study group a strict protocol was followed covering usage of all blood products according to TEG patterns . In the control group , the physician directed product administration with reference to activated partial thromboplastin time ( APTT ) , international normalised ratio ( INR ) , fibrinogen and platelet count . Bleeding , re-sternotomy , minimum haemoglobin , intubation time , and ICU stay were documented . RESULTS TEG-based management reduced total product usage by 58.8 % in the study group but this was not statistically significant . This was associated with a statistically insignificant trend towards better short-term outcomes . CONCLUSIONS This pilot study suggests that a strict protocol for blood product replacement based on the TEG might be highly effective in reducing usage without impairing short-term outcome OBJECTIVE Bleeding and allogeneic transfusion remain constant problems in cardiac surgical procedures . In this study , we aim ed to test the role of a routine thromboelastography (TEG)-based algorithm on bleeding and transfusions in patients undergoing elective coronary artery bypass grafting ( CABG ) . METHODS Patients ( n = 224 ) undergoing elective CABG with cardiopulmonary bypass were prospect ively r and omized into two groups according to transfusion strategy : in group 1 ( clinician-directed transfusion , n = 110 ) need for blood transfusion was based on clinician 's discretion and st and ard coagulation tests and in group 2 ( TEG algorithm group , n = 114 ) kaolin-activated ( k ) TEG-based algorithm-guided perioperative transfusion management . Transfusion , blood loss , and outcome data were recorded . RESULTS There were no differences in consumption of packed cell units , blood loss , re-exploration for bleeding , and early clinical outcome between the groups . Patients in the TEG group had significantly lower median units of fresh frozen plasma and platelets compared with the other group ( p = 0.001 ) . The median number of total allogeneic units transfused ( packed cells and blood products ) was significantly reduced in the TEG group compared with the other group ( median 2 , range 1 - 3 units vs. median 3 , range 2 - 4 units , respectively , p = 0.001 ) . The need for tranexamic acid was significantly diminished in the TEG group compared with the other group ( 10.3 % vs. 19 % , respectively , p = 0.007 ) . CONCLUSION Our results show that routine use of a kTEG-guided algorithm reduces the consumption of blood products in patients undergoing elective CABG . Adopting such an algorithm into routine management of these patients may help to improve clinical outcome and reduce the potential risks of transfusion-related complications and total costs after CABG OBJECTIVES Rotational thromboelastometry (ROTEM)-guided transfusion algorithms in cardiac surgery have been proven to be successful in reducing blood loss in r and omized controlled trials . Using an institutional hemostasis registry of patients in cardiac surgery ( HEROES-CS ) , the authors hypothesized that the use of ROTEM-guided transfusion algorithms would save blood products and overall costs in cardiac surgery in every day practice . DESIGN Observational , prospect i ve open cohort data base . SETTING Single-center academic hospital . PARTICIPANTS Cardiac surgery patients . INTERVENTIONS Implementation of ROTEM-guided bleeding management . MEASUREMENTS AND MAIN RESULTS A classical-guided algorithm and a ROTEM-guided algorithm were used for patient blood management in 2 cohorts . Primary outcome was the use and amount of blood products and hemostatic medication . Secondary outcomes were amount of rethoracotomies , length of stay , and 30-day mortality . Finally , costs and savings were calculated . The classical-guided cohort comprised 204 patients , and ROTEM-guided cohort comprised 151 patients . Baseline characteristics showed excellent similarities after propensity score matching of 202 patients . Blood loss was lower after ROTEM guidance ( p < 0.001 ) . Absolute risk reduction was 17 % for red blood cells ( p = 0.024 ) , 12 % for fresh frozen plasma ( p = 0.019 ) , and 4 % for thrombocyte concentrates ( p = 0.582 ) . More tranexamic acid was given , but not more fibrinogen concentrate , while desmopressin was given less often . Hospital length of stay was reduced by an overall median of 2 and a mean of 4 days ( p < 0.001 ) . Mortality and rethoracotomy rates were not affected . Potential savings were about € 4,800 ( $ 5,630 ) per patient . CONCLUSIONS Implementation of a ROTEM-guided transfusion algorithm in cardiac surgery patients reduced the use of blood products and hemostatic medication , hereby saving costs . Reductions in mortality and rethoracotomy rates could not be found OBJECTIVES Proximal aortic surgery with hypothermic circulatory arrest ( HCA ) commonly involves perioperative transfusion of allogeneic blood products , including red blood cells , plasma , and platelets . The authors hypothesized that surgery with HCA could be performed without allogeneic blood products and that a thromboelastometry-guided algorithm would reduce the transfusion of allogeneic blood products . DESIGN A retrospective analysis of prospect ively collected data . Patients with and without thromboelastometry guidance were compared by case-control analysis ( n = 62 matched patients ) and multivariate regression ( n = 194 patients ) . SETTING Single-center university hospital . PARTICIPANTS This study included 194 patients undergoing elective and emergent procedures with HCA involving the proximal aorta . INTERVENTIONS A thromboelastometry-guided treatment algorithm during surgery was used in 153 patients ( 79 % ) , and conventional coagulation management was used in 41 patients ( 21 % ) . MEASUREMENTS AND MAIN RESULTS During surgery and the following 24 hours , allogeneic blood products were transfused in 106 patients ( 55 % ) . Median ( interquartile range ) number of allogeneic blood products transfused was 1 unit ( 0 - 6 units ) . Case-control analysis showed lower transfusion rates of red blood cells , plasma , and any allogeneic blood product ( all p<0.050 ) in patients with thromboelastometry guidance . In the multivariate analysis , thromboelastometry guidance was associated with an odds ratio of 0.26 ( 95 % confidence interval , 0.08 - 0.84 ; p = 0.025 ) for the transfusion of any allogeneic blood product . The use of thromboelastometry was not associated with adverse events ( odds ratio 0.72 ; 95 % confidence interval , 0.27 - 1.90 ; p = 0.507 ) . CONCLUSIONS Allogeneic blood products were avoided in a proportion of patients . The findings further suggest that thromboelastometry-guided coagulation management promoting the use of coagulation factor concentrates decreased the use of allogeneic blood products during complex cardiac surgery |
11,711 | 22,786,508 | Based on the median effect size estimates , no significant difference in patient health-related outcomes was found between patients assigned to interventions and those assigned to usual care .
Results from this Cochrane review do not allow us to conclude on the effectiveness of included interventions to improve continuity of care on patient , healthcare provider or process of care outcomes . | BACKGROUND Care from the family physician is generally interrupted when patients with cancer come under the care of second-line and third-line healthcare professionals who may also manage the patient 's comorbid conditions .
This situation may lead to fragmented and uncoordinated care , and results in an increased likelihood of not receiving recommended preventive services or recommended care .
OBJECTIVES To classify , describe and evaluate the effectiveness of interventions aim ing to improve continuity of cancer care on patient , healthcare provider and process outcomes . | PURPOSE To examine the effect of weekly completion of a patient-held quality -of-life ( QOL ) diary in routine oncology practice for palliative care patients . PATIENTS AND METHODS In a pragmatic r and omized controlled trial , 115 patients with inoperable lung cancer were r and omly assigned to receive either st and ard care or a structured QOL diary ( European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and the related lung cancer module LC13 ) that they completed at home each week for 16 weeks . Patients were encouraged to share the QOL information with health professionals involved in their care . Changes in QOL over time ( measured by the Functional Assessment of Cancer Therapy-Lung question naire and the Palliative Care Quality of Life Index ) , discussion of patient problems , and satisfaction with communication and general care were assessed at baseline and at 2 and 4 months after baseline . RESULTS Analysis of QOL indicated a small but consistent difference between patients in the diary group and the st and ard care group . The diary group had a poorer QOL in many domains . Two different QOL summary scores ( total and overall QOL ) indicated a statistically significant between-group difference . No effects were found in relation to satisfaction with care , communication , or the discussion of patient problems . CONCLUSION The regular completion of a QOL question naire without appropriate feedback to health care professionals and without the provision of appropriate support may have a negative impact on inoperable lung cancer patients . Further research should focus on identifying features such as feedback loops that are required for the successful and meaningful use of QOL question naires in routine patient care Sc and J Prim Health Care 2003;21:00 - 00 . ISSN 0281 - 3432 Objective r - r To investigate general practitioner ( GP ) assessment of a structured oncology information pack sent to GPs when newly referred patients had visited a department of oncology for the first time , and to compare their assessment of this material with their assessment of traditional information provided by the department . Design r - r R and omised , unblinded clinical trial . Setting r - r Patients and GPs in the catchment area of a regional oncology department . Subjects / patients r - r 248 cancer patients and their 199 GPs . Main outcome measures r - r GP assessment of the quality of the information material received for each patient . Results r - r 88.3 % of the 248 question naires were returned . The structured information pack improved GP knowledge of oncology ; GPs found themselves better equipped to support and counsel patients during the course of their illness , and practitioner satisfaction with the department rose . Conclusion r - r Intervention , though reasonably simple , inexpensive and not particularly time-consuming , improved cooperation between the specialist department and the GP . While this is a small step in the right direction , the need remains for new initiatives and further studies into how to improve cooperation and communication between the primary and secondary healthcare sectors OBJECTIVES --To measure effects on terminally ill cancer patients and their families of coordinating the services available within the NHS and from local authorities and the voluntary sector . DESIGN --R and omised controlled trial . SETTING --Inner London health district . PATIENTS --Cancer patients were routinely notified from 1987 to 1990 . 554 patients expected to survive less than one year entered the trial and were r and omly allocated to a coordination or a control group . INTERVENTION -- All patients received routinely available services . Coordination group patients received the assistance of two nurse coordinators , whose role was to ensure that patients received appropriate and well coordinated services , tailored to their individual needs and circumstances . MAIN OUTCOME MEASURES -- Patients and carers were interviewed at home on entry to the trial and at intervals until death . Interviews after bereavement were also conducted . Outcome measures included the presence and severity of physical symptoms , psychiatric morbidity , use of and satisfaction with services , and carers ' problems . Results from the baseline interview , the interview closest to death , and the interview after bereavement were analysed . RESULTS --Few differences between groups were significant . Coordination group patients were less likely to suffer from vomiting , were more likely to report effective treatment for it , and less likely to be concerned about having an itchy skin . Their carers were more likely to report that in the last week of life the patient had had a cough and had had effective treatment for constipation , and they were less likely to rate the patient 's difficulty swallowing as severe or to report effective treatment for anxiety . Coordination group patients were more likely to have seen a chiropodist and their carers were more likely to contact a specialist nurse in a night time emergency . These carers were less likely to feel angry about the death of the patient . CONCLUSIONS --This coordinating service made little difference to patient or family outcomes , perhaps because the service did not have a budget with which it could obtain services or because the professional skills of the nurse-coordinators may have conflicted with the requirements of the coordinating role Objective : To assess the effectiveness of nurse led follow up in the management of patients with lung cancer . Design : R and omised controlled trial . Setting : Specialist cancer hospital and three cancer units in southeastern Engl and Participants : 203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months . Intervention : Nurse led follow up of out patients compared with conventional medical follow up . Outcome measures : Quality of life , patients ' satisfaction , general practitioners ' satisfaction , survival , symptom-free survival , progression-free survival , use of re sources , and comparison of costs . Results : Patient acceptability of nurse led follow up was high : 75 % ( 203/271 ) of eligible patients consented to participate . Patients who received the intervention had less severe dyspnoea at 3 months ( P=0.03 ) and had better scores for emotional functioning ( P=0.03 ) and less peripheral neuropathy ( P=0.05 ) at 12 months . Intervention group patients scored significantly better in most satisfaction subscales at 3 , 6 , and 12 months ( P<0.01 for all subscales at 3 months ) . No significant differences in general practitioners ' overall satisfaction were seen between the two groups . No differences were seen in survival or rates of objective progression , although nurses recorded progression of symptoms sooner than doctors ( P=0.01 ) . Intervention patients were more likely to die at home rather than in a hospital or hospice ( P=0.04 ) , attended fewer consultations with a hospital doctor during the first 3 months ( P=0.004 ) , had fewer radiographs during the first 6 months ( P=0.04 ) , and had more radiotherapy within the first 3 months ( P=0.01 ) . No other differences were seen between the two groups in terms of the use of re sources . Conclusion : Nurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes This study reports results from a r and omised controlled trial of nurse-led care and was design ed to determine whether nurse-led follow up improved patients morbidity and satisfaction with care in men treated with radical radiotherapy for prostate and bladder cancer . The aim was to compare outcomes in terms of toxicity , symptoms experienced , quality of life , satisfaction with care and health care costs , between those receiving nurse-led care and a group receiving st and ard care . The study population was of men prescribed radical radiotherapy ( greater than 60 Gy ) . Participants completed self- assessment question naires for symptoms and quality of life within the first week of radiotherapy treatment , at week 3 , 6 and 12 weeks from start of radiotherapy . Satisfaction with clinical care was also assessed at 12 weeks post-treatment . Observer-rated RTOG toxicity scores were recorded pre-treatment , weeks 1 , 3 , 6 and 12 weeks from start of radiotherapy . The results presented in this paper are on 115 of 132 ( 87 % ) of eligible men who agreed to enter the r and omised trial . 6 men ( 4 % ) refused and 11 ( 8 % ) were missed for inclusion in the study . Data were analysed as a comparison at cross-sectional time points and as a general linear model using multiple regression . There was no significant difference in maximum symptom scores over the time of the trial between nurse-led follow-up care and conventional medical care . Differences were seen in scores in the initial self assessment of symptoms ( week 1 ) that may have been as a result of early nursing intervention . Those men who had received nurse-led care were significantly more satisfied ( P < 0.002 ) at 12 weeks and valued the continuity of the service provided . There were also significant ( P < 0.001 ) cost benefits , with a 31 % reduction in costs with nurse-led , compared to medically led care . Evidence from this study suggests that a specialist nurse is able to provide safe follow up for men undergoing radiotherapy . The intervention focused on coping with symptoms , and provided continuity of care and telephone support . Further work is required to improve the management of patients during and after radiotherapy . © 2001 Cancer Research Campaign Objective : To determine the effect of a shared care programme on the attitudes of newly referred cancer patients towards the healthcare system and their health related quality of life and performance status , and to assess patients ’ reports on contacts with their general practitioner ( GP ) . Setting : Department of Oncology at Aarhus University Hospital and general practice s. Design : R and omised controlled trial in which patients completed question naires at three time points . The shared care programme included transfer of knowledge from the oncologist to the GP , improved communication between the parties , and active patient involvement . Participants : 248 consecutive cancer patients recently referred to the department . Main outcome measures : Patients ’ attitudes towards the healthcare services , their health related quality of life , performance status , and reports on contacts with their GPs . Results : The shared care programme had a positive effect on patient evaluation of cooperation between the primary and secondary healthcare sectors . The effect was particularly significant in men and in younger patients ( 18–49 years ) who felt they received more care from the GP and were left less in limbo . Young patients in the intervention group rated the GP ’s knowledge of disease and treatment significantly higher than young patients in the control group . The number of contacts with the GP was significantly higher in the intervention group . The EORTC quality of life question naire and performance status showed no significant differences between the two groups . Conclusions : An intersectoral shared care programme in which GPs and patients are actively involved has a positive influence on patients ’ attitudes towards the healthcare system . Young patients and men particularly benefit from the programme Abstract Objective : To assess the medical and psychosocial effects of early hospital discharge after surgery for breast cancer on complication rate , patient satisfaction , and psychosocial outcomes . Design : R and omised trial comparing discharge from hospital 4 days after surgery ( with drain in situ ) with discharge after drain removal ( mean 9 days in hospital ) . Psychosocial measurements performed before surgery and 1 and 4 months after . Setting : General hospital and cancer clinic in Rotterdam with a socioeconomically diverse population . Subjects : 125 women with operable breast cancer . Main outcome measures : Incidence of complications after surgery for breast cancer , patient satisfaction with treatment , and psychosocial effects of short stay or long stay in hospital . Results : Patient satisfaction with the short stay in hospital was high ; only 4 % ( 2/56 at 1 month after surgery and 2/52 at 4 months after surgery ) of patients indicated that they would have preferred a longer stay . There were no significant differences in duration of drainage from the axilla between the short stay and long stay groups ( median 8 v 9 days respectively , P=0.45 ) or the incidence of wound complications ( 10 patients v 9 patients ) . The median number of seroma aspirations per patient was higher for the long stay group ( 1 v 3.5 , P=0.04 ) . Leakage along the drain occurred more frequently in short stay patients ( 21 v 10 patients , P=0.04 ) . The two groups did not differ in scores for psychosocial problems ( uncertainty , anxiety , loneliness , disturbed sleep , loss of control , threat to self esteem ) , physical or psychological complaints , or in the coping strategies used . Before surgery , short stay patients scored higher on scales of depression ( P=0.03 ) and after surgery they were more likely to discuss their disease with their families ( at 1 month P=0.004 , at 4 months P=0.04 ) . Conclusions : Early discharge from hospital after surgery for breast cancer is safe and is well received by patients . Early discharge seems to enhance the opportunity for social support within the family . Key messages Early discharge from hospital after breast cancer surgery does not lead to an increase in the incidence of wound infection or seroma formation A short stay in hospital , with support from community nurses on the patient 's return home , is acceptable to patients Psychosocial rehabilitation is not influenced by early discharge Recovery in the family environment may facilitate discussion of the illness Patients recovering from surgery for breast cancer need not spend more than three days in hospital provided that they are in good physical condition and there is adequate nursing support available in the PURPOSE To describe a r and omized trial of a cognitive behavioral intervention on reducing symptom severity among patients diagnosed with solid tumors and undergoing a first course of chemotherapy and to determine whether the intervention had an additive or interactive effect on symptom severity in the presence of supportive care medications . PATIENTS AND METHODS Patients ( N = 237 ) were accrued from comprehensive and community cancer centers , interviewed , and r and omly assigned to either the experimental intervention ( n = 118 ) or conventional care ( n = 119 ) . A symptom severity index , based on summed severity scores across 15 symptoms , was the primary outcome . Each patient 's site of cancer , stage at diagnosis , chemotherapy protocol s , and use of supportive medications were learned from medical records . RESULTS Groups were equivalent at baseline , and attrition by characteristics by group was not different . The proportion of patients not receiving chemotherapy at 10 and 20 weeks did not differ by group . At the 10- and 20-week observations , there was a significant interaction between the experimental group and baseline symptom severity . Patients in the experimental group who entered the trial with higher symptom severity reported significantly lower severity at 10 and 20 weeks . Controlling for chemotherapy treatment status at follow-up and supportive care medications did not alter the effect of the experimental intervention . CONCLUSION Compared with conventional care alone , the experimental intervention was effective among patients who entered the trial with higher levels of symptom severity . Age , sex , site or stage of cancer , and supportive medications did not modify the effect of this cognitive behavioral intervention on symptom severity In a prospect i ve controlled study , patients with incurable cancer and an estimated prognosis of three months to one year were allocated to two patient groups for evaluation of supportive interventions . One group , called " intensive , " received home visits by a nurse practitioner acting as an extension of a multidisciplinary team ; the other , termed " nonintensive , " did not receive such visits . Both patient groups were periodically evaluated in their homes by an observer and by self-ratings , to measure changes in quality of life as their disease progressed . Several method ologic problems were identified , which have implication s for future research . Pain problems later in the course of cancer seem to be predictable in those patients with higher scores on the Cornell Medical Index M-R scales ( greater emotional disturbance ) and on the Rotter Locus of Control ( I-E ) scale ( expectation of more external control of self ) . The study also found that the home visiting nurse practitioners , specially trained in pain treatment , improved pain control in the " intensive " group of patients over the last 90 days of life , when pain was an increasingly major problem . Such nurses can significantly improve the quality of life for patients dying outside of institutions OBJECTIVE Women with gynecological cancers have reported poor health-related quality of life ( QOL ) , with complex physical and psychological needs post-surgery and during chemotherapy treatment . There are no studies reporting interventions addressing these needs post-hospital discharge in this population . METHODS Patients were r and omized into two groups . The intervention group received 6 months of specialized care by an Advanced Practice Nurse ( APN ) ; in addition , women with high distress were evaluated and monitored by a psychiatric consultation-liaison nurse ( PCLN ) . The attention control group was assisted with symptom management by a research assistant . The effects of the 6-month intervention were evaluated using self-report question naires at baseline ( 24 - 48 h after surgery ) , 1 , 3 , and 6 months post- surgery . QOL assessment s included the Center for Epidemiological Studies -Depression Scale , the ambiguity subscale of the Mishel Uncertainty in Illness Scale , the Symptom Distress Scale , and the Short-Form Health Survey ( SF-12 ) . The sample for the longitudinal analysis included 123 who completed QOL outcome measures across three occasions post-surgery . RESULTS The APN intervention result ed in significantly less uncertainty than the attention control intervention 6 months after surgery . When the sub-group who received the APN plus PCLN intervention was compared with the total attention control group , the sub-group had significantly less uncertainty , less symptom distress , and better SF-12 mental and physical QOL over time . CONCLUSION Nurse tailored interventions that target both physical and psychological aspects of QOL in women recovering from cancer surgery and undergoing chemotherapy produce stronger outcomes than interventions that target solely one QOL aspect Australian palliative care is delivered by general practitioners ( GPs ) and specialist palliative care teams . Patient outcomes should improve if they work in formal partnership . We conducted a multi-centred r and omised controlled trial of specialist- GP case conferences , with the GP participating by teleconference , or usual care and communication methods . Primary outcome measure was global Quality of Life ( QoL ) scores at 3 weeks from intervention . Secondary measures included subscale QoL scores and carer burden . Two a priori intention-to-treat analyses were conducted using recruitment , and time of death , as fixed time points . There was no difference between groups in the magnitude of change in global QoL measures from baseline to any time point up to 9 weeks post-case conference , or at any time before death . The case conference group showed better maintenance of some physical and mental health measures of QoL in the 35 days before death . Case conferences may improve clinical relationships and care plans at referral , which are not implemented until severe symptoms develop . Case conferences between GPs and specialist palliative care services may be warranted for palliative care patients Abstract Objective : To evaluate a palliative care home support team based on an inpatient unit . Design : R and omised controlled trial with waiting list . Patients in the study group received the service immediately , those in the control group received it after one month . Main comparison point was at one month . Setting - A city of 300 000 people with a publicly funded home care service and about 200 general practitioners , most of whom provide home care . Main outcome measures : Pain and nausea levels were measured at entry to trial and at one month , as were quality of life for patients and care givers ' health . Results : Because of early deaths , problems with recruitment , and a low compliance rate for completion of question naires , the required sample size was not attained . Conclusion : In design ing evaluations of palliative care services , investigators should be prepared to deal with the following issues : attrition due to early death , opposition to r and omisation by patients and referral sources , ethical problems raised by r and omisation of dying patients , the appropriate timing of comparison points , and difficulties of collecting data from sick or exhausted patients and care givers . Investigators may choose to evaluate a service from various perspectives using different methods : controlled trials , qualitative studies , surveys , and audits . R and omised trials may prove to be impracticable for evaluation of palliative care PURPOSE There is limited consensus about the most appropriate measures to evaluate the adequacy of pain treatment in cancer patients . There are no known studies describing commonly used measures to simultaneously evaluate the adequacy of cancer pain treatment . The purpose of this study was to compare measures , which are frequently reported in the literature , to assess the adequacy of pain treatment in cancer patients with chronic pain . This study was part of a r and omized controlled trial . PATIENTS AND METHODS In total , 313 cancer patients with a pain duration of at least 1 month were evaluated . After a baseline measure in the hospital , patients were followed up at 2 , 4 , and 8 weeks after discharge at home . Adequacy of cancer pain treatment was evaluated by means of four different types of outcome measures . The four types included three pain intensity markers based on patients ' pain intensity , a pain relief scale , a patient satisfaction scale , and three pain management indexes that related patients ' pain medication with pain intensity . RESULTS The proportion of inadequately treated pain patients varied extremely . Depending on the outcome measure used , the percentage of inadequately treated patients ranged from 16 % to 91 % . The choice of measure , rather than pain treatment itself , determined the proportion of inadequacy . CONCLUSION There is an urgent need for consensus about how to evaluate the effectiveness of pain treatment . Studies that evaluate adequacy of pain treatment should be interpreted with caution . Further research is necessary to eluci date the validity and reliability of outcome measures simultaneously The purpose of this r and omized , controlled , home care intervention was to test the effectiveness of two nurse-targeted , e-mail-based interventions to increase home care nurses ' adherence to pain assessment and management guidelines , and to improve patient outcomes . Nurses from a large urban non-profit home care organization were assigned to usual care or one of two interventions upon identification of an eligible cancer patient with pain . The basic intervention consisted of a patient-specific , one-time e-mail reminder highlighting six pain-specific clinical recommendations . The augmented intervention supplemented the initial e-mail reminder with provider prompts , patient education material , and clinical nurse specialist outreach . Over 300 nurses were r and omized and outcomes of 673 of their patients were review ed . Data collection involved clinical record abstract ion of nurse care practice s and patient interviews completed approximately 45 days after start of care . The intervention had limited effect on nurse-documented care practice s but patient outcomes were positively influenced . Patients in the augmented group improved significantly over the control group in ratings of pain intensity at its worst , whereas patients in the basic group had better ratings of pain intensity on average . Other outcomes measures were also positively influenced but did not reach statistical significance . Our findings suggest that although reminders have some role in improving cancer pain management , a more intensive approach is needed for a generalized nursing workforce with limited recent exposure to state-of-the-art pain management practice Despite advances in the technology of cancer pain assessment and control , cancer pain often remains undertreated even in hospital setting s. To determine whether a graphical display of cancer patients ' pain levels might improve their treatment , the investigators conducted a r and omized controlled trial . Patients assigned to the intervention group ( N = 40 ) had periodic pain assessment s by study staff , who graphically recorded their reported pain-intensity levels on bedside wall charts . Control group patients ( N = 38 ) had periodic pain assessment s by study staff but did not have this information displayed . The results failed to show a significant beneficial effect of the intervention on pain control , sleep , cancer-related symptoms , or analgesic dosing , but confidence intervals were broad . More research is needed to improve the quality of care for in patients with cancer-related pain Most seriously ill Americans live at home under the care of their primary physician and with the support of family caregivers . To reduce costs while simultaneously improving the quality of patient care , insurers have increasingly turned to the concept of case management . While case management is targeted to individuals with life-threatening illnesses , palliative care assessment and interventions are typically not included in the management protocol s. An academic/care management/health plan partnership between Mount Sinai School of Medicine , Franklin Health , a care management organization , and South Carolina Blue Cross Blue Shield , was formed in 1998 to test the utility of integration of case management with formal palliative care assessment , feedback and recommendations to treating physicians , and ongoing support for implementation of a palliative care plan . The goal of the project was to ensure identification and optimal care of seriously ill patients ' complex needs , while facilitating doctor-patient continuity , improving patient/family/physician communication , providing assistance with decision-making , ensuring quality care at home , and promoting efficient use of health care re sources . Care management nurses were r and omly assigned to a control ( usual care ) group or to the intervention ( palliative care ) group . Intervention nurses were trained in formal palliative care assessment and interventions , supported by treatment protocol s and communication strategies with treating physicians . Measurements included symptom burden , prescribing practice s , advance care planning status , satisfaction , and health care utilization . These results are pending completion of study run-out and analysis . Preliminary programmatic results indicate that combining palliative care with the case management approach is a logical , feasible , and effective strategy to improve the care of seriously ill patients living in the community . Franklin Health has offered the program to their entire client base because they feel that the integration of palliative care into their case management program improved the st and ard of patient care . Blue Cross Blue Shield of South Carolina has also chosen to sustain this enhanced model of care management for seriously ill patients Systematic assessment of pain is the basis for adequate pain treatment . In the home situation , however , it is difficult to assess patients ' pain intensity . A group of 159 cancer patients who had been admitted to a cancer hospital with pain caused by cancer , cancer therapy , or illness that persisted for at least 1 month received a pain diary . These patients were asked to register their pain intensity at home . Patients were instructed by a nurse to record their Present Pain Intensity on a scale from 0 - 10 once every morning and every evening for a period of 2 months . In this study , the use of a pain diary in cancer pain patients at home was evaluated . To determine the effects of the pain diary , patients were interviewed at baseline , at 2 , 4 , and 8 weeks postdischarge . Pain intensity scores were obtained both by patient interviews and from the pain diary . Results show that the use of a pain diary is an appropriate way to assess patients ' pain intensity at home . Patients ' compliance was high ( 86 % ) , even in seriously ill patients . When comparing pain scores obtained by patient interview with scores obtained by pain diary , results showed that Present Pain Intensity scores , rather than Average Pain Intensity scores , should be used in both the clinical and the home setting because patients ' recall accuracy depends , in part , on the stability of the pain . Because the pain intensity scores fluctuate greatly during the day and over a period of time , the use of a pain diary is useful in the home setting . In 60 % of the patients , completing the pain scores helped them to cope with the pain Background After curative treatment for breast cancer women frequently attend scheduled follow-up examinations . Usually the follow-up is most frequent in the first 2–3 years ( 2–4 times a year ) ; thereafter the frequency is reduced to once a year in most countries . Its main aim is to detect local disease recurrence , or a second primary breast cancer , but also to provide information and psychosocial support . However , the cost-effectiveness of these frequent visits is under much debate , leading to a search for less intensive and more cost-effective follow-up strategies . In this paper the design of the MaCare trial is described . This trial compares the cost-effectiveness of four follow-up strategies for curatively treated breast cancer patients . We investigate the costs and effects of nurse-led telephone follow-up and a short educational group programme . Methods / design The MaCare trial is a multi centre r and omised clinical trial in which 320 breast cancer patients are r and omised into four follow-up strategies , focussed on the first 18 months after treatment : 1 ) st and ard follow-up ; 2 ) nurse-led telephone follow-up ; 3 ) arm 1 with the educational group programme ; 4 ) arm 2 with the educational group programme . Data is collected at baseline and 3 , 6 , 12 and 18 months after treatment . The primary endpoint of the trial is cancer-specific quality of life as measured by the global health/QoL scale of the EORTC QLQ-C30 . Secondary outcomes are perceived feelings of control , anxiety , patients ' satisfaction with follow-up and costs . A cost-effectiveness analysis will be performed from a societal perspective . Discussion Reduced follow-up strategies for breast cancer have not yet been widely applied in clinical practice . Improvement of psychosocial support and information to patients could lead to a better acceptance of reduced follow-up . The MaCare trial combines a reduced follow-up strategy with additional psychosocial support . Less frequent follow-up can reduce the burden on medical specialists and costs . The educational group programme can improve QoL of patients , but also less frequent follow-up can improve QoL by reducing the anxiety experienced for each follow-up visit . Results of the trial will provide knowledge on both costs and psychosocial aspects regarding follow-up and are expected in 2009 BACKGROUND Routine follow-up of breast cancer patients in specialist clinics is st and ard practice in most countries . Follow-up involves regularly scheduled breast cancer check-ups during the disease-free period . The aims of follow-up are to detect breast cancer recurrence and to provide psychosocial support to the patient ; however , little is known about patients ' views on breast cancer follow-up . AIM To assess the effect on patient satisfaction of transferring primary responsibility for follow-up of women with breast cancer in remission from hospital outpatient clinics to general practice . METHOD R and omized controlled trial with 18 months ' follow-up in which women received routine follow-up either in hospital outpatient clinics or from their own general practitioner . Two hundred and ninety-six women with breast cancer in remission receiving regular follow-up care at two district general hospitals in Engl and were included in the study . Patient satisfaction was measured by means of a self-administered question naire supplied three times during the 18-month study period . RESULTS The general practice group selected responses indicating greater satisfaction than did the hospital group on virtually every question . Furthermore , in the general practice group there was a significant increase in satisfaction over baseline ; a similar significant increase in satisfaction over baseline was not found in the hospital group . CONCLUSION Patients with breast cancer were more satisfied with follow-up in general practice than in hospital outpatient departments . When discussing follow-up with breast cancer patients , they should be provided with complete and accurate information about the goals , expectations , and limitations of the follow-up programme so that they can make an informed choice 8517 Background : Evidence -based palliative care service delivery models are needed . General practitioner ( GP ) and patient-centered case conferences may increase multidisciplinary interaction and enhance patient care . Educational outreach visiting in pain management may empower learners and improve care . METHODS Three interventions were tested against a routine care control in a 2 × 2 × 2 cluster factorial r and omized controlled trial . Interventions were case conferencing , educational visiting for GPs , and educational visiting for patients . Subjects were adult patients referred to palliative care services in southern Adelaide , Australia , with any pain in the preceding 3 months . Participants were followed longitudinally until death . Main outcomes included performance status ( Australian-modified Karnofsky Performance Status ( AKPS ) ) and hospitalization rates . Longitudinal intention-to-treat analyses using cluster-specific methods were conducted . The sample goal was 460 . RESULTS 461 participants were enrolled from 4/02 - 6/04 . Mean age was 71 yrs , 50 % were male , 91 % had cancer . Mean and median survival was 146 and 87 days ; median baseline AKPS was 60 % . When participants had AKPS < 70 ( i.e. required a caregiver ) at referral , those r and omized to case conferencing or patient education had higher mean performance status than routine care ( case conferencing : average daily AKPS , 54.9 % vs 46.3 % , p=0.0106 ; patient education : 54.7 % vs 46.4 % , p=0.0120 ) . GP education did not improve performance status . Both case conferencing and patient education significantly decreased hospitalization rates compared to routine care ( case conferencing : least-squares mean number of hospitalizations , 1.4 ( st and ard error ( SE ) 0.1 ) vs 1.9 ( SE 0.1 ) , p=0.0002 ; patient education : 1.4 ( SE 0.1 ) vs 1.8 ( SE 0.1 ) , p=0.0078 ) . The addition of both interventions decreased hospitalizations to 1.2 ( SE 0.1 ) . CONCLUSION At a time when declining function and higher healthcare utilization is the norm , palliative care that includes a case conference or patient educational visiting for pain leads to improved performance status and decreased hospitalizations . Patients with deteriorating performance status derive the greatest benefit . No significant financial relationships to disclose Patients with breast cancer who require axillary clearance traditionally remain in hospital until their wound drains are removed . Early discharge has been shown to improve clinical outcomes , but there has been little assessment of the psychosocial and financial impact of early discharge on patients , carers and the health service . This study aim ed to evaluate the effectiveness of a nurse-led model of early discharge from hospital . Main outcome measures were quality of life and carer burden . Secondary outcomes included patient satisfaction , arm morbidity , impact on community nurses , health service costs , surgical cancellations and in-patient nursing dependency . A total of 108 patients undergoing axillary clearance with mastectomy or wide local excision for breast cancer were r and omised to nurse-led early discharge or conventional stay . Nurse-led early discharge had no adverse effects on quality of life or patient satisfaction , had little effect on carer burden , improved communication between primary and secondary care , reduced cancellations and was safely implemented in a mixed rural/urban setting . In total , 40 % of eligible patients agreed to take part . Non participants were significantly older , more likely to live alone and had lower emotional well being before surgery . This study provides further evidence of the benefits of early discharge from hospital following axillary clearance for breast cancer . However , if given the choice , most patients prefer to stay in hospital until their wound drains are removed BACKGROUND Geriatric assessment has been suggested as a possibly useful approach in dealing with frail elderly cancer patients . METHODS This was a secondary subset analysis from a r and omized 2 x 2 factorial trial in 11 Department of Veterans Affairs medical centers . Hospitalized , frail patients at least 65 years old , after stabilization of their acute illness , were r and omized to receive care in a geriatric inpatient unit , a geriatric outpatient clinic , both , or neither . The interventions involved core teams that provided geriatric assessment and patient management . We identified 99 patients with a diagnosis of cancer by The International Classification of Diseases , 9th Revision ( ICD-9 ) codes , excluding all nonmelanoma skin cancers . Outcomes collected at discharge , 6 months , and 1 year after r and omization were survival , changes in health-related quality of life ( using the Medical Outcomes Study 36-Item Short-Form general health survey [ SF-36 ] ) , activities of daily living , physical performance , health service utilization , and costs . RESULTS There was no effect on mortality ( 1-year survival 59.6 % ) . The changes in the SF-36 scores from r and omization for emotional limitation , mental health and bodily pain ( also sustained at 1 year ) on the SF-36 were better for geriatric inpatient care cancer patients at discharge . There was no difference in SF-36 scores between geriatric outpatient and usual outpatient care . Days of hospitalization and overall costs were equivalent for the interventions and usual care over the 1-year study . CONCLUSIONS This study suggests that inpatient geriatric assessment and management may be an effective approach to the management of pain and psychological status in the elderly cancer inpatient at no greater length of hospitalization or extra cost than usual care Abstract Objective : To assess the effect on time to diagnosis of recurrence and on quality of life of transferring primary responsibility for follow up of women with breast cancer in remission from hospital to general practice . Design : R and omised controlled trial with 18 month follow up in which women received routine follow up either in hospital or in general practice . Subjects and setting : 296 women with breast cancer in remission receiving regular follow up care at district general hospitals in Engl and . Main outcome measures : Time between first presentation of symptoms to confirmation of recurrence ; quality of life measured by specific dimensions of the SF-36 schedule , the EORTC symptom scale , and hospital anxiety and depression scale . Results : Most recurrences ( 18/26 , 69 % ) presented as interval events , and almost half ( 7/16 , 44 % ) of the recurrences in the hospital group presented first to general practice . The median time to hospital confirmation of recurrence was 21 days in the hospital group ( range 1 - 376 days ) and 22 days in the general practice group ( range 4 - 64 ) . The differences between groups in the change in SF-36 mean scores from baseline were small : -1.8 ( 95 % confidence interval -7.2 to 3.5 ) for social functioning , 0.5 ( -4.1 to 5.1 ) for mental health , and 0.6 ( -3.6 to 4.8 ) for general health perception . The change from baseline in the mean depression score was higher in the general practice group at the mid-trial assessment ( difference 0.6 , 0.1 to 1.2 ) but there was no significant difference between groups in the anxiety score or the EORTC scales . Conclusion : General practice follow up of women with breast cancer in remission is not associated with increase in time to diagnosis , increase in anxiety , or deterioration in health related quality of life . Most recurrences are detected by women as interval events and present to the general practitioner , irrespective of continuing hospital follow up . Key messages Broadly , the goals of follow up are to detect recurrence , detect new contralateral primaries , and provide psychosocial support For women who are free of disease , general prac- tice follow up was not associated with increased time to diagnosis of recurrence or deterioration in health related quality of The purpose of this study was to explore the roles of continuing supportive care in increasing the social support and reducing the perceived uncertainty among women newly diagnosed with breast cancer in Taiwan . A longitudinal , quasi-experimental design was used in this study . Sixty-one women younger than 60 years , newly diagnosed with breast cancer and undergoing surgery , were recruited from 2 urban teaching hospitals in northern Taiwan . The experimental group was provided with additional continuing supportive care for 3 months . Two instruments , including the Social Support Question naire and an uncertainty question naire , were administered to participants at 3 time points : presurgery within 2 weeks after diagnosis , 1 month after surgery , and 3 months after diagnosis . The experimental group reported significantly higher social support and lower disease uncertainty compared with the control group at 1 month after surgery and 3 months after diagnosis . With knowledge of the role that continuing-care intervention plays in social support and disease uncertainty , nurses and other healthcare professionals can continue to explore and strengthen strategies to enhance the coping ability of women with breast cancer in Taiwan PURPOSE To evaluate oncology out patients ' level of adherence to their analgesic regimen during a 5-week period . PATIENTS AND METHODS A r and om sample of 65 adult oncology out patients with a Karnofsky performance status score of > or= 50 , an average pain intensity score of > or= 2.5 , and radiographic evidence of bone metastasis were recruited for this longitudinal study from seven outpatient setting s. On a daily basis , patients rated their level of pain intensity and recorded pain medication intake . Adherence rates for opioid analgesics prescribed on an around-the-clock ( ATC ) and on an as-needed ( PRN ) basis were calculated on a weekly basis . RESULTS Overall adherence rates for ATC opioid analgesics ranged from 84.5 % to 90.8 % and , for PRN analgesics , from 22.2 % to 26.6 % . No significant differences over time were found in either of these adherence rates . CONCLUSION One factor that seems to contribute to ineffective cancer pain management is poor adherence to the analgesic regimen Background All patients who undergo surgery for colon cancer are followed up according to the guidelines of the Norwegian Gastrointestinal Cancer Group ( NGICG ) . These guidelines state that the aims of follow-up after surgery are to perform quality assessment , provide support and improve survival . In Norway , most of these patients are followed up in a hospital setting . We describe a multi-centre r and omized controlled trial to test whether these patients can be followed up by their general practitioner ( GP ) without altering quality of life , cost effectiveness and /or the incidence of serious clinical events . Methods and Design Patients undergoing surgery for colon cancer with histological grade Dukes 's Stage A , B or C and below 75 years of age are eligible for inclusion . They will be r and omized after surgery to follow-up at the surgical outpatient clinic ( control group ) or follow-up by the district GP ( intervention group ) . Both study arms comply with the national NGICG guidelines . The primary endpoints will be quality of life ( QoL ) ( measured by the EORTC QLQ C-30 and the EQ-5D instruments ) , serious clinical events ( SCEs ) , and costs . The follow-up period will be two years after surgery , and quality of life will be measured every three months . SCEs and costs will be estimated prospect ively . The sample size was 170 patients . Discussion There is an ongoing debate on the best method of follow-up for patients with CRC . Due to a wide range of follow-up programmes and paucity of r and omized trials , it is impossible to draw conclusions about the best combination and frequency of clinic ( or family practice ) visits , blood tests , endoscopic procedures and radiological examinations that maximize the clinical outcome , quality of life and costs . Most studies on follow-up of CRC patients have been performed in a hospital outpatient setting . We hypothesize that postoperative follow-up of colon cancer patients ( according to national guidelines ) by GPs will not have any impact on patients ' quality of life . Furthermore , we hypothesize that there will be no increase in SCEs and that the incremental cost-effectiveness ratio will improve . Trial registration This trial has been registered at Clinical Trials.gov . The trial registration number is : This trial examined the optimal setting for follow-up of patients after treatment for colon cancer by either general practitioners or surgeons . In all , 203 consenting patients who had undergone potentially curative treatment for colon cancer were r and omised to follow-up by general practitioners or surgeons . Follow-up guidance recommended three monthly clinical review and annual faecal occult blood tests ( FOBT ) and were identical in both study arms . Primary outcome measures ( measured at baseline , 12 and 24 months were ( 1 ) quality of life , SF-12 ; physical and mental component scores , ( 2 ) anxiety and depression : Hospital Anxiety and Depression Scale and ( 3 ) patient satisfaction : Patient Visit-Specific Question naire . Secondary outcomes ( at 24 months ) were : investigations , number and timing of recurrences and deaths . In all , 170 patients were available for follow-up at 12 months and 157 at 24 months . At 12 and 24 months there were no differences in scores for quality of life ( physical component score , P=0.88 at 12 months ; P=0.28 at 24 months : mental component score , P=0.51 , P=0.47 ; adjusted ) , anxiety ( P=0.72 ; P=0.11 ) depression ( P=0.28 ; P=0.80 ) or patient satisfaction ( P=0.06 , 24 months ) . General practitioners ordered more FOBTs than surgeons ( rate ratio 2.4 , 95 % CI 1.4–4.4 ) , whereas more colonoscopies ( rate ratio 0.7 , 95 % CI 0.5–1.0 ) , and ultrasounds ( rate ratio 0.5 , 95 % CI 0.3–1.0 ) were undertaken in the surgeon-led group . Results suggest similar recurrence , time to detection and death rates in each group . Colon cancer patients with follow-up led by surgeons or general practitioners experience similar outcomes , although patterns of investigation vary Summary A r and omized controlled trial ( RCT ) comparing primary -care-centred follow-up of breast cancer patients with the current st and ard practice of specialist-centred follow-up showed no increase in delay in diagnosing recurrence , and no increase in anxiety or deterioration in health-related quality of life . An economic evaluation of the two schemes of follow-up was conducted concurrent with the RCT . Because the RCT found no difference in the primary clinical outcomes , a cost minimization analysis was conducted . Process measures of the quality of care such as frequency and length of visits were superior in primary care . Costs to patients and to the health service were lower in primary care . There was no difference in total costs of diagnostic tests , with particular tests being performed more frequently in primary care than in specialist care . Data are provided on the average frequency and length of visits , and frequency of diagnostic testing for breast cancer patients during the follow-up period Abstract Previously , we demonstrated , in a r and omized clinical trial , the effectiveness of a psychoeducational intervention to decrease pain intensity scores and increase patients ’ knowledge of cancer pain management with a sample of oncology patients with pain from bone metastasis . In the present study , we evaluated for changes in mood states ( measured using the Profile of Mood States ) , quality of life ( QOL ; measured using the Medical Outcomes Study Short Form‐36 ( SF‐36 ) ) , and pain ’s level of interference with function ( measured using the Brief Pain Inventory ( BPI ) ) from baseline to the end of the intervention first between the intervention and the st and ard care groups and then within the intervention group based on the patients ’ level of response to the intervention ( i.e. , patients were classified as non‐responders , partial responders , or responders ) . No differences were found in any of these outcome measures between patients in the st and ard care and intervention groups . However , when patients in the intervention group were categorized using a responder analysis approach , significant differences in the various outcome measures were found among the three respondent groups . Differences in the physical and mental component summary scores on the SF‐36 and the interference items on the BPI , among the three respondent groups , were not only statistically significant but also clinical ly significant . The use of responder analysis in analgesic trials may help to identify unique subgroups of patients and lead to the development of more effective psychoeducational interventions A r and omised controlled trial was undertaken to assess the effectiveness of a hospital Palliative Care Team ( PCT ) on physical symptoms and health-related quality of life ( HRQoL ) ; patient , family carer and primary care professional reported satisfaction with care ; and health service re source use . The full package of advice and support provided by a multidisciplinary specialist PCT ( ‘ full-PCT ’ ) was compared with limited telephone advice ( ‘ telephone-PCT ’ , the control group ) in the setting of a teaching hospital trust in the SW of Engl and . The trial recruited 261 out of 684 new inpatient referrals ; 175 were allocated to ‘ full-PCT ’ , 86 to ‘ telephone-PCT ’ ( 2 : 1 r and omisation ) ; with 191 ( 73 % ) being assessed at 1 week . There were highly significant improvements in symptoms , HRQoL , mood and ‘ emotional bother ’ in ‘ full-PCT ’ at 1 week , maintained over the 4-week follow-up . A smaller effect was seen in ‘ telephone-PCT ’ ; there were no significant differences between the groups . Satisfaction with care in both groups was high and there was no significant difference between them . These data reflect a high st and ard of care of patients dying of cancer and other chronic diseases in an acute hospital environment , but do not demonstrate a difference between the two models of service delivery of specialist palliative care OBJECTIVE To evaluate the effect of telephone follow-up on the physical well-being dimension of health-related quality of life in patients with cancer . DESIGN R and omized , controlled trial . SETTING Public teaching hospital . PATIENTS One hundred fifty patients with cancer who were discharged to home from the hospital . INTERVENTION Patients received a telephone follow-up call 48 - 72 hours after discharge . Information was solicited regarding drug-related ( and other ) problems . Problems were addressed , and advice and support were given . MEASUREMENTS AND MAIN RESULTS Analysis of variance revealed no differences in the physical well-being dimension of health-related quality of life between patients who received telephone follow-up and a control group who did not . Sixty-eight percent of the follow-up group and 40 % of the control group ( p = 0.007 ) reported having had at least one contact with a health professional . CONCLUSION One possible explanation for the lack of effect of the intervention is that high-risk patients in the control group received a similar intervention from other health care professionals . We suggest that telephone follow-up be coordinated among health professionals BACKGROUND Method ological challenges such as recruitment problems and participant burden make clinical trials in palliative care difficult . In 2001 - 2004 , two community-based r and omized controlled trials ( RCTs ) of case conferences in palliative care setting s were independently conducted in Australia -- the Queensl and Case Conferences trial ( QCC ) and the Palliative Care Trial ( PCT ) . DESIGN A structured comparative study of the QCC and PCT was conducted , organized by known practical and organizational barriers to clinical trials in palliative care . RESULTS Differences in funding dictated study design s and recruitment success ; PCT had 6 times the budget of QCC . Sample size attainment . Only PCT achieved the sample size goal . QCC focused on reducing attrition through gate-keeping while PCT maximized participation through detailed recruitment strategies and planned for significant attrition . Testing sustainable interventions . QCC achieved a higher percentage of planned case conferences ; the QCC strategy required minimal extra work for clinicians while PCT superimposed conferences on normal work schedules . Minimizing participant burden . Differing strategies of data collection were implemented to reduce participant burden . QCC had short survey instruments . PCT incorporated all data collection into normal clinical nursing encounters . Other . Both studies had acceptable withdrawal rates . Intention-to-treat analyses are planned . Both studies included sub- studies to vali date new outcome measures . CONCLUSIONS Health service interventions in palliative care can be studied using RCTs . Detailed comparative information of strategies , successes and challenges can inform the design of future trials . Key lessons include adequate funding , recruitment focus , sustainable interventions , and mechanisms to minimize participant burden PURPOSE To assess the impact of comprehensive palliative care on patients ' quality of life . The intervention was based on cooperation between a palliative medicine unit and the community service and was compared with conventional care . PATIENTS AND METHODS A cluster r and omized trial was carried out , with community health care districts defined as the clusters . Patients from these districts who had malignant disease and survival expectancy between 2 to 9 months were entered onto the trial . The main quality -of-life end points were physical and emotional functioning , pain , and psychologic distress assessed monthly by using the European Organization for Research and Treatment of Cancer Quality of Life Question naire-C30 ( EORTC QLQ-C30 ) question naire and Impact of Event scale ( IES ) . In total , 235 intervention patients and 199 controls were included . RESULTS During the initial 4 months of follow-up , the compliance was good ( 72 % ) and comparable among treatment groups . No significant differences on any of the quality -of-life scores were found . At later assessment s and for scores that were made within 3 months before death , there was also no consistent tendency in favor of any treatment group on the main outcomes or other EORTC QLQ-C30 scales/items . CONCLUSION A general program of palliative care may be important to ensure flexibility and to meet the needs of terminally ill patients . However , to achieve improvements on a group level of the various dimensions of quality of life , specific interventions directed toward specific symptoms or problems may have to be defined , evaluated , and included in the program Terminally ill cancer patients at a Veterans Administration hospital were r and omly assigned to receive hospice or conventional care . The hospice care was provided both in a special inpatient unit and at home . 137 hospice patients and 110 control patients and their familial care givers ( FCGs ) were followed until the patient 's death . No significant differences were noted between the patient groups in measures of pain , symptoms , activities of daily living , or affect . Hospice patients expressed more satisfaction with the care they received ; and hospice patients ' FCGs showed somewhat more satisfaction and less anxiety than did those of controls . Hospice care was not associated with a reduced use of hospital inpatient days or therapeutic procedures and was at least as expensive as conventional care The value of routine follow-up with frequent visits to a breast cancer specialist-both in terms of detection of recurrence and patient satisfaction-has been question ed . The aim of this study was to compare nurse-led follow-up on dem and versus physician follow-up after breast cancer treatment with regards to patients ' well-being , satisfaction , access to medical care and medical safety . Two hundred and sixty-four consecutively selected women with newly diagnosed breast cancer , classified as UICC stage I or stage II , were r and omised to follow-up at two hospitals in Sweden , either by routine medical follow-up , the physician group ( PG , n=131 ) , or on dem and by a specialist nurse , the nurse group ( NG , n=133 ) . Measures were done at baseline and twice a year over a period of 5 years by means of a question naire containing the Hospital Anxiety and Depression Scale ( HAD ) , and the Satisfaction and Accessibility ( SaaC ) scale . Number of contacts with the health care services , number of diagnostic procedures , and time to recurrence or death were monitored . The ratings of HAD and SaaC did not show any statistically significant differences between the groups . The levels of anxiety and depression were generally low and levels of patient satisfaction high . There were no differences between the groups concerning time to recurrence or death . This study indicates that women with breast cancer in stages I to II can be followed up by a specialist nurse with high patient satisfaction and good medical safety Although there is an underst and able emphasis on the side effects of individual medications , the cumulative effects of medications have received little attention in palliative care prescribing . Anticholinergic load reflects a cumulative effect of medications that may account for several symptoms and adverse health outcomes frequently encountered in palliative care . A secondary analysis of 304 participants in a r and omised controlled trial had their cholinergic load calculated using the Clinician-Rated Anticholinergic Scale ( modified version ) longitudinally as death approached from medication data collected prospect ively by study nurses on each visit . Mean time from referral to death was 107 days , and mean 4.8 visits were conducted in which data were collected . Relationships to key factors were explored . Data showed that anticholinergic load rose as death approached because of increasing use of medications for symptom control . Symptoms significantly associated with increasing anticholinergic load included dry mouth and difficulty concentrating ( P < 0.05 ) . There were also significant associations with increasing anticholinergic load and decreasing functional status ( Australia-modified Karnofsky Performance Scale ; and quality of life ( P < 0.05 ) . This study has documented in detail the longitudinal anticholinergic load associated with medications used in a palliative care population between referral and death , demonstrating the biggest contributor to anticholinergic load in a palliative care population is from symptom-specific medications , which increased as death approached All admissions to a 1,100-bed Department of Veterans Affairs ( VA ) hospital were screened to identify 171 terminally ill patients with informal caregivers who were then r and omly assigned to VA hospital-based team home care ( HBHC , N = 85 ) or customary care ( N = 86 ) . Patient functioning , and patient and caregiver morale and satisfaction with care were measured at baseline , one month , and six months . Health services utilization was monitored over the six-month study period and converted to cost . Findings included no differences in patient survival , activities of daily living ( ADL ) , cognitive functioning , or morale , but a significant increase in patient ( p = .02 ) and caregiver ( p = .005 ) satisfaction with care at one month . A substitution effect of HBHC was seen . Those in the experimental group used 5.9 fewer VA hospital days ( p = .03 ) , result ing in a $ 1,639 or 47 percent per capita saving in VA hospital costs ( p = .02 ) . As a result , total per capita health care costs , including HBHC , were $ 769 or 18 percent ( n.s . ) lower in the HBHC sample , indicating that expansion of VA HBHC to serve terminally ill veterans would increase satisfaction with care at no additional cost PURPOSE / OBJECTIVES To examine the impact on continuity of nursing care delivered by a pivot nurse in oncology to improve symptom relief and outcomes for patients with lung or breast cancer . DESIGN R and omized controlled trial in which participants were r and omly assigned to an intervention group ( n = 93 ) with care by a pivot nurse in oncology and usual care by clinic nurses or to a control group ( n = 97 ) with usual care only . SETTING Three outpatient ambulatory oncology clinics in a large university health center in Quebec , Canada . SAMPLE 113 patients with lung cancer and 77 patients with breast cancer . METHODS Participants in both groups completed the Symptom Distress Scale , Brief Fatigue Inventory , and Functional Assessment of Cancer Therapy Scale-General version 4 at eight intervals over six months . Healthcare usage was evaluated through a review of hospital records . MAIN RESEARCH VARIABLES Symptom distress , fatigue level , quality of life , and healthcare usage . FINDINGS Research ers found no significant differences in symptom distress , fatigue , quality of life , and healthcare usage between groups . CONCLUSIONS The new nursing role did not have an impact on the patient outcomes under study . IMPLICATION S FOR NURSING Experienced nurses with specialized knowledge of oncology symptom assessment and management may reduce the symptom burden experienced by ambulatory patients with breast or lung cancer during active treatment The purpose of this study was to determine if continued access to information following a baseline pain education program would increase knowledge and positive beliefs about cancer pain management , thus result ing in improved pain control during a 6-month follow-up period . Patients with cancer-related pain and their primary caregivers received a brief pain education program , and were then r and omized into one of three information groups : a ) usual care , b ) pain hot line , and c ) weekly provider-initiated follow-up calls for 1 month post-education . Sixty-four patients and their primary caregivers were recruited . Both patients and caregivers showed an improvement in knowledge and beliefs after the baseline pain education program . Continued access to pain information with either the pain hot line or provider-initiated weekly follow-up calls did not affect long-term outcomes of pain intensity , interference because of pain , adequacy of analgesics used , or pain relief . In addition , long-term outcomes did not differ between patients who had improvement and those who showed decline in knowledge and beliefs pre-post education . These findings suggest that a brief pain education program can improve knowledge and beliefs of both patient and primary caregiver . Continued access to pain related information using either a patient- or provider-initiated format did not affect long-term pain outcomes PURPOSE General practitioners ( GPs ) play a critical role in the treatment of patients with cancer ; yet often lack information for optimal care . We developed st and ardized information for GPs about chemotherapy ( CT ) . In a r and omized controlled trial we assessed the impact of sending , by fax , information tailored to the particular patient 's CT regimen . Primary end points were : confidence treating patients who were receiving CT ( confidence ) , knowledge of adverse effects and reasons to refer the patient to the treatment center ( knowledge ) , and satisfaction with information and shared care of patients ( satisfaction ) . METHODS Focus group work informed the development of the CT information which focused on potential adverse effects and recommended management strategies . GPs of patients due to commence CT were r and omly assigned to receive usual correspondence with or without the faxed patient/regimen-specific information . Telephone question naire at baseline and 1 week postintervention assessed knowledge , confidence , and satisfaction . RESULTS Ninety-seven GPs managed 97 patients receiving 23 types of CT . Eighty-one ( 83.5 % ) completed the follow-up question naire . GPs in the intervention group demonstrated a significantly greater increase in confidence ( mean difference , 0.28 ; 95 % CI , 0.10 to 0.47 ) and satisfaction ( mean difference , 0.57 ; 95 % CI , 0.27 to 0.88 ) compared with usual care , reflecting a 7.1 % and 10.5 % difference in score , respectively . No differences were detected for knowledge . GPs receiving the CT sheet found correspondence significantly more useful ( P < .001 ) and instructive ( P < .001 ) than GPs who received st and ard correspondence alone . CONCLUSION Information about CT faxed to GPs is a simple , inexpensive intervention that increases confidence managing CT adverse effects and satisfaction with shared care . This intervention could have widespread application 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 OBJECTIVES To evaluate the effect of nurse case management on the treatment of older women with breast cancer . DESIGN R and omized prospect i ve trial . SETTING Sixty surgeons practicing at 13 community and two public hospitals in southeast Texas . PARTICIPANTS Three hundred thirty-five women ( 166 control and 169 intervention ) aged 65 and older newly diagnosed with breast cancer . INTERVENTION Women seeing surgeons r and omized to the intervention group received the services of a nurse case manager for 12 months after the diagnosis of breast cancer . MEASUREMENTS The primary outcome was the type and use of cancer-specific therapies received in the first 6 months after diagnosis . Secondary outcomes were patient satisfaction and arm function on the affected side 2 months after diagnosis . RESULTS More women in the intervention group received breast-conserving surgery ( 28.6 % vs 18.7 % ; P=.031 ) and radiation therapy ( 36.0 % vs 19.0 % ; P=.003 ) . Of women undergoing breast-conserving surgery , greater percentages in the case management group received adjuvant radiation ( 78.3 % vs 44.8 % ; P=.001 ) and axillary dissection ( 71.4 % vs 44.8 % ; P=.057 ) . Women in the case management group were also more likely to receive more breast reconstruction surgery ( 9.3 % vs 2.6 % , P=.054 ) , and women in the case management group with advanced cancer were more likely to receive chemotherapy ( 72.7 % vs 30.0 % , P=.057 ) . Two months after surgery , higher percentages of women in the case manager group had normal arm function ( 93 % vs 84 % ; P=.037 ) and were more likely to state that they had a real choice in their treatment ( 82.2 % vs 69.9 % , P=.020 ) . Women with indicators of poor social support were more likely to benefit from nurse case management . CONCLUSION Nurse case management results in more appropriate management of older women with breast cancer 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 Introduction . Breast cancer follow-up programmes consume large re sources and despite the indications that several alternative approaches could be used effectively , there is no coherent discussion about costs and /or cost-effectiveness of follow-up programmes . Patient and methods . In a prospect i ve trial there were 264 breast cancer patients , stage I and II , r and omised to two different follow-up programmes- PG ( physician group ) and NG ( nurse group ) . The trial period was 5 years . The women in the two intervention groups did not differ in anxiety and depression , their satisfaction with care , their experienced accessibility to the medical centre or their medical outcome as measured by recurrence or death . The analyses were done from different lists representing costs at three hospitals in Sweden according to the principles of a cost minimization study . Results : The cost per person year of follow-up differed between the groups , with € 630 per person year in PG compared to € 495 per person year in NG . Thus , specialist nurse intervention with check-ups on dem and was 20 % less expensive than routine follow-up visits to the physician . The main difference in cost between the groups was explained by the numbers of visits to the physician in the respective study arms . There were 21 % more primary contacts in PG than NG . Discussion . The difference in cost per year and patient by study arm is modest , but transforms to nearly € 900 per patient and 5-year period , offering a substantial opportunity for reallocating re sources since breast cancer is the most prevalent tumour worldwide CONTEXT Changes in the healthcare system have result ed in shortened hospital stays , moving the focus of care from the hospital to the home . Patients are discharged post-operatively with ongoing needs , and whether they receive nursing care post-hospitalization can influence their recovery and survival . Little information is available about the factors that influence outcomes , including the survival of older cancer patients after cancer surgery . OBJECTIVE To compare the length of survival of older post-surgical cancer patients who received a specialized home care intervention provided by advanced practice nurses ( APNs ) with that of patients who received usual follow-up care in an ambulatory setting . We also assessed potential predictors of survival in terms of depressive symptoms , symptom distress , functional status , comorbidities , length of hospital stay , age of patient , and stage of disease . DESIGN A r and omized controlled intervention study . SETTING Discharged older cancer patients after surgery at a Comprehensive Cancer Center in southeastern Pennsylvania . PATIENTS Three hundred seventy-five patients aged 60 to 92 , newly diagnosed with solid cancers , were treated surgically between February 1993 and December 1995 . One hundred ninety patients were r and omized to the intervention groups and 185 to the usual care group . INTERVENTION The intervention was a st and ardized protocol that consisted of st and ard assessment and management post-surgical guidelines , doses of instructional content , and schedules of contacts . The intervention lasted 4 weeks and consisted of three home visits and five telephone contacts provided by APNs . Both the patients and their family caregivers received comprehensive clinical assessment s , monitoring , and teaching , including skills training . MAIN OUTCOME MEASURE Time from enrollment of patients into the study until death or last date known alive at the end of November 1996 . RESULTS During the 44-month follow-up period , 93 ( 24.8 % ) of 375 patients died . Forty-one ( 22 % ) of those who died were patients in the specialized home care intervention group , compared with 52 ( 28 % ) in the usual care group . Stage of disease at diagnosis differed between the two groups at baseline ( 38 % late stage patients in the intervention group compared with 26 % in the control group , P = .01 ) , so stratified analysis was performed . Overall , the specialized home care intervention group was found to have increased survival ( P = .002 using stratified log-rank test ) . Among early stage patients only , there was no difference in survival between the intervention and control groups . Among late stage patients , there was improved survival in the intervention group . For example , 2-year survival among late stage intervention group cases was 67 % compared with 40 % among control cases . When Cox 's proportional hazard model was used to adjust for significant baseline covariates , the relative hazard of death in the usual care group was 2.04 ( CI : 1.33 to 3.12 ; P = .001 ) after adjusting for stage of disease and surgical hospitalization length of stay . CONCLUSIONS This is the first empirical study of post-surgical cancer patients to link a specialized home care intervention by advanced practice nurses with improved survival . Additional research is needed to test home care interventions aim ed at maintaining quality of life outcomes and their effects on survival of post-surgical cancer patients PURPOSE To determine the effectiveness of a multicomponent clinical intervention to reduce pain in out patients with cancer . METHODS AND MATERIAL S Sixty-four patients were r and omly assigned to receive either a clinical intervention including an information session , the use of a pain diary , and the possibility to contact a physician to adjust the pain medication , or the usual treatment of pain by the staff radiation oncologist . All patients reported their average and worst pain levels at baseline and 2 and 3 weeks after the start of the intervention . RESULTS The study groups were similar with respect to their baseline characteristics and pain levels at r and omization . After 3 weeks , the average and worst pain experienced by patients r and omized to the clinical intervention group was significantly inferior to the average pain experienced by patients in the control group ( 2.9/10 vs. 4.4/10 and 4.2/10 vs. 5.5/10 , respectively ) . Results showed that the experimental group patients decreased their pain levels more than the control group patients did over time . CONCLUSION An intervention including patient education , a pain diary , and defining a procedure for therapeutic adjustments can be effective to improve pain relief in out patients with cancer PURPOSE This study was performed as part of a large depression screening project in cancer patients to determine the degree of physician recognition of levels of depressive symptoms in cancer patients and to describe patient characteristics that influence the accuracy of physician perception of depressive symptoms . METHODS Twenty-five ambulatory oncology clinics affiliated with Community Cancer Care , Inc of Indiana enrolled and surveyed 1,109 subjects treated by 12 oncologists . Subjects completed the Zung Self-Rating Depression Scale ( ZSDS ) and physicians were asked to rate their patients ' level of depressive symptoms , anxiety , and pain using numerical rating scales . Subjects ' sex , age , primary tumor type , medications , primary caregiver , and disease stage at diagnosis were also recorded . RESULTS Physician ratings of depression were significantly associated with their patients ' levels of endorsement of depressive symptoms on the ZSDS . However , agreement between physicians and patients is most frequently clustered when patients report little or no depressive symptoms . While physician ratings are concordant with patient endorsement of no significant depressive symptomatology 79 % of the time , they are only concordant 33 % and 13 % of the time in the mild-to-moderate/severe ranges , respectively . Physician ratings were most influenced by patient endorsement of frequent and obvious mood symptoms , ie , sadness , crying , and irritability . Physician ratings also appeared to be influenced by medical correlates of patients ' level of depressive symptoms ( functional status , stage of disease , and site of tumor ) . Additionally , patients whose depression was inaccurately classified reported significantly higher levels of pain and had higher levels of disability . Physicians ' ratings of depression were most highly correlated with physicians ' ratings of patients ' anxiety and pain . CONCLUSION Physicians ' perceptions of depressive symptoms in their patients are correlated with patient 's ratings , but there is a marked tendency to underestimate the level of depressive symptoms in patients who are more depressed . They are most influenced by symptoms such as crying and depressed mood , and medical factors that are useful , but not the most reliable , indicators of depression in this population . Physicians ' ratings of their patients ' distress symptoms seem to be global in nature -- they are highly correlated with anxiety , pain , and global dysfunction . Physician assessment might be improved if they were instructed to assess and probe for the more reliable cognitive symptoms such as anhedonia , guilt , suicidal thinking , and hopelessness . Screening instruments and the use of brief follow-up interviews would help to identify patients who are depressed BACKGROUND The burden of cancer care in general practice is increasing . Patient-held records may facilitate effective , coordinated care , but no r and omised controlled trials of their use in cancer care have been conducted , and concerns about possible negative effects remain . AIM To evaluate the use of a supplementary patient-held record in cancer care . METHOD Six hundred and fifty radiotherapy out patients with any form of cancer were r and omised either to hold a supplementary record or to receive normal care . It was explained to record holders that the supplementary record was intended to improve communication with health professionals and act as an aide memoire . After three months , patients ' satisfaction with communication and with participation in their own care were assessed . Global health status , emotional functioning , and cognitive functioning were measured using the European Organization for Research and Treatment of Cancer QLQ-C30 question naire . RESULTS There were no significant differences between groups in any of the outcome measures . Patients in both groups expressed a high level of satisfaction with communication and participation in their care . Mean ( SD ) scores in the intervention and control groups were : global health status , 66.8 ( 24.2 ) and 65.3 ( 23.7 ) ; emotional functioning , 75.0 ( 24.6 ) and 77.4 ( 22.8 ) ; cognitive functioning , 84.5 ( 21.0 ) and 84.0 ( 21.3 ) . CONCLUSION A supplementary patient-held record for radiotherapy out patients appears to have no effect on satisfaction with communication , participation in care , or quality of life This paper describes an intervention study aim ed at improving communication between hospital services and the primary health care team . A series of information cards were developed by breast specialist secondary care professionals for members of the primary health care team . Women with breast cancer were involved in the communication pathway and were asked to take the information cards to their own general practitioner ( GP ) practice . It was envisaged that women would be more likely to utilize the primary health care team for information if they were aware that the primary health care team was in receipt of information specific to the treatment they had received . Women newly diagnosed with breast cancer were allocated to either an intervention ( n=38 ) or non-intervention ( n=38 ) group . Patient interviews were carried out around the time of diagnosis and at 4 months from diagnosis . Interviews were also carried out with 31 GPs to ascertain their views on the provision of information for women with breast cancer , and on the information cards if relevant . The study findings were interesting although not significant in terms of the direction anticipated . The cards did not impact on the utilization of the primary health care team and women in the intervention group were no more likely to utilize primary care sources of information than women in the non-intervention group . Factors such as the long-st and ing relationship women had with their GP , the perceived lack of specialist knowledge on the part of GPs and district nurses , and the women 's perception that information seeking was not a tangible reason for primary care contact had an impact on information-seeking behaviour 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 Although some studies have examined the effects of terminal illness care models such as hospice care on survivor outcomes , no studies could be found that examined whether nursing care affected such outcomes . OBJECTIVE To determine whether specialized oncology home care services provided to terminally ill patients with lung cancer positively influenced bereavement psychological distress among survivors , compared with other models of care . METHODS A secondary analysis was performed to test the effects of home nursing care for terminally ill patients on spousal psychological distress during bereavement . Forty-six patient-spousal dyads were r and omly assigned to either an oncology home care group ( OHC ) , a st and ard home care group , or an office care control group . Patient-spousal dyads were entered into the study 2 months after the patient 's diagnosis of lung cancer and received follow-up until the patient died . Bereaved spouses continued to receive follow-up for 25 months after the patient 's death . RESULTS Psychological distress was significantly lower initially among spouses of patients that received the OHC intervention compared with the other two groups . Significant mean group differences were found on the subscales of depression and paranoid ideation ; marginal group differences were found on the subscales of hostility and psychoticism . There were no significant differences among the groups at 25 months . CONCLUSIONS These results suggest that the bereaved 's psychological distress can be positively influenced depending on how their loved one is cared for during the terminal phase of illness Although pain management education results in improved pain control for some patients , it does not work for all patients because some patients remain reluctant or unwilling to use prescribed analgesics to their optimal effect . In a r and omized clinical trial that tested the effectiveness of the PRO-SELF © Pain Control Program , 11 patients declined to increase their analgesic use despite moderate to severe pain . These patients were selected for a qualitative analysis of their audiotaped discussion s about pain management with their intervention nurses . This analysis revealed that these patients often spontaneously provided detailed explanations about why they were reluctant or unwilling to take analgesics in general or opioids in particular . We termed these explanatory accounts pain management autobiographies because of their narrative character and multilayered , richly detailed quality . Pain management autobiographies included stories about ( 1 ) previous experience with chronic pain management , including stigmatizing interactions with clinicians and family members ; ( 2 ) bad experiences with cancer pain management , including severe constipation ; and 3 ) strongly held conventions about medication use , including the belief that all medications are “ toxins ” that should be avoided . The study findings suggest that a small subset of patients with cancer pain may need interventions such as individual or family counseling or alternative pain management strategies to augment education about opioids PURPOSE To determine whether making patient-reported cancer needs , quality -of-life ( QOL ) , and psychosocial information available to the health care team , allowing coordinated specifically targeted psychosocial interventions , result ed in reduced cancer needs , improved QOL , and increased satisfaction with care received . METHODS Self-reported cancer needs , QOL , and psychosocial information was collected from 450 people with cancer , using st and ardized question naires via a touch-screen computer . For a r and omly chosen two thirds , this information was made available to the health care team who coordinated targeted psychosocial interventions . Information from the remaining one third was not seen . Patients were assessed 2 and 6 months after r and omization for changes in their cancer needs , QOL , and psychosocial functioning and satisfaction with overall care received . RESULTS There were no significant differences between the two arms with respect to changes in cancer needs , QOL , or psychosocial functioning between the baseline and follow-up assessment s , nor with respect to satisfaction with care . However , for the subgroup of patients who were moderately or severely depressed at baseline , there was a significant reduction in depression for the intervention arm relative to the control arm at the 6-month assessment ( P = .001 ) . CONCLUSION Making patient-reported cancer needs , QOL , and psychosocial data available to the health care team at a single consultation together with coordinated psychosocial interventions does not seem to reduce cancer needs nor improve QOL , psychosocial functioning , or satisfaction with the care received . However , identification of patients with moderate or severe levels of depression may be valuable in reducing subsequent levels of depression BACKGROUND The Palliative Medicine Unit at University Hospital of Trondheim , Norway , started an intervention programme that aims to enable patients to spend more time at home and die there if they prefer . Close cooperation was needed with the community health-care professionals , who acted as the principal formal caregivers , and a multidisciplinary consultant team coordinated the care . We did a cluster r and omised trial to assess the intervention 's effectiveness compared with conventional care METHODS Community health-care districts in and around Trondheim , Norway , were defined as the clusters to be r and omised . We enrolled 434 patients ( 235 assigned intervention and 199 conventional care [ controls ] ) in these districts who had incurable malignant disease and an expected survival of 2 - 9 months . Main outcomes were place of death and time spent in institutions in the last month of life . FINDINGS 395 patients died . Of these , more intervention patients than controls died at home ( 54 [ 25 % ] vs 26 [ 15 % ] , p<0.05 ) . The time spent at home was not significantly increased , although intervention patients spent a smaller proportion of time in nursing homes in the last month of life than did controls ( 7.2 vs 14.6 % , p<0.05 ) . Hospital use was similar in the two groups . INTERPRETATION The palliative-care intervention enabled more patients to die at home . More re sources for care in the home ( palliative care training and staff ) and an increased focus on use of nursing homes would be necessary , however , to increase time at home and reduce hospital admissions PURPOSE / OBJECTIVES To describe how nurse case managers care for older women with breast cancer . DESIGN A r and omized , prospect i ve trial . SETTING Thirteen community hospitals and two public hospitals in southeastern Texas . SAMPLE 335 older women aged 60 - 89 years newly diagnosed with breast cancer and being cared for by 60 surgeons . Most participants were Caucasian . A total of 166 women were in the control group , and 159 were in the intervention nurse case management group . METHODS The nurses implemented multiple nursing interventions in each nursing process phase over a period of 12 months . MAIN RESEARCH VARIABLES Independent variables were participants ' demographic characteristics , depressive symptomatology , and cognitive impairment . Nurse case management contact was a dependent variable . FINDINGS In each nursing phase , a greater number of nurse case management contacts were made in the first quarter . Bivariate analysis illustrated statistical differences among race , income , education , and living alone with respect to the mean amount of nurse case management . Multivariate analysis revealed that age , income , living alone , and stage of cancer predicted more nurse case management contact . CONCLUSIONS Nurse case managers may play a role in helping older women with breast cancer achieve positive health outcomes . IMPLICATION S FOR NURSING Based on the findings of this study , nurses can develop specific nursing interventions to meet the needs of older women with breast cancer . Nurses can use the Model of Nurse Case Management to plan and manage care for older women with breast cancer A federally-funded demonstration project was conducted by the Illinois Cancer Council and the Illinois Department of Public Health to determine if the introduction of modest changes in the home health system would effect certain cancer patient patterns of care and outcomes . Certified home health agencies in two health planning regions of Illinois were r and omized into one of three study groups , two of which received an intervention ( oncology nurse specialist with continuing education on cancer , or continuing education on cancer alone ) , and the third was an " observation only " group . The pre/post differences of a number of evaluation parameters were investigated . Overall , the group which received the services of the oncology nurse specialist and continuing education on cancer demonstrated the largest percentage increase in cancer patient referrals to home care , and experienced a significant decrease in cancer patient mortality . No significant difference among cancer patients in the three study groups was noted for hospitalization rate or incidence of physiologic complications while on agency caseload & NA ; The effectiveness of a Pain Education Program in cancer patients with chronic pain offered by nurses was investigated in a r and omized controlled clinical trial . A multi‐ method approach was used in which verbal instruction , written material , an audio cassette tape , and the use of a pain diary were combined to inform and instruct patients about pain and pain management . The Pain Education Program was tailored to the needs of the individual patient and consisted of three elements : ( 1 ) educating patients about the basic principles regarding pain and pain management ; ( 2 ) instructing patients how to report their pain in a pain diary ; and ( 3 ) instructing patients how to communicate about pain and how to contact health care providers . Following pretesting in 313 patients , patients who needed district nursing and who did not need district nursing at home were r and omly assigned to a control or intervention group . Intervention group patients received the Pain Education Program in the hospital , and 3 and 7 days postdischarge by telephone ; this was done by nurses who were specially trained as pain counselors . Follow‐up assessment s were at 2 , 4 and 8 weeks postdischarge . Results of the pretest showed that many patients lacked knowledge about pain and pain management . The majority of pain topics had to be discussed . The Pain Education Program proved to be feasible : 75.0 % of the patients had read the entire pain brochure , 55.7 % had listened to the audio cassette , and 85.6 % of pain scores were completed in the pain diary . Results showed a significant increase in pain knowledge in patients who received the Pain Education Program and a significant decrease in pain intensity . However , pain relief was mainly found in the intervention group patients without district nursing . It can be concluded that the tailored Pain Education Program is effective for cancer patients in chronic pain . The use of the Pain Education Program by nurses should be seriously considered on oncology units The aim of this study was to evaluate the effect of an individual support ( IS ) intervention including intensified primary healthcare on the utilisation of specialist care among cancer patients , and to investigate if such an effect was modified by the patient 's age ( less than 70 years or 70 years and more ) . Newly diagnosed cancer patients ( n=416 ) were r and omised between the intervention and a control condition , and data were collected on the utilisation of specialist care within 3 months from inclusion . Intensified primary healthcare comprised extended information from the specialist clinics , and education and supervision in cancer care for general practitioners ( GPs ) and home-care nurses . The support given also included interventions design ed to diminish problems of weight loss and psychological distress . The intervention reduced the number of admissions ( NoA ) and the days of hospitalisation ( DoH ) after adjustment for weight loss and psychological distress , but only for older patients . Older patients r and omised to the intervention ( n=82 ) experienced 393 fewer DoH than the older control patients ( n=79 ) . In addition , the proportion of older patients in the IS group who utilised acute specialist care was smaller compared with older control patients group . The conclusion is that older cancer patients ' utilisation of specialist care may be reduced by intensified primary healthcare services As part of a r and omized controlled trial of a new district co-ordinating service for the care of terminally ill cancer patients , the activities of the nurse co-ordinators and the acceptability and perceived effectiveness of the service were assessed . Co-ordinators ' activities were self-recorded ; professional caregivers completed a postal question naire ; and family carers were interviewed at home . Thirty-eight per cent of patients allocated to the co-ordinators were not visited at home . Overall , 41 % of professionals had heard of the co-ordinating service and 20 % had been contacted . A third of relatives , whether allocated or not to the co-ordinating service , felt that terminal care of their patient was not well co-ordinated and that they did not know how to get the help they needed for their dying relative . It may be that the nurse co-ordinators were unwilling or unable to relinquish their skills in order to provide a ' broker ' style of co-ordination . Perhaps less skilled co-ordinators would have been more successful . Moreover , the co-ordinating service had no budgetary responsibility . Those concerned with quality assurance in co-ordination of terminal care might consider the skill mix and professional training of the co-ordinators as well as their budgetary responsibilities and authority PURPOSE Pain and symptom management is an integral part of the clinical practice of oncology . A number of guidelines have been developed to assist the clinician in optimizing comfort care . We implemented clinical guidelines for cancer pain management in the community setting and evaluated whether these guidelines improved care . PATIENTS AND METHODS Eighty-one cancer patients , aged 37 to 76 years , were enrolled onto a prospect i ve , longitudinal , r and omized controlled study from the outpatient clinic setting s of 26 western Washington-area medical oncologists . A multilevel treatment algorithm based on the Agency for Health Care Policy and Research Guidelines for Cancer Pain Management was compared with st and ard- practice ( control ) pain and symptom management therapies used by community oncologists . The primary outcome of interest was pain ( Brief Pain Inventory ) ; secondary outcomes of interest were all other symptoms ( Memorial Symptom Assessment Scale ) and quality of life ( Functional Assessment of Cancer Therapy Scale ) . RESULTS Patients r and omized to the pain algorithm group achieved a statistically significant reduction in usual pain intensity , measured as slope scores , when compared with st and ard community practice ( P < .02 ) . Concurrent chemotherapy and patient adherence to treatment were significant mediators of worst pain . There were no significant differences in other symptoms or quality of life between the two treatment groups . CONCLUSION This guideline implementation study supports the use of algorithmic decision making in the management of cancer pain . These findings suggest that comprehensive pain assessment and evidence -based analgesic decision-making processes do enhance usual pain outcomes An unbiased evaluation of hospice effectiveness requires a r and omized controlled trial ( RCT ) , but the implementation of such a design is difficult . This paper describes the methods of the only RCT to date and reports on the validity and reliability of scales selected or developed to assess attainment of hospice goals . The patients involved are those in a VA hospital in Los Angeles who have cancer and a prognosis of about 6 months and who consent . They and their significant others are interviewed periodically until the patient 's death to measure such hospice variables as pain , depression , anxiety , satisfaction with care and the environment , activities of daily living , and bereavement effects . Many of the scales , including McGill Pain , CES-D Depression , and Satisfaction with Care scales , have been vali date d in other studies with similar sample s. The authors ' test – retest reliability analyses show that these scales are reliable with advanced cancer patients and their significant others with coefficients ranging from 0.77 to 0.97 The objective of this paper is to compare the cost effectiveness of a co- ordination service with st and ard services for terminally ill cancer patients with a prognosis of less than one year . We design ed a r and omized controlled trial , with patients r and omized by the general practice with which they were registered . Co-ordination group patients received the assistance of two nurse coordinators whose role was to ensure that patients had access to appropriate services . The setting was in a South London health authority . Complete service use and outcome data were collected on 167 patients , 86 in the co-ordination group , and 81 in the control group . Our results , as previously reported , show that no differences in outcomes were detected between the co-ordination and control groups ; the mean total costs incurred by the co-ordination group were significantly less than those of the control group . The co-ordinated group used significantly fewer inpatient days ( mean 24 versus 40 inpatient days ; t = 2.4 , p = 0.002 ) and nurse home visits ( mean 14.5 versus 37.5 visits ; t = 0.3 , p = 0.01 ) . Mean cost per co- ordinated patient was almost half that of the control group patients ( £ 4774 versus £ 8034 , t = 2.8 , p = 0.006 ) . Although the unit cost data were relatively crude , these cost reductions were insensitive to a wide range of unit costs . These differences persisted when , in order to control for any putative differences in severity between the two groups , the analysis was restricted to patients who had died by the end of the study . The ratio of potential cost savings to the cost of co-ordination service was between 4:1 and 8:1 . In conclusion , the co-ordination service for cancer patients who were terminally ill with a prognosis of less than one year was more cost effective than st and ard services , due to achieving the same outcomes at lower service use , particularly inpatient days in acute hospital . Assuming that the observed effects are real , improved co-ordination of palliative care offers the potential for considerable savings . Further research is needed to explore this issue PURPOSE / OBJECTIVES To describe the usefulness of daily pain management diaries to out patients with cancer who participated in a r and omized clinical trial of the PRO-SELF Pain Control Program . DESIGN R and omized clinical trial in which a daily pain management diary was used for data collection in the control group and for data collection and nurse coaching regarding the pain management program in the intervention group . SETTING Seven outpatient oncology setting s. SAMPLE 155 patients with pain from bone metastases and 90 family caregivers . METHODS Content and statistical analysis of audiotaped answers to a semistructured question naire . MAIN RESEARCH VARIABLES Patients ' and family caregivers ' perceptions of the usefulness of a daily pain management diary ; specific ways in which the diary was used . FINDINGS Patients in both the intervention ( 75 % ) and control groups ( 73 % ) found the diary useful . The diary was used to heighten awareness of pain , guide pain management behavior , enhance a sense of control , and facilitate communication . Family caregivers in both groups also reported that the diary was useful . CONCLUSIONS The completion of a daily pain management diary is useful to patients and family caregivers and may function as an intervention for self-care . IMPLICATION S FOR NURSING Research -based evidence supports the importance of using a daily pain management diary in clinical practice We are conducting a three-year study of telehealth in 11 home care offices that serve rural clients in Alberta . Three hundred and twenty palliative home care clients are being recruited to participate in a r and omized controlled trial ( RCT ) to answer three questions about the use of video-phones and their effect on symptom management , quality of life and cost , as well as readiness to use the technology . Both successes and challenges have been identified in three main areas : technology , people/organizational issues and study design . Maintaining study integrity has been the key factor in decision making , as adjustments from the original proposal are made . It is already clear that field-based RCTs are feasible , but require commitment and flexibility on the part of research ers and community partners to work through the study implementation BACKGROUND Over the past 20 years , both inpatient units and outpatient clinics have developed programs for geriatric evaluation and management . However , the effects of these interventions on survival and functional status remain uncertain . METHODS We conducted a r and omized trial involving frail patients 65 years of age or older who were hospitalized at 11 Veterans Affairs medical centers . After their condition had been stabilized , patients were r and omly assigned , according to a two-by-two factorial design , to receive either care in an inpatient geriatric unit or usual inpatient care , followed by either care at an outpatient geriatric clinic or usual outpatient care . The interventions involved teams that provided geriatric assessment and management according to Veterans Affairs st and ards and published guidelines . The primary outcomes were survival and health-related quality of life , measured with the use of the Medical Outcomes Study 36-Item Short-Form General Health Survey ( SF-36 ) , one year after r and omization . Secondary outcomes were the ability to perform activities of daily living , physical performance , utilization of health services , and costs . RESULTS A total of 1388 patients were enrolled and followed . Neither the inpatient nor the outpatient intervention had a significant effect on mortality ( 21 percent at one year overall ) , nor were there any synergistic effects between the two interventions . At discharge , patients assigned to the inpatient geriatric units had significantly greater improvements in the scores for four of the eight SF-36 subscales , activities of daily living , and physical performance than did those assigned to usual inpatient care . At one year , patients assigned to the outpatient geriatric clinics had better scores on the SF-36 mental health subscale , even after adjustment for the score at discharge , than those assigned to usual outpatient care . Total costs at one year were similar for the intervention and usual-care groups . CONCLUSIONS In this controlled trial , care provided in inpatient geriatric units and outpatient geriatric clinics had no significant effects on survival . There were significant reductions in functional decline with inpatient geriatric evaluation and management and improvements in mental health with outpatient geriatric evaluation and management , with no increase in costs Educational interventions , aim ing to increase patients ' knowledge and attitude regarding pain , can affect pain treatment . The purpose of this study was to evaluate the effects of a Pain Education Programme ( PEP ) , on adequacy of pain treatment , and to describe characteristics predicting change in adequacy . The PEP consists of a multi- method approach in which patients are educated about the basic principles regarding pain , instructed how to report pain in a pain diary , how to communicate about pain , and how to contact healthcare providers . The effects of the PEP were evaluated taking into consideration the lack of well-established outcome measures to evaluate adequacy of pain treatment , the lack of long-term follow-up , and the influence of missing data .A prospect i ve , r and omized study was utilized in which 313 chronic cancer patients were followed-up until 8 weeks postdischarge . Adequacy of pain treatment was evaluated by means of the Amsterdam Pain Management Index ( APMI ) , consisting of an integrated score of patients ' Present Pain Intensity , Average Pain Intensity , and Worst Pain Intensity , corrected for patients ' Tolerable Present Pain , with the analgesics used by the patient . At pretest , 60 % of the patients in the hospital were treated inadequately for their pain . Postdischarge , the control group patients were significantly more inadequately treated at 2 weeks after discharge ( 56 % vs 41 % ) , at 4 weeks after discharge ( 62 % vs 42 % ) and at 8 weeks after discharge ( 57 % vs 51 % ) than the intervention group patients . While the level of inadequacy in the control groups remained relatively stable at all assessment points , a slight increase in the percentage of patients being treated inadequately was found in the intervention group patients over time . A beneficial effect of the PEP was found for patients both with and without district nursing . Variables predicting an improvement in adequacy of pain treatment consisted of the PEP , the APMI score at baseline , patients ' level of physical functioning , patients ' level of social functioning , the extent of adherence to pain medication , patients ' pain knowledge , and the amount of analgesics used . These findings suggest that quality of pain treatment in cancer patients with chronic pain can be enhanced by educating patients about pain and improving active participation in their own pain treatment . The benefit from the PEP , however , decreases slightly over time , pointing at a need for ongoing education PURPOSE / OBJECTIVES To evaluate quality of life ( QOL ) and cost outcomes of advanced practice nurses ' ( APNs ' ) interventions with women diagnosed with breast cancer . DESIGN R and omized clinical trial . SETTING Integrated healthcare system in a midwestern suburban community . SAMPLE 210 women with newly diagnosed breast cancer with an age range of 30 - 85 years . METHODS The control group ( n = 104 ) received st and ard medical care . The intervention group ( n = 106 ) received st and ard care plus APN interventions based on Brooten 's cost- quality model and the Oncology Nursing Society 's st and ards of advanced practice in oncology nursing QOL was measured using the Functional Assessment of Cancer Therapy , Mishel Uncertainty in Illness Scale and Profile of Mood States at seven intervals over two years . Information about costs ( charges and reimbursement ) was collected through billing systems . MAIN RESEARCH VARIABLES Uncertainty , mood states , well-being , charges , and reimbursement . FINDINGS Uncertainty decreased significantly more from baseline in the intervention versus control group at one , three , and six months after diagnosis ( p = 0.001 , 0.026 , and 0.011 , respectively ) , with the strongest effect on subscales of complexity , inconsistency , and unpredictability . Unmarried women and women with no family history of breast cancer benefited from nurse interventions in mood states and well-being . No significant cost differences were found . CONCLUSIONS APN interventions improved some QOL indicators but did not raise or lower costs . IMPLICATION S FOR NURSING PRACTICE The first six months after breast cancer diagnosis is a critical time during which APN interventions can improve QOL outcomes . More research is necessary to define cost-effective interventions A r and omized clinical trial was conducted to assess the effects of home nursing care for patients with progressive lung cancer . One hundred sixty‐six patients were assigned to either an oncology home care group ( OHC ) that received care from oncology home care nurses , a st and ard home care group ( SHC ) that received care from regular home care nurses , or an office care group ( OC ) that received whatever care they needed except for home care . Patients were entered into the study 2 months after diagnosis and followed for 6 months . Patients were interviewed at 6‐week intervals across five occasions . At the end of the study , there were no differences in pain , mood disturbance , and concerns among the three groups . There were significant differences in symptom distress , enforced social dependency , and health perceptions . The two home nursing care groups had less distress and greater independence 6 weeks longer than the office care group . In addition , the two home nursing care groups steadily reported worse health perceptions over time . Thus , it was remarkable that the office care group , which indicated more symptom distress and social dependency with time , also indicated perceptions of improved health with time . These results suggest that home nursing care assists patients with forestalling distress from symptoms and maintaining their independence longer in comparison to no home nursing care . Home care may also include assisting patients in acknowledging the reality of their situation Despite their wishes , terminal cancer patients are frequently readmitted to hospitals . This appears in part to be due to poor communication amongst professional caregivers and /or the overburdening of their ( informal ) caregivers . This quasi-experimental study investigated the effects of a transmural home care programme on re-hospitalization , quality of life and place of death for terminal cancer patients . The programme intended to optimize communication , cooperation and coordination between intra- and extra-mural health care organizations ( transmural care ) . Initial patient characteristics of the intervention group ( n = 79 ) matched those of the control group ( n = 37 ) well . When compared to the control group , which received the st and ard community care , patients in the intervention group underwent significantly less re-hospitalization during the terminal phase of their illness ( 5.8 versus 11.5 days ; P < 0.01 ) while the intervention contributed significantly positive to the patients ' " physical " quality of life 1 month after the start of the intervention . A higher , but not significant ( P = 0.06 ) percentage of patients in the intervention group also died at home ( 81 versus 65 % ) . The introduction of measures to enhance coordination and cooperation of intra- and extramural care , seems to be an improvement compared to st and ard community care OBJECTIVE To describe the role of the General Practitioner ( GP ) in the care of one specified cancer patient per GP , and to explore the GP 's knowledge about that patient 's disease and treatments , and what information she/he wanted versus received from the specialist clinic . A further aim was to evaluate the effects of an Extended Information Routine ( EIR ) , including increased information from the specialist clinic to the GP . DESIGN Semi-structured interviews with GPs about a patient r and omised between an extended information routine and st and ard information from the specialist clinics . SETTING S Primary Health Care . SUBJECTS 20 GPs , 10 who received extended information about the specified patient and 10 who did not . MAIN OUTCOME MEASURES The extent of GPs ' contact with the patient , GPs ' potential or actual possibilities to support the patient , desired and received information from the specialist clinic . RESULTS AND CONCLUSIONS GPs are commonly involved in the care of cancer patients , particularly in the diagnostics of the disease but also during the periods of treatment and follow-up . The information from the specialist clinic to the GP is insufficient in st and ard care . The extended information routine increased the GPs ' knowledge of the disease and treatments , and facilitated their possibilities to determine patients ' need for support Abstract Objective : To evaluate the effect of support from a nurse specialising in breast care and a voluntary support organisation on prevalence of psychological morbidity after surgery for breast cancer . Design : Prospect i ve r and omised study . Setting : Three teaching hospitals in Glasgow with established breast clinics . Subjects : 272 women aged less than 70 years undergoing surgery for breast cancer . Interventions : Patients were r and omly allocated to receive routine care from ward staff , routine care plus support from breast care nurse , routine care plus support from voluntary organisation , or routine care plus support from nurse and organisation . Main outcome measures : Prevalence of psychological morbidity as assessed by self rating scales : 28 item general health question naire and its subscales , and hospital anxiety and depression scale . Measurements were made at first postoperative clinic visit and at three , six , and 12 months after surgery . Results : On each self rating scale , psychological morbidity tended to fall over the 12 month period . For each scale , scores were consistently lower in patients offered support from breast care nurse alone compared with the other groups , which were similar to each other . Differences were significant or nearly so : P values were 0.015 ( 28 item general health question naire ) , 0.027 ( anxiety and insomnia ) , 0.072 ( severe depression ) , 0.053 ( somatic symptoms ) , 0.031 ( social dysfunction ) , 0.093 ( hospital anxiety ) , and 0.003 ( hospital depression ) . Conclusion : Support from breast care nurse can significantly reduce psychological morbidity , as measured by self rating scales , in women undergoing breast cancer surgery . Key messages Key messages The value of different forms of psychological support for breast cancer patients is uncertain We compared effect of four different types of support for patients undergoing surgery for breast cancer : routine care from ward staff , routine care plus support from specialist breast care nurse , routine care plus support from voluntary organisation , or routine care plus support from nurse and organisation Scores of psychological morbidity were consistently lower in patients offered support from breast care nurse alone compared with the other groups , which were similar to each other Psychological support from an experienced breast care nurse can reduce psychological morbidity in patients undergoing surgery for breast BACKGROUND The study aim ed to improve continuity of care for patients undergoing major gynaecological surgery , by increasing their general practitioners ' contact with the hospital and providing a comprehensive discharge summary . METHODS Prospect i ve r and omised study of 200 patients admitted to a gynaecological oncology ward , and their GPs . Visits and telephone calls by GPs to hospital during their patients ' admission were measured , with and without invitation and offer of payment for contact . A discharge summary was distributed . Postdischarge question naires surveyed patient satisfaction with care , confidence in future management by the GPs , and GP confidence in continuing patient care . RESULTS Significant increases in contact rates by the GPs followed invitation . The discharge summary was not effectively distributed . No significant differences in patient satisfaction and confidence in future management by their GPs were found . General practitioners valued hospital contact most in meeting their patients ' needs for information . CONCLUSION Personal invitation increases GP contact with hospitals . While no statistically significant improvements in patient satisfaction or GP confidence were shown , the data suggested that GPs value contact to meet patient information needs PURPOSE This r and omized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with st and ard care in decreasing pain intensity scores , increasing appropriate analgesic prescriptions , and increasing analgesic intake in oncology out patients with pain from bone metastasis . PATIENTS AND METHODS Patients were r and omly assigned to the PRO-SELF intervention ( n = 93 ) or st and ard care ( n = 81 ) . Patients in the st and ard care arm were seen by a research nurse three times and were called three times by phone between the home visits . PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention , were taught how to use a pillbox , and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions . Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management . RESULTS Pain intensity scores decreased significantly from baseline ( all P < .0001 ) in the PRO-SELF group ( ie , least pain , 28.4 % ; average pain , 32.5 % ; and worst pain , 27.0 % ) compared with the st and ard care group ( ie , least increased by 14.6 % , average increased by 1.9 % , and worst decreased by 1.2 % ) . The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3 % to 37.0 % ( P = .008 ) compared with a change from 29.6 % to 32.5 % in the st and ard care group . CONCLUSION The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain BACKGROUND Population trends in aging and improved cancer survival are likely to result in increased cancer prevalence in the United States , but few estimates of the burden of illness among cancer survivors are currently available . The purpose of this study was to estimate the burden of illness in cancer survivors in a national , population -based sample . METHODS A total of 1823 cancer survivors and 5469 age- , sex- , and educational attainment-matched control subjects were identified from the 2000 National Health Interview Survey . Multiple measures of burden , including utility , a summary measure of health , and days lost from work , were compared using two-sided tests of statistical significance for the two groups overall and for subgroups stratified by tumor site and time since diagnosis . RESULTS Compared with matched control subjects , cancer survivors had poorer outcomes across all burden measures ( P<.01 ) . Cancer survivors had lower utility values ( 0.74 versus 0.80 ; P<.001 ) and higher levels of lost productivity and were more likely to report their health as fair or poor ( 31.0 % versus 17.9 % ; P<.001 ) than matched control subjects . Cancer survivors reported statistically significantly higher burden than did control subjects across tumor sites and across time since diagnosis ( i.e. , within the past year , 2 - 5 years , 6 - 10 years , and > or = 11 years for the majority of measures . CONCLUSIONS Cancer survivors have poorer health outcomes than do similar individuals without cancer across multiple burden measures . These decrements are consistent across tumor sites and are found in patients many years following reported diagnosis . Improved measurement of long-term burden of illness will be important for future prospect i ve research The dem and for palliative care is increasing , yet there are few data on the best models of care nor well-vali date d interventions that translate current evidence into clinical practice . Supporting multidisciplinary patient-centered palliative care while successfully conducting a large clinical trial is a challenge . The Palliative Care Trial ( PCT ) is a pragmatic 2 x 2 x 2 factorial cluster r and omized controlled trial that tests the ability of educational outreach visiting and case conferencing to improve patient-based outcomes such as performance status and pain intensity . Four hundred sixty-one consenting patients and their general practitioners ( GPs ) were r and omized to the following : ( 1 ) GP educational outreach visiting versus usual care , ( 2 ) Structured patient and caregiver educational outreach visiting versus usual care and ( 3 ) A coordinated palliative care model of case conferencing versus the st and ard model of palliative care in Adelaide , South Australia ( 3:1 r and omization ) . Main outcome measures included patient functional status over time , pain intensity , and re source utilization . Participants were followed longitudinally until death or November 30 , 2004 . The interventions are aim ed at translating current evidence into clinical practice and there was particular attention in the trial 's design to addressing common pitfalls for clinical studies in palliative care . Given the need for evidence about optimal interventions and service delivery models that improve the care of people with life-limiting illness , the results of this rigorous , high quality clinical trial will inform practice . Initial results are expected in mid 2005 End-of-life care must be informed by method ologically rigorous , high- quality research , but well-documented barriers make the conduct of palliative care clinical trials difficult . With careful consideration to study design and procedures , these barriers are surmountable . This paper discusses the approach used in a large scale , r and omised , controlled trial of service-based interventions in a regional palliative care service in South Australia , and the impact of this trial on palliative care research more broadly , the changes to the service in which it was conducted , and on health policy beyond palliative care . The Palliative Care Trial evaluated three interventions in a 2 × 2 × 2 factorial cluster r and omised design : case conferences , general practitioner education , and patient education . Main outcomes were performance status , pain intensity , and re source utilisation . A total of 461 patients were enrolled in the study . Pre- study planning and piloting is crucial , and accurately estimated withdrawal and death rates in the study . Other study design elements that facilitated this research included assessment of three interventions at one time , a dedicated recruitment role , a single clinical triage point , embedding data collection into routine clinical assessment s , and meaningful outcome measures . Recruitment and retention of participants is possible if barriers are systematic ally identified and addressed . This study challenged and developed the research culture within our clinical team and subsequently translated into further research Although health care in The Netherl and s is of a high quality with strong emphasis on primary care and high accessibility to hospital care , care deficits may arise in patients with chronic complex health problems who need the attention of several caregivers . Because no regular coordinating centre or person exists , coordination of care may be deficient leading to a poor continuity of care . This may be particularly true for those patients being cared for by both primary and hospital care teams , as is the case for most terminal cancer patients . Therefore , a transmural home care intervention programme for terminal cancer patients was introduced which intended to optimize coordination of care and thereby improve continuity of care . This quasi-experimental study investigated the effects of this intervention ( intervention group 79 patients ) on indicators of coordination and continuity of care . When compared to st and ard care ( control group 37 patients ) moderate positive effects ( mainly for the nursing disciplines ) on the various indicators of coordination and continuity of care by the transmural home care intervention programme were found . Future prospect i ve studies are needed to further eluci date the effects of transmural care on these aspects of care The purpose of this study was to describe the difficulties with pain management that patients and family caregivers bring to a nurse 's attention during a teaching and coaching intervention . Data were obtained from audiotaped and transcribed interactions between intervention nurses and patients ( n = 52 ) and their family caregivers ( n = 33 ) who were participating in a r and omized clinical trial of a nursing intervention called the PRO-SELF Copyright Pain Control Program . Using qualitative content analysis , we found that patients had difficulty in seven areas when they attempted to put a pain management regimen into practice , namely : obtaining the prescribed medication(s ) , accessing information , tailoring prescribed regimens to meet individual needs , managing side effects , cognitively processing information , managing new or unusual pain , and managing multiple symptoms simultaneously . The findings from this study suggest that the provision of information about cancer pain management to patients and their family caregivers is not sufficient to improve pain control in the home care setting . Patients and their family caregivers require ongoing assistance with problem-solving to optimize their pain management regimen 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 PURPOSE : To determine the effectiveness of a clinical - practice intervention in improving the control of pain in out patients with cancer . METHOD : Between July 5 and September 30 , 1995 , a r and omized , controlled trial of 510 cancer out patients and 13 oncologists was conducted at 23 clinics in Indiana . All the patients completed assessment s of their pain , their pain regimens , and the degrees of relief received ; they were surveyed again by mail four weeks after their clinic visits . The intervention group 's clinical charts contained a summary of the completed pain scales ; the oncologists who treated these patients were instructed to review the summary sheet prior to an evaluation . This summary was not available for the oncologists treating the patients in the control group . Each patient 's pain management index ( PMI ) was calculated : the patient 's pain medication level was rated on a scale of 0 to 3 ; the patients 's pain level was rated on a scale of 0 to 3 and then subtracted from the first rating . A negative PMI was interpreted as representing insufficient treatment . Data were analyzed with several statistical tests . RESULTS : In all , only 320 patients who reported cancer-related pain were used in the analysis : 160 to 260 in the control group and 160 of 250 in the intervention group . The groups were similar with respect to demographics , cancer sites , and performance status . A significant difference ( p = .0162 ) in the physicians ' prescription patterns was found . In the control group , prescriptions for 86 % of the patients did not change , with no decrease in analgesic prescriptions ; for 14 % of the patients analgesic prescriptions increased . In the intervention group , analgesic prescriptions changed for 25 % of the patients , decreasing for 5 % and increasing for 20 % . A decrease in the incidence of pain described as more than life 's usual aches and pains was found for the intervention group ( p = .05 ) . No significant difference was found between the groups for the patients undertreated for pain , as measured by PMIs . CONCLUSION : Although analgesic regimens were altered significantly when the physicians understood more about the patient 's pain , cancer pain management remains a complex problem . Future studies should focus on the long-term systematic incorporation of simple pain- assessment tools into daily outpatient oncology practice s as well as on innovative ways to address other aspects of managing cancer pain The main aim of this study was to examine similarities and differences in satisfaction with care between 112 family members who were close to patients who had participated in an intervention with a comprehensive palliative care program and the 68 family members in a conventional care program ( controls ) . The FAMCARE Scale measured satisfaction with care at one month after the time of death . The majority of respondents reported high satisfaction with care . The respondents related to the patients in the intervention group reported significantly higher satisfaction with care than the respondents related to the patients in the control group . This difference remained unchanged after controlling for a range of other relevant factors : relationship to the deceased , sex and age of the respondent , sex and age of the patient , time since inclusion in the study , and place of death Newly diagnosed cancer patients ( n=527 ) were r and omised to intensified primary care or a control group . Intensified primary care comprised routines to improve general practitioners ' and home care nurses ' possibilities to support and monitor patients , i.e. increased information from specialist care , education and supervision in cancer care . The aims of this paper are to evaluate the effects of intensified primary care on cancer patients ' home care nurse contacts , and to study if patients ' use of home care services 6 months after diagnosis can be predicted . The intervention result ed in a marked increase of follow-up contacts . About 90 % of intensified primary care patients reported such contacts , compared to 26 % of control patients . The results indicate that st and ard care does not routinely include follow-up contacts , not even for the oldest ( 80 + years ) or those with advanced disease . Only 27 % and 36 % of these groups of control patients reported follow-ups . Logistic regression analysis identified intensified primary care as the strongest predictor for reporting a continuing contact 6 months after diagnosis . Intensified primary care patients were 14 times more likely than controls to report a such contact . The strongest predictor of a continuing contact in the intensified primary care group was high age . Patients with advanced disease were more likely than patients with non-advanced disease to report a continuing contact , and living in a rural district was positively associated with reporting a contact . A majority of the patients ( 70 % ) assessed the time for the first contact as the ' right time ' and estimated that the nurse gave expected support to a very large or large extent ( 67 % ) . The results suggest that routines like those implemented through intensified primary care may be an effective strategy to increase the accessibility and continuity of care , especially for elderly people and for patients with a need for long-term contacts & NA ; There is no ‘ gold st and ard ’ to assess the adequacy of pain treatment in cancer patients . The purpose of the study is to explore the Amsterdam Pain Management Index , a newly design ed measure to evaluate the adequacy of cancer pain treatment , and to compare it with eight frequently used outcome measures . The Amsterdam Pain Management Index compares patients ’ Present Pain Intensity , Average Pain Intensity , and Worst Pain Intensity with a composite score of analgesics used , while correcting for what a patient considers as a tolerable level of pain . The eight frequently used outcome measure consisted of three Pain Intensity Markers , the Pain Relief Scale , the Patient Satisfaction Scale , and three Pain Management Indexes . In a r and omized controlled trial , 313 cancer patients with a pain duration of at least 1 month were included and followed‐up three times until 2 months postdischarge at home . The experimental group received a Pain Education Program , consisting of tailored pain information and instruction . Results showed that , except for the three Pain Management Indexes , the agreement between the measures was very low to moderate . The test of known‐groups comparisons and equivalence between groups indicated that the Amsterdam Pain Management Index showed promising results . The Pain Intensity Markers and the Pain Relief Scale were limited in discriminating between groups , while the Patient Satisfaction Scale showed no differences between patient groups . Although it was possible for the Pain Management Indexes to distinguish between patient groups , the differences were not in the expected direction . The ability of the outcome measures to detect changes over time was clearly demonstrated by all outcome measures . Effects of the intervention were only found for the Amsterdam Pain Management Index and patients ’ Substantial Worst Pain score . Although support was provided for the use of the Amsterdam Pain Management Index , more research is warranted PURPOSE Most women with breast cancer are diagnosed at an early stage and more than 80 % will be long-term survivors . Routine follow-up marks the transition from intensive treatment to survivorship . It is usual practice for routine follow-up to take place in specialist clinics . This study tested the hypothesis that follow-up by the patient 's family physician is a safe and acceptable alternative to specialist follow-up . PATIENTS AND METHODS A multicenter , r and omized , controlled trial was conducted involving 968 patients with early-stage breast cancer who had completed adjuvant treatment , were disease free , and were between 9 and 15 months after diagnosis . Patients may have continued receiving adjuvant hormonal therapy . Patients were r and omly allocated to follow-up in the cancer center according to usual practice ( CC group ) or follow-up from their own family physician ( FP group ) . The primary outcome was the rate of recurrence-related serious clinical events ( SCEs ) . The secondary outcome was health-related quality of life ( HRQL ) . RESULTS In the FP group , there were 54 recurrences ( 11.2 % ) and 29 deaths ( 6.0 % ) . In the CC group , there were 64 recurrences ( 13.2 % ) and 30 deaths ( 6.2 % ) . In the FP group , 17 patients ( 3.5 % ) compared with 18 patients ( 3.7 % ) in the CC group experienced an SCE ( 0.19 % difference ; 95 % CI , -2.26 % to 2.65 % ) . No statistically significant differences ( P < .05 ) were detected between groups on any of the HRQL question naires . CONCLUSION Breast cancer patients can be offered follow-up by their family physician without concern that important recurrence-related SCEs will occur more frequently or that HRQL will be negatively affected Treatments for clinical ly localized prostate carcinoma are accompanied by sexual , urinary , and bowel dysfunction and other sequelae that can result in significant distress and reduced well being . Methods capable of improving quality of life are needed that can be integrated into clinical practice . To address this need , a nurse‐driven , cancer care intervention was developed and tested |
11,712 | 29,106,711 | Catheter exchange was reported to be superior to sheath disruption with respect to catheter survival ( 30 participants : MD 213.00 days , 95 % CI 205.70 to 220.30).There is insufficient evidence to suggest any specific intervention is superior in terms of ensuring either dialysis adequacy or reduced risk of adverse events .
AUTHORS ' CONCLUSIONS Thrombolysis , fibrin sheath disruption and over-the-wire catheter exchange are effective and appropriate therapies for immediately restoring catheter patency in dysfunctional cuffed and tunnelled HD catheters .
On current data there is no evidence to support physical intervention over the use of pharmaceutical agents in the acute setting .
Pharmacological interventions appear to have a bridging role and long-term catheter survival may be improved by fibrin sheath disruption and is probably superior following catheter exchange .
There is no evidence favouring any of these approaches with respect to dialysis adequacy or risk of adverse events . | BACKGROUND Adequate haemodialysis ( HD ) in people with end-stage kidney disease ( ESKD ) is reliant upon establishment of vascular access , which may consist of arteriovenous fistula , arteriovenous graft , or central venous catheters ( CVC ) .
Although discouraged due to high rates of infectious and thrombotic complications as well as technical issues that limit their life span , CVC have the significant advantage of being immediately usable and are the only means of vascular access in a significant number of patients .
Previous studies have established the role of thrombolytic agents ( TLA ) in the prevention of catheter malfunction .
Systematic review of different thrombolytic agents has also identified their utility in restoration of catheter patency following catheter malfunction .
To date the use and efficacy of fibrin sheath stripping and catheter exchange have not been evaluated against thrombolytic agents .
OBJECTIVES This review aim ed to evaluate the benefits and harms of TLA , preparations , doses and administration as well as fibrin-sheath stripping , over-the-wire catheter exchange or any other intervention proposed for management of tunnelled CVC malfunction in patients with ESKD on HD . | Introduction Thrombosis of tunneled central venous catheters ( CVC ) in hemodialysis ( HD ) patients is common and it can lead to the elimination of vascular sites . To compare the efficacy of alteplase vs. urokinase in reestablishing adequate blood flow through completely occluded vascular catheters . Methods In this r and omized study , patients with completely occluded tunneled HD catheters received 40 minutes intracatheter dwell with alteplase ( 1 mg/mL ) or urokinase ( 5000 IU/mL ) . Primary endpoint was the proportion of patients with occluded catheters achieving post-thrombolytic blood flow of ≥250 mL/min . Safety endpoints included the incidence of hemorrhagic and infectious complications . Findings Eligible adult patients ( n = 100 ) were treated with alteplase ( n = 44 ) or urokinase ( n = 56 ) . The two groups were similar in gender ( male : 51.8 % vs. 56.8 % , P = 0.35 ) , age ( 60 ± 12 vs. 59 ± 13 years , P = 0.71 ) , time on dialysis ( 678 ± 203 vs. 548 ± 189 days , P = 0.77 ) , diabetes and cardiovascular disease ( 55.6 % vs. 70.4 % , P = 0.08 and 17.8 % vs. 22.7 % , P = 0.38 , respectively ) , jugular vein as main vascular access ( 54.8 % vs. 62.5 % , P = 0.57 ) , and time of CVC ( 278 ± 63 vs. 218 ± 59 days , P = 0.67 ) . Primary success with alteplase and urokinase occurred in 42/44 ( 95 % ) vs. 46/56 ( 82 % ) , P = 0.06 . Success was not achieved after the second dose of alteplase and urokinase in 1 and 7 cases , respectively ( 2 % vs. 12 % , P = 0.075 ) . Serious adverse effects were not observed in both groups . There was no difference between the two groups in infectious complications ( P = 0.94 ) . Discussion Alteplase and urokinase are effective thrombolytic agents for restoring HD catheter patency . Our study has revealed a likely slight superiority of alteplase over urokinase for unblocking central lines , but which has enrolled too few patients to be able to detect a difference of this size BACKGROUND The effectiveness of various solutions instilled into the central venous catheter lumens after each hemodialysis session ( catheter locking solutions ) to decrease the risk of catheter malfunction and bacteremia in patients undergoing hemodialysis is unknown . METHODS We r and omly assigned 225 patients undergoing long-term hemodialysis in whom a central venous catheter had been newly inserted to a catheter-locking regimen of heparin ( 5000 U per milliliter ) three times per week or recombinant tissue plasminogen activator ( rt-PA ) ( 1 mg in each lumen ) substituted for heparin at the midweek session ( with heparin used in the other two sessions ) . The primary outcome was catheter malfunction , and the secondary outcome was catheter-related bacteremia . The treatment period was 6 months ; treatment assignments were concealed from the patients , investigators , and trial personnel . RESULTS A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only ( 34.8 % ) and 22 of the 110 patients assigned to rt-PA (20.0%)--an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly ( hazard ratio , 1.91 ; 95 % confidence interval [ CI ] , 1.13 to 3.22 ; P = 0.02 ) . Catheter-related bacteremia occurred in 15 patients ( 13.0 % ) assigned to heparin only , as compared with 5 ( 4.5 % ) assigned to rt-PA ( corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups , respectively ; P = 0.02 ) . The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 ( hazard ratio , 3.30 ; 95 % CI , 1.18 to 9.22 ; P = 0.02 ) . The risk of adverse events , including bleeding , was similar in the two groups . CONCLUSIONS The use of rt-PA instead of heparin once weekly , as compared with the use of heparin three times a week , as a locking solution for central venous catheters significantly reduced the incidence of catheter malfunction and bacteremia . ( Current Controlled Trials number , IS RCT N35253449 . ) Objective : To compare dialysis catheter function according to catheter site . Design : Multicenter , open , r and omized controlled trial . Setting : Nine university-affiliated hospitals and three general hospitals in France . Patients : Seven hundred thirty-six patients in intensive care units who required a first venous catheterization to perform either intermittent hemodialysis ( 470 patients with 1275 sessions ) or continuous renal replacement therapy ( 266 patients with 1003 days ) . Intervention : Patients r and omly received either femoral ( n = 370 ) or jugular ( n = 366 ) catheterization . For the jugular site , right-side position ( n = 252 ) was recommended . Measurements and Main Results : Time to catheter ablation for dysfunction , urea reduction ratio ( intermittent hemodialysis ) , and downtime ( continuous renal replacement therapy ) were assessed for all participants and evaluated by r and omly assigned catheterization site ( femoral or jugular ) . Baseline demography and dialysis prescriptions were similar between the site arms . In modified intent-to-treat , catheter dysfunction occurred in 36 of 348 ( 10.3 % ) and 38 of 342 ( 11.1 % ) patients in the femoral and jugular groups , respectively . The risk of catheter dysfunction did not significantly differ between r and omized groups ( hazard ratio , 1.06 ; 95 % confidence interval , 0.67–1.68 ; p = .80 ) . Compared to the femoral site , the observed risk of dysfunction decreased in the right jugular position ( 15 of 226 ; 6.6 % ; adjusted hazard ratio , 0.58 ; 95 % confidence interval , 0.31–1.07 ; p = .09 ) and significantly increased in the left jugular position ( 23 of 118 ; 19.5 % ; adjusted hazard ratio , 1.89 ; 95 % confidence interval , 1.12–3.21 ; p < .02 ) . The postintermittent hemodialysis mean urea reduction ratio per session was 50.8 % ( st and ard deviation , 16.1 ) for femoral vs. 52.8 % ( st and ard deviation , 15.8 ) for jugular ( p = .30 ) sites , and the median continuous renal replacement therapy downtime per patient-day was 1.17 hrs ( interquartile range , 0.75–1.50 ) for both sites ( p = .98 ) . Conclusions : In terms of catheter dysfunction and dialysis performance among critically ill adults requiring acute renal replacement therapy , jugular site did not significantly outperform femoral site placement . ( Crit Care Med 2010 ; 38:1118–1125 PURPOSE To compare the effectiveness of two treatments for tunneled hemodialysis catheter malfunction : percutaneous fibrin sheath stripping ( PFSS ) and over-the-wire catheter exchange ( EX ) . MATERIAL S AND METHODS Adult patients with poorly functioning tunneled hemodialysis catheters ( flow rates < 200 mL/min ) were r and omly assigned to receive either PFSS or EX . Over the course of 20 months , 30 patients ( 37 encounters ) referred to a single institution met the inclusion criteria and consented to participate . PFSS employed transcatheter snares via femoral vein puncture , whereas EX was performed over a guide wire with use of fluoroscopic guidance . Patients were followed up to determine the duration of continued adequate hemodialysis via manipulated catheters for up to 4 months ( primary outcome measure ) . RESULTS Overall technical success rate was 97 % . Mean catheter patency for the PFSS group was 24.5 + /- 29.3 days , and 52.2 + /- 43 days for the EX group ( P < .0001 ) . After EX , patency rates at 1 , 2 , 3 , and 4 months were 71 % , 33 % , 27 % , and 27 % , compared to 31 % , 16 % , 7 % , and 0 % after PFSS ( P = .04 , logrank test ) . Exchanged catheters were significantly more likely to be patent for as long as 4 months ( 23 % versus 0 % ; P < .05 , chi2 test ) . CONCLUSIONS Malfunctioning tunneled hemodialysis catheters treated by means of EX are significantly more likely to remain patent for up to 4 months than are those treated by means of PFSS . According to the results of this trial , PFSS should not be performed as a routine therapy for catheter malfunction Background . A well-functioning vascular access ( VA ) is essential to efficient dialysis therapy . Guidelines have been implemented improving care , yet access use varies widely across countries and VA complications remain a problem . This study took advantage of the unique opportunity to utilize data from the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) to examine international trends in VA use and trends in patient characteristics and practice s associated with VA use from 1996 to 2007 . DOPPS is a prospect i ve , observational study of haemodialysis ( HD ) practice s and patient outcomes at > 300 HD units from 12 countries and has collected data thus far from > 35 000 r and omly selected patients . Methods . VA data were collected for each patient at study entry ( 1996–2007 ) . Practice pattern data from the facility medical director , nurse manager and VA surgeon were also analysed . Results . Since 2005 , a native arteriovenous fistula ( AVF ) was used by 67–91 % of prevalent patients in Japan , Italy , Germany , France , Spain , the UK , Australia and New Zeal and , and 50–59 % in Belgium , Sweden and Canada . From 1996 to 2007 , AVF use rose from 24 % to 47 % in the USA but declined in Italy , Germany and Spain . Moreover , graft use fell by 50 % in the USA from 58 % use in 1996 to 28 % by 2007 . Across three phases of data collection , patients consistently were less likely to use an AVF versus other VA types if female , of older age , having greater body mass index , diabetes , peripheral vascular disease or recurrent cellulitis/gangrene . In addition , countries with a greater prevalence of diabetes in HD patients had a significantly lower percentage of patients using an AVF . Despite poorer outcomes for central vein catheters , catheter use rose 1.5- to 3-fold among prevalent patients in many countries from 1996 to 2007 , even among non-diabetic patients 18–70 years old . Furthermore , 58–73 % of patients new to end-stage renal disease ( ESRD ) used a catheter for the initiation of HD in five countries despite 60–79 % of patients having been seen by a nephrologist > 4 months prior to ESRD . Patients were significantly ( P < 0.05 ) less likely to start dialysis with a permanent VA if treated in a faciity that ( 1 ) had a longer time from referral to access surgery evaluation or from evaluation to access creation and ( 2 ) had longer time from access creation until first AVF cannulation . The median time from referral until access creation varied from 5–6 days in Italy , Japan and Germany to 40–43 days in the UK and Canada . Compared to patients using an AVF , patients with a catheter displayed significantly lower mean Kt/V levels . Conclusions . Most countries meet the contemporary National Kidney Foundation 's Kidney Disease Outcomes Quality Initiative goal for AVF use ; however , there is still a wide variation in VA preference . Delays between the creation and cannulation must be improved to enhance the chances of a future permanent VA . Native arteriovenous fistula is the VA of choice ensuring dialysis adequacy and better patient outcomes . Graft is , however , a better alternative than catheter for patients where the creation of an attempted AVF failed or could not be created for different reasons BACKGROUND AND OBJECTIVES Hemodialysis catheters are frequently complicated by dysfunction from fibrin sheaths . Previous studies of sheath disruption have method ologic limitations but suggest that the patency after disruption is short . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A r and omized , controlled , pilot trial was conducted to investigate the impact of angioplasty sheath disruption on catheter patency and function . Forty-seven long-term hemodialysis patients with secondary , refractory catheter dysfunction underwent guidewire exchange to replace their catheters . RESULTS Sheaths were present in 33 ( 70 % ) of the 47 patients . In 18 patients who were r and omly assigned to disruption , the median time to repeat dysfunction was 373 d compared with 97.5 d in patients who did not undergo disruption ( P = 0.22 ) , and the median time to repeat catheter exchange was 411 and 198 d , respectively ( P = 0.17 ) . Mean blood flow ( 340 versus 329 ml/min ; P < 0.001 ) and urea reduction ratio ( 72 versus 66 % ; P < 0.001 ) were higher in the disruption group . Fourteen patients had no sheaths , and their median times to repeat dysfunction and repeat exchange were 849 and 879 d , respectively . Patients with no sheaths had higher urea reduction ratio ( 73 versus 66 % ; P < 0.001 ) and a lower percentage of inadequate hemodialysis treatments ( 9.8 versus 27 % ; P = 0.01 ) and treatments that required thrombolytics ( 1.8 versus 5.0 % ; P = 0.03 ) than patients with sheaths that were not disrupted . CONCLUSIONS Disrupting sheaths by angioplasty balloon results in durable catheter patency and modestly improves blood flow and clearance over the duration of catheter use BACKGROUND The optimal vascular access for chronic maintenance haemodialysis ( HD ) is the native arteriovenous fistula ( AVF ) . Vascular access practice patterns are reported for a Canadian cohort of patients from the Dialysis Outcomes and Practice Patterns Study ( DOPPS II ) . METHODS DOPPS II is a prospect i ve , observational study in 12 countries , including Canada . A representative r and om sample of 20 Canadian HD facilities and patients within those units were studied during 2002 - 2004 . Canadian results were compared with those found in Europe and the USA . RESULTS AVF use in Canadian prevalent ( 53 % ) and incident ( 26 % ) patients was lower than Canadian guidelines recommend ( 60 % ) , and lower than in Europe [ prevalent ( 74 % ) , incident ( 50 % ) ] . Despite 85 % of Canadian HD patients having seen a nephrologist for > 1 month prior to starting dialysis , central venous catheter use in Canada ( 33 % in prevalent patients , 70 % in incident patients ) was much higher than in Europe ( prevalent 18 % , incident 46 % ) and slightly higher than in the USA ( prevalent 25 % , incident 66 % ) . This pattern is contrary to the preferences of Canadian medical directors and vascular access surgeons . The typical time from referral until permanent vascular access creation is substantially longer in Canada ( 61.7 days ) than in Europe ( 29.4 days ) or the USA ( 16 days ) . This longer delay time and higher catheter use in Canada may be a consequence of the significantly lower number of access surgeons per 100 HD patients in Canada ( 2.9 ) compared with the USA ( 8.1 ) and Europe ( 4.6 ) . Furthermore , the median hours per week devoted to vascular access-related surgery per 100 patients is substantially lower in Canada ( 0.027 h ) compared with the USA ( 0.082 h ) and Europe ( 0.059 h ) . CONCLUSION These findings suggest that Canadian chronic HD patients often rely on central venous catheters for vascular access , despite their known association with numerous detrimental outcomes in HD . Nephrologists , vascular access surgeons , interventional radiologists , other physicians and health care funding bodies must be more broadly educated about the priority of AVF creation as the preferred vascular access for chronic HD patients . They must work together to secure both the human and financial re sources and other health care system enhancements to increase AVF creation rates in a timely manner AIMS Catheter-related thrombosis is a frequent complication of providing hemodialysis via central venous catheters . The primary aim of this study was to compare the efficacy of an alteplase " dwell " protocol over 30 minutes ( with an additional 90 minutes where necessary ) to a new 30 minute " push " protocol in restoring function to occluded hemodialysis catheters . METHODS This was a prospect i ve , r and omized , parallel arm , multicenter study . Participants included hemodialysis patients using central venous catheters for vascular access . A new alteplase push protocol was the intervention and was compared to an alteplase dwell protocol . The primary outcome of this study was the proportion of patients with pre-thrombolytic blood flows less than 200 ml/min achieving a post thrombolytic blood flow ≥ 300 ml/ min . Secondary outcomes included recovery of Kt/V and liters processed per hour at the hemodialysis session following the intervention , time from thrombolytic to future catheter interventions , and the presence of serious adverse events . RESULTS 82 patients were included in the intention-to-treat analysis . 65 % ( 28/43 ) of catheters receiving the dwell protocol achieved blood flow ≥ 300 ml/min compared to 82 % ( 32/39 ) in the push protocol . The difference was not statistically significant despite a 17 % separation in the point estimates , p = 0.84 . A non-significant result may have been associated with an inability to enrol the required a priori sample size . Kt/V , liters processed per hour and time to next catheter event were not significantly different . There were no serious adverse events attributed to the study medication . CONCLUSIONS The alteplase push protocol was effective and safe for managing dysfunctional hemodialysis catheters and was more practical than a 2 h dwell BACKGROUND Despite the US Dialysis Outcome Quality Initiative ) DOQI ( guidelines , for various reasons , increasing numbers of end-stage renal disease patients are becoming dependent on cuffed haemodialysis catheters ( HCs ) for chronic haemodialysis access . Their use is complicated by frequent failure due to thrombosis and catheter-related sepsis . In our unit , all HCs are put in place by the radiology department . METHODS In a prospect i ve study we looked at the outcome of all HCs over a three-year period , during which time 573 consecutive HCs were placed in 336 patients . Each line was followed individually until it was removed or until the end of the study . RESULTS In a survival analysis of those HCs removed following HC failure , HC half-life was 312 days and one-year HC survival was 47.5 % . The most frequent indications for HC removal were non-function ( 36.6 % ) , clinical suspicion of line sepsis ( 16.4 % ) and patient death ( 14.4 % ) . Using a Cox proportional hazards model , catheter number in a given patient and the presence of diabetes mellitus were found to be independent predictors of HC failure . The total incidence of HC-related sepsis was 1.3 episodes/1000 catheter days . The probability of developing bacteraemic HC-related sepsis was 27.5 % at one year . CONCLUSIONS Less than half of the HCs were removed electively because of availability of a more permanent mode of renal replacement , thereby illustrating the level of dependence that has developed on them as permanent access . Consequently , their limitations ( infection and malfunction ) are placing an ever increasing burden on the healthcare services Bacterial overgrowth in the inner layer of the catheter as a biofilm is highly encountered in routine medical care , and it may occur in a few days after inserting a catheter as an access in hemodialysis ( HD ) patients . Catheter-induced bacteremia is often due to the development of biofilms . Locking catheters with antimicrobial agents is an effective way of reducing the risk of catheter-related infection . In a controlled , r and omized clinical trial , 64 chronic HD patients ( 32 men and 32 women with a mean age of 57.5 ± 15.6 years ) were divided into case and control groups , with 32 patients in each group . The case group received systemic antibiotic and a lock of catheters with 60 % ethanol and the control group received only systemic antibiotic . The results were evaluated after three weeks of treatment . The success rate of clearing infection in group A ( 29 patients ) and group B ( 18 patients ) was 90.6 % and 56.2 % , respectively ( P = 0.002 ) . We conclude that the significant difference in the success rate of clearing catheter infection in HD patients is due to the use of 60 % ethanol-lock along with antibiotic therapy , and suggest this for routine use The native arteriovenous fistula ( AVF ) is the preferred vascular access because of its longevity and its lower rates of infection and intervention . Recent studies suggest that the AVF may offer a survival advantage . Because these data were derived from observational studies , they are prone to potential bias . The use of propensity scores offers an additional method to reduce bias result ing from nonr and omized treatment assignment . Adult ( age 18 yr or more ) patients who commenced hemodialysis in Australia and New Zeal and on April 1 , 1999 , until March 31 , 2002 , were studied by using the Australian and New Zeal and Dialysis and Transplant Association ( ANZ DATA ) Registry . Cox regression was used to determine the effect of access type on total mortality . Propensity scores were calculated and used both as a controlling variable in the multivariable model and to construct matched cohorts . The catheter analysis was stratified by dialysis duration at entry to ANZ DATA to satisfy the proportional-hazard assumption . There were 612 deaths in 3749 patients ( median follow-up , 1.07 yr ) . After adjustment for confounding factors and propensity scores , catheter use was predictive of mortality . Patients with arteriovenous grafts ( AVG ) also had a significantly increased risk of death . Effect estimates were also consistent in the smaller propensity score-matched cohorts . Both AVG and catheter use in incident hemodialysis patients are associated with significant excess of total mortality . Reducing catheter use and increasing the proportion of patients commencing hemodialysis with a mature AVF remain important clinical objectives Although endogenous fistulae and grafts are preferred for permanent hemodialysis access , central venous catheters are often required for varying intervals when creating permanent access is not feasible . The prospect i ve experience with 118 catheters in over a 3.5-yr period is reported ; 93 ( 79 % ) were placed by percutaneous techniques , and 25 ( 21 % ) were placed by operative techniques . Seventy seven catheters ( 65 % ) were placed in the subclavian vein , 36 ( 31 % ) were placed in the internal jugular vein ( usually right side ) , and 5 ( 4 % ) were placed in the femoral vein . Early postplacement complications were infrequent . Catheter function at last local follow-up ranged from several days to nearly 2 yr , averaging approximately 3 mo , even though many patients returned to their referring centers with a functioning catheter after only a short follow-up . Actuarial survival for percutaneously placed catheters was approximately 60 % at 6 mo and 30 % at 12 mo . Catheter failure occurred in 36 % of cases , equally divided between malfunction ( thrombosis refractory to fibrinolysis , extrusion , kinking , or related event ) and infection with septicemia requiring removal . Such failure was not more frequent after percutaneous placement than after operative placement . Failure due to mechanical malfunction , but not that due to infection , tended to be less frequent among catheters placed in the internal jugular vein than among catheters placed in the subclavian vein . Finally , infection with septicemia involved 22 % of all catheters and occurred at an average cumulated rate of approximately one infection per patient-year . Coagulase-positive staphylococcus was the most common organism isolated . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To explore the clinical efficacy and safety of the early use of urokinase in the prevention and treatment on tunneled hemodialysis catheter related fibrin sheaths . METHODS Thirty-eight hemodialysis patients with tunneled central venous catheter and good catheter function were r and omly divided into experimental group and control group . Urokinase was given after 3 days of indwelling catheter in the experimental group and after the onset of catheter dysfunction in the control group . The catheter function , mean blood flow and venous pressure of dialysis , coagulation , and side effects in the two groups were observed for 6 months . RESULTS The rates of catheter dysfunction on the arterial side were 0.65 % and 2.71 % in the experimental group and control group , respectively ( P<0.05 ) , with catheter dysfunction rates on the vein side of 0.92 % and 2.41 % , respectively ( P<0.05 ) . Catheter dysfunction occurred for the first time at 87.9 ± 24.1 days in the experimental group , and at 31.3 ± 11.5 days in the control group ( P<0.05 ) . The mean blood flow showed no significant difference between the two groups at 1 month after tube insertion ( P>0.05 ) , but was higher in the experimental group at 3 and 6 months after the tube insertion ( P<0.05 ) . The mean venous pressure in two groups was similar 1 and 3 months after tube insertion ( P>0.05 ) , but was significantly lower in the experimental group at 6 months ( P<0.05 ) . Compared with control group , the experimental group showed significantly prolonged prothrombin time ( P<0.05 ) but similar rest coagulation parameters . No serious drug-related side effects occurred in these two groups . CONCLUSION Early use of urokinase is safe and effective for prevention and treatment of tunneled hemodialysis catheter-related fibrin sheaths with minimal side effects BACKGROUND The management of tunneled cuffed catheter (TCC)-associated bacteremias varies among nephrologists . To determine whether patient outcomes after TCC-associated bacteremia can be improved by modifying the management model , we performed an interventional controlled trial comparing a collaborative team model , intervention ( INT ) , with the usual physician-managed model , usual care ( UC ) . METHODS INT consisted of an infection manager who worked closely with nephrologists and dialysis staff and made treatment recommendations using the available published guidelines at the time of the study 's conception ( Dialysis Outcomes Quality Initiative guideline no. 26 , 1997 ) and additional literature -based recommendations . Nephrologists made the final treatment decisions . TCC-associated bacteremia was physician managed in the UC group . RESULTS Two hundred twenty-three episodes of TCC-associated bacteremia occurred in 7 outpatient hemodialysis units during the 2-year study period . The INT was associated with a significantly lower incidence of recurrent bacteremia with the same organism ( INT , 6 % versus UC , 18 % ; odds ratio , 0.28 ; 95 % confidence interval , 0.09 to 0.8 ; P = 0.015 ) and death from sepsis ( INT , 0 % versus UC , 6 % ; P < 0.02 ) . In INT units , there was a 45 % decrease in the practice of TCC salvage ( TCC not removed ; P = 0.05 ) . Antibiotic prescribing practice s ( final antibiotic selection , dose , and duration of therapy ) were improved in INT units compared with UC units . By using multivariate analysis , the INT was associated with a 73 % decrease in the combined outcome of recurrent bacteremia or septic death ( P < 0.02 ) . CONCLUSION Implementation of a collaborative team model for the management of TCC-associated bacteremic episodes is associated with improvement in the quality of heath care delivery and patient outcomes BACKGROUND Hemodialysis catheter dysfunction ( CD ) is the inability to attain adequate blood pump speeds ( BPS ) and is attributed to thrombus or catheter malposition ; alteplase ( TPA ) is often given in a variety of dwell times to treat CD . The purpose of this study was to determine if TPA dwell time affects short- or long-term catheter patency rates . METHODS Sixty hemodialysis ( HD ) patients with CD , as defined by BPS of < 250 mL/min , were r and omized to receive either 1- or > 48-hr ( to subsequent HD run ) TPA dwell . The primary outcomes were catheter patency ( BPS of > 250 mL/min ) at the subsequent HD run and catheter patency at 2 weeks . The secondary outcome was the time from study entry to the next catheter intervention ( including subsequent TPA installation ) . RESULTS After TPA installation , a 78 % overall catheter patency rate was observed at the subsequent HD run , falling to 48 % patency at 2 weeks . There is no statistically significant difference between the short and long TPA dwell groups for catheter patency at the subsequent HD run ( 76.9 % vs. 79.4 % ) or at 2 weeks ( 42.3 % vs. 52.9 % ) . Multivariate analysis demonstrates that the use of TPA on two or more previous occasions is a predictor of TPA failure both at the subsequent HD run and at 2 weeks . TPA installation achieves a median catheter function time of only 14 days , after which CD reoccurs . CONCLUSION This study demonstrates that although patency for the next HD run can be achieved with either short or long TPA dwell , neither is reliable in terms of long-term patency . Strategies that employ TPA for CD are temporary and allow a 2-week window during which more definitive therapies for HD access should be sought BACKGROUND Minidose warfarin ( 1 mg/day ) has been associated with a 74 % reduction in the thrombosis rate of central venous catheters used in oncology patients . To determine the efficacy of minidose warfarin on late malfunction caused by thrombosis or fibrin sheath formation in tunneled , cuffed catheters ( TCC ) used for hemodialysis ( HD ) , we performed a r and omized , placebo-controlled trial . METHODS One hundred five chronic HD patients with TCCs were initially r and omized . Of these , 85 ( warfarin 41 and placebo 44 ) completed the first two weeks of the protocol and were followed for the first year of TCC life or until TCC removal . RESULTS Sixteen TCCs failed with late TCC malfunction , eight in each group . In a multivariate analysis , there was no significant effect of warfarin on thrombosis-free TCC survival or time to the first urokinase ( UK ) instillation for incipient thrombosis . The presence of a low hemoglobin ( Hgb ; < 10.5 g/dL ) or a low international normalized ratio ( INR ; < 1.00 ) was significantly associated with a higher risk of late TCC malfunction ( RR 5.2 and 4.0 , respectively ) , a higher risk of incipient TCC thrombosis requiring UK ( RR 2.0 and 2.8 , respectively ) , and higher rates of UK dosing . Diabetics had a 3.6-fold higher risk of late TCC malfunction and a twofold higher risk of incipient thrombosis requiring UK , although these findings were not statistically significant . Aspirin use , race , age , number of hospitalizations , erythropoietin dose , intradialytic heparin dose , serum albumin , and the number of episodes of TCC-associated infection were not significantly associated with late TCC malfunction . CONCLUSIONS Thrombosis prophylaxis using fixed minidose warfarin is not efficacious in TCCs used for HD . However , the present data suggest improved TCC survival in patients with an INR > 1.00 . Patients with diabetes and those with a low Hgb or INR have a higher risk of late TCC malfunction Background Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters ( TCCs ) for hemodialysis ( HD ) . The aim of the study was to assess the efficacy of early warfarin administration , after TCC placement , in comparison to its administration after the first thrombosis or malfunction event of the TCC . Patients and methods One hundred and forty-four chronic dialysis patients , who underwent TCC placement between June 2001 and June 2005 , were r and omized into two groups : 81 patients , group A , started oral anticoagulation 12 hr after the TCC placement ( target international normalized ratio ( INR ) 1.8–2.5 ) , in association with ticlopidine 250 mg/die ; 63 patients , group B , started warfarin after the first thrombosis/malfunction episode ( target INR 1.8–2.5 ) in association with ticlopidine 250 mg/die . The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period , after TCC placement , in terms of : a ) the number of patients with thrombotic-malfunction events ; b ) the number of thrombotic-malfunction events with urokinase infusion ( events/patient/year ) ; c ) intradialytic blood flow rate ( BFR , ml/min ) ; d ) negative blood pressure ( BP ) from the arterial line of the TCC ( AP , mmHg ) ; e ) positive BP , in the extracorporeal circuit from the venous line ( VP , mmHg ) ; and f ) bleeding complications . Results Ten patients ( 12 % ) in group A showed TCC thrombosis/malfunction vs. 33 patients ( 52 % ) in group B ( p<0.01 ) . In group A , 0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B ( p<0.001 ) were observed . BFR was respectively 305 ± 34 vs. 246 ± 42 ml/min ( p<0.001 ) . AP was –124 ± 13 in group A vs. –174 ± 21 mmHg in group B ( p<0.05 ) . VP was 112 ± 28 in group A vs. 168 ± 41 mmHg in group B ( p<0.05 ) . No patient showed any bleeding events . Conclusions Early warfarin therapy allows a significant reduction in TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event . This therapy did not induce any bleeding complications in the patients included in the study BACKGROUND Microinflammation is linked to cardiovascular disease , and is highly prevalent in dialysis patients . It is logical to postulate that septicemia , a common macroinflammatory occurrence in dialysis patients , contributes to their large burden of cardiovascular disease . METHODS The Dialysis Morbidity and Mortality Wave 2 was a r and omly selected prospect i ve cohort of incident dialysis patients . Admission cl aims data were used to define and calculate rates of septicemia or bacteremia and cardiovascular events in those with Medicare as the primary payer . Utilizing Cox proportional hazard models we determined the association between baseline access and the development of bacteremia or sepsis , and also the association between bacteremia or sepsis episodes and subsequent cardiovascular events . RESULTS The 2358 ( 59 % ) patients with Medicare as primary payer were older and more likely to have heart failure than those with other payers , but had similar comorbidity-adjusted mortality hazards . Rates of first septicemia , bacteremia , or either condition , were 7.0 , 5.9 and 10.4 events per 100-patient years , respectively . Cox regression identified initial dialysis access as the main antecedent of septicemia or bacteremia . Hazards ratios for hemodialysis with permanent catheters , temporary catheters , and grafts were 1.95 ( 95 % CI 1.47 - 2.57 ) , 1.76 ( 95 % CI 1.29 - 2.41 ) , and 1.05 ( 95 % CI 0.82 - 1.35 ) , respectively , while that for peritoneal dialysis was 0.96 ( 95 % CI 0.75 - 1.23 ) ( reference arteriovenous fistula ) . After adjustment for baseline factors , septicemia or bacteremia , as a time-dependent covariate , was associated with subsequent death [ hazards ratio ( HR ) 2.33 , 95 % CI 1.38 - 2.28 ] , myocardial infa rct ion ( HR 1.78 , 95 % CI 1.38 - 2.28 ) , heart failure ( HR 1.64 , 95 % CI 1.39 - 1.95 ) , peripheral vascular disease ( HR 1.64 , 95 % CI 1.34 - 2.0 ) , and stroke ( HR 2.04 , 95 % CI 1.27 - 3.28 ) . CONCLUSION Septicemia appears to be an important , potentially preventable , cardiovascular risk factor in dialysis patients AIM Initial heparin locks instilled after tunnelled dialysis catheter ( TDC ) insertion can leak causing systemic anticoagulation and also promote staphyloccocal biofilm formation , predisposing to catheter-related infection ( CRI ) . The 1000 U/mL concentration is thus advocated as the optimal dose for preventing catheter bleeding and malfunction . The effect of lower heparin concentrations on further lowering these complications is not known . We compared early TDC outcomes between a non-st and ard ultra-low ( 500 U/mL ) and st and ard initial heparin locks ( 1000 and 5000 U/mL ) . METHODS This was a retrospective study on prospect ively collected data on 238 de novo internal jugular TDCs placed by nephrologists . Cases were categorized into groups 1 , 2 and 3 , according to initial heparin lock : 500 [ n = 30 ] , 1000 [ n = 180 ] and 5000 U/mL [ n = 28 ] respectively . Bleeding and malfunction within 24 h of TDC insertion , 30 days CRI-free catheter survival and the effects of clinical and laboratory factors on bleeding were evaluated . RESULTS Bleeding events were similar in groups 1 , 2 and 3 ( 7 vs 14 vs 13 % , respectively , P = 0.61 ) . Malfunction was only seen in group 2 ( 3.3 % ) . Thirty-day CRI-free catheter survival was comparable ( 96 vs 98 vs 97 % , respectively , P = 0.22 ) , giving a cumulative CRI rate of 0.76/1000 catheter days . All CRIs were staphylococcal . Univariate analysis did not reveal any significant predictors of catheter bleeding . CONCLUSION Immediate TDC bleeding , malfunction and CRI rate are not influenced by heparin lock concentrations ≤5000 U/mL in this low-risk cohort . However this needs to be corroborated in higher risk patients BACKGROUND AND OBJECTIVES Despite widespread use of tunneled hemodialysis ( HD ) catheters , their utility is limited by the development of thrombotic complications . To address this problem , this study investigated whether the thrombolytic agent tenecteplase can restore blood flow rates ( BFRs ) in dysfunctional HD catheters . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In this r and omized , double-blind study , patients with dysfunctional tunneled HD catheters , defined as a BFR < 300 ml/min at -250 mmHg pressure in the arterial line , received 1-hour intracatheter dwell with tenecteplase ( 2 mg ) or placebo . The primary endpoint was the percentage of patients with BFR > or = 300 ml/min and an increase of > or = 25 ml/min above baseline 30 minutes before and at the end of HD . Safety endpoints included the incidence of hemorrhagic , thrombotic , and infectious complications . RESULTS Eligible patients ( n = 149 ) were treated with tenecteplase ( n = 74 ) or placebo ( n = 75 ) . Mean baseline BFR was similar for the tenecteplase and placebo groups at 151 and 137 ml/min , respectively . After a 1-hour dwell , 22 % of patients in the tenecteplase group had functional catheters compared with 5 % among placebo controls ( P = 0.004 ) . At the end of dialysis , mean change in BFR was 47 ml/min in the tenecteplase group versus 12 ml/min in the placebo group ( P = 0.008 ) . Four catheter-related bloodstream infections ( one tenecteplase , three placebo ) and one thrombosis ( tenecteplase ) were observed . There were no reports of intracranial hemorrhage , major bleeding , embolic events , or catheter-related complications . CONCLUSIONS Tenecteplase improved HD catheter function and had a favorable safety profile compared with placebo The interval occlusion of central venous access devices ( CVADs ) remains a significant clinical problem , often requiring re-intervention for catheter exchange or replacement . The purpose of this Phase 3 , multi-center , double-blinded study was to test the hypothesis that instillation of recombinant urokinase ( r-UK ) 5000 IU/ml is superior to placebo in restoring total catheter patency to an unselected cohort of occluded CVADs . After obtaining informed consent , adult and pediatric patients with occluded , non-hemodialysis CVADs of any duration or type were r and omized ( 2 : 1 ) to receive either r-UK 5000 IU/ml or placebo instilled into all occluded lumens of their catheter . Catheter function was assessed at 5 , 15 and 30 min after the first instillation . If the catheter remained occluded after 30 min , a second dose was instilled with repeat assessment s at 5 , 15 and 30 min . The primary efficacy variable was the restoration of catheter function to all treated lumens ( i.e. , total catheter patency ) after one or two instillations . Catheters that were not successfully recanalized after two instillations were allowed to receive up to two instillations of open-label r-UK administered in the same manner . The primary safety variable was the occurrence of hemorrhagic and non-hemorrhagic events within 72 hr after instillation . A total of 180 patients were enrolled at 43 sites in the United States and Canada . Most patients were adults , although 20 % were < /=18 years of age . CVAD types included totally implanted subcutaneous ports ( 45 % ) , PICC lines ( 26 % ) , non-tunneled percutaneous catheters ( 18 % ) , and tunneled percutaneous catheters ( 10 % ) . All CVADs were occluded by virtue of their inability to withdraw blood ( withdrawal occlusion ) . Additionally , 32 % of catheters were completely dysfunctional as blood could not be withdrawn and fluids could not be infused ( total occlusion ) . Analysis of the results showed that r-UK was significantly better than placebo in restoring catheter function ( 54 % versus 30 % , p = 0.002 ) . There were no major hemorrhagic events within 72 hr after up to four r-UK instillations , and the incidence of non-hemorrhagic events was similar among the r-UK and placebo groups . In conclusion , r-UK is superior to placebo in restoring total catheter patency to occluded CVADs . In patients with occluded CVADs , intra-catheter thrombolysis can restore patency and may obviate the need for catheter replacement PURPOSE To compare central dialysis catheter patency rates after stripping procedures with those after urokinase ( UK ) infusion . MATERIAL S AND METHODS Fifty-seven tunneled catheters with either ( i ) flow rates less than 250 mL/min and established baseline flow rates > or = 300 mL/min or ( ii ) flow rates 50 mL/min less than higher established baseline flows were prospect ively r and omized to undergo stripping procedures ( n = 28 ) or UK infusion ( n = 29 ) at 30,000 U/h via each port concurrently , for a total 250,000 U. Success and patency were determined by dialysis at normal flow rates ( > or = 300 mL/min ) or at the previously established higher baseline rate . Flow rates were monitored weekly . Primary patency ended with catheter malfunction or removal . Kaplan-Meier survival analysis was used to construct survival curves . RESULTS In the stripping group , initial clinical success was 89 % ( 25 of 28 ) . The 15- , 30- , and 45-day primary patency rates were 75 % ( n = 20 ) , 52 % ( n = 13 ) , and 35 % ( n = 8) , respectively . The median duration of additional function was 32 days ( 95 % CI : 18 - 48 d ) . In the UK group , initial clinical success was 97 % ( 28 of 29 ) . The 15- , 30- , and 45-day primary patency rates were 86 % ( n = 21 ) , 63 % ( n = 13 ) , and 48 % ( n = 9 ) , respectively . The median duration of additional patency was 42 days ( 95 % CI : 22 - 153 d ) . The Wilcoxon test for e quality detected no significant difference in the survival curves for the two treatment groups ( P = .236 ) . CONCLUSION There is no significant difference in time to primary patency between the two methods . Both allow temporary catheter salvage in most patients UNLABELLED Cuffed central -venous haemodialysis catheters are emerging as an alternative permanent haemodialysis vascular access . There is limited data regarding the adequacy of dialysis with prolonged used of these catheters . We conducted a prospect i ve study comparing three commonly used cuffed central -venous haemodialysis catheters : ( 1 ) PermCath , Quinton Instrument Co , Seattle ; ( 2 ) Tesio , Med Comp , Inc , Harleysville PA ; ( 3 ) VasCath Soft Cell , Bard Instrument Company , Toronto , and compared them with control patients dialysing with arteriovenous access ( AV ) access . We r and omly assigned 64 patients who needed prolonged temporary vascular access to placement of one of three catheters . The control group comprised 222 patients dialysing simultaneously in the same units with AV access . METHODS All patients were dialysed with identical machines and kidneys . Maximal effort were made with every catheter to optimize achievable blood flow . Catheters with mechanical problems were treated first with urokinase and then fibrin sheath catheter stripping . The mean blood flow was determined by averaging mean blood flows from 30 consecutive treatments . Reliability of catheter was defined as percentage of treatments that were performed at a median blood flow of 350 ml/min or above during these 30 treatments . Kt/V was measured monthly and calculated using the single-pool Daugirdas formula . Haemodialysis prescription were adjusted for Kt/V above 1.2 . Recirculation was measured using two-needle low-blood-flow technique . RESULTS The mean blood flows were ( PermCath 383.6 ml/min , Tesio 396.3 ml/min , VasCath 320.4 ml/min ) . PermCath and Tesio had comparable mean blood flows and were significantly higher than VasCath ( P<0.005 ) . Reliability of catheters were ( PermCath 86.9 % , Tesio 81.6 % , VasCath 42.3 % ) . Tesio and PermCath were equally reliable and both were more reliable than VasCath ( P<0.005 ) . Had the target for reliability been 300 ml/min all three catheters would have been equally reliable . Negative arterial pressure in excess of 300 mmHg prevented faster blood flows in 98 % of instances . None of the catheters performed as well as the control population with AV access ( mean blood flow 437ml/min , reliability 96 % , P<0.005 ) . Recirculation rates were 3.7 % for PermCath 3.9 % for Tesio , and 4 % for VasCath . All patients weighing less than 85 kg acheived a Kt/V of 1.2 with a 4-h treatment . For comparison purpose s when Kt/V was normalized to a 70-kg patient the results were PermCath 1.42 . Tesio 1.44 , VasCath 1.19 , AV access 1.64 . SUMMARY All three catheters are capable of providing adequate haemodialysis although large patients will need extended treatment times . The PermCath and Tesio provide blood flow and reliability superior to the VasCath . Blood flow is limited in all catheters by inflow , as evidence d by negative arterial pressure . All catheters had acceptable recirculation . AV access is superior in terms of blood flow and reliability to all tested catheters Background : Thrombotic occlusion is a frequent complication of central venous catheters used to provide temporary blood access on hemodialysis therapy . Heparin-lock is conventionally used to maintain patency of the catheter , but the necessity of heparin-lock has not been determined yet . Methods : After the immobilized-urokinase double-lumen central venous catheter was inserted into 48 Japanese hemodialysis patients , 22 patients r and omized to the heparin group received a 20-ml saline-flush , followed by 2 ml of 1,000 U/ml heparin-lock , and 26 patients r and omized to the saline group received only the 20-ml saline-flush once a day for each lumen . Results : Thrombotic occlusion was observed in only 1 out of 22 patients in the heparin group and 1 out of 26 patients in the saline group . No significant difference of the catheter survival was observed between the two groups ( p = 0.8599 ) . Conclusions : Natural saline-flush is sufficient for maintaining the patency of an immobilized-urokinase double-lumen central venous catheter Number of hemodialysis patients each day is increasing . The quality of their lives is largely determined by the quality of hemodialysis treatment . One of the most important factors is the type of applied blood approach . The type of blood approach in the most case is artery venous fistula , permanent , temporary catheters , grafts . Any complications of blood str and approach inevitably leads to lower quality of hemodialysis treatment which is connected with not adequate dialysis and poorer general state of patients . Our research was carried out as a prospect i ve study , for the period of 36 months . In the study were included 31 patients , which are on chronic haemodialysis treatment . During this study , we are followed all complications , which occurred at temporary , and permanent tunneled haemodialysis catheters . Complications have occurred in terms of thrombotic problems , low blood flow , occurrence of infection . All patients are divided in two groups , 16 patients with permanent and 15 patients with temporary catheters . In the course of the study was analyzed blood flow and dialysis adequacy ( Kt/Vdp ) as well as complications and results was compared with r and omly selected 16 patients who haemodialysis treatment performed by artery venous fistula ( AVF ) . Two patients were lost to further follow-up to the end of the study . 26 patients at the end of the study had functional catheters , while in the case of 3 patients the catheter was removed . Infection was found in 10 patients while thrombotic complications were observed in 27 cases regardless of catheter type . Mean blood flow in patients with permanent catheter was significantly higher ( 296,9+/-28,45 cm3/min ) compared to patients with temporary catheter ( 226,3+/-39,8 cm3/min ) ( p<0,001 ) . Kt/Vdp delivered was 1,22+/-0,15 on patients with permanent catheter and 1,30+/-0,18 for artery venous fistula ( AVF ) access respectively . The loss of dialysis efficacy using catheters was estimated at 6 % . However , in all cases Kt/Vdp values remained above the recommended values ( Kt/Vdp > or = 1,2 ) Thrombosis-related malfunction of tunneled-cuffed central venous catheters ( TCC ) for hemodialysis ( HD ) currently leads to a high rate of untimely catheter removal . Urokinase ( UK ) therapy is used for TCC thrombosis/malfunction , but no consensus exists on the adequate dose to obtain thrombolysis . We selected 72 HD patients with TCC and a mean age and HD vintage of 74 years ( range 65 - 87 ) and 36 months ( range 12 - 61 ) , respectively . All patients received warfarin therapy with a target international normalized ratio ( INR ) of 1.8 - 2.5 . Coagulative assessment of the patients was obtained by checking the INR , activated partial thromboplastin time , fibrinogen , hemoglobin , and platelets . Sixty-five thrombotic events were recorded during a 3-year follow-up ( median 0.3 events/patient/year ) . The patients selected were r and omized into two groups according to a different thrombolytic therapy . Group A comprised 29 thrombotic events in 32 patients who received UK 25,000 IU in both arterial and venous lines of the TCC for each event . UK restored an adequate blood flow rate ( BFR ) for HD ( ≥ 250 mL/min ) in 4/29 events ( 13.7 % ) , whereas addition of 50,000 IU to both arterial and venous lines was required in 25/29 events ( 86.3 % ) . For the same 25 events in the second HD session , a further 75,000 IU of UK was needed for each TCC lumen . Group B comprised 36 thrombotic events in 40 patients who received 100 000 IU of UK in the arterial and venous lumen of the TCC for each event . An adequate BFR was recovered in all events . In 12/36 events ( 33.3 % ) , 100,000 IU UK for both lumens were needed in the second HD . In conclusion , group B patients obtained ( i ) a significantly better TCC patency than group A patients ; ( ii ) a low UK administration in the following HD sessions ; and ( iii ) no bleeding complications One hundred sixteen subclavian hemodialysis catheter placements in 88 patients were prospect ively evaluated for catheter-related infections . Semiquantitative culture techniques and a rigid infection control protocol were used . The overall catheter colonization rate was 21.6 % and catheter-associated bacteremia occurred in 9.4 % . Catheters removed from febrile patients had much higher colonization ( 48.3 % ) and bacteremia ( 34.5 % ) rates . In a r and omized study comparing infection rates in catheters tunneled subcutaneously or not tunneled , there was no significant difference in the incidence of infection . Catheters inserted over a guidewire to replace clotted or malfunctioning catheters were not associated with higher infection rates BACKGROUND Reducing the use of tunneled catheters in hemodialysis patients requires concerted efforts to convert them to a usable permanent vascular access . The goal of this study is to evaluate the reasons for tunneled catheter use in our prevalent hemodialysis population and the success in converting them to a permanent vascular access . METHODS We identified all catheter-dependent hemodialysis patients at our center on a single date . These patients were followed up prospect ively during a 1-year period to evaluate access procedures and conversion to permanent access use . RESULTS Of 458 prevalent hemodialysis patients , 108 patients ( 23.6 % ) were dialyzing through cuffed tunneled catheters : 18.5 % had no further options for creation of a permanent vascular access , 28.7 % had an immature access , 43.5 % had access placement pending , and 9.2 % had repeatedly refused access surgery . For 78 catheter-dependent patients ( excluding patients with no access options and those who refused permanent access surgery ) , the likelihood of using a permanent access was 53 % by 6 months and 80 % by 1 year . In patients with an immature access , 50 % were using a permanent access at 3 months , and 80 % , at 6 months . Of patients with access surgery pending , 45 % had access surgery performed within 3 months , and 70 % , at 6 months . Finally , of all patients , the likelihood of catheter-related bacteremia was 48 % at 6 months . On multivariable analysis , only duration of catheter dependence predicted subsequent use of a permanent access ( hazard ratio , 3.11 ; 95 % confidence interval , 1.70 to 5.68 ; P = 0.0002 ) for catheter dependence less than versus greater than 6 months . CONCLUSION Almost one quarter of our hemodialysis population is catheter dependent . Despite concerted efforts , there remain very long delays in achieving a usable permanent access , attributable to delays in both surgical access placement and access maturation . In the interim , this patient population developed a high frequency of catheter-related bacteremia Objectives : To determine whether the tissue plasminogen activator , alteplase , is more effective than heparin in preventing blood clots developing in children ’s haemodialysis central lines between dialysis sessions . Design : A prospect i ve double-blind , within-patient multiperiod cross-over controlled trial of instilling a “ lock ” of either heparin 5000 U/ml or alteplase 1 mg/ml into the central lines of two children haemodialysed twice weekly , and seven dialysed thrice weekly , over 10 weeks . Setting : A UK paediatric nephrology unit . Main outcome measures : Weight of blood clot aspirated from the line at the start of the next dialysis session . Results : The odds of a clot forming was 2.4 times greater with heparin than alteplase ( 95 % CI 1.4 to 4.0 ; p = 0.001 ) , and when present they were 1.9 times heavier ( 31 vs 15 mg ; 95 % CI 1.5 to 2.4 ; p<0.0005 ) . There was no effect of inter-dialytic interval . One child required an alteplase infusion to clear a blocked line following a heparin lock . We subsequently changed our routine locks from heparin to alteplase . Comparing the year before and after that change , the incidence of blocked lines requiring an alteplase or urokinase infusion fell from 2.7 to 1.2 per child ( p<0.03 ) , and the need for surgical replacements from 0.7 to nil ( p<0.02 ) . Conclusion : Alteplase is significantly more effective than heparin in preventing clot formation in central haemodialysis lines . This reduces morbidity and improves preservation of central venous access . It is more expensive , though relatively economic if packaged into syringes and stored frozen until needed , but reduces the costs of unblocking or replacing clotted lines In a recent r and omized trial , weekly recombinant tissue plasminogen activator ( rt-PA ) , 1 mg per lumen , once per week , and twice-weekly heparin as a locking solution ( rt-PA/heparin ) result ed in lower risks of hemodialysis catheter malfunction and catheter-related bacteremia compared with thrice-weekly heparin ( heparin alone ) . We collected detailed costs within this trial to determine how choice of locking solution would affect overall health care costs , including the cost of locking solutions and all other relevant medical costs over the course of the 6-month trial . Nonparametric bootstrap estimates were used to derive 95 % confidence intervals ( CIs ) and mean cost differences between the treatment groups . The cost of the locking solution was higher in patients receiving rt-PA/heparin , but this was partially offset by lower costs for managing complications . Overall , the difference in unadjusted mean cost for managing patients with rt-PA/heparin versus heparin alone was Can$323 ( 95 % CI , -$935 to $ 1581 ; P=0.62 ) . When the costs were extrapolated over a 1-year time horizon using decision analysis , assuming ongoing rt-PA effectiveness , the overall costs of the strategies were similar . This finding was sensitive to plausible variation in the frequency and cost of managing patients with catheter-related bacteremia , and whether the benefit of rt-PA on catheter-related bacteremia was maintained in the long term . In summary , we noted no significant difference in the mean overall cost of an rt-PA/heparin strategy as a locking solution for catheters compared with thrice-weekly heparin . Cost savings due to a lower risk of hospitalization for catheter-related bacteremia partially offset the increased cost of rt-PA |
11,713 | 23,171,381 | Obesity is associated with elevated levels of CRP and the association is stronger in women and North Americans/Europeans .
The sex difference only emerges in adulthood | Obesity has been associated with elevated levels of C-reactive protein ( CRP ) , a marker of inflammation and predictor of cardiovascular risk .
The objective of this systematic review and meta- analysis was to estimate the associations between obesity and CRP according to sex , ethnicity and age . | CONTEXT Associations between adiposity and circulating inflammation markers are assumed to be causal , although the direction of the relationship has not been proven . OBJECTIVE The aim of the study was to explore the causal direction of the relationship between adiposity and inflammation using a bidirectional Mendelian r and omization approach . METHODS In the PROSPER study of 5804 elderly patients , we related C-reactive protein ( CRP ) single nucleotide polymorphisms ( SNPs ) ( rs1800947 and rs1205 ) and adiposity SNPs ( FTO and MC4R ) to body mass index ( BMI ) as well as circulating levels of CRP and leptin . We gave each individual two allele scores ranging from zero to 4 , counting each pair of alleles related to CRP levels or BMI . RESULTS With increasing CRP allele score , there was a stepwise decrease in CRP levels ( P for trend < 0.0001 ) and a 1.98 mg/liter difference between extremes of the allele score distribution , but there was no associated change in BMI or leptin levels ( P > or= 0.89 ) . By contrast , adiposity allele score was associated with 1 ) an increase in BMI ( 1.2 kg/m(2 ) difference between extremes ; P for trend 0.002 ) ; 2 ) an increase in circulating leptin ( 5.77 ng/ml difference between extremes ; P for trend 0.0027 ) ; and 3 ) increased CRP levels ( 1.24 mg/liter difference between extremes ; P for trend 0.002 ) . CONCLUSIONS Greater adiposity conferred by FTO and MC4R SNPs led to higher CRP levels , with no evidence for any reverse pathway . Future studies should extend our findings to other circulating inflammatory parameters . This study illustrates the potential power of Mendelian r and omization to dissect directions of causality between intercorrelated metabolic factors This study was performed to evaluate the relation of high-sensitivity C-reactive protein ( hsCRP ) with several cardiovascular risk factors such as age , blood pressure , smoking habit and serum lipids , body mass index , blood glucose , regular exercise , alcohol drinking , white blood cell counts in a cross-sectional survey . Plasma hsCRP was measured by immunoturbidimetry in 202 subjects , aged over 50 yr , who participated in health-check survey in a rural area of Jeollanamdo , Korea . Plasma hsCRP level was 1.9±3.0 mg/dL. There were significant associations between hsCRP levels and age , white blood cell counts , blood glucose , diastolic blood pressure , HDL-cholesterol , body mass index and smoking status . In stepwise multivariate regression analysis , white blood cell counts , age , blood glucose , smoking status and body mass index were independent correlates of hsCRP levels . In conclusion , plasma hsCRP levels were associated with several cardiovascular risk factors , and these data are compatible with the hypothesis that CRP levels may be a marker for pre clinical cardiovascular disease . Further what we need now are prospect i ve studies to evaluate the association of C-reactive protein concentrations with subsequent cardiac events CONTEXT There are few data directly comparing the effects of physical activity and body weight on cardiovascular biomarkers . OBJECTIVE To examine the association of physical activity and body mass index ( BMI , defined as weight in kilograms divided by the square of height in meters ) alone and in combination with cardiovascular biomarkers . DESIGN , SETTING , AND PARTICIPANTS Cross-sectional analysis of 27,158 apparently healthy US women ( mean age , 54.7 years ) at the time of enrollment ( 1992 - 1995 ) in the Women 's Health Study , a r and omized , double-blind , placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer . MAIN OUTCOME MEASURES The association of physical activity and BMI with high-sensitivity C-reactive protein ( CRP ) , fibrinogen , soluble intracellular adhesion molecule 1 ( ICAM-1 ) , homocysteine , low- and high-density lipoprotein ( LDL and HDL ) cholesterol , total cholesterol , apolipoprotein A-1 and B100 , lipoprotein(a ) , and creatinine . RESULTS Lower levels of physical activity and higher levels of BMI were independently associated ( P for trend < .001 ) with adverse levels of nearly all lipid and inflammatory biomarkers . High BMI showed stronger associations with these biomarkers than physical inactivity . For example , using the reference group of physically active , normal weight women ( energy expenditure > or = 1000 kcal/week ; BMI , 18.5 - 24.9 ) and adjusting for age , race , smoking , blood pressure , diabetes , menopausal status , and hormone use , the odds ratios ( 95 % confidence intervals [ CIs ] ) for having CRP > 3 mg/L were : for inactive , normal weight women 1.26 ( 1.15 - 1.37 ) ; active , overweight 2.68 ( 2.41 - 2.98 ) ; inactive , overweight 3.11 ( 2.84 - 3.41 ) ; active , obese 8.25 ( 7.15 - 9.51 ) ; and inactive , obese 9.86 ( 8.84 - 10.99 ) . In similar analyses , the odds ratios ( 95 % CIs ) for having HDL cholesterol < 50 mg/dL were 1.20 ( 1.11 - 1.30 ) ; 2.25 ( 2.04 - 2.49 ) ; 2.62 ( 2.41 - 2.85 ) ; 4.21 ( 3.68 - 4.81 ) ; and 5.27 ( 4.77 - 5.84 ) , respectively , and for having apolipoprotein B100 > 120 mg/dL they were 1.21 ( 1.11 - 1.33 ) ; 1.86 ( 1.66 - 2.08 ) ; 2.06 ( 1.88 - 2.67 ) ; 2.35 ( 2.04 - 2.70 ) ; and 2.33 ( 2.09 - 2.59 ) . Fibrinogen , ICAM-1 , apolipoprotein A1 , total cholesterol , and LDL cholesterol showed similar associations . By contrast , homocysteine , lipoprotein ( a ) , and creatinine showed weak or nonsignificant associations . CONCLUSIONS High BMI was more strongly related to adverse cardiovascular biomarker levels than physical inactivity . However , within BMI categories , physical activity was generally associated with more favorable cardiovascular biomarker levels than inactivity BACKGROUND Recent prospect i ve data suggest that intake of rapidly digested and absorbed carbohydrates with a high dietary glycemic load is associated with an increased risk of ischemic heart disease . OBJECTIVE We examined whether a high dietary glycemic load was associated with elevated hs-CRP concentrations and whether this association was modified by body mass index ( BMI ; in kg/m(2 ) ) . DESIGN In 244 apparently healthy women , we measured plasma hs-CRP concentrations and determined average dietary glycemic loads with a vali date d semiquantitative food-frequency question naire . Using multiple regression models , we evaluated the association between dietary glycemic load and plasma hs-CRP after adjusting for age ; treatment status ; smoking status ; BMI ; physical activity level ; parental history of myocardial infa rct ion ; history of hypertension , diabetes , and high cholesterol ; postmenopausal hormone use ; alcohol intake ; and other dietary variables . RESULTS We found a strong and statistically significant positive association between dietary glycemic load and plasma hs-CRP . The median hs-CRP concentration for the lowest quintile of dietary glycemic load was 1.9 mg/L and for the highest quintile was 3.7 mg/L ; corresponding multivariate-adjusted geometric means were 1.4 and 3.8 mg/L , respectively ( P for trend < 0.01 ) . This association was significantly modified by BMI . Among women with a BMI greater-than-or-equal 25 , the multivariate-adjusted geometric mean hs-CRP concentration in the lowest quintile was 1.6 mg/L and in the highest quintile was 5.0 mg/L ; however , among women with a BMI < 25 , the corresponding means were 1.1 and 3.1 mg/L , respectively ( P = 0.01 for interaction ) . CONCLUSIONS Dietary glycemic load is significantly and positively associated with plasma hs-CRP in healthy middle-aged women , independent of conventional risk factors for ischemic heart disease . Exacerbation of the proinflammatory process may be a mechanism whereby a high intake of rapidly digested and absorbed carbohydrates increases the risk of ischemic heart disease , especially in overweight women prone to insulin resistance CONTEXT The link between C-reactive protein ( CRP ) and adiposity deserves to be further explored , considering the controversial diabetogenic role of CRP . OBJECTIVE We explored the potential causal role of CRP on measures of adiposity . DESIGN We used a Mendelian r and omization approach with the CRP and LEPR genes as instrumental variables in a cross-sectional Caucasian population -based study comprising 2526 men and 2836 women . Adiposity was measured using body mass index ( BMI ) , fat and lean mass estimated by bioelectrical impedance , and waist circumference . RESULTS Log-transformed CRP explained by the rs7553007 single-nucleotide polymorphism tagging the CRP gene was significantly associated with BMI [ regression coefficient : 1.22 ( 0.18 ; 2.25 ) , P = 0.02 ] and fat mass [ 2.67 ( 0.65 ; 4.68 ) , P = 0.01 ] but not with lean mass in women , whereas no association was found in men . Log-transformed CRP explained by the rs1805096 LEPR single-nucleotide polymorphism was also positively associated , although not significantly , with BMI or fat mass . The combined CRP-LEPR instrument explained 2.24 and 0.77 % of CRP variance in women and men , respectively . Log-transformed CRP explained by this combined instrument was significantly associated with BMI [ 0.98 ( 0.32 ; 1.63 ) , P = 0.004 ] , fat mass [ 2.07 ( 0.79 ; 3.34 ) , P = 0.001 ] , and waist [ 2.09 ( 0.39 ; 3.78 ) , P = 0.01 ] in women but not men . CONCLUSION Our data suggest that CRP is causally and positively related to BMI in women and that this is mainly due to fat mass . Results on the combined CRP-LEPR instrument suggest that leptin may play a role in the causal association between CRP and adiposity in women . Results in men were not significant OBJECTIVE We evaluated the association of obesity with various markers of chronic inflammation , in a population -based sample of 3,042 adults . METHODS During 2001 - 2002 , we r and omly enrolled 1,514 men ( 18 - 87 years old ) and 1,528 women ( 18 - 89 years old ) , from the Attica area , Greece ; the sampling was stratified by the age-sex distribution of the region ( census 2001 ) . Among several variables , we also measured various inflammatory markers ( C-reactive protein , tumor necrosis factor alpha , amyloid A , white blood cells and interleukin-6 ) and anthropometric variables ( weight , height , waist and hip circumferences ) . Central fat was defined as waist-to-hip ratio > or=0.95 in men and > or=0.8 in women , while obesity as body mass index ( BMI ) > 29.9 kg/m(2 ) . RESULTS Central fat prevailed in 36 % of men and 43 % of women ( p<0.001 ) , while obesity prevailed in 20 % of men and 15 % of women , respectively . Compared to participants with normal body fat distribution , those with central fat exhibited 53 % higher C-reactive protein levels , 30 % higher tumor necrosis factor , alpha levels , 26 % higher amyloid A levels , 17 % higher white blood cell counts and 42 % higher interleukin-6 levels ( all p<0.05 ) . We observed that all inflammation markers were related to BMI ( index for obesity ) , waist and to waist-to-hip ratio ( indices for central fat ) , in both genders . Moreover , the models that included waist or waist-to-hip ratio as independent variable had higher explanatory ability ( i.e. R(2 ) ) than the models included BMI , especially in women , even after adjusting for age and various other potential confounders . CONCLUSION Our results suggest a relationship between central adiposity and inflammation process , irrespective of age and other potential confounders . This association was more prominent than the relationship between total obesity and inflammation . It could be hypothesized that a disproportionate accumulation of visceral fat mass could be partially associated with increased coronary risk , through inflammation process Several prospect i ve studies have demonstrated a direct association between C-reactive protein ( CRP ) levels and the risks of developing cardiovascular disease . Few studies , however , have explored the interrelations between CRP levels and other risk factors for cardiovascular disease . We evaluated the relation of CRP with several cardiovascular risk factors in a cross-sectional survey of 1,172 apparently healthy men . There were significant positive associations between CRP levels and age , number of cigarettes smoked per day , body mass index , systolic and diastolic blood pressure , total cholesterol , triglycerides , lipoprotein(a ) , apolipoprotein B , tissue-type plasminogen activator antigen , D-dimers , total homocysteine , and fibrinogen ( all p values < 0.05 ) . Significant inverse associations were observed for exercise frequency , high-density lipoprotein cholesterol , and apolipoprotein A-I and A-II ( all p values < 0.02 ) . In multivariate analysis , age , smoking status , and serum levels of tissue-type plasminogen activator antigen , fibrinogen , lipoprotein(a ) , and total homocysteine were independent correlates of CRP levels . Finally , in an analysis controlled either for all the independent correlates or for several usual risk factors , we observed progressive increases in levels of CRP with increasing prevalence of risk factors ( p for trend < 0.001 for independent correlates and < 0.01 for usual risk factors ) . In conclusion , in a large cohort of apparently healthy men , CRP levels were associated with several cardiovascular risk factors . These data are compatible with the hypothesis that CRP levels may be a marker for pre clinical cardiovascular disease Objective : To investigate whether the nature of the relationship between body mass index ( BMI ( kg/m2 ) ) and all-cause mortality is direct , J- or U-shaped , and whether this relationship changes as people age . Design : Prospect i ve nationwide cohort study of US radiologic technologists (USRT).Subjects : Sixty-four thous and seven hundred and thirty-three female and 19 011 male certified radiation technologists . Methods : We prospect ively followed participants from the USRT study who completed a mail survey in 1983–1989 through 2000 . During an average of 14.7 years of follow-up or 1.23 million person-years , 2278 women and 1495 men died . Using Cox 's proportional-hazards regression analyses , we analyzed the relationship between BMI and all-cause mortality by gender and by age group ( < 55 years ; ⩾55 years ) . We also examined risk in never-smokers after the first 5 years of follow-up to limit bias owing to the confounding effects of smoking and illness-related weight loss on BMI and mortality . Results : Risks were generally J-shaped for both genders and age groups . When we excluded smokers and the first 5 year of follow-up , risks were substantially reduced in those with low BMI s. In never-smoking women under the age of 55 years ( excluding the initial 5-year follow-up period ) , risk rose as BMI increased above 21.0 kg/m2 , whereas in older women , risk increased beginning at a higher BMI ( ⩾25.0 kg/m2 ) . Among younger men who never smoked ( excluding the initial 5-year follow-up period ) , risk began to rise above a BMI of 23.0 kg/m2 , whereas in older men , risk did not begin to increase until exceeding a BMI of 30.0 kg/m2 . Conclusions : In younger/middle-aged , but not older , women and men , mortality risks appear directly related to BMI . The more complicated relationship between BMI and mortality in older subjects suggests the importance of assessing whether other markers of body composition better explain mortality risk in older adults Context : The assignment of direction and causality within networks of observational associations is problematic outside r and omized control trials , and the presence of a causal relationship between body mass index ( BMI ) and C-reactive protein ( CRP ) is disputed . Objective : Using reciprocal Mendelian r and omization , we aim to assess the direction of causality in relationships between BMI and CRP and to demonstrate this as a promising analytical technique . Participants and methods : The study was based on a large , cross-sectional European study from Copenhagen , Denmark . Genetic associates of BMI ( FTO(rs9939609 ) ) and circulating CRP ( CRP(rs3091244 ) ) have been used to reexamine observational associations between them . Results : Observational analyses showed a strong , positive association between circulating CRP and BMI ( change in BMI for a doubling in logCRP of 1.03 kg m−2 ( 95 % confidence interval ( 95 % CI ) : 1.00 , 1.07 ) , P<0.0001 ) . Analysis using CRP(rs3091244 ) to re-estimate the causal effect of circulating CRP on BMI yielded null effects ( change in BMI for a doubling in logCRP of −0.24 kg m−2 ( 95 % CI : −0.58 , 0.11 ) , P=0.2 ) . In contrast , analysis using FTO(rs9939609 ) to assess the causal effect of BMI on circulating CRP confirmed observational associations ( ratio of geometric means of CRP per s.d . increase in BMI 1.41 ( 95 % CI : 1.10 , 1.80 ) , P=0.006 ) . Conclusions : Taken together , these data suggest that the observed association between circulating CRP and measured BMI is likely to be driven by BMI , with CRP being a marker of elevated adiposity . More generally , the method of reciprocal r and omization has general applicability in determining the direction of causation within inter-correlated networks of metabolic components Estrogen lowers lipoprotein(a ) [ Lp(a ) ] levels , but the mechanisms involved have not been clarified . To address the relationship between estrogenic effects on Lp(a ) and serum lipids , and on other plasma proteins of hepatic origin , 15 healthy postmenopausal women participated in a r and omized , double-blinded , placebo-controlled , crossover study with 4 weeks of oral conjugated estrogens ( 0.625 mg/d ) and placebo , separated by a 6-week period . Lp(a ) levels decreased during estrogen treatment in 14 of the 15 subjects ( mean decrease , 23 % ; P < .001 ) . In response to estrogen , apolipoprotein A-I ( apoA-I ) , HDL cholesterol , and triglyceride levels increased by 12 % ( P = .001 ) , 11 % ( P < .001 ) , and 10 % ( P = .02 ) , respectively . Apolipoprotein B ( apoB ) and LDL cholesterol levels decreased by 7 % ( P = .01 ) and 12 % ( P = .03 ) , respectively , ApoB , LDL cholesterol , and Lp(a ) levels fell within 1 week of treatment , whereas apoA-I and HDL cholesterol levels rose more slowly . Levels of acid alpha 1-glycoprotein ( AAG ) and haptoglobin ( HPT ) , two hepatically derived acute phase proteins , also decreased during estrogen treatment by 18 % ( P < .001 ) and 25 % ( P = .002 ) , respectively . Although the changes in AAG and HPT in response to estrogen were highly correlated ( r = .67 , P = .009 ) , we were unable to detect a correlation between change in either acute phase protein and change in Lp(a ) ( r = -.14 and -.24 , P = .64 and .41 ) . The lack of correlation between the changes in two acute phase reactants and Lp(a ) suggests different underlying mechanisms for the effects of estrogen on these liver-derived proteins BACKGROUND Obesity is a growing global health problem . Obesity-associated inflammatory and metabolic consequences may vary in different ethnic population s , and data in Chinese adolescents are sparse . In this study , we analysed the clinical and biochemical factors associated with overweight and obesity in Chinese adolescents . METHODS This is a cross-sectional cohort study with 2102 Chinese adolescents r and omly selected from 14 secondary schools in Hong Kong . Clinical and biochemical parameters including inflammatory markers , among different groups stratified by degrees of obesity , were compared by multivariate logistic regression analysis . RESULTS The median age was 16 yr ( interquartile range : 14 - 17 yr ) ( 45.6 % boys and 54.4 % girls ) . Among the boys , 16.5 % were overweight and 6.8 % were obese . The respective percentages in girls were 8.2 and 5.8 % . Compared with the group with normal weight in both boys and girls , high systolic blood pressure ( SBP ) , increased insulin resistance ( by homoeostasis model assessment , HOMA-IR ) , elevated high-sensitivity C-reactive protein ( hsCRP ) level and low high-density lipoprotein cholesterol ( HDL-C ) level were independently associated with overweight/obesity . In boys , the respective odds ratio ( 95 % CI ) was 1.03 ( 1.01 - 1.05 ) for SBP , 21.0 ( 12.0 - 36.8 ) for HOMA-IR , 3.65 ( 2.10 - 6.35 ) for hsCRP and 0.24 ( 0.11 - 0.51 ) for HDL-C. In girls , the respective figures were 1.02 ( 1.00 - 1.04 ) , 9.82 ( 5.65 - 17.1 ) , 6.28 ( 3.12 - 12.6 ) and 0.18 ( 0.08 - 0.41 ) . In girls , low-density lipoprotein cholesterol was also independently associated with overweight/obesity [ 1.56 ( 1.09 - 2.24 ) ] . CONCLUSIONS In Chinese adolescents , overweight/obesity is independently associated with SBP , insulin resistance , hsCRP and low HDL-C. Early intervention in overweight and obese adolescents may potentially retard the development of these cardiovascular risk factors C-reactive protein ( CRP ) , a nonspecific marker of inflammatory status , is associated with cardiovascular disease ( CVD ) risk factors and the late occurrence of heart disease in adults . However , few studies assess the plasma CRP levels in healthy children . The purpose of this study is to evaluate the relationship between plasma CRP levels and anthropometric and lipid characteristics among children in Taiwan . After a multi-stage sampling of 85 junior high schools in Taipei , we r and omly selected 835 children ( 410 boys and 425 girls ) aged 12 to 16 years . Anthropometric and lipid profiles , including total cholesterol , triglyceride , high-density lipoprotein cholesterol ( HDL-C ) , and lipoprotein ( a ) were measured . We also calculated low-density lipoprotein cholesterol levels and the total cholesterol-to-HDL-C ratio as shown on the atherosclerotic index . In both genders , plasma CRP levels were significantly positively correlated with anthropometrics measures and inversely correlated with HDL-C levels . After adjusting for age , cigarette smoking , alcohol consumption , heart rate , and puberty development , children in the fourth quartile CRP subgroups were heavier and had significantly higher body mass index ( BMI ) and lower HDL-C levels than children with nondetected CRP . In multivariate regression models , CRP was significantly negatively associated with HDL-C levels even after adjusting for BMI in both genders . In this study , anthropometrics measures , especially BMI , were positively associated with plasma CRP levels . Furthermore , elevated CRP levels were associated with adverse lipids profiles . These data suggest that elevated plasma CRP levels might be associated with CVD risk factors that may be related to the late development of CVD in some Taiwanese children Body mass index ( BMI ) has various deficiencies as a measure of obesity , especially when the BMI measure is based on self-reported height and weight . BMI is an indirect measure of body fat compared with more direct approaches such as bioelectrical impedance . Moreover , BMI does not necessarily reflect the changes that occur with age . The proportion of body fat increases with age , whereas muscle mass decreases , but corresponding changes in height , weight and BMI may not reflect changes in body fat and muscle mass . Both the sensitivity and specificity of BMI have been shown to be poor . Additionally , the relation between BMI and percentage of body fat is not linear and differs for men and women . The consequences of the errors in the measurement of obesity with BMI depend on whether they are differential or nondifferential . Differential misclassification , a potentially greater problem in case – control and cross-sectional studies than in prospect i ve cohort studies , can produce a bias toward or away from the null . Nondifferential misclassification produces a bias toward the null for a dichotomous exposure ; for measures of exposure that are not dichotomous , the bias may be away from the null . In short , the use of BMI as a measure of obesity can introduce misclassification problems that may result in important bias in estimating the effects related to obesity CONTEXT Leptin and C-reactive protein ( CRP ) concentrations are increased in inflammation , and both have been linked to increased risk for cardiovascular diseases . OBJECTIVE The objective of the study was to explore in a population -based sample whether the relation between leptin and CRP is independent of obesity level and whether genetic causes of CRP elevation contribute to leptin levels . DESIGN This was a population -based study including 1862 young adults ( 971 women ; 891 men ) aged 24 - 39 yr . SETTING The study was conducted at five centers in Finl and . MAIN OUTCOME MEASURES Associations between leptin and CRP adjusted for obesity indices , risk factors , genetic variables , and lifestyle variables were measured . RESULTS Women had 3.0-fold higher median concentrations of leptin ( 12.5 vs. 4.1 ng/ml ) and 1.3-fold higher median concentrations of CRP ( 0.75 vs. 0.56 mg/liter ) than men ( P < 0.0001 in both comparisons ) . In univariate analyses , CRP and leptin were significantly intercorrelated ( r = 0.47 , P < 0.0001 for women ; r = 0.46 , P < 0.0001 for men ) . In multiple regression analysis including age , body mass index , waist circumference , insulin , lipids , systolic and diastolic blood pressures , smoking status , and use of oral contraceptives in women , leptin was the main determinant of CRP in men ( P < 0.0001 ) and the second most important determinant in women ( P < 0.0001 ) . A Mendelian r and omization test based on genetic variants in the CRP gene ( five single nucleotide polymorphisms ) provided no support for CRP as a causal agent for leptin . CONCLUSIONS Leptin , obesity , and oral contraceptive use in women were the main factors related to CRP . The relation between leptin and CRP was independent of obesity and cardiovascular risk factors |
11,714 | 29,299,954 | No significant impact of regular therapeutic opioid agonists on people ’s driving-related psychomotor skills was reported . | Background : Driving cessation is associated with poor health-related outcomes .
People with chronic diseases are often prescribed long-term opioid agonists that have the potential to impair driving .
Studies evaluating the impact of opioids on driving-related psychomotor skills report contradictory results likely due to heterogeneous design s , assessment tools and study population s. A better underst and ing of the effects of regular therapeutic opioid agonists on driving can help to inform the balance between individual ’s independence and community safety .
Aim : To identify the literature assessing the impact of regular therapeutic opioid agonists on driving-related psychomotor skills for people with chronic pain or chronic breathlessness . | PURPOSE The purpose of this article was to investigate the role of control beliefs in mediating the relationship between driving cessation and change in depressive symptoms in a population -based sample of older adults . DESIGN AND METHODS We report results from a prospect i ve , community-based cohort study that included two waves of data collected in 1992 and 1994 . Participants consisted of 700 men and women aged 70 and older , including 647 drivers and 53 participants who ceased driving between baseline ( 1992 ) and follow-up ( 1994 ) . Participants took part in interviews that included assessment s of driving status , sociodemographic characteristics , self-rated health , sensory function , depressive symptoms ( through the Center for Epidemiologic Studies -Depression scale ) , and expectancy of control . Using multilevel general linear models , we examined the extent to which driving status , expectancy of control , and relevant covariates explained change in depressive-symptom scores between baseline and follow-up . RESULTS Driving cessation was associated with an increase in depressive symptoms from baseline to follow-up . The higher depressive-symptom scores of ceased drivers relative to those of individuals who remained drivers at both waves was partly explained by a corresponding decrease in the sense of control among ceased drivers , and increased control beliefs among drivers . IMPLICATION S Interventions aim ed at promoting the maintenance of personal agency and associated control beliefs could be protective against the negative psychological concomitants of driving cessation Driving has been regarded as an activity of daily living that is important in maintaining a person 's independence in the community , access to employment , and social activities . Many patients , however , using opioid medications on a regular basis ( Chronic Opioid Analgesic Therapy : COAT ) to ameliorate their intractable pain have been restricted from driving out of concern that skills would be impaired and driving safety compromised by these medications . Yet there are no driving studies which have explored the effects of using opioid analgesics for an extended period of time . This pilot study was design ed to determine the effects of medically prescribed , stable opioid use on the driving abilities of patients with persistent , nonmalignant pain . Sixteen patients with chronic nonmalignant pain on COAT , who met criteria for participation in the study , underwent a comprehensive off-road driving evaluation using measures which have been shown to be sensitive in predicting on-road driving performance . The evaluation consisted of a pre-driver evaluation ( PDE ) , a simulator evaluation ( SDE ) , and behavioral observation during simulator performance . Patients in the COAT group were compared to a historical control group of 327 cerebrally compromised patients ( CComp ) who had undergone the same evaluation and then passed an on-road , behind-the-wheel evaluation ( BTW Pass ; n = 162 ) or failed ( BTW Fail ; n = 165 ) . Results revealed that COAT patients generally outperformed the CComp patients as a group by equaling or exceeding PDE and SDE scores of the BTW Fail patients as well as the BTW Pass patients on all measures that differentiated the groups . Notably , COAT patients had a relatively poorer performance than CComp patients on specific neuropsychometric tests in the PDE ; however , the differences were not statistically significant and did not imply a systematic pattern of scores that reflected domain-specific deficits . Behaviorally , COAT patients were generally superior to CComp patients , also ; however , COAT patients had greater difficulty in following instructions and as well as a tendency toward impulsivity , like the BTW fail group . While there was general support for the notion that COAT did not significantly impair the perception , cognition , coordination , and behavior measured in off-road tests that have been regarded as requisite for on-road driving , method ological problems may limit the generalizability of results and recommendations are made for research beyond a pilot study & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Abstract Objective To determine the efficacy of oral morphine in relieving the sensation of breathlessness in patients in whom the underlying aetiology is maximally treated . Design R and omised , double blind , placebo controlled crossover study . Setting Four outpatient clinics at a hospital in South Australia . Participants 48 participants who had not previously been treated with opioids ( mean age 76 , SD 5 ) with predominantly chronic obstructive pulmonary disease ( 42 , 88 % ) were r and omised to four days of 20 mg oral morphine with sustained release followed by four days of identically formulated placebo , or vice versa . Laxatives were provided as needed . Main outcome measures Dyspnoea in the morning and evening as shown on a 100 mm visual analogue scale , quality of sleep , wellbeing , performance on physical exertion , and side effects as measured at the end of the four day treatment period . Results 38 participants completed the study ; three withdrew because of definite and two because of possible side effects of morphine ( nausea , vomiting , and sedation ) . Participants reported significantly different dyspnoea scores when treated with morphine : an improvement of 6.6 mm ( 95 % confidence interval 1.6 mm to 11.6 mm ) in the morning and of 9.5 mm ( 3.0 mm to 16.1 mm ) in the evening ( P = 0.011 and P = 0.006 , respectively ) . During the period in which they were taking morphine participants also reported better sleep ( P = 0.039 ) . More participants reported distressing constipation while taking morphine ( 9 v 1 , P = 0.021 ) in spite of using laxatives . All other side effects were not significantly worse with morphine , although the study was not powered to address side effects . Conclusions Sustained release , oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting OBJECTIVES Increasing age , socioeconomic factors , and declining function and health have been linked to driving cessation , but little is known about the consequences of stopping driving . This study was design ed to test the hypothesis that driving cessation leads to a decline in out-of-home activity levels . METHODS In 1989 a survey of driving practice s was administered to surviving noninstitutionalized members of the New Haven Established Population s for Epidemiologic Studies of the Elderly ( EPESE ) cohort . Of 1,316 respondents , 502 were active drivers as of 1988 , 92 had stopped driving between 1982 and 1987 , and 722 never drove or stopped before 1982 . Information on sociodemographic and health-related variables came from in-home EPESE interviews in 1982 , 1985 , and 1988 , and from yearly phone interviews . Activity was measured at all three in-home interviews , and an activity measure was created based on self-reported participation in nine out-of-home activities . A repeated measures r and om-effects model was used to test the effect of driving cessation on activity while controlling for potential confounders . RESULTS Driving cessation was strongly associated with decreased out-of-home activity levels ( coefficient-1.081 , st and ard error 0.264 , p < .001 ) after adjustment for sociodemographic and health-related factors . DISCUSSION The potential consequences of driving limitations or cessation should be taken into account when advising older drivers and developing alternative transportation strategies to help maintain their mobility Context Obstructive sleep apnea ( OSA ) is associated with sleepiness and poor concentration , symptoms that could impair driving performance . Contribution This study evaluated simulated driving performance in 38 patients with untreated OSA and 20 control participants under 3 conditions : unrestricted sleep , sleep restriction , and consumption of alcohol . Compared with control participants , patients with untreated OSA had worse simulated driving performance . Patients with OSA also had greater decrements in driving performance after sleep restriction and after alcohol consumption . Implication Consider alerting patients about the potential negative influence of untreated OSA on driving performance and their heightened vulnerability after sleep deprivation and alcohol consumption . The Editors Obstructive sleep apnea ( OSA ) causes excessive daytime somnolence and reduced vigilance , concentration , and neurocognitive function ( 1 , 2 ) . Patients with OSA , particularly those with moderate to severe disease , have a 2- to 7-fold increased risk for motor vehicle accidents ( 310 ) . Community surveys have shown that approximately 7 % of the middle-aged population has at least mild OSA ( > 10 obstructive events per hour of sleep ) ( 1113 ) , and up to 80 % of these cases are undiagnosed ( 1416 ) . For patients whose condition is diagnosed , delays in instituting treatment are common ( 17 ) . Between 46 % and 83 % of patients do not adhere to treatment over the long term ( 18 ) . The many patients with undiagnosed or untreated OSA represent a serious public health concern with respect to road safety . Accidents related to OSA result in an estimated 1400 road fatalities and cost $ 15.9 billion annually in the United States alone ( 19 ) . Improving access to diagnosis and treatment may help reduce this public health burden . However , even with improved sleep medicine services , many unidentified or untreated patients with OSA will probably remain at increased risk for motor vehicle accidents . A better underst and ing of the factors contributing to motor vehicle accidents among patients with OSA is therefore needed to develop cost-effective prevention strategies . This study was design ed to compare the effects of 2 common lifestyle factors , low-dose alcohol and acute partial sleep deprivation , on driving simulator performance between untreated patients with OSA and healthy matched control participants . We postulated that because of previous chronic sleep disruption and possible hypoxia-induced brain damage ( 2 , 2026 ) , patients with OSA would be more vulnerable to the effects of these common , mild central nervous system stressors and would experience significantly greater decrements in driving performance . Methods The study was approved by the Human Research Ethics Committees of the Repatriation General Hospital , University of South Australia , and University of Adelaide . Participants were introduced to the study objectives and protocol during an introductory session , gave written informed consent , and were remunerated for their participation . Study Design Patients with OSA and control participants underwent driving simulator assessment s under 3 conditions that were presented in r and om and counterbalanced order : after a normal nighttime sleep , after a single night of sleep restriction ( 4 hours in bed from 2:00 a.m. to 6:00 a.m. ) , and after acute administration of low-dose alcohol ( target blood alcohol concentration , 0.05 g/dL ) . All driving simulator sessions began at 2:00 p.m. and were conducted at least 5 days apart to avoid carryover effects from the previous interventions . Participant Selection Thirty-eight untreated patients with OSA of varying severity were recruited after diagnostic polysomnography . Neither they nor their referring physician had specific concerns about their driving . To minimize selection bias , patients were told that the study objective was to investigate general neurocognitive performance ; they were unaware that the trial measured driving performance until after they agreed to attend an introductory session . Twenty healthy control participants matched for age and sex were recruited from the general population through newspaper advertisements , which only generally described the study and did not mention driving performance measures . Exclusion criteria were employment as a professional driver or shift worker ; history of driving less than 2 years or less than 2 hours per week ; notable medical comorbid conditions ( such as cardiac or respiratory failure ) , periodic limb movement disorder ( periodic limb movement arousal index > 5 per hour ) , or past head injury or depression ; use of alertness-altering prescription medications that may change neurocognitive function ( such as antihistamines , opiates , or antidepressants ) ; and history of alcohol abuse or current use of recreational drugs . Control participants were also excluded if they had higher-than-normal scores on sleep quality and daytime drowsiness question naires . Baseline Measures Before the driving simulator assessment , all participants completed question naires that evaluated general health ( medical conditions , medication , alcohol intake , caffeine and drug use ) , sleep quality and habits , and daytime drowsiness using the Pittsburgh Sleep Quality Index ( 27 ) and the Epworth Sleepiness Scale ( 28 ) . All participants underwent overnight st and ard diagnostic polysomnography with the following recordings : electroencephalography ( C3/A2 , C4/A1 lead placements ) , left and right electrooculography , submental electromyography , nasal cannulization to measure nasal pressure , limb movement sensors , inductive plethysmography for thoracoabdominal motion , lead II electrocardiography , and finger pulse oximetry ( to measure arterial oxygen saturation ) . All signals were digitized and stored by using a Compumedics-E Series sleep system ( Melbourne , Australia ) . Sleep and sleep arousals were scored by using st and ardized methods ( 29 , 30 ) . Apneas and hypopneas were scored according to internationally agreed-on criteria ( 30 ) . All studies were scored by 1 staff member certified by the Board of Registered Polysomnographic Technicians . Table 1 shows participant characteristics , sleep study results , caffeine and alcohol consumption , and medication use . Table 1 . Patient Characteristics , Polysomnography Results , and Medication Use Main Outcome Measures The main outcome measures were performance on the driving simulator , including lateral steering deviation , braking reaction time , crash frequency , and precrash electroencephalography and electrooculography results . Driving performance was assessed by using the AusEd driving simulator ( Woolcock Institute for Medical Research , Sydney , Australia ) , which ran on a purpose -built Windows 2000 workstation ( Microsoft , Redmond , Washington ) with a 19-inch FP937s monitor ( BenQ , Taipei , Taiwan ) ; the MOMO steering wheel and pedals ( Logitech , Fremont , California ) were used to assess the driving variables . Steering deviation was measured as the average deviation in centimeters from the driver 's median lane position sample d at 30 Hz . Participants were instructed to maintain speed within 60 to 80 km/h but to apply the brakes as quickly as possible whenever a slow-moving truck appeared ahead in the driving lane . The latter occurred 7 times during the drive , and the mean braking reaction time was computed for the 7 truck-ahead incidents . Crashes occurring throughout the driving task were defined as follows : car deviating from the road ( all 4 wheels completely off the road ) , collision with a truck , or stationary position of the car for more than 3 seconds . The main outcome measure for crashes was the number of control participants and patients with OSA who experienced at least 1 crash incident . A secondary crash analysis was undertaken to determine whether crashes were associated with brief falling-asleep episodes and prolonged eye closures . Fifteen-second epochs of electroencephalography , electrooculography , and synchronized video ( head and shoulders ) before each crash ( crash epoch ) were scored for the presence of prolonged eye closure ( > 2 seconds ) and microsleeps ( > 2 seconds of continuous electroencephalographic theta activity ) within each crash epoch . A r and om sample of an equal number of 15-second noncrash epochs was selected and matched within participants and condition so that they could be compared with the crash epochs . The simulated driving task used in the study consisted of a 90-minute country nighttime drive on a predominantly straight dual-lane road with bends occurring at 10-minute intervals , each taking approximately 30 seconds to negotiate . There was no oncoming traffic or traffic lights . Driving simulator studies have been shown to correlate reasonably well with on-road driving ( 31 , 32 ) , and the AusEd simulator has been vali date d and shown to be sensitive to fatigue in a range of experimental setting s ( 3337 ) . Detailed Experimental Procedures For all 3 conditions , participants ' sleep patterns and duration were monitored throughout the study by using actigraphy monitors ( Actiwatch Model-AW64 , Mini-Mitter Co. , Bend , Oregon ) worn from at least 5 days before the experiments began until study completion to estimate sleep/wake timing , to ensure adherence to the sleep restriction protocol , and to ensure that patients did not nap in the 24 hours before the experiments ( 38 ) . In addition , during the night of sleep restriction , participants left a message on a time- and date -stamped answering machine at bedtime ( 2:00 a.m. ) and wake time ( 6:00 a.m. ) , again to ensure adherence to the protocol . Participants were instructed to abstain from alcohol and caffeinated beverages , not to nap for 24 hours before each experimental session , and to consume breakfast before 9:00 a.m. on the day of each experiment . They were transported by taxi to and from the laboratory . Upon arrival at the laboratory at 12:00 p.m. , each participant 's blood alcohol concentration was estimated by using a calibrated breathalyzer ( & NA ; A titration procedure using immediate‐release morphine given 4‐hourly is recommended during start of oral morphine for cancer pain . This recommendation is not based on evidence from controlled studies , and many physicians start morphine treatment with controlled‐release morphine . We included 40 patients with malignant disease and pain despite treatment with opioids for mild to moderate pain in a r and omized , double‐blind , double‐dummy , parallel‐group study comparing titration with immediate‐release morphine given 4‐hourly with titration with sustained‐release morphine given once daily . The primary end point was the time needed to achieve adequate pain relief Secondary end points were other symptoms ( nausea , tiredness , lack of sleep , vertigo , appetite and constipation ) , health related quality of life and patient satisfaction . The mean times needed for titration were 2.1 ( 95 % CI ; 1.4–2.7 ) days using immediate‐release morphine and 1.7 ( 95 % CI ; 1.1–2.3 ) days using sustained‐release morphine . Patients titrated with immediate‐release reported statistically significant more tiredness at the end of titration . We observed no other differences in adverse effects or health related quality of life functions between the two treatments . Similar global satisfactions with the morphine treatments were reported . In conclusion , a simplified titration using sustained‐release morphine once daily is equally effective as immediate‐release morphine given 4‐hourly Potential iatrogenic mood and cognitive declines associated with long-acting opioid therapy were examined in 19 patients receiving long-acting oral opioid medications and compared to ten patients receiving usual care . Pain , mood , and cognitive function were measured before and after achieving stable doses . In addition to reducing pain , long-acting opioid medication reduced anxiety and hostility . No declines in cognitive function were associated with the long-acting opioid medications , and the group receiving long-acting opioid medications showed significant improvement on a measure of psychomotor speed and sustained attention . Both patient groups reported significant reductions in perceived impairment in daily activities due to pain . Treatment responders taking long-acting opioid medications ( 63 % ) were taking a significantly lower dose at follow-up than the treatment non-responder group . These findings suggest that long-acting opioid medications can improve mood and do not impair cognitive functioning in patients with chronic non-cancer pain OBJECTIVE To evaluate driving performance , cognition , and balance in patients with chronic nonmalignant pain before and after the addition of transdermal fentanyl to their treatments . DESIGN Prospect i ve , one-group pretest-posttest design . SETTING Outpatient pain center associated with a large , urban medical school . INTERVENTIONS Patients taking less than a 15-mg equivalent of oxycodone per day took baseline driving performance , cognitive , and balance tests . Transdermal fentanyl was initiated and titrated in 25-microg/hour increments , weighing benefits and side effects . At the end of a 1-month period , the achieved dose was maintained for another month . After they were stabilized for 1 month , patients repeated driving , cognitive , and balance tests . RESULTS Twenty three patients completed the study ; three discontinued secondary to side effects . The median dose at the end of the titration period was 50 microg/hour ( 48 % ) . No differences were found in driving simulation measures between the pretreatment and posttreatment periods . No decrements in cognitive performance were found . Improvements in visual motor tracking , visual memory , and attention were found during treatment with transdermal fentanyl . No differences in balance or body sway were found . Pain decreased over the course of treatment . CONCLUSIONS The addition of transdermal fentanyl to a treatment regimen containing no opiates or small amounts of opiates for patients with chronic nonmalignant pain did not negatively affect their driving performances , reaction times , cognition , or balance . Future studies in this area are needed to guide treatment decisions CONTEXT R and omized controlled trials can answer questions of efficacy , but long-term pharmacovigilance studies generate complementary safety data . OBJECTIVES Level I evidence supports short-term efficacy of opioids in reducing chronic refractory dyspnea . This study aim ed to determine the minimum effective once-daily dose of sustained-release morphine , and whether net clinical benefits are sustained safely . METHODS In a Phase II dose increment study , 10 mg daily of sustained-release morphine was administered , and increased in nonresponders by 10 mg daily each week to a maximum of 30 mg daily . The participant was withdrawn if there were unacceptable side effects or no response to maximum dose . If participants had a 10 % improvement in dyspnea over their own baseline , they joined a long-term Phase IV effectiveness/safety study at that dose . Complying with Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) guidelines , response and side effects are described , with demographic and clinical characteristics of responders . RESULTS Eighty-three participants ( 53 males , mean age 75 years , 54 % with chronic obstructive pulmonary disease ) provided more than 30 patient-years of data . Fifty-two participants derived ≥ 10 % benefit ( on average 35 % improvement over baseline ) , giving a response rate of 62 % ( number needed to treat of 1.6 : number needed to harm 4.6 ) ; for 70 % , this dose was 10mg/24h . Benefit was maintained at three months for 28 ( 33 % ) people . Ranking of breathlessness was reduced significantly ( P<0.001 ) , but constipation increased ( P<0.001 ) despite laxatives . There were no episodes of respiratory depression or hospitalizations as a result of the sustained-release morphine . Overall , one in three people continued to derive benefit at three months . CONCLUSION Ten milligrams of sustained-release oral morphine once daily is safe and effective for most people who respond The purpose of this study was to establish and vali date a driving simulator method for assessing drug effects on driving . To achieve this , we used ethanol as a positive control , and examined whether ethanol affects driving performance in the simulator , and whether these effects are consistent with performance during real driving on a test track , also under the influence of ethanol . Twenty healthy male volunteers underwent a total of six driving trials of 1h duration ; three in an instrumented vehicle on a closed-circuit test track that closely resembled rural Norwegian road conditions , and three in the simulator with a driving scenario modelled after the test track . Test subjects were either sober or titrated to blood alcohol concentration ( BAC ) levels of 0.5g/L and 0.9g/L. The study was conducted in a r and omised , cross-over , single-blind fashion , using placebo drinks and placebo pills as confounders . The primary outcome measure was st and ard deviation of lateral position ( SDLP ; " weaving " ) . Eighteen test subjects completed all six driving trials , and complete data were acquired from 18 subjects in the simulator and 10 subjects on the test track , respectively . There was a positive dose-response relationship between higher ethanol concentrations and increases in SDLP in both the simulator and on the test track ( p<0.001 for both ) . In the simulator , this dose-response was evident already after 15min of driving . SDLP values were higher and showed a larger inter-individual variability in the simulator than on the test track . Most subjects displayed a similar relationship between BAC and SDLP in the simulator and on the test track ; however , a few subjects showed striking dissimilarities , with very high SDLP values in the simulator . This may reflect the lack of perceived danger in the simulator , causing reckless driving in a few test subjects . Overall , the results suggest that SDLP in the driving simulator is a sensitive measure of ethanol impaired driving . The comparison with real driving implies relative external validity of the simulator Abstract Twenty‐four patients with severe pain related to cancer completed a r and omised , double‐blind , double‐dummy , crossover study examining morphine pharmacokinetics and pharmacodynamics when the same 24‐h morphine dose was administered using two modified release oral morphine formulations ; either one dose of KapanolTM ( a new sustained release polymer coated pellet formulation administered in capsule form , Glaxo Wellcome group of companies ) per 24 h , or MS Contin ® ( Purdue Frederick Company , Connecticut , USA ) administered at 12‐h intervals . The morphine dose was optimised for each patient using an immediate release morphine solution in the lead‐in period to provide the most favourable balance between pain relief and side‐effects . Patients were then r and omly allocated to receive their 24‐h morphine dose as either Kapanol or MS Contin in period 1 . Patients recorded daily measures of pain relief and morphine related side‐effects ( morphine pharmacodynamics ) in a diary . Patients were admitted to the Pain Management Unit on the morning of day 7 ( ±1 day ) and frequent blood sample s were collected for 24 h following the 10:00 h dose to fully characterise the pharmacokinetic profile for morphine and its metabolites at steady state . Morphine pharmacodynamics and the amount and timing of rescue medication ( dextromoramide ) were also recorded during this time . Period 2 , which commenced at 10:00 h on day 8 , was identical to period 1 except the modified release formulations were changed . The pharmacokinetic profile of Kapanol exhibited a significantly higher Cmin ( minimum plasma morphine concentration ) , less fluctuation in plasma morphine concentration throughout the dosing interval , a longer Tmax ( time associated with the maximum morphine concentration ) and a greater time that the plasma morphine concentration was ≥75 % of Cmax ( an index of the control the formulation exerts over the morphine release rate ) compared to that of MS Contin . Some of these pharmacokinetic differences ( e.g. , Cmin and fluctuation in plasma morphine concentration ) were surprising given that the dosing interval for Kapanol ( 24 h ) was double that of MS Contin ( 12 h ) . There was no significant difference between the Kapanol and MS Contin treatment phases in any of the pharmacodynamic parameters , morphine related side‐effects , the percentage of patients taking rescue medication as well as the amount or time to the first dose of rescue analgesia on day 7 in periods 1 and 2 , patient or investigator assessment s of global efficacy at the end of periods 1 and 2 , or patient treatment preference at the end of the study . Once a day Kapanol provided the same degree of pain relief and morphine related side‐effects as 12‐h MS Contin OBJECTIVES The objective of this study was to evaluate the impact of driving cessation on social integration and perceived support from relatives and friends among older adults . METHODS Data came from the population -based Baltimore Epidemiologic Catchment Area Study . We restricted analyses to participants aged 60 + with a history of driving ( n=398 ) . Social integration ( number and frequency of contact ) and perceived social support from relatives/friends , driving status ( continuing or ceased ) , and demographic and health characteristics were assessed at interviews 13 years apart . The potential mediating role of ability to use public transit was also investigated . We used repeated measures r and om-intercept models to evaluate the effect of driving cessation on social network characteristics over time . RESULTS Former drivers were older , were more likely to be female and non-White , had lower education , had poorer self-rated health , and had lower Mini-Mental State Examination scores relative to continuing drivers . Over the follow-up period , cessation was associated with reduced network of friends ( odds ratio=0.49 , p<.05 ) . This association was not mediated by ability to use public transportation . Cessation had no impact on support from friends or relatives . DISCUSSION Social integration is negatively affected by driving cessation even among elders who feel competent in using alternative forms of transportation , at least concerning networks of friends BACKGROUND There are epidemiological data indicating that medical and /or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances . One of those substances is benzodiazepines . It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone . METHODS Twenty volunteers participated in a crossover , r and omized , double-blind study in which they received placebo , 0.5 mg alprazolam , 10 mg oxycodone , and 0.5 mg alprazolam combined with 10 mg oxycodone , all p.o . Subjective , psychomotor , and physiological measures were assessed during each of the four sessions . RESULTS Oxycodone by itself increased drug liking and " take again " ratings relative to placebo , but these ratings were not increased when oxycodone was taken with alprazolam , which by itself did not increase either of these ratings . The two drugs in combination produced stronger effects ( larger in magnitude or longer lasting ) than when either was taken alone on a number of measures , including psychomotor performance impairment . CONCLUSIONS In healthy volunteers , abuse liability-related subjective effects of oxycodone were not enhanced by alprazolam . There was enhanced behavioral toxicity when the drugs were taken together , and thus , this is of significant concern from a public safety st and point & NA ; Forty patients with cancer pain receiving intermittent narcotics were admitted to a prospect i ve study design ed to assess the cognitive effects of narcotics . Twenty patients had undergone no change in narcotic dose or type ⩾ 7 days ( stable dose , SD , group ) , and 20 patients had undergone an increase of ⩾ 30 % in dose ⩽ 3 days before ( increased dose , ID , group ) . Age , primary tumor , type , dose and route of narcotic were not different between the SD and ID group . Cognitive tests ( finger tapping , FT , 10 and 30 sec , arithmetics , A , reverse memory of digits , RM , and visual memory , VM ) were performed in all patients before and 45 min after their morning dose of narcotics for 2 consecutive days . Mean percentual change in FT 10 sec , FT 30 sec , A , RM , and VM after the narcotic dose were 97 ± 9 % , 100 ± 14 % , 100 ± 13 % , 100 ± 15 % , 98 ± 19 % , in the SD group , vs. 77 ± 14 % ( P < 0.001 ) , 83 ± 13 % ( P < 0.001 ) , 124 ± 21 % ( P < 0.001),60 ± 21 % ( P < 0.001 ) and 68 ± 21 % ( P < 0.001 ) in the ID group , respectively . Our results suggest that patients who undergo a significant increase in the dose of intermittent narcotics experience significant cognitive impairment , that disappears after 1 week of the increase . More research is needed to better characterize the cognitive toxicity of intermittent narcotics , and to determine the cognitive effects of long acting narcotics , continuous infusions , or of the addition of amphetamines Previous studies have only partially characterized the road‐accident risks linked to driving while taking opioid analgesics used for moderate pain . 1 , 2 , 3 , 4 A prospect i ve cohort design with data from national population –based registries — the Norwegian Prescription Data base and the Norwegian Road Accident Registry— and observation of > 8 million person‐years were used in order to examine whether a driver who has filled a prescription for codeine or tramadol is at increased risk of being involved in a road accident result ing in injury to persons |
11,715 | 32,015,455 | We found no significant differences in prolactin levels between CYP2D6 metabolic groups .
Current evidence does not support using CYP2D6 genotyping to reduce risk of antipsychotic-induced hyperprolactinemia . | Hyperprolactinemia is a known adverse drug reaction to antipsychotic treatment .
Antipsychotic blood levels are influenced by cytochrome P450 enzymes , primarily CYP2D6 .
Variation in CYP450 genes may affect the risk of antipsychotic-induced hyperprolactinemia .
We undertook a systematic review and meta- analysis to assess whether CYP2D6 functional genetic variants are associated with antipsychotic-induced hyperprolactinemia . | Quetiapine is an atypical antipsychotic used for treatment of schizophrenia . Variability in response to this drug may be associated with pharmacogenetics . The aim of this study was to identify genetic markers related to the pharmacokinetics , pharmacodynamics , and adverse effects of quetiapine . The study population comprised 79 healthy volunteers from two bioequivalence trials who were genotyped to identify polymorphisms in genes encoding enzymes , receptors , and transporters . Quetiapine plasma levels were quantified using high-performance liquid chromatography/mass spectrometry . Prolactin plasma levels were detected by indirect chemiluminescence . Possible adverse effects were recorded throughout the study . Factors with P value of 0.1 or less in the univariate analysis were included in a multiple regression analysis ( logistic regression for adverse reactions ) . The area under the curve and clearance of quetiapine were affected by polymorphisms in CYP1A2 and DRD3 , respectively . Men had a lower quetiapine area under the curve compared with women . Prolactin iCmax was higher in volunteers harboring polymorphisms in CYP2C19 and AGT . An association was detected between polymorphisms in CYP1A1 and CYP2C9 and somnolence . Several polymorphisms are responsible for differences in the pharmacokinetics , pharmacodynamics , and safety of quetiapine in healthy individuals Objectives Hyperprolactinemia is a common side effect of first-generation antipsychotics mediated by antagonism of dopaminergic neurotransmission in the pituitary . Most first-generation antipsychotics are metabolized by CYP2D6 in the liver . Further , CYP2D6 is expressed in the human brain as a 5-methoxyindolethylamine O-demethylase potentially contributing to regeneration of serotonin from 5-methoxytryptamine . As dopaminergic neurotransmission is subject to regulation by serotonin , CYP2D6 may exert a nuanced ( serotonergic ) influence on dopaminergic tone in the pituitary . CYP2D6 * 10 is an allele associated with reduced enzyme function and occurs in high frequency ( about 50 % ) in Asians . We prospect ively evaluated significance of CYP2D6 genetic variation for prolactin response to perphenazine ( a model first-generation antipsychotic ) in Asians . Methods A single oral dose of perphenazine ( 0.1 mg/kg ) or placebo was administered to 22 medication-free nonsmoker healthy male Chinese – Canadian volunteers , following a double-blind within-subject r and omized design . Blood sample s were drawn at baseline and 2 , 3 , 4 , 5 and 6 h after drug administration . Results In volunteers with CYP2D6 * 10/CYP2D6 * 10 genotype , the mean area under curve ( AUC0−6 ) for perphenazine concentration was 2.9-fold higher than those who carry the CYP2D6 * 1 allele ( P<0.01 ) . Notably , volunteers homozygous for CYP2D6 * 10 exhibited a significant reduction ( 66 % ) in mean pharmacodynamic tissue sensitivity as measured by the ( prolactin-AUC0−6/perphenazine-AUC0−6 ) ratio ( P=0.02 ) . Conclusions CYP2D6 genotype is a significant contributor to perphenazine concentration in Chinese – Canadians . Importantly , prolactin response , when normalized per unit perphenazine concentration , appears to be blunted in volunteers homozygous for CYP2D6 * 10 . We suggest that CYP2D6 genetic variation may potentially influence pharmacodynamic tissue sensitivity in the pituitary , presumably through disposition of an endogenous substrate ( e.g. 5-methoxytryptamine ) The effect of pharmacogenetic testing for CYP450 2D6 and 2C19 on treatment costs have not yet been documented . This study used Danish patient registers to calculate healthcare costs of treating patients with diagnoses within the schizophrenic spectrum for 1 year with or without pharmacogenetic testing for polymorphisms in the genes for the CYP2D6 and CYP2C19 enzymes . In a r and omized , controlled trial , stratified with respect to metabolizer genotype , 104 patients were assigned to treatment based on pharmacogenetic testing and 103 patients to treatment as usual . R and om exclusion of extensive and intermediate metabolizers was used to increase the frequency of extreme metabolizers ( poor metabolizers and ultrarapid metabolizers for CYP2D6 ) to 20 % in both groups . Cost differences were analysed at several levels including ( i ) overall healthcare expenditure , ( ii ) psychiatric hospital cost ( iii ) nonpsychiatric hospital cost , ( iv ) primary care spending and ( v ) pharmaceuticals . Statistically significant differences in costs of psychiatric care dependent on metabolizer status were found between intervention groups . Pharmacogenetic testing significantly reduced costs among the extreme metabolizers ( poor metabolizers and ultrarapid metabolizers ) to 28 % . Use of primary care services and pharmaceuticals was also affected by the intervention . This study confirms earlier findings that extreme metabolizers ( poor and ultrarapid metabolizers ) incur higher costs than similar patients with a normal metabolizer genotype . However , this study shows that these excess costs can be reduced by pharmacogenetic testing . Pharmacogenetic testing for CYP2D6 and CYP2C19 could thus be considered as a means of curtailing high psychiatric treatment costs among extreme metabolizers Abstract The role of the polymorphic cytochrome P450 2D6 ( CYP2D6 ) in the metabolism of risperidone to its major active metabolite , 9-hydroxyrisperidone ( 9-OH-risperidone ) , has been documented after single oral doses of the drug . In this study , the influence of the CYP2D6 polymorphism on the steady-state plasma concentrations of risperidone and 9-OH-risperidone was investigated . Thirty-seven schizophrenic patients on monotherapy with risperidone , 4–8 mg/day , were genotyped by RFLP and PCR for the major functional variants of the CYP2D6 gene . Steady state plasma levels of risperidone and 9-OH-risperidone were analysed by HPLC . Based on the genotype analysis , three patients were classified as ultrarapid metabolizers ( UM ) with an extra functional CYP2D6 gene , 16 were homozygous extensive metabolizers ( EM ) , 15 heterozygous EM and three poor metabolizers ( PM ) . The median steady-state plasma concentration-to-dose ( C/D ) ratios of risperidone were 0.6 , 1.1 , 9.7 and 17.4 nmol/l per mg in UM , homozygous EM , heterozygous EM and PM , respectively , with statistically significant differences between PM and the other genotypes ( P<0.02 ) . The C/D of 9-OH-risperidone also varied widely but was not related to the genotype . The risperidone/9-OH-risperidone ratio was strongly associated with the CYP2D6 genotype , with the highest ratios in PM ( median 0.79 ) . Heterozygous EM also had significantly higher ratios than homozygous EM ( median value 0.23 versus 0.04 ; P<0.01 ) or UM ( median 0.03 ; P<0.02 ) . No significant differences were found in the C/D of the sum of the plasma concentrations of risperidone and 9-OH-risperidone between the genotype groups . In conclusion , the steady-state plasma concentrations of risperidone and the risperidone/9-OH-risperidone ratio are highly dependent on the CYP2D6 genotype . However , as risperidone and 9-OH-risperidone are considered to have similar pharmacological activity , the lack of relationship between the genotype and the sum of risperidone and 9-OH-risperidone indicates that the CYP2D6 polymorphism may be of limited importance for the clinical outcome of the treatment OBJECTIVE The prevalence of hyperprolactinemia during treatment with conventional antipsychotic drugs or risperidone is under-recognized and requires further investigation . This open-label study was design ed to determine the extent of this potential problem in a routine clinical setting . METHODS Four hundred and two adult in patients or out patients with a diagnosis of schizophrenia , schizophreniform disorder , or schizoaffective disorder were studied in a 1-day , point prevalence trial . Neither clinicians nor patients had any prior knowledge of serum prolactin levels or any potential associated adverse events , and patients were required to have been treated with a conventional antipsychotic drug or risperidone for a minimum of 3 months prior to study entry . Patients taking concomitant medications known to elevate prolactin were excluded . Rigorous assessment of serum prolactin was performed to estimate the prevalence rate of hyperprolactinemia , defined as a level above the upper limit of normal ( > 18.77 ng/ml for males , and > 24.20 ng/ml for females ) . Patients were stratified within antipsychotic treatment by gender and , for females , by menopausal status . RESULTS Serum prolactin was obtained from 147 females ( age range : 21 - 69 years ; mean age=44.51 years ) and 255 males ( age range : 18 - 66 years ; mean age=40.76 years ) . The prevalence of hyperprolactinemia among women of reproductive age ( n=90 ) was 65.6 % ( mean serum prolactin=69.0 ng/ml ) , and among postmenopausal women ( n=51 ) , it was 45.1 % ( mean serum PRL=49.0 ng/ml ) . The prevalence of hyperprolactinemia across all males ( n=255 ) was 42.4 % ( mean serum PRL= 32.4 ng/ml ) . The prevalence of hyperprolactinemia among females taking risperidone ( N=42 ) was 88 % versus 47.6 % of those taking conventional antipsychotic drugs ( N=105 ) , with 48 % of those females of reproductive age on risperidone experiencing abnormal menstrual cycles ( secondary amenorrhea , oligomenorrhea , or polymenorrhea ) . Of all premenopausal females with hyperprolactinemia , 31.6 % had estradiol levels < or=19.8 pg/ml ( which is the mean estradiol level in postmenopausal female patients with normal prolactin ) . Across both genders , there were trends of low key reproductive hormone levels associated with prolactin elevations . Additionally , there was a trend correlation ( p=0.064 ) between prolactin concentration and the risk of menstrual abnormality among females of reproductive age . CONCLUSIONS Hyperprolactinemia is very prevalent among women and men treated with conventional antipsychotic medications or risperidone . Due to the adverse effects associated with hyperprolactinemia , this likelihood should be seriously considered when choosing an antipsychotic suitable for the patient Part I of this article discussed the potential functional importance of genetic mutations and alleles of the human cytochrome P450 2D6 ( CYP2D6 ) gene . The impact of CYP2D6 polymorphisms on the clearance of and response to a series of cardiovascular drugs was addressed . Since CYP2D6 plays a major role in the metabolism of a large number of other drugs , Part II of the article highlights the impact of CYP2D6 polymorphisms on the response to other groups of clinical ly used drugs . Although clinical studies have observed a gene-dose effect for some tricyclic antidepressants , it is difficult to establish clear relationships of their pharmacokinetics and pharmacodynamic parameters to genetic variations of CYP2D6 ; therefore , dosage adjustment based on the CYP2D6 phenotype can not be recommended at present . There is initial evidence for a gene-dose effect on commonly used selective serotonin reuptake inhibitors ( SSRIs ) , but data on the effect of the CYP2D6 genotype/phenotype on the response to SSRIs and their adverse effects are scanty . Therefore , recommendations for dose adjustment of prescribed SSRIs based on the CYP2D6 genotype/phenotype may be premature . A number of clinical studies have indicated that there are significant relationships between the CYP2D6 genotype and steady-state concentrations of perphenazine , zuclopenthixol , risperidone and haloperidol . However , findings on the relationships between the CYP2D6 genotype and parkinsonism or tardive dyskinesia treatment with traditional antipsychotics are conflicting , probably because of small sample size , inclusion of antipsychotics with variable CYP2D6 metabolism , and co-medication . CYP2D6 phenotyping and genotyping appear to be useful in predicting steady-state concentrations of some classical antipsychotic drugs , but their usefulness in predicting clinical effects must be explored . Therapeutic drug monitoring has been strongly recommended for many antipsychotics , including haloperidol , chlorpromazine , fluphenazine , perphenazine , risperidone and thioridazine , which are all metabolized by CYP2D6 . It is possible to merge therapeutic drug monitoring and pharmacogenetic testing for CYP2D6 into clinical practice .There is a clear gene-dose effect on the formation of O-demethylated metabolites from multiple opioids , but the clinical significance of this may be minimal , as the analgesic effect is not altered in poor metabolizers ( PMs ) . Genetically caused inactivity of CYP2D6 renders codeine ineffective owing to lack of morphine formation , decreases the efficacy of tramadol owing to reduced formation of the active O-desmethyltramadol and reduces the clearance of methadone . Genetically precipitated drug interactions might render a st and ard opioid dose toxic . Because of the important role of CYP2D6 in tamoxifen metabolism and activation , PMs are likely to exhibit therapeutic failure , and ultrarapid metabolizers ( UMs ) are likely to experience adverse effects and toxicities . There is a clear gene-concentration effect for the formation of endoxifen and 4-OH-tamoxifen . Tamoxifen-treated cancer patients carrying CYP2D6 * 4 , * 5 , * 10 , or * 41 associated with significantly decreased formation of antiestrogenic metabolites had significantly more recurrences of breast cancer and shorter relapse-free periods . Many studies have identified the genetic CYP2D6 status as an independent predictor of the outcome of tamoxifen treatment in women with breast cancer , but others have not observed this relationship . Thus , more favourable tamoxifen treatment seems to be feasible through a priori genetic assessment of CYP2D6 , and proper dose adjustment may be needed when the CYP2D6 genotype is determined in a patient . Dolasetron , ondansetron and tropisetron , all in part metabolized by CYP2D6 , are less effective in UMs than in other patients . Overall , there is a strong gene-concentration relationship only for tropisetron . CYP2D6 genotype screening prior to antiemetic treatment may allow for modification of antiemetic dosing . An alternative is to use a serotonin agent that is metabolized independently of CYP2D6 , such as granisetron , which would obviate the need for genotyping and may lead to an improved drug response . To date , the functional impact of most CYP2D6 alleles has not been systematic ally assessed for most clinical ly important drugs that are mainly metabolized by CYP2D6 , though some initial evidence has been identified for a very limited number of drugs . The majority of reported in vivo pharmacogenetic data on CYP2D6 are from single-dose and steady-state pharmacokinetic studies of a small number of drugs . Pharmacodynamic data on CYP2D6 polymorphisms are scanty for most drug studies . Given that genotype testing for CYP2D6 is not routinely performed in clinical practice and there is uncertainty regarding genotype-phenotype , gene-concentration and gene-dose relationships , further prospect i ve studies on the clinical impact of CYP2D6-dependent metabolism of drugs are warranted in large cohorts |
11,716 | 25,143,742 | No effects by IPost on ST-segment resolution or on the majority of adverse clinical events were observed during follow up , except the incidence of congestive heart failure was found .
Evidence from this study suggests no cardioprotection from IPost , on surrogate and the majority of clinical end points . | OBJECTIVE We aim ed to summarize the evidence from r and omized clinical trials studies examining the efficacy of ischemic postconditioning ( IPost ) in ST-elevation myocardial infa rct ion . | Reproducibility and validity are prerequisites for a useful clinical scale . We therefore prospect ively tested the reproducibility and validity of the New York Heart Association criteria and the Canadian Cardiovascular Society criteria for the assessment of cardiac functional class and compared these criteria with a new Specific Activity Scale based on the metabolic costs of specific activities . The New York Heart Association estimates made by two physicians had a reproducibility of only 56 % , and only 51 % of the estimates agreed with treadmill exercise performance . Functional estimates based on the Canadian Cardiovascular Society criteria were significantly more reproducible ( 73 % ) , but not significantly more valid . The Specific Activity Scale was as reproducible as the Canadian Cardiovascular Society criteria , and its 68 % validity was significantly higher than the validities of the other systems . The easily administered Specific Activity Scale was equally reproducible and valid when used by a nonphysician . It was especially better than the other systems for the evaluation of true class II patients and was significantly less likely to underestimate treadmill performance . Although no set of questions can perfectly predict exercise tolerance , the Specific Activity Scale deserves wider prospect i ve testing Background — In animal models , brief periods of ischemia performed just at the time of reperfusion can reduce infa rct size , a phenomenon called postconditioning . In this prospect i ve , r and omized , controlled , multicenter study , we investigated whether postconditioning may protect the human heart during coronary angioplasty for acute myocardial infa rct ion . Methods and Results — Thirty patients , su bmi tted to coronary angioplasty for ongoing acute myocardial infa rct ion , contributed to the study . Patients were r and omly assigned to either a control or a postconditioning group . After reperfusion by direct stenting , control subjects underwent no further intervention , whereas postconditioning was performed within 1 minute of reflow by 4 episodes of 1-minute inflation and 1-minute deflation of the angioplasty balloon . Infa rct size was assessed by measuring total creatine kinase release over 72 hours . Area at risk and collateral blood flow were estimated on left ventricular and coronary angiograms . No adverse events occurred in the postconditioning group . Determinants of infa rct size , including ischemia time , size of the area at risk , and collateral flow , were comparable between the 2 groups . Area under the curve of creatine kinase release was significantly reduced in the postconditioning compared with the control group , averaging 208 984±26 576 compared with 326 095±48 779 ( arbitrary units ) in control subjects , ie , a 36 % reduction in infa rct size . Blush grade , a marker of myocardial reperfusion , was significantly increased in postconditioned compared with control subjects : 2.44±0.17 versus 1.95±0.27 , respectively ( P<0.05 ) . Conclusions — This study suggests that postconditioning by coronary angioplasty protects the human heart during acute myocardial infa rct ion Background Reduction of infa rct size by ischemic postconditioning ( IPost ) has been reported in smaller proof‐of‐concept clinical studies , but has not been confirmed in other smaller studies . The principle needs to be evaluated in larger groups of ST‐elevation myocardial infa rct ion ( STEMI ) patients before being implemented in clinical practice . This study assessed the effect of ischemic postcoditioning ( IPost ) on infa rct size in patients with STEMI treated by primary percutaneous coronary intervention ( PCI ) . Methods and Results Patients with first‐time STEMI , < 6 hours from symptom onset , referred to primary PCI were r and omized to IPost or control groups . IPost was administered by 4 cycles of 1‐minute reocclusion and 1‐minute reperfusion , starting 1 minute after opening , followed by stenting . In the control group , stenting was performed immediately after reperfusion . The primary endpoint was infa rct size measured by cardiac magnetic resonance after 4 months . A total of 272 patients were r and omized . Infa rct size ( percent of left ventricular mass ) after 4 months ( median values and interquartile range ) was 14.4 % ( 7.7 , 24.6 ) and 13.5 % ( 8.1 , 19.3 ) in the control group and IPost group , respectively ( P=0.18 ) . No significant impact of IPost was found when controlling for baseline risk factors of infa rct size in a multivariate linear regression model ( P=0.16 ) . The effects of IPost on secondary endpoints , including markers of necrosis , myocardial salvage , and ejection fraction , as well as adverse cardiac events during follow‐up , were consistently neutral . Conclusions In contrast to several smaller trials reported previously , we found no significant effects of IPost on infa rct size or secondary study outcomes . Clinical Trial Registration URL : http://www . clinical trials.gov Unique identifier : NCT.No . PO1506 Background —Postconditioning has been suggested to reduce myocardial damage during primary percutaneous coronary intervention ( PPCI ) in patients with ST-segment – elevation myocardial infa rct ion . However , because clinical experience is limited , we examined the cardioprotective effects of postconditioning , using cardiac MRI in patients treated with PPCI . Methods and Results —One hundred eighteen patients with ST-segment – elevation myocardial infa rct ion referred for PPCI were r and omly assigned to have either conventional PPCI or PPCI with postconditioning . Postconditioning was performed immediately after obtained reperfusion with 4 balloon occlusions , each lasting 30 seconds , followed by 30 seconds of reperfusion . The primary end point was myocardial salvage after 3 months as judged by delayed enhancement cardiac MRI . We found a 19 % relative reduction of infa rct size in the postconditioning group ( 51±16 % of total area at risk versus 63±17 % , P<0.01 ) , corresponding to a 31 % increase in salvage ratio . The number of patients developing heart failure was significantly fewer in the postconditioning group ( 27 % versus 46 % , P=0.048 ) . No significant evidence of interaction between the impact of postconditioning and the location of the culprit lesion or size of the myocardium at risk was detected ( P=0.21 and P=0.71 ) . Conclusions —Mechanical postconditioning reduces infa rct size in patients with ST-segment – elevation myocardial infa rct ion treated with PPCI . The impact of mechanical postconditioning seems to be independent of the size of myocardium at risk . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique Identifier : NCT00507156 AIMS To assess the short- and long-term effects of postconditioning ( p-cond ) on infa rct size , extent of myocardial salvage , and left ventricular ejection fraction ( LVEF ) in a series of patients presenting with evolving ST-elevation myocardial infa rct ion ( STEMI ) . Previous studies have shown that p-cond during primary percutaneous coronary intervention ( PCI ) confers protection against ischaemia-reperfusion injury and thus might reduce myocardial infa rct size . METHODS AND RESULTS Seventy-nine patients undergoing PCI for a first STEMI with TIMI grade flow 0 - 1 and no collaterals were r and omized to p-cond ( n= 39 ) or controls ( n= 40 ) . Postconditioning was performed by applying four consecutive cycles of 1 min balloon inflation , each followed by 1 min deflation . Infa rct size , myocardial salvage , and LVEF were assessed by cardiac-MRI 1 week and 6 months after MI . Postconditioning was associated with lower myocardial salvage ( 4.1 ± 7.2 vs. 9.1 ± 5.8 % in controls ; P= 0.004 ) and lower myocardial salvage index ( 18.9 ± 27.4 vs. 30.9 ± 20.5 % in controls ; P= 0.038 ) . No significant differences in infa rct size and LVEF were found between the groups at 1 week and 6 months after MI . CONCLUSION This r and omized study suggests that p-cond during primary PCI does not reduce infa rct size or improve myocardial function recovery at both short- and long-term follow-up and might have a potential harmful effect Background — We previously demonstrated that ischemic postconditioning decreases creatine kinase release , a surrogate marker for infa rct size , in patients with acute myocardial infa rct ion . Our objective was to determine whether ischemic postconditioning could afford ( 1 ) a persistent infa rct size limitation and ( 2 ) an improved recovery of myocardial contractile function several months after infa rct ion . Methods and Results — Patients presenting within 6 hours of the onset of chest pain , with suspicion for a first ST-segment – elevation myocardial infa rct ion , and for whom the clinical decision was made to treat with percutaneous coronary intervention , were eligible for enrollment . After reperfusion by direct stenting , 38 patients were r and omly assigned to a control ( no intervention ; n=21 ) or postconditioned group ( repeated inflation and deflation of the angioplasty balloon ; n=17 ) . Infa rct size was assessed both by cardiac enzyme release during early reperfusion and by 201thallium single photon emission computed tomography at 6 months after acute myocardial infa rct ion . At 1 year , global and regional contractile function was evaluated by echocardiography . At 6 months after acute myocardial infa rct ion , single photon emission computed tomography rest-redistribution index ( a surrogate for infa rct size ) averaged 11.8±10.3 % versus 19.5±13.3 % in the postconditioned versus control group ( P=0.04 ) , in agreement with the significant reduction in creatine kinase and troponin I release observed in the postconditioned versus control group ( −40 % and −47 % , respectively ) . At 1 year , the postconditioned group exhibited a 7 % increase in left ventricular ejection fraction compared with control ( P=0.04 ) . Conclusions — Postconditioning affords persistent infa rct size reduction and improves long-term functional recovery in patients with acute myocardial infa rct ion 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 No-reflow phenomenon is a serious complication of percutaneous coronary intervention ( PCI ) which is closely related to the incidence of major adverse cardiovascular events . It has been demonstrated that Postconditioning ( PostC ) during primary PCI confers protection against ischemia – reperfusion injury and thus might reduce infa rct size . However , whether PostC may exert its beneficial effects on acute myocardial infa rct ion ( AMI ) patients by reducing no-reflow phenomenon is still unknown . Sixty two patients diagnosed with ST-elevation AMI were r and omly assigned to study group ( n = 32 ) or control group ( n = 30 ) . Blood sample s were obtained and assayed for creatine kinase MB ( CK-MB ) and high-sensitive C-reactive protein ( hs-CRP ) . Determinants of reflow , including final thrombolysis in myocardial infa rct ion ( TIMI ) grade -3 flow , ST-segment resolution ( STR ) , myocardial blush grade s-3 ( MBG-3 ) and corrected thrombolysis in myocardial infa rct ion frame count ( cTFC ) , were comparative between the two groups . Compared with control group , more patients in study group were identified as the final TIMI grade -3 flow ( 81.3 vs. 56.7 % , P = 0.036 ) , MBG-3 ( 23 vs. 14 % , P = 0.043 ) and STR ≥50 % ( 93.8 vs. 73.3 % , P = 0.029 ) , while patients in study group had less cTFC ( 28.5 ± 9.1 vs. 37.4 ± 12.4 , P = 0.002 ) After PCI , study group was associated with lower levels of CK-MB ( 2,397.6 ± 470.2 vs. 2,159.9 ± 485.5 , P = 0.028 ) , Troponin-I ( 197.5 ± 32.5 vs. 154 ± 43.1 , P = 0.041 ) and hs-CRP ( 5.5 ± 4.5 vs. 9.5 ± 5.2 mg/L , P = 0.019 ) in comparison with control group . Left ventricle ejection fraction was better in the study group than in the control group ( 55.1 ± 9.8 vs. 42.9 ± 10.7 , P = 0.042 ) . PostC could improve myocardial reperfusion in patients with ST-elevation AMI undergoing PCI by reducing no-reflow . However , due to the limited sample size , the results of our study should not be considered conclusive BACKGROUND Postconditioning has been shown to reduce infa rct size during reperfusion ( < 72 hours ) . However , it is unknown whether the infa rct size reduction with postconditioning is a long-term effect after clinical percutaneous coronary intervention ( PCI ) . The present study tested the hypothesis that postconditioning during primary PCI preserves global cardiac function and reduces infa rct size in patients after prolonged reperfusion . METHODS Fortyone patients undergoing PCI were r and omly assigned to a control ( n = 18 ) or postconditioning ( n = 23 ) group within 90 minutes after admission . After predilatation , in the Control group , no intervention was applied in the first 3 minutes of reperfusion , while in the Postconditioning group , three cycles of 30-second angioplasty balloon deflation and 30-second inflation were repetitively applied . RESULTS There was a trend toward increased ejection fraction quantified by echocardiography in the Postconditioning group compared to that in the Control group ( 54 + /- 12.9 % vs. 44 + /- 16.7 % ; p > 0.05 ) . Infa rct size represented by the area under the curve of creatine-kinase activity during the first 72 hours of reperfusion was significantly less by 27 % in the Postconditioning group than that in the Control group ( 58,002 + /- 593 vs. 79,787 + /- 681 ; p = 0.04 ) . After 7 days of reperfusion , infa rct size quantified by single-photon emission computed tomography was 27 % smaller in the Postconditioning group than that measured in the Control group ( 31.3 + /- 8.6 % vs. 22.8 + /- 6.7 % of left ventricle ; p < 0.05 ) . CONCLUSION This study demonstrates that postconditioning following PCI significantly protects the heart against ischemia/reperfusion-induced injury . More importantly , this study indicates that protection with postconditioning is still apparent 1 week following reperfusion , suggesting long-term protection Dropout in r and omised controlled trials is common and threatens the validity of results , as completers may differ from people who drop out . Differing dropout rates between treatment arms is sometimes called differential dropout or attrition . Although differential dropout can bias results , it does not always do so . Similarly , equal dropout may or may not lead to biased results . Depending on the type of missingness and the analysis used , one can get a biased estimate of the treatment effect with equal dropout rates and an unbiased estimate with unequal dropout rates . We reinforce this point with data from a r and omised controlled trial in patients with renal cancer and a simulation study AIMS Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning ( PostC ) reduces infa rct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infa rct ion ( STEMI ) patients with thrombolysis in myocardial infa rct ion 0 - 1 ( TIMI 0 - 1 ) flow grade at admission . Whether PostC might also be protective in patients with a TIMI 2 - 3 flow grade on admission ( corresponding to a delayed application of the post-conditioning algorithm ) remains undetermined . METHODS AND RESULTS In this multi-centre , r and omized , single-blinded , controlled study , STEMI patients with a 2 - 3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion , followed ( PostC group ) or not ( control group ) by four cycles of ( 1 min inflation/1 min deflation ) of the angioplasty balloon to trigger post-conditioning . Infa rct size was assessed both by cardiac magnetic resonance at Day 5 ( primary endpoint ) and cardiac enzymes release ( secondary endpoint ) . Ninety-nine patients were prospect ively enrolled . Baseline characteristics were comparable between control and PostC groups . Despite comparable size of area at risk ( AAR ) ( 38 ± 12 vs. 38 ± 13 % of the LV circumference , respectively , P = 0.89 ) and similar time from onset to intervention ( 249 ± 148 vs. 263 ± 209 min , respectively , P = 0.93 ) in the two groups , PostC did not significantly reduce cardiac magnetic resonance infa rct size ( 23 ± 17 and 21 ± 18 g in the treated vs. control group , respectively , P = 0.64 ) . Similar results were found when using creatine kinase and troponin I release , even after adjustment for the size of the AAR . CONCLUSION This study shows that infa rct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2 - 3 flow grade at admission . This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients . CLINICAL TRIAL NUMBER NCT01483755 AIM To define the long-term outcome of patients presenting with acute coronary syndrome [ ST-segment elevation myocardial infa rct ion ( STEMI ) , and non-STEMI and unstable angina acute coronary syndrome ( ACS ) without biomarker elevation ] and to test the hypothesis that the GRACE ( Global Registry of Acute Coronary Events ) risk score predicts mortality and death/MI at 5 years . METHODS AND RESULTS In the GRACE long-term study , UK and Belgian centres prospect ively recruited and followed ACS patients for a median of 5 years ( 1797 days ) . Primary outcome events : deaths , cardiovascular deaths ( CVDs ) and MIs . Secondary events : stroke and re-hospitalization for ACS . There were 736 deaths , 19.8 % ( 482 CVDs , 13 % ) and 347 ( 9.3 % ) MIs ( > 24 h ) , 261 strokes ( 7.7 % ) , and 452 ( 17 % ) subsequent revascularizations . Rehospitalization was common : average 1.6 per patient ; 31.2 % had > 1 admission , 9.2 % had 5 + admissions . These events were despite high rates of guideline indicated therapies . The GRACE score was highly predictive of all-cause death , CVD , and CVD/MI at 5 years ( death : χ(2 ) likelihood ratio 632 ; Wald 709.9 , P < 0.0001 , C-statistic 0.77 ; for CVD C-statistic 0.75 , P < 0.0001 ; CVD/MI C-statistic 0.70 , P < 0.0001 ) . Compared with the low-risk GRACE stratum ( ESC Guideline criteria ) , those with intermediate [ hazard ratio ( HR ) 2.14 , 95 % CI 1.63 , 2.81 ] and those with high-risk ( HR 6.36 , 95 % CI 4.95 , 8.16 ) had two- and six-fold higher risk of later death ( Cox proportional hazard ) . A l and mark analysis after 6 months confirmed that the GRACE score predicted long-term death ( χ(2 ) likelihood ratio 265.4 ; Wald 289.5 , P < 0.0001 ) . Although in-hospital rates of death and MI are higher following STEMI , the cumulative rates of death ( and CVD ) were not different , by class of ACS , over the duration of follow-up ( Wilcoxon = 1.5597 , df = 1 , P = 0.21 ) . At 5 years after STEMI 269/1403 ( 19 % ) died ; after non-STEMI 262/1170 ( 22 % ) after unstable angina ( UA ) 149/850 ( 17 % ) . Two-thirds ( 68 % ) of STEMI deaths occurred after initial hospital discharge , but this was 86 % for non-STEMI and 97 % for UA . CONCLUSION The GRACE risk score predicts early and 5 year death and CVD/MI . Five year morbidity and mortality are as high in patients following non-ST MI and UA as seen following STEMI . Their morbidity burden is high ( MI , stroke , readmissions ) and the substantial late mortality in non-STE ACS is under-recognized . The findings highlight the importance of pursuing novel approaches to diminish long-term risk Reperfusion injury may offset the optimal salvage of myocardium achieved during primary coronary angioplasty . Thus , coronary reperfusion must be combined with cardioprotective adjunctive therapies in order to optimize myocardial salvage and minimize infa rct size . Forty-three patients with their first ST-elevation myocardial infa rct ion were r and omized to myocardial postconditioning or st and ard of care at the time of primary coronary angioplasty . Postconditioning was performed immediately upon crossing the lesion with the guide wire and consisted of four cycles of 30 s occlusion followed by 30 s of reperfusion . End-points included infa rct size , myocardial perfusion grade ( MPG ) , left-ventricular ejection fraction ( LVEF ) , and long-term clinical events ( death and heart failure ) . Despite similar ischemic times ( ≅4.5 h ) ( p = 0.9 ) a reduction in infa rct size was observed among patients treated with the postconditioning protocol . Peak creatine phosphokinase ( CPK ) , as well as its myocardial b and ( MB ) fraction , was significantly lower in the postconditioning group when compared with the control group ( CPK — control , 2,444 ± 1,928 IU/L vs. PC , 2,182 ± 1,717 IU/L ; CPK-MB — control , 242 ± 40 IU/L vs. PC , 195 ± 33 IU/L ; p = 0.64 and p < 0.01 , respectively ) . EF in the postconditioning group was improved when compared with the control group ( control , 43 % ± 15 vs. PC , 52 % ± 9 ; p = 0.05 ) . After a mean follow-up of 3.4 years , a 6-point absolute difference in LVEF was still evident in the postconditioning group ( p = 0.18 ) . MPG was better among patients treated with the postconditioning protocol compared with control ( 2.5 ± 0.5 vs. 2.1 ± 0.6 ; p = 0.02 ) . Due to the small sample size no significant differences in clinical events were detected ( p value for death = 0.9 ; p value for heart failure = 0.2 ) . A simple postconditioning protocol applied at the onset of mechanical reperfusion , result ed in reduction of infa rct size , better epicardial and myocardial flow , and improvement in left ventricular function . The beneficial effects of postconditioning on cardiac function persist beyond 3 years After acute myocardial infa rct ion , the presence of no-reflow ( or microvascular obstruction : MVO ) has been associated with adverse left ventricular ( LV ) remodeling and worse clinical outcome . This study examined the effects of mechanical ischemic postconditioning on early and late MVO size in acute ST-elevation myocardial infa rct ion ( STEMI ) patients . Fifty patients undergoing primary coronary angioplasty for a first STEMI with TIMI grade flow 0–1 and no collaterals were r and omized to ischemic postconditioning ( PC ) ( n = 25 ) or control ( n = 25 ) groups . Ischemic PC consisted in the application of four consecutive cycles of a 1-min balloon occlusion , each followed by a 1-min deflation at the onset of reperfusion . Early ( 3 min post-contrast ) and late ( 10 min post-contrast ) MVO size were assessed by contrast-enhanced cardiac-MRI within 96 h after reperfusion . PC was associated with smaller early and late MVO size ( 3.9 ± 4.8 in PC versus 7.8 ± 6.6 % of LV in controls for early MVO , P = 0.02 ; and 1.8 ± 3.1 in PC versus 4.1 ± 3.9 % of LV in controls for late MVO ; P = 0.01 ) . This significant reduction was persistent after adjustment for thrombus aspiration , which neither had any significant effect on infa rct size , nor on early or late MVO ( P = NS for all ) . Attenuation of MVO was associated to infa rct size reduction . Mechanical postconditioning significantly reduces MVO in patients with acute STEMI treated with primary angioplasty OBJECTIVE Postconditioning is a novel approach to myocardial protection during ischemia reperfusion . Our study observed the effect of postconditioning on coronary blood flow velocity and endothelial function in patients who underwent emergency percutaneous coronary intervention ( PCI ) . METHODS Ninety-four patients with their first acute myocardial infa rct ion who underwent revascularization within 12 hours of onset by primary PCI were recruited in the study . All the patients were r and omized to two groups , IR group ( PCI without postconditioning ) and Postcond group ( PCI with postconditioning ) . Corrected TIMI frame count ( CTFC ) was used to evaluate velocity of coronary blood after PCI . Creatine phosphokinase ( CK ) , CK-MB , and malondialdehyde ( MDA ) were measured before and after PCI . Arterial endothelial function was studied noninvasively by examination of brachial artery responses to endothelium-dependent and endothelium-independent stimuli by echo Doppler technique . Wall motion score index ( WMSI ) was assessed by two-dimensional echocardiography before and 8 weeks after angioplasty . RESULTS There were no significant differences between the two groups with regard to age , sex , presence of angiographically visible collaterals , and elapsed time from the onset of symptoms until perfusion . Patients with postconditioning had much faster CTFC than patients without postconditioning ( 25.38 + /- 5.35 vs 29.23 + /- 5.54 ) . After 8 weeks , the WMSI improved significantly in both groups , but the DeltaWMSI in Postcond group was significantly larger than that of IR group ( 1.20 + /- 0.30 vs 1.04 + /- 0.36 , P < 0.05 ) . There was a significant negative correlation between DeltaWMSI and CTFC in IR group and Postcond group ( r = -0.9032 , P < 0.01 ; r = -0.7884 , P < 0.01 ) . The peaks of CK and CK-MB of Postcond group were much lower than that of IR group ( 1236.57 + /- 813.21 U/L vs 1697.36 + /- 965.74 U/L ; 116.92 + /- 75.83 U/L vs 172.41 + /- 92.64 U/L ) , and MDA-reactive products were significantly lower than that in the IR group at any same time after PCI . All patients with acute myocardial infa rct ion had a depressed endothelium-dependent vasodilation function , while the endothelium-dependent vasodilation function was improved in Postcond group . CONCLUSION Postconditioning is a simple , operative procedure for salvaging the coronary endothelial function and cardiomyocyte . It could be used widely in clinic and to better the prognosis of acute myocardial infa rct ion Objective : To assess the effect of ischemic postconditioning on indices of coronary microvascular function during percutaneous coronary intervention ( PCI ) for acute ST segment elevation myocardial infa rct ion ( STEMI ) . Background : Myocardial tissue level perfusion remains suboptimal in many patients with STEMI despite restoration of ante grade flow in the epicardial coronary artery . Methods : Twenty‐four patients with an evolving anterior STEMI were r and omized to undergo a previously‐vali date d ischemic postconditioning protocol or usual care during PCI . The extent of resolution of ST segment elevation along with Doppler‐tip catheter velocimetry was used as indices of myocardial reperfusion and microvascular function , respectively . Results : Postconditioned patients exhibited a greater , and therefore more rapid , extent of ST segment resolution ( postconditioning , 70 % ± 15 % ; control , 48 % ± 16 % ; P = 0.0002 ) by the end of the procedure . Postconditioned patients also exhibited a greater hyperemic coronary vasodilator response at the completion of the procedure ( coronary flow velocity reserve , CFVR : postconditioning , 2.2 ± 0.1 ; control , 1.5 ± 0.1 ; P < 0.0001 ) . The end‐procedure CFVR was directly related to the extent of the ST segment resolution ( r = 0.85 ) but inversely related to the absolute magnitude of ST segment elevation at end procedure ( r = −0.76 ) . Peak serum creatine kinase was significantly lower in postconditioned patients ( postconditioning , 1,524 ± 435 IU/l ; control , 1,862 ± 561 IU/l ; P = 0.03 ) . Conclusions : Ischemic postconditioning , as described , can be expeditiously performed during PCI for STEMI . Concordant changes in coronary flow reserve and ST segment resolution , measures of microcirculatory function , and myocardial perfusion , were greater in postconditioned patients . © 2008 Wiley‐Liss , INTRODUCTION A key method in the treatment of ST-elevation myocardial infa rct ion ( STEMI ) is recanalization of the infa rct -related artery , but this causes heart reperfusion injury . One of the methods to reduce this injury is postconditioning . The available data on the efficacy of this method are contradictory . OBJECTIVES The aim of the study was to determine the safety of postconditioning as well as its effect on infa rct ion size , improvement in left ventricular ejection fraction ( LVEF ) , and adverse LV remodeling during a 3-month follow-up . PATIENTS AND METHODS The study involved 39 patients with first anterior STEMI ( aged 58 ± 10 years ) up to 12 hours from the onset of symptoms . They were r and omly assigned to a traditional-reperfusion group ( n = 21 ) or to a postconditioning group ( n = 18 ) . The area at risk ( AAR ) was assessed angiographically . LV remodeling and LVEF were evaluated using echocardiography at 6 days and at 3 months . The infa rct ion size was defined on the basis of magnetic resonance imaging ( MRI ) at 3 months . RESULTS In a univariate logistic regression analysis , postconditioning did not affect the improvement of LVEF ( odds ratio [ OR ] , 1.63 ; 95 % confidence interval [ CI ] , 0.34 - 7.7 ; P = 0.52 ) or the development of adverse LV remodeling ( OR , 0.62 ; 95 % CI , 0.15 - 2.53 ; P = 0.5 ) . Moreover , there were no significant differences in infa rct ion size between the groups as measured by MRI after adjustment for the AAR , time to reperfusion , and ST-segment elevation prior to percutaneous coronary intervention . CONCLUSIONS Postconditioning is a safe method but its application did not affect the volume of the infa rct ion as well as did not improve LVEF or the development of adverse LV remodeling in a 3-month follow-up Background Small studies suggest that postconditioning reperfusion interrupted by brief repetitive cycles of reocclusions , may protect the myocardium in the clinical setting . Objective To test the hypothesis that postconditioning limits infa rct size in relation to the area at risk in patients with ST elevation myocardial infa rct ion ( STEMI ) . Methods 76 patients ( aged 37–87 years ) eligible for primary percutaneous coronary intervention due to STEMI were r and omised to st and ard percutaneous coronary intervention ( n=38 ) or postconditioning , consisting of four cycles of 60 s reperfusion and 60 s of reocclusion before permanent reperfusion ( n=38 ) . Results The area at risk was determined from angiographic abnormally contracting segments . Infa rct size was quantified from delayed enhancement MRI on days 6–9 . Infa rct size , expressed in relation to the area at risk , did not differ between the control group ( 44 % ; 30 , 56 ) ( median and quartiles ) and the post-conditioned group ( 47 % ; 23 , 63 ) . The slope of the regression lines relating infa rct size to the area at risk differed between the two groups . Infa rct size was significantly ( p=0.001 ) reduced by postconditioning in patients with large areas at risk . The area under the curve and peak troponin T release and CKMB during 48 h did not differ between patients in the control and postconditioning groups . Conclusions This prospect i ve , r and omised trial suggests that postconditioning does not reduce infa rct size in patients with STEMI in the overall study group . The data indicate that postconditioning may be of value in patients with large areas at risk . Clinical trial registration information Karolinska Clinical Trial Registration ( http://www.kctr.se ) . Unique identifier : CT20080014 BACKGROUND Postconditioning ( PC ) has been suggested to reduce myocardial damage during primary percutaneous coronary intervention ( PPCI ) , nevertheless clinical experience is limited . We aim ed to explore the cardioprotective effect of PC using cardiac magnetic resonance ( CMR ) in ST-elevation myocardial infa rct ion ( STEMI ) patients treated by PPCI . METHODS A total of 78 patients with first STEMI ( aged 59±12 years ) referred for PPCI , were stratified for STEMI location and r and omly assigned to conventional PPCI or PPCI with PC . All patients , with occluded infa rct related artery and no collateral circulation , received abciximab intravenously before PPCI . After reperfusion by effective direct stenting , control subjects underwent no further intervention , while in treated patients PC was performed within 1 min of reflow by 4 cycles of 1-minute inflation and 1-minute deflation of the angioplasty balloon . Primary end-point was infa rct size ( IS ) reduction , expressed as percentage of left ventricle mass assessed by delayed enhancement on CMR at 30±10 days after index PPCI . RESULTS All baseline characteristics but diabetes ( p=0.06 ) were balanced between groups . Postconditioning patients trended toward a larger IS compared to those treated by st and ard PPCI ( 20±12 % vs 14±10 % , p=0.054 ) . After exclusion of diabetics , PC group still showed a trend to larger IS ( p=0.116 ) . Major adverse events seem to be more frequent in PC group irrespective to diabetic status ( p=0.053 and p=0.080 , respectively ) . CONCLUSIONS This prospect i ve , r and omized trial suggests that PC did not have the expected cardioprotective effect and on the contrary it might harm STEMI patients treated by PPCI plus abciximab . ( Clinical Trial Registration -unique identifier : NCT01004289 ) Generally , before a new drug can be accepted for the use in clinical practice , its efficacy and safety needs to be rigorously assessed in a series of clinical trials . This process of testing a new therapy can ( and , in fact , does ) take many years . One of the reasons is the use of long-term clinical endpoints like clinical progression or survival . However , recent advances in the underst and ing of the biological mechanisms of disease development have result ed in the emergence of a large number of potentially effective new agents . There is also increasing public pressure for promising new drugs to receive marketing approval as rapidly as possible , in particular for life threatening diseases such as cancer . For these reasons , there is an urgent need to find ways of shortening the duration of cancer clinical trials . A possible solution to this problem is to replace the endpoint of interest , the ‘ true ’ endpoint , by another one , a ‘ surrogate ’ endpoint , which might be measured earlier or more frequently . However , before a surrogate can replace a true endpoint , it should be vali date d. This means that it should be checked whether the use of the surrogate leads to correct conclusions about the effect of the treatment on the true endpoint . The validation of a c and i date surrogate endpoint is not straightforward . Merely establishing a correlation between both endpoints is not sufficient.1 Formal methods , allowing for validation of surrogate endpoints , have become the subject of intensive research over the past decades.2 Until recently , the statistical approaches developed for this purpose were based on the definition of a surrogate proposed by Prentice,3 according to which a surrogate endpoint is ‘ a response variable for which a test of the null hypothesis of no relationship to the treatment groups under comparison is also a valid test of the corresponding null hypothesis based on the true endpoint . ’ The methods assumed the availability of data from a single trial.3–5 These methods suffer from numerous drawbacks : some of them are too stringent to be of practical value , while others are based on non-testable assumptions.6 To overcome these limitations , ‘ meta-analytic ’ validation approaches have recently been developed.7–10 They are based on an alternate definition , according to which ‘ a surrogate endpoint is expected to predict clinical benefit ( or harm or lack of benefit or harm)’.11 These methods use large data bases from multiple r and omized clinical trials and aim at measuring directly the association between the treatment effects on the surrogate and the true endpoint . At the 33rd International Biometric Conference , which took place on 16–21 July , 2006 , in Montreal , a special Topic Contributed Session ‘ Surrogate Endpoints : Wishful Thinking or Reality ? ’ was devoted to the issue of surrogate endpoint validation . Each speaker was provided with two data sets , containing data from multiple r and omized clinical trials in colorectal cancer . The speakers were asked to evaluate , using BACKGROUND Postconditioning has been shown to reduce infa rct size , ischemic/reperfusion injury and myocardial injury in patients with acute myocardial infa rct ion ( AMI ) undergoing percutaneous coronary intervention ( PCI ) . This study tested the hypothesis that postconditioning attenuates the elevation of tumor necrosis factor-alpha ( TNF-alpha ) and improves heart function in patients with AMI after PCI . METHODS A total of 75 patients were r and omly assigned to 1 of 3 groups : the routine group ( n = 26 ) , in which no intervention was given at the onset of reperfusion ; and the Postcon-30s ( n = 25 ) or Postcon-60 s ( n = 24 ) groups , in which 3 cycles of 30- or 60-second balloon deflation and inflation were repetitively performed . TNF-alpha serum concentration was measured by ELISA . Global and regional left ventricular systolic function was determined by echocardiography at 1 year . Thirty-four normal controls ( NC ) were enrolled in the study . RESULTS The TNF-alpha concentration in patients with AMI was significantly elevated at baseline compared to controls ( P < 0.01 ) . Concentration levels increased in the routine and Postcon-30s , but not in Postcon-60s group at 7 days ( P < 0.05 ) . As for linear associations among the three groups , left ventricular ejection fraction ( LVEF ) and wall motion score index ( WMSI ) were ranked as follows : Postcon-60s > Postcon-30s > routine ( P values all < 0.05 , 65 % vs. 57 % vs. 52 % and 1.10 vs. 1.27 vs. 1.53 ) after 1 year . More importantly , there was a significant relevance between the soluble TNF-alpha serum concentration at 7 days and LVEF or WMSI after 1 year ( P values all < 0.0001 ) . CONCLUSIONS Postconditioning , in particular Postcon-60s was associated with long-term cardioprotective effects for inhibition of the inflammatory response and reperfusion injury . The soluble TNF-alpha serum concentration provided powerful prognostic information of global and regional left ventricular systolic function in patients with AMI The objective of this study was to determine whether acutely ischemic myocardium may be conditioned during percutaneous coronary intervention for acute myocardial infa rct ion . Ischemic preconditioning is a powerful cardioprotective mechanism that limits infa rct size in animal investigations and ischemic sequelae during percutaneous coronary intervention in man . However , the conditioning stimulus in all these studies has been applied prior to the defining episode of ischemia . Seventeen patients undergoing percutaneous coronary intervention for acute myocardial infa rct ion were r and omly assigned to a st and ard ischemic preconditioning protocol ( n = 10 ) or a usual‐care control group ( n = 7 ) . ST segment shift response and Doppler‐derived distal coronary velocity data were compared . Despite similar degrees of baseline ST segment elevation , the magnitude of final ST segment elevation in the conditioning group was less than that in controls at the protocol conclusion ( conditioning , 1.60 ± 0.8 mV ; control , 4.0 ± 0.5 mV ; P < 0.001 ) . The rate of ST segment resolution was greater in the conditioning group ( conditioning , 0.28 ± 0.1 mV/min ; control , 0.12 ± 0.1 mV/min ; P = 0.02 ) . Distal coronary velocimetry indicated significant improvement in coronary flow velocity reserve in the conditioning group at the protocol conclusion ( conditioning , 1.8 ± 0.2 ; control , 1.4 ± 0.1 ; P < 0.008 ) . Brief periods of occlusion and reperfusion during percutaneous intervention for acute myocardial infa rct ion mitigate the extent of ischemic injury and improve distal myocardial perfusion . Such ischemic conditioning represents a potentially useful adjunct to strategies for enhancing reperfusion during acute myocardial infa rct ion . © 2005 Wiley‐Liss , OBJECTIVE To observe the effect of ischemia postconditioning during the first minutes of reperfusion for the myocardial reperfusion injury in ST-segment elevation acute myocardial infa rct ion ( STEMI ) patients undergoing emergency percutaneous coronary intervention ( PCI ) . METHODS STEMI patients undergoing emergency PCI in affiliated hospital of Beihua University between October 2006 and January 2009 were r and omly divided into two groups : the control group ( n = 34 ) without any intervention after PTCA , and the postconditioning group ( n = 30 ) with ischemia postconditioning within first minutes of reflow by 3 episodes of 30-second inflation and 30-second deflation with the angioplasty balloon . Reperfusion arrhythmias , CK and CKMB , corrected TIMI frame count ( CTFC ) , wall motion score index ( WMSI ) and left ventricular ejection fraction ( LVEF ) by echocardiography were compared between the two groups . MI areas were evaluated with the ECG-54 criteria /32 system and myocardial blush grade ( MBG ) was measured . RESULTS The incidence of reperfusion arrhythmias-frequent ventricular premature ( 26.7 % vs. 52.9 % ) and short array ventricular tachycardia beat ( 23.3 % vs. 58.8 % ) as well as values of peaks CK [ ( 1162 ± 548 ) U/L vs. ( 1732 ± 480 ) U/L , P < 0.01 ] , CKMB [ ( 165 ± 70 ) U/L vs. ( 280 ± 99 ) U/L , P < 0.01 ] , CTFC ( 22.23 ± 3.81 vs. 26.97 ± 3.42 ) , WMSI ( 1.27 ± 0.52 vs. 1.82 ± 0.83 ) , and infa rct ion areas determined by ECG methods ( 10.60 % ± 4.97 % vs.14.65 % ± 6.88 % , all P < 0.05 ) were all significantly lower in the postconditioning group than in control group while LVEF ( 0.55 ± 0.08 vs. 0.47 ± 0.10 ) and MBG ( 2.27 ± 0.64 vs. 1.47 ± 0.61 , all P < 0.05 ) were significantly higher in the postconditioning group than in control group . CONCLUSIONS Ischemia postconditioning can significantly reduce myocardial reperfusion injury in patients with STEMI OBJECTIVE : This study investigated whether ischaemic postconditioning can improve recovery of myocardial contractile function in acute myocardial infa rct ion patients 1 week and 6 months after angioplasty . METHODS : A total of 62 patients undergoing direct percutaneous coronary intervention after acute myocardial infa rct ion were r and omly assigned to receive four episodes of inflation and deflation of the angioplasty balloon in the early reperfusion period ( postconditioned group , n = 32 ) , or no additional intervention ( control group , n = 30 ) . Two-dimensional size and left ventricular ( LV ) global and regional contractile functions were then evaluated by echocardiography at 1 week and 6 months after angioplasty . RESULTS : At 1 week , there were no significant differences in left atrial diameter , LV end-diastolic diameter , LV end-diastolic volume , cardiac output , LV ejection fraction or wall motion score index between the two groups . At 6 months , LV ejection fraction was significantly increased and the wall motion score index significantly reduced in the postconditioned group compared with the control group . CONCLUSION : Ischaemic postconditioning can improve long-term LV contractile function 6 months after reperfusion following acute myocardial infa rct ion BACKGROUND Ischemic postconditioning ( IPost ) during primary percutaneous coronary intervention ( PPCI ) is suggested to reduce myocardial damage . However , the association with ST-segment resolution ( STR ) and clinical outcome is not determined . The primary aim of this study was to evaluate the association of IPost with STR and clinical outcome . Secondly , we sought to determine the relationship between STR and cardiac magnetic resonance ( CMR ) parameters in these patients . METHODS One hundred eighteen patients referred for PPCI were r and omly assigned to either conventional PPCI or PPCI with IPost . In a single electrocardiographic lead , STR was determined . Treatment modalities were compared as regards STR , ST-segment elevation , and the number of patients achieving complete-STR ( ≥70 % ) , incomplete-STR ( 30%-70 % ) , and no-STR ( < 30 % ) . Patients were evaluated for clinical outcome after 15 months . Furthermore , patients with and without complete-STR were compared as regards CMR parameters . RESULTS There was a tendency toward a better outcome with IPost for the number of patients achieving complete-STR ( 55 % vs 63 % ; P=.09 ) , ST-segment elevation ( 1.41 vs 1.12 mm ; P=.07 ) , and New York Heart Association class ( P=.06 ) . No difference in other cardiac events was observed . Furthermore , data determine that patients with complete-STR have smaller infa rct size ( 12.9 % vs 21.1 % ; P<.01 ) and a better ejection fraction ( 55.7 % vs 47.7 % ; P<.01 ) . CONCLUSIONS Patients treated with IPost are suggested to have improved STR and New York Heart Association classification . Infa rct size and the functional CMR parameters were better in the patients with complete-STR ; as to this , single-lead STR remains an important predictor for successful treatment in patients treated with IPost OBJECTIVES This study aim ed to determine whether post-conditioning at the time of percutaneous coronary intervention could reduce reperfusion-induced myocardial edema in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) . BACKGROUND Myocardial edema is a reperfusion injury with potentially severe consequences . Post-conditioning is a cardioprotective therapy that reduces infa rct size after reperfusion , but no previous studies have analyzed the impact of this strategy on reperfusion-induced myocardial edema in humans . METHODS Fifty patients with STEMI were r and omly assigned to either a control or post-conditioned group . Cardiac magnetic resonance imaging was performed within 48 to 72 h after admission . Myocardial edema was measured by T2-weighted sequences , and infa rct size was determined by late gadolinium enhancement sequences and creatine kinase release . RESULTS The post-conditioned and control groups were similar with respect to ischemia time , the size of the area at risk , and the ejection fraction before percutaneous coronary intervention . As expected , post-conditioning was associated with smaller infa rct size ( 13 ± 7 g/m(2 ) vs. 21 ± 14 g/m(2 ) ; p = 0.01 ) and creatine kinase peak serum level ( median [ interquartile range ] : 1,695 [ 1,118 to 3,692 ] IU/l vs. 3,505 [ 2,307 to 4,929 ] IU/l ; p = 0.003 ) . At reperfusion , the extent of myocardial edema was significantly reduced in the post-conditioned group as compared with the control group ( 23 ± 16 g/m(2 ) vs. 34 ± 18 g/m(2 ) ; p = 0.03 ) ; the relative increase in T2W signal intensity was also significantly lower ( p = 0.02 ) . This protective effect was confirmed after adjustment for the size of the area at risk . CONCLUSIONS This r and omized study demonstrated that post-conditioning reduced infa rct size and edema in patients with reperfused STEMI OBJECTIVES The aim of the AIDA STEMI ( Abciximab i.v . Versus i.c . in ST-elevation Myocardial Infa rct ion ) cardiac magnetic resonance ( CMR ) sub study was to investigate potential benefits of intracoronary versus intravenous abciximab bolus administration on infa rct size and reperfusion injury in ST-segment elevation myocardial infa rct ion . BACKGROUND The AIDA STEMI trial r and omized 2,065 patients to intracoronary or intravenous abciximab and found similar rates of major adverse cardiac events at 90 days with significantly less congestive heart failure in the intracoronary abciximab group . CMR can directly visualize myocardial damage and reperfusion injury , thereby providing mechanistic and pathophysiological insights . METHODS We enrolled 795 patients in the AIDA STEMI CMR sub study . CMR was completed within 1 week after ST-segment elevation myocardial infa rct ion . Central core laboratory-masked analyses for quantified ventricular function , volumes , infa rct size , microvascular obstruction , hemorrhage , and myocardial salvage were performed . RESULTS The area at risk ( p = 0.97 ) and final infa rct size ( 16 % [ interquartile range : 9 % to 25 % ] versus 17 % [ interquartile range : 8 % to 25 % ] , p = 0.52 ) did not differ significantly between the intracoronary and the intravenous abciximab groups . Consequently , the myocardial salvage index was similar ( 52 [ interquartile range : 35 to 69 ] versus 50 [ interquartile range : 29 to 69 ] , p = 0.25 ) . There were also no differences in microvascular obstruction ( p = 0.19 ) , intramyocardial hemorrhage ( p = 0.19 ) , or ejection fraction ( p = 0.95 ) between both treatment groups . Patients in whom major adverse cardiac events occurred had significantly larger infa rcts , less myocardial salvage , and more pronounced ventricular dysfunction . CONCLUSIONS This largest multicenter CMR study in ST-segment elevation myocardial infa rct ion patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and /or reperfusion injury . Infa rct size determined by CMR was significantly associated with major adverse cardiac events BACKGROUND Postconditioning is a potential cardioprotective strategy that has demonstrated conflicting and variable reductions in infa rct size in human trials . OBJECTIVES To determine whether postconditioning could increase the extent of myocardial salvage in patients with acute ST-segment elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention ( PPCI ) . METHODS One hundred two patients ( aged 57 ± 11 years ; 88 % male ) were r and omly assigned to a postconditioning or st and ard protocol . Cardiovascular magnetic resonance imaging was performed 3 days after PPCI to measure the volumetric extent of myocardial necrosis and the area at risk . RESULTS With similar time-to-reperfusion ( 170 ± 84 minutes in the postconditioning group vs. 150 ± 70 minutes in the st and ard group , P = 0.22 ) , the myocardial salvage index was not significantly different between the postconditioned group and the control group , averaging 42 ± 22 % vs. 33 ± 21 % , respectively ( P = 0.08 ) . Furthermore , postconditioning was not associated with a smaller infa rct size compared to controls ( 13 ± 7 g/m(2 ) vs. 15 ± 8 g/m(2 ) , respectively , P = 0.18 ) . CONCLUSIONS Postconditioning does not significantly increase myocardial salvage or reduce infa rct size in patients with STEMI undergoing PPCI . However , the possibility of a more modest impact of postconditioning can not be excluded with our sample size Background — Ischemic postconditioning has been reported to reduce infa rct size in patients with ST-segment – elevation myocardial infa rct ion . However , cardioprotective effects of postconditioning have not been demonstrated in a large-scale trial . Methods and Results — We performed a multicenter , prospect i ve , r and omized , open-label , blinded end-point trial . A total of 700 patients undergoing primary percutaneous coronary intervention ( PCI ) for ST-segment – elevation myocardial infa rct ion within 12 hours after symptom onset were r and omly assigned to the postconditioning group or to the conventional primary PCI group in a 1:1 ratio . Postconditioning was performed immediately after restoration of coronary flow as follows : The angioplasty balloon was positioned at the culprit lesion and inflated 4 times for 1 minute with low-pressure ( < 6 atm ) inflations , each separated by 1 minute of deflation . The primary end point was complete ST-segment resolution ( percentage resolution of ST-segment elevation > 70 % ) measured at 30 minutes after PCI . Complete ST-segment resolution occurred in 40.5 % of patients in the postconditioning group and 41.5 % of patients in the conventional PCI group ( absolute difference , −1.0 % ; 95 % confidence interval , −8.4 to 6.4 ; P=0.79 ) . The rate of myocardial blush grade of 0 or 1 and the rate of major adverse cardiac events ( a composite of death , myocardial infa rct ion , severe heart failure , or stent thrombosis ) at 30 days did not differ significantly between the postconditioning group and the conventional PCI group ( 17.2 % versus 22.4 % [ P=0.20 ] and 4.3 % versus 3.7 % [ P=0.70 ] , respectively ) . Conclusion — Ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment – elevation myocardial infa rct ion undergoing primary PCI with current st and ard practice . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique identifier : NCT00942500 |
11,717 | 23,849,851 | In the sensitivity analysis , adefovir showed lower cost-utility than telbivudine in some situations .
In this study , tenofovir presented the best cost-utility ratio . | The aim of this study was to conduct a cost-utility study of adefovir , entecavir , interferon alpha , pegylated interferon alpha , lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System . | BACKGROUND AND AIM Entecavir is a potent inhibitor of both wild-type and lamivudine-resistant hepatitis B virus ( HBV ) with proven clinical efficacy . We conducted a r and omized , double-blind , multicenter study in Japan ( ETV-052 ) evaluating the efficacy and safety of two doses of entecavir in adult patients with lamivudine-refractory chronic hepatitis B infection . METHODS Eighty-four patients with chronic hepatitis B who were refractory to lamivudine therapy were switched from lamivudine to daily oral doses of 0.5 mg entecavir ( 41 patients ) or 1 mg entecavir ( 43 patients ) for 52 weeks . RESULTS The proportions of patients achieving the primary end-point ( > or=2 log(10 ) reduction in HBV-DNA from baseline by polymerase chain reaction assay or undetectable HBV-DNA levels [ < 400 copies/mL ] at week 48 ) were 90 % and 93 % for entecavir 0.5 mg and 1 mg , respectively , with 33 % of patients in each dosing group achieving < 400 copies/mL. The mean reduction in HBV-DNA from baseline was 3.58 and 3.75 log(10 ) copies/mL for entecavir 0.5 mg and 1 mg , respectively . High proportions of patients achieved alanine aminotransferase normalization at week 48 ( 0.5 mg 86 % , 1 mg 78 % ) . Histological improvement was observed in most patients ( 0.5 mg 52 % , 1 mg 60 % ) . Virological breakthrough ( increase in HBV-DNA of > or=1 log(10 ) copies/mL from nadir ) was observed in one patient but was not associated with selection of entecavir-associated resistance substitutions . Entecavir was well tolerated , with no patients discontinuing study drug due to adverse events . CONCLUSIONS These findings indicate that entecavir is safe and effective for the treatment of Japanese adults with lamivudine-refractory chronic hepatitis BACKGROUND Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus ( HBV ) . METHODS In this phase 3 , double-blind trial , we r and omly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) at week 48 . Secondary end points included a reduction in the serum HBV DNA level , HBeAg loss and seroconversion , and normalization of the alanine aminotransferase level . RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group ( 72 percent ) and 195 of 314 patients in the lamivudine group ( 62 percent , P=0.009 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay ( 67 percent vs. 36 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 68 percent vs. 60 percent , P=0.02 ) . The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine ( 6.9 vs. 5.4 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine ( P=0.33 ) . No viral resistance to entecavir was detected . Safety was similar in the two groups . CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B , the rates of histologic , virologic , and biochemical improvement are significantly higher with entecavir than with lamivudine . The safety profile of the two agents is similar , and there is no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035633 . ) BACKGROUND Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS In this phase 3 , double-blind trial , we r and omly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks . The primary efficacy end point was histologic improvement ( a decrease by at least two points in the Knodell necroinflammatory score , without worsening of fibrosis ) . RESULTS Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated ( 70 percent ) , as compared with 174 of 287 such patients in the lamivudine group ( 61 percent , P=0.01 ) . More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus ( HBV ) DNA levels according to a polymerase-chain-reaction assay ( 90 percent vs. 72 percent , P<0.001 ) and normalization of alanine aminotransferase levels ( 78 percent vs. 71 percent , P=0.045 ) . The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine ( 5.0 vs. 4.5 log [ on a base-10 scale ] copies per milliliter , P<0.001 ) . There was no evidence of resistance to entecavir . Safety and adverse-event profiles were similar in the two groups . CONCLUSIONS Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue , the rates of histologic improvement , virologic response , and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine . The safety profile of the two agents was similar , and there was no evidence of viral resistance to entecavir . ( Clinical Trials.gov number , NCT00035789 . ) AIM To compare the efficacy of a combination of a-interferon ( IFN-a ) and lamivudine with IFN-a alone in the treatment of patients with HBeAg-positive chronic hepatitis B ( CHB ) . METHODS Sixty-eight treatment-naove patients with HBeAg-positive CHB were r and omized to receive either 9 MU of IFN-a2a three times a week and lamivudine 100 mg daily ( Group 1 ) , or IFN-a2a alone in the same dosage ( Group 2 ) , for 12 months . Serum ALT , HBeAg , anti-HBe and HBV DNA were tested at the end of treatment and 6 months later . Complete response was defined as normal ALT , negative HBeAg and negative HBV DNA , six months after stopping treatment . RESULTS Of the 68 patients , 64 completed the study . In Group 1 ( n=31 ) , mean ( SD ) ALT levels decreased from 124 ( 59 ) IU/L to 39 ( 18 ) IU/L at 12 months ; corresponding values in Group 2 ( n=33 ) were 128 ( 57 ) and 56 ( 11 ) IU/L ( p < 0.05 ) . Absence of HBV DNA at the end of treatment was more common in Group 1 ( 28/31 ) than in Group 2 ( 22/33 ; p < 0.022 ) . The number of patients with seroconversion to anti-HBe ( 4/31 [ 13 % ] vs. 4/33 [ 12 % ] , respectively ; p>0.05 ) , as also those with complete response ( 4/31 [ 13 % ] and 4/33 [ 12 % ] , respectively ; p>0.05 ) six months after completion of treatment was similar in Group 1 and Group 2 . CONCLUSION Combination treatment with IFN-a and lamivudine was better than IFN-a monotherapy in normalization of ALT and clearance of HBV DNA ; however , it did not have a better sustained response rate than IFN-a alone BACKGROUND Pegylated interferon (PEG-IFN)-alpha monotherapy is the current st and ard of care for short-term antiviral treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B ( CHB ) . We aim ed to assess the safety and efficacy of PEG-IFN-alpha plus adefovir dipivoxil ( ADV ) versus PEG-IFN-alpha monotherapy for compensated HBeAg-negative CHB . METHODS A multicentre r and omized controlled trial was performed in eight outpatient hepatology/infectious disease clinics in central Italy . A total of 60 patients ( 67 % male and median age 48 years ) with biopsy-proven HBeAg-negative compensated CHB ( mean alanine aminotranferase [ ALT ] levels 3.3 + /-3x the upper normal limit and serum hepatitis B virus [ HBV ] DNA 5.8 + /-0.9 log(10 ) IU/ml ) were r and omized at baseline to receive PEG-IFN-alpha2a 180 microg/week plus ADV 10 mg/day or PEG-IFN-alpha2a monotherapy for 48 weeks . Post-treatment follow-up was for 24 additional weeks . The primary end point was sustained HBV DNA suppression defined as serum HBV DNA<2,000 IU/ml after 24 weeks of post-treatment follow-up . The secondary end point was ALT normalization at the end of follow-up . RESULTS At week 48 , HBV DNA was undetectable in 20/30 ( 67 % ) in the combination group versus 11/30 ( 37 % ) patients in the monotherapy group ( P=0.02 ) . ALT normalization was achieved in 17/30 ( 57 % ) versus 10/30 ( 30 % ) patients , respectively ( P=0.03 ) . At week 72 , sustained virological response was achieved in 7/30 ( 23.3 % ) in the combination group versus 6/30 ( 20 % ) patients in the monotherapy group ( P=0.75 ) ; 5 ( 16 % ) patients in each group dropped out because of adverse events or non-compliance . CONCLUSIONS In HBeAg-negative CHB , combination PEG-IFN-alpha2a plus ADV for 48 weeks is safe and result ed in greater on-treatment efficacy than PEG-IFN-alpha2a monotherapy . No difference in sustained virological and biochemical response rates were observed between the two treatment regimens BACKGROUND & AIMS Entecavir demonstrated superior benefit to lamivudine at 48 weeks in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B ( CHB ) . We evaluated continued entecavir and lamivudine treatment through 96 weeks . METHODS 709 HBeAg-positive CHB patients were r and omized to entecavir 0.5 mg ( n = 354 ) or lamivudine 100 mg ( n = 355 ) once daily . At week 52 , protocol -defined virologic responders could continue blinded treatment for up to 96 weeks . Patients continuing in year 2 ( entecavir , n = 243 ; lamivudine , n = 164 ) were assessed for serum hepatitis B virus ( HBV ) DNA , alanine aminotransferase ( ALT ) normalization , HBeAg seroconversion , and safety . Cumulative confirmed proportions of all treated patients who achieved these responses were also analyzed . RESULTS Among patients treated in year 2 , 74 % of entecavir-treated versus 37 % of lamivudine-treated patients achieved HBV DNA < 300 copies/mL by polymerase chain reaction ( PCR ) , and 79 % of entecavir-treated versus 68 % of lamivudine-treated patients normalized ALT levels . Similar proportions of entecavir-treated and lamivudine-treated patients achieved HBeAg seroconversion ( 11 % vs 12 % , respectively ) . Higher proportions of entecavir-treated than lamivudine-treated patients achieved cumulative confirmed HBV DNA < 300 copies/mL by PCR ( 80 % vs 39 % ; P < .0001 ) and ALT normalization ( 87 % vs 79 % ; P = .0056 ) through 96 weeks . Cumulative confirmed HBeAg seroconversion occurred in 31 % of entecavir-treated versus 25 % of lamivudine-treated patients ( P = NS ) . Through 96 weeks , no patient experienced virologic breakthrough due to entecavir resistance . The safety profile was comparable in both groups . CONCLUSIONS Entecavir treatment through 96 weeks results in continued benefit for patients with HBeAg-positive CHB BACKGROUND / AIMS We aim ed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B ( CHB ) . METHODS One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo ( monotherapy ) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily ( combination therapy ) for 104 weeks in a r and omized double-blind study . RESULTS Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups ( p=0.936 ) . At week 104 , median serum HBV DNA change from baseline ( log(10)copies/mL ) for monotherapy and combination therapy was -3.41 versus -5.22 , respectively . HBV DNA breakthrough was detected in 44 % of monotherapy and 19 % of combination therapy patients . The M204V/I mutation was detected in 43 % ( 15/35 ) and 15 % ( 6/41 ) of each group , respectively . ALT normalization at week 100 and 104 was 34 % ( 19/56 ) in the monotherapy group and 45 % ( 23/51 ) in the combination therapy group ( p=0.018 ) . By week 104 , HBeAg seroconversion occurred in 20 % of monotherapy and 13 % of combination therapy patients . Both regimens were well tolerated . CONCLUSIONS Lower rates of resistance to lamivudine , lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years . However , serological outcomes were similar BACKGROUND Adefovir dipivoxil , a nucleotide analogue , demonstrated clinical ly significant antiviral activity in patients with chronic hepatitis B in phase 1 and 2 clinical trials . METHODS We r and omly assigned 185 patients with chronic hepatitis B who were negative for hepatitis B e antigen ( HBeAg ) to receive either 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks in a 2:1 ratio and a double-blind manner . The primary end point was histologic improvement . RESULTS At week 48 , 64 percent of patients who had base-line liver-biopsy specimens available in the adefovir dipivoxil group had improvement in histologic liver abnormalities ( 77 of 121 ) , as compared with 33 percent of patients in the placebo group ( 19 of 57 , P<0.001 ) . Serum hepatitis B virus ( HBV ) DNA levels were reduced to fewer than 400 copies per milliliter in 51 percent of patients in the adefovir dipivoxil group ( 63 of 123 ) and in 0 percent of those in the placebo group ( 0 of 61 , P<0.001 ) . The median decrease in log-transformed HBV DNA levels was greater with adefovir dipivoxil treatment than with placebo ( 3.91 vs. 1.35 log copies per milliliter , P<0.001 ) . Alanine aminotransferase levels had normalized at week 48 in 72 percent of patients receiving adefovir dipivoxil ( 84 of 116 ) , as compared with 29 percent of those receiving placebo ( 17 of 59 , P<0.001 ) . No HBV polymerase mutations associated with resistance to adefovir were identified . The safety profile of adefovir dipivoxil was similar to that of placebo . CONCLUSIONS In patients with HBeAg-negative chronic hepatitis B , 48 weeks of adefovir dipivoxil treatment result ed in significant histologic , virologic , and biochemical improvement , with an adverse-event profile similar to that of placebo . There was no evidence of the emergence of adefovir-resistant HBV polymerase mutations BACKGROUND Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most . A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response . METHODS 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy ( 100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine ) or monotherapy ( 100 microg/week pegylated interferon alfa-2b and placebo ) for 52 weeks . During weeks 32 - 52 the pegylated interferon dose was 50 microg/week in both treatment groups . The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct , ten who lost HBeAg before the study start , and seven who received no study medication . All included patients were followed up for 26 weeks after treatment . FINDINGS 49 ( 36 % ) of 136 patients assigned monotherapy and 46 ( 35 % ) of 130 assigned combination therapy had lost HBeAg at the end of follow-up ( p=0.91 ) . More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment ( 57 [ 44 % ] vs 40 [ 29 % ] ; p=0.01 ) but relapsed during follow-up . Patterns were similar when response was assessed by suppression of serum hepatitis B virus ( HBV ) DNA or change in concentrations of alanine aminotransferase . Response rates ( HBeAg loss ) varied by HBV genotype ( p=0.01 ) : A , 42 ( 47 % ) patients ; B , ten ( 44 % ) ; C , 11 ( 28 % ) ; and D , 26 ( 25 % ) . INTERPRETATION Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy . HBV genotype is an important predictor of response to treatment We compared the use of prolonged synchronous combination therapy with interferon (IFN)-alpha-2b and lamivudine with the use of IFN-alpha-2b monotherapy in patients with untreated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus ( HBV ) infection . Thirty-three patients received therapy with lamivudine ( 100 mg daily ) and IFN-alpha-2b ( 10 million U 3 times per week ) for 12 months ; 16 patients received IFN-alpha-2b alone ( 10 million U 3 times per week for 12 months ) . The primary end point was sustained suppression of HBV DNA and HBeAg seroconversion , which was observed in 15 ( 45 % ) of 33 patients treated with combination therapy and in 3 ( 19 % ) of 16 patients treated with monotherapy ( P=.133 ) . Both therapeutic regimens were well tolerated . Combination therapy increased the rate of sustained suppression of HBeAg and result ed in significant improvement in Knodell histologic activity index scores , compared with monotherapy . However , there was no significant difference in rates of sustained suppression between the 2 groups at the end of follow-up Hepatitis B virus infection is an important public-health issue . Chronic patients have a higher risk of death due to complications , which increases health-care expenses in . Cost-effectiveness analysis of entecavir ( ETV ) versus lamivudine ( LVD ) for treatment of chronic hepatitis B , in e antigen (AgHBe)-positive and negative patients , based on two phase 3 , controlled and r and omized studies . A decision analysis model was developed , using the following endpoints : cost per patient with undetectable viral load and cost per quality life year ( QALY ) gained . Risks for complications ( compensated or decompensated cirrhosis and hepatocellular carcinoma ) were based on the cohort study REVEAL , published in 2006 . The REVEAL parameters were applied to the results of the viral load levels obtained from the clinical assay data . The complication costs were based on a study of the disease cost conducted in Brazil , in 2005 . The cost data were obtained predominantly from Sistema Unico de Saúde [ SUS - Brazilian public health system ] payment tables and drug price lists . The utility data were obtained from literature and life expectancy information was based on IBGE data . The analysis perspective was that of SUS . A discount rate of 3 % per year was used . For the horizon of time of 10 years , the ETV had an incremental cost of approximately two million Brazilian Reais ( R$ ) compared to LVD . Reducing the number of complications , ETV treatment reduced costs by around 3 million , reducing final costs by 1 million , for AgHBe-positive patients . ETV also reduced the incremental cost per QALY gained . ETV was found to be the most cost-effective alternative for AgHBe-positive and negative patients Context Because current treatment options for chronic hepatitis B virus ( HBV ) infection have varying effects and costs , choosing among them is often difficult . Contribution Using a third-party payer perspective and lifetime horizon , this costutility analysis found that monotherapy with interferon but not lamivudine or adefovir was cost-effective . A salvage strategy that used adefovir only in case of lamivudine-associated viral resistance also seemed cost-effective . Caution s The findings apply only to patients with persistently elevated aminotransferase levels and no cirrhosis . The authors did not model the cost-effectiveness of nucleoside analogue salvage after interferon therapy failure . The Editors Chronic hepatitis B virus ( HBV ) infection is a prevalent and expensive condition , affecting 350 million people worldwide and 1.25 million people in the United States ( 1 ) at a cost of more than $ 700 million annually ( 2 ) . Chronic HBV infection can progress to cirrhosis , liver failure , and hepatocellular carcinoma and is a major cause of morbidity and mortality ( 1 , 3 ) . Traditional therapy for chronic HBV infection with either interferon-2b ( interferon ) or lamivudine is difficult and has limited long-term efficacy ( 4 ) . Interferon has clinical ly significant side effects and results in durable virologic response in only 15 % to 30 % of patients ( 5 - 8 ) . Lamivudine is easy to administer and is associated with minimal side effects ( 9 - 11 ) , but it has a higher rate of viral resistance ( 12 ) , lower durable response rate ( 9 - 11 ) , and greater need for prolonged therapy ( 9 , 11 ) compared with interferon . The efficacy of both interferon and lamivudine is even more limited in patients with hepatitis B e antigennegative ( HBeAg-negative ) disease ( 4 ) . This burgeoning population now accounts for more than half of patients with HBV in the United States ( 13 ) and up to 80 % of patients with HBV in Asia ( 14 , 15 ) . Data from 2 r and omized , controlled trials indicate that adefovir is efficacious in HBeAg-positive and HBeAg-negative patients ( 16 , 17 ) . Adefovir has a low risk for side effects and viral resistance ( 18 ) compared with interferon and lamivudine , but it is more expensive ( 19 ) . Therefore , the improved therapeutic benefits of adefovir in chronic HBV infection may offset its increased cost compared with interferon and lamivudine , therapies that are less effective yet less expensive . The most effective and cost-effective therapeutic approach to chronic HBV infection must be established . Given the uncertainty on how best to initiate therapy in HBV , this information may assist clinicians in everyday clinical decision making . We therefore performed an economic analysis to estimate the cost-effectiveness of 5 competing strategies for managing chronic HBV infection in patients with elevated liver enzyme levels and no evidence of cirrhosisthe most prevalent and clinical ly relevant presentation of chronic HBV infection in the primary care setting . We sought to determine whether and under what circumstances the improved therapeutic benefits of adefovir offset its increased cost compared with lamivudine or interferon in managing chronic HBV infection . Methods Decision Model Framework Model Overview Using decision analysis software ( DATA , version 4.0 , TreeAge Software , Inc. , Williamstown , Massachusetts ) , we evaluated a hypothetical cohort of patients 40 years of age with chronic HBV infection , elevated aminotransferase levels , and no clinical or histologic evidence of cirrhosis . To emulate the case mix in clinical practice in the United States ( 13 ) , we assumed that 55 % of the cohort was HBeAg-negative . We subsequently varied this estimate between 0 % and 100 % in our sensitivity analysis . Patients entered the hypothetical model without previous treatment for HBV infection and received 1 of 5 competing strategies for managing chronic HBV infection : 1 ) no pharmacologic treatment of chronic HBV infection ( do nothing strategy ) , 2 ) interferon monotherapy , 3 ) lamivudine monotherapy , 4 ) adefovir monotherapy , or 5 ) lamivudine with crossover to adefovir upon development of viral resistance ( adefovir salvage strategy ) . Because the clinical course , prognosis , and response to therapy vary in patients with HBeAg-positive and HBeAg-negative HBV ( 4 ) , we stratified our analysis by HBeAg status and assigned separate probability estimates for each group . Patients entering the model received either no treatment ( do nothing strategy ) or active treatment for chronic HBV infection . We then followed the cohort over a lifetime horizon through a series of Markov cycles governing patient transitions between relevant health states . The Appendix describes the model structure in detail . Competing Strategies Do Nothing Strategy . In this strategy , which served as the referent case for our analysis , we assumed that patients were followed clinical ly but did not receive pharmacologic therapy for chronic HBV infection . Patients followed the natural history of chronic HBV infection according to their HBeAg status . We further assumed that all patients received regular ongoing care , including hepatocellular cancer screening , and that patients developing cirrhosis were managed for complications , as outlined by published management guidelines ( 4 , 20 ) . We assumed that a proportion of patients with cirrhosis became eligible for liver transplantation and that a subgroup of these patients subsequently underwent liver transplantation at the rate reported by the United Network for Organ Sharing ( 21 ) . Interferon Monotherapy Strategy . Patients in this strategy received up-front active therapy with interferon , 10 million units subcutaneously 3 times per week . We assumed that HBeAg-positive and HBeAg-negative patients received 4 and 12 months of treatment , respectively , as suggested by published guidelines ( 4 , 20 ) . Patients without virologic response did not receive additional HBV therapy and followed the natural history of chronic HBV infection . Lamivudine Monotherapy Strategy . Patients in this strategy received up-front lamivudine , 100 mg orally once daily . Lamivudine therapy was discontinued 6 months after a virologic response . Patients without virologic response , including those developing viral resistance , continued to receive long-term lamivudine therapy as recommended by published guidelines ( 4 , 20 ) . We then assigned patients to receive lifetime lamivudine therapy and discontinued therapy if patients developed a subsequent virologic response . Adefovir Monotherapy Strategy . Patients in this strategy received up-front adefovir , 10 mg orally once daily . Adefovir therapy was discontinued 6 months after a virologic response . Patients without virologic response , including those developing viral resistance , continued to receive long-term adefovir therapy as recommended by published guidelines ( 20 ) . We then assigned patients to receive lifetime adefovir therapy and discontinued therapy if patients developed a subsequent virologic response . Adefovir Salvage Strategy ( Lamivudine to Adefovir Crossover ) . A relevant therapeutic alternative available to clinicians is a hybrid strategy of up-front lamivudine followed by adefovir salvage if lamivudine-related viral resistance develops . We assumed that patients in this strategy initially received lamivudine as described in the lamivudine monotherapy strategy . We then crossed patients over to adefovir when they developed viral resistance , and we subsequently managed patients as described in the adefovir monotherapy strategy . Patients without viral resistance continued to receive lamivudine . Therefore , we reserved adefovir therapy only for patients developing viral resistance while they were receiving lamivudine therapy . Tables 1 and 2 and the Appendix describe the probability estimates governing all 5 strategies . Table 1 . Base-Case Probability Estimates Table 2 . Base-Case Treatment-Related Probability Estimates Model Assumptions The Appendix contains information about our key model assumptions , including base-case patient characteristics , survival assumptions , definition of virologic response , relationship between virologic response or resistance and subsequent health , and effect of treatment-related adverse events . Clinical Probability Estimates Our base-case model incorporated a wide range of estimates governing relevant clinical probabilities in the management and natural history of chronic HBV infection ( Tables 1 and 2 ) . To derive these estimates , we systematic ally review ed MEDLINE to identify relevant English- language studies published from January 1970 to February 2005 . The Appendix describes our systematic review methods . Outcomes Because the main objective of cost-effectiveness analysis is to permit comparisons among different interventions in medicine , and because quality -adjusted life-years ( QALYs ) are the exchange currency that allows these comparisons to be made , we adopted QALYs as our main outcome ( 120 ) . Our analysis reports the incremental cost per QALY gained among the competing strategies , along with the respective 2.5th and 97.5th percentiles around the point estimates as generated by a Monte Carlo analysis of 1000 trials ( see Sensitivity Analyses section for details ) . Utilities We incorporated a wide range of relevant health state utilities in our model . Table 1 contains the specific utility estimates , and the Appendix describes these estimates in detail . Cost Estimates We conducted our analysis from the perspective of a third-party payer and incorporated the direct health care costs for many therapies , physician visits , diagnostic tests , and complications of chronic liver disease ( Table 3 ) . We obtained costs for physician services and procedures from the 2004 American Medical Association Current Procedural Terminology codebook and the 2004 Medicare Fee Schedule ( 121 ) and derived our base-case pharmaceutical costs from the average wholesale prices listed in the 2004 Red Book ( 19 ) . Because large buying consortiums can often obtain prices lower BACKGROUND The efficacy of nucleoside and nucleotide analogues for hepatitis B has been linked to the magnitude and durability of hepatitis B virus ( HBV ) suppression . OBJECTIVE To compare the antiviral efficacy of telbivudine and adefovir dipivoxil , and the effects of switching from adefovir to telbivudine , in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B. DESIGN R and omized , controlled , open-label trial . SETTING 16 outpatient clinics . PATIENTS 135 treatment-naive , HBeAg-positive adults with chronic hepatitis B. INTERVENTION Patients were r and omly assigned in a 1:1:1 ratio to 52 weeks of telbivudine ( group A ) or adefovir ( group B ) , or 24 weeks of adefovir and then telbivudine for the remaining 28 weeks ( group C ) . One hundred thirty-one patients completed 52 weeks of treatment . MEASUREMENTS The primary efficacy comparison was serum HBV DNA reduction at week 24 , with a secondary comparison at week 52 . RESULTS At week 24 , mean HBV DNA reduction was greater in group A than in pooled groups B and C ( -6.30 vs. -4.97 log10 copies/mL ; difference , -1.33 log10 copies/mL [ 95 % CI , -1.99 to -0.66 log(10 ) copies/mL ] ; P < 0.001 ) , and more patients in group A were polymerase chain reaction-negative ( 39 % vs. 12 % ; odds ratio , 4.46 [ CI , 1.86 to 10.72 ] ; P = 0.001 ) . At week 52 , the mean residual HBV DNA level was lower in group A and group C than in group B ( 3.01 log10 copies/mL [ group A ] and 3.02 log10 copies/mL [ group C ] vs. 4.00 log10 copies/mL [ group B ] ; difference , -0.99 log10 copies/mL [ CI , -1.67 to -0.32 log10 copies/mL ] and -0.98 log10 copies/mL [ CI , -1.64 to -0.32 log10 copies/mL ] ; P = 0.004 ) . Adverse events were similar across groups ; the most common were upper respiratory symptoms , headache , back pain , and diarrhea . LIMITATIONS The trial was open-label and was not of sufficient size or duration to compare clinical outcomes and long-term efficacy . CONCLUSION Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment . After 52 weeks , HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir To determine whether combination treatment of HBeAg(- ) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(- ) , HBV DNA-positive chronic hepatitis B who were r and omized to lamivudine , 100 mg , qd , for 12 months or lamivudine-interferon ( 9 MU , t.i.w . ) in combination . In the combination arm , 2 months of lamivudine treatment preceded 10 months of combination treatment . Biochemical , virologic and histologic responses were assessed at the end of treatment , after six and a median 27 months of drug-free follow-up ( short- and long-term follow-up , respectively ) . Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase ( ALT ) . Change in HBV DNA was also assessed by real-time polymerase chain reaction ( PCR ) . Presence of YMDD mutants at the end of treatment was investigated with a line probe assay . Both treatment regimes led to a median 2 log decline in HBV DNA levels . Virologic end of treatment responses were 90 and 92 % with mono- and combination treatment , respectively . Corresponding virologic responses at short- and long-term follow-up were 59 and 54 % , and 27 and 25 % , respectively . Patients having a baseline HBV DNA value > or = 200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level < 200 pg/mL ( P = 0.041 ) . YMDD mutants were observed in 53 % of patients receiving lamivudine compared with 24 % of patients receiving the combination regime ( P = 0.017 ) . In conclusion , efficacy of combination treatment is similar to lamivudine monotherapy . However , combination treatment decreases the development of YMDD mutant strains compared with lamivudine monotherapy OBJECTIVE We conducted a multicentre , double-blind , placebo-controlled , r and omized study to investigate the efficacy of 2-year lamivudine treatment in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS One-hundred- and -thirty-nine treatment-naive patients with HBeAg-negative chronic hepatitis B were r and omized to receive either lamivudine ( 100 mg daily ) or placebo in a 2:1 ratio for 24 months and were followed for an additional 6 months . The primary endpoint was complete response , defined as hepatitis B virus ( HBV ) DNA < 10,000 copies/ml and normalization of alanine aminotransferase ( ALT ) levels at month 24 . RESULTS On intent-to-treat analysis at month 24 , significantly more patients in the lamivudine group than in the placebo group had complete response ( 56 % and 11 % , respectively ; P < 0.001 ) or negative HBV DNA ( 26 % and 6 % , respectively ; P = 0.006 ) . After adjustment of baseline HBV DNA and ALT , the odds ratio for complete response of the lamivudine group versus the placebo group was 10.8 ( 95 % confidence interval : 3.8 - 30.2 ; P < 0.001 ) . The median log HBV DNA reduction was 3.21 copies/ml for the lamivudine group compared with 0.47 copies/ml for the placebo group ( P < 0.001 ) . Genotypic resistance was detected in 23 % and 31 % of patients in the lamivudine group at months 12 and 24 , respectively . Negative HBV DNA at month 6 was associated with high complete response ( 84 % ) and low drug resistance ( 1 % ) at month 24 . At month 30 , there was no difference between lamivudine and placebo groups in the rates of complete response ( 26 % vs 19 % , respectively ; P = 0.38 ) or negative HBV DNA ( 10 % vs 2 % , respectively ; P = 0.09 ) . CONCLUSIONS Two-year lamivudine treatment is effective in HBeAg-negative chronic hepatitis B. However , the response is not sustained after treatment cessation AIM The HBeAg negative form of chronic hepatitis B ( CHB ) predominates in the Mediterranean area and has a rising frequency in Europe and North America . At present there are three approved therapies for patients with CHB : interferon-alpha ( IFN-alpha ) , lamivudine and adefovir dipivoxil . Unfortunately , none of these drugs are effective in achieving a sustained response in patients with HBeAg negative CHB . Therefore , new therapeutic approaches have been examined . Our aim was to investigate the efficacy of combination treatment of IFN-alpha and lamivudine compared to lamivudine monotherapy , after 24 mo of administration in HBeAg-negative hepatitis B patients . METHODS Fifty consecutive patients were r and omly assigned to receive IFN-alpha-2b ( 5 MU thrice per week , n = 24 ) plus lamivudine ( 100 mg daily ) or lamivudine only ( n = 26 ) for 24 mo . Patients were followed up for further 6 mo . The primary outcome was the proportion with sustained virological response ( undetectable serum HBV DNA concentrations ) and or sustained biochemical response ( transaminase levels within normal range ) at 30 mo ( 6 mo after the end of therapy ) . Secondary end-points were timed from initial virological ( biochemical ) response to VBR ( BBR , respectively ) and the emergence of YMDD mutants across the two arms . RESULTS Five of twenty-four ( 21 % ) patients in the combination arm vs 3/26 ( 12 % ) in the lamivudine arm had sustained response ( i.e. , normal serum transaminase levels and undetectable HBV DNA by PCR assay ) 6 mo after treatment discontinuation . A reduction in the emergence of YMDD mutants and in the development of virological breakthroughs was observed in patients receiving combination treatment ( 10 % vs 46 % , P = 0.01 and 14 % vs 46 % , P = 0.03 , respectively ) . Time from initial virologic response to virologic breakthrough ( VBR ) was greater among initial responders receiving combination treatment compared to those receiving lamivudine ( 22.9 mo vs 15.9 mo , respectively ; P = 0.005 ) . CONCLUSION Our results demonstrate that IFN-alpha plus lamivudine combination therapy did not increase the sustained response , compared to lamivudine . However , combination therapy reduces the likelihood of VBR due to YMDD mutants and prolongs the time period until the breakthrough development BACKGROUND Available treatments for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are associated with poor sustained responses . As a result , nucleoside and nucleotide analogues are typically continued indefinitely , a strategy associated with the risk of resistance and unknown long-term safety implication s. METHODS We compared the efficacy and safety of peginterferon alfa-2a ( 180 microg once weekly ) plus placebo , peginterferon alfa-2a plus lamivudine ( 100 mg daily ) , and lamivudine alone in 177 , 179 , and 181 patients with HBeAg-negative chronic hepatitis B , respectively . Patients were treated for 48 weeks and followed for an additional 24 weeks . RESULTS After 24 weeks of follow-up , the percentage of patients with normalization of alanine aminotransferase levels or hepatitis B virus ( HBV ) DNA levels below 20,000 copies per milliliter was significantly higher with peginterferon alfa-2a monotherapy ( 59 percent and 43 percent , respectively ) and peginterferon alfa-2a plus lamivudine ( 60 percent and 44 percent ) than with lamivudine monotherapy ( 44 percent , P=0.004 and P=0.003 , respectively ; and 29 percent , P=0.007 and P=0.003 , respectively ) . Rates of sustained suppression of HBV DNA to below 400 copies per milliliter were 19 percent with peginterferon alfa-2a monotherapy , 20 percent with combination therapy , and 7 percent with lamivudine alone ( P<0.001 for both comparisons with lamivudine alone ) . Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups , as compared with 0 patients in the group given lamivudine alone . Adverse events , including pyrexia , fatigue , myalgia , and headache , were less frequent with lamivudine monotherapy than with peginterferon alfa-2a monotherapy or combination therapy . CONCLUSIONS Patients with HBeAg-negative chronic hepatitis B had significantly higher rates of response , sustained for 24 weeks after the cessation of therapy , with peginterferon alfa-2a than with lamivudine . The addition of lamivudine to peginterferon alfa-2a did not improve post-therapy response rates BACKGROUND / AIMS To evaluate the therapeutic efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. METHODS One hundred and fifty-one patients were r and omly assigned to receive either recombinant interferon alpha-2b ( nine million units three times per week ) and lamivudine ( 100 mg/daily per os ) for 24 weeks or lamivudine alone ( 100 mg/daily per os ) for 52 weeks . Patients were followed up for a further 48 weeks . RESULTS Sustained HBeAg seroconversion with undetectable serum levels of HBV DNA was observed in 25 of 76 patients ( 33 % ) treated with the combination therapy and in 11 of 75 patients ( 15 % ) treated with monotherapy ( P=0.014 ) . Histological improvement defined as a reduction of at least two points in the inflammation score as compared with pretreatment score was observed in 35 of 76 patients ( 46 % ) treated with combination therapy and in 20 of 75 patients ( 27 % ) treated with monotherapy ( P=0.021 ) . Both therapeutic regimens were well tolerated . CONCLUSIONS Six-month treatment with interferon alpha-2b and lamivudine in combination appeared to increase the rate of sustained HBeAg seroconversion compared to 1-year lamivudine monotherapy . However , the potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy BACKGROUND In pre clinical and phase 2 studies , adefovir dipivoxil demonstrated potent activity against hepatitis B virus ( HBV ) , including lamivudine-resistant strains . METHODS We r and omly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen ( HBeAg ) to receive 10 mg of adefovir dipivoxil ( 172 patients ) , 30 mg of adefovir dipivoxil ( 173 ) , or placebo ( 170 ) daily for 48 weeks . The primary end point was histologic improvement in the 10-mg group as compared with the placebo group . RESULTS After 48 weeks of treatment , significantly more patients who received 10 mg or 30 mg of adefovir dipivoxil per day than who received placebo had histologic improvement ( 53 percent [ P<0.001 ] , 59 percent [ P<0.001 ] , and 25 percent , respectively ) , a reduction in serum HBV DNA levels ( by a median of 3.52 [ P<0.001 ] , 4.76 [ P<0.001 ] , and 0.55 log copies per milliliter , respectively ) , undetectable levels ( fewer than 400 copies per milliliter ) of serum HBV DNA ( 21 percent [ P<0.001 ] , 39 percent [ P<0.001 ] , and 0 percent , respectively ) , normalization of alanine aminotransferase levels ( 48 percent [ P<0.001 ] , 55 percent [ P<0.001 ] , and 16 percent , respectively ) , and HBeAg seroconversion ( 12 percent [ P=0.049 ] , 14 percent [ P=0.01 ] , and 6 percent , respectively ) . No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene . The safety profile of the 10-mg dose of adefovir dipivoxil was similar to that of placebo ; however , there was a higher frequency of adverse events and renal laboratory abnormalities in the group given 30 mg of adefovir dipivoxil per day . CONCLUSIONS In patients with HBeAg-positive chronic hepatitis B , 48 weeks of 10 mg or 30 mg of adefovir dipivoxil per day result ed in histologic liver improvement , reduced serum HBV DNA and alanine aminotransferase levels , and increased the rates of HBeAg seroconversion . The 10-mg dose has a favorable risk-benefit profile for long-term treatment . No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene BACKGROUND & AIMS Cirrhosis develops as a result of hepatic inflammation and subsequent fibrosis in chronic hepatitis B infection . We report on the relationship between hepatitis B viremia and progression to cirrhosis in chronic hepatitis B infection . METHODS This was a population -based prospect i ve cohort study of 3582 untreated hepatitis B-infected patients established in Taiwan from 1991 to 1992 . Serum sample s were tested for HBV DNA on cohort entry serum sample s and the diagnosis of cirrhosis was by ultrasound . RESULTS During a mean follow-up time of 11 years , the 3582 patients contributed 40,038 person-years of follow-up evaluation and 365 patients were newly diagnosed with cirrhosis . The cumulative incidence of cirrhosis increased with the HBV-DNA level and ranged from 4.5 % to 36.2 % for patients with a hepatitis B viral load of less than 300 copies/mL and 10(6 ) copies/mL or more , respectively ( P < .001 ) . In a Cox proportional hazards model adjusting for hepatitis B e-antigen status and serum alanine transaminase level among other variables , hepatitis B viral load was the strongest predictor of progression to cirrhosis relative risk [ 95 % confidence interval ] was 2.5 [ 1.6 - 3.8 ] ; 5.6 [ 3.7 - 8.5 ] ; and 6.5 [ 4.1 - 10.2 ] for HBV-DNA levels > /=10(4 ) - < 10(5 ) ; > /=10(5 ) - < 10(6 ) ; > /=10(6 ) copies/mL , respectively . CONCLUSIONS These data show that progression to cirrhosis in hepatitis B-infected persons is correlated strongly with the level of circulating virus . The risk for cirrhosis increases significantly with increasing HBV-DNA levels and is independent of hepatitis B e-antigen status and serum alanine transaminase level BACKGROUND The efficacy of pegylated interferon alfa-2b alone or in combination with lamivudine for the treatment of patients with hepatitis B e antigen ( HBeAg ) negative ( - ) chronic hepatitis B ( CHB ) is understudied . MATERIAL / METHODS One hundred twenty-six patients with HBeAg(-)chronic hepatitis B received pegylated interferon alfa-2b > or = 1.5 micro g/kg/wk for 48 weeks . Ninety of those subjects were r and omly selected to receive concomitant treatment with lamivudine 100 mg/d . The co primary end points were the subjects ' virologic ( hepatitis B virus deoxyribonucleic acid [ HBV DNA ] < 60 IU/mL ) and biochemical ( normalization of alanine aminotransferase levels ) responses 24 weeks after treatment cessation . RESULTS The scores for necroinflammatory activity and fibrosis in patients r and omly assigned to receive monotherapy were statistically significantly lower than those in patients receiving combination therapy . HBV DNA levels were statistically significantly higher and alanine aminotransferase levels were statistically significantly lower in patients receiving monotherapy than in those receiving combination therapy . Virologic responses in the monotherapy and combination therapy groups were similar at weeks 48 and 72 ( 59.1 vs 42.9 % ) . The biochemical response at week 72 was also similar in the treatment groups . The results of multiple regression analysis showed that the virologic response at week 72 was independently correlated with the pegylated interferon alfa-2b dose and that the biochemical response was independently correlated with necroinflammatory activity , the pegylated interferon alfa-2b dose , and lamivudine therapy . CONCLUSIONS These data support the use of pegylated interferon alfa-2b in patients with HBeAg(- ) chronic hepatitis B ; however , the concomitant use of lamivudine produced no additional clinical benefit Context Few studies have evaluated combination therapies for chronic hepatitis B. Contribution In this single-center , open-label trial , 100 patients with hepatitis B e antigenpositive chronic hepatitis B and moderately elevated alanine aminotransferase levels were r and omly assigned to a staggered regimen of pegylated interferon-2b for 32 weeks plus lamivudine for 52 weeks or lamivudine monotherapy . Patients receiving combination therapy more often had virologic responses and less often developed lamivudine-resistant mutants than those receiving monotherapy . Transient influenza-like symptoms , alopecia , and local erythematous reactions were more common with combination therapy . Caution s Patients assigned to combination therapy received treatment for 8 weeks longer than those assigned to monotherapy . The Editors Chronic hepatitis B virus ( HBV ) infection affects more than 300 million people globally ( 1 ) . Patients who have HBV infection with positivity for hepatitis B e antigen ( HBeAg ) and persistently active disease have increased risks for progressive disease leading to liver cirrhosis and hepatocellular carcinoma ( 2 ) . Conventional interferon treatment with injections given up to 3 times per week for 12 to 24 weeks may lead to HBeAg seroconversion in 33 % of treated patients compared with 12 % of untreated controls ( 3 ) . The treatment response to conventional interferon treatment among Asian patients seems less satisfactory ( 4 , 5 ) . Pegylated interferon-2b is synthesized by bonding recombinant interferon-2b to polyethylene glycol and is given once weekly rather than 3 times weekly ( 6 ) . The antiviral efficacy of pegylated interferon-2b for treating chronic hepatitis C is superior to that of conventional interferon ( 7 , 8) , but few studies have evaluated pegylated interferon in patients with chronic hepatitis B. Lamivudine is an oral nucleoside analogue that effectively suppresses HBV replication ( 9 , 10 ) . Studies suggest that only 16 % to 18 % of patients treated with lamivudine for 1 year develop HBeAg seroconversion ( 9 - 11 ) . Extending lamivudine treatment for up to 4 years is associated with development of drug-resistant viral mutants in about 70 % of patients ( 12 ) . The durability of HBeAg seroconversion is estimated to be 46 % to 64 % up to 3 years after the cessation of lamivudine treatment ( 13 - 15 ) . Successful elimination of HBV depends on a durable immune clearance of the existing pool of intrahepatic HBV , particularly the closed covalent circular DNA ( 16 ) . Combining an immunomodulator ( such as interferon ) and an antiviral agent ( such as lamivudine ) is an appealing approach for treating chronic hepatitis B. However , past studies in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B showed conflicting results about the superiority of combination therapy over lamivudine monotherapy ( 11 , 17 - 20 ) . We evaluated whether the combination of pegylated interferon-2b and lamivudine improves antiviral efficacy and increases HBeAg seroconversion rates more than lamivudine monotherapy in patients with HBeAg-positive chronic hepatitis B and moderately elevated alanine aminotransferase ( ALT ) levels . Since extending interferon treatment from 16 to 32 weeks is associated with higher rates of HBeAg seroconversion ( 21 ) , combination therapy includes pegylated interferon-2b given for 32 weeks . Methods Patients We recruited consecutive patients 18 to 65 years of age with chronic hepatitis B from the Hepatitis Clinic of the Prince of Wales Hospital , Hong Kong , China , a secondary referral center serving around 1 million people . All patients had been positive for hepatitis B surface antigen ( HBsAg ) for at least 6 months , were HBeAg-positive , and had a serum HBV DNA level of at least 500000 copies/mL and an ALT level that was 1.3 to 5 times the upper limit of normal . We excluded patients who had decompensated liver disease or a history of interferon or antiviral agent use . Other exclusion criteria were co-infection with hepatitis C virus , hepatitis D virus , or HIV ; history of hepatocellular carcinoma ; other causes of liver disease , including autoimmune hepatitis ; Wilson disease ; hemochromatosis and 1-antitrypsin deficiency ; serious medical or psychiatric illness ; concurrent use of corticosteroid or immunosuppressive agents ; and pregnancy . We conducted the study in accordance with the guidelines of the Declaration of Helsinki . The ethics committee of The Chinese University of Hong Kong approved the protocol , and all patients gave witnessed , written informed consent . Study Design The study was a phase III , open-label , r and omized trial . Within 4 weeks of screening for eligibility criteria , patients were r and omly assigned to either combination therapy with pegylated interferon-2b ( PegIntron , Shering-Plough Corp. , Kenilworth , New Jersey ) and lamivudine ( Zeffix , GlaxoSmithKline , Middlesex , United Kingdom ) or lamivudine monotherapy in a ratio of 1:1 . We based study group assignment on a computer-generated list , and research staff who were not involved in patient management placed the r and om numbers in opaque envelopes . A research nurse prescribed study drugs after receiving the information about treatment allocation at the baseline visit . Figure 1 shows the study design . Pegylated interferon-2b was given as a subcutaneous injection at a dosage of 1.5 g/kg of body weight per week for patients who weighed less than 65 kg or 100 g per week for patients who weighed more than 65 kg for 32 weeks ( 6 ) . Lamivudine was administered as 100 mg orally daily for 52 weeks in both groups of patients . In patients receiving combination therapy , pegylated interferon-2b was administered 8 weeks before lamivudine was administered . Then both treatments were given in combination for 24 weeks , followed by lamivudine monotherapy for a further 28 weeks . Patients in the combination group were asked to return at weeks 1 , 2 , 4 , 8 , 12 , 16 , 20 , 24 , 32 , 40 , 52 , and 60 ( end of treatment ) . Patients in the lamivudine monotherapy group received lamivudine for 52 weeks and were asked to return for follow-up at weeks 4 , 8 , 12 , 16 , 24 , 32 , 40 , 48 , and 52 ( end of treatment ) . We followed patients in both groups every 8 weeks in the post-treatment period for 24 more weeks . We gave open-label lamivudine treatment to patients who experienced severe post-treatment relapse of chronic hepatitis B ( defined as an ALT level > 10 times the upper limit of normal and HBV DNA level > 500000 copies/mL ) . Figure 1 . Study design . Safety The investigators interviewed patients for symptomatic adverse effects and closely monitored laboratory tests at each follow-up visit . They recorded symptoms and events that patients reported spontaneously , symptoms and events elicited in response to open-ended questions , and adverse effects observed at the follow-up visits . They assessed all adverse events on the likelihood of causality by the study drug or drugs . They assessed the severity of adverse events according to a preset table and classified the event as mild ( grade 1 ) , moderate ( grade 2 ) , severe ( grade 3 ) , or life-threatening ( grade 4 ) . The dosage of pegylated interferon was reduced , as necessary , according to the severity of the adverse events . The dosage was reduced from 100 g per week ( or 1.5 g/kg per week if body weight < 65 kg ) to 50 g per week ( or 1.0 g/kg per week if body weight < 65 kg ) for grade 3 adverse events ( or sometimes grade 2 adverse events at the discretion of the investigator ) . The dosage could be further reduced to 25 g per week ( or 0.5 g/kg per week if body weight < 65 kg ) if the adverse recurred despite initial dosage reduction . Pegylated interferon therapy was stopped in case of grade 4 adverse events . Patients receiving combination treatment were allowed to continue lamivudine if investigators thought that the adverse effect was related to pegylated interferon use . Lamivudine therapy was stopped if the adverse event persisted despite cessation of pegylated interferon therapy . We tested serum for HBV DNA levels , HBeAg , and antibody to HBeAg ( at baseline , then 8 weekly until the end of treatment , and weeks 8 , 16 , and 24 after treatment ) and HBsAg and antibody to HBsAg ( at baseline , end of treatment , and 24 weeks after treatment ) . We determined the presence of lamivudine-resistant mutations in the serum sample at the end of treatment . Liver biopsy was performed within 4 weeks before treatment began and at the end of treatment . Laboratory Assays Serologic Assays We tested for HBsAg and antibodies to hepatitis C virus , hepatitis D virus , and HIV by using commercially available enzyme-linked immunosorbant assay kits ( Abbott GmBH Diagnostika , Wiesbaden-Delkenheim , Germany ) . We measured HBeAg and antibody to HBeAg by using an enzyme-linked immunosorbant assay ( Sanofi Diagnostics , Pasteur , France ) . Virologic Assays We based our sample size calculations and initial screening for eligibility on the DNA cross-linking assay ( NAXCOR XLnt , NAXCOR , Menlo Park , California ) , which has a lower limit of detection of 500000 copies/mL for quantification of HBV DNA ( 22 ) . Since the TaqMan real-time polymerase chain reaction assay ( Applied Biosystem , Foster City , California ) became available in our laboratory , we used this assay to measure HBV DNA levels at baseline and in all follow-up visits ( 23 , 24 ) . The range of HBV DNA detection was from 102 to 109 copies/mL ; the correlation coefficient of the st and ard curve was routinely greater than 0.990 . We performed HBV genotyping by restriction fragment length polymorphism in a residual serum sample taken from each patient at their initial visit ( 25 , 26 ) . We determined the presence of lamivudine-resistant mutants by using the INNO-LiPA HBV DR line probe assay ( Innogenetics N.V. , Ghent , Belgium ) according to the instruction of the manufacturer ( 27 ) . End Points We defined virologic response as HBeAg seroconversion ( that is , loss of HBeAg ) , detection of antibody to HBeAg , and HBV DNA level less than 500000 copies/mL and biochemical response as normalization Chronic hepatitis B and its life‐threatening sequelae are highly prevalent in China . There is a need for effective new therapies to suppress hepatitis B virus ( HBV ) replication and ameliorate liver disease . In this study , we compared the efficacy of telbivudine , a nucleoside analogue , with lamivudine in Chinese patients . In this phase III , double‐blind , multicenter trial conducted in China , 332 patients with compensated hepatitis B e antigen (HBeAg)–positive or HBeAg‐negative chronic hepatitis B were r and omly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks . The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment . Secondary endpoints included clearance of HBV DNA to undetectable levels , HBeAg loss and seroconversion , therapeutic response , and alanine aminotransferase ( ALT ) normalization . Viral resistance and safety were assessed . At week 52 , among 290 HBeAg‐positive patients , mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients ( 6.3 log10 versus 5.5 log10 , P < 0.001 ) , and HBV DNA was polymerase chain reaction – negative in significantly more telbivudine recipients than lamivudine recipients ( 67 % versus 38 % , P < 0.001 ) . ALT normalization ( 87 % versus 75 % , P = 0.007 ) , therapeutic response ( 85 % versus 62 % , P = 0.001 ) , and HBeAg loss ( 31 % versus 20 % , P = 0.047 ) were also significantly more common in the telbivudine group . Treatment effects showed similar patterns in the smaller HBeAg‐negative group ( n = 42 ) . Viral resistance in telbivudine recipients was approximately half that observed with lamivudine ; however , this difference was not statistically significant . Clinical adverse events were similar in the two treatment groups . Conclusion : In Chinese patients with chronic hepatitis B , telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine , with less resistance . ( HEPATOLOGY 2007 . BACKGROUND Tenofovir disoproxil fumarate ( DF ) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus ( HBV ) polymerase . METHODS In two double-blind , phase 3 studies , we r and omly assigned patients with hepatitis B e antigen (HBeAg)-negative or HBeAg-positive chronic HBV infection to receive tenofovir DF or adefovir dipivoxil ( ratio , 2:1 ) once daily for 48 weeks . The primary efficacy end point was a plasma HBV DNA level of less than 400 copies per milliliter ( 69 IU per milliliter ) and histologic improvement ( i.e. , a reduction in the Knodell necroinflammation score of 2 or more points without worsening fibrosis ) at week 48 . Secondary end points included viral suppression ( i.e. , an HBV DNA level of < 400 copies per milliliter ) , histologic improvement , serologic response , normalization of alanine aminotransferase levels , and development of resistance mutations . RESULTS At week 48 , in both studies , a significantly higher proportion of patients receiving tenofovir DF than of those receiving adefovir dipivoxil had reached the primary end point ( P<0.001 ) . Viral suppression occurred in more HBeAg-negative patients receiving tenofovir DF than patients receiving adefovir dipivoxil ( 93 % vs. 63 % , P<0.001 ) and in more HBeAg-positive patients receiving tenofovir DF than patients receiving adefovir dipivoxil ( 76 % vs. 13 % , P<0.001 ) . Significantly more HBeAg-positive patients treated with tenofovir DF than those treated with adefovir dipivoxil had normalized alanine aminotransferase levels ( 68 % vs. 54 % , P=0.03 ) and loss of hepatitis B surface antigen ( 3 % vs. 0 % , P=0.02 ) . At week 48 , amino acid substitutions within HBV DNA polymerase associated with phenotypic resistance to tenofovir DF or other drugs to treat HBV infection had not developed in any of the patients . Tenofovir DF produced a similar HBV DNA response in patients who had previously received lamivudine and in those who had not . The safety profile was similar for the two treatments in both studies . CONCLUSIONS Among patients with chronic HBV infection , tenofovir DF at a daily dose of 300 mg had superior antiviral efficacy with a similar safety profile as compared with adefovir dipivoxil at a daily dose of 10 mg through week 48 . ( Clinical Trials.gov numbers , NCT00116805 and NCT00117676 . This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir ( ETV ) versus adefovir ( ADV ) in hepatitis B e antigen positive nucleoside‐naïve adults with chronic hepatitis B ( CHB ) . Sixty‐nine nucleoside‐naïve CHB patients with baseline HBV DNA of 108 copies/mL or more were r and omized 1:1 to open‐label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks . The primary efficacy analysis compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using linear regression . Entecavir was superior to adefovir for mean change from baseline in HBV DNA at week 12 ( −6.23 log10 copies/mL versus −4.42 log10 copies/mL , respectively ; mean difference −1.58 log10 copies/mL ; P < 0.0001 ) . Both drugs demonstrated biphasic viral kinetics , with a first phase of rapid decline lasting 10 days . A significant difference favoring ETV was reached at day 10 ( day 10 ETV−ADV difference estimate : −0.66 log10 copies/mL ; 95 % CI [ −0.30 , −0.01 ] ) . Early virological response was found to be predictive of subsequent virological response , with those having lower HBV DNA levels at day 10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48 . In addition , there was considerably less variability in the extent of HBV DNA reductions in patients treated with entecavir versus adefovir . Both the mean decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less than 300 copies/mL were greater in entecavir‐treated than adefovir‐treated patients at weeks 2 , 4 , 8 , 12 , 24 , and 48 . At week 48 , one ( 3 % ) ETV‐treated versus 15 ( 47 % ) ADV‐treated patients had HBV DNA of 105 copies/mL or more . Both antivirals were well tolerated . Conclusion : Entecavir therapy result ed in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside‐naïve HBeAg‐positive patients with CHB . ( HEPATOLOGY 2009;49:72‐79 . |
11,718 | 26,225,134 | Key Messages : We did not find a positive association between ARA exposure and cerebral ischemia risk .
Eligible studies reported inconsistent findings : cerebral ischemia risk did not change or significantly decreased . | Background : Arachidonic acid ( ARA ) is a precursor of various lipid mediators .
ARA metabolites such as thromboxane A2 cause platelet aggregation and vasoconstriction , thus may lead to atherosclerotic disease .
It is unclear whether dietary ARA influences the ARA-derived lipid mediator balance and the risk for atherosclerotic diseases , such as cerebral ischemia .
Considering the function of ARA in atherosclerosis , it is reasonable to focus on the atherothrombotic type of cerebral ischemia risk .
However , no systematic review s or meta-analyses have been conducted to evaluate the effect of habitual ARA exposure on cerebral ischemia risk . | Stroke incidence in Copenhagen , Denmark was recorded in a r and om population sample of 19,327 persons invited for two health examinations with 5 years ' interval from 1976 to 1983 . Stroke incidence increased exponentially with age . After adjustment to the age and sex distribution of the Danish population in 1980 , the estimated incidence of first stroke was 1.41/1000 women and 2.48/1000 men ; the total incidence was 1.94/1000 population . Risk factor analysis was based on the initial examination of 13,088 persons greater than 35 years old without previous stroke who responded to the first invitation , in whom 295 first strokes were subsequently observed . We used the regression model of Cox . However , our use of this model differs from the somewhat automatic procedures normally used to develop prognostic models . Evaluation of the causative effect of a particular risk factor requires that the direction of mutual influences between the factor in question and other risk factors is established/postulated . Among the 16 potential risk factors for stroke we examined , significant effects were found for age , sex , household income , smoking habits , systolic blood pressure , diabetes , plasma cholesterol concentration , ischemic heart disease , and atrial fibrillation . No significant effect could be demonstrated for a positive family history of stroke , years of school education , marital status , alcohol consumption , daily use of tranquilizers , body mass index , or postmenopausal hormone treatment Background and Purpose — The role of serum fatty acids as a risk factor for stroke and stroke subtypes is largely unknown . Methods — A prospect i ve nested case-control study of Japanese 40 to 85 years of age was conducted through the use of frozen serum sample s from 7450 participants in cardiovascular risk surveys collected from 1984 to 1989 for 1 community and 1989 to 1992 for the other 2 communities . By the end of 1998 , we identified 197 incident strokes whose subtypes were confirmed by imaging studies . Three controls per case were selected by matching for sex , age , community , year of serum storage , and fasting status . Results — Compared with controls , total ( n=197 ) , hemorrhagic ( n=75 ) , and ischemic ( n=122 ) strokes had similar proportions of n3 polyunsaturated fatty acids , lower proportions of linoleic and arachidonic acids , and higher proportions of saturated and monosaturated acids , determined by gas chromatography . The multivariate odds ratios associated with a 1-SD increase in linoleic acid ( 5 % ) after adjustment for hypertension , diabetes , serum total cholesterol , and other cardiovascular risk factors were 0.72 [ 95 % confidence interval ( CI ) , 0.59 to 0.89 ] for total stroke , 0.66 ( 95 % CI , 0.49 to 0.88 ) for ischemic stroke , 0.63 ( 95 % CI , 0.46 to 0.88 ) for lacunar infa rct ion , and 0.81 ( 95 % CI , 0.59 to 1.12 ) for hemorrhagic stroke . The respective odds ratios for saturated fatty acids ( 4 % ) were 1.13 ( 95 % CI , 1.05 to 1.65 ) , 1.35 ( 95 % CI , 1.01 to 1.79 ) , 1.44 ( 95 % CI , 1.03 to 2.01 ) , and 1.21 ( 95 % CI , 0.82 to 1.80 ) . Further adjustment for other fatty acids attenuated these relations , but the relation between linoleic acid and risk of ischemic stroke remained statistically significant . Conclusions — A higher intake of linoleic acid may protect against ischemic stroke , possibly through potential mechanisms of decreased blood pressure , reduced platelet aggregation , and enhanced deformability of erythrocyte cells Background and Purpose — Although aspirin is effective in prevention of stroke , fewer studies have examined the impact of aspirin on stroke morbidity . Methods — The Women ’s Health Study is a completed r and omized , placebo-controlled trial design ed to test the effect of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer , which enrolled 39 876 women . We used multinomial logistic regression to evaluate the relationship between r and omized aspirin assignment and functional outcomes from stroke . Possible functional outcomes were neither stroke nor transient ischemic attack ( TIA ) , modified Rankin scale ( mRS ) score 0 to 1 , 2 to 3 , and 4 to 6 . Results — After a mean of 9.9 years of follow-up , 460 confirmed strokes ( 366 ischemic , 90 hemorrhagic , and 4 unknown type ) and 405 confirmed TIAs occurred . With regard to total and ischemic stroke , women who were r and omized to aspirin had a nonsignificant decrease in risk of any outcome compared to women not r and omized to aspirin . This decrease in risk only reached statistical significance for those experiencing TIA compared to participants without stroke or TIA ( odds ratio=0.77 ; 95 % confidence interval , 0.63–0.94 ) . For hemorrhagic stroke , a nonsignificant increase in the risk of achieving an mRS score 2 to 3 or 4 to 6 compared with no stroke or TIA was observed for the women r and omized to aspirin compared to those r and omized to placebo . Conclusions — Results from this large r and omized clinical trial provide evidence that 100 mg of aspirin every other day may reduce the risk of ischemic cerebral vascular events but does not have differential effects on functional outcomes from stroke OBJECTIVE ω-3 fatty acids , including eicosapentaenoic acid ( EPA ) , prevent ischemic stroke . However , the clinical importance of EPA for ischemic stroke and its subtype has not been fully eluci date d. METHODS In a cross-sectional study , we determined whether ω-3 fatty acids were predictive factors for ischemic stroke . We compared common clinical parameters among 65 patients with ischemic stroke and 65 control subjects . The parameters included blood chemistry data ; concentrations of EPA , docosahexaenoic acid , and arachidonic acid ( AA ) ; EPA/AA ratio ; smoking ; alcohol intake ; fish consumption more than four times per week ; and the incidence of underlying diseases . The comparisons were performed using the Mann-Whitney U test , and multiple logistic regression analysis was applied to the significant factors in the non-parametric test . We also applied the same approach to the ischemic stroke subtypes , cardioembolism and large-artery atherosclerosis . RESULTS In the multiple logistic regression analysis after the Mann-Whitney U test , a lower EPA concentration was one of the significant risk factors for ischemic stroke , as were a lower body mass index , lower high-density lipoprotein cholesterol , and smoking ( sensitivity 0.846 , specificity 0.831 , positive predictive value 0.833 ) . In the analysis of subtypes , a lower EPA/AA ratio and a lower body mass index were the significant risk factors for cardioembolism ( sensitivity 0.800 , specificity 0.733 , positive predictive value 0.750 ) . However , large-artery atherosclerosis was not related to the EPA concentration or the EPA/AA ratio . CONCLUSIONS In this study , the plasma EPA concentration and the EPA/AA ratio were potential predictive risk factors for ischemic stroke , especially for cardioembolism . Further prospect i ve studies are necessary Background and Purpose The etiology of ischemic stroke affects prognosis , outcome , and management . Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke . A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) . Methods A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies . “ Possible ” and “ probable ” diagnoses can be made based on the physician 's certainty of diagnosis . The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria . The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients , first based only on clinical features and then after review ing the results of diagnostic tests . Results The TOAST classification denotes five subtypes of ischemic stroke : 1 ) large-artery atherosclerosis , 2 ) cardioembolism , 3 ) small-vessel occlusion , 4 ) stroke of other determined etiology , and 5 ) stroke of undetermined etiology . Using this rating system , interphysician agreement was very high . The two physicians disagreed in only one patient . They were both able to reach a specific etiologic diagnosis in 11 patients , whereas the cause of stroke was not determined in nine . Conclusions The TOAST stroke subtype classification system is easy to use and has good interobserver agreement . This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke . Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke Arachidonic acid ( AA ) is the precursor of thromboxane and prostacyclin , two of the most active compounds related to platelet function . The effect of dietary AA on platelet function in humans is not understood although a previous study suggested dietary AA might have adverse physiological consequences on platelet function . Here normal healthy male volunteers ( n=10 ) were fed diets containing 1.7 g/d of AA for 50 d. The control diet contained 210 mg/d of AA . Platelet aggregation in the platelet-rich plasma was determined using ADP , collagen , and AA . No statistical differences could be detected between the aggregation before and after consuming the high-AA diet . The prothrombin time , partial thromboplastin time , and the antithrombin III levels in the subjects were determined also . There were no statistically significant differences in these three parameters when the values were compared before and after they consumed the high-AA diet . The in vivo bleeding times also did not show a significant difference before and after the subjects consumed the high-AA diet . Platelets exhibited only small changes in their AA content during the AA feeding period . The results from this study on blood clotting parameters and in vitro platelet aggregation suggest that adding 1.5 g/d of dietary AA for 50 d to a typical Western diet containing about 200 mg of AA produces no observable physiological changes in blood coagulation and thrombotic tendencies in healthy , adult males compared to the unsupplemented diet . Thus , moderate intakes of foods high in AA have few effects on blood coagulation , platelet function , or platelet fatty acid composition Background and Purpose — Although studies have linked types of fatty acids with coronary heart disease , data on individual fatty acids and risk of ischemic stroke are limited . We aim ed to examine the associations between serum fatty acid concentrations and incidence of ischemic stroke and its subtypes . Methods — We conducted a prospect i ve case – control study nested in the Women ’s Health Initiative Observational Study cohort of postmenopausal US women aged 50 to 79 years . Between 1993 and 2003 , incident cases of ischemic stroke were matched 1:1 to controls on age , race , and length of follow-up ( 964 matched pairs ) . Conditional logistic regression was used to estimate odds ratios and 99.9 % confidence intervals ( CI ) for ischemic stroke and its subtypes . Results — The multivariable-adjusted odds ratios and 99.9 % CI of ischemic stroke associated with a 1-SD increment in serum fatty acid concentration were 1.38 ( 99.9 % CI , 1.05–1.83 ) for linoelaidic acid ( 18:2tt , SD=0.04 % ) , 1.27 ( 99.9 % CI , 1.06–1.51 ) for palmitic acid ( 16:0 , SD=2.74 % ) , 1.20 ( 99.9 % CI , 1.01–1.43 ) for oleic acid ( 18:1n9 , SD=2.32 % ) , 0.72 ( 99.9 % CI , 0.59–0.87 ) for docosapentaenoic acid ( 22:5n3 , SD=0.18 % ) , 0.72 ( 99.9 % CI , 0.59–0.87 ) for docosahexaenoic acid ( 22:6n3 , SD=0.91 % ) , and 0.81 ( 99.9 % CI , 0.67–0.98 ) for arachidonic acid ( 20:4n6 , SD=2.02 % ) . These associations were generally consistent for atherothrombotic and lacunar stroke but not cardioembolic stroke . Conclusions — These findings suggest that individual serum trans , saturated , and monounsaturated fatty acids are positively associated with particular ischemic stroke subtypes , whereas individual n3 and n6 polyunsaturated fatty acids are inversely associated Background and Purpose We sought to improve the reliability of the Trial of ORG 10172 in Acute Stroke Treatment ( TOAST ) classification of stroke subtype for retrospective use in clinical , health services , and quality of care outcome studies . The TOAST investigators devised a series of 11 definitions to classify patients with ischemic stroke into 5 major etiologic/pathophysiological groupings . Interrater agreement was reported to be substantial in a series of patients who were independently assessed by pairs of physicians . However , the investigators caution ed that disagreements in subtype assignment remain despite the use of these explicit criteria and that trials should include measures to ensure the most uniform diagnosis possible . Methods In preparation for a study of outcomes and management practice s for patients with ischemic stroke within Department of Veterans Affairs hospitals , 2 neurologists and 2 internists first retrospectively classified a series of 14 r and omly selected stroke patients on the basis of the TOAST definitions to provide a baseline assessment of interrater agreement . A 2-phase process was then used to improve the reliability of subtype assignment . In the first phase , a computerized algorithm was developed to assign the TOAST diagnostic category . The reliability of the computerized algorithm was tested with a series of synthetic cases design ed to provide data fitting each of the 11 definitions . In the second phase , critical disagreements in the data abstract ion process were identified and remaining variability was reduced by the development of st and ardized procedures for retrieving relevant information from the medical record . Results The 4 physicians agreed in subtype diagnosis for only 2 of the 14 baseline cases ( 14 % ) using all 11 TOAST definitions and for 4 of the 14 cases ( 29 % ) when the classifications were collapsed into the 5 major etiologic/pathophysiological groupings ( & kgr;=0.42 ; 95 % CI , 0.32 to 0.53 ) . There was 100 % agreement between classifications generated by the computerized algorithm and the intended diagnostic groups for the 11 synthetic cases . The algorithm was then applied to the original 14 cases , and the diagnostic categorization was compared with each of the 4 physicians ’ baseline assignments . For the 5 collapsed subtypes , the algorithm-based and physician-assigned diagnoses disagreed for 29 % to 50 % of the cases , reflecting variation in the abstract ed data and /or its interpretation . The use of an operations manual design ed to guide data abstract ion improved the reliability subtype assignment ( & kgr;=0.54 ; 95 % CI , 0.26 to 0.82 ) . Critical disagreements in the abstract ed data were identified , and the manual was revised accordingly . Reliability with the use of the 5 collapsed groupings then improved for both interrater ( & kgr;=0.68 ; 95 % CI , 0.44 to 0.91 ) and intrarater ( & kgr;=0.74 ; 95 % CI , 0.61 to 0.87 ) agreement . Examining each remaining disagreement revealed that half were due to ambiguities in the medical record and half were related to otherwise unexplained errors in data abstract ion . Conclusions Ischemic stroke subtype based on published TOAST classification criteria can be reliably assigned with the use of a computerized algorithm with data obtained through st and ardized medical record abstract ion procedures . Some variability in stroke subtype classification will remain because of inconsistencies in the medical record and errors in data abstract ion . This residual variability can be addressed by having 2 raters classify each case and then identifying and resolving the reason(s ) for the disagreement Ethyl arachidonate was administered orally to 4 healthy male volunteers in a dose of 6 gm daily for a 2 to 3 wk period after a 1O‐day control period . The increased intake of this precursor of the dienoic prostagl and ins result ed in significant increases in the relative and absolute amount of arachidonate in plasma triglycerides , phospholipids , and cholesteryl esters . Similar changes in lipid composition were noted in platelets . The excretion of 7 α‐hydroxy‐5 , 11‐diketotetranorprostane‐1 , 16‐dioic acid , the major urinary metabolite of E prostagl and ins in man , was increased by an average of 47 % in 3 of the 4 volunteers . Platelet reactivity was assessed by determining the threshold concentration of adenosine diphosphate ( ADP ) necessary to induce secondary , irreversible aggregation of platelet‐rich plasma . This threshold concentration dropped significantly in all volunteers ( 10 % to 60 % of control values ) . It is concluded that the bio synthesis and function of prostagl and ins can be augmented in man by oral administration of an esterified precursor fatty acid We describe the incidence and natural history of four clinical ly identifiable subgroups of cerebral infa rct ion in a community-based study of 675 patients with first-ever stroke . Of 543 patients with a cerebral infa rct , 92 ( 17 % ) had large anterior circulation infa rcts with both cortical and subcortical involvement ( total anterior circulation infa rcts , TACI ) ; 185 ( 34 % ) had more restricted and predominantly cortical infa rcts ( partial anterior circulation infa rcts , PACI ) ; 129 ( 24 % ) had infa rcts clearly associated with the vertebrobasilar arterial territory ( posterior circulation infa rcts , POCI ) ; and 137 ( 25 % ) had infa rcts confined to the territory of the deep perforating arteries ( lacunar infa rcts , LACI ) . There were striking differences in natural history between the groups . The TACI group had a negligible chance of good functional outcome and mortality was high . More than twice as many deaths were due to the complications of immobility than to direct neurological sequelae of the infa rct . Patients in the PACI group were much more likely to have an early recurrent stroke than were patients in other groups . Those in the POCI group were at greater risk of a recurrent stroke later in the first year after the index event but had the best chance of a good functional outcome . Despite the small anatomical size of the infa rcts in the LACI group , many patients remained substantially h and icapped . The findings have important implication s for the planning of stroke treatment trials and suggest that various therapies could be directed specifically at the subgroups From 1965 to 1968 , the Honolulu Heart Program began following up a cohort of men in a prospect i ve study of cardiovascular disease . For this report , we examined the 12-year risk of stroke in 690 diabetic and 6908 nondiabetic subjects free of coronary heart disease and a history of stroke at study entry . In 12 years of follow-up , 62.3 per 1000 diabetic men and 32.7 per 1000 nondiabetic men experienced a stroke . The relative risk of thromboembolic stroke for those with diabetes compared with those without diabetes was 2.0 ( 95 % confidence limits , 1.4 to 3.0 ) . Although diabetes was usually associated with an atherogenic risk profile , control of hypertension , complicating myocardial infa rct ion , and other risk factors failed to diminish the effect of diabetes on stroke . Among those without diabetes , the relative risk of thromboembolic stroke for those at the 80th percentile of serum glucose level compared with those at the 20th percentile ( 199 vs 115 mg/dL [ 11.0 vs 6.4 mmol/L ] ) was 1.4 ( 95 % confidence limits , 1.1 to 1.8 ) . In the nondiabetic sample , the relative risk of thromboembolic stroke for those with glucosuria compared with those without glucosuria was 2.7 ( 95 % confidence limits , 1.6 to 4.5 ) . There was no association between diabetes , or measures of glucose intolerance , and hemorrhagic stroke . We conclude that diabetes , even in a possibly undiagnosed subset of hyperglycemic individuals , imparts an additional independent risk of stroke unexplained by clinical ly measured risk factors Based on prospect i ve data from the Framingham study relating systolic pressure , diastolic pressure , age , and pulse-wave configuration to future stroke incidence , it would appear that isolated systolic hypertension predisposes to stroke independent of arterial rigidity . The prevalence of isolated systolic hypertension increased with age and with the degree of blunting of the dicrotic notch in the pulse wave . Subjects with isolated systolic hypertension experienced two to four times as many strokes as did normotensive persons . While diastolic pressure is related to stroke incidence , in the subject with systolic hypertension , the diastolic component adds little to risk assessment and in men , in this subgroup , appears unrelated to stroke incidence |
11,719 | 26,100,092 | The study supported PMWT regarding cost saving and patient satisfaction .
The results showed that the PMWT model is superior to UMC in managing warfarin therapy based on observational studies .
As well , it is comparable to UMC based on RCT studies | Despite a growing body of literature supporting the potential benefit of pharmacist-managed warfarin therapy ( PMWT ) , comprehensive review s regarding this topic are still lacking . | Background s Limited evidence is available regarding pharmacist managed anticoagulation clinic in the Southeast Asian region where there is marked difference in terms of care model , genetic composition and patient demographics . Objectives This study aim ed at comparing the anticoagulation clinic managed by the pharmacist with physician advisory and the usual medical care provided in Kuala Lumpur Hospital ( KLH ) in terms of anticoagulation control and adverse outcomes . Setting A 2,302 bedded government tertiary referral hospital in Malaysia . Methods A 6-month retrospective cohort study of the effectiveness of two models of anticoagulation care , the pharmacist managed anticoagulation clinic which is known as warfarin medication therapy adherence clinic ( WMTAC ) and usual medical clinic ( UMC ) in KLH was conducted , where a r and om number generator was used to recruit patients . The UMC patients received st and ard medical care where they are managed by rotational medical officers in the physicians ’ clinic . As for the WMTAC with physician advisory , the pharmacist will counsel and review the patients internationalised normalization ratio at each clinic visit and also adjust the patients ’ warfarin dose accordingly . Patients are referred to physicians if immediate attention is required . Main outcome measure The main therapeutic outcome is time in therapeutic range ( TTR ) both actual and exp and ed TTR and thromboembolic and bleeding complications . Results Each of the WMTAC and usual medical care recruited 92 patients , which totals to 184 patients . The patient demographics in terms of age , race and indication of treatment were comparable . At the end of the 6 months follow-up , patients in the WMTAC group had significantly higher actual-TTR ( 65.1 vs. 48.3 % ; p < 0.05 ) compared to those in usual medical care group . Rates of admission were 6.5 versus 28.2 events per 100 person-years for the WMTAC and UMC groups , respectively . Though the bleeding incidences were not significantly different , it was reduced . Conclusions These findings will impact local warfarin patient management services and policies because there was no available evidence supporting the role of pharmacists in the management of warfarin patients prior to this study Background The beneficial outcomes of oral anticoagulation therapy are dependent upon achieving and maintaining an optimal INR therapeutic range . There is growing evidence that better outcomes are achieved when anticoagulation is managed by a pharmacist with expertise in anticoagulation management rather than usual care by family physicians . This study compared a pharmacist managed anticoagulation program ( PC ) to usual physician care ( UC ) in a family medicine clinic . Methods A retrospective cohort study was carried out in a family medicine clinic which included a clinical pharmacist . In 2006 , the pharmacist assumed anticoagulation management . For a 17-month period , the PC group ( n = 112 ) of patients on warfarin were compared to the UC patients ( n = 81 ) for a similar period prior to 2006 . The primary outcome was the percentage of time patients ' INR was in the therapeutic range ( TTR ) . Secondary outcomes were the percentage of time in therapeutic range within ± 0.3 units of the recommended range ( exp and ed TTR ) and percentage of time the INR was > 5.0 or < 1.5 . Results The baseline characteristics were similar between the groups . Fifty-five percent of the PC group was male with a mean age of 67 years ; 51 % of the UC group was male with a mean age of 71 years . The most common indications for warfarin in both groups were atrial fibrillation , mechanical heart valves and deep vein thrombosis . The TTR was 73 % for PC and 65 % for UC ( p < 0.0001 ) . The exp and ed TTR for PC was 91 % and 85 % for UC ( p < 0.0001 ) . The percentage of time INR values were < 1.5 was 0.7 % for PC patients and 1.9 % for UC patients ( p < 0.0001 ) , and > 5 were 0.3 % for PC patients and 0.1 % for UC ( p < 0.0001 ) . Conclusion The pharmacist-managed anticoagulation program within a family practice clinic compared to usual care by the physicians achieved significantly better INR control as measured by the percentage of time patients ' INR values were kept in both the therapeutic and exp and ed range . Based on the results of this study , a collaborative family practice clinic using pharmacists and physicians may be an effective model for anticoagulation management with these results verified in future prospect i ve r and omized studies BACKGROUND There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians . We carried out a r and omized controlled trial to evaluate these 2 models of anticoagulant care . METHODS We r and omly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practice s. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio ( INR ) of patients receiving warfarin sodium was within the target therapeutic range + /- 0.2 INR units ( exp and ed therapeutic range ) while they were managed in anticoagulation clinics as opposed to family physicians ' care over 3 months . We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups . RESULTS Of the 221 patients enrolled , 112 were r and omly assigned to anticoagulation clinics and 109 to family physicians . The INR values of patients who were managed by anticoagulation clinics were within the exp and ed therapeutic range 82 % of the time versus 76 % of the time for those managed by family physicians ( p = 0.034 ) . High-risk INR values ( defined as being < 1.5 or > 5.0 ) were more commonly observed in patients managed by family physicians ( 40 % ) than in patients managed by anticoagulation clinics ( 30 % , p = 0.005 ) . More INR measurements were performed by family physicians than by anticoagulation clinics ( 13 v. 11 , p = 0.001 ) . Major bleeding events ( 2 [ 2 % ] v. 1 [ 1 % ] ) , thromboembolic events ( 1 [ 1 % ] v. 2 [ 2 % ] ) and deaths ( 5 [ 4 % ] v. 6 [ 6 % ] ) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively . Of the 170 ( 77 % ) patients who completed the patient satisfaction question naire , more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by their family physicians ( p = 0.001 ) . INTERPRETATION Anticoagulation clinics provided better oral anticoagulant management than family physicians , but the differences were relatively modest AIM To compare the treatment outcomes of a clinical pharmacist-managed anticoagulation service with physician-managed service in Chinese patients . METHODS A prospect i ve , r and omized clinical trial was conducted at the anticoagulation clinic of a teaching hospital in Hong Kong . Patients aged > or = 18 years who would required warfarin therapy for at least 3 months were recruited . Patients were r and omized to the pharmacist-managed or physician-managed group . Primary clinical outcome was assessed by the percentage of patient time spent within the target international normalized ratio ( INR ) range . The incidence of major thromboembolic events ( TEs ) and major bleeding was assessed as secondary clinical outcomes . The cost per patient per month ( cPPPM ) was calculated and patient satisfaction was assessed by patient satisfaction question naire (PSQ)-18 . RESULTS One hundred and forty-one patients were recruited at the anticoagulation clinic and 137 patients completed the study . Patients in the pharmacist-managed group ( n = 68 ) were in the target INR 64 % of patient time vs. 59 % in the physician-managed group ( n = 69 ) ( P < 0.001 ) . There was no significant difference in incidence of major TEs or bleeding . The cPPPM in the pharmacist-managed group ( 76 + /- 95 US dollar ) ( 43 + /- 53 British pound ) was lower than in the physician-managed group ( 98 + /- 158 US dollar ) ( 55 + /- 89 British pound ) ( P < 0.001 ) . The PSQ-18 score of the pharmacist-managed group ( 3.8 + /- 0.2 ) was higher than that of the physician-managed group ( 3.6 + /- 0.3 ) ( P < 0.001 ) . CONCLUSION The pharmacist-managed anticoagulation service was more effective and less costly than the physician-managed service in achieving target anticoagulation control for Chinese patients on warfarin therapy Hospitalized patients receiving anticoagulants such as warfarin are at increased risk for adverse events because of difficulties maintaining a therapeutic international normalized ratio ( INR ) . We sought to determine whether a detailed warfarin dosing protocol administered by pharmacists with minimal physician oversight significantly reduced the proportion of hospitalized patients with a supratherapeutic INR . We conducted a prospect i ve , nonr and omized trial with patients on cardiology , internal medicine , and family medicine inpatient services who received at least 1 dose of warfarin while hospitalized . The baseline group included 293 patients , and the intervention group comprised 217 patients . Baseline characteristics were similar in each group , except that more patients received antibiotics in the intervention group . The defect rate ( INR > 5 after receiving warfarin ) in the baseline group was significantly higher than in the intervention group ( 7.85 vs. 1.85 % ) . Conversely , the percentage of patients with an INR less than 1.7 after 4 warfarin doses was lower in the intervention patients , indicating overall improvement in therapeutic levels . Dosing discussion s were required between the pharmacist and a physician for only 6 % of intervention patients . The protocol effectively reduced overanticoagulation without increasing under anticoagulation during hospitalization and reduced the need for close physician oversight 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 STUDY OBJECTIVE To evaluate the safety and economic impact of three models of anticoagulation management services : usual medical care , a nurse-managed service , and a pharmacist-managed service . DESIGN Retrospective medical record review . SETTING An eight-county health care system in central New York State . PATIENTS Nine hundred ninety-six patients ( age range 19 - 99 yrs ) who were receiving warfarin therapy for at least 6 months and who had three or more international normalized ratio ( INR ) values reported during the 1-year study period ; 489 patients ( 6243 INR values ) were in the pharmacist-managed group , 307 patients ( 3618 INR values ) were in the nurse-managed group , and 200 patients ( 3142 INR values ) were in the usual care group . MEASUREMENTS AND MAIN RESULTS All INR measurements were performed by the central laboratory or by on-site point-of-care testing . Data were queried from calendar year 2003 for the usual care and nurse-managed services and calendar year 2006 for the pharmacist-managed service . Anticoagulation indication , INR goal , baseline characteristics , and rates and costs of hospitalization and emergency department visits directly related to anticoagulation therapy were extracted from the medical record . If the INR goal was not documented , a range was assigned as appropriate from the American College of Chest Physicians anticoagulation guidelines . Markers of anticoagulation control -- time in range ( percentage of time a patient is maintained within their therapeutic range ) and percentage of INR values in range -- were calculated for each study group . Baseline characteristics were similar among all study groups . The pharmacist-managed service yielded the lowest rates of hospitalization and emergency department visits , with hospitalizations reduced by 56 % versus nurse-managed service and 61 % versus usual care ( p<0.01 ) . Emergency department visits were reduced by 78 % in both the nurse-managed and usual care models ( p<0.002 ) . Based on visit rates , the pharmacist-managed service averted $ 141,277.34 in hospitalization costs and $ 10,183.76 in emergency department visit costs versus the nurse-managed service and $ 95,579.08 in hospitalization costs and $ 5511.21 in emergency department costs compared with the usual care model . CONCLUSION Pharmacist-managed anticoagulation management services reduced the rates of anticoagulation-related emergency department visits and hospitalizations , with significant financial impact . Based on results of this study , a collaborative clinic using pharmacists , nurses , and physicians may be the optimal structure for an anticoagulation management service , with these results verified in future prospect i ve r and omized studies BACKGROUND Warfarin is implicated in approximately 30 % of reported anticoagulant-related errors . In order to improve anticoagulation management and safety , our institution implemented an inpatient Pharmacist-Directed Anticoagulation Service ( PDAS ) . OBJECTIVE To evaluate the impact of this service on both transition of care and safety of patients receiving warfarin anticoagulation . DESIGN Cluster r and omized trial . SETTING Large , urban teaching hospital and level 1 trauma center . PATIENTS All patients receiving warfarin on two medical and two cardiology units . INTERVENTION A PDAS provided dosing , monitoring , and coordination of transition from the inpatient-to-outpatient setting . MEASUREMENTS Endpoints were assessed during hospitalization and 30 days after discharge . Transition of care was considered effective if compliance with all of the transition of care metrics occurred . The transition of care metrics included : appropriate enrollment in the anticoagulation clinic , documented inpatient-to-outpatient provider contact , documented inpatient provider-to-anticoagulation clinic communication and patient follow-up with the anticoagulation clinic within five days of discharge . Safety was measured by the composite endpoint of thromboembolism , major bleeding , or international normalized ratio ( INR ) ≥5 . RESULTS This study included 500 patients . Transition of care metric compliance occurred in 73 % more patients in the PDAS group ( P < 0.001 ) . There was also a 32 % reduction in the composite safety endpoint in the PDAS group ( P = 0.103 ) . This finding was driven by a reduction in rate of INR ≥5 ( P = 0.076 ) . CONCLUSIONS Implementation of a PDAS provides a net improvement in quality of care for the patient taking warfarin in the inpatient setting Background Warfarin prescription for anticoagulation after cardiac surgery has always been a challenge for junior medical staff . Methods A prospect i ve study was carried out to assess the quality of anticoagulation control by junior doctors compared with clinical pharmacists at South Manchester University hospitals NHS Trust . The junior medical staff prescribed warfarin for 50 consecutive patients from April to September 2006 ( group A , n = 50 ) and experienced clinical pharmacists dosed 46 consecutive patients between February and May 2007 ( group B , n = 46 ) . Results In group A , 9 ( 18 % ) patients discharge was delayed because of lack of attainment of therapeutic International Normalised Ratio ( INR ) compared to 3 ( 6.5 % ) in group B. The total number of bed days result ing from the delay in group A was 21 compared to 4 in group B. Extrapolated over a year this would amount to approximately £ 15,750 extra cost incurred in group A opposed to £ 3000 in group B. Conclusions The pharmacists were significantly better than junior doctors in achieving therapeutic INR , result ing in fewer discharge delays . The clinical pharmacists with experience in outpatient anticoagulation clinic can play an important role in inpatient oral anticoagulation management in post cardiac surgery patients thereby providing improved cost effective quality of care . Keywords Warfarin ; Pharmacist ; STUDY OBJECTIVES To determine whether the impact of anticoagulant control achieved in an Anticoagulation Management Service ( AMS ) is sustained after transfer of anticoagulation management to the primary care physician ( PCP ) , and to assess patient satisfaction with their anticoagulation management by both the AMS and PCP . DESIGN Prospect i ve , r and omized trial . SETTING Pharmacist-directed ambulatory AMS located in a tertiary medical care facility and PCP practice s in Canada . PATIENTS Sixty-two adults who had received at least 6 months of warfarin therapy managed by the AMS . INTERVENTION Patients were r and omly assigned to remain with AMS care ( 32 patients ) or to transfer their anticoagulation management care to their PCP ( 30 patients ) . After 4.5 months of care , patients in both groups completed a vali date d survey instrument assessing their satisfaction with the management of their warfarin therapy . MEASUREMENTS AND MAIN RESULTS Of 295 patients screened , most were excluded from the study for denying consent or for having previous bleeding or clotting complications while taking warfarin . Patients in the AMS and PCP groups who completed the study were similar in age ( median 70 and 76 yrs , respectively ) , and most had atrial fibrillation as an indication for warfarin ( 75 % and 83 % , respectively ) . The primary outcome measure-mean percentage of time within the desired international normalized ratio ( INR ) range after 6 months-was compared between the two groups , using both the actual range ( INR 2.5 ± 0.5 ) and an exp and ed range ( INR 2.5 ± 0.7 ) . No significant difference was noted in this outcome between the groups ( 73.5 ± 19.1 % vs 76.9 ± 24.5 % for the AMS vs PCP groups , p=0.54 ) . Other outcome measures were rates of thrombotic and hemorrhagic events result ing in emergency department visits or hospitalizations , patients ' overall satisfaction with warfarin therapy , and patients ' preferred anticoagulation management strategy . Two hemorrhagic events and one thrombotic event occurred in each group . Patients were more satisfied with their anticoagulant management by the AMS relative to PCP care ( p=0.01 ) , and given the choice , patients preferred AMS care ( p=0.001 ) . CONCLUSION During this 6-month trial , anticoagulation control did not significantly differ between patients who continued to receive anticoagulation management by the AMS and those who transferred to their PCP for anticoagulation management , indicating that the effects of AMS care were sustained . Although patients were more satisfied and preferred to stay with AMS care , this study shows that select patients could have their anticoagulation care transferred to their PCP without compromising anticoagulation control OBJECTIVES A number of studies have reported that the risk of bleeding associated with warfarin is highest early in the course of therapy . This study examined the effect of a programme focused on the transition of newly anticoagulated patients from hospital to the community . DESIGN Open-label r and omized controlled trial . SETTING Home-based follow-up of patients discharged from acute care hospital in southern Tasmania , Australia . SUBJECTS A total of 128 patients initiated on warfarin in hospital and subsequently discharged to general practitioner ( GP ) care were enrolled in the study . Sixty were r and omized to home monitoring ( HM ) and 68 received usual care ( UC ) . INTERVENTIONS HM patients received a home-visit by the project pharmacist and point-of-care international normalized ratio ( INR ) testing on alternate days on 4 occasions , with the initial visit two days after discharge . The UC group was solely managed by the GP and only received a visit 8 days after discharge to determine anticoagulant control . RESULTS At discharge , 42 % of the HM group and 45 % of the UC group had a therapeutic INR . At day 8 , 67 % of the HM patients had a therapeutic INR , compared with 42 % of UC patients ( P < 0.002 ) . In addition , 26 % of UC patients had a high INR , compared with only 4 % of HM patients . Bleeding events were assessed 3 months after discharge and occurred in 15 % of HM patients , compared with 36 % of the UC group ( P < 0.01 ) . CONCLUSIONS This programme improved the initiation of warfarin therapy and result ed in a significant decrease in haemorrhagic complications in the first 3 months of therapy Oral anticoagulant therapy has been shown to be effective for several indications . The optimal intensity of anticoagulation for each indication , however , is largely unknown . To determine this optimal intensity , r and omised clinical trials are conducted in which two target levels of anticoagulation are compared . This approach is inefficient , since the choice of the target levels will be arbitrary . Moreover , the achieved intensity is not taken into account . We propose a method to determine the optimal achieved intensity of anticoagulation . This method can be applied within a clinical trial as an " efficacy- analysis " , but also on data gathered in day-to-day patient care . In this method , INR-specific incidence rates of events , either thromboembolic or hemorrhagic , are calculated . The numerator of the incidence rate is based on data on the INR at the time of the event . The denominator consists of the person-time at each INR value , summed over all patients , and is calculated from all INR measurements of all patients during the follow-up interval . This INR-specific person-time is calculated with the assumption of a linear increase or decrease between two consecutive INR determinations . Since the incidence rates may be substratified on covariates , efficient assessment of the effects of other factors ( e.g. age , sex , comedication ) by multivariate regression analysis becomes possible . This method allows the determination of the optimal pharmacological effects of anticoagulation , which can form a rational starting point for choosing the target levels in subsequent clinical trials To assess the rates of therapeutic international normalized ratio ( INR ) levels between pharmacist-managed clinics compared to traditional physician-management and to determine the variation in rates of therapeutic INR levels between pharmacist-managed clinic data compared to physician-management . Retrospective , r and omized , chart review . Referral only , outpatient , pharmacist based anticoagulation clinic under a community based tertiary care health system . Sixty-four patients with at least 1 year ’s worth of visits to the pharmacist managed clinic were review ed for INR stability . The average percentage of visits within the defined therapeutic range , was 71.1 % for the physician-managed group versus 81.1 % for the pharmacist-managed group ( P < 0.0001 ) . The estimated variance in average therapeutic INR rates was double for the physician-managed group ( 365.7 ) versus the pharmacist-managed group ( 185.2 ) ( P = 0.004 ) . The pharmacist-managed anti-coagulation clinic had higher rates of INRs determined to be therapeutic and also exhibited significantly less variability in therapeutic INR rates relative to the physician-managed service We conducted a prospect i ve cohort study to evaluate clinical and economic end points achieved by a pharmacist-managed anticoagulation service compared with usual care ( 50 patients /group ) . The primary therapeutic end point was the time between starting heparin therapy and surpassing the activated partial thromboplastin time therapeutic threshold . The primary economic end point was the direct variable cost of hospitalization from admission to discharge . No significant differences between groups were noted for the primary therapeutic end point . Total hospital costs were significantly lower for patients receiving pharmacist-managed care than for those receiving usual care ( $ 1594 and $ 2014 , respectively , 1997 dollars , p=0.04 ) . Earlier start of warfarin ( p=0.05 ) and shorter hospital stay ( 5 and 7 days , p=0.05 ) were associated with the pharmacist-managed group STUDY OBJECTIVE To evaluate the impact of a pharmacist-led warfarin patient self-management program on quality of life and anticoagulation control compared with management in a physician-led specialized anticoagulation clinic . DESIGN Prospect i ve , r and omized , controlled , open-label trial . SETTING Tertiary care academic medical center . PATIENTS A total of 114 patients aged 18 - 75 years who were followed at a specialized anticoagulation clinic , had received warfarin for at least 6 months , and were expected to continue warfarin for a minimum of 4 months . INTERVENTION All patients attended an educational session on anticoagulation provided by a pharmacist . Patients r and omized to the self-management group ( 58 patients ) also received practical training to use the CoaguChek XS device and a self-management dosing algorithm . Patients in the control group ( 56 patients ) continued to undergo st and ard management at the anticoagulation clinic . MEASUREMENTS AND MAIN RESULTS Patients completed a vali date d quality -of-life question naire and the vali date d Oral Anticoagulation Knowledge test at the beginning and end of the study . The quality of anticoagulation control was evaluated by using the time spent in therapeutic range . After 4 months of follow-up , a significant improvement in the self-management group was observed compared with the control group in four of the five quality -of-life topics ( p<0.05 ) . Improvements in knowledge were observed in both groups after the training session and persisted after 4 months ( p<0.05 for all ) . The time spent in the therapeutic range ( 80.0 % in the self-management group vs 75 % in the control group , p=0.79 ) and in the extended therapeutic range ( [ target international normalized ratio ± 0.3 ] 93.2 % in the self-management group vs 91.1 % in the control group , p=0.30 ) were similar between groups . CONCLUSION A self-management warfarin program led by pharmacists result ed in significant improvement in the quality of life of patients receiving warfarin therapy as well as a reduction in the time required for anticoagulation monitoring , while maintaining a level of anticoagulation control similar to a high- quality specialized anticoagulation clinic OBJECTIVE : To determine the effect of daily consultation by a team of hospital pharmacists on the accuracy and rapidity of optimizing warfarin therapy . DESIGN : Comparison of a historical control cohort with a prospect i ve cohort matched for treatment indication . SETTING : A 400-bed university teaching hospital . PATIENTS : Sixty consecutive patients hospitalized in 1992 and starting warfarin for the first time , with anticoagulation therapy managed by physicians , were compared with 60 patients matched for warfarin indication hospitalized in 1995 , but with anticoagulation therapy managed with pharmacy consultation . RESULTS : Pharmacist management of initial warfarin therapy result ed in a significant reduction in the length of hospitalization compared with physician dosing , from 9.5 ± 5.6 days to 6.8 ± 4.4 days ( p = 0.009 ) . The number of patients and patient-days with international normalized ratio ( INR ) values > 3.5 were reduced by pharmacist dosing from 37 patients and 142 days to 16 patients and 29 days , respectively ( p < 0.001 ) . Similarly , the number of patients and patient-days with INR > 6.0 were reduced from 20 patients and 50 days to two patients and six days , respectively ( p < 0.001 ) . There were six documented bleeding complications in 1992 compared with one in 1995 ( p = 0.11 ) . The mean INR at discharge was significantly lower in the pharmacy surveillance group , 2.6 ± 0.58 , compared with the physician cohort , 3.3 ± 2.1 ( p = 0.07 ) . Readmissions after discharge due to bleeding or recurrent thrombosis were reduced from five ( at 1 mo ) and 10 ( at 3 mo ) to two and five readmissions , respectively , by pharmacist intervention ( p = 0.43 ) . The number of patients with concurrently prescribed drugs known to significantly interact with warfarin was significantly lower ( 6 vs. 13 ; p = 0.02 ) in the pharmacy surveillance group . CONCLUSIONS : Among patients starting warfarin for the first time , daily consultation by a pharmacist significantly decreased the length of hospital stay and the number of patients who received excessive anticoagulation therapy . These findings translate into improved quality of care and potentially significant cost savings OBJECTIVE The purpose of this study was to evaluate the efficacy , safety and patient satisfaction outcomes of our pharmacist-managed , emergency department (ED)-based outpatient treatment program for venous thromboembolism ( VTE ) disease . METHODS We conducted a prospect i ve cohort study of all patients who were enrolled in the Vancouver General Hospital ( VGH ) outpatient VTE treatment program over a 7-year period ( 1999 - 2006 ) . Efficacy outcomes include recurrent VTE events at 3 and 6 months following discharge from the program . Safety evaluation included major and minor bleeding complications and the development of thrombocytopenia during the acute phase of therapy . Patient satisfaction was assessed using an 18- question patient satisfaction survey , which was mailed to all patients following discharge from the program . RESULTS Overall , 305 patients were included in the study . Of the 260 evaluable patients , 2 patients ( 0.8 % , 95 % confidence interval [ CI ] 0.2 - 2.7 ) experienced a recurrent VTE at 3 months and 5 patients ( 1.9 % , 95 % CI 0.8 - 4.4 ) had a recurrence at 6 months . One patient ( 0.3 % , 95 % CI 0.1 - 1.8 ) experienced a major bleeding complication . Seven patients ( 2.3 % , 95 % CI 1.1 - 4.7 ) experienced a minor bleeding complication and no patient developed thrombocytopenia . Overall , 96.1 % were comfortable having their condition treated as an outpatient and 85.7 % felt it was more convenient to return to hospital daily for medications and assessment than to be admitted to hospital . Finally , 96.9 % of respondents were very satisfied or satisfied with the treatment they received in the outpatient program , and 96.1 % would enroll again if future treatment was indicated . CONCLUSION Our pharmacist-managed , ED-based outpatient treatment program for VTE disease is safe , effective and achieves a high level of patient satisfaction BACKGROUND Older adults frequently have conditions requiring oral anticoagulation . Although clearly benefiting from oral anticoagulation , they are at increased risk for bleeding complications . Regular monitoring to optimize anticoagulation and to reduce the chance of major bleeding complications is required . The impact of oral anticoagulation monitoring by pharmacists in patients older than 75 years of age has not been described well . OBJECTIVE To compare warfarin therapy prescribed and monitored by physicians to a pharmacist-monitored anticoagulation service in a cohort of older veterans . METHODS Retrospective chart review utilizing the Houston VA Medical Center 's pharmacy data base . Among all out patients aged 75 years or older filling warfarin prescriptions between 1 March 2003 to 1 March 2005 , and who were either monitored in a pharmacist 's clinic or not , 103 patients per group were r and omly selected . Information on demographics , indication for and length of warfarin therapy , INR values , and thromboembolic and bleeding events were abstract ed . Differences were analysed using chi-squared test , Fisher 's Exact test , and unpaired Student t-test . RESULTS A total of 1521 patients ( 440 in the pharmacist-monitored group , 1081 in the traditionally monitored group ) met our inclusion criteria . One hundred and three patients per group were r and omly selected for chart review . Although no significant difference in percentage of therapeutic INR values ( 48.1 % pharmacist group , 46.4 % conventional group ) or in the incidence of major bleeding events was found , thromboembolic events occurred significantly less frequently in the pharmacist-monitored group ( 2 events vs. 12 events , P = 0.01 ) . Minor bleeding events were more frequent in the pharmacist-monitored group ( 50 vs. 17 , P < 0.01 ) . However , time to follow-up after a sub- or supra-therapeutic INR was significantly shorter in the pharmacist monitored group ( 22 days vs. 68 days , and 14 days vs. 32 days , respectively ) . CONCLUSION Pharmacist-monitored anticoagulation was associated with reduced thromboembolic events , an increase in minor bleeding events , and no difference in major bleeding events . Overall such monitoring by pharmacists should be recommended for older adults Background : In patients undergoing oral anticoagulation treatment , correct control of the international normalized ratio ( INR ) is necessary . This study sought to assess the effectiveness of a pharmacotherapeutic follow-up programme ( PTP ) on achieving an optimal INR range , reducing the need for rescue medications and for monitoring the development of possible adverse events associated with poor oral anticoagulation therapy control ( haemorrhagic events and thromboembolic disease ) . Objective : The aim of this study was to evaluate the effectiveness of a PTP targeted at the anticoagulated patient to ensure proper self-control of anticoagulation . Methods : This was a prospect i ve , controlled , multicentre cohort study conducted at four primary care centres in Galicia ( northwest Spain ) , covering a group of patients receiving anticoagulation treatment exposed to pharmacotherapeutic follow-up by a primary care pharmacist ( n = 272 ) , and a concurrent control group ( n = 460 ) . The intervention consisted of a patient health-education programme plus activities involving collaboration with the physician . The educational intervention exposure period was 12 months ( starting from February 2006 and finishing in February 2007 ) , during which time a minimum of one INR determination per month was performed . To assess the quality of haematological control , the British Committee for St and ards in Haematology criteria were used , namely ( i ) 50 % or more determinations per patient within a range of 0.5 units above or below the target INR ; and ( ii ) 80 % or more determinations per patient within a range of 0.75 units above or below the target INR . As an indicator of correct control of coagulation , we also assessed the occurrence of oral anticoagulation therapy-related adverse events , such as active bleeding , haematomas ( jointly referred to as haemorrhagic events ) and thromboembolic events . Depending on the type of response variable , negative binomial regression or Cox proportional risks models were fitted . Results : Compared with the control group , the PTP managed to improve correct INR ranges by ( i ) 25 % ( relative risk [ RR ] = 0.75 ; 95 % CI 0.69 , 0.82 ) in terms of the number of patients who had their determinations within ±0.5 units of the target range ; and ( ii ) 26 % ( RR = 0.74 ; 95 % CI 0.67 , 0.81 ) in terms of the number of patients who had their determinations within ±0.75 units of the target range . Patients belonging to the intervention group registered a 75 % reduction in bleeding ( hazard ratio [ HR ] = 0.25 ; 95 % CI 0.18 , 0.36 ) . For every 3.27 patients exposed to the PTP , one event would be prevented ( number needed to treat = 3.27 ; 95 % CI 2.73 , 4.07 ) . Conclusions : Including patients receiving oral anticoagulant treatment in a PTP enhances INR control , efficacy and safety of treatment , and efficiency of primary healthcare services BACKGROUND Some pharmacist-managed anticoagulation services ( PMAS ) provide initial follow-up to patients on oral anticoagulant , who are transferred to their physician once they are stabilized . This may be as effective as and less expensive than long-term PMAS follow-up . METHODS Once PMAS patients were stabilized and ready for discharge , they were r and omized to be transferred to their physician or stay with the PMAS . Quality of international normalized ratio ( INR ) control , incidence of complications , health-related quality of life , use of health care services , and direct incremental cost of PMAS follow-up were evaluated . RESULTS One hundred thirty-eight physicians and 250 patients participated . Patients were initially followed at the PMAS for a mean of 11.3 weeks and afterwards were followed by their physician ( n = 122 ) or by the PMAS pharmacists ( n = 128 ) for a mean of 14.9 and 14.5 weeks , respectively . Pharmacist-managed anticoagulation services ' and physician 's patients were within the exact target range 77.3 % and 76.7 % of the time ( 95 % CI of the difference -4.9 % to 6.0 % ) and within the extended range 93.0 % and 91.6 % of the time ( 95 % CI -2.1 % to 4.7 % ) , respectively . Pharmacist-managed anticoagulation services patients have seen their family physician less often ( 95 % CI -3.1 to -0.1 visit per year ) . Number of INR tests , incidence of complications , and health-related quality of life were similar in both groups . The incremental cost of PMAS follow-up was estimated at CAN$123.80 per patient year . CONCLUSION Once PMAS patients are well stabilized , maintaining a PMAS follow-up or transferring them to their physician is associated with excellent INR control . However , long-term PMAS follow-up may be more expensive |
11,720 | 24,885,250 | Conclusions Longitudinal observational studies show an association between higher levels of physical activity and a reduced risk of cognitive decline and dementia . | Background By 2050 , it has been estimated that approximately one-fifth of the population will be made up of older adults ( aged ≥60 years ) .
Old age often comes with cognitive decline and dementia .
Physical activity may prevent cognitive decline and dementia . | To evaluate the predictive effects of subjective measures of physical activity ( PA ) and objective measures of physical fitness ( PF ) on dementia risk , Participants of the prospect i ve population -based ILSE- study ( * 1930 - 1932 ; 12-year follow-up ) were examined at three examination waves ( t1 : 1993/94 ; t2 : 1997/98 ; t3 : 2005/07 ) . 381 subjects of the original cohort ( n = 500 ) were re-examined at t3 . 29 % of the subjects who were cognitively healthy at baseline received the diagnosis of mild cognitive impairment ( MCI ) and 7 % of Alzheimer 's disease ( AD ) . Subjects were screened for physical and mental health using medical interviews , physical , and neuropsychological examinations . Participants completed a question naire on their current and past PA at t1 . Subjects were classified as physically active if they reported a regular sport activity for at least 2 hours per week in the past year . Muscular strength ( h and grip ) and motor coordination ( balance ) served as objective indicators of PF . Subjects who passed the balance-test at t1 had a reduced risk of developing MCI/AD at t3 ( OR = 0.35 , 95%CI 0.19 - 0.66 , p < 0.01 ) and performed significantly better on various neuropsychological measures . Muscular strength or subjective reports of PA did not predict MCI/AD development . Our results confirm the hypothesis that PF acts as a protective factor for the development of cognitive disorders . In our study , context , motor coordination served as a better predictor than muscular strength or self-rated PA . Since subjects with cognitive disorders due to cerebral and /or systemic disorders were excluded from the analyses , our findings suggest that the effect of skill-related PF extends beyond the reduction of cardiovascular risk factors BACKGROUND Participation in leisure activities has been associated with a lower risk of dementia . It is unclear whether increased participation in leisure activities lowers the risk of dementia or participation in leisure activities declines during the pre clinical phase of dementia . METHODS We examined the relation between leisure activities and the risk of dementia in a prospect i ve cohort of 469 subjects older than 75 years of age who resided in the community and did not have dementia at base line . We examined the frequency of participation in leisure activities at enrollment and derived cognitive-activity and physical-activity scales in which the units of measure were activity-days per week . Cox proportional-hazards analysis was used to evaluate the risk of dementia according to the base-line level of participation in leisure activities , with adjustment for age , sex , educational level , presence or absence of chronic medical illnesses , and base-line cognitive status . RESULTS Over a median follow-up period of 5.1 years , dementia developed in 124 subjects ( Alzheimer 's disease in 61 subjects , vascular dementia in 30 , mixed dementia in 25 , and other types of dementia in 8) . Among leisure activities , reading , playing board games , playing musical instruments , and dancing were associated with a reduced risk of dementia . A one-point increment in the cognitive-activity score was significantly associated with a reduced risk of dementia ( hazard ratio , 0.93 [ 95 percent confidence interval , 0.90 to 0.97 ] ) , but a one-point increment in the physical-activity score was not ( hazard ratio , 1.00 ) . The association with the cognitive-activity score persisted after the exclusion of the subjects with possible pre clinical dementia at base line . Results were similar for Alzheimer 's disease and vascular dementia . In linear mixed models , increased participation in cognitive activities at base line was associated with reduced rates of decline in memory . CONCLUSIONS Participation in leisure activities is associated with a reduced risk of dementia , even after adjustment for base-line cognitive status and after the exclusion of subjects with possible pre clinical dementia . Controlled trials are needed to assess the protective effect of cognitive leisure activities on the risk of dementia Background Older adults free of dementia but with subjective memory complaints ( SMC ) or mild cognitive impairment ( MCI ) are considered at increased risk of cognitive decline . Vascular risk factors ( VRF ) , including hypertension , heart disease , smoking , hypercholesterolemia and lack of physical activity ( PA ) have been identified as modifiable risk factors contributing to cognitive decline , and white matter hyperintensities ( WMH ) are associated with VRF , SMC and cognitive impairment . Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function , but few studies are investigating these benefits in high-risk population s. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging ( MRI ) . Methods / design This single-blind r and omized controlled trial ( RCT ) is offered to 156 participants , aged 60 and older , in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging ( AIBL ) . Participants must have SMC with or without MCI and at least one VRF . The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI ( Fitness for the Ageing Brain Study ) . It comprises 24 months of moderate , home-based PA ( 150 minutes per week ) and a behavioral intervention package . The primary outcome measure will be change in WMH after 24 months on MRI . Cognition , quality of life , functional fitness , level of physical activity , plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography ( PET ) imaging comprise secondary measures . Discussion Currently , there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk . Should our findings show that physical activity can slow down the progression of WMH , this RCT would provide an important proof of concept . Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer 's disease pathologies . Trial Registration Australia New Zeal and Clinical Trials Registry BACKGROUND Data regarding the relationship between physical activity and cognitive impairment are limited and controversial . We examined whether physical activity is associated with incident cognitive impairment during follow-up . METHODS As part of a community-based prospect i ve cohort study in southern Bavaria , Germany , 3903 participants older than 55 years were enrolled between 2001 and 2003 and followed up for 2 years . Physical activity ( classified as no activity , moderate activity [ <3 times/wk ] , and high activity [ > or =3 times/wk ] ) , cognitive function ( assessed by the 6-Item Cognitive Impairment Test ) , and potential confounders were evaluated . The main outcome measure was incident cognitive impairment after 2 years of follow-up . RESULTS At baseline , 418 participants ( 10.7 % ) had cognitive impairment . After a 2-year follow-up , 207 of 3485 initially unimpaired subjects ( 5.9 % ) developed incident cognitive impairment . Compared with participants without physical activity , fully adjusted multiple logistic regression analysis showed a significantly reduced risk of incident cognitive impairment after 2 years for participants with moderate or high physical activity at baseline ( odds ratio [ OR ] , 0.57 ; 95 % confidence interval [ CI ] , 0.37 - 0.87 [ P = .01 ] ; and OR , 0.54 ; 95 % CI , 0.35 - 0.83 [ P = .005 ] ; respectively ) . Further sub analysis including participants ( n = 2029 ) without functional impairment and without prodromal phase of dementia result ed in an even higher reduction of risk of incident cognitive impairment for participants with moderate or high physical activity ( OR , 0.44 ; 95 % CI , 0.24 - 0.83 [ P = .01 ] ; and OR , 0.46 ; 95 % CI , 0.25 - 0.85 [ P = .01 ] ; respectively ) compared with no activity . CONCLUSION Moderate or high physical activity is associated with a reduced incidence of cognitive impairment after 2 years in a large population -based cohort of elderly subjects CONTEXT Evidence suggests that physical activity may be related to the clinical expression of dementia . Whether the association includes low-intensity activity such as walking is not known . OBJECTIVE To examine the association between walking and future risk of dementia in older men . DESIGN Prospect i ve cohort study . SETTING AND PARTICIPANTS Distance walked per day was assessed from 1991 to 1993 in 2257 physically capable men aged 71 to 93 years in the Honolulu-Asia Aging Study . Follow-up for incident dementia was based on neurological assessment at 2 repeat examinations ( 1994 - 1996 and 1997 - 1999 ) . MAIN OUTCOME MEASURES Overall dementia , Alzheimer disease , and vascular dementia . RESULTS During the course of follow-up , 158 cases of dementia were identified ( 15.6/1000 person-years ) . After adjusting for age , men who walked the least ( < 0.25 mile/d ) experienced a 1.8-fold excess risk of dementia compared with those who walked more than 2 mile/d ( 17.8 vs 10.3/1000 person-years ; relative hazard [ RH ] , 1.77 ; 95 % confidence interval [ CI ] , 1.04 - 3.01 ) . Compared with men who walked the most ( > 2 mile/d ) , an excess risk of dementia was also observed in those who walked 0.25 to 1 mile/d ( 17.6 vs 10.3/1000 person-years ; RH , 1.71 ; 95 % CI , 1.02 - 2.86 ) . These associations persisted after accounting for other factors , including the possibility that limited amounts of walking could be the result of a decline in physical function due to pre clinical dementia . CONCLUSIONS Findings suggest that walking is associated with a reduced risk of dementia . Promoting active lifestyles in physically capable men could help late-life cognitive function CONTEXT Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease ( AD ) risk but their combined association has not been investigated . OBJECTIVE To investigate the combined association of diet and physical activity with AD risk . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York , New York , with both diet and physical activity information available . St and ardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006 . Adherence to a Mediterranean-type diet ( scale of 0 - 9 ; trichotomized into low , middle , or high ; and dichotomized into low or high ) and physical activity ( sum of weekly participation in various physical activities , weighted by the type of physical activity [ light , moderate , vigorous ] ; trichotomized into no physical activity , some , or much ; and dichotomized into low or high ) , separately and combined , were the main predictors in Cox models . Models were adjusted for cohort , age , sex , ethnicity , education , apolipoprotein E genotype , caloric intake , body mass index , smoking status , depression , leisure activities , a comorbidity index , and baseline Clinical Dementia Rating score . MAIN OUTCOME MEASURE Time to incident AD . RESULTS A total of 282 incident AD cases occurred during a mean ( SD ) of 5.4 ( 3.3 ) years of follow-up . When considered simultaneously , both Mediterranean-type diet adherence ( compared with low diet score , hazard ratio [ HR ] for middle diet score was 0.98 [ 95 % confidence interval { CI } , 0.72 - 1.33 ] ; the HR for high diet score was 0.60 [ 95 % CI , 0.42 - 0.87 ] ; P = .008 for trend ) and physical activity ( compared with no physical activity , the HR for some physical activity was 0.75 [ 95 % CI , 0.54 - 1.04 ] ; the HR for much physical activity was 0.67 [ 95 % CI , 0.47 - 0.95 ] ; P = .03 for trend ) were associated with lower AD risk . Compared with individuals neither adhering to the diet nor participating in physical activity ( low diet score and no physical activity ; absolute AD risk of 19 % ) , those both adhering to the diet and participating in physical activity ( high diet score and high physical activity ) had a lower risk of AD ( absolute risk , 12 % ; HR , 0.65 [ 95 % CI , 0.44 - 0.96 ] ; P = .03 for trend ) . CONCLUSION In this study , both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD Objective : This study evaluated the protective role of physical activity ( PA ) against cognitive impairment ( CI ) in the oldest old ( age ≥ 85 ) . Method : Prospect i ve data on 66 optimally healthy , oldest old adults ( mean age 88.5 ) were analyzed using survival analysis . Results : In all , 12 men and 11 women reported exercising > 4 hours per week , and 38 participants developed CI ( mean onset age 93 ; mean follow-up 4.7 years ) . The effect of exercise was modified by gender . In more active women ( > 4 hours/week ) , the risk of CI was reduced by 88 % ( 95 % confidence interval 0.03 , 0.41 ) compared to those less active . Less active women had 2 times the incidence rate of CI compared to less active men and almost 5 times the rate compared to active women . Discussion : This study demonstrates the beneficial effects of exercise on healthy brain aging even in the oldest old and emphasizes the importance of increasing PA in older women BACKGROUND Cognitive impairment that does not meet the criteria for dementia ( " Cognitive Impairment , No Dementia " -- CIND ) is a heterogeneous category with an increased risk of dementia . While greater physical activity is generally associated with a lower odds of both dementia and CIND , whether this effect applies across subgroups is not known . OBJECTIVES To investigate the association between physical activity and the risk of vascular CIND ( VCI-ND ) or mild cognitive impairment ( MCI ) . METHODS In the Canadian Study of Health and Aging community-dwelling cohort , of 4683 people who were not impaired at baseline , 3945 remained without cognitive impairment at 5 years , 454 were diagnosed with CIND , and 284 with dementia . Incident CIND and VCI-ND ( n=163 ) and MCI ( n=100 ) subtypes were investigated in relation to baseline physical activity , stratified by sex . RESULTS In women , moderate-high exercise was associated with a lower odds of CIND ( OR=0.62 , 95 % CI=0.46 - 0.84 ) and VCI-ND ( 0.34 , 0.18 - 0.63 ) relative to low exercise . There was no association for men or for MCI . CONCLUSION Exercise appears to reduce the risk of VCI-ND in women . Whether the lack of an effect of exercise on the odds of MCI reflects that ' prevented AD ' is indistinguishable from MCI is an intriguing possibility that merits further study Objectives : Mental disorders such as depression , anxiety and dementia are common in elderly . However , physical activity is suggested to be effective in preventing such aging-related disorders . The aim of this study was to investigate the role of physical activity on mental health in later life . Methods : Four hundred elderly people were r and omly divided into the intervention and control groups . The intervention consisted of exercise twice a week for two months . Mental health status before , just after , and three months after the study was assessed with the 28-item General Health Question naire ( GHQ-28 ) . Results : The mean of the GHQ-28 total scale decreased in the case group and this change remained significant after three months ( before : 8 ± 5.5 , after three months : 5.6 ± 4.6 , p < .001 ) . GHQ subscales including somatization , anxiety , social dysfunction , and depression decreased significantly in the case group just after and three months after the intervention . Conclusions : Physical activity significantly prevents mental disorder in older adults . Although it has effects on anxiety , social dysfunction , and depression , the greatest influence is on improving the somatization symptoms OBJECTIVES We examined the association between physical activity and cognitive functioning in middle age . METHODS Data were derived from a prospect i ve occupational cohort study of 10308 civil servants aged 35 - 55 years at baseline ( phase 1 ; 1985 - 1988 ) . Physical activity level , categorized as low , medium , or high , was assessed at phases 1 , 3 ( 1991 - 1994 ) , and 5 ( 1997 - 1999 ) . Cognitive functioning was tested at phase 5 , when respondents were 46 - 68 years old . RESULTS In both prospect i ve ( odds ratio [ OR ] = 1.65 ; 95 % confidence interval [CI]=1.30 , 2.10 ) and cross-sectional ( OR=1.79 ; 95 % CI=1.38 , 2.32 ) analyses , low levels of physical activity were a risk factor for poor performance on a measure of fluid intelligence . Analyses aim ed at assessing cumulative effects ( summary of physical activity levels at the 3 time points ) showed a grade d linear relationship with fluid intelligence , with persistently low levels of physical activity being particularly harmful ( OR=2.21 ; 95 % CI=1.37 , 3.57 ) . CONCLUSIONS Low levels of physical activity are a risk factor for cognitive functioning in middle age , fluid intelligence in particular CONTEXT Dementia is common , costly , and highly age related . Little attention has been paid to the identification of modifiable lifestyle habits for its prevention . OBJECTIVE To explore the association between physical activity and the risk of cognitive impairment and dementia . DESIGN , SETTING , AND SUBJECTS Data come from a community sample of 9008 r and omly selected men and women 65 years or older , who were evaluated in the 1991 - 1992 Canadian Study of Health and Aging , a prospect i ve cohort study of dementia . Of the 6434 eligible subjects who were cognitively normal at baseline , 4615 completed a 5-year follow-up . Screening and clinical evaluations were done at both waves of the study . In 1996 - 1997 , 3894 remained without cognitive impairment , 436 were diagnosed as having cognitive impairment-no dementia , and 285 were diagnosed as having dementia . MAIN OUTCOME MEASURE Incident cognitive impairment and dementia by levels of physical activity at baseline . RESULTS Compared with no exercise , physical activity was associated with lower risks of cognitive impairment , Alzheimer disease , and dementia of any type . Significant trends for increased protection with greater physical activity were observed . High levels of physical activity were associated with reduced risks of cognitive impairment ( age- , sex- , and education-adjusted odds ratio , 0.58 ; 95 % confidence interval , 0.41 - 0.83 ) , Alzheimer disease ( odds ratio , 0.50 ; 95 % confidence interval , 0.28 - 0.90 ) , and dementia of any type ( odds ratio , 0.63 ; 95 % confidence interval , 0.40 - 0.98 ) . CONCLUSION Regular physical activity could represent an important and potent protective factor for cognitive decline and dementia in elderly persons Physical activity may help preserve cognitive function and decrease dementia risk , but epidemiologic findings are inconsistent . The authors conducted a prospect i ve study to determine the association between physical activity and risk of dementia , Alzheimer 's disease , and vascular dementia . The US study population comprised 3,375 men and women aged 65 years or older , free of dementia at baseline , who participated in the Cardiovascular Health Cognition Study in 1992 - 2000 . Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated . Analyses were based on Cox proportional hazards models . There were 480 incident cases of dementia over an average of 5.4 years of follow-up . After multivariate adjustment , participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 ( 95 % confidence interval : 0.61 , 1.19 ) compared with those in the lowest quartile , and participants engaging in > or=4 activities had a relative risk of dementia of 0.51 ( 95 % confidence interval : 0.33 , 0.79 ) compared with those engaging in 0 - 1 activity . These associations were more marked in apolipoprotein E genotype ( APOE ) epsilon4 allele noncarriers but were absent in carriers . A similar pattern was observed for Alzheimer 's disease and vascular dementia . Mechanisms to explain the observed relations deserve further study As noted by Wesley Salmon and many others , causal concepts are ubiquitous in every branch of theoretical science , in the practical disciplines and in everyday life . In the theoretical and practical sciences especially , people often base cl aims about causal relations on applications of statistical methods to data . However , the source and type of data place important constraints on the choice of statistical methods as well as on the warrant attributed to the causal cl aims based on the use of such methods . For example , much of the data used by people interested in making causal cl aims come from non-experimental , observational studies in which r and om allocations to treatment and control groups are not present . Thus , one of the most important problems in the social and health sciences concerns making justified causal inferences using non-experimental , observational data . In this paper , I examine one method of justifying such inferences that is especially widespread in epidemiology and the health sciences generally – the use of causal criteria . I argue that while the use of causal criteria is not appropriate for either deductive or inductive inferences , they do have an important role to play in inferences to the best explanation . As such , causal criteria , exemplified by what Bradford Hill referred to as " aspects of [ statistical ] associations " , have an indispensible part to play in the goal of making justified causal cl aims Context Some studies suggest that people with high levels of physical activity are less likely to develop dementia . Content All 1740 participants in this cohort study were 65 years of age or older and were cognitively intact at baseline . Over 6.2 years , the rate of dementia was 13.0 per 1000 person-years in those who exercised 3 or more times per week and 19.7 per 1000 person-years in those who exercised less than 3 times per week . Limitations The only measure of exercise intensity was self-reported frequency . The cohort was largely white and well-educated . Implication s This study adds to the evidence that regular exercise is associated with a lower risk for dementia . However , the existing evidence does not prove that regular exercise is associated with a lower dementia risk . The Editors Alzheimer disease and other dementing illnesses are major sources of morbidity and mortality ( 1 - 3 ) that affect millions of persons in the increasingly aging society of the United States . Research design ed to discover strategies to delay onset and progression of these potentially devastating illnesses is ongoing worldwide . Effective prevention strategies would result in substantial benefits through improved quality of life , prolonged independent life expectancy , and reduced economic cost and social burdens . Regular physical exercise is an important element in overall health promotion ( 4 ) and might also be an effective strategy to delay onset of dementia ( 5 ) . A biological basis for how physical exercise might preserve brain function includes improved cerebral blood flow and oxygen delivery ( 6 ) and inducing fibroblast growth factor in the hippocampus ( 7 ) . More recent evidence suggests that reduced loss of hippocampal brain tissue in the aging brain is related to level of physical fitness ( 8) . Evidence from some longitudinal studies and r and omized trials suggests that physical exercise enhances cognitive function in older adults ( 9 - 15 ) , whereas other studies have failed to observe the benefits of physical exercise in preserving cognitive function ( 16 - 19 ) . Many people regard Alzheimer disease as one of the most dreaded consequences of aging . If regular physical exercise were shown to be effective in reducing the risk or delaying the onset of dementing illnesses , it would be another compelling reason to promote physical exercise . Few population -based longitudinal studies have examined the role of physical exercise on the risk for dementia in elderly persons . One recent longitudinal study showed that physical exercise was associated with decreased risk for decline in cognitive function ( odds ratio [ OR ] , 0.58 ) , Alzheimer disease ( OR , 0.50 ) , and any dementia ( OR , 0.63 ) ( 11 ) , whereas another longitudinal study showed no association between physical exercise and dementia ( 16 ) . More recent studies showed that walking was associated with a reduced risk for dementia and Alzheimer disease in a cohort of Japanese-American men ( 20 ) and that engaging in more diverse physical activities was associated with a reduced risk for dementia in the Cardiovascular Health Study ( 21 ) . The purpose of this study was 2-fold : 1 ) to determine whether regular exercise is associated with a reduced risk for incidence of dementia ( in particular , Alzheimer disease ) in a cohort followed biennially over 6 years and 2 ) to examine whether the association of physical exercise with incident dementia is modulated by other potential risk factors , such as depression , cardiovascular and cerebrovascular disease , diabetes , apolipoprotein E 4 allele , cognitive function , physical function , self-rated health , and lifestyle characteristics . Methods Study Sample The Adult Changes in Thought ( ACT ) study is a population -based , longitudinal study of aging and dementia . The ACT study was design ed to determine the incidence of Alzheimer disease , other types of dementia , and cognitive impairment as well as to determine risk factors for these conditions . The details of the ACT study have been described elsewhere ( 22 , 23 ) . Briefly , a r and om sample of 6782 individuals was drawn from Seattle-area members of Group Health Cooperative ( GHC ) , a consumer-governed health maintenance organization . The participants were 65 years of age and older when the study began in 1994 to 1996 . Those who had an existing diagnosis of dementia , were current residents of a nursing home , or were participating in other studies were ineligible ( n= 1360 ) . Of 5422 eligible persons , 2581 participated and 2841 declined participation . Age , sex , and ethnicity of the remaining 2581 participants did not differ significantly from those who were excluded . Nonresponse has been described elsewhere ( 22 ) . Declining to participate was more common among the oldest age group ( > 85 years ) , women , and African-American and minority groups ( 22 ) . Additional details regarding the incident rates of dementia and Alzheimer disease from the ACT study have been published elsewhere and are consistent with rates reported in U.S. and European cohort studies ( 22 ) . The institutional review boards of the University of Washington and Group Health Cooperative approved the ACT study . Participants received the Cognitive Ability Screening Instrument ( CASI ) ( 24 ) as initial screening for cognitive function and were interviewed with structured question naires to obtain data , including demographic characteristics , medical history , memory and general functioning , and potential epidemiologic risk factors . Persons scoring 86 or higher on the CASI were entered directly into the ACT cohort as being cognitively intact . ( The CASI scores range from 0 to 100 ; a score of 86 corresponds to a Mini-Mental State Examination score of 25 to 26 . ) Persons with a score lower than 86 had additional medical record review and st and ardized clinical and neuropsychological evaluation for dementia . Persons who did not meet established criteria for dementia ( 25 ) were included in the ACT cohort . The current study sample was selected from the 2581 ACT participants to examine the temporal relationship of physical exercise preceding development of dementia . By design , we selected the 1895 persons whose CASI scores were above the 25th percentileCASI scores 91 to 100 . We excluded 686 persons whose CASI scores were in the lowest quartileCASI scores 62 to 90because the lowest quartile group might include persons who had mild cognitive impairment or impending dementia ( 26 ) . We did not collect information about the history of exercise before the participants entered the study . Therefore , in the group with low CASI scores , we could not be certain whether a reported low level of physical exercise preceded the development of dementia or was a consequence of the development of cognitive impairment or dementia . Of 1895 participants selected , 155 withdrew after the baseline visit and did not have a follow-up examination and were thus excluded from the analyses , leaving the analytic sample of 1740 persons . Incident Dementia We conducted biennial examinations to identify cases of incident dementia , when participants were rescreened with the CASI . Those who scored 86 or higher on the CASI remained in the ACT cohort . Scores on the CASI that were less than 86 at follow-up prompted a full st and ardized clinical examination . The results of rescreening by the CASI and by the clinical and neuropsychological examinations were review ed at a consensus diagnosis conference that included at least the examining physician , a neuropsychologist , another study physician , and the study nurse . Persons who did not meet the criteria for dementia were considered as not having dementia and were followed in the ACT cohort ( 22 , 23 ) . Persons who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) , criteria ( 25 ) for dementia were considered to have incident dementia . Dementia type was determined by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer 's Disease and Related Disorders Association ( NINCDS-ADRDA ) criteria ( 27 ) for Alzheimer disease and by the DSM-IV criteria ( 25 ) for other types of dementia . Level of physical activity was not considered at the consensus conference . Physical Exercise Physical exercise was assessed at baseline by asking participants the number of days per week they did each of the following activities for at least 15 minutes at a time during the past year : walking , hiking , bicycling , aerobics or calisthenics , swimming , water aerobics , weight training or stretching , or other exercise . The frequency of exercise was calculated by the times per week that participants engaged in any of these forms of exercise . In this study , persons who exercised at least 3 times a week , above the lowest quartile , were classified as exercising regularly . Baseline Variables as Potential Confounders Numerous factors may influence the relationship between exercise and risk for dementia , including physical functioning , cognitive function , depression , health conditions , and lifestyle characteristics . Physical function was assessed by a performance-based physical function ( PPF ) test ( 23 ) , which consisted of 4 performance tests : 10-foot timed walk , time to st and from a seated position in a chair to a st and ing position 5 times , balance test , and grip strength in the dominant h and . Each test was scored from 0 to 4 points . The final PPF score was the sum of the scores for the 4 performance tests and ranged from 0 to 16 ; higher scores indicated better physical function . Details of the PPF test have been reported elsewhere ( 23 ) . Cognitive function was assessed by using the CASI , which provides quantitative assessment of attention , concentration , orientation , short-term memory , long-term memory , language ability , visual construction , list-generating fluency , abstract ion , and judgment ( 24 ) . At baseline , depression was measured by using the 11-item Center for Epidemiologic Studies Depression ( CES-D ) scale ( 28 ) . The CES-D scores ranged from 0 to 33 , with higher scores Several studies have associated physical activity with the risk of dementia , but mostly did so during short follow-up . It remains unclear whether physical activity also affects dementia during longer follow-up . We examined the association between physical activity and risk of dementia during a follow-up period up to 14 years . From 1997 to 1999 , physical activity was assessed using a vali date d question naire in 4,406 elderly persons ( age range 61–97 ) from the prospect i ve , population -based Rotterdam Study . Follow-up for dementia was complete until January 1 , 2011 . We used Cox proportional hazards models to assess the association between physical activity and incident dementia . Next , we stratified follow-up time using a cut-off of 4 years . We separately investigated dementia due to Alzheimer disease . During 38,631 person-years , 583 participants developed dementia . When adjusting for age and sex , we found a borderline significant association between higher physical activity and lower risk of dementia ( HR 0.95 ; 95 % CI 0.87–1.04 ) . This association was confined to follow-up up to 4 years ( HR 0.82 ; 95 % CI 0.71–0.95 ) , and not to follow-up of at least 4 years ( HR 1.04 ; 95 % CI 0.93–1.16 ) . Additional adjustments only slightly attenuated the associations . A similar pattern was present for Alzheimer disease . We found a higher level of physical activity to be associated with a lower risk of dementia . This association was confined to follow-up for up to 4 years and not to longer follow-up , suggesting either a role for reverse causality or only a short term effect of late-life physical activity in an elderly population BACKGROUND We evaluated the combined and differential effects of physical , social and productive activities on cognitive decline and whether they were modified by the presence of the APOE-epsilon 4 allele . METHODS In a prospect i ve cohort study of 1635 community-dwelling Chinese older adults aged 55 or older participating in the ongoing Singapore Longitudinal Aging Study , physical , social and productive leisure activities were assessed at baseline , and cognitive decline ( at least one point drop ) in MMSE scores between baseline and follow-up after one year . RESULTS Cognitive decline was observed in 30 % of the respondents . Controlling for age , gender , education and other risk factors , odds ratios ( ORs ) were significantly reduced in those with medium ( OR : 0.60 , 95 % CI : 0.45 - 0.79 ) and high activity levels ( OR : 0.62 , 95 % CI : 0.46 - 0.84 ) . A stronger association was shown for productive activity ( OR = 0.36 ) , than for physical ( OR = 0.78 ) and social activities ( OR = 0.85 ) . These associations showed statistically significant interactions with APOE genotype , being more pronounced in those with the APOE-epsilon 4 allele . CONCLUSION Increased leisure activity , especially productive activities more than physical or social activities , was associated with a lowered risk of cognitive decline . APOE-epsilon 4 genotype individuals appeared to be more vulnerable to the effects of low and high levels of leisure activities Purpose . To examine the relationship between vigorous physical activity and dementia risk . Design . Prospect i ve study design utilizing physical activity data from the Health and Retirement Study and cognitive outcome data from the Aging , Demographics , and Memory Study . Setting . Community-based . Subjects . Adults age 71 and over ( N = 808 ) with 3 to 7 years of physical activity information prior to dementia/no dementia diagnosis . Measures . Physical activity was measured by participation in vigorous activities such as aerobics , sports , running , bicycling , and heavy housework three or more times per week ( yes/no ) . Dementia diagnosis was based on an expert panel ( e.g. , neuropsychologists , neurologists , geropsychiatrists ) who performed and review ed a battery of neuropsychological tests . Analysis . Binary logistic regression models were used to account for demographic characteristics , genetic risk factors ( one or two apolipoprotein E ε4 alleles ) , health behaviors ( e.g. , smoking , drinking alcohol ) , health indicators ( body mass index ) , and health conditions ( e.g. , diabetes , heart disease ) in a sequential model-building process . Results . The relationship between vigorous physical activity and dementia risk remained robust across models . In the final model , older adults who were physically active were 21 % ( p ≤ .05 ) less likely than their counterparts to be diagnosed with dementia . Conclusion . Vigorous physical activity may reduce the risk for dementia independently of the factors examined here . This study 's findings are important given that few preventative strategies for dementia have been explored beyond hormonal therapy and anti-inflammatory drugs OBJECTIVE This study aim ed to clarify the longitudinal relationship between leisure activities and cognitive decline among Japanese community-dwelling older adults , using a 5-year prospect i ve cohort study design . METHODS A total of 567 men and women , aged 70years and over , participated in the study . The Mini-Mental State Examination was used in baseline and follow-up surveys to assess cognitive function . The change in cognitive function from baseline to follow-up was determined , and cognitive decline over 5years was used as the outcome variable . Leisure activities ( hobby , social activity , and physical activity ) were assessed at baseline and used as independent variables . Age , gender , number of years of education , presence of chronic diseases , instrumental activities of daily living , depressive symptoms , smoking , hearing deficits , and level of cognitive function at baseline were used as covariates . RESULTS Multivariate logistic regression analysis , adjusted for potential confounders , showed that non-participation in a hobby was significantly and independently associated with cognitive decline ( odds ratio : 1.87 , 95 % confidence interval : 1.16 - 3.02 , p<0.01 ) . There were no significant relationships between social activity , physical activity and cognitive decline . CONCLUSIONS Our study found a longitudinal inverse relationship between hobby participation and cognitive decline among elderly Japanese community-dwelling individuals , suggesting that engaging in a hobby in later life can contribute to preserving cognitive function BACKGROUND Physical activity may help maintain cognitive function and decrease dementia risk , but epidemiological findings remain controversial . The aim of our study was to investigate the association between leisure-time physical activity at midlife and the subsequent development of dementia and Alzheimer 's disease ( AD ) . METHODS Participants were r and omly selected from the survivors of a population -based cohort previously surveyed in 1972 , 1977 , 1982 , or 1987 . 1449 persons ( 72.5 % ) age 65 - 79 years participated in the re-examination in 1998 ( mean follow-up , 21 years ) . 117 persons had dementia and 76 had AD . Multiple logistic regression methods were used to analyse the association between leisure-time physical activity and dementia or AD . FINDINGS Leisure-time physical activity at midlife at least twice a week was associated with a reduced risk of dementia and AD ( odds ratio [ OR ] 0.48 [ 95 % CI 0.25 - 0.91 ] and 0.38 [ 0.17 - 0.85 ] , respectively ) , even after adjustments for age , sex , education , follow-up time , locomotor disorders , APOE genotype , vascular disorders , smoking , and alcohol drinking . The associations were more pronounced among the APOE epsilon4 carriers . INTERPRETATION Leisure-time physical activity at midlife is associated with a decreased risk of dementia and AD later in life . Regular physical activity may reduce the risk or delay the onset of dementia and AD , especially among genetically susceptible individuals The associations of diastolic blood pressure ( DBP ) with stroke and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally " hypertensive " or " normotensive " , a lower blood pressure should eventually confer a lower risk of vascular disease ` ` Vascular cognitive impairment ' ' refers to cognitive impairment caused or associated with vascular risk factors , and encompasses a cognitive spectrum ranging from mild cognitive impairment to dementia . We examined the association of leisure activity participation to risk of developing VCI in the Bronx aging study . Over 21 years , 71 of the 401 participants who were free of dementia or VCI at entry developed VCI ( 49 participants with VCI without dementia ) . We derived Cognitive and Physical Activity Scales based on frequency of leisure activity participation . A 1-point increase on the Cognitive , but not Physical Activity Scale , was associated with lower risk of VCI ( hazard ratio 0.931 , 95 % confidence interval [ CI ] 0.895 - 0.970 ) in Cox analysis . Participation in cognitive but not physical leisure activities is associated with lower risk of VCI with or without dementia . Prospect i ve studies and clinical trials are needed to define the causal role of cognitive leisure activities in influencing vascular risk for cognitive decline BACKGROUND Several studies have suggested that physical activity is positively associated with cognitive function in elderly persons . Evidence about this association has been limited by the cross-sectional design of most studies and by the frequent lack of adjustment for potential confounding variables . We determined whether physical activity is associated with cognitive decline in a prospect i ve study of older women . METHODS We studied 5925 predominantly white community-dwelling women ( aged > or = 65 years ) who were recruited at 4 clinical centers and were without baseline cognitive impairment or physical limitations . We measured cognitive performance using a modified Mini-Mental State Examination at baseline and 6 to 8 years later . Physical activity was measured by self-reported blocks ( 1 block approximately 160 m ) walked per week and by total kilocalories ( energy ) expended per week in recreation , blocks walked , and stairs climbed . Cognitive decline was defined as a 3-point decline or greater on repeated modified Mini-Mental State Examination . RESULTS Women with a greater physical activity level at baseline were less likely to experience cognitive decline during the 6 to 8 years of follow-up : cognitive decline occurred in 17 % , 18 % , 22 % , and 24 % of those in the highest , third , second , and lowest quartile of blocks walked per week ( P < .001 for trend ) . Almost identical results were obtained by quartile of total kilocalories expended per week . After adjustment for age , educational level , comorbid conditions , smoking status , estrogen use , and functional limitation , women in the highest quartile remained less likely than women in the lowest quartile to develop cognitive decline ( for blocks walked : odds ratio , 0.66 [ 95 % confidence interval , 0.54 - 0.82 ] ; for total kilocalories : odds ratio , 0.74 [ 95 % confidence interval , 0.60 - 0.90 ] ) . CONCLUSIONS Women with higher levels of baseline physical activity were less likely to develop cognitive decline . This association was not explained by differences in baseline function or health status . This finding supports the hypothesis that physical activity prevents cognitive decline in older community-dwelling women BACKGROUND Increased physical activity may have beneficial effects on cognitive outcomes ; a role of brain-derived neurotrophic factor ( BDNF ) has been suggested in animal models but not yet tested in humans . This study investigated modification by BDNF val66met polymorphism of the association between physical activity , incident dementia and other cognitive outcomes . METHODS Of 732 community elders , 107 had dementia at baseline , and 518 ( 83 % ) of the remainder were followed over 2.4 years . Cognitive impairment and decline were defined from Mini-Mental State Examination scores . Self-reported level of physical activity was recorded on a 4-point scale . BDNF val66met and apolipoprotein E genotypes were ascertained . Covariates included age , sex , education , depression , vascular risk factors , and instrumental activities of daily living . RESULTS Baseline lower physical activity was significantly associated with incident dementia as well as with baseline dementia and cognitive impairment and incident cognitive decline . BDNF val66met polymorphism itself was not associated with any cognitive outcome . However , the strength of association between lower activity and all cognitive outcomes increased incrementally with the number of met alleles , and was strongest in those with the met/met genotype . BDNF × activity interaction terms were stronger for prospect i ve outcomes ( incident dementia , cognitive decline ) compared to cross-sectional outcomes ( prevalent dementia , cognitive impairment no dementia ) . CONCLUSIONS This study supports a previously suggested neurobiological basis for the effects of physical activity on dementia involving the BDNF system since the met allele is recognised to be associated with lower activity-dependent secretion of BDNF OBJECTIVE To study the relationship between social and leisure activities and risk of subsequent dementia in older community residents . SETTING A cohort study of people aged 65 and older were followed-up 1 and 3 years after a baseline screening ( the Paquid study ) . PARTICIPANTS 2040 older subjects living at home in Gironde ( France ) were r and omly selected and followed for at least 3 years . DATA COLLECTION Information about social and leisure activities was collected during the baseline screening with an interview by a psychologist . Incident cases of dementia were detected during the first and third year follow-up screenings according to the DSM-III-R criteria . MAIN RESULTS All but one of the social and leisure activities noted were significantly associated with a lower risk of dementia . Only golden club participation was not significantly associated with this risk . After adjustment for age and cognitive performance measured by the Mini-Mental State Exam , visual memory test , and verbal fluency test , only traveling ( Relative risk ( RR ) = .48,95 % Confidence Interval ( 95 % CI ) = .24-.94 ) , odd jobs or knitting ( RR = .46,95 % CI = .26-.85 ) , and gardening ( RR = .53 , 95 % CI = .28-.99 ) remained significant . CONCLUSIONS Regular participation in social or leisure activities such as traveling , odd jobs , knitting , or gardening were associated with a lower risk of subsequent dementia BACKGROUND Leisure-time physical activity has been related with a reduced risk of dementia and Alzheimer 's disease ( AD ) . The effects of occupational and commuting physical activity ( physical activity at work and on the way to work ) on cognitive health are still unclear . This study aim ed to clarify the association between work-related physical activity and dementia/AD . METHODS Participants of the Cardiovascular Risk Factors , Aging , and Dementia ( CAIDE ) study were derived from r and om , population -based sample s previously studied in a survey carried out in 1972 , 1977 , 1982 , or 1987 . After an average follow-up of 21 years , 1449 individuals ( 73 % ) aged 65 to 79 years participated in the re-examination in 1998 . RESULTS Neither occupational [ Odds Ratio ( OR ) 1.45 ; 95 % Confidence Intervals ( CI ) 0.66 - 3.17 ] nor commuting physical activity ( OR 0.46 ; 95 % CI 0.10 - 2.17 ) were associated with the risk of dementia or AD after adjustments for age , sex , education , follow-up time , locomotor symptoms , main occupation during life , income at midlife , leisure-time physical activity , other subtype of work-related physical activity , ApoE genotype , vascular disorders and the smoking status . There were also no interactions between work-related physical activity and the ApoE epsilon4 genotype , leisure-time physical activity or sex . CONCLUSIONS In this study , work-related physical activity was not found to be sufficient to protect against dementia and AD later in life . The lack of effect might be partly due to a residual confounding . Nevertheless , physical activity during leisure-time may be beneficial even for people who are physically active at work or when commuting Growing evidence suggests that physical exercise may be protective against cognitive impairment and decline . A prospect i ve study of a representative rural community sample ( N = 1,146 ) aged 65 + years examined self-reported exercise habits and measured global cognitive function using the Mini-Mental State Examination ( MMSE ) . A composite variable “ exercise level ” combining type , frequency , and duration of exercise was created with three levels : “ high exercise ” ( aerobic exercise of ≥ 30 minute duration ≥ 3 times a week ) , “ low exercise ” ( all other exercise groups ) , and “ no exercise . ” Cognitive decline was defined as being in the 90th percentile of decline in this cohort , ie , declining by 3 or more MMSE points during the 2-year interval between two assessment s. In a multiple regression model , high exercise level at the baseline assessment was negatively associated with , ie , was protective against , being in the group with the greatest amount of decline at the follow-up assessment , after adjusting for likely confounders ( odds ratio = 0.39 ; 95 % confidence interval , 0.19 , 0.78 ) . When high exercise was redefined using frequency as ≥ 5 days per week as the threshold , as per the Surgeon General ’s guidelines , both low exercise and high exercise were negatively associated with cognitive decline . Exercise may have implication s for prevention of cognitive decline |
11,721 | 23,885,994 | Most fibers do not reduce appetite or energy intake in acute study design s. KEY TEACHING POINTS : • Dietary fiber intake is associated with lower body weight in epidemiologic studies . •
Most acute fiber treatments ( 61 % ) did not enhance satiety . •
Most acute fiber treatments ( 78 % ) did not reduce food intake . •
Neither fiber type nor fiber dose were related to satiety response or food intake | Epidemiologic studies have shown that fiber intake is associated with a lower body weight .
Satiety and energy intake are possible explanations for this effect .
The purpose of this study was to recommend fiber types and doses that are effective in reducing appetite and energy intake . | Resistant starch ( RS ) , a non-viscous dietary fibre , may have postpr and ial effects on appetite regulation and metabolism , although the exact effects and mechanisms are unknown . An acute r and omised , single-blind crossover study , aim ed to determine the effects of consumption of 48 g RS on appetite compared to energy and available carbohydrate-matched placebo . Twenty young healthy adult males consumed either 48 g RS or the placebo divided equally between two mixed meals on two separate occasions . Effects on appetite were assessed , using an ad libitum test meal and 24-h diet diaries for energy intake , and using visual analogue scales for subjective measures . Changes to postpr and ial glucose , insulin and C-peptide were also assessed . There was a significantly lower energy intake following the RS supplement compared to the placebo supplement at both the ad libitum test meal ( 5241 ( sem 313 ) v. 5606 ( sem 345 ) kJ , P = 0.033 ) and over the 24 h ( 12 603 ( sem 519 ) v. 13 949 ( sem 755 ) kJ , P = 0.044 ) . However , there was no associated effect on subjective appetite measures . Postpr and ial plasma glucose concentrations were not significantly different between supplements , but there was a significantly lower postpr and ial insulin response following the RS supplement ( P = 0.029 ) . The corresponding C-peptide concentrations were not significantly different , although the ratio of C-peptide to insulin was higher following the RS supplement compared to placebo ( P = 0.059 ) . These results suggest that consumption of 48 g RS , over a 24-h period , may be useful in the management of the metabolic syndrome and appetite . Further studies are required to determine the exact mechanisms Fibres which are soluble or insoluble in water have different physiochemical properties and may therefore be expected to exert different effects on post-ingestive satiety signals . This study compared the effects on short-term ( 24 h ) appetite of two equienergetic high ( 22 g ) fibre breakfasts , an equienergetic low fibre breakfast and a low energy , ' light ' breakfast . Psyllium gum ( the soluble fibre ) and wheat bran ( the insoluble fibre ) were incorporated into breakfast cereals and consumed at breakfast by sixteen healthy , normal weight males after an overnight fast using a repeated measures , counterbalanced design . Ad libitum energy intake was assessed at a test snack 1.5 h after breakfast , later in the day using food boxes and the following day using food diaries . Motivation to eat and gastrointestinal sensations were tracked for the next 24 h. Hunger ratings showed a trend towards the subjects being less hungry and they consumed significantly less energy at snack time after the high insoluble than after the high soluble fibre breakfast cereal . The soluble fibre breakfast produced a greater suppression of snack intake than the light breakfast , but smaller suppression than the other breakfasts . Interestingly there was a trend toward reduced hunger and voluntary energy consumption following the soluble fibre compared with the insoluble fibre much later in the day ( 9.5 - 13.5 h after breakfast ) although this was not significant . There was no significant effect of breakfast type on total day energy intake . The results suggest that different types of fibre modulate the timecourse of appetite control and may produce alterations in the experience of motivation and patterns of eating without necessarily effecting total energy intake Objective : To assess whether the addition of viscous fiber at an amount recommended by the US FDA to allow a ‘ low saturated fat , cholesterol , soluble fiber and coronary heart disease ’ , health cl aim label on a food package ( 1.7 g psyllium ) and /or fat ( 30 g sunflower oil and 3 g sodium propionate ) to a pasta meal would affect gastric emptying , postpr and ial glucose , insulin and GLP-1 concentrations . Design : Ten subjects participated in a two-by-two single blind r and omized crossover study . Four meals containing 50 g of available carbohydrate were consumed : pasta with or without psyllium enrichment served with a tomato sauce with ( 520 kcal per meal ) and without ( 240 kcal per meal ) fat . Blood sample s were taken for 240 min following the meal and all subjects consumed a buffet meal at the end of the study . Gastric empting was measured using the paracetamol absorption test . Blood was analysed for glucose , insulin , GLP-1 . Visual analog scales were used to record feelings of hunger , pleasantness and nausea . Results : The psyllium-enriched pasta had no significant effect on gastric emptying or the incremental area under the curve ( IAUC ) for GLP-1 , insulin or glucose compared with the control pasta . The addition of polyunsaturated fat and sodium propionate significantly increased the IAUC for GLP-1 ( P<0.001 ) , delaying gastric emptying ( P<0.002 ) , and decreasing glucose ( P<0.002 ) . Conclusions : A dose of 1.7 g psyllium did not evoke measurable effects on gastric emptying , postpr and ial GLP-1 , insulin or glucose metabolism . However the addition of 30 g of oil and 3 g of sodium propionate to the pasta did reduce gastric emptying , increase GLP-1 and reduce glucose and insulin concentrations . While this short-term study may have implication s in terms of reducing the risk of diabetes and improving coronary risk factor profiles the long term effects of these nutrients need to be studied . Sponsorship : This study was supported by Kellogg Company Dietary fibre consumption may help to control appetite and to reduce calorie intake . Underlying molecular mechanisms were not fully investigated . The aim of this study was to evaluate the effect of barley beta-glucans on short-term appetite and on satiety-related hormones in healthy subjects . Fourteen volunteers were selected and r and omly assigned to have isocaloric breakfasts including a 3 % beta-glucan-enriched bread ( betaGB ) or a control bread ( CB ) . Post-breakfast individual self-records of appetite ratings and measure of calorie intake at an ad libitum lunch as well as measure of blood glucose , insulin , ghrelin and PYY concentrations , were performed . betaGB determined a significant higher reduction of hunger and increase of fullness and satiety than CB . Accordingly , a 19 % reduction of energy intake at lunch subsequent to betaGB consumption compared to CB , was recorded . A 23 % lower AUC(60 - 180 ) of plasma ghrelin and a 16 % higher total AUC of PYY response after betaGB than CB consumption , independent from insulin response , was found . Glucose response was also blunted by betaGB vs CB . Barley beta-glucans were able to control appetite in the short term by modulating sensations and reducing energy intake . Data suggested for the first time that satiety effect of beta-glucans are mediated by ghrelin and PYY Although subjective appetite scores are widely used , studies on the reproducibility of this method are scarce . In the present study nine healthy , normal weight , young men recorded their subjective appetite sensations before and during 5 h after two different test meals A and B. The subjects tested each meal twice and in r and omized order . Visual analogue scale ( VAS ) scores , 10 cm in length , were used to assess hunger , satiety , fullness , prospect i ve food consumption and palatability of the meals . Plasma glucose and lactate concentrations were determined concomitantly . The repeatability was investigated for fasting values , delta-mean 5 h and mean 5 h values , delta-peak/nadir and peak/nadir values . Although the profiles of the postpr and ial responses were similar , the coefficients of repeatability ( CR = 2SD ) on the mean differences were large , ranging from 2.86 to 5.24 cm for fasting scores , 1.36 to 1.88 cm for mean scores , 2.98 to 5.42 cm for delta-mean scores , and 3.16 to 6.44 cm for peak and delta-peak scores . For palatability ratings the CR values varied more , ranging from 2.38 ( taste ) to 8.70 cm ( aftertaste ) . Part of the difference in satiety ratings could be explained by the differences in palatability ratings . However , the low reproducibility may also be caused by a conditioned satiation or hunger due to the subjects ' prior experience of the meals and therefore not just be a reflection of r and om noise . It is likely , however , that the variation in appetite ratings is due both to method ological day-to-day variation and to biological day-to-day variation in subjective appetite sensations BACKGROUND Cholecystokinin is associated with satiety . Fat stimulates cholecystokinin release , and fiber appears to prolong cholecystokinin elevation during the alimentary period . OBJECTIVE We tested whether adding fiber or fat to a low-fat , low-fiber meal increases cholecystokinin release and enhances subjective measures of satiety and whether the cholecystokinin response correlates with subjective measures of satiety . DESIGN Three isoenergetic breakfast meals were tested in a r and omized crossover design : low fiber , low fat ; high fiber , low fat ; and low fiber , high fat . Blood sample s were drawn from fasted subjects ( 7 men and 8 women ) before and at different time points after test meal consumption for 6 h. Plasma was analyzed for cholecystokinin , insulin , glucose , and triacylglycerols . Visual analogue scales were used to assess subjects ' hunger , desire to eat , fullness , and prospect i ve consumption . RESULTS In the women , the meals higher in fiber or in fat result ed in greater feelings of satiety and in significantly higher cholecystokinin responses than did the low-fat , low-fiber meal . In the men , the increase in cholecystokinin concentration did not differ between meals , but the 2 low-fat meals elicited a greater feeling of satiety than did the high-fat meal . The insulin response was significantly higher for the low-fiber , low-fat meal than for the other 2 meals , and the triacylglycerol response was greatest for the high-fat , low-fiber meal . CONCLUSION In women , the feeling of satiety caused by cholecystokinin release is enhanced by increasing either the fiber or fat content of a low-fat , low-fiber meal BACKGROUND Protein and fiber may be important determinants of satiety . Lupin kernel flour is a novel food ingredient that is rich in protein and fiber . OBJECTIVE The objective was to investigate the effects of lupin kernel flour-enriched bread ( LB ) on satiety and energy intake in humans . DESIGN Two r and omized controlled crossover trials were performed to compare the acute effects of LB with those of white bread ( WB ) . In study 1 , the subjects ( n = 16 ) completed 4 treatments 1 wk apart : WB breakfast ( as toast ) and WB lunch ( as s and wiches ) , WB breakfast and LB lunch , LB breakfast and WB lunch , and LB breakfast and LB lunch . Energy intake at all breakfast meals was matched ( 1655 kJ ) , and ad libitum energy intake at lunch , 3 h after breakfast , was measured . In study 2 , the subjects ( n = 17 ) completed 2 treatments 1 wk apart : WB breakfast and LB breakfast ( each 1655 kJ ) . Blood sample s were taken at baseline and at regular intervals for 3 h after breakfast . RESULTS In study 1 , the LB breakfast result ed in significantly higher self-reported satiety ( P < 0.001 ) and lower energy intake ( kJ ) at lunch ( -488 ; 95 % CI : -798 , -178 ) than did the WB breakfast . The LB lunch result ed in a significantly lower within-meal energy intake ( kJ ) at lunch ( -1028 ; 95 % CI : -1338 , -727 ) than did the WB lunch . In study 2 , compared with the WB breakfast , the LB breakfast significantly altered the 3-h postmeal plasma ghrelin response ( P = 0.04 ) and result ed in significantly lower mean 3-h plasma ghrelin concentrations ( P = 0.009 ) . CONCLUSION A novel food enriched in protein and fiber derived from lupin kernel flour significantly influences energy intake acutely BACKGROUND The pattern of substrate utilization with diets containing a high or a low proportion of unavailable and slowly digestible carbohydrates may constitute an important factor in the control , time course , and onset of hunger in humans . OBJECTIVE We tested the hypothesis that isoenergetic diets differing only in their content of unavailable carbohydrates would result in different time courses of total , endogenous , and exogenous carbohydrate oxidation rates . DESIGN Two diets with either a high ( H diet ) or a low ( L diet ) content of unavailable carbohydrates were fed to 14 healthy subjects studied during two 24-h periods in a metabolic chamber . Substrate utilization was assessed by whole-body indirect calorimetry . In a subgroup of 8 subjects , endogenous and exogenous carbohydrate oxidation were assessed by prelabeling the body glycogen stores with [(13)C]carbohydrate . Subjective feelings of hunger were estimated with use of visual analogue scales . RESULTS Total energy expenditure and substrate oxidation did not differ significantly between the 2 diets . However , there was a significant effect of diet ( P : = 0.03 ) on the carbohydrate oxidation pattern : the H diet elicited a lower and delayed rise of postpr and ial carbohydrate oxidation and was associated with lower hunger feelings than was the L diet . The differences in hunger scores between the 2 diets were significantly associated with the differences in the pattern of carbohydrate oxidation among diets ( r = -0.67 , P : = 0 . 006 ) . Exogenous and endogenous carbohydrate oxidation were not significantly influenced by diet . CONCLUSIONS The pattern of carbohydrate utilization is involved in the modulation of hunger feelings . The greater suppression of hunger after the H diet than after the L diet may be helpful , at least over the short term , in individuals attempting to better control their food intake BACKGROUND Diets with a low glycemic index ( GI ) have been shown to improve glucose tolerance in both healthy and diabetic subjects . Two potential mechanisms are discussed in relation to long-term metabolic effects : a decreased dem and for insulin in the postpr and ial phase and formation of short-chain fatty acids from fermentation of indigestible carbohydrates in the colon . OBJECTIVE The objective was to study the effect of the GI and the indigestible carbohydrate -- resistant starch ( RS ) and dietary fiber (DF)--content of cereal-based breakfasts on glucose tolerance at a second meal ( lunch ) in healthy subjects . DESIGN The effects of 7 test breakfasts with known GIs ( GI : 52 - 99 ) and RS + DF contents ( 2 - 36 g ) were evaluated . White-wheat bread was used as a reference breakfast ( high GI , low RS + DF content ) . Glucose and insulin responses after the second meal were measured in healthy subjects . In addition , the satiating capacity of 4 of the 7 test breakfasts was estimated before and during the second meal . RESULTS Two of the 4 low-GI breakfasts improved glucose tolerance at the second meal . Only these 2 breakfasts were capable of postponing the in-between-meal fasting state . There was no measurable effect of fermentable carbohydrates on glucose tolerance at the second meal . The highest satiety score was associated with the barley breakfast that had a low GI and a high RS + DF content . CONCLUSIONS Glucose tolerance can improve in a single day . Slow absorption and digestion of starch from the breakfast meal , but not the content of indigestible carbohydrates in the breakfast meal , improved glucose tolerance at the second meal ( lunch ) Dietary fiber ( DF ) and protein are essential constituents of a healthy diet and are well known for their high satiety impact . However , little is known about their influence on postpr and ial gastrointestinal ( GI ) peptide release . Our aim in this single-blind , r and omized , cross-over study was to investigate the effects of DF and /or protein enrichments on satiety-related metabolic and hormonal responses . Sixteen healthy , nonobese volunteers participated in the study and ingested 1 of 5 isoenergetic test meals in a r and omized order on separate days . The test meals were as follows : 1 ) low in protein ( 2.8 g ) and fiber ( 7.6 g ) ; 2 ) low in protein ( 2.6 g ) and high in soluble fiber ( psyllium , 23.0 g ) ; 3 ) high in protein ( soy , 19.7 g ) and low in fiber ( 6.2 g ) ; 4 ) high in protein ( 18.4 g ) and fiber ( 23.0 g ) ; and 5 ) white wheat bread . Serum insulin and plasma glucose , ghrelin , glucagon-like peptide 1 ( GLP-1 ) , and peptide YY ( PYY ) concentrations were determined for 2 h following the meals . In addition , hunger and satiety ratings were collected . Postpr and ial glucose , insulin , ghrelin , GLP-1 , and PYY responses all differed among the meals ( P < or= 0.05 ) . Fiber-enriched meals decreased glucose , insulin , ghrelin , and PYY responses ; in addition , PYY secretion was prolonged compared with the other meals . The postpr and ial GLP-1 concentration was significantly suppressed after a fiber- and protein-rich meal , in contrast to the initial increases following the other meals . However , postpr and ial ratings of appetite were mostly similar after the test meals . In conclusion , solid meals enriched with psyllium fiber strongly modified postpr and ial signals arising from the GI tract Some studies suggest high-fiber foods are more satiating than foods with little or no fiber . However , we hypothesized that certain types of dietary fiber may enhance satiety more than others . Healthy men and women ( N = 20 ) participated in this acute , r and omized double-blind , crossover study comparing the effects of 4 fibers and a low-fiber ( LF ) treatment on satiety . On 5 separate visits , fasting subjects consumed either a LF muffin ( 1.6 g fiber ) or 1 of 4 high-fiber muffins ( 8.0 - 9.6 g fiber ) for breakfast . The subjects used 4 questions on 100 mm visual analogue scales to rate satiety at baseline and at regular intervals for 180 minutes after muffin consumption . Responses were analyzed as area under the curve and significant differences from baseline . Satiety differed among treatments . Resistant starch and corn bran had the most impact on satiety , whereas polydextrose had little effect and behaved like the LF treatment . Results from this study indicate that not all fibers influence satiety equally Weight gain and risk of type 2 diabetes are inversely associated with a high intake of insoluble cereal fibres . Because nutrient-induced changes of ' satiety hormones ' from the gut may play a role in this process , we evaluated the effects of purified insoluble fibres on postpr and ial responses of plasma peptide YY ( PYY ) , serum ghrelin and satiety as secondary outcome measures of a study investigating effects of cereal fibres on parameters of glucose metabolism . Fourteen healthy women were studied on six occasions in a r and omized , single-blind , controlled crossover design . After 24 h run-in periods and 10 h overnight fasts , subjects ingested isoenergetic and macronutrient matched portions of control white bread or fibre-enriched bread ( wheat-fibre or oat-fibre ) at 08.15 hours . Gut hormones and hunger scores were measured for 300 min . Basal PYY and ghrelin concentrations were not different between the test meals ( P>0.15 ) . Postpr and ial responses of PYY and ghrelin were blunted after the intake of wheat-fibre ( total area under the curve ( AUC ) PYY , 177.9 ( SEM 8.1 ) ( pmol/l ) min ; P=0.016 ; ghrelin 51.0 ( SEM 2.5 ) ( pmol/l ) min ; P=0.003 ) , but not after oat-fibre ( PYY 226.7 ( SEM 25.7 ) ( pmol/l ) min ; P>0.15 ; ghrelin 46.2 ( SEM 1.6 ) ( pmol/l ) min ; P=0.127 ) , compared to control ( PYY 247.5 ( SEM 25.6 ) ( pmol/l ) min ; ghrelin 42.5 ( SEM 1.3 ) ( pmol/l ) min ) . Postpr and ial hunger scores were unaffected by the different test meals ( P>0.15 ) . Thus , oat- and wheat-fibre consumption result in different postpr and ial responses of PYY and ghrelin , but interestingly do not differ in satiety effects Background Several studies report that dietary fibre from different sources promotes the feeling of satiety and suppresses hunger . However , results for cereal fibre from rye are essentially lacking . The aim of the present study was to investigate subjective appetite during 8 h after intake of iso-caloric rye bread breakfasts varying in rye dietary fibre composition and content . Methods The study was divided into two parts . The first part ( n = 16 ) compared the satiating effect of iso-caloric bread breakfasts including different milling fractions of rye ( bran , intermediate fraction ( B4 ) and sifted flour ) . The second part ( n = 16 ) investigated the dose-response effect of rye bran and intermediate rye fraction , each providing 5 or 8 g of dietary fibre per iso-caloric bread breakfast . Both study parts used a wheat bread breakfast as reference and a r and omised , within-subject comparison design . Appetite ( hunger , satiety and desire to eat ) was rated regularly from just before breakfast at 08:00 until 16:00 . Amount , type and timing of food and drink intake were st and ardised during the study period . Results The Milling fractions study showed that each of the rye breakfasts result ed in a suppressed appetite during the time period before lunch ( 08:30 - 12:00 ) compared with the wheat reference bread breakfast . At a comparison between the rye bread breakfasts the one with rye bran induced the strongest effect on satiety . In the afternoon the effect from all three rye bread breakfasts could still be seen as a decreased hunger and desire to eat compared to the wheat reference bread breakfast . In the Dose-response study both levels of rye bran and the lower level of intermediate rye fraction result ed in an increased satiety before lunch compared with the wheat reference bread breakfast . Neither the variation in composition between the milling fractions nor the different doses result ed in significant differences in any of the appetite ratings when compared with one another . Conclusion The results show that rye bread can be used to decrease hunger feelings both before and after lunch when included in a breakfast meal . Rye bran induces a stronger effect on satiety than the other two rye fractions used when served in iso-caloric portions . Trial Registration Trial registration number Background Dietary fibre food intake is related to a reduced risk of developing diabetes mellitus . However , the mechanism of this effect is still not clear . The aim of this study was to evaluate the effect of commercial fibre cereals on the rate of gastric emptying , postpr and ial glucose response and satiety in healthy subjects . Methods Gastric emptying rate ( GER ) was measured by st and ardized real time ultrasonography . Twelve healthy subjects were assessed using a r and omized crossover blinded trial . The subjects were examined after an 8 hour fast and after assessment of normal fasting blood glucose level . Satiety scores were estimated and blood glucose measurements were taken before and at 0 , 20 , 30 , 40 , 60 , 80 , 100 and 120 min after the end of the meal . GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 min after ingestion of sour milk with corn flakes ( GER1 ) , cereal bran flakes ( GER2 ) or wholemeal oat flakes ( GER3 ) . Results The median value was , respectively , 42 % for GER1 , 33 % for GER2 and 51 % for GER3 . The difference between the GER after ingestion of bran flakes compared to wholemeal oat flakes was statistically significant ( p = 0.023 ) . The postpr and ial delta blood glucose level was statistically significantly lower at 40 min ( p = 0.045 ) and 120 min ( p = 0.023 ) after the cereal bran flakes meal . There was no statistical significance between the areas under the curve ( AUCs ) of the cereals as far as blood glucose and satiety were concerned . Conclusion The result of this study demonstrates that the intake of either bran flakes or wholemeal oat flakes has no effect on the total postpr and ial blood glucose response or satiety when compared to corn flakes . However , the study does show that the intake of cereal bran flakes slows the GER when compared to oat flakes and corn flakes , probably due to a higher fibre content . Since these products do not differ in terms of glucose response and satiety on healthy subjects , they should be considered equivalent in this respect . Trial registration IS RCT Overweight and obesity is one of the risk factors for developing CVD . At present , very little is known about the acute effects of dietary fibre on lipids , glucose and insulin , resting energy expenditure and diet-induced thermogenesis in overweight and obese individuals . This study examined the postpr and ial metabolic effects of dietary fibre in overweight and obese men . Ten overweight and obese men consumed a mixed meal accompanied by either a high-fibre or low-fibre supplement on two separate visits , in a r and om order , 1 week apart . Two isoenergetic breakfast meals with similar composition were consumed by ten overweight/obese men . The meals contained either a low ( 3 g ) or high ( 15 g ) amount of fibre , low-fibre meal ( LFM ) and high-fibre meal ( HFM ) respectively . Analysis was carried out using paired t test and ANOVA . Serum TAG incremental area under the curve during 6 h of the postpr and ial period was significantly lower after the consumption of HFM compared with LFM . At the first hour of the postpr and ial period , plasma apo B48 concentration after consumption of HFM was significantly lower compared with LFM . The resting energy expenditure and diet-induced thermogenesis after both meals was similar during 6 h of the postpr and ial period . Collectively , these findings suggest that a single acute dose of dietary fibre in the form of psyllium supplement can decrease arterial exposure to TAG and modify chylomicron responses in the postpr and ial period A novel substance called liquid fibre ( LF ) has been developed which gels in the stomach and dramatically delays gastric emptying . The prolonged stomach distension LF causes would be expected to reduce food intake . The present study tested whether LF affected psychological factors connected with eating behaviour and short-term food intake . Paired studies were carried out on seventeen healthy but overweight volunteers ( ten male , seven female ) with body mass indices of 24 - 34 kg/m2 who were non-restricted eaters . On one occasion ( r and omized ) they took drinks of LF ( 300 ml each ) at 09.05 , 11.55 and 18.00 hours , and on the other they took placebo drinks . Subjective feelings were assessed by visual analogue scales . The amount of food consumed at an appetizing pre-selected meal presented at 12.15 hours was measured covertly . Food diaries were kept until 16.00 hours on the following day . The visual analogue scales indicated that LF reduced hunger and the amount of food desired , and increased fullness , all of which would be expected to cause a reduction in food intake . However , there were no differences in the amount or type of food eaten at the appetizing test-meal ( 6073 v. 5824 kJ , P = 0.41 ) . Food eaten later in the day was significantly delayed by LF ( 7.0 v. 5.9 h , P = 0.030 ) , and the amount tended to be reduced ( 4328 v. 5439 kJ , P = 0.088 ) . The energy consumed on the following day also tended to be lower after LF ( 3802 v. 4737 kJ , P = 0.130 ) . This suggests that gastric distension is a relatively unimportant influence on eating behaviour when non-restricted eaters are presented with an appetizing meal and that intestinal factors seem more important for prolonging satiety and reducing subsequent food intake BACKGROUND In cohort studies , insoluble fiber has been associated with a reduced risk of obesity and diabetes ; however , compared with soluble fiber , its role in the regulation of short-term food intake ( FI ) and satiety has received little attention . OBJECTIVE Our aim was to compare the effects of a high-insoluble-fiber ( HF ) cereal with a low-fiber ( LF ) cereal on FI , subjective appetite ( SA ) , and plasma glucose ( PG ) in healthy individuals . DESIGN Males and females ( n = 32 ) were r and omly assigned to consume 60 g of either HF ( 26 g insoluble fiber , 120 kcal ) or LF ( 1 g fiber , 217 kcal ) breakfast cereal . Pre- and postlunch SA and PG were measured regularly for 4 h , and ad libitum FI was measured at 3 h. RESULTS The prelunch SA area under the curve did not differ between the 2 cereals , but when expressed as change in appetite per kilocalorie of cereal , HF suppressed SA more than did LF ( -17.6 + /- 1.8 compared with -10.0 + /- 1.1 mm . min . kcal(-)(1 ) , respectively ; P < 0.01 ) . Lunchtime FI did not differ between cereals , but cumulative energy intake ( cereal + lunch ) was lower after the HF than after the LF cereal ( 1330 + /- 57 compared with 1422 + /- 66 kcal , respectively ; P = 0.01 ) . The prelunch PG area under the curve ( P < 0.0001 ) and the immediate postlunch PG ( P = 0.01 ) were lower after HF cereal consumption . CONCLUSIONS An HF breakfast cereal contributes to a cumulative reduction in breakfast and lunch energy intake , possibly due to its high satiety value per kilocalorie . A short-term benefit of the HF cereal , compared with LF cereal , was lower PG concentration before and immediately after lunch The present study was conducted to assess whether glucagon-like peptide-1 ( GLP-1 ) release and appetite after a breakfast with or without an additional galactose/guar gum stimulation is different in normal-weight compared with overweight/obese subjects . Twenty-eight overweight/obese ( BMI 30.3 ( sd 2.7 ) kg/m2 ; age 44.3 ( sd 9.7 ) years ) and thirty normal-weight subjects ( BMI 22.8 ( sd 1.4 ) , age 31.5 ( sd12.8 ) years ) participated in a crossover study . Fasting and postpr and ial plasma GLP-1 , insulin , glucose and free fatty acid concentrations were measured in response to either a galactose ( 50 g)/guar gum ( 2.5 g ) load ( 836 kJ ) and a st and ard breakfast ( 1.9 MJ ; GG ) , or water ( 250 ml ) and the st and ard breakfast ( W ) every 30 min relative to the ingestion for 120 min . Appetite was assessed using 100 mm visual analogue scales . GLP-1 concentrations were significantly increased after GG at 30 and 60 min compared with W in both groups . Plasma GLP-1 concentrations in the W condition were higher in normal-weight than overweight/obese subjects ( P=0.03 ) . No difference was observed in the GG condition between groups . Satiety was increased in normal-weight compared with overweight/obese subjects in the GG condition at 30 ( P=0.02 ) and 60 ( P=0.04 ) min . We conclude that after a st and ard breakfast with water , GLP-1 release was lower in the overweight/obese than the normal-weight subjects . However , postpr and ial GLP-1 release in overweight/obese subjects was no different from that of normal-weight subjects when galactose/guar gum was added to the breakfast . The latter was not mirrored by subjective feelings of satiety . Disturbed perception of the physiological feedback of a satiety hormone rather than disturbed feedback itself might contribute to obesity Background Rye products have previously been shown to induce comparatively low post-pr and ial insulin responses ; irrespectively of their glycaemic indices ( GI ) . However , the mechanism behind this lowered insulin dem and remains unknown . An improved insulin economy might contribute to the benefits seen in epidemiological studies with whole grain diets on metabolic risk factors and weight regulation . The objective of this study was to explore the mechanism for a reduced post-pr and ial insulin dem and with rye products . Methods 12 healthy subjects were given flour based rye products made from endosperm , whole grain or bran , produced with different methods ( baking , simulated sour-dough baking and boiling ) as breakfasts in r and om order in a cross-over design . White wheat bread ( WWB ) was used as a reference . Blood glucose , serum insulin , plasma ghrelin and subjective satiety were measured during 180 minutes . To evaluate the course of post-meal glycaemia , a measure of the glycaemic profile ( GP ) was introduced defined as the duration for the incremental post-pr and ial blood glucose response divided with the blood glucose incremental peak ( min/mM ) . Results The study shows that whole grain rye breads and endosperm rye products induced significantly ( p < 0.05 ) lower insulinaemic indices ( II 's ) than WWB . Rye bran bread ( RBB ) produced significantly higher II compared with all the other rye products . Furthermore , the acute insulin response showed better correlations with the GP than with the GI of the products . The endosperm rye bread and the whole grain rye bread with lactic acid induced a significantly higher GP than RBB , WWB , white wheat- and whole grain rye porridge , respectively . A low insulin incremental peak was associated with less severe late post-pr and ial hypoglycaemia ( r = 0.38 , p < 0.001 ) , and hypoglycaemia was negatively correlated to subjective satiety at 180 min ( r = -0.28 , p < 0.05 ) . A low insulin incremental peak was also associated with a milder recovery of plasma ghrelin in the late post-pr and ial phase ( 180 min , r = 0.34 , p < 0.01 ) . Conclusion Our study shows that endosperm and wholegrain rye products induce low acute insulinaemic responses and improved glycaemic profiles . The results also suggest that the rye products possess beneficial appetite regulating properties . Further studies are needed to identify the unknown property or bioactive component(s ) responsible for these beneficial metabolic features of rye Objective : To examine the effect of barley flour ( barley cultivar , Hordeum Vulgare var Himalaya 292 ) incorporated into breakfast and lunch compared with otherwise identical meals containing white wheat flour on the thermic effect of food ( TEF ) , subsequent food intake and metabolic parameters . Design : R and omized single blinded crossover study . Setting : Outpatient setting .Subjects and methods : Fourteen healthy women consumed a test breakfast at 0700 h. Energy expenditure , respiratory quotient ( RQ ) , appetite ratings using a visual analogue scale ( VAS ) , insulin and glucose levels were measured before and after a test lunch at 1330 h. Food intake was recorded for the remainder of the day . Results : The TEF was 5 % for both test lunches and meal type did not affect any variable measured by the VAS . There was an increase in post-pr and ial RQ above baseline ( 0.80 ) independent of treatment ( 0.88 and 0.90 for barley and wheat-containg meals , respectively , P<0.001 ) . Mean area under the glycaemic response curve ( AUC ) for wheat-containing meals was 4.68±1.67 mmol/l/h , 22 % higher than for the barley-containing meals ( 3.67±1.91 mmol/l/h ) , P=0.05 . AUC of insulin in response to wheat-containing meals ( 78.1±35.3 mIU/l/h ) was 32 % greater than barley-containing meals ( 52.8±24.7 mU/l/h ) , P<0.02 . Ad libitum food intake over the next 10 h was reduced by 23 % ( 9.6 vs 11.0 MJ , P<0.05 ) after the wheat-containing meals compared to the barley-containing glycaemic index meals . Conclusion : Inclusion of an ingredient containing increased soluble fibre and amylose did not reduce spontaneous food intake but rather was associated with higher subsequent energy intakes despite its reduced glycaemic and insulinemic effects . Sponsorship : CSIRO , Human Nutrition , Adelaide , Australia Objective : To assess whether psyllium , a soluble dietary fibre , could , at an acceptable dose ( 7.4 g ) , delay gastric emptying of a low-calorie meal , and reduce hunger feeling and energy intake , without requiring intimate mixing with the meal . Design : A double blind r and omized cross over study with 14 normal volunteers , to evaluate the effect of this dose of psyllium on postpr and ial serum glucose , triglycerides and insulin levels , and on gastric fullness , hunger feeling and food intake . Methods : Gastric emptying was measured using a st and ard double-radiolabeled 450 kcal meal and feelings by visual analogic scales . The postpr and ial serum glucose , triglycerides and insulin levels were also determined . Results : No delay in the gastric emptying of the solid and liquid phases of the meal was observed with psyllium . After the meal , hunger feelings and energy intake were significantly lower during the psyllium session than during the placebo session ( 13 % and 17 % lower respectively ; P<0.05 ) . Postpr and ial increase in serum glucose , triglycerides and insulin levels was less with psyllium than with placebo ( P<0.05 ) . Conclusions : Psyllium reduces hunger feelings and energy intake in normal volunteers at reasonable dose and without requiring mixing with the meal . It does not act by slowing down the gastric emptying of hydrosoluble nutrients , but by increase in the time allowed for intestinal absorption , as suggested by the flattening of the postpr and ial serum glucose , insulin and triglycerides curves . Sponsorship : University , Faculté de Médecine X. Bichat , 75018 Paris , France Fourteen subjects consumed four realistic isoenergetic ( 2035 kJ ) breakfasts , varying in macronutrient content ( two fat-rich , two carbohydrate-rich ( low- and high-fibre ) ) , in r and om order on separate mornings . After breakfast , subjects left the laboratory and completed appetite and alertness ratings at specific times and recorded all subsequent fluid and food intake for the rest of the day . The high-fibre , carbohydrate-rich breakfast was the least palatable but most filling meal and was associated with less food intake during the morning and at lunch . Hunger returned at a slower rate after this meal than after the low-fibre , carbohydrate-rich meal . Both fat-rich breakfasts were more palatable but less satiating than the carbohydrate-rich meals and were followed by greater food intake during the morning , which may be a compensatory response to ingest a sufficient amount of food and /or carbohydrate to match the level of fullness produced by the subjects ' habitual breakfasts . By the end of the day , the average total energy intake was significantly greater after the fat-rich EB meal than after the high-fibre , carbohydrate-rich meal ( P < 0.05 ) . Total day fat intakes were also significantly greater when the high-fat breakfasts were eaten . For every individual test , alertness ratings increased immediately after breakfast was consumed . On average , the high-fibre carbohydrate-rich meal was associated with the highest post-breakfast alertness ratings and with the greatest cumulative amount of alertness during the period between breakfast and lunch ( AUC ) . Alertness AUC values up until lunch correlated positively with fullness AUC values ( r = 0.36 , P < 0.01 , n = 56 ) . The results confirm the relatively weak satiating power of fat-rich meals observed in controlled laboratory-based studies and indicate that a high-fibre , carbohydrate-rich breakfast may assist weight control efforts by maintaining fullness . Further research is required to determine whether satiety directly enhances alertness and whether low-GI carbohydrate-rich meals enhance alertness to a greater degree than high-GI meals The effects of vegetables in mixed meals on satiety were evaluated by varying the dose ( portions 150 and 250 g containing 4.3 and 7.2 g of dietary fibre , respectively ) and structure ( cut and minced ) of microwaved spinach . A control meal without spinach and the test meals with spinach were balanced regarding energy ( 2000 kJ ) and digestible carbohydrates ( 59 g , 51 E% ) and with protein and fat as far as possible similar . The meals were served in the morning , after an overnight fast , to ten healthy male volunteers . Satiety was registered and blood glucose as well as plasma insulin and C-peptide were analysed at regular intervals until 3.5 h postpr and ially . The largest spinach portions augmented satiety and reduced the postpr and ial glucose response . The total satiety scores seemed to be correlated positively to both the dietary fibre and the water content in the vegetable . Differences in structure had no influence on satiety scores Objective : To compare starch digestibility from a maize-soy blended food with and without extrusion cooking . Design : Resistant starch , soluble and insoluble dietary fibres were measured in vitro before and after extrusion . Starch digestibility was assessed in 8 volunteers who took , in a r and omised order , a test meal with either 100 g extruded ( EF ) or non-extruded ( NEF ) blended flour cooked 15 min at 80 ° C in 500 ml of water . Setting : Research ward for healthy volunteers . Subjects : Healthy volunteers . Main outcome measures : Starch digestibility was measured by 13C enrichment of breath sample s for 8 h. Breath H2 concentration was measured during 12 h to assess bacterial fermentation in the colon . Volunteers reported hunger on a visual scale every hour for 8 h. Results : In vitro resistant starch , soluble and insoluble dietary fibers were higher in NEF than in EF ( 5.4 vs 1.1 , 0.7 vs 0.5 , and 13.3 vs 10.4 % dw respectively ) . In vivo , the area under curve ( AUC ) for 13CO2 excretion during 8 h was not significantly different for NEF and EF ( 10.3±1.3 vs 9.1±0.5 mmol/min , respectively ) . AUC for H2 excretion during 12 h was significantly higher for EF than for NEF ( 26.9±5.6 vs 14.1±4.7 mL , P<0.05 ) . AUC for satiety was marginally higher with EF ( 12.6±1.6 ) than for NEF ( 10.0±2.1 ) ( P=0.06 ) . Conclusions : Extrusion cooking does not seem to substantially improve blended foods digestibility . Extrusion of high fibre flours may promote carbohydrate fermentation in the colon and increase satiety . Sponsorship : Supported by a grant from Nutriset ( Malaunay , France ) and ANVAR ( Agence Nationale de la Valorisation de la Recherche , Contract No A9703021P ) Research investigating fiber intake and changes in weight over time has not controlled for important covariates , especially physical activity . Moreover , studies have rarely examined the influence of fiber on changes in body fat , only weight . Hence , this study was conducted to determine whether changes in fiber intake ( total , soluble , and insoluble ) influence risk of gaining weight and body fat over time . Another objective was to examine the influence of age , energy intake , activity , season , and other potential confounders . A prospect i ve cohort design was used and 252 women completed baseline and follow-up assessment s 20 mo apart . Diet was measured using 7-d weighed food records . Fiber was expressed per 1000 kcal ( 4187 kJ ) . Body fat was assessed via the Bod Pod and physical activity was measured using accelerometers over 7 consecutive days . Across the 20 mo , almost 50 % of the women gained weight and fat . For each 1 g increase in total fiber consumed , weight decreased by 0.25 kg ( P = 0.0061 ) and fat decreased by 0.25 percentage point ( P = 0.0052 ) . Controlling for potential confounders did not affect the relationships , except changes in energy intake , which weakened the associations by 24 - 32 % . Soluble and insoluble fibers were borderline predictors of changes in weight and fat . In conclusion , increasing dietary fiber significantly reduces the risk of gaining weight and fat in women , independent of several potential confounders , including physical activity , dietary fat intake , and others . Fiber 's influence seems to occur primarily through reducing energy intake over time Objective : Products enriched with oat β-glucan have been shown to reduce postpr and ial glucose and insulinemic responses . The aim of this study was to evaluate the effect of an extruded muesli product based on oat β-glucan on the rate of gastric emptying , postpr and ial blood glucose and satiety in healthy subjects . Methods : Gastric emptying rate ( GER ) was measured by st and ardized real-time ultrasonography . Twelve healthy subjects were assessed using a r and omized crossover double blind trial . The meals were administered after 8 hours ’ fasting after measuring the subject 's normal fasting blood glucose level . Blood glucose measurements were made before , 30 and 60 min after the end of the meal . Satiety scores were estimated 15 and 90 min after the end of the meal . The GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 minutes after ingestion of vanilla yoghurt with muesli containing 4 g oat β-glucan ( GER1 ) or vanilla yoghurt with muesli containing cornflakes ( GER2 ) . Results : The median values were 60 % for GER1 and 44 % for GER2 . The effect of 4 g oat β-glucan on the rate of gastric emptying was not statistically significant compared with corn flakes . Muesli with 4 g oat β-glucan lowered the postpr and ial glucose response significantly compared to the cornflakes meal ( p = 0.045 ) . The effect of oat β-glucan on satiety was not statistically significantly . Conclusions : The results of this study suggest that intake of muesli with 4 g oat β-glucan does not affect the gastric emptying rate or satiety but lowers the postpr and ial blood glucose response , indicating that the GER does not regulate the blood glucose level BACKGROUND Dietary fiber may play a role in obesity prevention . Until now , the role that fiber from different sources plays in weight change had rarely been studied . OBJECTIVE Our aim was to investigate the association of total dietary fiber , cereal fiber , and fruit and vegetable fiber with changes in weight and waist circumference . DESIGN We conducted a prospect i ve cohort study with 89,432 European participants , aged 20 - 78 y , who were free of cancer , cardiovascular disease , and diabetes at baseline and who were followed for an average of 6.5 y. Dietary information was collected by using vali date d country-specific food-frequency question naires . Multiple linear regression analysis was performed in each center studied , and estimates were combined by using r and om-effects meta-analyses . Adjustments were made for follow-up duration , other dietary variables , and baseline anthropometric , demographic , and lifestyle factors . RESULTS Total fiber was inversely associated with subsequent weight and waist circumference change . For a 10-g/d higher total fiber intake , the pooled estimate was -39 g/y ( 95 % CI : -71 , -7 g/y ) for weight change and -0.08 cm/y ( 95 % CI : -0.11 , -0.05 cm/y ) for waist circumference change . A 10-g/d higher fiber intake from cereals was associated with -77 g/y ( 95 % CI : -127 , -26 g/y ) weight change and -0.10 cm/y ( 95 % CI : -0.18 , -0.02 cm/y ) waist circumference change . Fruit and vegetable fiber was not associated with weight change but had a similar association with waist circumference change when compared with intake of total dietary fiber and cereal fiber . CONCLUSION Our finding may support a beneficial role of higher intake of dietary fiber , especially cereal fiber , in prevention of body-weight and waist circumference gain Stress may induce eating in the absence of hunger , possibly involving changes in food reward , i.e. ' liking ' and ' wanting ' . The objective of this study was to assess the effects of acute psychological stress on food reward , and on energy intake , in visceral overweight ( VO ) vs. normal weight ( NW ) subjects . Subjects ( 27 NW , age=26 ± 9 yrs , BMI = 22 ± 2 kg/m² ; 15 VO , age=36 ± 12 yrs , BMI = 28 ± 1 kg/m² ) came to the university twice , fasted , for either a rest or stress condition ( r and omized cross-over design ) . Per test-session ' liking ' and ' wanting ' for 72 items divided in six categories ( bread , filling , drinks , dessert , snacks , and stationery ( control ) ) were measured twice , each time followed by a wanted meal . Appetite profile ( visual analogue scales , VAS ) , heart rate , mood state and level of anxiety ( POMS/STAI question naires ) were measured . High hunger and low satiety ( 64 ± 19 , 22 ± 20 mmVAS ) confirmed the fasted state . Elevated heart rate , anger and confusion scores ( p ≤ 0.03 ) confirmed the stress vs. rest condition . Consumption of the first meal decreased hunger , increased satiety , and decreased ranking of ' liking ' of bread vs. increased ranking of ' liking ' of the control ( p<0.001 ) . ' Wanting ' for dessert and snacks , energy intake , carbohydrate and fat intake for the second meal stress vs. rest relatively increased in VO vs. decreased in NW ( p<0.02 ) . During stress vs. rest VO showed a 6 ± 9 % increase in percentage of daily energy requirements consumed over the two meals ( p=0.01 ) . To conclude , visceral overweight subjects showed stress-induced food intake in the absence of hunger , result ing in an increased energy intake Eighteen healthy obese subjects participated in a single blind , r and omized , crossover study of three test breakfasts , containing 0 g ( control ) , 4 g or 8 g of isolated fenugreek fiber . Subjects recorded ratings of hunger , satiety , fullness and prospect i ve food consumption using visual analog scales ( VAS ) every 30 min for 3.5 h. Postpr and ial blood glucose and insulin responses were measured . Energy intake from an ad libitum lunch buffet and for the remainder of the day was assessed . The 8 g dose of fenugreek fiber significantly increased mean ratings of satiety and fullness , and reduced ratings of hunger and prospect i ve food consumption ( P < 0.05 ) . Palatability was significantly reduced with increasing doses of fenugreek fiber ( P < 0.05 ) . No differences were observed for area under the curve ( AUC ) for blood glucose among treatments . An increase in insulin AUC was found with 8 g fenugreek fiber . Energy intake at an ad libitum lunch buffet was significantly lower for 8 g than 4 g fenugreek fiber , but not significantly different from control , although there was a trend towards a lower intake ( p = 0.11 ) . No differences were observed for energy intake for the remainder of the day . Fenugreek fiber ( 8 g ) significantly increased satiety and reduced energy intake at lunch , suggesting it may have short-term beneficial effects in obese subjects . Satiety results were not related to postpr and ial blood glucose OBJECTIVE : To examine reproducibility and validity of visual analogue scales ( VAS ) for measurement of appetite sensations , with and without a diet st and ardization prior to the test days . DESIGN : On two different test days the subjects recorded their appetite sensations before breakfast and every 30 min during the 4.5 h postpr and ial period under exactly the same conditions . SUBJECTS : 55 healthy men ( age 25.6±0.6 y , BMI 22.6±0.3 kg/m2 ) . MEASUREMENTS : VAS were used to record hunger , satiety , fullness , prospect i ve food consumption , desire to eat something fatty , salty , sweet or savoury , and palatability of the meals . Subsequently an ad libitum lunch was served and energy intake was recorded . Reproducibility was assessed by the coefficient of repeatability ( CR ) of fasting , mean 4.5 h and peak/nadir values . RESULTS : CRs ( range 20–61 mm ) were larger for fasting and peak/nadir values compared with mean 4.5 h values . No parameter seemed to be improved by diet st and ardization . Using a paired design and a study power of 0.8 , a difference of 10 mm on fasting and 5 mm on mean 4.5 h ratings can be detected with 18 subjects . When using desires to eat specific types of food or an unpaired design , more subjects are needed due to considerable variation . The best correlations of validity were found between 4.5 h mean VAS of the appetite parameters and subsequent energy intake ( r=±0.50−0.53 , P<0.001 ) . CONCLUSION : VAS scores are reliable for appetite research and do not seem to be influenced by prior diet st and ardization . However , consideration should be given to the specific parameters being measured , their sensitivity and study power Previous research indicates that vegetables yield relatively high satiety scores , and that fibre content and structure may both contribute to these effects . This study evaluated the effects of the fibre content and physical structure ( gross anatomy and cell structure ) of carrots on postpr and ial satiety and subsequent food intakes when consumed as part of a mixed meal . Using a r and omised , repeated- measures , within-subject cross-over design , young women consumed a st and ardised breakfast and test lunches on three occasions , 4 weeks apart . The test lunches ( 3329 kJ ) comprised boiled rice ( 200 g ) with sweet and sour sauce ( 200 g ) that included chicken ( 200 g ) and carrots ( 200 g ) in three conditions : whole carrots ( fibre and structure ; n 34 ) , blended carrots ( fibre but no structure ; n 34 ) or carrot nutrients ( no fibre or structure ; n 32 ) . The carrot nutrients had the same energy , major nutrients and portion weight as the other two conditions . Post-lunch satiety was assessed by visual analogue scales . Intakes were covertly weighed at a meal eaten ad libitum ( 3 h later ) , and for the remainder of the day using food diaries . Compared with the meal with carrot nutrients , meals with whole carrots and blended carrots result ed in significantly ( P<0.05 ) higher satiety . There were significant ( P<0.05 ) differences between conditions in intakes at the meal eaten ad libitum and for the remainder of the day , and intakes consistently decreased in the order : carrot nutrients , blended carrots , whole carrots , indicating that both fibre content and structure played a role in these effects |
11,722 | 24,635,650 | RESULTS Thirteen articles reporting 12 studies ( 1 study was reported in 2 articles ) demonstrated that caffeine ( 5 studies ) ; acarbose ; 3,4-DL-threo-dihydroxyphenylserine ; guar gum ( 3 studies ) ; and octreotide ( 2 studies ) statistically attenuated the postpr and ial reduction in BP .
For symptomatic participants , there was improvement with acarbose but none with caffeine .
Drug interventions can attenuate postpr and ial reductions in BP , but they may not necessarily be effective in people with symptomatic PPH | OBJECTIVES To systematic ally review the current literature on the pharmacological treatment of postmeal reductions in blood pressure ( BP ) . | Postpr and ial hypotension is an important clinical condition that predisposes to syncope , falls , angina , and cerebrovascular events . The magnitude of the fall in blood pressure after meals depends on enteric glucose availability . We hypothesized that acarbose , an & agr;-glucosidase inhibitor that decreases glucose absorption in the small intestine , would attenuate postpr and ial hypotension . Acarbose or placebo was given 20 minutes before a st and ardized meal in 13 patients with postpr and ial hypotension in the setting of autonomic failure ( age : 65±2.64 years ; body mass index : 25±1.08 kg/m2 ; supine plasma norepinephrine : 110±26.6 pg/mL ) . Four patients were studied in a single-blind protocol and 9 patients in a double-blind , r and omized , crossover fashion . Patients were studied supine , and blood pressure , heart rate , and neuroendocrine parameters were obtained at baseline and for 90 minutes after meal intake . After adjusting for potential confounders , acarbose significantly attenuated the postpr and ial fall in systolic and diastolic blood pressures by 17 mm Hg ( 95 % CI : 7 to 28 ; P=0.003 ) and 9 mm Hg ( 95 % CI : 5 to 14 ; P=0.001 ) , respectively . Furthermore , acarbose effectively reduced plasma levels of insulin , a known vasodilator , by 11 & mgr;U/mL ( 95 % CI : 5 to 18 ; P=0.001 ) compared with placebo . After adjusting for insulin levels , the attenuation of postpr and ial hypotension by acarbose remained significant , indicating that additional mechanisms contribute to this effect . In conclusion , 100 mg of acarbose successfully improved postpr and ial hypotension in patients with severe autonomic failure . This effect is not explained solely by a reduction in insulin levels Postpr and ial hypotension occurs commonly in patients with autonomic failure and may be due to attenuation of the normal sympathetic nervous system activation in response to meal ingestion . In a r and omized , double-blind , placebo-controlled study , we investigated the therapeutic effect of the norepinephrine precursor 3,4-DL-threo-dihydroxyphenylserine ( DL-DOPS ) on this condition . We measured blood pressure , heart rate , forearm vascular resistance , and plasma DL-DOPS and norepinephrine in 11 patients with autonomic failure . DL-DOPS attenuated the postpr and ial fall in blood pressure . This was associated with an increase in plasma norepinephrine and forearm vascular resistance . DL-DOPS therapy did not change the postpr and ial increase in heart rate . There was a trend toward increased supine hypertension associated with DL-DOPS treatment . This study shows that DL-DOPS is a promising treatment for postpr and ial hypotension and provides support for the hypothesis that postpr and ial hypotension is , at least in part , due to decreased activation of the sympathetic nervous system . NEUROLOGY 1996;47 : 1414 - 1 . The aim of this study was to determine the effects of caffeine on haemodynamic and neurohumoral responses to meal ingestion in elderly patients with a history of symptomatic postpr and ial hypotension . 2 . Postpr and ial hypotension is a common disorder of blood pressure regulation in the elderly , associated with falls and syncope . The pathophysiological mechanism is thought to be related to impaired vascular compensation for splanchnic blood pooling after a meal . Since caffeine inhibits vasodilatory adenosine receptors in the splanchnic circulation , we postulated that caffeine would reduce splanchnic blood pooling and prevent the development of postpr and ial hypotension . 3 . We conducted a r and omized , double-blind , placebo-controlled , cross-over study in nine elderly patients [ age 76 + /- 9 ( SD ) years ] with histories of symptomatic postpr and ial hypotension . St and ardized 1674kJ liquid meals with 250 mg of caffeine or placebo were given on two occasions , at least 1 week apart . Blood pressure , heart rate , forearm vascular resistance ( by venous occlusion plethysmography ) , and plasma caffeine and catecholamine levels were measured . Cardiac and splanchnic blood volume were determined by radionuclide scans . 4 . By 30 min after both caffeine and placebo meal studies , supine mean arterial blood pressure fell significantly ( P = 0.006 ) by 31 + /- 7 and 19 + /- 6 mmHg , respectively ( mean + /- SEM , between group difference was not significant ) . Heart rate , cardiac output and splanchnic blood volume increased significantly , but to a similar extent , after caffeine and placebo . Forearm vascular resistance was unchanged after both meals . 5 . Oral caffeine given with a meal does not reduce splanchnic blood pooling nor prevent postpr and ial hypotension in symptomatic elderly patients Objective To investigate the effects of the somatostatin analogue octreotide , which inhibits the release of various peptides , on 24-h ambulatory blood pressure profiles in subjects with primary ( idiopathic ) autonomic failure due to sympathetic denervation , and in particular to determine whether octreotide reduces daytime hypotension and whether it causes or accentuates nocturnal hypertension . Subjects and methods Eighteen subjects with primary autonomic failure , confirmed by detailed physiological and biochemical autonomic tests , were studied in a r and omized manner on two occasions , with and without octreotide treatment ( 1 μg/kg body weight subcutaneously , twice a day at 0800 and 1800 h ) . Blood pressure was measured using the SpaceLabs 90207 system . This was connected at 0900 h with programmed recordings at 30-min intervals until 2300 h and at 60-min intervals until the next morning . There were additional subject-initiated recordings after 5 min each of lying , sitting and st and ing four times during the day , while sitting after lunch at noon and while st and ing following walking in the evening . Additional analyses included calculation of cumulative sum (cusum)-derived parameters and construction of cusum plots . Results After octreotide treatment , the overall mean daytime systolic/diastolic blood pressure ( mmHg ) was raised ( 123 ± 2/77 ± 1 without treatment versus 128 ± 2/79 ± 1 with treatment ) . There was a reduction in postural ( supine versus st and ing : from 96 ± 3/62 ± 3 without treatment to 106 ± 5/67 ± 4 with treatment ) , postpr and ial ( 107 ± 3/65 ± 2 to 122 ± 5/75 ± 4 ) and exertion-induced ( 96 ± 5/61 ± 5 to 113 ± 6/71 ± 5 ) hypotension . Symptoms of hypotension were reduced by octreotide . Nocturnal blood pressure was lower after octreotide ( 139 ± 3/84 ± 1 versus 129 ± 3/78 ± 2 ) . Analyses with the cusum technique further demonstrated blood pressure recovery during the day , with a reduction in the magnitude of change at night after octreotide treatment . Conclusions In primary autonomic failure , 24-h ambulatory blood pressure profiles and cusum analyses indicate that octreotide has beneficial effects in reducing postural , postpr and ial and exertion-induced hypotension , without causing or increasing nocturnal hypertension 1 . Postpr and ial hypotension is now recognized as an important clinical problem , particularly in the elderly and in patients with autonomic dysfunction . The mechanisms responsible are poorly understood ; however , impaired regulation of splanchnic blood flow and the release of gastrointestinal hormones appear to be important . The effect of gastric emptying on the magnitude of the postpr and ial fall in blood pressure has not been evaluated . 2 . The aim of this study was to determine whether there is a relationship between changes in blood pressure and the rate of gastric emptying after ingestion of 75 g of glucose in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) and both young and older normal subjects . Sixteen patients with recently diagnosed NIDDM , median age 57 ( 39 - 79 ) years , 10 ' young ' subjects with a median age of 23 ( 19 - 26 ) years and nine ' older ' subjects , median age 48 ( 40 - 68 ) years , were measured simultaneously for gastric emptying of 75 g of glucose in 350 ml of water blood pressure and blood glucose concentrations , commencing at approximately 10.00 hours after an overnight fast . Measurements of blood pressure were made in the sitting position immediately before glucose ingestion and at 15 min intervals up to 180 min . 3 . Gastric emptying of glucose was not significantly different between the three groups [ 50 % emptying time ( T50 ) : 95 + /- 7.3 min in patients with NIDDM compared with 120 + /- 13.2 min in the ' young ' group and 97 + /- 8.1 min in the ' older ' group ] . There was a significant fall in mean blood pressure after the glucose load in the patients with NIDDM ( P < 0.0001 ) and the ' older ' normal subjects ( P < 0.05 ) , but not the ' young ' normal subjects . Postpr and ial hypotension ( fall in systolic blood pressure > or = 20 mmHg ) was evident in seven ( 44 % ) patients with NIDDM and three ( 33 % ) ' older ' normal subjects . The area under the change in mean blood pressure curve was related significantly to the gastric emptying T50 ( r = 0.67 , P < 0.005 ) in the patients with NIDDM , but not in either control group . 4 . In conclusion , in patients with recently diagnosed NIDDM the fall in blood pressure after an oral glucose load is ( i ) greater than in both young and older normal subjects and ( ii ) related to the rate of gastric emptying In a double-blind placebo-controlled study , we examined the effect of caffeine pretreatment on the haemodynamic and humoral changes after a st and ardized breakfast in 15 healthy elderly subjects ( mean age 75.4 + /- 6.6 years ) . After placebo , the prepr and ial blood pressure did not change and the postpr and ial blood pressure declined by a maximum of 6.1 % . After oral ingestion of 250 mg caffeine , 60 min before breakfast , the prepr and ial blood pressure increased by 12.5 % . Although the decrease of the postpr and ial blood pressure was not altered , blood pressure remained above its basal value . The increase in plasma noradrenaline after the meal was similar in the placebo and the caffeine tests . Plasma adrenaline decreased after placebo ( -19 % ) but did not change after caffeine . Thus , despite the unchanged decrease of the postpr and ial blood pressure , the prepr and ial pressor effect of caffeine prevented the decline of the postpr and ial blood pressure below its baseline value . The clinical relevance of this finding has still to be determined 1 . A postpr and ial fall in blood pressure ( BP ) in older men and women increases the risks of falls and impaired cerebral perfusion . Postpr and ial hypotension has been suggested to be greater in hypertensive subjects , particularly in those on antihypertensive medication Postpr and ial hypotension occurs frequently in diabetes ; the fall in blood pressure is greatest after ingestion of carbohydrate , particularly glucose and , in type 2 diabetes , is related to the rate of gastric emptying . The aim of this study was to determine whether slowing of gastric emptying by guar gum reduces the fall in blood pressure after oral glucose in patients with type 2 diabetes . Eleven type 2 patients managed by diet alone , age 61.9 ± 1.3 years , had measurements of gastric emptying , blood pressure , blood glucose , and serum insulin on two occasions after ingestion of 300 ml water containing 50 g glucose , with or without 9 g guar gum . The magnitude of the fall in blood pressure was less ( P < 0.05 ) and gastric emptying slower ( P < 0.05 ) after guar . Blood glucose ( P < 0.05 ) and serum insulin ( P < 0.01 ) concentrations were lower after guar . The magnitude of the fall in systolic blood pressure was related to gastric emptying of glucose at 30 min on the control day ( r = 0.67 , P < 0.05 ) . We conclude that guar gum attenuates the fall in blood pressure after oral glucose in patients with type 2 diabetes mellitus , presumably by slowing glucose absorption OBJECTIVE To determine whether slowing of gastric emptying and glucose absorption with guar gum would reduce the fall in blood pressure after an oral glucose load in older subjects . DESIGN A r and omized , experimental , cross-over study . SETTING Department of Nuclear Medicine , Royal Adelaide Hospital , Adelaide , SA , Australia . PARTICIPANTS Ten healthy subjects , age 67 to 78 . MEASUREMENTS Simultaneous measurements of gastric emptying , blood pressure , blood glucose , serum insulin , and oral glucose absorption ( 3-O-methyl-D-glucose [ 3-OMG ] ) on two occasions after ingestion of 300 mL water containing 50 g glucose and 30 mL lemon juice , 3 g 3-OMG labeled with 99mTc-sulphur colloid ; with or without 9 g guar gum . Blood pressure and gastric emptying were monitored for 180 minutes . RESULTS The magnitude of the falls in systolic ( P = .02 ) , diastolic ( P < .05 ) , and mean arterial ( P = .05 ) blood pressure were less , and gastric emptying slower ( P < .05 ) , after guar . Blood glucose , insulin , and 3-OMG concentrations were reduced ( P < .001 for all ) by guar . 3-OMG concentrations were inversely related to the intragastric retention of glucose ( r = -0.72 , P = .02 ) and blood pressure was inversely related to 3-OMG ( r = -0.64 , P < .05 ) after the drink without guar . The blood glucose concentration was related to 3-OMG ( r > 0.64 , P < .05 ) . CONCLUSION Guar gum reduces the magnitude of the fall in blood pressure after oral glucose . Slowing of gastric emptying and glucose absorption may represent a novel approach to the treatment of postpr and ial hypotension We examined the effects of caffeine and meals on blood pressure and heart rate in 12 patients with autonomic failure . The influence of caffeine on plasma norepinephrine , epinephrine , and renin activity was also studied . Caffeine 250 mg , raised blood pressure by 12/6 mm Hg , from 129 + /- 25/78 + /- 12 ( mean + /- S.D. ) to a maximum of 141 + /- 30/84 + /- 16 mm Hg at 45 minutes ( P less than 0.01 ) , but did not change heart rate , levels of norepinephrine , or epinephrine , or plasma renin activity . Blood pressure fell by 28/18 mm Hg after a st and ardized meal , from 133 + /- 32/80 + /- 15 to a minimum of 105 + /- 21/62 + /- 12 mm Hg at 60 minutes ( P less than 0.01 ) . After pretreatment with 250 mg of caffeine , the st and ardized meal induced a fall of only 11/10 mm Hg , from 140 + /- 33/79 + /- 7 to 129 + /- 31/69 + /- 13 mm Hg at 60 minutes ( P less than 0.05 vs. values after the control per day for seven days ) in five patients , postpr and ial blood pressures remained higher after caffeine than after placebo ( P less than 0.05 ) . We conclude that caffeine is a pressor agent and attenuates postpr and ial hypotension in autonomic failure , and that this effect is not primarily due to elevations in sympathoadrenal activity or activation of the renin-angiotensin system . Caffeine may be useful in the treatment of orthostatic hypotension due to autonomic failure , especially in the postpr and ial state 1 . The effects of four meals of similar energy , but different nutritional , composition on postpr and ial blood pressure , heart rate , autonomic function , catecholamines , insulin and packed cell volume levels were studied in seven fit elderly subjects . 2 . The high carbohydrate and high protein meals led to a significant overall fall in supine systolic and diastolic blood pressure compared either with no change or a rise after the normal ( i.e. mixed ) and high fat meals . Similar between-meal differences were seen with erect diastolic but not erect systolic blood pressure . No significant postural blood pressure fall occurred after any of the meals . Supine heart rate was unaffected by meal type or by time , and although erect heart rate showed a small increase during the study there was no between-meal difference . 3 . Parasympathetic function was unaffected by meal type . Plasma noradrenaline rose after the high carbohydrate and mixed meals only , remaining elevated for 120 min after meal consumption . This increase was not related to the changes in blood pressure or plasma insulin levels . 4 . Plasma insulin and glucose rose after the high carbohydrate and mixed meals , but were unchanged after the high protein and high fat meals . Packed cell volume showed a small decrease towards the end of the study , although there was no between-meal variation . 5 . The differences in the cardiovascular changes after the different meals could not be ascribed to alterations in autonomic function , insulin release or fall in plasma volume . We propose that the postpr and ial changes in blood pressure are due to the nutrient composition of the meal rather than the actual energy load The mechanism of postpr and ial blood pressure reduction in the elderly is unknown but it has been suggested that insulin and /or vasoactive gut hormones play a role in this phenomenon . The increase in insulin and other gut hormones induced by the glucose loading can be blocked by a synthetic long-acting somatostatin analogue , SMS 201–995 . We carried out a double-blind r and omized study on the effects of SMS 201–995 on the responses of blood pressure , heart rate , insulin and plasma noradrenaline to oral glucose loading in normotensive and hypertensive elderly subjects . After placebo was administered , mean arterial pressure fell by 15 ± 1 mmHg ( P < 0.001 ) in hypertensive elderly and by 7 ± 2 mmHg ( P < 0.01 ) in normotensive elderly subjects . In contrast , when SMS 201–995 was administered , blood pressure remained essentially unchanged in both groups . These data indicate that treatment with SMS 201–995 might be of value in patients with symptomatic postpr and ial hypotension OBJECTIVE To present baseline data from a prospect i ve study of postpr and ial hypotension in 499 elderly persons in a long-term health care facility . DESIGN Analyses of baseline data for a prospect i ve study . SETTING A large long-term health care facility where 499 ambulatory or wheelchair-bound residents were studied . PATIENTS The 499 residents were > or = 62 years of age , mean age 80 + /- 9 years ( range 62 - 100 ) , 71 % female , 29 % male , 66 % white , 27 % black , 7 % Hispanic , 68 % ambulatory , and 32 % wheelchair-bound . MEASUREMENTS AND MAIN RESULTS The mean maximal decrease in postpr and ial systolic and diastolic blood pressures was 15 + /- 6 mm Hg/6 + /- 2 mm Hg . The mean maximal decrease in postpr and ial systolic blood pressure occurred 15 minutes after eating in 13 % of residents , 30 minutes after eating in 20 % of residents , 45 minutes after eating in 26 % of residents , 60 minutes after eating in 30 % of residents , and 75 minutes after eating in 11 % of residents . Of 499 residents , 118 ( 24 % ) had a maximal decrease in postpr and ial systolic blood pressure of > or = 20 mm Hg . The mean maximal decrease in postpr and ial systolic blood pressure was 24 + /- 5 mm Hg in residents with syncope in the prior 6 months and 14 + /- 5 mm Hg in residents without syncope ( P < 0.0001 ) . The mean maximal decrease in postpr and ial systolic blood pressure was 21 + /- 5 mm Hg in residents with falls in the preceding 6 months and 13 + /- 4 mm Hg in residents without falls ( P < 0.0001 ) . The mean maximal decrease in postpr and ial systolic blood pressure was significantly greater in residents treated with angiotensin-converting enzyme inhibitors , calcium channel blockers , diuretics , nitrates , digoxin , and psychotropic drugs than in residents not treated with these drugs . The mean maximal decrease in postpr and ial systolic and diastolic blood pressures was not significantly different in elderly blacks , Hispanics , and whites . CONCLUSIONS A more severe reduction in postpr and ial systolic blood pressure correlates with a history of syncope or falls in the previous 6 months . Long-term follow-up is being planned to determine whether a marked reduction in postpr and ial systolic blood pressure in elderly persons correlates with a higher incidence of falls , syncope , new coronary events , new stroke , and total mortality The objective of the research was to determine the blood pressure ( BP ) lowering effects in older people of 50 g carbohydrate drinks with varying carbohydrate content using a r and omised , cross-over study with ten ( six females ) healthy older subjects ( mean age 72.20 ( sem 1.50 ) years ) . BP , heart rate and glucometer-derived blood glucose levels were determined at baseline and following the ingestion of equal volumes ( 300 ml ) of water and carbohydrate drinks with varying nutrient content ( glucose , sucrose and fructose ) . A significant decline in BP over the first 60 min was seen following glucose ( systolic BP ( SBP ) P<0.01 , diastolic BP ( DBP ) P<0.01 , mean arterial BP ( MAP ) P=0.03 ) and sucrose ( SBP P<0.01 , DBP P<0.01 , MAP P<0.01 ) ingestion , although the decrease occurred earlier after glucose than sucrose ingestion ( SBP 7.33 ( sem 2.19 ) v. 21.00 ( sem 4.30 ) min ( P=0.03 ) and MAP 11.22 ( sem 3.10 ) v. 17.00 ( sem 3.78 ) min ( P=0.03 ) ) . BP increased after water ingestion ( SBP P=0.04 , DBP P=0.18 , MAP P=0.02 ) but did not change after fructose ingestion ( SBP P=0.36 , DBP P=0.81 , MAP P=0.34 ) . Post hoc analyses revealed that the BP ( SBP , DBP and MAP ) decrease following glucose and sucrose ingestion were similar but significantly greater than following fructose or water ingestion . Sucrose , which is used widely ( table sugar ) , reduces BP as much as glucose . In contrast to this , fructose ingestion causes no change in BP . Further studies are required to determine if the substitution of glucose or sucrose with fructose may be beneficial in the medical management of older people with severe symptomatic postpr and ial hypotension In elderly subjects blood pressure ( BP ) may fall after a meal . The mechanism of this phenomenon is unknown , but it has been suggested that it may be mediated by insulin and /or vasoactive gut hormones . We studied in normo- and hypertensive elderly subjects the effects of the synthetic long-acting somatostatin analog octreotide ( SMS 201 - 995 ) on the BP reduction that follows oral glucose administration in subjects who are recumbent and on their postglucose plasma vasoactive intestinal polypeptide ( VIP ) and insulin concentrations . After placebo treatment , mean arterial pressure fell by 15 + /- 1 mm Hg ( P less than 0.001 ) in the 10 hypertensive subjects and by 7 + /- 2 mm Hg ( P less than 0.01 ) in the 10 normotensive subjects . In contrast , when 50 micrograms octreotide were given sc , BP did not change significantly in either group . Oral glucose did not induce a rise in plasma VIP after either octreotide or placebo administration . The postglucose rises in plasma glucose concentrations were similar after octreotide and placebo treatments in both groups . After placebo administration the postglucose plasma insulin levels increased from 79 to 519 pmol/L in the hypertensive subjects and from 63 to 464 pmol/L in the normotensive subjects , whereas after octreotide treatment plasma insulin increased little in either group . These data indicate that treatment with octreotide holds promise for patients with symptomatic postpr and ial hypotension , and that VIP does not seem to play a role in this phenomenon In a double-blind , r and om-order , cross-over study the effects of placebo and 100 mg of caffeine on postpr and ial sitting and erect blood pressure and heart rate were studied in 20 frail elderly subjects ( mean age 84 , range 75 - 93 years ) after a st and ardized 400 K-calorie glucose drink . Maximal postpr and ial reduction in sitting systolic blood pressure occurred , at 60 minutes post-placebo , of - 11 mmHg ( 95 % confidence interval -5 to -17 mmHg , P less than 0.01 ) , and was attenuated by caffeine ( P less than 0.05 ) with changes in systolic blood pressure , at 60 minutes post-drink , of 1 mmHg ( 95 % CI -6 to 7 mmHg , not significant ) . Four subjects developed symptomatic postpr and ial hypotension after placebo which was prevented by caffeine . There were no significant changes in erect systolic blood pressure , postural systolic blood pressure change , sitting and erect , diastolic blood pressure and heart rate between treatment phases . Caffeine attenuates the postpr and ial fall in sitting blood pressure in frail elderly subjects and in particular prevented symptomatic blood pressure reductions in subjects with postpr and ial hypotension BACKGROUND The variability of postpr and ial hypotension ( PPH ) during the day in elderly patients is unknown . We examined the effect of meals administered at different mealtimes on postpr and ial blood pressure ( BP ) responses in geriatric patients . METHODS In 14 geriatric patients ( 6 men and 8 women , aged 66 - 97 ) previously diagnosed with PPH , st and ardized liquid test meals were given in r and om order at breakfast , lunchtime , or dinnertime on 3 separate days . Systolic BP ( SBP ) , diastolic BP ( DBP ) , and heart rate ( HR ) were measured with an ambulatory BP device every 10 minutes from 20 minutes before until 90 minutes after each meal . Postpr and ial symptoms were observed continuously . RESULTS Significant decreases in SBP and DBP were present after each meal ( p < .050 ) . The maximum SBP decrease was significantly smaller at dinnertime ( -18 + /- 3 mmHg ) than at breakfast ( -29 + /- 2 mmHg ) or lunchtime ( -34 + /- 4 mmHg ) ( p < .005 between groups ) . Eight patients showed no PPH in the evening , whereas all patients had PPH after breakfast and lunch . The duration of PPH was significantly shorter ( p < .001 ) , and postpr and ial symptoms were less frequent and less severe after dinner compared to breakfast and lunch . CONCLUSIONS In geriatric patients , postpr and ial BP responses show a variation during the day , with significantly less PPH and fewer symptoms in the evening . Clinical implication is that , in the diagnostic process and management of PPH , the variation of the occurrence of PPH during the day should be taken into account . Through adjustment of BP decreasing activities to the time PPH is least prevalent , the risk of developing symptomatic PPH can be reduced OBJECTIVES Postpr and ial hypotension occurs frequently in older people and may result in syncope and falls . It has recently been established that the magnitude of the fall in blood pressure is related to the rate at which glucose enters the small intestine . We addressed the hypothesis that the fall in blood pressure induced by an intraduodenal glucose infusion is influenced by the interaction of glucose with the small intestinal absorptive epithelium . METHODS Eight healthy older participants ( four male , four female , age 70.3 + /- 3.4 years ) were studied on two separate occasions , in single-blind , r and omized order . Participants received an intraduodenal glucose infusion ( 3 kcal/min ) with or without guar gum ( 4 g ) for 60 minutes ( 0 - 60 minutes ) , followed by 0.9 % saline intraduodenally for a further 60 minutes ( 60 - 120 minutes ) . Blood pressure and heart rate were measured every 3 minutes . Levels of blood glucose , plasma insulin , glucagon-like peptide-1 ( GLP-1 ) , and glucose-dependant insulinotropic-polypeptide ( GIP ) were also determined . RESULTS Between t = 0 and t = 30 minutes , the magnitude of the fall in systolic blood pressure ( p = .03 ) and increase in heart rate ( p = .027 ) were lower after guar . The blood glucose ( p = .009 ) , plasma insulin ( p = .027 ) , plasma GLP-1 ( p = .018 ) , and GIP ( p < .001 ) responses to intraduodenal glucose were attenuated by guar . CONCLUSIONS In healthy older participants , the magnitude of the fall in systolic blood pressure and increase in heart rate induced by intraduodenal glucose are attenuated when the exposure of glucose to the small intestinal mucosa and subsequent glucose absorption is slowed by guar In a double-blind , r and omized trial the effects of caffeinated and decaffeinated drinks on postpr and ial hemodynamic and neurohumoral changes were studied in seven fit , elderly subjects after a st and ard 2.4MJ meal . There was a significant difference in supine postpr and ial systolic blood pressure between the placebo and caffeine phases ( P less than 0.01 ) ; at 60 minutes , supine systolic blood pressure had fallen 14 mmHg [ 95 % confidence interval (CI)-7 to-21 mmHg , p less than 0.01 ) after placebo , but was unchanged after caffeine ( + 9 mmHg , CI 0 to 18 mmHg , NS ] . Similar differences between placebo and caffeine were seen in erect systolic and diastolic blood pressure ( P less than 0.01 ) , although orthostatic tolerance was maintained throughout each study period . Postpr and ial plasma noradrenaline levels were higher ( P less than 0.02 ) and the increase greater ( P less than 0.02 ) after caffeine than after placebo . Caffeine administered at the end of a st and ard test meal prevents the postpr and ial fall in blood pressure in fit , elderly subjects . The clinical relevance of this finding has yet to be determined , but it may offer a simple remedy for patients with symptomatic postpr and ial hypotension |
11,723 | 24,360,819 | Goals with moderate quality evidence were sublingual microcirculation flow , the oxygen extraction ratio , cardiac index , cardiac output , and SVC collapsibility index . | PURPOSE To review the literature on goal directed fluid therapy and evaluate the quality of evidence for each combination of goal and monitoring method . | BACKGROUND Optimal fluid management in patients with acute lung injury is unknown . Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion . METHODS In a r and omized study , we compared a conservative and a liberal strategy of fluid management using explicit protocol s applied for seven days in 1000 patients with acute lung injury . The primary end point was death at 60 days . Secondary end points included the number of ventilator-free days and organ-failure-free days and measures of lung physiology . RESULTS The rate of death at 60 days was 25.5 percent in the conservative- strategy group and 28.4 percent in the liberal- strategy group ( P=0.30 ; 95 percent confidence interval for the difference , -2.6 to 8.4 percent ) . The mean ( + /-SE ) cumulative fluid balance during the first seven days was -136+/-491 ml in the conservative- strategy group and 6992+/-502 ml in the liberal- strategy group ( P<0.001 ) . As compared with the liberal strategy , the conservative strategy improved the oxygenation index ( [ mean airway pressure x the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen]x100 ) and the lung injury score and increased the number of ventilator-free days ( 14.6+/-0.5 vs. 12.1+/-0.5 , P<0.001 ) and days not spent in the intensive care unit ( 13.4+/-0.4 vs. 11.2+/-0.4 , P<0.001 ) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days ( 10 percent vs. 14 percent , P=0.06 ) . CONCLUSIONS Although there was no significant difference in the primary outcome of 60-day mortality , the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures . These results support the use of a conservative strategy of fluid management in patients with acute lung injury . ( Clinical Trials.gov number , NCT00281268 [ Clinical Trials.gov ] . ) 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 : An individualized fluid optimization strategy , based on maximization of cardiac stroke volume ( SV ) with colloid boluses ( goal ‐directed therapy ) , improves outcome after surgery . Oesophageal Doppler ( OD ) is used for SV maximization in most r and omized studies , but evidence ‐based guidelines for the SV maximization procedure are lacking and variation in SV may influence the indication for fluid administration . We measured beat‐to‐beat OD SV before and after fluid optimization in order to estimate the number of heartbeats for which SV needs to be averaged to provide an acceptable accuracy for goal ‐directed therapy with this technology Objective To test whether fluid responsiveness can be predicted by the respiratory variation in aortic blood flow and /or the flow time corrected for heart rate monitored with esophageal Doppler . Design and setting Prospect i ve study in a 24-bed medical intensive care unit of a university hospital . Patients 38 mechanically ventilated patients with sinus rhythm and without spontaneous breathing activity in whom volume expansion was planned . Interventions The aortic blood flow was measured using an esophageal Doppler monitoring device before and after fluid infusion ( 500 ml NaCl 0.9 % over 10 min ) . The variation in aortic blood flow over a respiratory cycle between its minimal and maximal values was calculated . The flow time was also measured . Measurements and results Aortic blood flow increased by at least 15 % after volume expansion in 20 patients ( defined as responders ) . Before fluid infusion the respiratory variation in aortic flow was higher in responders than in nonresponders ( 28±12 % vs. 12±5 % ) . It significantly decreased after volume expansion ( 18±11 % ) in responders only . A respiratory variation in aortic flow before volume expansion of at least 18 % predicted fluid responsiveness with a sensitivity of 90 % and a specificity of 94 % . Flow time increased with fluid infusion in responders and nonresponders . A flow time corrected for heart rate below 277 ms predicted fluid responsiveness with a sensitivity of 55 % and a specificity of 94 % . The area under the ROC curve generated for variation in aortic blood flow ABF was greater than that generated for flow time . Conclusions The respiratory variation in aortic blood flow reliably predicts fluid responsiveness in patients with sinus rhythm and without breathing activity 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 Objective To test the hypothesis that , in resuscitated septic shock patients , central venous-to-arterial carbon dioxide difference [ P(cv-a)CO2 ] may serve as a global index of tissue perfusion when the central venous oxygen saturation ( ScvO2 ) goal value has already been reached . Design Prospect i ve observational study . Setting A 22-bed intensive care unit ( ICU ) . Patients After early resuscitation in the emergency unit , 50 consecutive septic shock patients with ScvO2 > 70 % were included immediately after their admission into the ICU ( T0 ) . Patients were separated in Low P(cv-a)CO2 group ( Low gap ; n = 26 ) and High P(cv-a)CO2 group ( High gap ; n = 24 ) according to a threshold of 6 mmHg at T0 . Measurements Measurements were performed every 6 h over 12 h ( T0 , T6 , T12 ) . Results At T0 , there was a significant difference between Low gap patients and High gap patients for cardiac index ( CI ) ( 4.3 ± 1.6 vs. 2.7 ± 0.8 l/min/m² , P < 0.0001 ) but not for ScvO2 values ( 78 ± 5 vs. 75 ± 5 % , P = 0.07 ) . From T0 to T12 , the clearance of lactate was significantly larger for the Low gap group than for the High gap group ( P < 0.05 ) as well as the decrease of SOFA score at T24 ( P < 0.01 ) . At T0 , T6 and T12 , CI and P(cv-a)CO2 values were inversely correlated ( P < 0.0001 ) . Conclusion In ICU-resuscitated patients , targeting only ScvO2 may not be sufficient to guide therapy . When the 70 % ScvO2 goal -value is reached , the presence of a P(cv-a)CO2 larger than 6 mmHg might be a useful tool to identify patients who still remain inadequately resuscitated Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery , which increases re source use and health care costs . Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients . Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves . The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit ( ICU ) stay . Four hundred three elective cardiac surgical patients were enrolled in the study and r and omly assigned to either the control or the protocol group . Goals of the protocol group were to maintain Svo2 > 70 % and lactate concentration ≤2.0 mmol/L from admission to the ICU and up to 8 h thereafter . Hemodynamics , oxygen transport data , and organ dysfunctions were recorded . The median hos-pital stay was shorter in the protocol group ( 6 vs 7 days , P < 0.05 ) , and patients were discharged faster from the hospital than those in the control group ( P < 0.05 ) . Discharge from the ICU was similar between groups ( P = 0.8 ) . Morbidity was less frequent at the time of hospital discharge in the protocol group ( 1.1 % vs 6.1 % , P < 0.01 ) . Increasing oxygen delivery to achieve normal Svo2 values and lactate concentration during the immediate postoperative period after cardiac surgery can shorten the length of hospital stay . Implication s Health care economics has challenged clinicians to reduce costs and improve re source use in cardiac surgery and anesthesia in a patient population increasing in age and in severity of disease . Optimizing cardiovascular function to maintain adequate oxygen delivery during the immediate postoperative period after cardiac surgery can decrease morbidity and reduce length of hospital stay 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 investigate whether the respiratory variation in inferior vena cava diameter ( ΔDIVC ) could be related to fluid responsiveness in mechanically ventilated patients . Design Prospect i ve clinical study . Setting Medical ICU of a non-university hospital . Patients Mechanically ventilated patients with septic shock ( n=39 ) . Interventions Volume loading with 8 mL/kg of 6 % hydroxyethylstarch over 20 min . Measurements and results Cardiac output and ΔDIVC were assessed by echography before and immediately after the st and ardized volume load . Volume loading induced an increase in cardiac output from 5.7±2.0 to 6.4±1.9 L/min ( P<0.001 ) and a decrease in ΔDIVC from 13.8±13.6 vs 5.2±5.8 % ( P<0.001 ) . Sixteen patients responded to volume loading by an increase in cardiac output ≥15 % ( responders ) . Before volume loading , the ΔDIVC was greater in responders than in non-responders ( 25±15 vs 6±4 % , P<0.001 ) , closely correlated with the increase in cardiac output ( r=0.82 , P<0.001 ) , and a 12 % ΔDIVC cut-off value allowed identification of responders with positive and negative predictive values of 93 % and 92 % , respectively . Conclusion Analysis of ΔDIVC is a simple and non-invasive method to detect fluid responsiveness in mechanically ventilated patients with septic shock Abstract Objective : The mixed venous-arterial ( v-a ) pCO2 difference has been shown to be inversely correlated with the cardiac index ( CI ) . A central venous pCO2 , which is easier to obtain , may provide similar information . The purpose of this study was to examine the correlation between the central venous-arterial pCO2 difference and CI . Design : Prospect i ve , cohort study . Setting : Intensive care unit of an urban tertiary care hospital . Patients and participants : Eighty-three consecutive intensive care unit patients . Measurements : Simultaneous blood gases from the arterial , pulmonary artery ( PA ) , and central venous ( CV ) catheters were obtained . At the same time point , cardiac indices were measured by the thermodilution technique ( an average of three measurements ) . The cardiac indices obtained by the venous-arterial differences were compared with those determined by thermodilution . Results : The correlation ( R2 ) between the mixed venous-arterial pCO2 difference and cardiac index was 0.903 ( p < 0.0001 ) , and the correlation between the central venous-arterial pCO2 difference and cardiac index was 0.892 ( p < 0.0001 ) . The regression equations for these relationships were natural log (CI)=1.837−0.159 ( v-a ) CO2 for the PA and natural log (CI)=1.787−0.151 ( v-a ) CO2 for the CV ( p < 0.0001 for both ) . The root-mean-squared error for the PA and CV regression equations were 0.095 and 0.101 , respectively . Conclusion : Venous-arterial pCO2 differences obtained from both the PA and CV circulations inversely correlate with the cardiac index . Substitution of a central for a mixed venous-arterial pCO2 difference provides an accurate alternative method for calculation of cardiac output CONTEXT Goal -directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department . OBJECTIVE To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation ( ScvO2 ) as goals of early sepsis resuscitation . DESIGN , SETTING , AND PATIENTS Multicenter r and omized , noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals . INTERVENTIONS We r and omly assigned patients to 1 of 2 resuscitation protocol s. The ScvO2 group was resuscitated to normalize central venous pressure , mean arterial pressure , and ScvO2 of at least 70 % ; and the lactate clearance group was resuscitated to normalize central venous pressure , mean arterial pressure , and lactate clearance of at least 10 % . The study protocol was continued until all goals were achieved or for up to 6 hours . Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment . MAIN OUTCOME MEASURE The primary outcome was absolute in-hospital mortality rate ; the noninferiority threshold was set at Delta equal to -10 % . RESULTS Of the 300 patients enrolled , 150 were assigned to each group and patients were well matched by demographic , comorbidities , and physiological features . There were no differences in treatments administered during the initial 72 hours of hospitalization . Thirty-four patients ( 23 % ) in the ScvO2 group died while in the hospital ( 95 % confidence interval [ CI ] , 17%-30 % ) compared with 25 ( 17 % ; 95 % CI , 11%-24 % ) in the lactate clearance group . This observed difference between mortality rates did not reach the predefined -10 % threshold ( intent-to-treat analysis : 95 % CI for the 6 % difference , -3 % to 15 % ) . There were no differences in treatment-related adverse events between the groups . CONCLUSION Among patients with septic shock who were treated to normalize central venous and mean arterial pressure , additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00372502 Background Monitoring left ventricular preload is critical to achieve adequate fluid resuscitation in patients with hypotension and sepsis . This prospect i ve study tested the correlation of the pulmonary artery occlusion pressure , the left ventricular end‐diastolic area index measured by transesophageal echocardiography , the arterial systolic pressure variation ( the difference between maximal and minimal systolic blood pressure values during one mechanical breath ) , and its delta down ( dDown ) component (= apneic ‐ minimum systolic blood pressure ) with the response of cardiac output to volume expansion during sepsis . Methods Preload parameters were measured at baseline and during grade d volume expansion ( increments of 500 ml ) in 15 patients with sepsis‐induced hypotension who required mechanical ventilation . Each volume‐loading step ( VLS ) was classified as a responder ( increase in stroke volume index > or= to 15 % ) or a nonresponder . Successive VLSs were performed until a nonresponder VLS was obtained . Results Thirty‐five VLSs ( 21 responders ) were performed . Fluid loading caused an overall significant increase in pulmonary artery occlusion pressure and end‐diastolic area index , and a significant decrease in systolic pressure variation and delta down ( P < 0.01 ) . There was a significant difference between responder and nonresponder VLSs in end‐diastolic area index , systolic pressure variation , and dDown , but not in pulmonary artery occlusion pressure . Receiver‐operator curve analysis showed that dDown was a more accurate indicator of the response of stroke volume index to volume loading than end‐diastolic area index and pulmonary artery occlusion pressure . A dDown component of more than 5 mmHg indicated that the stroke volume index would increase in response to a subsequent fluid challenge ( positive and negative predictive values : 95 % and 93 % , respectively ) . Conclusion The dDown component of the systolic pressure variation is a sensitive indicator of the response of cardiac output to volume infusion in patient with sepsis‐induced hypotension who require mechanical ventilation 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 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 Introduction Esophageal Doppler was confirmed as a useful non-invasive tool for management of fluid replacement in elective surgery . The aim of this study was to assess the effect of early optimization of intravascular volume using esophageal Doppler on blood lactate levels and organ dysfunction development in comparison with st and ard hemodynamic management in multiple-trauma patients . Methods This was a r and omized controlled trial . Multiple-trauma patients with blood loss of more than 2,000 ml admitted to the intensive care unit ( ICU ) were r and omly assigned to the protocol group with esophageal Doppler monitoring and to the control group . Fluid resuscitation in the Doppler group was guided for the first 12 hours of ICU stay according to the protocol based on data obtained by esophageal Doppler , whereas control patients were managed conventionally . Blood lactate levels and organ dysfunction during ICU stay were evaluated . Results Eighty patients were r and omly assigned to Doppler and 82 patients to control treatment . The Doppler group received more intravenous colloid during the first 12 hours of ICU stay ( 1,667 ± 426 ml versus 682 ± 322 ml ; p < 0.0001 ) , and blood lactate levels in the Doppler group were lower after 12 and 24 hours of treatment than in the control group ( 2.92 ± 0.54 mmol/l versus 3.23 ± 0.54 mmol/l [ p = 0.0003 ] and 1.99 ± 0.44 mmol/l versus 2.37 ± 0.58 mmol/l [ p < 0.0001 ] , respectively ) . No difference in organ dysfunction between the groups was found . Fewer patients in the Doppler group developed infectious complications ( 15 [ 18.8 % ] versus 28 [ 34.1 % ] ; relative risk = 0.5491 ; 95 % confidence interval = 0.3180 to 0.9482 ; p = 0.032 ) . ICU stay in the Doppler group was reduced from a median of 8.5 days ( interquartile range [ IQR ] 6 to16 ) to 7 days ( IQR 6 to 11 ) ( p = 0.031 ) , and hospital stay was decreased from a median of 17.5 days ( IQR 11 to 29 ) to 14 days ( IQR 8.25 to 21 ) ( p = 0.045 ) . No significant difference in ICU and hospital mortalities between the groups was found . Conclusion Optimization of intravascular volume using esophageal Doppler in multiple-trauma patients is associated with a decrease of blood lactate levels , a lower incidence of infectious complications , and a reduced duration of ICU and hospital stays Introduction The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures . In the evolution of these recommendations , indirect measures of the balance between systemic oxygen delivery and dem and s using central venous or superior vena cava oxygen saturation ( ScvO2 ≥ 70 % ) in a goal -directed approach have been added . However , while these additional goal -directed endpoints are based on evidence -based adult studies , the extrapolation to the paediatric patient remains unvali date d. Objective The purpose of this study was to compare treatment according to ACCM/PALS guidelines , performed with and without ScvO2 goal -directed therapy , on the morbidity and mortality rate of children with severe sepsis and septic shock . Design , participants and interventions Children and adolescents with severe sepsis or fluid-refractory septic shock were r and omly assigned to ACCM/PALS with or without ScvO2 goal -directed resuscitation . Measurements Twenty-eight-day mortality was the primary endpoint . Results Of the 102 enrolled patients , 51 received ACCM/PALS with ScvO2 goal -directed therapy and 51 received ACCM/PALS without ScvO2 goal -directed therapy . ScvO2 goal -directed therapy result ed in less mortality ( 28-day mortality 11.8 % vs. 39.2 % , p = 0.002 ) , and fewer new organ dysfunctions ( p = 0.03 ) . ScvO2 goal -directed therapy result ed in more crystalloid ( 28 ( 20–40 ) vs. 5 ( 0–20 ) ml/kg , p < 0.0001 ) , blood transfusion ( 45.1 % vs. 15.7 % , p = 0.002 ) and inotropic ( 29.4 % vs. 7.8 % , p = 0.01 ) support in the first 6 h. Conclusions This study supports the current ACCM/PALS guidelines . Goal -directed therapy using the endpoint of a ScvO2 ≥ 70 % has a significant and additive impact on the outcome of children and adolescents with septic shock Introduction Patients undergoing lung resection are vulnerable to fluid overhydration . Recently , goal -directed fluid therapy using transoesophageal Doppler monitoring ( TDM ) has been shown to improve postoperative clinical outcome . The aim of this study was to assess the feasibility of TDM during open-chest procedures for guiding fluid and hemodynamic treatment . Methods We performed an observational prospect i ve study including 127 high-risk patients undergoing lung cancer resection . A restrictive fluid strategy was targeted to achieve a stroke volume index ( SVI ) ≥ 30 ml/min/m2 . Besides st and ard hemodynamic measurements , stroke volume index ( SVI ) , corrected flow time ( FTc ) , maximal acceleration ( MA ) and velocity ( PV ) were recorded during two-lung ventilation ( TLV ) and one-lung ventilation ( OLV ) . Results Doppler flow tracings could not be obtained in 4 patients during TLV ( 3.1 % ) and in 6 patients during OLV ( 4.9 % ) . Preoperatively , 96 pts had SVI ≥ 30 ml/min/m2 ( N-SVI group ) whereas 21 patients had SVI < 30 ml/min/m2 ( L-SVI group ) associated with lower FTc values . After OLV , SVI transiently decreased ( −17 ± 9 % ; P < 0.05 ) in the N-SVI group whereas in the L-SVI group , SVI increased steadily until the end of surgery ( + 40 ± 12 % ) . Other flow-related parameters as well as heart rate and mean arterial pressure remained unchanged . Surgical and medical characteristics did not differ between the two groups , except that larger volumes of colloids were administered intraoperatively in the L-SVI group ( + 2.2 ± 0.6 ml/min/h compared with N-SVI group , P < 0.05 ) . Conclusion In thoracic surgical patients , TDM can be used to detect and correct low flow conditions and to guide hemodynamic support during the intraoperative period Abstract Objective To assess whether a nurse led , flow monitored protocol for optimising circulatory status in patients after cardiac surgery reduces complications and shortens stay in intensive care and hospital . Design R and omised controlled trial . Setting Intensive care unit and cardiothoracic unit of a university teaching hospital . Participants 174 patients who underwent cardiac surgery between April 2000 and January 2003 . Interventions Patients were allocated to conventional haemodynamic management or to an algorithm guided by oesophageal Doppler flowmetry to maintain a stroke index above 35 ml/m2 . Results 26 control patients had postoperative complications ( two deaths ) compared with 17 ( four deaths ) protocol patients ( P = 0.08 ) . Duration of hospital stay in the protocol group was significantly reduced from a median of nine ( interquartile range 7 - 12 ) days to seven ( 7 - 10 ) days ( P = 0.02 ) . The mean duration of hospital stay was reduced from 13.9 to 11.4 days , a saving in hospital bed days of 18 % ( 95 % confidence interval −12 % to 47 % ) . Usage of intensive care beds was reduced by 23 % ( −8 % to 59 % ) . Conclusion A nurse delivered protocol for optimising circulatory status in the early postoperative period after cardiac surgery may significantly shorten hospital stay Introduction Despite recent interest in measurement of central venous oxygen saturation ( ScvO2 ) , there are no published data describing the pattern of ScvO2 changes after major general surgery or any relationship with outcome . Methods ScvO2 and other biochemical , physiological and demographic data were prospect ively measured for 8 hours after major surgery . Complications and deaths occurring within 28 days of enrolment were included in the data analysis . Independent predictors of complications were identified with the use of logistic regression analysis . Optimum cutoffs for ScvO2 were identified by receiver operator characteristic analysis . Results Data from 118 patients was analysed ; 123 morbidity episodes occurred in 64 these patients . There were 12 deaths ( 10.2 % ) . The mean ± SD age was 66.8 ± 11.4 years . Twenty patients ( 17 % ) underwent emergency surgery and 77 patients ( 66 % ) were male . The mean ± SD P-POSSUM ( Portsmouth Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity ) score was 38.6 ± 7.7 , with a predicted mortality of 16.7 ± 17.6 % . After multivariate analysis , the lowest cardiac index value ( odds ratio ( OR ) 0.58 ( 95 % confidence intervals 0.37 to 0.9 ) ; p = 0.018 ) , lowest ScvO2 value ( OR 0.94 ( 0.89 to 0.98 ) ; p = 0.007 ) and P-POSSUM score ( OR 1.09 ( 1.02 to 1.15 ) ; p = 0.008 ) were independently associated with post-operative complications . The optimal ScvO2 cutoff value for morbidity prediction was 64.4 % . In the first hour after surgery , significant reductions in ScvO2 were observed , but there were no significant changes in CI or oxygen delivery index during the same period . ConclusionS ignificant fluctuations in ScvO2 occur in the immediate post-operative period . These fluctuations are not always associated with changes in oxygen delivery , suggesting that oxygen consumption is also an important determinant of ScvO2 . Reductions in ScvO2 are independently associated with post-operative complications Introduction Goal -directed therapy ( GDT ) has been shown to improve outcome when commenced before surgery . This requires pre-operative admission to the intensive care unit ( ICU ) . In cardiac surgery , GDT has proved effective when commenced after surgery . The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery . Methods This was a r and omised controlled trial with concealed allocation . High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min-1 m-2 or to conventional management . Cardiac output was measured by lithium indicator dilution and pulse power analysis . Patients were followed up for 60 days . Results Sixty-two patients were r and omised to GDT and 60 patients to control treatment . The GDT group received more intravenous colloid ( 1,907 SD ± 878 ml versus 1,204 SD ± 898 ml ; p < 0.0001 ) and dopexamine ( 55 patients ( 89 % ) versus 1 patient ( 2 % ) ; p < 0.0001 ) . Fewer GDT patients developed complications ( 27 patients ( 44 % ) versus 41 patients ( 68 % ) ; p = 0.003 , relative risk 0.63 ; 95 % confidence intervals 0.46 to 0.87 ) . The number of complications per patient was also reduced ( 0.7 SD ± 0.9 per patient versus 1.5 SD ± 1.5 per patient ; p = 0.002 ) . The median duration of hospital stay in the GDT group was significantly reduced ( 11 days ( IQR 7 to 15 ) versus 14 days ( IQR 11 to 27 ) ; p = 0.001 ) . There was no significant difference in mortality ( seven patients ( 11.3 % ) versus nine patients ( 15 % ) ; p = 0.59 ) . Conclusion Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay . The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission 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 : The intravascular volume of surgical patients should be optimized to avoid complications associated with both overhydration and underresuscitation . In patients undergoing intraoperative acute normovolemic hemodilution , we investigated whether stroke volume variation ( SVV ) derived from an arterial pressure-based cardiac output ( CO ) monitor system ( FloTrac/Vigileo ™ , Edwards Lifesciences , Irvine , CA ) tracked the changes associated with blood removal and replacement . We further evaluated the correlations between SVV and 3-dimensional ( 3D ) transesophageal echocardiographic ( TEE ) left ventricular ( LV ) volume measurements . METHODS : Twenty-five patients had procedures during which acute normovolemic hemodilution was a planned part of the intraoperative management . We defined 7 measurement timepoints : baseline , after the removal of 5 % , 10 % , and 15 % of the estimated blood volume ( EBV ) and after replacement with an equal volume of 6 % hetastarch to −10 % , −5 % , and baseline EBV . At each timepoint , heart rate and systolic , diastolic , and mean arterial blood pressure were obtained from st and ard monitors , CO and SVV measurements were obtained from the FloTrac/Vigileo monitor , and TEE images were recorded for subsequent off-line reconstruction and determination of LV end-systolic and end-diastolic volumes . For statistical evaluations , we used a mixed models analysis of variance and Dunnett ’s test for post hoc comparisons with baseline values . Pearson ’s correlation was used to examine the relationships between SVV and LV volume . RESULTS : Analysis of variance demonstrated no significant change in heart rate or mean arterial blood pressure over the duration of study . CO decreased from 4.9 ± 0.3 to 4.5 ± 0.3 L/min after removal of 15 % of the EBV and then increased to a final value of 5.4 ± 0.3 L/min after replacement of 15 % of the EBV . SVV increased from 9.2 % ± 0.9 % to 20.3 % ± 2.0 % ( P < 0.001 ) after removal of 15 % of the EBV and returned to a final value of 7.2 % ± 0.9 % after replacement of 15 % of the EBV . The indexed LV end-diastolic volume decreased from 42.1 ± 8.3 to 36.9.3 ± 8.3 mL/m2 ( P < 0.001 ) after removal of 15 % of the EBV and then returned to a final volume of 45.9 ± 10.3 mL/m2 after replacement of 15 % of the EBV . The measurements of SVV correlated inversely with the 3D TEE LV volume measurements . CONCLUSIONS : The SVV derived from the FloTrac/Vigileo system changes significantly as blood is removed and replaced during hemodilution . These changes correlate with 3D TEE measurements of LV volume . The utility of SVV in guiding optimization of intravascular volume merits further study Objective We examined whether guiding therapy by an algorithm based on optimizing the global end-diastolic volume index ( GEDVI ) reduces the need for vasopressor and inotropic support and helps to shorten ICU stay in cardiac surgery patients . Design and setting Single-center clinical study with a historical control group at an university hospital . Patients Forty cardiac bypass surgery patients were included prospect ively and compared with a control group . Interventions In the goal -directed therapy ( GDT ) group hemodynamic management was guided by an algorithm based on GEDVI . Hemodynamic goals were : GEDVI above 640 ml/m2 , cardiac index above 2.5 l/min/m2 , and mean arterial pressure above 70 mmHg . The control group was treated at the discretion of the attending physician based on central venous pressure , mean arterial pressure , and clinical evaluation . Results In the GDT group duration of catecholamine and vasopressor dependence was shorter ( 187 ± 70 vs. 1458 ± 197 min ) , and fewer vasopressors ( 0.73 ± 0.32 vs. 6.67 ± 1.21 mg ) and catecholamines ( 0.01 ± 0.01 vs. 0.83 ± 0.27 mg ) were administered . They received more colloids ( 6918 ± 242 vs. 5514 ± 171 ml ) . Duration of mechanical ventilation ( 12.6 ± 3.6 vs. 15.4 ± 4.3 h ) and time until achieving status of fit for ICU discharge ( 25 ± 13 vs. 33 ± 17 h ) was shorter in the GDT group . Conclusions Guiding therapy by an algorithm based on GEDVI leads to a shortened and reduced need for vasopressors , catecholamines , mechanical ventilation , and ICU therapy in patients undergoing cardiac surgery 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 Improved postoperative outcome has been demonstrated by perioperative maximization of cardiac stroke volume ( SV ) with fluid challenges , so-called goal -directed therapy . Oesophageal Doppler ( OD ) has been the most common technique for goal -directed therapy , but other flow-related techniques and parameters are available and they are potentially easier to apply in clinical practice . The objective of this investigation was therefore to use OD for preoperative SV maximization and compare the findings with a Modelflow determined SV , with an OD estimated corrected flow time ( FTc ) , with central venous oxygenation ( Svo2 ) and with muscle and brain oxygenation assessed with near infrared spectroscopy ( NIRS ) . METHODS Twelve patients scheduled for radical prostatectomy were anaesthetized before optimization of SV estimated by OD . A fluid challenge of 200 ml colloid was provided and repeated if at least a 10 % increment in OD SV was obtained . Values were compared with simultaneously measured values of Modelflow SV , FTc , Svo2 and muscle and cerebral oxygenation estimated by NIRS . RESULTS Based upon OD assessment , optimization of SV was achieved after the administration of 400 - 800 ml ( mean 483 ml ) of colloid . The hypothetical volumes administered for optimization based upon Modelflow and Svo2 differed from OD in 10 and 11 patients , respectively . Changes in FTc and NIRS were inconsistent with OD guided optimization . CONCLUSION Preoperative SV optimization guided by OD for goal -directed therapy is preferable compared with Modelflow SV , FTc , NIRS and Svo2 until outcome studies for the latter are available 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 BACKGROUND : The arterial pulse pressure variation induced by mechanical ventilation ( & Dgr;PP ) has been shown to be a predictor of fluid responsiveness . Until now , & Dgr;PP has had to be calculated offline ( from a computer recording or a paper printing of the arterial pressure curve ) , or to be derived from specific cardiac output monitors , limiting the widespread use of this parameter . Recently , a method has been developed for the automatic calculation and real-time monitoring of & Dgr;PP using st and ard bedside monitors . Whether this method is to predict reliable predictor of fluid responsiveness remains to be determined . METHODS : We conducted a prospect i ve clinical study in 59 mechanically ventilated patients in the postoperative period of cardiac surgery . Patients studied were considered at low risk for complications related to fluid administration ( pulmonary artery occlusion pressure < 20 mm Hg , left ventricular ejection fraction ≥40 % ) . All patients were instrumented with an arterial line and a pulmonary artery catheter . Cardiac filling pressures and cardiac output were measured before and after intravascular fluid administration ( 20 mL/kg of lactated Ringer ’s solution over 20 min ) , whereas & Dgr;PP was automatically calculated and continuously monitored . RESULTS : Fluid administration increased cardiac output by at least 15 % in 39 patients ( 66 % = responders ) . Before fluid administration , responders and nonresponders were comparable with regard to right atrial and pulmonary artery occlusion pressures . In contrast , & Dgr;PP was significantly greater in responders than in nonresponders ( 17 % ± 3 % vs 9 % ± 2 % , P < 0.001 ) . The & Dgr;PP cut-off value of 12 % allowed identification of responders with a sensitivity of 97 % and a specificity of 95 % . CONCLUSION : Automatic real-time monitoring of & Dgr;PP is possible using a st and ard bedside monitor and was found to be a reliable method to predict fluid responsiveness after cardiac surgery . Additional studies are needed to determine if this technique can be used to avoid the complications of fluid administration in high-risk patients Changes in arterial blood pressure induced by mechanical ventilation allow assessment of cardiac preload . In this study , stroke volume variation ( SVV ) , which is the percentage change between the maximal and minimal stroke volumes ( SV ) divided by the average of the minimum and maximum over a floating period of 30 s , continuously displayed by the PiCCO continuous cardiac output monitor , was evaluated as a predictor of fluid responsiveness . Fifteen patients undergoing brain surgery were included . During surgery , grade d volume loading was performed with each volume loading step ( VLS ) consisting of 100 mL of 6 % hydroxyethylstarch given for 2 min . Successive responsive VLSs were performed ( increase in SV > 5 % after a VLS ) until a change in SV of < 5 % was reached ( nonresponsive ) . A total of 140 VLSs were performed . Responsive and nonresponsive VLSs differed in their pre-VLS values of systolic blood pressure , SV , and SVV , but not in the values of heart rate and central venous pressure . By using receiver operating characteristic analysis , the area under the curve for SVV ( 0.870 , 95 % confidence interval [ CI ] : 0.809 to 0.903 ) was statistically more than those for central venous pressure ( 0.493 , 95 % CI : 0.397 to 0.590 , P = 7 × 10−10 ) , heart rate ( 0.593 , 95 % CI : 0.443 to 0.635 , P = 5.7 × 10−10 ) , and systolic blood pressure ( 0.729 , 95 % CI : 0.645 to 0.813 , P = 4.3 × 10 - 3 ) . An SVV value of 9.5 % or more , will predict an increase in the SV of at least 5 % in response to a 100-mL volume load , with a sensitivity of 79 % and a specificity of 93 % Objective In mechanically ventilated patients inspiratory increase in pleural pressure during lung inflation may produce complete or partial collapse of the superior vena cava . Occurrence of this collapse suggests that at this time external pressure exerted by the thoracic cavity on the superior vena cava is greater than the venous pressure required to maintain the vessel fully open . We tested the hypothesis that measurement of superior vena caval collapsibility would reveal the need for volume expansion in a given septic patient . Design and setting Prospect i ve data collection for 66 successive patients in septic shock admitted in a medical intensive care unit and mechanically ventilated for an associated acute lung injury . Measurements and results We simultaneously measured superior vena caval collapsibility by echocardiography and cardiac index by the Doppler technique at baseline and after a 10 ml/kg volume expansion by 6 % hydroxyethyl starch in 30 min . The threshold superior vena caval collapsibility of 36 % , calculated as ( maximum diameter on expiration−minimum diameter on inspiration)/maximum diameter on expiration , allowed discrimination between responders ( defined by an increase in cardiac index of at least 11 % induced by volume expansion ) and nonresponders , with a sensitivity of 90 % and a specificity of 100 % . Conclusions Superior vena cava measurement should be systematic ally performed during routine echocardiography in septic shock as it gives an accurate index of fluid responsiveness OBJECTIVE To record pulmonary artery occlusion pressures ( PAOPs ) in patients whose left ventricular preload reserve was subjectively determined using transesophageal echocardiography ( TEE ) . DESIGN Prospect i ve , blinded , nonr and omized . SETTING University hospital . PARTICIPANTS Twenty-three patients with well-preserved left ventricular function during nonemergent cardiac surgery . INTERVENTIONS After separation from cardiopulmonary bypass , patients received repeated boluses of fluid volume through the aortic inflow cannula while being monitored with TEE . The endpoint for this fluid administration was a plateau in left ventricular fractional area change and end-diastolic area . This point at which additional fluid failed to cause noticeable increases in left ventricular end-diastolic area and fractional area change was defined as the preload reserve volume . After reaching the preload reserve volume , the PAOP was measured , as were the systolic blood pressure , left ventricular fractional area change , and end-diastolic area . MEASUREMENTS AND MAIN RESULTS The mean PAOP for all patients at the time of achieving preload reserve volume was 18.6 + /- 2.9 mmHg . In 8 patients , the PAOP corresponding to preload reserve volume was elevated ( 20 to 25 mmHg ) . The remaining 15 patients had PAOPs ranging from 13 to 19 mmHg . When these 2 groups were compared with respect to left ventricular end-diastolic area , fractional area change , and systolic blood pressure , there were no significant differences between groups . The left ventricular wall thickness was significantly greater , however , in the group with elevated PAOP ( 1.37 + /- 0.04 cm ) when compared with the group with normal ventricular filling pressures ( 1.05 + /- 0.15 cm ) ( p = 0.001 ) . CONCLUSIONS In patients with well-preserved left ventricular function and normal wall thickness , preload reserve volumes subjectively determined by TEE corresponded to a range of filling pressures historically targeted to maximize cardiac performance ( 13 to 19 mmHg ) . In a subset of patients with increased wall thickness , however , subjective determination of preload reserve was associated with filling pressures that were higher than traditionally considered optimal ( 20 to 25 mmHg ) . Similarities in left ventricular fractional area change and end-diastolic area between these 2 groups suggest that patients with elevated filling pressures had decreased ventricular compliance and were managed correctly with higher than usual PAOPs Early goal -directed therapy is a term used to describe the guidance of intravenous fluid and vasopressor/inotropic therapy by using cardiac output or similar parameters in the immediate post-cardiopulmonary bypass in cardiac surgery patients . Early recognition and therapy during this period may result in better outcome . In keeping with this aim in the cardiac surgery patients , we conducted the present study . The study included 30 patients of both sexes , with EuroSCORE > or=3 undergoing coronary artery bypass surgery under cardiopulmonary bypass . The patients were r and omly divided into two groups , namely , control and early goal -directed therapy ( EGDT ) groups . All the subjects received st and ardized care ; arterial pressure was monitored through radial artery , central venous pressure through a triple lumen in the right internal jugular vein , electrocardiogram , oxygen saturation , temperature , urine output per hour and frequent arterial blood gas analysis . In addition , cardiac index monitoring using FloTrac and continuous central venous oxygen saturation using PreSep was used in patients in the EGTD group . Our aim was to maintain the cardiac index at 2.5 - 4.2 l/min/m2 , stroke volume index 30 - 65 ml/beat/m2 , systemic vascular resistance index 1500 - 2500 dynes/s/cm5/m2 , oxygen delivery index 450 - 600 ml/min/m2 , continuous central venous oximetry more than 70 % , stroke volume variation less than 10 % ; in addition to the control group parameters such as central venous pressure 6 - 8 mmHg , mean arterial pressure 90 - 105 mmHg , normal arterial blood gas analysis values , pulse oximetry , hematocrit value above 30 % and urine output more than 1 ml/kg/h . The aims were achieved by altering the administration of intravenous fluids and doses of inotropic or vasodilator agents . Three patients were excluded from the study and the data of 27 patients analyzed . The extra volume used ( 330+/-160 v/s 80+/-80 ml , P=0.043 ) number of adjustments of inotropic agents ( 3.4+/-1.5 v/s 0.4+/-0.7 , P=0.026 ) in the EGDT group were significant . The average duration of ventilation ( 13.8+/-3.2 v/s 20.7+/-7.1 h ) , days of use of inotropic agents ( 1.6+/-0.9 v/s 3.8+/-1.6 d ) , ICU stay ( 2.6+/-0.9 v/s 4.9+/-1.8 d ) and hospital stay ( 5.6+/-1.2 v/s 8.9+/-2.1 d ) were less in the EGDT group , compared to those in the control group . This study is inconclusive with regard to the beneficial aspects of the early goal -directed therapy in cardiac surgery patients , although a few benefits were observed Initial therapy of shock in the emergency department ( ED ) emphasizes the normalization of physiologic variables such as heart rate ( HR ) , mean arterial pressure ( MAP ) , and central venous pressure ( CVP ) rather than restoration of adequate tissue oxygenation . After hemodynamic stabilization of MAP , CVP , and HR , the authors examined tissue oxygenation as indicated by continuous central venous oximetry ( SCVO2 ) , lactic acid concentration , and shock index ( SI ) . Sixteen consecutive nonr and omized patients presenting to the ED of a large urban hospital in shock ( MAP < 60 mm Hg , HR > 120 beats/min , and altered sensorium ) were initially resuscitated with fluid , blood , inotropes , and /or vasoactive drug therapy to normalize MAP , CVP , and HR . In addition , SCVO2 , arterial lactate concentration , and SI were measured after completion of resuscitation in the ED . Eight patients ( group no. 1 ) had inadequate tissue oxygenation reflected by low SCVO2 ( less than 65 % ) . Four patients in group no. 1 had elevated arterial lactic acid concentration . All group no. 1 patients had an elevated SI ( > 0.7 ) suggesting persistent impairment of left ventricular stroke work . Eight patients ( group no. 2 ) had normal or elevated SCVO2 ( > 65 % ) . In group no. 2 , arterial lactic acid concentration was elevated in six and SI in seven patients . Normalization of hemodynamic variables does not adequately reflect the optimal endpoint of initial therapy in shock in the ED . Most ( 94 % ) of these patients continue to have significant global ischemia and cardiac dysfunction as indicated by reduced SCVO2 and elevated lactic acid concentration and SI . Systemic tissue oxygenation should be monitored and optimized in the ED in these critically ill patients . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Early goal -directed therapy for severe sepsis or septic shock improves outcomes but requires placement of a central venous catheter to measure central venous pressure ( CVP ) , which may delay timely resuscitation and cause catheter-related complications . In addition , nonintensivists may not start early aggressive fluid resuscitation because of difficulty estimating CVP and concerns for inadvertent volume overload . OBJECTIVE To determine if the CVP target of 8 to 12 mm Hg can be accurately assessed using noninvasive ultrasound to measure the internal jugular vein aspect ratio ( height/width ) . DESIGN Prospect i ve observational study . SETTING Two academic medical centers . PARTICIPANTS Nineteen euvolemic volunteers and a convenience sample of 44 spontaneously breathing , critically ill patients . MEASUREMENTS Ultrasound imaging of internal jugular vein aspect ratio ; invasive CVP measurement in critically ill patients . RESULTS For the volunteers , mean ( st and ard deviation [ SD ] ) aspect ratio of both the right and left internal jugular vein was 0.82 ( 0.07 ) . Bl and -Altman analysis indicated moderate intraobserver and interobserver agreement . Aspect ratio was similar for right and left sides and between men and women . In the critically ill patients , ultrasound accurately estimated a CVP of 8 mm Hg ; area under the receiver operating characteristics curve was 0.84 . For an invasively measured CVP of < 8 mm Hg , the likelihood ratio for a positive ultrasound test ( aspect ratio < 0.83 ) was 3.5 and for a negative test ( aspect ratio > or = 0.83 ) was 0.30 . CONCLUSIONS In this exploratory study , noninvasive ultrasound imaging of internal jugular vein aspect ratio accurately estimated a CVP of 8 mm Hg in spontaneously breathing , critically ill patients Background : Haemodynamic instability during off‐pump coronary artery bypass surgery ( OPCAB ) may appear rapidly , and continuous monitoring of the cardiac index ( CI ) during the procedure is advisable . With the PiCCO monitor , CI can be measured continuously and almost real time with pulse‐contour analysis and intermittently with transthoracic thermodilution . The agreement between pulmonal artery thermodilution CI ( Tpa ) , transthoracic thermodilution CI ( Tpc ) and pulse‐contour CI ( PCCI ) during OPCAB surgery has not been evaluated sufficiently BACKGROUND Our objective was to compare the effect of a restricted intravenous fluid regimen adjusted by serum lactate level with a st and ard restricted regimen on complications after major elective surgery for gastrointestinal malignancy . METHODS This is a r and omized , observer-blinded , single-center trial conducted across a time span of 13 months . A total of 299 patients were allocated to either a restricted intravenous fluid regimen with supplementary intravenous fluids given based on serum lactate level ( group A ) or a st and ard restricted regimen ( group R ) . In group A , the serum lactate level was monitored closely postoperatively to maintain a normal pre-operative serum lactate level . Group R involved patients treated with a restricted fluid regimen in whom additional fluid and electrolytes were administered when deemed necessary based on the usual clinical criteria . The primary outcome measure was complications ; the secondary measures were death and adverse effects . RESULTS Additional fluid supplementation was needed in some patients in both groups ( group A [ 28 % ] vs group R [ 26 % ] ) . In group A , the time for additional fluid infusion occurred earlier in the postoperative period than group R. Patients in group A received their first supplementary fluid treatment within the first 12 h more commonly than those in group R ( 74 % vs 37 % , respectively ; P < .004 ) . The regimen adjusted by serum lactate decreased systemic postoperative complications in group A versus group R ( 10 % vs 22 % , respectively ; P = .023 ) but not overall total complications ( 23 % vs 33 % , respectively ; P = .090 ) . In contrast , in patients who required additional fluid infusion , the difference in complications between the 2 groups was greater ( overall complication , 45 % vs 85 % , respectively ; P = .023 ; major complication , 16 % vs 44 % , respectively ; P = .018 ; systemic complications , 19 % vs 63 % , respectively ; P = .001 ) . One patient died in group A and 4 died in group R ( 1 % vs 4 % , respectively ; P = .206 ) . CONCLUSION A fluid-restricted regimen after elective gastrointestinal operations for malignancy may lead to fluid insufficiency and low tissue perfusion in up to 28 % of patients . Close monitoring of serum lactate levels with adjustment of intravenous fluid administration intraoperatively and in the early postoperative period may improve the early detection and correction of inadequate tissue perfusion , thereby decreasing the rate of complications OBJECTIVE Continuous measurement of cardiac output ( CCO ) is of great importance in the critically ill . However , pulmonary artery thermodilution has been question ed for possible complications associated with right heart catheterization . Furthermore , measurements are delayed in the continuous mode during rapid hemodynamic changes . A new pulmonary artery catheter CCO device ( Aortech , Bellshill , Scotl and ) enabling real-time up date of cardiac output was compared with 2 different , less-invasive methods of CCO determination , esophageal Doppler and pulse contour analysis . DESIGN Prospect i ve , observational study . SETTING University hospital , single institution . PARTICIPANTS Patients scheduled for elective coronary artery bypass grafting ( CABG ) . INTERVENTIONS None . MEASUREMENTS AND MAIN RESULTS CCO measurements were analyzed using a Bl and -Altman plot . Bias between CCO and pulse contour cardiac output ( PCCO ) , and Doppler-derived cardiac output ( UCCO ) was ( mean + /- 1 SD ) -0.71 + /- 1 L/min versus -0.15 + /- 1.09 L/min , and between UCCO and PCCO -0.58 + /- 1.06 L/min . Bias was not significantly different among methods , nor were comparative values before and after cardiopulmonary bypass ( p > 0.05 ) . CONCLUSIONS Agreement between the CCO method and both less-invasive measurements was clinical ly acceptable . There were no adverse events associated with the use of either device BACKGROUND Ever since Charles Baxter 's recommendations the st and ard regime for burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn in the first 24h following the thermal injury . A growing number of studies on invasive monitoring in burn shock , however , have raised a debate regarding the adequacy of this regime . The purpose of this prospect i ve , r and omised study was to compare goal -directed therapy guided by invasive monitoring with st and ard care ( Baxter formula ) in patients with burn shock . PATIENTS AND METHODS Fifty consecutive patients with burns involving more than 20 % body surface area were r and omly assigned to one of two treatment groups . The control group was resuscitated according to the Baxter formula ( 4 ml/kg BW/% BSA burn ) , the thermodilution ( TDD ) group was treated according to a volumetric preload endpoint ( intrathoracic blood volume ) obtained by invasive haemodynamic monitoring . RESULTS The baseline characteristics of the two treatment groups were similar . Fluid administration in the initial 24h after burn was significantly higher in the TDD treatment group than in the control group ( P = 0.0001 ) . The results of haemodynamic monitoring showed no significant difference in preload or cardiac output parameters . Signs of significant intravasal hypovolemia as indicated by subnormal values of intrathoracic and total blood volumes were present in both treatment groups . Mortality and morbidity were independent on r and omisation . CONCLUSION Burn shock resuscitation due to the Baxter formula leads to significant hypovolemia during the first 48 h following burn . Haemodynamic monitoring results in more aggressive therapeutic strategies and is associated with a significant increase in fluid administration . Increased crystalloid infusion does not improve preload or cardiac output parameters . This may be due to the fact that a pure crystalloid resuscitation is incapable of restoring cardiac preload during the period of burn shock BACKGROUND Although aggressive fluid hydration prevents a decrease in renal cortical perfusion ( RCP ) during laparoscopic donor nephrectomy , excess fluid is deleterious . We assessed whether goal -directed fluid administration , based on hemodynamic measures , would maintain RCP during pneumoperitoneum with less fluid loading . METHODS In a pilot study of 7 pigs , goal -directed fluid administration was guided by monitoring of stroke volume ( SV ) by esophageal Doppler measurement . During 15 mmHg CO(2 ) pneumoperitoneum , a bolus of 5 mL/kg 0.9 % NaCl was given when SV decreased to 90 % of baseline . Next , 18 pigs were r and omized into 3 groups : low fluid ( 5 mL/kg per hour ) , high fluid ( 25 mL/kg per hour ) and goal directed . Urine output , heart rate , mean arterial pressure , cardiac output , SV , and RCP were recorded every 15 minutes . RESULTS Pilot data revealed mean RCP ( mL/min per 100 g ) was maintained ( 40 vs 39 ) during pneumoperitoneum using goal -directed therapy . In the r and omized study , RCP was decreased in the low fluid group ( 43 vs 29 ; P= .02 ) , but maintained in the high ( 46 vs 40 ) and goal -directed ( 42 vs 39 ) groups . Mean fluid administered in the goal -directed group during pneumoperitoneum was 10 mL/kg and only 3 of 6 of pigs required boluses . Urine output was decreased in all 3 groups . CONCLUSION A goal -directed strategy during pneumoperitoneum allows for tailored fluid administration and maintains RCP with lower volumes of intravenous fluid 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 ABSTRACT We evaluated whether a goal -directed protocol , without measurement of central venous oxygen saturation , would improve survival in medical intensive care unit ( ICU ) patients with septic shock . This is a prospect i ve , controlled study in a 24-bed medical ICU at a tertiary care hospital . From a total of 241 consecutive patients with septic shock , 224 were r and omly assigned to receive therapy with or without a written protocol using central venous pressure , mean arterial pressure , and urine output as therapeutic goals . Baseline characteristics were similar between groups . Implementation of goal -directed therapy caused a more rapid reversal of persistent shock ( 47 ± 22.8 vs. 65.4 ± 32.1 h , P = 0.006 ) and decreases of ICU ( 50 % vs. 67.2 % , P = 0.009 ) and in-hospital ( 53.7 % vs. 71.6 % , P = 0.006 ) mortality rates compared with non- goal -directed therapy . Patients receiving goal -directed therapy also had less risk for developing central nervous system or renal failure than patients without . Patients with goal -directed therapy received more fluid during the period of persistent shock ( 136.2 ± 119 vs. 88.6 ± 57.7 mL h−1 , P = 0.034 ) and less delay in vasopressor administration ( 78 ± 22.2 vs. 104.4 ± 29 min , P = 0.001 ) than patients with non- goal therapy . Implementation of a goal -directed protocol improves survival and clinical outcomes in ICU patients with septic shock . These benefits may arise from adequate fluid resuscitation , earlier vasopressor administration , rapid shock reversal , and protection of major organ function . With central venous oxygen saturation measurement to detect tissue perfusion , the clinical outcomes may be further improved 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 A predictive index based on cardiorespiratory-monitored values of an earlier series of postoperative critically ill patients was tested in prospect i ve clinical trials and found to be reasonably accurate , sensitive , and specific . The hypothesis was tested that the median values of patients who survived life-threatening postoperative conditions , rather than the norms of unstressed , healthy volunteer subjects , constitute a first approximation to the optimal therapeutic goals for critically ill postoperative patients . In a prospect i ve series of 223 consecutive , critically ill postoperative patients , normal values were used as the therapeutic goals of the control patients , whereas the median values of surviving patients were used as the goals of therapy for the protocol group . The clinical conditions of the protocol group were at least as severe as those of the control group , but the mortality was significantly less in the protocol group ( 12.5 percent ) than in the control group ( 35 percent ) ; the number of life-threatening complications were also greater in the control group . These data suggest that at least half and possibly as much as two thirds of postoperative deaths may be due to physiologic problems that can be identified , described , predicted , and prevented . Therapy for the critically ill patient should be defined by physiologic criteria , and administration of therapy should be monitored to attain prophylactically optimal physiologic goals rather than giving therapy after a deficiency has occurred to attain normal values BACKGROUND Treatment of burn shock according to empirical resuscitation formulas is still considered the gold st and ard , and the burn community does not advocate the use of invasive cardiorespiratory monitoring in general . As a consequence , data dealing with early postburn hemodynamics are sparse , and only few studies have paid attention to the topic of end-point burn shock resuscitation . However , recent studies have suggested that burn survival may be improved when invasive monitoring is used to guide fluid therapy during the shock phase . MATERIAL S AND METHODS In an observational study of 24 patients with severe burns , the transpulmonary double indicator dilution technique was used for semi-invasive hemodynamic monitoring . The clinical utility of the intrathoracic blood volume ( ITBV ) as an end-point variable for fluid resuscitation was evaluated , comparing correlation of filling pressure obtained by a pulmonary artery catheter and intrathoracic blood volume to cardiac index and oxygen delivery . In addition fluid volume predicted by the Parkl and burn formula was compared with the actual fluid volume given when ITBV was used as end point for resuscitation . RESULTS ITBV-guided resuscitation was associated with restoration of preload and peripheral delivery of oxygen within 24 hours in the majority of patients . Augmentation of ITBV was significantly correlated with changes in cardiac index and oxygen transport rate . No such correlation could be demonstrated for the conventional preload parameters such as central venous pressure and pulmonary capillary wedge pressure . Thus , ITBV seemed in burned , hypovolemic patients a better indicator of the preload component of the cardiac output than the conventional preload parameters obtained with the pulmonary artery catheter . Significantly larger volumes of crystalloids than predicted by the Parkl and formula were administered when ITBV was used as end point for resuscitation . The extravascular lung water remained normal during this extraordinary high volume load . CONCLUSION ITBV may be a reliable preload indicator to guide volume therapy in life-threatening burns , and end-point-fixed resuscitation to this parameter seems to be associated with significantly higher fluid administration than calculated compared with traditional burn formulas . The effects of burn resuscitation to fixed end points on survival and multiple organ failure should be evaluated in future r and omly assigned trials OBJECTIVE To test the hypothesis that perioperative plasma volume expansion would preserve gut mucosal perfusion during elective cardiac surgery . DESIGN Prospect i ve r and omized open study . SETTING Teaching hospital . PATIENTS Sixty American Society of Anesthesiology grade III patients with a preoperative left ventricular ejection fraction of 50 % or greater undergoing elective cardiac surgery . INTERVENTIONS Patients were allocated r and omly to a control or protocol group . The control group was treated according to st and ard practice s. After induction of general anesthesia , the protocol group received , in addition , 200-mL boluses of a 6 % hydroxyethyl starch solution to obtain a maximum stroke volume . This procedure was repeated every 15 minutes until the end of surgery , except when the patient underwent cardiopulmonary bypass . MEASUREMENTS AND RESULTS Cardiac stroke volume was estimated by an esophageal Doppler system , and gastric mucosal perfusion was measured by tonometric assessment of gastric intramucosal pH in all patients . Patients were followed up postoperatively until discharge from the hospital or death . The incidence of gut mucosal hypoperfusion ( gastric intramucosal pH < 7.32 ) at the end of surgery was reduced in the protocol group ( 7 % vs 56 % ) ( P < .001 ) , as were the number of patients in whom major complications developed ( 0 vs 6 ) ( P = .01 ) , mean number of days spent in the hospital ( 6.4 [ range , 5 to 9 ] vs 10.1 [ range , 5 to 48 ] ) ( P = .011 ) , and mean number of days spent in the intensive care unit ( 1 [ range , 1 to 1 ] vs 1.7 [ range 1 to 11 ] days ) ( P = .023 ) . CONCLUSIONS Perioperative plasma volume expansion with colloid during cardiac surgery , guided by esophageal Doppler measurement of cardiac stroke volume , reduced the incidence of gut mucosal hypoperfusion . This group of patients also had an improved outcome when compared with controls BACKGROUND : The intrathoracic blood volume index ( ITBVI ) and central venous pressure ( CVP ) are routinely used to predict fluid responsiveness in critically ill patients with acute circulatory failure ( systolic blood pressure < 90 mm Hg or vasopressor requirement ) . However , they have never been compared . METHODS : In this prospect i ve interventional study , we included 35 ( 21 men ) mechanically ventilated and se date d patients with acute cardiovascular failure requiring cardiac output measurement ( transpulmonary thermodilution technique ) . Fluid responsiveness was defined as an increase in stroke index ( cardiac output/heart rate/body surface area ) ≥15 % . Receiver operating characteristic curves were generated for ITBVI and CVP . RESULTS : Fluid challenge induced a stroke index increase ≥15 % in 18 ( 51 % ) patients ( responders ) . At baseline , no studied hemodynamic variables were different between responders and nonresponders . The areas under the receiver operating characteristic curves were 0.64 [ 95 % CI : 0.46–0.80 ] for ITBVI and 0.68 [ 95 % CI : 0.50–0.83 ] for CVP , without any statistical difference ( P = 0.73 ) . The best cut-off values for CVP and ITBVI were 9 mm Hg ( sensitivity = 61 % ; specificity = 82 % ) and 928 mL · m−2 ( sensitivity = 78 % ; specificity = 53 % ) . CONCLUSION : ITBVI is similar to CVP in its ability to predict fluid responsiveness in critically ill patients with acute circulatory failure 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 Making a diagnosis is the bread and butter of clinical practice , but in light of the number of tests now available to clinician , diagnosing illness has become a complicated process . Guidelines for making an evidence -based diagnosis abound , but those making recommendations about diagnostic tests or test strategies must realize that clinicians require support to make diagnostic decisions that they can easily implement in daily practice . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group has developed a rigorous , transparent , and increasingly adopted approach for grading the quality of research evidence and strength of recommendations to guide clinical practice . This editorial summarizes GRADE 's process for developing recommendations for tests ( 1 ) . Clinicians are trained to use tests for screening and diagnosis ; identifying physiologic derangements ; establishing a prognosis ; and monitoring illness and treatment response by assessing signs and symptoms , imaging , biochemistry , pathology , and psychological testing techniques ( 2 ) . Sensitivity , specificity , positive predictive value , likelihood ratios , and diagnostic odds ratios are among the challenging terms that diagnostic studies typically deliver to clinicians , and all have to do with diagnostic accuracy . Not only do clinicians have difficulties remembering the definitions and calculations for these terms , application of the concepts to individual patients is often complicated . Many clinicians order a test despite uncertainty about how to interpret the result , and they also contribute to testing errors by incorrectly ordering tests ( 3 , 4 ) . GRADE 's framework for developing recommendations for diagnostic management studies is based on what is needed for practical clinical applicationthat is , how to weigh the benefits and harms of ordering and using a diagnostic test in caring for patients ( 1 ) . The approach begins with specifying the PICO : the relevant population ( P ) , diagnostic intervention or test ( I ) ( including its purpose , such as triage , replacement , or an add-on test ) , comparison test ( C ) , and patient-important outcomes ( O ) related to the use of a test for a focused clinical question . If a test fails to improve patient-important outcomes , there is no reason to use it , whatever its accuracy . For example , the results of genetic testing for Huntington chorea , an untreatable condition , may provide either welcome reassurance that a patient will not have the condition or the ability to plan for his future knowing that he will sadly fall victim ( 1 ) . Here , the ability to plan is analogous to an effective treatment , and the benefits of planning need to be balanced against the downsides of receiving an early diagnosis ( 5 - 7 ) . The best evidence of test performance comes from large r and omized trials of diagnostic strategies that directly measure patient-important outcomes ( 1 ) . However , these trials are few and far between : An informal review of the Cochrane data base of r and omized trials revealed < 100 such studies . Therefore , most recommendations about diagnostic testing are based on an implicit 2-step process of how the accuracy of a test indirectly changes patient-important outcomes . In the first step , a diagnostic-test accuracy study ( Figure ) , patients may receive both a new test and a reference test ( i.e. , the best available method for detecting the target condition ) . Investigators can then calculate the accuracy of the test compared with the reference test ( first step ) . In the second step , judgments about the patient importance of test accuracy are based on the consequences of being correctly or incorrectly classified as having or not having the disease . These include the benefits and harms of receiving treatment or follow-up tests for those correctly classified as having the disease , reassurance or receipt of other follow-up tests for those correctly classified as not having the disease , receipt of unnecessary treatment or additional tests for those incorrectly classified as having the disease , delayed or no treatment for those incorrectly classified as not having the disease , and any adverse effects of the diagnostic test ( e.g. , from invasive tests ) . Those making recommendations about diagnostic tests must then compare patient-important outcomes ( and costs ) in all patients receiving the new test with all patients receiving the old , or comparator , test . For the first step ( i.e. , assessing test accuracy ) , there are well-described method ological criteria for assessing risk for bias in an estimate of test accuracy , ideally based on a systematic review of relevant studies . For instance , studies of diagnostic test accuracy with a low risk for bias enroll consecutive patients for whom there is legitimate diagnostic uncertaintythat is , the type of patients to whom clinicians would apply the test in the course of regular clinical practice . If studies fail this criterion ( e.g. , only enroll patients with severe disease and healthy controls ) , the apparent accuracy of a test is likely to be misleadingly high ( 8 , 9 ) . The second step shown in the Figure is , in most situations , based on judgments of test accuracy as a surrogate for patient-important outcomes . The key issue about these judgments is that they should be made transparent to those using the recommendations . For example , in the diagnosis of suspected acute urolithiasis , well- design ed studies demonstrate fewer false-negative results with noncontrast helical computed tomography ( CT ) than with intravenous pyelography ( IVP ) ( 10 ) . However , those ureteric stones that CT detects but IVP misses are smaller and therefore are more likely to spontaneously pass . Before r and omized trials evaluating outcomes in patients treated for smaller stones , evidence from observational studies was of lower quality . Thus , it remained uncertain how patients were affected by missed cases and follow-up of incidental findings unrelated to renal calculi with CT . Recommendations about using one test ( IVP ) over the other ( helical CT ) were based on judgments of how the cases that were detected or missed would fare with or without treatment ( 11 ) . These judgments were likely to be based on indirect evidence and would be less certain than judgments based on direct evidence from a r and omized trial comparing the 2 tests . The GRADE approach requires making these judgments about the relation between accuracy and patient-important outcomes transparent . The example of IVP versus helical CT for patients with suspected acute shows exemplifies how the quality of evidence for an accurate test would be down grade d because of the lack of direct evidence on patient-important outcomes . Uncertainty about patient-important consequences and associated uncertainty about benefits and harms would probably have result ed in weak GRADE recommendations about the use of IVP compared with helical CT . Those making recommendations using the GRADE approach should also explicitly consider judgments and evidence about the values and preferences that patients attach to important consequences , as described more fully elsewhere ( 1 ) . Acknowledgments : This work was partially funded by a The human factor , mobility and Marie Curie Actions Scientist Reintegration European Commission Grant ( IGR 42192 ) GRADE to Dr. Schnemann ObjectiveS epsis mortality is closely linked to multi-organ failure , and impaired microcirculatory blood flow is thought to be pivotal in the pathogenesis of sepsis-induced organ failure . We hypothesized that changes in microcirculatory flow during resuscitation are associated with changes in organ failure over the first 24 h of sepsis therapy . Design Prospect i ve observational study . Setting Emergency Department and Intensive Care Unit . Participants Septic patients with systolic blood pressure < 90 mmHg despite intravenous fluids or lactate ≥4.0 mM/L treated with early goal -directed therapy ( EGDT ) . Measurements and results We performed Sidestream Dark Field ( SDF ) videomicroscopy of the sublingual microcirculation <3 h from EGDT initiation and again within a 3–6 h time window after initial . We imaged five sites and determined the mean microcirculatory flow index ( MFI ) ( 0 no flow to 3 normal ) blinded to all clinical data . We calculated the Sequential Organ Failure Assessment ( SOFA ) score at 0 and 24 h , and defined improved SOFA a priori as a decrease ≥2 points . Of 33 subjects ; 48 % improved SOFA over 0–24 h. Age , APACHE II , and global hemodynamics did not differ significantly between organ failure groups . Among SOFA improvers , 88 % increased MFI during EGDT , compared to 47 % for non-improvers ( P = 0.03 ) . Median change in MFI was 0.23 for SOFA improvers versus −0.05 for non-improvers ( P = 0.04 ) . Conclusions Increased microcirculatory flow during resuscitation was associated with reduced organ failure at 24 h without substantial differences in global hemodynamics . These data support the hypothesis that targeting the microcirculation distinct from the macrocirculation could potentially improve organ failure in sepsis STUDY OBJECTIVE Abnormal ( both low and high ) central venous saturation ( ScvO(2 ) ) is associated with increased mortality in emergency department ( ED ) patients with suspected sepsis . METHODS This was a secondary analysis of 4 prospect ively collected registries of ED patients treated with early goal -directed therapy-based sepsis resuscitation protocol s from 4 urban tertiary care hospitals . Inclusion criteria were sepsis , hypoperfusion defined by systolic blood pressure less than 90 mm Hg or lactate level greater than or equal to 4 mmol/L , and early goal -directed therapy treatment . ScvO(2 ) levels were stratified into 3 groups : hypoxia ( ScvO(2 ) < 70 % ) ; normoxia ( ScvO(2 ) 71 % to 89 % ) ; and hyperoxia ( ScvO(2 ) 90 % to 100 % ) . The primary exposures were initial ScvO(2 ) and maximum ScvO(2 ) achieved , with the primary outcome as inhospital mortality . Multivariate analysis was performed . RESULTS There were 619 patients who met criteria and were included . For the maximum ScvO(2 ) , compared with the mortality rate in the normoxia group of 96 of 465 ( 21 % ; 95 % confidence interval [ CI ] 17 % to 25 % ) , both the hypoxia mortality rate , 25 of 62 ( 40 % ; 95 % CI 29 % to 53 % ) and hyperoxia mortality rate , 31 of 92 ( 34 % ; 95 % CI 25 % to 44 % ) were significantly higher , which remained significant in a multivariate modeling . When the initial ScvO(2 ) measurement was analyzed in a multivariate model , only hyperoxia was significantly higher . CONCLUSION The maximum ScvO(2 ) value achieved in the ED ( both abnormally low and high ) was associated with increased mortality . In multivariate analysis for initial ScvO(2 ) , the hyperoxia group was associated with increased mortality , but not the hypoxia group . This study suggests that future research aim ed at targeting methods to normalize high ScvO(2 ) values by therapies that improve microcirculatory flow or mitochondrial dysfunction may be warranted 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 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 |
11,724 | 16,235,339 | AUTHORS ' CONCLUSIONS There is insufficient evidence to confirm or refute that albendazole co-administered with DEC or ivermectin is more effective than DEC or ivermectin alone in clearing microfilariae or killing adult worms .
Albendazole combined with ivermectin appears to have a small effect on microfilaraemia , but this was not consistently demonstrated . | BACKGROUND Mass treatment with albendazole co-administered with another antifilarial drug is part of a global programme to eliminate lymphatic filariasis .
We sought reliable evidence of the effects of albendazole on the disease and the parasite .
OBJECTIVES To summarize the effects of albendazole alone or in combination with antifilarial drugs for clinical treatment and community control of lymphatic filariasis . | Filariasis control programmes are moving towards a strategy of repeated single-dose mass treatment of endemic population s. Using a combination , such as albendazole ( ALB ) to diethylcarbamazine ( DEC ) gives both macrofilaricidal and anti-helmintic activity . However , the safety of the combination versus DEC alone should be established in field studies in large population s prior to incorporation into national programmes . The present study compared the safety , tolerability , and efficacy of single doses of DEC 6 mg/kg + ALB placebo with DEC 6 mg/kg + ALB 400 mg in population s living in two filariasis endemic villages in the district of Wardha in western India . The study was double blind , parallel group , and r and omized . Safety and tolerability study were studied in males and females older than 5 years . Safety was assessed by monitoring if adverse events ( AEs ) over 5 days affected daily acivities . Subjects in the 2 treatment groups experienced insignificantly different effects on daily activities and the combination was shown to be safe . Efficacy was evaluated by microfilaraemia ( Mf ) , immunochromatographic test ( ICT ) and ultrasonography ( USG ) at 0 , 3 , 6 , and 12 months of follow up . The efficacy study enrolled 103 male patients ( aged 18 - 50 years ) in microfilariae positive , clinical disease and asymptomatic , amicrofilaremic groups . There was no significant difference in efficacy between groups at 12 months . Within the Mf positive group , significant differences were seen in microfilaraemia ( P < 0.001 ) with both treatments , and in USG ( P < 0.001 and P < 0.004 respectively ) , at 12 months . The present field study has shown the combination of DEC + ALB to be as safe as the single drug DEC and thus the combination can be put in use in the national filariasis control programmes . Both drugs were adequately absorbed . The study at present does not provide evidence for the greater efficacy of the combination at 12 months follow up . While the safety of the combination has been ascertained , the incorporation or otherwise of ALB into national programmes for greater efficacy must await results of studies with longer follow up This r and omized , placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths ( albendazole ) and lymphatic filariasis ( ivermectin ) . Children were infected with Ascaris ( 29.2 % ) , Trichuris ( 42.2 % ) , and hookworm ( 6.9 % ) , with 54.7 % of children having one or more of these parasites . Wuchereria bancrofti microfilaria were found in 13.3 % of the children . Children were r and omly assigned to treatment with placebo , albendazole , ivermectin , or combined therapy . Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone . Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone . Only combination therapy result ed in significantly greater gains in height ( hookworm-infected children ) or weight ( Trichuris-infected children ) compared with the placebo group . Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and result ed in nutritional benefits not found with either drug alone The efficacy of two strategies for control of Bancroftian filariasis using selective rather than community-wide diethylcarbamazine ( DEC ) chemotherapy was evaluated and compared in two endemic communities of north-eastern Tanzania , with pretreatment microfilariae ( mf ) prevalences of 22 % and 38 % , and geometric mean intensities ( GMIs ) of 668 mf/ml and 735 mf/ml of blood . All mf-positive cases in the first community were offered treatment with 6 mg of DEC/kg of body weight a day for 12 days ( group 1 ) , and those in the second community were offered treatment with two doses of 6 mg of DEC/kg of body weight at an interval of six months ( group 2 ) . The effect of treatment was followed both among those treated and at the community level . In treated individuals , there was a rapid decrease in the mf load that was significantly greater among those receiving the 12-day st and ard dose . One year after the start of treatment , the mf clearance rates were 59 % and 39 % and the GMIs were reduced by 99 % and 97 % among treated individuals in groups 1 and 2 , respectively . However , at the community level , the mf prevalences were 16.3 % and 27.9 % ( reduced by 27 % and 26 % ) and the GMIs were 129 mf/ml and 224 mf/ml ( reduced by 81 % and 70 % ) one year after the start of treatment with the two regimens , respectively , suggesting that transmission continued at a significant level in the villages after treatment . The limitations of selective chemotherapy are discussed , and it is argued that strategies based on mass DEC chemotherapy would be more effective in reducing the microfilarial load in the community and thereby in reducing transmission Forty male Polynesian W. bancrofti carriers with mf counts greater than or equal to 20/ml were treated with a single ivermectin 50 , 100 , 150 or 200 mcg/kg dose . Following therapy , mf levels fell to less than 1 % of pretreatment levels in the carriers treated with the 3 highest doses . After one month , negativation rate was 40 % in patients treated with a 50 mcg/kg dose , significantly lower than in patients treated with higher doses . Recurrence of microfilaremia was observed by 3 months , mf recurrence percentages were significantly lower in patients treated with the 3 highest doses than in patients treated with a 50 mcg/kg dose . At 6 months , mf recurrence percentages reached 49.8 , 12.6 , 14 and 5.4 % of pretreatment levels in carriers treated with 50 , 100 , 150 and 200 mcg/kg , respectively . No significant difference was observed between mf levels by group at 6 and 12 months . With respect to efficacy , a dose greater than or equal to 100 mcg/kg appeared superior to 50 mcg/kg dose ; no significant difference between the 3 highest doses was observed . Some patients developed headache , myalgia and fever within 24 hours following therapy , none of adverse reactions were considered serious . In vector Ae . polynesiensis fed on carriers 6 months after treatment , average numbers of mf ingested and average numbers of L3 cephalic larvae were lower than those observed in mosquitoes fed on non-treated carriers with comparable mf counts . ( ABSTRACT TRUNCATED AT 250 WORDS In a ' blinded ' trial ( in Sri Lanka , 1996 - 98 ) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection , the safety , tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared : albendazole 400 mg with ivermectin 200 micrograms/kg , albendazole 400 mg with diethylcarbamazine citrate ( DEC ) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg . Treated subjects were followed-up for 24 months . This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis . All subjects had pre-treatment microfilaria ( mf ) counts over 100/mL. All 3 treatments significantly reduced mf counts , with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment . Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti ; albendazole-DEC combination had the greatest activity according to this test , with antigen levels decreasing to 30.5 % of pre-treatment antigen levels , 24 months after therapy . All 3 treatments were clinical ly safe and well tolerated . These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic population This r and omized , placebo-controlled trial investigated the tolerance , efficacy , and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis . Children were infected with Ascaris ( 30.7 % ) , Trichuris ( 53.4 % ) , and hookworm ( 9.7 % ) with 69.9 % having more than one of these parasites . A total of 15.8 % of the children had Wuchereria bancrofti microfilariae . Children were r and omly assigned treatment with placebo , albendazole ( ALB ) , diethylcarbamazine ( DEC ) , or combined therapy . The combination of DEC/ALB reduced microfilarial density compared with placebo , ALB , or DEC ( P < or = 0.03 ) . Albendazole and DEC/ALB reduced the prevalence of Ascaris , Trichuris , and hookworm more than placebo or DEC ( P < or = 0.03 ) . Among Trichuris-infected children , those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo ( P < or = 0.05 ) . Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia , DEC/ALB was more effective than DEC , with no increase in severity of adverse reactions Several new chemotherapeutic tools are now available for the control of lymphatic filariasis . Combinations of single doses of antifilarial drugs are generally superior to single drugs . The efficacy and safety of albendazole in combination with diethylcarbamazine ( DEC ) or ivermectin , for the treatment of Brugia malayi infection , were investigated , for the first time , in an open , hospital-based study . Fifty-one asymptomatic microfilaraemics ( with 108 - 4034 microfilariae/ml ; median = 531 ) of both sexes and aged 14 - 70 years were r and omly allocated to receive single-dose treatments of ivermectin ( 200 micrograms/kg ) with diethylcarbamazine ( DEC ; 6 mg/kg ) , ivermectin ( 200 micrograms/kg ) with albendazole ( 400 mg ) , DEC ( 6 mg/kg ) with albendazole ( 400 mg ) , or albendazole ( 400 mg ) alone . Albendazole alone had no effect on the microfilarial levels at the 1-year follow-up but both groups given DEC had significantly lower microfilaraemias ( P < 0.015 and P < 0.02 ) than that given ivermectin with albendazole . Overall , 47%-64 % of those given DEC but only 14 % of those given ivermectin with albendazole appeared to be amicrofilaraemic 1 year post-treatment . The adverse reactions seen in the study were mild , transient and qualitatively similar to those seen earlier with ivermectin and DEC . The combination of DEC and albendazole , both well tested drugs , offers a new option for countries such as India where there is no onchocerciasis or loiasis and where ivermectin may not be immediately available . The direct and indirect effects of albendazole on intestinal helminths would be additional benefits The efficacy of re-treatment with the combination of ivermectin ( 150 - 200 micrograms/kg bodyweight ) and albendazole ( 400 mg ) on Wuchereria bancrofti microfilaraemia was assessed in 1997 - 99 in 4 groups of individuals from coastal Ghana , which 1 year previously had received a primary treatment with placebo ( n = 38 ) , albendazole ( n = 39 ) , ivermectin ( n = 34 ) or combination of albendazole and ivermectin ( n = 42 ) , respectively . One year after the re-treatment , an overall mean reduction in microfilarial intensity of 76.2 % in relation to the intensity before re-treatment was observed , with no statistical significant difference between the 4 groups . The groups given primary treatment with placebo or the drug combination showed re-treatment reductions which were lower ( 72.5 % and 69.8 % , respectively ) but not statistically significantly different from the reduction observed 1 year after the primary treatment with the combination ( 86.7 % ) . The efficacy of the combination treatment thus appeared to be largely independent of the type of primary treatment given and multiplicative when used repeatedly To assess the efficacy of diethylcarbamazine ( DEC ) in clearing Wuchereria bancrofti microfilariae ( mf ) from the circulation , we conducted a single blind hospital-based therapeutic trial of 3 DEC regimens . All patients were assessed by filtration of 1 mL of venous blood taken before and 1 , 3 , 6 and 12 months after DEC administration . The efficacy of a 12 d course of 6 mg/kg DEC once daily was identical to that of a similar course with 2 mg/kg given 3 times daily , indicating that split-dose treatment does not improve mf clearance over single daily drug administration . Microfilarial densities in patients treated only once with 6 mg/kg DEC remained significantly higher at 1 , 3 , and 6 months after treatment . However , all 3 treatment regimens proved equally effective in controlling microfilaraemia after 12 months , when 41 , 42 and 40 % of patients in the 3 treatment groups were amicrofilaraemic . These results suggest that a single DEC dose of 6 mg/kg administered annually or biannually may be a suitable regimen to control bancroftian filariasis in Recife , Brazil The effect of single-dose ivermectin ( 150 - 200 micrograms/kg ) and albendazole ( 400 mg ) treatment alone and in combination on Wuchereria bancrofti microfilaraemia , antigenaemia and clinical manifestations was compared 12 months after treatment in a double-blind placebo-controlled field trial carried out in Ghana in 1996 - 98 , to evaluate the potential of these treatments for control . Both ivermectin and combination treatments result ed in pronounced reductions in microfilaraemia among individuals who were microfilaria positive before treatment . Among individuals who were positive for circulating filarial antigen before treatment , antigen levels increased considerably over the 1-year period after treatment in the placebo group , whereas they decreased in the ivermectin and combination groups . However , the post-treatment difference reached statistical significance in neither microfilaraemia nor antigenaemia between the ivermectin and the combination groups . Albendazole treatment alone showed only a minor effect on microfilaraemia and antigenaemia . No effect of the treatments on the incidence of new cases of microfilaraemia or antigenaemia , or on clinical manifestations , was observed . Both ivermectin and combination treatment thus appeared effective for control of W. bancrofti infections , but the difference in efficacy between the 2 treatments after 12 months appeared to be minimal Abstract The pharmacokinetics , safety and tolerability of single , oral doses of diethylcarbamazine ( DEC ) and albendazole , given alone or in combination , were investigated in a double-blind , r and omized and placebo-controlled trial involving 42 amicrofilaraemic subjects living in an area of India where lymphatic filariasis is endemic . The subjects ( 34 males and eight females , aged 18 - 52 years and weighing 46 - 66.5 kg ) were r and omly allocated to one of the three drug groups . Fourteen were given just DEC ( 6 mg/kg ) , another 14 were given just albendazole ( 400 mg ) and the remaining 14 were given both DEC ( 6 mg/kg ) and albendazole ( 400 mg ) . Blood sample s for pharmacokinetic study were collected at specified intervals before and after drug administration . Plasma concentrations of DEC and albendazole/albendazole sulphoxide were estimated using gas chromatography and HPLC , respectively . The safety and tolerability of the treatments were evaluated through clinical and laboratory assessment s. Both the DEC and albendazole were well tolerated when given alone or in combination , no adverse events being observed . In all three treatment groups , the drugs were rapidly absorbed from the gastro-intestinal tract although there was marked inter-individual variation . The pharmacokinetics of DEC , albendazole and albendazole sulphoxide were similar , whether each drug was given alone or in combination . These results indicate that there is no adverse pharmacokinetic or pharmacodynamic reason why DEC and albendazole should not be co-administered to control lymphatic filariasis To assess directly the effect of various doses of diethylcarbamazine ( DEC ) on adult Wuchereria bancrofti , 31 infected men were r and omly assigned to receive an initial single DEC dose of 1 mg/kg ( n = 7 ) , 6 mg/kg ( n = 10 ) , or 12 mg/kg ( n = 14 ) . Beginning 7 d later , the dosage of DEC and duration of treatment were progressively increased for 7 - 10 weeks . Physical examinations were performed to detect scrotal nodules and the scrotal area was examined by ultrasound ( 7.5 MHz transducer ) to monitor the ' filaria dance sign ' ( FDS ) , the characteristic pattern of adult worm movement . Of 53 adult worm ' nests ' that were detected by ultrasound , 22 ( 41.5 % ) were DEC-sensitive ( FDS became non-detectable and a nodule became palpable at the site ) ; 20 ( 37.7 % ) were not sensitive ( FDS remained unchanged and detectable and no nodule developed ) , and 11 ( 20.8 % ) showed mixed responses ( FDS remained detectable but a palpable nodule developed ) . All but one sensitive or mixed response occurred within 1 week after the initial single dose . Of 39 ' nests ' in men who initially received a single 6 or 12 mg/kg dose of DEC , 20 ( 51.3 % ) had sensitive responses compared to 2 ( 14.3 % ) of 14 ' nests ' in men who received a single 1 mg/kg dose ( P = 0.04 ) . Above 6 mg/kg , the macrofilaricidal effect of DEC did not increase with dose ; a significant proportion of adult W. bancrofti were not susceptible to DEC during the study period BACKGROUND Lymphatic filariasis and intestinal helminth infections are important disorders in tropical areas . Periodic treatment with albendazole is now used in many school-based intestinal helminth-control programmes . However , few such programmes exist for lymphatic filariasis , despite evidence that single-dose treatment with ivermectin can greatly reduce the concentration of Wuchereria bancrofti microfilariae in the blood for months to years . We aim ed to assess the potential for school-based control of lymphatic filariasis by investigating the efficacy and tolerability or combined ivermectin and albendazole in Haitian schoolchildren . METHODS In January , 1996 , we collected 832 20 microL capillary blood sample s for inclusion in a r and omised controlled study from children aged 5 - 11 years , and examined them by microscopy for W bancrofti microfilariae . Infected children were r and omly assigned treatment with placebo ( n = 29 ) , a single 200 - 400 micrograms/kg dose of ivermectin ( mean , 273 micrograms/kg , n = 28 ) , 400 mg albendazole ( n = 29 ) , or a combination of 200 - 400 micrograms/kg ivermectin and 400 mg albendazole ( n = 24 ) . Children with high concentrations of microfilariae in the blood were admitted to hospital and adverse reactions were monitored for 3 - 5 days , otherwise children were examined at school or during a visit to their home . 4 months after treatment , we examined blood sample s again for microfilariae . FINDINGS 113 microfilaraemic children were enrolled ( mean age 7.8 years ) . 4 months after treatment , the proportion of children who remained positive for microfilariae was significantly lower in the ivermectin plus albendazole group ( four [ 17 % ] ) , but there were no significant changes in the other three groups ( 20 [ 69 % ] placebo , 22 [ 76 % ] albendazole alone , 17 [ 61 % ] ivermectin alone remained positive ; p = 0.004 ) . Geometric mean microfilarial concentration decreased from 9.3 to 5.3 per 20 microL blood among children who received placebo ; from 15.5 to 1.5 per 20 microL blood among those who received ivermectin only ( p = 0.032 ) ; from 14.1 to 5.1 per 20 microL blood among those who received albendazole alone ; and from 13.7 to 0.3 per 20 microL blood among those who received both ivermectin and albendazole ( p = 0.0001 ) . Systemic adverse reactions did not differ significantly between children who received ivermectin alone and those who were treated with ivermectin and albendazole [ corrected ] . INTERPRETATION For children with W bancrofti microfilaraemia , combined treatment with ivermectin and albendazole was more effective than treatment with ivermectin only , with no measurable increase in severity of adverse reactions Repeated , single , oral doses of combinations of ivermectin , diethylcarbamazine ( DEC ) or albendazole are recognized as important tools for parasite control in lymphatic filariasis . In order to assess the effects of re-treatment using these combinations in Brugia malayi infections , 40 asymptomatic microfilaraemics were re-treated at the end of the first year , with an additional , single , dose of the combination they had previously received . They were then followed-up for another year . The subjects , of both sexes and aged 14–70 years , each received a two-drug combination : ivermectin ( 200 µg/kg ) with DEC ( 6 mg/kg ) ; ivermectin ( 200 µg/kg ) with albendazole ( 400 mg ) ; or DEC ( 6 mg/kg ) with albendazole ( 400 mg ) . The kinetics of microfilarial clearance were similar to that seen during the first treatment , the members of the two groups given DEC having less intense microfilaraemias , 1 year after the re-treatment , than those given ivermectin with albendazole ( P<0.001 for each comparison ) . At this time , the two DEC groups also had a higher proportion of amicrofilaraemic individuals ( 22 of 26 ) than the ivermectin + albendazole group ( three of nine ) . There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment . In countries such as India , where there is no co-endemicity of onchocerciasis or loiasis , the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole . Where there is no access to ivermectin , transmission control must be based on DEC alone or in combination with albendazole To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 micrograms/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment , the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife , Brazil . Follow-up at one year indicated equivalent efficacy for the 20- , 100- , and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means of 13 - 25 % of pretreatment levels . Adverse clinical reactions ( predominantly fever , headache , weakness , and myalgia ) occurred to some degree in almost all patients but generally lasted only 24 - 48 hr and were easily managed symptomatically . Adverse reactions were significantly milder in those receiving the lowest ( 20 micrograms/kg ) ivermectin dose , and they were significantly correlated with individuals ' pretreatment microfilaremia levels in all groups . Posttreatment eosinophilia was a regular feature of the response to treatment , with the magnitude and kinetics also proportional to pretreatment microfilarial levels . Transient pulmonary function abnormalities ( 16 of 42 , 38 % ) , liver enzyme elevations ( 10 of 43 , 23 % ) , and hematuria ( 9 of 42 , 22 % ) developed posttreatment , but all cleared without significant complications . The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin , that the drug 's systemic adverse reactions are essentially those result ing from parasite clearance , and that the intensity of these reactions can be significantly reduced by using the low ( 20 micrograms/kg ) dose of ivermectin . This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications Examination of 1829 children from 6 primary schools in coastal Tanzania revealed overall Wuchereria bancrofti microfilaria ( mf ) and circulating filarial antigen ( CFA ) prevalences of 17.3 % and 43.7 % , respectively . A r and omized double-blind field trial with a single dose of ivermectin ( 150 - 200 microg/kg body weight ) alone or in combination with albendazole ( 400 mg ) was subsequently carried out among these children . Both treatment regimens result ed in a considerable decrease in mean mf intensities , with overall reductions being slightly but statistically significantly higher for the combination than for ivermectin alone . The difference in effect between the two treatment regimens was most pronounced at 6 months , whereas it was minor at 12 months after treatment . The relative effect of treatment on mean CFA units was less pronounced than on mf . For both treatment regimens , reductions in CFA intensity appeared to be higher in children who were both CFA and mf positive before treatment , which may suggest that treatment mainly affected the survival and /or production of mf , rather than the survival of adult worms . New cases of infection appeared after treatment with both regimens among the pre-treatment mf and CFA negative children . Adverse reactions were few and mild in both groups , and mainly reported from pre-treatment mf and CFA positive children . The alarmingly high prevalence of W. bancrofti infection in primary school children highlights the importance of also determining the reversibility of already acquired early lesions , and the development of new measures and strategies to specifically protect children from later developing clinical disease The efficacy and safety of single-dose ivermectin ( 150 - 200 micrograms/kg ) and albendazole ( 400 mg ) treatment administered separately or in combination for Wuchereria bancrofti infections were assessed in 1996 - 98 in a r and omized double-blind placebo-controlled field trial in Ghana : 1425 individuals from 4 lymphatic filariasis-endemic villages , 340 of whom were microfilaria (mf)-positive before treatment , were r and omized into 4 groups to receive albendazole alone , ivermectin alone , combination of albendazole and ivermectin , or placebo , respectively . Individuals were followed for 5 days after treatment to record any adverse reactions , and the effect of treatment on microfilaraemia was monitored in night-blood sample s after 3 , 6 and 12 months . Treatment efficacy was analysed for 236 mf-positive individuals who had > or = 100 mf/mL of blood and who were also present for examination at 12 months after treatment . Compared to the placebo group , the ivermectin and combination groups both showed statistically significant reductions in geometric mean mf intensities at the follow-up examinations ( to 6.7 % and 0.9 % , 9.9 % and 6.9 % , and 21.7 % and 11.4 % of pre-treatment levels , respectively , at 3 , 6 and 12 months after treatment ) . Compared to the ivermectin group , however , the reduction in the combination group was significantly greater only at 3 months after treatment , but not after 6 or 12 months . The albendazole group showed a slow but non-significant reduction over the same period . Adverse reactions were few and mostly mild ( no severe reactions were recorded ) , and no significant differences were observed between the treatment groups . Both ivermectin and combination treatment thus appeared effective and safe for treatment of lymphatic filariasis , but the difference in efficacy was minor and the study did not provide clear evidence for the combination drug therapy , as compared to ivermectin therapy alone , to be superior for control of lymphatic filariasis To determine the tolerance to diethylcarbamazine ( DEC ) treatment of patients with Bancroftian filariasis , 193 individuals ( 138 asymptomatic microfilaraemic , 30 amicrofilaraemic diseased patients and 25 asymptomatic amicrofilaraemic endemic residents ) were enrolled in a prospect i ve trial with different dose schedules , in a hospital and outpatient clinic setting in Brazil . Systemic adverse reactions , localized adverse reactions , and side effects , related to microfilariae , adult worms and the drug itself , were evaluated . Systemic reactions occurred irrespective of the DEC dose and schedule in about 40 % of the microfilariae carriers , but not in amicrofilaraemic diseased patients or residents ; they usually consisted of microscopic haematuria , followed by fever and malaise . Localized reactions were manifested by the appearance of inflammatory reactions , mainly in the scrotal area . Nodules containing degenerating adult worms developed mainly in the scrotal lymphatics of microfilaraemic patients , diseased amicrofilaraemic patients , and residents . Drowsiness , which increased with higher doses of DEC , was the most common side effect in both microfilaraemic and amicrofilaraemic individuals , followed by nausea and gastric upset . The results indicate that the occurrence of systemic and local adverse reactions was unrelated to either the dose of DEC or the pretreatment microfilarial density . The severity of systemic reactions was proportional to the microfilarial density . Side effects were dependent on the drug dosage irrespective of infection status |
11,725 | 21,475,042 | A benefit from a salt-reduced diet in patients with high blood pressure is not proven with regard to patient-relevant outcomes based on systematic review s and RCTs published up to 2010 .
The results indicate a blood pressure-lowering effect through reduced salt intake in hypertensive patients | OBJECTIVE We assessed the benefits and harm of reduced salt intake in patients with essential hypertension focusing on patient-relevant outcomes and blood pressure . | A reduction in salt intake lowers blood pressure . However , most previous trials were in whites with few in blacks and Asians . Salt reduction may also reduce other cardiovascular risk factors ( eg , urinary albumin excretion , arterial stiffness ) . However , few well-controlled trials have studied these effects . We carried out a r and omized double-blind crossover trial of salt restriction with slow sodium or placebo , each for 6 weeks , in 71 whites , 69 blacks , and 29 Asians with untreated mildly raised blood pressure . From slow sodium to placebo , urinary sodium was reduced from 165±58 ( ±SD ) to 110±49 mmol/24 hours ( 9.7 to 6.5 g/d salt ) . With this reduction in salt intake , there was a significant decrease in blood pressure from 146±13/91±8 to 141±12/88±9 mm Hg ( P<0.001 ) , urinary albumin from 10.2 ( IQR : 6.8 to 18.9 ) to 9.1 ( 6.6 to 14.0 ) mg/24 hours ( P<0.001 ) , albumin/creatinine ratio from 0.81 ( 0.47 to 1.43 ) to 0.66 ( 0.44 to 1.22 ) mg/mmol ( P<0.001 ) , and carotid-femoral pulse wave velocity from 11.5±2.3 to 11.1±1.9 m/s ( P<0.01 ) . Subgroup analysis showed that the reductions in blood pressure and urinary albumin/creatinine ratio were significant in all groups , and the decrease in pulse wave velocity was significant in blacks only . These results demonstrate that a modest reduction in salt intake , approximately the amount of the current public health recommendations , causes significant falls in blood pressure in all 3 ethnic groups . Furthermore , it reduces urinary albumin and improves large artery compliance . Although both could be attributable to the falls in blood pressure , they may carry additional benefits on reducing cardiovascular disease above that obtained from the blood pressure falls alone Sodium restriction can reduce blood pressure in hypertensive patients . The present study indicates that if hypertension is well controlled then the reemergence of hypertension can be decreased by the use of a reduced sodium intake . The present paper demonstrates that in such patients on a normal salt diet , 90 % become hypertensive within 6 months while only 40 % of people on a reduced sodium diet become hypertensive . It is proposed that a high sodium intake activates a number of amplifiers that causes a shift of the dose-response curve to sodium to the left and if not prevented or interrupted leads to the development of hypertension BACKGROUND Few trials have evaluated the effects of reduced sodium intake in older individuals , and no trial has examined the effects in relevant subgroups such as African Americans . PATIENTS AND METHODS The effects of sodium reduction on blood pressure ( BP ) and hypertension control were evaluated in 681 patients with hypertension , aged 60 to 80 years , r and omly assigned to a reduced sodium intervention or control group . Participants ( 47 % women , 23 % African Americans ) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication . Three months after the start of intervention , medication was withdrawn . The primary end point was occurrence of an average systolic BP of 150 mm Hg or more , an average diastolic BP of 90 mm Hg or more , the resumption of medication , or a cardiovascular event during follow-up ( mean , 27.8 months ) . RESULTS Compared with control , mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group ( P<.001 ) ; significant reductions in sodium excretion occurred in subgroups defined by sex , race , age , and obesity . Prior to medication withdrawal , mean reductions in systolic and diastolic BPs from the reduced sodium intervention , net of control , were 4.3 mm Hg ( P<.001 ) and 2.0 mm Hg ( P = .001 ) . During follow-up , an end point occurred in 59 % of reduced sodium and 73 % of control group participants ( relative hazard ratio = 0.68 , P<.001 ) . In African Americans , the corresponding relative hazard ratio was 0.56 ( P = .005 ) ; results were similar in other subgroups . In dose-response analyses , end points were progressively less frequent with greater sodium reduction ( P for trend = .002 ) . CONCLUSION A reduced sodium intake is a broadly effective , nonpharmacologic therapy that can lower BP and control hypertension in older individuals BACKGROUND The effect of dietary composition on blood pressure is a subject of public health importance . We studied the effect of different levels of dietary sodium , in conjunction with the Dietary Approaches to Stop Hypertension ( DASH ) diet , which is rich in vegetables , fruits , and low-fat dairy products , in persons with and in those without hypertension . METHODS A total of 412 participants were r and omly assigned to eat either a control diet typical of intake in the United States or the DASH diet . Within the assigned diet , participants ate foods with high , intermediate , and low levels of sodium for 30 consecutive days each , in r and om order . RESULTS Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg ( P<0.001 ) during the control diet and by 1.3 mm Hg ( P=0.03 ) during the DASH diet . Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet ( P<0.001 ) and 1.7 mm Hg during the DASH diet ( P<0.01 ) . The effects of sodium were observed in participants with and in those without hypertension , blacks and those of other races , and women and men . The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level ; and the difference was greater with high sodium levels than with low ones . As compared with the control diet with a high sodium level , the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension , and 11.5 mm Hg lower in participants with hypertension . CONCLUSIONS The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially , with greater effects in combination than singly . Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods 31 patients with a diastolic blood-pressure between 95 and 109 mm Hg have been treated for two years with a regimen involving a moderate restriction of salt in the diet . The results are compared with those in a control group and in a drug-treated group . Salt restriction has reduced the diastolic blood-pressure by 7.3+/-1.6 mm Hg , a result similar to that in patients treated with antihypertensive drugs . In the untreated group the diastolic blood-pressure rose by 1.8+/-1.1 mm Hg . Most patients did not achieve the desired amount of salt restriction and a stricter adherence to the diet might have caused further falls in blood-pressure . Excessive salt intake is probably a major cause of the epidemic of hypertension in " civilised " countries and a reduction in salt intake may help to control the epidemic . In persons with a diastolic blood-pressure between 90 and 105 mm Hg salt restriction should be tried before drugs OBJECTIVE The aim of this study was to describe the effect of intensified antihypertensive therapy based on a structured teaching and treatment programme on the prognosis of hypertensive type 1 ( insulin-dependent ) diabetic patients with kidney disease . DESIGN The study was a controlled , prospect i ve , parallel , 10-year follow-up trial . PATIENTS AND INTERVENTIONS A sequential sample of 91 hypertensive type 1 diabetic patients with overt diabetic nephropathy was prospect ively followed for 10 years . Forty-five patients ( intensified antihypertensive therapy ; IT group ) participated in an intensified antihypertensive therapy programme and 46 patients received routine antihypertensive treatment as provided by family physicians , consultants and local hospitals ( routine antihypertensive therapy ; RT group ) . OUTCOME MEASURES The main endpoint was death ; secondary endpoints were renal replacement therapy , blindness and amputation . RESULTS Blood pressure was reduced in the IT group and increased in the RT group . During the follow-up period , 29 patients died , seven in the IT group and 22 in the RT group . The survival curves were significantly different ( P = 0.0008 ) . The main causes of death were cardiac . In a multiple Cox proportional hazards model , allocation to the IT group reduced the mortality risk [ relative risk ( RR ) = 0.213 ; 95 % confidence interval 0.089 - 0.509 , P = 0.00051 , while age ( P = 0.0039 ) and mean blood pressure ( P= 0.0113 ) increased this risk . In multiple Cox or multiple logistic regression models , the risks of dialysis ( RR = 0.269 , 95 % confidence interval 0.110 - 0.656 , P = 0.0039 ) , blindness ( odds ratio = 0.158 , 95 % confidence interval 0.037 - 0.684 , P= 0.0136 ) , and amputation ( RR = 0.181 , 95 % confidence interval 0.047 - 0.703 , P= 0.0135 ) were significantly lower in the IT group compared with the RT group ( log rank P = 0.0008 ) . CONCLUSION We conclude that intensified antihypertensive treatment , based on a hypertension teaching and treatment programme , reduces long-term morbidity and mortality in patients with diabetic nephropathy BACKGROUND Although the DASH ( Dietary Approaches to Stop Hypertension ) diet has been shown to lower blood pressure ( BP ) in short-term feeding studies , it has not been shown to lower BP among free-living individuals , nor has it been shown to alter cardiovascular biomarkers of risk . OBJECTIVE To compare the DASH diet alone or combined with a weight management program with usual diet controls among participants with prehypertension or stage 1 hypertension ( systolic BP , 130 - 159 mm Hg ; or diastolic BP , 85 - 99 mm Hg ) . DESIGN AND SETTING R and omized , controlled trial in a tertiary care medical center with assessment s at baseline and 4 months . Enrollment began October 29 , 2003 , and ended July 28 , 2008 . PARTICIPANTS Overweight or obese , unmedicated out patients with high BP ( N = 144 ) . INTERVENTIONS Usual diet controls , DASH diet alone , and DASH diet plus weight management . OUTCOME MEASURES The main outcome measure is BP measured in the clinic and by ambulatory BP monitoring . Secondary outcomes included pulse wave velocity , flow-mediated dilation of the brachial artery , baroreflex sensitivity , and left ventricular mass . RESULTS Clinic-measured BP was reduced by 16.1/9.9 mm Hg ( DASH plus weight management ) ; 11.2/7.5 mm ( DASH alone ) ; and 3.4/3.8 mm ( usual diet controls ) ( P < .001 ) . A similar pattern was observed for ambulatory BP ( P < .05 ) . Greater improvement was noted for DASH plus weight management compared with DASH alone for pulse wave velocity , baroreflex sensitivity , and left ventricular mass ( all P < .05 ) . CONCLUSION For overweight or obese persons with above-normal BP , the addition of exercise and weight loss to the DASH diet result ed in even larger BP reductions , greater improvements in vascular and autonomic function , and reduced left ventricular mass . CLINICAL TRIAL REGISTRATION clinical trials.gov Identifier : NCT00571844 AIM To determine the effect on blood pressure from brisk walking with or without salt restriction in a community based sample of treated hypertensives . METHODS The intervention was undertaken in a community setting with a factorial r and omised controlled trial and blinded assessment of blood pressure . One hundred and eighty one healthy adult volunteers with a sedentary lifestyle and on pharmacological therapy for hypertension briskly walked for 40 minutes three times per week with or without salt restriction . Systolic and diastolic blood pressure were assessed at three and six months . RESULTS Of the original 208 participants 181 ( 87 % ) completed the study . significant reductions of up to 7 mm Hg were found in systolic blood pressure at 3 months for brisk walking alone ( p = 0.04 ) and salt restriction alone ( p = 0.03 ) but not for the combined intervention ( p = 0.17 ) . No significant change was found for diastolic blood pressure . There was no significant change in blood pressure at 6 months . CONCLUSIONS Simple advice on exercise and sodium restriction in a community setting can significantly lower systolic blood pressure at least for 3 months . The combination of the two interventions was less effective than each therapy alone BACKGROUND To our knowledge , no single investigation concerning the long-term effects of overweight status on the risk for hypertension , hypercholesterolemia , diabetes mellitus , and cardiovascular sequelae has been reported . METHODS Relations between categories of body mass index ( BMI ) , cardiovascular disease risk factors , and vascular disease end points were examined prospect ively in Framingham Heart Study participants aged 35 to 75 years , who were followed up to 44 years . The primary outcome was new cardiovascular disease , which included angina pectoris , myocardial infa rct ion , coronary heart disease , or stroke . Analyses compared overweight ( BMI [ calculated as weight in kilograms divided by the square of height in meters ] , 25.0 - 29.9 ) and obese persons ( BMI > or = 30 ) to a referent group of normal-weight persons ( BMI , 18.5 - 24.9 ) . RESULTS The age-adjusted relative risk ( RR ) for new hypertension was highly associated with overweight status ( men : RR , 1.46 ; women : RR , 1.75 ) . New hypercholesterolemia and diabetes mellitus were less highly associated with excess adiposity . The age-adjusted RR ( confidence interval [ CI ] ) for cardiovascular disease was increased among those who were overweight ( men : 1.21 [ 1.05 - 1.40 ] ; women : 1.20 [ 1.03 - 1.41 ] ) and the obese ( men : 1.46 [ 1.20 - 1.77 ] ; women : 1.64 [ 1.37 - 1.98 ] ) . High population attributable risks were related to excess weight ( BMI > or = 25 ) for the outcomes hypertension ( 26 % men ; 28 % women ) , angina pectoris ( 26 % men ; 22 % women ) , and coronary heart disease ( 23 % men ; 15 % women ) . CONCLUSIONS The overweight category is associated with increased relative and population attributable risk for hypertension and cardiovascular sequelae . Interventions to reduce adiposity and avoid excess weight may have large effects on the development of risk factors and cardiovascular disease at an individual and population level 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 The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice . After screening and a run-in phase of 6 - 8 weeks , a total of 77 previously undiagnosed mildly hypertensive patients were identified . Half of them were r and omized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage ; the others were r and omized to receive no advice . The patients were followed up for 12 months with quarterly visits . A total of 56 patients ( 72.7 % ) completed the study , 26 on a low-sodium diet ( LD ) and 30 on their usual diet ( UD ) . At each visit in the diet phase , patients provided 24h urine , which was analysed for volume and sodium concentration in order to assess their sodium intake . Blood pressure , heart the rate and body weight were recorded . The mean urinary sodium excretion for all diet phase visits overlapped in the two groups ( 177.0 + /- 32.9 vs. 169.3 + /- 49.4 mEq/24h respectively in the LD and UD groups ) . Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group ( 144.2 + /- 11.1/91.6 + /- 6.4 and 148.0 + /- 13.7/95.6 + /- 4.7 mmHg respectively , P less than 0.01 ) . Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions , the only ones suitable for widespread application in general practice BACKGROUND AND PURPOSE The relationship between the pattern of alcohol intake and the risk of stroke is unclear , in particular the increased risk observed in abstainers and the possible protective effect of light to moderate drinking . For that reason , we examined in a large prospect i ve study the role of alcohol consumption in the risk of a first major cerebrovascular event ( stroke ) . METHODS We prospect ively studied 7735 middle-aged men drawn from general practice s in 24 British towns . With exclusion of those who had recall of physician diagnosis of ischemic heart disease or stroke , data were available for 7273 men all followed for 13.5 years , with 216 major stroke events ( fatal and nonfatal ) . RESULTS Compared with occasional drinkers , nondrinkers ( lifelong abstainers plus ex-drinkers ) had an increased risk of stroke even after adjustment for age , lifestyle factors , and preexisting cardiovascular disease ( relative risk [ RR ] = 1.6 ; 95 % CI , 1.0 to 2.7 ) . All regular weekend drinkers ( 1 to 2 , 3 to 6 , and > 6 drinks/d ) and daily 1 to 2 and 3 to 6 drinkers showed no significant difference in adjusted risk of stroke compared with occasional drinkers . Heavy drinkers ( daily > 6 drinks ) showed significantly increased risk evident within the first 8 years of follow-up only ( RR = 1.9 ; 95 % CI , 1.0 to 3.5 ) ; however , this finding was attenuated after additional adjustment for systolic blood pressure ( RR = 1.5 ; 95 % CI , 0.8 to 2.7 ) . Information obtained 5 years after screening was used to separate lifelong abstainers and ex-drinkers . On subsequent 8.5 years of follow-up , both groups showed similar increased risk ( RR = 1.5 ) compared with occasional drinkers , but the risk in ex-drinkers was reduced after adjustment for lifestyle factors and cardiovascular disease status ( RR = 1.2 ) . Lifelong abstainers , however , showed an increase in risk after adjustment of 1.8 ( 95 % CI , 0.7 to 4.6 ) . CONCLUSIONS Heavy drinking is associated with an increased risk of total stroke that is largely mediated through blood pressure . The apparent increased risk seen in lifelong abstainers but not in ex-drinkers or occasional drinkers is unexplained but is unlikely to be attributed to abstinence from alcohol . There is no convincing evidence that light or moderate drinking is beneficial for stroke risk compared with occasional drinking CONTEXT Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly , but there is a paucity of evidence from r and omized controlled trials in support of this recommendation . OBJECTIVE To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension . DESIGN R and omized controlled trial . PARTICIPANTS A total of 975 [ corrected ] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication . SETTING Four academic health centers . INTERVENTION The 585 obese participants were r and omized to reduced sodium intake , weight loss , both , or usual care , and the 390 nonobese participants were r and omized to reduced sodium intake or usual care . Withdrawal of antihypertensive medication was attempted after 3 months of intervention . MAIN OUTCOME MEASURE Diagnosis of high blood pressure at 1 or more follow-up visits , or treatment with antihypertensive medication , or a cardiovascular event during follow-up ( range , 15 - 36 months ; median , 29 months ) . RESULTS The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake ( relative hazard ratio , 0.69 ; 95 % confidence interval [ CI ] , 0.59 - 0.81 ; P<.001 ) and , in obese participants , among those assigned vs not assigned to weight loss ( relative hazard ratio , 0.70 ; 95 % CI , 0.57 - 0.87 ; P<.001 ) . Relative to usual care , hazard ratios among the obese participants were 0.60 ( 95 % CI , 0.45 - 0.80 ; P<.001 ) for reduced sodium intake alone , 0.64 ( 95 % CI , 0.49 - 0.85 ; P=.002 ) for weight loss alone , and 0.47 ( 95 % CI , 0.35 - 0.64 ; P<.001 ) for reduced sodium intake and weight loss combined . The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups . CONCLUSION Reduced sodium intake and weight loss constitute a feasible , effective , and safe nonpharmacologic therapy of hypertension in older persons BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P<0.001 ) . After 10 years , the weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P<0.001 ) . Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline Objective . Previous studies , mainly evaluating short-term very low salt diets , suggest that salt restriction may influence glucose and insulin metabolism , catecholamines , renin , aldosterone , and lipid levels adversely . The authors wanted to explore whether sodium restriction for eight weeks influenced insulin secretion unfavourably , and evaluate the efficacy and safety of such treatment also in terms of other parameters important in the management of hypertensive patients . Design . A double-blind r and omized controlled parallel group design ed trial . All participants received dietary advice aim ed at a moderate salt-restricted diet . Half of the participants received salt capsules , the others received identical placebo capsules . Setting . General practice . Subjects . Forty-six hypertensive patients inadequately controlled by drug treatment . Main outcome measures . Fasting serum insulin C-peptide and glucose and levels of these measures after oral glucose , blood pressure , serum aldosterone and lipids , peripheral resistance , and skin conductance . Results . Salt restriction did not influence glucose and insulin metabolism , aldosterone , or lipid levels adversely . We observed better blood pressure regulation in the low salt group than in the high salt group , with a systolic and diastolic blood pressure difference of 5/5 mmHg after eight weeks . The difference was only statistically significant for diastolic blood pressure , p 0.02 . Conclusion . This study revealed a modest diastolic blood pressure reducing effect of moderate sodium restriction . This reduction was obtained without any apparent unfavourable side effects such as increased insulin secretion , impaired glucose tolerance or dyslipidaemia |
11,726 | 26,544,539 | These outcomes are likely all related to the lower incidence of preterm birth seen with other tocolytics , which for all these comparisons were betamimetics .
There is no evidence that to suggest that ethanol is an effective tocolytic compared to placebo .
Ethanol appears to be inferior to betamimetics for preventing preterm birth in threatened preterm labor .
Ethanol is generally no longer used in current practice due to safety concerns for the mother and her baby . | BACKGROUND Preterm birth is the leading cause of death and disability in newborns worldwide .
A wide variety of tocolytic agents have been utilized to delay birth for women in preterm labor .
One of the earliest tocolytics utilized for this purpose was ethanol infusion , although this is not generally used in current practice due to safety concerns for both the mother and her baby .
OBJECTIVES To determine the efficacy of ethanol in stopping preterm labor , preventing preterm birth , and the impact of ethanol on neonatal outcomes . | Using data collected as a follow-up to a r and omized trial , Melissa Gladstone and colleagues show that during the first two years of life , infants born preterm in southern Malawi are disadvantaged in terms of mortality , growth , and development The effectivity of Partusisten or ethanol long term respectively short term tocolysis by combination of a retrospective and a prospect ive-r and omised study has been compared . Long term tocolysis was better than short term tocolysis . Partusisten was more effective than ethanol . Partusisten long term tocolysis was different to other forms or treatment with a high significance . 70 % of newborns after Partusisten long term tocolysis had a birth weight of 2500 g or more Abstract . In this study , 194 imminent premature deliveries were treated . The pregnancies were in the 28th to 36th week . Uterine contractions were demonstrable in all patients and amniotic membranes were intact . All patients were treated with bedrest . Two betasympathomimetics were used in a double‐blind study : Nylidrin hydrochloride ( 43 cases ) and Isoxuprine hydrochloride ( 60 cases ) . A placebo was given to 41 patients , and ethyl alcohol to 50 patients . Intravenous and intramuscular treatment given in the hospital was continued with oral administration ' at home , and follow‐up examinations were repeated at short intervals . Taking a minimum birth weight of 2 500 g as the criteria of successful treatment , the success rate in the placebo group was 71 % , in the Nylidrin hydrochloride group 86 % , the Isoxuprine hydrochloride group 75 % and the alcohol group 70 % . When premature delivery was postponed 7 days , the pregnancy advanced , to the 37th week or later in 73 , 77 , 62 and 56 % in their respective groups . The betasympathomimetics , especially the Nylidrin hydrochloride , were in every respect more efficient than placebo or alcohol . The therapeutic effect of alcohol was no better than that obtained with placebo . From the fetal point of view , the drugs used in the present study showed no adverse effects Ninety-two women in preterm labor were r and omly assigned to either terbutaline or ethanol . In women with intact membranes , terbutaline was significantly more effective than ethanol in preventing progressive cervical dilation during the first 36 hours of treatment while betamethasone was given to the mother . Additionally , pregnancy was maintained significantly longer in women with intact membranes who were treated with terbutaline ( 15 + /- 4 days ) rather than with ethanol ( 10 + /- 3 days ) . However , only 18 % of women in each treatment group maintained their pregnancy beyond 36 weeks ' gestation . In women with ruptured membranes and cervical dilation less than 4 cm , terbutaline was significantly better than ethanol in maintaining pregnancy for a minimum of 36 hours . Serious maternal side effects were not observed with terbutaline or ethanol , although a majority of women also received betamethasone . Neither drug caused serious adverse neonatal effects Intravenous salbutamol and ethanol were compared as treatments for preterm labour , 42 patients being assigned r and omly to salbutamol and 46 to ethanol . There was no statistically significant difference in outcome between patients in the two groups , the mean delay in delivery achieved being 15 days with salbutamol and 20 days with ethanol . Neither treatment was very effective since only 10 patients given salbutamol and 14 given ethanol had their delivery postponed to 37 weeks or later . Salbutamol was more rapidly acting than ethanol but produced more cardiovascular side effects Abstract Ethanol was administered intravenously to 26 near-term and term pregnant patients before labour and during early labour in various doses to determine the effect on bilirubin levels in the newborn . 18 patients at term , free from obstetric complications , were r and omly selected as controls . A statistically significant reduction of serum-bilirubin levels in infants in the third , fourth , and fifth days of life was observed in the group whose mothers were treated with more than 100 g. of ethanol prior to delivery . The findings suggest a simple , safe , and expedient agent which may be used to prevent raised levels of bilirubin in the newborn — levels which may affect mental and motor development in the first year of the infant 's life 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 Abstract A controlled study , design ed to permit sequential analysis , of the use of ethanol to inhibit premature labor was carried out . Only a total of 42 patients was required to prove the efficacy of the ethanol treatment statistically In travenous magnesium sulfate and alcohol were compared as treatments for premature labor . A successful treatment was the absence of contractions for a 24 hour interval . Early treatment was found to be essential for successful management of premature labor . There is a significant correlation of cervical dilatation at the onset of treatment to success at controlling premature labor . There was no statistically significant relation to weeks of gestation or parity to success at controlling premature labor . In this study magnesium sulfate was the better agent for controlling premature labor A r and omized controlled study was carried out at three medical centers to compare the efficacy and side effects of ethanol and ritodrine in the treatment of threatened premature labor . One hundred and thirty-five patients judged to be between the twentieth and thirty-sixth week of gestation and presenting with clinical symptoms of premature labor were included . Sixty-seven patients were treated with intravenous infusion of 10 per cent ethanol . Sixty-eight patients were treated with intravenous infusion of ritodrine for 12 hours followed by oral ritodrine . If labor recurred prematurely , up to two additional courses of ethanol or ritodrine were given . Delivery was postponed for more than 72 hours in 49 of 67 patients ( 73 per cent ) with ethanol and in 61 of 68 patients ( 90 per cent ) with ritodrine ; this difference was significant . Patients in the ethanol group gained a mean of 27.6 days while patients in the ritodrine group gained a mean of 44.0 days . Fifty-four per cent of the ethanol group and 72 per cent of the ritodrine group carried their infants to 36 weeks of gestation . Five infants in the ethanol group and one infant in the ritodrine group died from respiratory distress syndrome . The most frequent side effect of ethanol were nausea and vomiting . The most frequent side effects of ritodrine were tachycardia and blood pressure changes which were easily controlled by lowering the infusion rate . Ethanol and ritodrine were both found to be effective inhibitors of premature labor with ritodrine giving the most favorable results |
11,727 | 12,137,670 | REVIEW ER 'S CONCLUSIONS At present , radiofrequency thermal ablation is an insufficiently studied intervention for HCC | BACKGROUND Hepatocellular carcinoma ( HCC ) is one of the most common malignant diseases worldwide .
The only possibly curative therapeutic option is surgical resection .
Due to impaired liver function and /or anatomical reasons only a low percentage of patients can be treated surgically .
For the remainder , several non-surgical treatment approaches have been developed .
In addition to percutaneous ethanol injection , transarterial interventions , and several medical interventions , radiofrequency thermal ablation has been investigated in coagulating HCC lesions .
OBJECTIVES To evaluate the effects of radiofrequency thermal ablation in HCC patients with respect to clinical ly relevant outcomes ( mortality , rate of recurrences , adverse events , quality of life , and duration of hospital stay ) . | PURPOSE To evaluate the effectiveness of radio-frequency ( RF ) ablation and percutaneous microwave coagulation ( PMC ) for treatment of hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS Seventy-two patients with 94 HCC nodules were r and omly assigned to RF ablation and PMC groups . Thirty-six patients with 48 nodules were treated with RF ablation , and 36 patients with 46 nodules were treated with PMC . Therapeutic effect , residual foci of untreated disease , and complications of RF ablation and PMC were prospect ively evaluated with statistical analyses . RESULTS The number of treatment sessions per nodule was significantly lower in the RF ablation group than in the PMC group ( 1.1 vs 2.4 ; P < .001 ) . Complete therapeutic effect was achieved in 46 ( 96 % ) of 48 nodules treated with RF ablation and in 41 ( 89 % ) of 46 nodules treated with PMC ( P = .26 ) . Major complications occurred in one patient treated with RF ablation and in four patients treated with PMC ( P = .36 ) . During follow-up ( range , 6 - 27 months ) , residual foci of untreated disease were seen in four of 48 nodules treated with RF ablation and in eight of 46 nodules treated with PMC . No significant difference in rates of residual foci of untreated disease was noted ( P = .20 , log-rank test ) . CONCLUSION RF ablation and PMC thus far have had equivalent therapeutic effects , complication rates , and rates of residual foci of untreated disease . However , RF tumor ablation can be achieved with fewer sessions BACKGROUND Radiofrequency ablation ( RFA ) is emerging as a new therapeutic method for management of solid tumors . We report here our experience in the use of this technique for management of primary and secondary unresectable liver cancers . METHODS Thirty-five patients with liver cancers were considered not suitable for curative resection at presentation : 8 with primary hepatocellular carcinoma ( [ HCC ] 6 HCC and 2 fibrolamellar ) ; 27 with metastatic liver cancer ( 17 colorectal carcinoma and 10 others ) . They were treated either with radiofrequency heat ablation ( Radionics Europe N.V. , Wettdren , Belgium ) alone percutaneously and /or intraoperatively or in conjunction with surgical resections . The quality of RFA was based on the subjective feeling of whether the tumor was completely destroyed or not . The effectiveness of RFA was assessed according to clinical findings , radiographic images , and tumor markers at follow-up . RESULTS In 8 primary liver cases , 4 patients with a high level of alpha fetoprotein ( AFP ) benefited from the RFA with a 83.3 % to 99.7 % reduction of AFP . One with fibrolamellar hepatocellular carcinoma died 2 months after an incomplete percutaneous RFA from recurrence . The rest all had stable disease at the time of follow-up ( mean 10.4 months ) . In patients with colorectal liver metastases , there were 4 deaths : 1 patient died postoperatively on the 30th day from a severe chest infection having shown a considerable reduction of carcinoembryonic antigen level ( CEA , 8 versus 36 microg/L ) ; 3 died from local and systemic disease , 1 at 12 months and 2 at 1 month , having had an incomplete RFA . The others had stable disease at follow-up ( mean 7.6 months ) . Five patients underwent liver resections successfully with the application of RFA for residual lesions in the remaining contralateral lobe . In 10 patients with other liver tumors , 7 patients had stable disease at follow-up ( mean 13.4 months ) ; 1 patient had evidence of local and systemic recurrence 10 months after surgical resections with the intraoperative RFA and 2 patients died of systemic recurrence of disease 3 and 6 months after RFA alone . Two patients had liver resections in conjunction with the intraoperative RFA . The mean follow-up in our series was 8.5 months . CONCLUSION Radiofrequency heat ablation is useful as a primary treatment for unresectable liver cancers . The procedure can be used to treat the small residual tumor load in the contralateral lobe following liver resection in those considered unresectable at the first presentation . This new therapeutic strategy seems to increase surgical resectability in patients judged unresectable BACKGROUND AND STUDY AIMS Radiofrequency ( RF ) thermal ablation has been applied almost exclusively through the percutaneous approach under radiological/external ultrasound guidance . We have embarked on a programme of laparoscopic ultrasound-guided RF ablation of hepatic tumours in view of the potential advantages of this approach , i. e. reduced heat sink effect , greater precision and improved assessment of the thermal ablative zone . PATIENTS AND METHODS RF thermal ablation using the Zomed International generator and multielectrode probes in two patients with hepatoma arising on a background of cirrhosis and in eight patients with multiple deposits from primary colorectal cancer . RESULTS Total ablation was performed in two patients with hepatoma and 7/8 patients with secondary deposits . Total ablation with a minimum of 0.5-cm margin was achieved in 32 lesions . No complications were encountered postoperatively and all patients were discharged within 2 days of the intervention . One patient in whom thermal ablation was not completed has since died of progressive disease , eight appear to be free of tumour ( follow-up 6 - 20 months ) but one patient has developed further secondary hepatic deposits . CONCLUSIONS The initial experience with laparoscopic ultrasound-guided RF ablation of hepatic tumours indicates its safety and therapeutic potential in patients with inoperable hepatic tumours PURPOSE To compare the effectiveness of radio-frequency ( RF ) thermal ablation with that of percutaneous ethanol injection ( PEI ) for the treatment of small hepatocellular carcinoma ( HCC ) in patients with cirrhosis . MATERIAL S AND METHODS A series of 102 patients with hepatic cirrhosis and either single HCC 5 cm in diameter or smaller or as many as three HCCs each 3 cm or smaller ( overall number of lesions , 142 ) r and omly received either RF ablation ( n = 52 ) or PEI ( n = 50 ) as the sole first-line anticancer treatment . Mean follow-up was 22.9 months + /- 9.4 ( SD ) in the RF group and 22.4 months + /- 8.6 in the PEI group . Prognostic value of treatment techniques was assessed with univariate and multivariate Cox proportional hazards regression models . RESULTS One- and 2-year survival rates were 100 % and 98 % in the RF group and 96 % and 88 % in the PEI group , respectively ( univariate relative risk [ RR ] = 0.20 ; 95 % CI : 0.02 , 1.69 ; P = .138 ) . One- and 2-year local recurrence-free survival rates were 98 % and 96 % in the RF group and 83 % and 62 % in the PEI group , respectively ( univariate RR = 0.17 ; 95 % CI : 0.06 , 0.51 ; P = .002 ) . One- and 2-year event-free survival rates were 86 % and 64 % for the RF group and 77 % and 43 % for the PEI group , respectively ( univariate RR = 0.48 ; 95 % CI : 0.27 , 0.85 ; P = .012 ) . RF treatment was confirmed as an independent prognostic factor for local recurrence-free survival rates with multivariate analysis ( adjusted RR = 0.20 ; 95 % CI : 0.05 , 0.73 ; P = .015 ) . CONCLUSION RF ablation is superior to PEI with respect to local recurrence-free survival rates In two consecutive series of patients with hepatocellular carcinoma ( HCC ) , we compared clinico-laboratory and ultrasonographic characteristics , diagnostic work-up , survival of untreated patients and , finally , therapeutic choices . In addition of the clinical examination , we tested for blood serum alpha-fetoprotein levels , HBsAg and anti-HCV antibodies . Ultrasonography was performed in all the patients . In most cases , a pathologic diagnosis was obtained by ultrasound-guided fine-needle biopsy . As curative treatment we considered open surgery , percutaneous alcohol injection and radio frequency thermal ablation . In the second series , we observed an increased number of patients with compensated cirrhosis and with small HCCs , therefore the number of patients undergoing a potentially curative treatment was higher . The percentage of multiple tumours was comparable in two series implying the presence of two kinds of HCC , different ¿ ab initio ' . The survival rate of untreated patients was better in the second series |
11,728 | 24,357,528 | Interventions that demonstrated reductions in subsequent utilization targeted children with specific chronic conditions , providing enhanced inpatient feedback and education reinforced with postdischarge support . | BACKGROUND Reducing avoidable readmission and posthospitalization emergency department ( ED ) utilization has become a focus of quality -of-care measures and initiatives .
For pediatric patients , no systematic efforts have assessed the evidence for interventions to reduce these events .
PURPOSE We sought to synthesize existing evidence on pediatric discharge practice s and interventions to reduce hospital readmission and posthospitalization ED utilization . | Background : The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze . Methods : A prospect i ve , r and omised , partially blinded , controlled trial was design ed at two secondary care centres . Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children 's ward or attendance at an accident and emergency department or children 's ( emergency ) assessment unit ( A&E/CAU ) with a primary diagnosis of acute severe asthma or wheezing were recruited . 101 children were r and omised into the control group and received usual care and 99 were assigned to the intervention group and received : ( 1 ) a pre-school asthma booklet ; ( 2 ) a written guided self-management plan ; and ( 3 ) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s ) and child . Subjects were assessed at 3 , 6 , and 12 months . The main outcomes were GP consultation rates , hospital re-admissions , and attendances at A&E/CAU . Secondary outcomes included disability score , caregivers ' quality of life , and parental knowledge of asthma . Results : There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures . Conclusions : These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months Context Research on patient safety has focused on adverse events in hospitalized patients . Adverse events following hospitalization have received little attention . Contribution Among 400 consecutive patients discharged from the general medical service of an academic hospital , 76 had adverse events during the 2 weeks following hospital discharge . Of the adverse events , the research ers categorized 23 as preventable , 24 as ameliorable , and the remainder as neither . Adverse drug events were the most frequent occurrence . Implication s Interventions to maximize patient safety should consider the vulnerable transition from hospital to home . The Editors Patient safety is a public concern that has received substantial attention , especially since the release of two reports from the U.S. Institute of Medicine . The first of these , To Err Is Human , review ed the literature on adverse events , or injuries result ing from medical care ( 1 ) . On the basis of data from two large population -based chart review studies , the report estimated that adverse events occur in 2.9 % ( 2 ) to 3.7 % ( 3 ) of hospitalizations . The first of these studies ( 2 ) found that although most injuries are minor , approximately 1 in 10 results in death . The research ers determined that approximately half of the adverse events were caused by errors ( 1 , 3 , 4 ) . The second report , Crossing the Quality Chasm , which proposes strategies for improving the health system , declared patient safety a fundamental component of care quality ( 5 ) . However , the estimated incidence of adverse events quoted in To Err Is Human may underestimate the overall safety problem , since injuries occurring after discharge were not included in the evaluation . Patients may be especially vulnerable to injuries during this period because they may still have functional impairments and because discontinuities may occur at the interface of acute and ambulatory care ( 6 ) . These discontinuities may be worsened by the current health care environment , in which patients are leaving the hospital quicker and sicker ( 7 ) and may receive care from hospitalists rather than their primary care physicians ( 8) . Despite these theoretical concerns , few studies are available to estimate the extent of the problem . Several studies have determined the risk for postdischarge wound infections in surgical patients ( 9 , 10 ) , but this is a specific type of safety problem and the risk can not be generalized . Other studies have used readmission rates to identify poor- quality hospital care ( 11 ) . However , this outcome is an insensitive and nonspecific marker of quality in general ( 11 ) and safety in particular . Information on the incidence and type of adverse events is vital for improving postdischarge safety . We wanted to determine the incidence and severity of adverse events affecting patients after discharge from the hospital to home . In addition , we wanted to identify the incidence of preventable and ameliorable adverse events , classify types of adverse events , and identify system improvements to reduce the incidence and severity of adverse events after discharge . Methods Overview To determine the rate of adverse events , we first created a case summary of every patient 's posthospital course by performing a medical record review and a telephone interview approximately 3 weeks after discharge . Using this information , we created event summaries , which two board-certified internists independently review ed to determine whether medical management caused an injury and , if so , whether it was preventable or ameliorable . The institutional review board at the study hospital approved the protocol . Definitions Adverse outcomes were any of the following patient experiences after discharge : new or worsening symptoms , unanticipated visits to health facilities for tests or treatments , or death . An adverse event was an injury result ing from medical management rather than the underlying disease . We evaluated all injuries result ing in symptoms after discharge , regardless of when the events occurred . Thus , we included adverse events that occurred in the hospital and after discharge as long as symptoms persisted until the patient went home . A preventable adverse event was an injury that could have been avoided , that is , an injury judged to probably be the result of an error or a system design flaw . An ameliorable adverse event was an injury whose severity could have been substantially reduced if different actions or procedures had been performed or followed . Patient Sample We used a prospect i ve cohort design to study adult medical patients at an 800-bed urban academic teaching hospital . Patients were included if they went home from the general medical service during a sequential 81-day period , had telephone service , and could complete a telephone interview in English . Patient surrogates were permitted to complete the interview if the patient could not . Telephone Interview A board-certified internist contacted patients by telephone within 2 to 5 weeks of discharge . If the patient was eligible and consented , he or she underwent a semi-structured interview over the telephone . If the patient was not available , we made up to 20 attempts to contact him or her at different times of the day and week . If the patient declined to participate or we were unable to contact him or her after 5 weeks , we rated the patient as a nonresponder . Responders underwent a telephone interview that had several components ( Appendix Figure ) . The principal component assessed the patient 's condition since discharge by using a full review of organ systems . If patients answered yes to any question , the interviewer asked them to elaborate about the symptom 's severity , timing in relation to hospitalization and treatments , and resolution . The survey also determined patients ' use of health services since discharge , including home care services , physician services , visits to laboratories , and readmissions to the hospital . Preparation of Case Summaries To create a case summary , the internist combined the information from the telephone interview with information obtained from a review of the patient 's electronic medical record . This computerized clinical record contains h and over notes from the hospitalization ; discharge summaries ; previous orders and written instructions ; emergency department and clinic notes ; operative and procedure notes ; and all laboratory results , including results of radiography , electrocardiography , and pathologic examination . If necessary , the paper chart was also review ed to clarify information that was in the discharge summary or h and over notes . If patients returned to the study hospital after discharge , we were able to vali date their history by review ing their records . However , for patients receiving care elsewhere , we had to rely on firsth and accounts . Preparation of Event Summaries The internist review ed every patient 's case summary for adverse outcomes . If any were found , an event summary that consisted of a detailed description of each outcome , including its onset , its severity , the health services used during its treatment , and its resolution , was created for each one . If there were no adverse outcomes , then the event summary consisted of the case summary . Determination of Adverse Events Two other board-certified internists independently rated each event summary by using st and ard techniques as described elsewhere ( 3 ) . Each event summary was evaluated separately . Review ers first rated on a scale of 1 to 6 their confidence that medical management caused an injury . If their rating was 5 or 6 , indicating that the injury was probably or definitely caused by management , the event was considered an adverse event . For adverse events , the internists used implicit criteria to determine their preventability and ameliorability . The two review ers ' assessment s were then compared for causality , preventability , and ameliorability . If there was disagreement , the two review ers discussed the case to attempt to come to consensus . If they did not agree , a third board-certified internist rated the event independently . Next , review ers rated injury severity , health services used , type of injury , and location . Injury severity was categorized as serious laboratory abnormality only , one day of symptoms , several days of symptoms , nonpermanent disability , permanent disability , or death . Differentiation between several days of symptoms and nonpermanent disability relied on evidence that symptoms interfered with patients ' activities of daily living . We categorized health services used as none , additional visit to a physician , additional visit for laboratory testing in addition to a physician visit , visit to an emergency department , readmission to the hospital , or death . We were able to determine whether health services were additional because during the interview we asked whether the health service was arranged before discharge or specifically for the particular symptom . We used a st and ard approach to classify the type of injury ( 2 , 3 ) , categorizing each as an adverse drug event , a procedure-related injury , a nosocomial infection , a fall , or other . We also classified the location of adverse events . Our primary objective was to evaluate adverse events affecting patients after discharge from the hospital to home . We felt that most of these events would occur after the patient went home , but we recognized a priori that some adverse events could occur in the hospital but lead to morbidity after discharge because of the severity of the injury or because health providers did not recognize the problem at discharge . Examples of injuries occurring in the hospital but affecting patients after discharge include pressure ulcers , missed diagnoses , and erroneous drug prescriptions . If it was determined that the adverse event occurred in the hospital , we examined whether the injury was recognized before discharge and , if so , whether definitive management was instituted at that time . To develop strategies CONTEXT Inner-city high-risk infants often receive limited and fragmented care , a problem that may increase serious illness . OBJECTIVE To assess whether access to comprehensive care in a follow-up clinic is cost-effective in reducing life-threatening illnesses among high-risk , inner-city infants . DESIGN R and omized controlled trial . SETTING AND PARTICIPANTS A total of 887 very-low-birth-weight infants born in a Texas county hospital between January 1988 and March 1996 and followed up in a children 's hospital clinic . One hundred four infants who became ineligible or died after r and omization but before nursery discharge were excluded from the analysis . INTERVENTIONS Infants were r and omly assigned to receive routine follow-up care ( well-baby care and care for chronic illnesses ; n = 441 ) or comprehensive care ( which included the components of routine care plus care for acute illnesses , with 24-hour access to a primary caregiver ; n = 446 ) . MAIN OUTCOME MEASURES Life-threatening illnesses ( ie , causing death or hospital admission for pediatric intensive care ) occurring between nursery discharge and age 1 year , assessed by blinded evaluators from inpatient charts and state Medicaid and vital statistics records ; and hospital costs ( estimated from department-specific cost-to-charge ratios ) . RESULTS Comprehensive care result ed in a mean of 3.1 more clinic visits and 6.7 more telephone conversations with clinic staff ( P<.001 for both ) . One-year outcomes were unknown for fewer comprehensive-care infants than routine-care infants ( 9 vs 28 ; P = .001 ) . Identified deaths were similar ( 11 in comprehensive care vs 13 in routine care ; P = .68 ) . The comprehensive-care group had 48 % fewer life-threatening illnesses ( 33 vs 63 ; P<.001 ) , 57 % fewer intensive care admissions ( 23 vs 53 ; P = .003 ) , and 42 % fewer intensive care days ( 254 vs 440 ; P = .003 ) . Comprehensive care did not increase the mean estimated cost per infant for all care ( $ 6265 with comprehensive care and $ 9913 with routine care ) . CONCLUSION Comprehensive follow-up care by experienced caregivers can be highly effective in reducing life-threatening illness without increasing costs among high-risk inner-city infants . JAMA . 2000;284:2070 - 2076 A r and omised controlled study of an educational programme for children with asthma and their families was carried out by community child health nurses . Three hundred and sixty eight children aged 2 to 14 years were enrolled in the study after admission to hospital for asthma . The intervention group was visited monthly by a nurse for six months . The subjects were assessed six months later by a postal , self administered question naire . European children in the intervention group were taking significantly more drugs for the treatment of asthma six months after the index admission to hospital than those in the control group ( mean ( SD ) intake 2.7 ( 1.1 ) v 2.1 ( 1.0 ) , respectively ) . In particular , they were using more theophylline ( 56.6 % v 37.0 % ) and inhaled steroids ( 34.9 % v 21.0 % ) . There was no difference between the groups for parental reports of improvement , of missed schooling , and in severe attacks of asthma of not responding to the usual treatment at home . European children in the intervention group used the hospital services for severe attacks of asthma more than controls ( 34.2 % v 10.5 % ) . There were more re-admissions in the European intervention group in the subsequent six months after the index admission than in the control group ( mean ( SD ) 0.51 ( 0.97 ) v 0.29 ( 0.65 ) . Re-admission continued to be higher in the 12 months after the nurse had stopped visiting ( 0.81 ( 1.65 ) v 0.25 ( 0.65 ] . There was no difference in the duration of hospital stay between the intervention and control groups . For Polynesian children there was no difference between the groups for any outcome measures The impact of parental smoking on children is enormous . Injury and illness related to parental smoking result in 6,200 excess pediatric deaths per year , which places smoking as the leading preventable cause of death in US children . Parental smoking doubles the risk of child hospitalization for respiratory illness therefore pediatricians have frequent contact with smoking parents . A single study has previously investigated the effect of child hospitalization on parental smoking cessation . Smoking caregivers of children hospitalized for respiratory illness at the University of New Mexico were offered a smoking cessation intervention during the child 's hospitalization . Participants were r and omized to receive either a brief anti-smoking message or more extensive counseling based on current clinical practice guidelines . Forty-two parents enrolled in the study . Fourteen percent of participants in the counseling group and 5 % in the brief message group were self-reported quitters at 6 months . A significant percentage of smoking parents of children hospitalized for respiratory illness are willing to receive smoking cessation counseling while their child is in the hospital . Abstinence rates appear similar to other pediatric office-based interventions . Child hospitalization should be considered an important opportunity to provide parents with smoking cessation services , particularly since many smoking parents will not have access to these services elsewhere To determine the safety , efficacy , and cost savings of early hospital discharge of very-low-birth-weight infants ( less than or equal to 1500 g ) , we r and omly assigned infants to one of two groups . Infants in the control group ( n = 40 ) were discharged according to routine nursery criteria , which included a weight of about 2200 g. Those in the early-discharge group ( n = 39 ) were discharged before they reached this weight if they met a st and ard set of conditions . For families of infants in the early-discharge group , instruction , counseling , home visits , and daily on-call availability of a hospital-based nurse specialist for 18 months were provided . Infants in the early-discharge group were discharged a mean of 11 days earlier , weighed 200 g less , and were two weeks younger at discharge than control infants . The mean hospital charge for the early-discharge group was 27 percent less than that for the control group ( $ 47,520 vs. $ 64,940 ; P less than 0.01 ) , and the mean physician 's charge was 22 percent less ( $ 5,933 vs. $ 7,649 ; P less than 0.01 ) . The mean cost of the home follow-up care in the early-discharge group was $ 576 , yielding a net saving of $ 18,560 for each infant . The two groups did not differ in the numbers of rehospitalizations and acute care visits , or in measures of physical and mental growth . We conclude that early discharge of very-low-birth-weight infants , with follow-up care in the home by a nurse specialist , is safe and cost effective OBJECTIVE Parental smoking is associated with increased rates and severity of childhood respiratory illness . No previous studies have examined child hospitalization as an opportunity for parental smoking cessation . We evaluated the feasibility of implementing a smoking cessation intervention for parents at the time of child hospitalization for respiratory illness . METHODS We performed a prospect i ve cohort study of smoking parents who had a child who was admitted to an academic children 's hospital for a respiratory illness between January and April 2000 . All enrollees were offered the Stop Tobacco Outreach Program , which includes an initial motivational interview , written material s , nicotine replacement therapy ( NRT ) , telephone counseling , and fax referral to parents ' primary clinician . The primary outcome was completion of all 3 counseling sessions . Two-month follow-up outcomes were quit attempts , cessation , NRT use , primary care visits , household smoking prohibition , and satisfaction . RESULTS A total of 126 smoking parents met eligibility criteria , and 71 ( 56 % ) enrolled in the study . Of the 71 , 80 % completed all counseling sessions and 56 % accepted free NRT at the time of enrollment . At the 2-month follow-up , of the 71 initial enrollees , 49 % reported having made a quit attempt that lasted at least 24 hours , 21 % reported not smoking a cigarette in the last 7 days , 27 % reported having used NRT , and 38 % had had a visit with their own primary clinician . The proportion of parents who reported rules prohibiting smoking in the house increased ( 29 % vs 71 % ) . Parental rating of the overall usefulness of the program was 4.3 + /- 0.9 ( 1 st and ard deviation ) on the 5-point scale 1 = not at all and 5 = a great extent . CONCLUSIONS This study demonstrates the feasibility of engaging parents in smoking cessation interventions at the time of child hospitalization for respiratory illness . Previous work done in a similar sample of parental smokers has shown extremely low ever-use rates of cessation programs . High rates of acceptance of in-hospital and telephone counseling in this study support the notion of child hospitalization as a teachable moment to address parental smoking BACKGROUND Re-admissions to hospital in childhood asthma are common with studies reporting that 25 % or more of children will be re-admitted within a year . There is a need for strategies to reduce re-admissions . METHODS A prospect i ve r and omised control study of an asthma home management training programme was performed in children aged two years or over admitted with acute asthma . Two hundred and one children were r and omised at admission to either an intervention group ( n = 96 ) which received the teaching programme or a control group ( n = 105 ) . A nurse-led teaching programme used the current attack as a model for the management of future attacks and included discussion , written information , subsequent follow up and telephone advice aim ed at developing and reinforcing individualised asthma management plans . Parents were also provided with a course of oral steroids and guidance on when to start them . RESULTS The groups were similar in degree of social deprivation , length of stay , number of previous admissions , acute asthma treatment , and asthma treatment at discharge . Subsequent re-admissions were significantly reduced in the intervention group from 25 % to 8 % in individual follow up periods that ranged from two to 14 months ( chi 2 = 9.63 ; p = 0.002 ) . This reduction was not accompanied by any increase in subsequent emergency room attendances nor , in the short term , by any increase in urgent community asthma treatment . The intervention group also showed significant reductions in day and night morbidity 3 - 4 weeks after admission to hospital . CONCLUSIONS A nurse-led asthma home management training programme administered during a hospital admission can significantly reduce subsequent admissions to hospital for asthma . Acute hospitalisation may be a particularly effective time to deliver home management training Goals of workThe purpose of this study was to investigate the effectiveness of a discharge-planning program on helping caregivers meet the physical care needs of children with cancer . Patients and methods This research is a quasi-experimental type of study in a pediatric oncology clinic at a university hospital in Izmir/Turkey . The control group had 25 and the experimental group had 24 patients with their caregivers . For the experimental group , discharge planning , discharge teaching , home visits , and telephone consultation were provided and has been planned to investigate the effectiveness of a discharge-planning program on helping caregivers meet the physical care needs of children with cancer between 0–18 years of age . Main results In the third assessment , the number of patients that needed physical care needs in the experimental and control groups was decreased , and children in the experimental group had a lower number of physical care needs . A decreased number of unplanned admissions to the hospital at the first and third follow-up times , a decrease in unplanned admissions , and higher satisfaction rate were seen in the experimental group caregivers . Conclusions A discharge-planning program and a hospital-based home care model had a very significant effect on the care needs of children with cancer and their caregivers . Our findings indicate that a discharge-planning program and a hospital-based home care model had a very significant effect on the care needs of children with cancer and their caregivers OBJECTIVE To evaluate factors contributing to optimal medical outcomes during the first year following discharge of very low birth weight infants from tertiary neonatal intensive care units . STUDY DESIGN This was a prospect i ve investigation of the health and development of 81 very low birth weight infants following discharge from two tertiary neonatal intensive care units in Los Angeles . Infants were assigned to four groups receiving a variety of after care services in their homes . Analyses of variance were computed to examine differences between groups for a variety of outcomes . RESULTS No statistically significant differences were seen between after care groups on use of hospital emergency rooms ( ER ) rehospitalization rates , or child abuse and neglect . Highest overall rates of optimal outcomes were seen in the group receiving the highest intensity of after care services . Those groups receiving long-term home visiting services had significantly higher rates of up-to- date immunizations . CONCLUSION There was no significant impact on infant mortality and morbidity of early discharge , regardless of the system of after care used . However , those infants who received the highest level of after care services had the most optimal health outcomes and were most likely to be receiving well-baby care . It is likely that the comprehensive , clinic-based system of health care available to all study infants was a significant factor in low rates of morbidity 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 OBJECTIVES We assessed the effectiveness of a community health worker intervention focused on reducing exposure to indoor asthma triggers . METHODS We conducted a r and omized controlled trial with 1-year follow-up among 274 low-income households containing a child aged 4 - 12 years who had asthma . Community health workers provided in-home environmental assessment s , education , support for behavior change , and re sources . Participants were assigned to either a high-intensity group receiving 7 visits and a full set of re sources or a low-intensity group receiving a single visit and limited re sources . RESULTS The high-intensity group improved significantly more than the low-intensity group in its pediatric asthma caregiver quality -of-life score ( P=.005 ) and asthma-related urgent health services use ( P=.026 ) . Asthma symptom days declined more in the high-intensity group , although the across-group difference did not reach statistical significance ( P=.138 ) . Participant actions to reduce triggers generally increased in the high-intensity group . The projected 4-year net savings per participant among the high-intensity group relative to the low-intensity group were 189 - 721 dollars . CONCLUSIONS Community health workers reduced asthma symptom days and urgent health services use while improving caregiver quality -of-life score . Improvement was greater with a higher-intensity intervention OBJECTIVE To test whether community health workers are able to reach low-income parents of African American children hospitalized for asthma and to reduce rehospitalization among them . DESIGN A r and omized controlled evaluation of usual care vs 2-year asthma coach intervention . SETTING An urban children 's hospital and the surrounding community . PARTICIPANTS A population -based sample of 306 children hospitalized for asthma met the inclusion criteria of being 2 to 8 years of age , of African American ethnicity , and having Medicaid coverage . Of these , 200 were contacted and 191 recruited with commitment to evaluation activities but , in order to assess reach , no commitment to participating in intervention . INTERVENTIONS Coaches reinforced basic asthma education and encouraged key management behaviors through home visits and phone calls tailored to parent 's readiness to adopt management practice s and emphasizing a nondirective supportive style ( cooperative and accepting of feelings and choices ) . OUTCOME MEASURES The reach of intervention to parents , contacts with coaches , and rehospitalization over 2 years based on hospital records . RESULTS Within 3 months of r and omization to the asthma coach group , 89.6 % of parents had at least 1 substantive contact with the coach , with an average of 21.1 contacts per parent over the 24-month intervention . The proportion of children rehospitalized was 35 of 96 ( 36.5 % ) in the asthma coach group and 55 of 93 ( 59.1 % ) in the usual care group ( P < .01 ) , controlling for parental education and child age , sex , and hospitalization in the year prior to the index hospitalization . In surveys , parents indicated the importance of the nondirective approach to support . CONCLUSIONS An asthma coach can reach low-income parents of African American children hospitalized for asthma and reduce rehospitalization among the children OBJECTIVE To describe parent perceptions of their child 's hospital discharge and assess the relationship between these perceptions and hospital readmission . DESIGN A prospect i ve study of parents surveyed with questions adapted from the care transitions measure , an adult survey that assesses components of discharge care . Participant answers , scored on a 5-point Likert scale , were compared between children who did and did not experience a readmission using a Fisher 's exact test and logistic regression that accounted for patient characteristics associated with increased readmission risk , including complex chronic condition and assistance with medical technology . SETTING A tertiary-care children 's hospital . PARTICIPANTS A total of 348 parents surveyed following their child 's hospital discharge between March and October 2010 . INTERVENTION None . MAIN OUTCOME MEASURE Unplanned readmission within 30 days of discharge . RESULTS There were 28 children ( 8.1 % ) who experienced a readmission . Children had a lower readmission rate ( 4.4 vs. 11.3 % , P = 0.004 ) and lower adjusted readmission likelihood [ odds ratio 0.2 ( 95 % confidence interval 0.1 , 0.6 ) ] when their parents strongly agreed ( n = 206 ) with the statement , ' I felt that my child was healthy enough to leave the hospital ' from the index admission . Parent perceptions relating to care management responsibilities , medications , written discharge plan , warning signs and symptoms to watch for and primary care follow-up were not associated with readmission risk in multivariate analysis . CONCLUSIONS Parent perception of their child 's health at discharge was associated with the risk of a subsequent , unplanned readmission . Addressing concerns with this perception prior to hospital discharge may help mitigate readmission risk in children OBJECTIVE : To determine whether pediatric readmissions within 15 days of discharge were considered preventable . METHODS : Retrospective chart review of 200 r and omly selected readmissions ( 8 % of all readmissions ) occurring within 15 days of discharge from a freest and ing children ’s hospital between January 1 , 2007 , and December 31 , 2008 . The degree of preventability was assessed independently for each case by 4 pediatricians using a 5-point Likert scale and was correlated with chronic conditions and reason for index admission with 3 M ’s Clinical Risk Groups and All Patient-Refined Diagnostic-Related Groups , respectively . RESULTS : The rate of 15-day readmissions considered more likely preventable by the discharging hospital was 20.0 % ( 1.7 % of total admissions , 95 % confidence interval 14.8%–26.4 % ) . Review ers failed to reach initial consensus in 62.5 % of cases , although final consensus was achieved after the panel review ed cases together . Consensus ratings served as the st and ard for the remainder of the study . Readmissions in children with malignancies were considered less preventable than those in children with other chronic illnesses ( 5.8 % vs 25.8 % , P = .003 ) . Readmissions following surgical admissions were considered more likely preventable than those following medical admissions ( 38.9 % vs 15.9 % , P = .002 ) . Central venous catheter infections and ventricular shunt malfunctions accounted for 8.5 % of all readmissions review ed . CONCLUSIONS : Although initial consensus about which readmissions were more likely preventable was difficult to achieve , the overall rate of preventable pediatric 15-day readmissions was low . Pediatric readmissions are unlikely to serve as a highly productive focus for cost savings or quality measurement BACKGROUND Adverse events ( AEs ) are adverse outcomes caused by medical care . Several studies have indicated that a substantial number of patients experience AEs before or during hospitalization . However , few data describe AEs after hospital discharge . We determined the incidence , severity , preventability and ameliorability of AEs in patients discharged from the general internal medicine service of a Canadian hospital . METHODS At a multisite Canadian teaching hospital , we prospect ively studied patients who were consecutively discharged home or to a seniors ' residence from the general internal medicine service during a 14-week interval in 2002 . We used telephone interview and chart review to identify outcomes after discharge . Two physicians independently review ed each outcome to determine if the patient experienced an AE . The severity , preventability and ameliorability of all AEs were classified . RESULTS During the study period , outcomes were determined for 328 of the 361 eligible patients , who averaged 71 years of age ( interquartile range 54 - 81 years ) . After discharge , 76 of the 328 patients experienced at least 1 AE ( overall incidence 23 % , 95 % confidence interval [ CI ] 19%-28 % ) . The AE severity ranged from symptoms only ( 68 % of the AEs ) or symptoms associated with a nonpermanent disability ( 25 % ) to permanent disability ( 3 % ) or death ( 3 % ) . The most common AEs were adverse drug events ( 72 % ) , therapeutic errors ( 16 % ) and nosocomial infections ( 11 % ) . Of the 76 patients , 38 had an AE that was either preventable or ameliorable ( overall incidence 12 % , 95 % CI 9%-16 % ) . INTERPRETATION Approximately one-quarter of patients in our study had an AE after hospital discharge , and half of the AEs were preventable or ameliorable BACKGROUND Discharge planning is becoming an important part of the management of childhood asthma in hospital . Readmission to hospital , although often inevitable , might represent a failure of the opportunity for intervention presented by a brief period of supervised care in hospital . AIM To examine the impact of a structured , nurse-led discharge package for children admitted to hospital with acute asthma on readmission to hospital , reattendance at the accident and emergency ( A&E ) department , and general practitioner consultations for asthma . METHODS A structured nurse-led discharge package , consisting of a 20 minute patient education programme and self management plan for children with asthma was developed on the wards of a busy children ’s hospital . A r and omised controlled trial was conducted involving 160 children aged 2–16 years admitted for asthma over a 12 month period . Readmission and A&E reattendance ’s over the six months after discharge from hospital were obtained from the hospital computerised information system and general practitioner consultations from practice records . RESULTS Children in the intervention group were significantly less likely to be readmitted to hospital in the next six months than those in the control group ( 12 of 80 v30 of 80 patients ) , and significantly less likely to attend the A&E department ( 6 of 80 v 31 of 80 ) . Significantly fewer children in the intervention group had visits to their general practitioner for problematic asthma ( 31 of 78v 72 of 77 for whom data were available ) . CONCLUSION By delivering the simplest form of education and support during a child ’s stay in hospital , readmissions over a six month period were reduced . The programme was design ed to be suitable for administration by nursing staff on the children ’s wards after a brief period of training Background . Formal education in primary care can reduce asthma exacerbations . However , there are few studies in hospitalized children , with none originating in Latin America . Methods . A prospect i ve r and omized study was design ed to evaluate whether a full education with self-management plan ( ESM ) was more effective than an education without self-management plan ( E ) in reducing asthma hospitalization . Children ( 5 to 15 years of age ) who were hospitalized for an asthma attack were divided in two groups . Children in the E group received general instructions based on a booklet . Those in the ESM group received the same booklet plus a self-management guide and a puzzle game that reinforces the lessons learned in the booklet . Patients were interviewed every 3 months , by telephone , for one year . Interviewers recording the number of hospitalizations , exacerbations , and emergency visits for asthma and oral steroid burst uses . Results . From 88 children who met the inclusion criteria , 77 ( 86 % ) completed one year of follow-up ( 41 from E and 36 from ESM group ) . Overall , after one year , the hospitalization decreased by 66 % and the inhaled corticosteroids therapy increased from 36 % to 79 % . At the end of the study , there was no difference in exacerbations , emergency visits , oral steroid burst uses , or hospitalizations between the two groups . Conclusions . Asthma education with or without a self-management plan during asthma hospitalization were effective in reducing exacerbations , emergency visits , oral steroid burst uses , and future rehospitalizations . This evidence supports the importance of providing a complete asthma education plan in any patient who is admitted for asthma exacerbation BACKGROUND Prolonged hospitalization of low birth weight infants increases the risk of medical and psychosocial complications . The feasibility of earlier discharge with community-based follow-up of infants of < or = 2000 g birth weight , without the use of home apnea monitors , was investigated . METHODS One hundred infants of < or = 2000 g birth weight were r and omized to either an intervention or control group . Intervention infants were discharged when readiness criteria were met . Based on assessed need , intervention group families received public health nursing and homemaker services for up to 8 weeks . Control infants were discharged to their homes at the discretion of the attending physician . All infants were assessed blindly at age 1 year with the Bayley and Home Observation for Measurement of the Environment ( HOME ) scales . RESULTS There were no group differences in baseline infants ' characteristics or in neonatal complications . Infants in the intervention group were discharged from the hospital at an earlier postconceptional age ( mean + /- SD 36.6 + /- 1.5 weeks vs 37.3 + /- 1.6 weeks ; P < .04 ) . Median length of hospital stay ( 23 days vs 31.5 days ) and mean weight at the time of discharge ( 2200 + /- 288 g vs 2275 + /- 301 g ) were lower , but not significantly , for infants in the intervention group . A secondary analysis by birth weight strata ( < or = 1500 g and 1501 through 2000 g ) revealed that the most significant reductions in hospital stay and weight at discharge were realized in infants of 1501 through 2000 g birth weight . The persistence of apneic episodes and need for electronic monitoring prevented earlier discharge of infants of < or = 1500 g birth weight . Postdischarge services to the intervention group included 185 public health nurse home visits ( 3.8 + /- 0.91 ) , 410 phone contacts ( 8.4 + /- 5 ) , and 2298 homemaker hours ( 46 + /- 78 ) of service . At 1 year , there were no deaths and no group differences in rehospitalization rates , use of ambulatory services , or Bayley scores . Intervention families had significantly higher 1-year HOME scores . Minimum cost of hospital care was $ 873 per day , while the total cost of community-based services averaged $ 626 per infant . CONCLUSIONS A significant reduction in average length of hospital stay was achieved for infants of 1501 through 2000 g birth weight . Earlier discharge of infants weighing < or = 1500 g at birth was hampered by persistent apneic episodes and feeding difficulties . A community-based program design ed to provide individualized support and education for families of low birth weight infants was cost-effective and had a positive influence on the home environment BACKGROUND Currently there are few data that brief violence intervention ( BVI ) and community case management services ( CCMS ) are effective for trauma patients admitted for interpersonal violence in terms of recidivism , service utilization , or alcohol abuse . The objective of this study is to assess outcomes for a cohort of young trauma patients in a prospect i ve , r and omized trial comparing BVI with BVI + CCMS . METHODS Intentionally injured patients , aged 10 years to 24 years , admitted to a Level I trauma center were r and omized to receive a brief in-hospital psychoeducational violence intervention alone ( Group I ) or in combination with a 6 months wraparound CCMS ( Group II ) that included vocational , employment , educational , housing , mental health , and recreational assistance . Recidivism , alcohol use , and hospital and community service utilization were assessed at 6 weeks ( 6W ) and 6 months ( 6 M ) . RESULTS Seventy-five of 376 eligible injured patients were r and omized into Group I and II . The two groups had similar demographics , injuries , and clinical outcomes . After discharge , percent clinic visits maintained was 57 % in both the groups . Group II showed better hospital service utilization , CMS , and risk factor reduction at 6W and 6 M . One patient in each group sustained a reinjury at 6 M . CONCLUSIONS In-hospital BVI with community wraparound case management interventions can improve hospital and community service utilization both short- and long-term for high-risk injured patients . Longer follow-up is needed to show sustained reduction |
11,729 | 22,696,375 | Simulation-based training , as compared with no training , generally appears to provide participants with some advantage over their untrained peers as measured by composite score of competency , independent procedure completion , performance time , independent insertion depth , overall rating of performance or competency error rate and mucosal visualization .
Alternatively , there was no conclusive evidence that simulation-based training was superior to conventional patient-based training , although data were limited .
The results of this systematic review indicate that virtual reality endoscopy training can be used to effectively supplement early conventional endoscopy training ( apprenticeship model ) in diagnostic oesophagogastroduodenoscopy , colonoscopy and /or sigmoidoscopy for health professions trainees with limited or no prior endoscopic experience . | BACKGROUND Traditionally , training in gastrointestinal endoscopy has been based upon an apprenticeship model , with novice endoscopists learning basic skills under the supervision of experienced preceptors in the clinical setting .
Over the last two decades , however , the growing awareness of the need for patient safety has brought the issue of simulation-based training to the forefront .
While the use of simulation-based training may have important educational and societal advantages , the effectiveness of virtual reality gastrointestinal endoscopy simulators has yet to be clearly demonstrated .
OBJECTIVES To determine whether virtual reality simulation training can supplement and /or replace early conventional endoscopy training ( apprenticeship model ) in diagnostic oesophagogastroduodenoscopy , colonoscopy and /or sigmoidoscopy for health professions trainees with limited or no prior endoscopic experience . | Background Colonoscopy insertion is difficult to teach due to the inability of current training models to provide realistic tactile sensation with simultaneous three-dimensional ( 3D ) colonoscope display . Aims To assess the influence of a simulator consisting of a colon model coupled with 3D instrument visualization on trainee colonoscopy performance . Methods Pilot study using the simulator model with three trainees who were not proficient in colonoscopy . At r and om times over a 6-week period , trainees participated in an individualized half-day session using the Colonoscope Training Model and a colonoscope equipped with a 3D magnetic probe imaging system ( ScopeGuide ) in six st and ardized cases . A blinded supervising instructor grade d patient-based colonoscopy performance over the 6-week period , and we independently analyzed the 2-week period before and after the intervention . We also measured cecal intubation and withdrawal times and medication requirements . Results Trainees performed 86 patient-based colonoscopies . Following the intervention , the colonoscopy performance score improved from 4.4 ± 2.3 to 5.9 ± 2.4 ( p = 0.005 ) . Trainees had a 76 % cecal intubation rate following the session as compared to 43 % before training ( p = 0.004 ) , while utilizing less time , 14 ± 7 versus 18 ± 11 min ( p = 0.056 ) and less medication ( p > 0.05 ) . Conclusions Colonoscopy simulation using the Colonoscope Training Model and the ScopeGuide produced an immediate and large effect on trainee colonoscopy performance BACKGROUND Little is known regarding the value of esophagogastroduodenoscopy ( EGD ) simulators in education . The purpose of the present paper was to vali date the use of computer simulation in novice EGD training . METHODS In phase 1 , expert endoscopists evaluated various aspects of simulation fidelity as compared to live endoscopy . Additionally , computer-recorded performance metrics were assessed by comparing the recorded scores from users of three different experience levels . In phase 2 , the transfer of simulation-acquired skills to the clinical setting was assessed in a two-group , r and omized pilot study . The setting was a large gastroenterology ( GI ) Fellowship training program ; in phase 1 , 21 subjects ( seven expert , intermediate and novice endoscopist ) , made up the three experience groups . In phase 2 , eight novice GI fellows were involved in the two-group , r and omized portion of the study examining the transfer of simulation skills to the clinical setting . During the initial validation phase , each of the 21 subjects completed two st and ardized EDG scenarios on a computer simulator and their performance scores were recorded for seven parameters . Following this , staff participants completed a question naire evaluating various aspects of the simulator 's fidelity . Finally , four novice GI fellows were r and omly assigned to receive 6 h of simulator-augmented training ( SAT group ) in EGD prior to beginning 1 month of patient-based EGD training . The remaining fellows experienced 1 month of patient-based training alone ( PBT group ) . Results of the seven measured performance parameters were compared between three groups of varying experience using a Wilcoxon ranked sum test . The staffs ' simulator fidelity survey used a 7-point Likert scale ( 1 , very unrealistic ; 4 , neutral ; 7 , very realistic ) for each of the parameters examined . During the second phase of this study , supervising staff rated both SAT and PBT fellows ' patient-based performance daily . Scoring in each skill was completed using a 7-point Likert scale ( 1 , strongly disagree ; 4 , neutral ; 7 , strongly agree ) . Median scores were compared between groups using the Wilcoxon ranked sum test . RESULTS Staff evaluations of fidelity found that only two of the parameters examined ( anatomy and scope maneuverability ) had a significant degree of realism . The remaining areas were felt to be limited in their fidelity . Of the computer-recorded performance scores , only the novice group could be reliably identified from the other two experience groups . In the clinical application phase , the median Patient Discomfort ratings were superior in the PBT group ( 6 ; interquartile range [ IQR ] , 5 - 6 ) as compared to the SAT group ( 5 ; IQR , 4 - 6 ; P = 0.015 ) . PBT fellows ' ratings were also superior in Sedation , Patient Discomfort , Independence and Competence during various phases of the evaluation . At no point were SAT fellows rated higher than the PBT group in any of the parameters examined . CONCLUSION This EGD simulator has limitations to the degree of fidelity and can differentiate only novice endoscopists from other levels of experience . Finally , skills learned during EGD simulation training do not appear to translate well into patient-based endoscopy skills . These findings suggest against a key element of validity for the use of this computer simulator in novice EGD training BACKGROUND AND AIMS The advantages of using a computer-based simulator during colonoscopy training are debated . We aim ed to explore its usefulness in objective ly measuring trainees ' competence in colonoscopy . METHODS Twelve colonoscopy trainees ( fully trained in upper GI endoscopy ) were evaluated using a computer-based simulator ( GI-Mentor , Symbionix ) before and during h and s-on training ( i.e. after 60 colonoscopies ) ; the controls were 15 experts ( > 90 % of caecal intubation ) . Both trainees and experts performed two " screening " simulations ( easy and difficult ) in a r and omised order , and the time to reach the caecum and withdrawal time was assessed . RESULTS The percentage of caecal intubation progressively increased during h and s-on training . All of the trainees intubated the caecum during the easy and difficult simulations , both before and during h and s-on training . The median time ( interquartile range ) to reach the caecum upon easy simulation was the only variable influenced by h and s-on training : 2.7 min ( 2.1 - 3.2 ) before and 1.9 min ( 1.6 - 2 ) during training ( p<0.01 ) . Withdrawal time was ≥6 min in the case of five trainees before training , and three during h and s-on training . Computer-based simulator performance did not correlate with h and s-on training performance . CONCLUSIONS The computer-based simulator was not found to be useful in evaluating competence during h and s-on training in colonoscopy Background Virtual reality ( VR ) simulators and Web-based instructional videos are valuable supplemental training re sources in surgical programs , but it is unclear how to optimally integrate them into minimally invasive surgical training . Methods Medical students were r and omized to proficiency-based training on VR laparoscopy and endoscopy simulators by two different methods : proctored training ( automated simulator feedback plus human expert feedback ) or independent training ( simulator feedback alone ) . After achieving simulator proficiency , trainees performed a series of laparoscopic and endoscopic tasks in a live porcine model . Prior to their entry into the animal lab , all trainees watched an instructional video of the procedure and were r and omly assigned to either observe or not observe the actual procedure before performing it themselves . The joint effects of VR training method and procedure observation on time to successful task completion were evaluated with Cox regression models . Results Thirty-two students ( 16 proctored , 16 independent ) completed VR training . Cox regression modeling with adjustment for relevant covariates demonstrated no significant difference in the likelihood of successful task completion for independent versus proctored training [ Hazard Ratio ( HR ) 1.28 ; 95 % Confidence Interval ( CI ) 0.96–1.72 ; p = 0.09 ] . Trainees who observed the actual procedure were more likely to be successful than those who watched the instructional video alone ( HR 1.47 ; 95 % CI 1.09–1.98 ; p = 0.01 ) . Conclusions Proctored VR training is no more effective than independent training with respect to surgical performance . Therefore , time-consuming human expert feedback during VR training may be unnecessary . Instructional videos , while useful , may not be adequate substitutes for actual observation when trainees are learning minimally invasive surgical procedures Background The hypothesis of this study is that working on the simulator without a structured feedback does not change performance ; hence , any effects shown after structured feedback would amount to useful learning of the procedure . The aim was to investigate the learning curve for the HT Immersion Medical Colonoscopy Simulator without any structured feedback . This could then be potentially applied to vali date the learning curve on the simulator when structured feedback is provided . There are no previous studies on this matter . Methods C and i date s were asked to perform colonoscopy on the HT Immersion Medical Colonoscopy Simulator . Modules 3 and 4 were used at r and om . In total , each c and i date was asked to perform five consecutive virtual colonoscopies on the same module . These five episodes were collectively referred to as one trial . A time result of 3,600 sec ( 1 h ) was used to denote perforation . No guidance or feedback was given to c and i date s before , during , or after each procedure . A total of 26 postgraduate doctors were recruited , including nine research fellows , five pre registration house officers , six specialist registrars , and six consultants . Fourteen c and i date s recorded five attempts each ( i.e. , one trial each ) on the same module of the colonoscopy simulator ( 14 trials over 70 episodes ) . Another 12 c and i date s recorded five attempts ( i.e. , one trial each ) on two modules of the colonoscopy simulator ( 24 trials over 120 episodes ) . Hence , 190 episodes were recorded in total , representing 38 trials . Results There was no improvement in performance on the simulator from first attempt to the fifth in the absence of feedback . If there was any initial gain in any measurable outcome , this was lost in subsequent attempts indicating lack of learning . The outcomes measured included time taken to complete the test , percentage of the mucosa visualized , depth of the instrument inserted , and the path length used . The results were statistically significant for all outcomes . Conclusions This study demonstrates that in the absence of feedback , it is not possible to improve performance on the HT Immersion Medical Colonoscopy Simulator . Thus , there is no learning curve for the machine . The information from this study is vital for using the simulators in training and assessment because any improvement in learning curves shown after training on simulators can be presumed to be due to learning the procedure and not the Background The Erlangen Active Simulator for Interventional Endoscopy ( EASIE ) using ex-vivo porcine organs was introduced in 1997 . The present study should analyze whether repeated EASIE simulator training in endoscopic hemostasis led to superior performance compared with a traditionally educated group . The results were compared with a similar project in New York . Methods Thirty-five French GI fellows were enrolled . Baseline skills evaluation was performed in four disciplines ( manual skills , injection/coagulation , clip application and variceal ligation ) using the compactEASIE-simulator equipped with an upper gastrointestinal organ package for bleeding simulation . The same , translated evaluation forms ( from the prior New York project ) were used . Subsequently , fellows were r and omized into group A ( n=17 , only clinical education ) and group B ( n=18 , additional three simulator trainings ) . Group B was trained the next day and after 4 and 7 months by experts of the French Society of Gastrointestinal Endoscopy . Both groups performed routine and emergency endoscopies at their home hospitals during the study period . Both groups were re-evaluated blindly after 9 months . Results The learning curve for group B showed a significant improvement in all disciplines ( P<0.004 ) whereas group A improved significantly in only two of four disciplines at blinded final evaluation ( manual skills P=0.02 , injection/coagulation P=0.013 ) . The direct comparison of groups B and A at blinded final evaluation showed significantly superior ratings for group B in all disciplines ( P<0.006 ) and significantly shorter performance times in two disciplines ( P=0.016 each ) . The comparison with the similar ‘ New York project ’ revealed that preexisting differences in skills were adjusted by the training . Conclusion Complementary trainings ( three workshops in 7 months ) in endoscopic hemostasis using the compactEASIE improved skills compared with a solely clinical education . The results of the ‘ New York project ’ were confirmed and benefits were independent from the medical educational system INTRODUCTION Colonoscopic simulators offer the opportunity for skill acquisition in the pre clinical setting . Currently available simulators vary widely with respect to level of fidelity and technological sophistication . Despite the belief that more realistic is better , there is a paucity of evidence regarding the relative effectiveness of simulator fidelity ( high vs low ) on the acquisition of basic colonoscopic skills . We hypothesized that novice learners can acquire basic colonoscopic skills using simulators , however fidelity of the simulator does not make a difference . METHODS We r and omly assigned novice third-year and fourth-year medical students to practice on either a low-fidelity or high-fidelity colonoscopy model . The low-fidelity model used is described in the module 16 of the American College of Surgeons/Association of Program Directors in Surgery surgical skills curriculum for residents , Phase 1 : basic or core skills and tasks < http://elearning.facs.org/mod/re source /view.php?1d=450 > . The high-fidelity model was the AccuTouch colonoscopy simulator , Immersion Medical ( AccuTouch CS ) that has 6 different simulated scenarios for diagnostic colonoscopy ( level 1 - 6 ) . Both groups had 16 students and were given st and ard instruction by an expert with respect to the procedure and instrument h and ling on both models . Both groups were pretested and posttested on level 1 of the AccuTouch CS . The high-fidelity group practice d on level 2 and 4 of the AccuTouch CS , whereas the low-fidelity group practice d on the low-fidelity model for 2 sessions of 1 hour each . The computer-based evaluation parameters available on the AccuTouch CS were used to compare performances . RESULTS Both groups had similar demographics . There were no significant differences in the baseline performances of either group . Each group demonstrated significant improvement for insertion time and percentage of mucosa visualized . However , there were no significant differences between the groups on posttesting on any of the measured parameters . CONCLUSIONS Colonoscopic skill training on a low-fidelity model appears to be as effective as high-fidelity model training for basic endoscopic skill acquisition for novice learners BACKGROUND AND STUDY AIM As for any manual procedure , the learning curves for medical interventions can have undesirable phases , occurring mostly in the early experience of applying a technique . There have been impressive advances in endoscopic procedures during recent years , and there is an emerging trend that the number of procedures is increasing in parallel with these . In addition , the introduction of screening programs for colorectal cancer will also increase the numbers of procedures needed . Recent developments in medical simulation seem promising with regard to the possibility of " training out " undesirable parts of the learning curve outside the operating room . The aim of this study was to investigate whether the use of the AccuTouch flexible endoscopy simulator improves the early part of the learning curve in colonoscopy training . METHOD 12 endoscopy trainees , 10 surgeons and two medical gastroenterologists , all with experience in gastroscopy but with no specific colonoscopy experience , were r and omly assigned to either simulator training or to a control group . They all received the same theoretical study package and the training group practice d with the AccuTouch colonoscopy simulator until a predefined expert level of performance was reached . All trainees performed their first ten individual colonoscopies described in detail in a separate protocol . RESULTS Trainees in the simulator-trained group performed significantly better ( P=0.0011 ) and managed to reach the cecum in 52 % of their cases ( vs. 19 % in the control group ) , and were 4.53 times more likely to succeed compared with the controls . Additionally , there was a significantly shorter procedure time and less patient discomfort in the h and s of the simulator-trained group . CONCLUSION Skills acquired using the AccuTouch simulator transfer well into the clinical colonoscopy environment . The results of this trial clearly support the plan to integrate simulator training into endoscopic education curricula BACKGROUND The GI Mentor is a virtual reality simulator that uses force feedback technology to create a realistic training experience . OBJECTIVE To define the benefit of training on the GI Mentor on competency acquisition in colonoscopy . DESIGN R and omized , controlled , blinded , multicenter trial . SETTING Academic medical centers with accredited gastroenterology training programs . PATIENTS First-year GI fellows . INTERVENTIONS Subjects were r and omized to receive 10 hours of unsupervised training on the GI Mentor or no simulator experience during the first 8 weeks of fellowship . After this period , both groups began performing real colonoscopies . The first 200 colonoscopies performed by each fellow were grade d by proctors to measure technical and cognitive success , and patient comfort level during the procedure . MAIN OUTCOME MEASUREMENTS A mixed-effects model comparison between the 2 groups of objective and subjective competency scores and patient discomfort in the performance of real colonoscopies over time . RESULTS Forty-five fellows were r and omized from 16 hospitals over 2 years . Fellows in the simulator group had significantly higher objective competency rates during the first 100 cases . A mixed-effects model demonstrated a higher objective competence overall in the simulator group ( P < .0001 ) , with the difference between groups being significantly greater during the first 80 cases performed . The median number of cases needed to reach 90 % competency was 160 in both groups . The patient comfort level was similar . CONCLUSIONS Fellows who underwent GI Mentor training performed significantly better during the early phase of real colonoscopy training OBJECTIVES : The impact of endoscopic retro grade cholangiopancreatography ( ERCP ) mechanical simulator ( EMS ) practice on trainee clinical performance is unknown . The hypothesis that trainees with EMS practice ( study group ( SG ) ) have improved clinical outcomes compared with those without such practice ( control group ( CG ) ) is tested . METHODS : This was a r and omized controlled trial involving six US academic centers . Sixteen trainees were r and omized after ERCP didactic teaching . SG ( n=8 ) participated in two sessions of EMS practice on selective cannulation ; CG ( n=8 ) did not undergo EMS practice . All participants ’ clinical performances were monitored in the subsequent 16 weeks . Intervention effects were assessed in multivariable regression models using generalizing estimating equations ( GEE ) to account for cluster r and omization of trainees . The primary outcome was successful biliary cannulation , and secondary outcomes were cannulation time and competency score . RESULTS : Cannulation success rate was 47.1 % for CG and 69.6 % for SG . SG had higher odds of successful cannulation ( adjusted odds ratio=3.01 , P=0.021 ) . SG trainees achieved faster cannulation time ( min ) ( 4.7±4.2 vs. 10.3±14.1 , P<0.001 ) . Trainee competency scores given by supervising physicians were comparable confirming adequate blinding of the trainers . Limitations included short observation period , small number of ERCPs performed by individual trainees , and variation in the number of ERCPs between trainees . CONCLUSIONS : In a prospect i ve multicenter r and omized controlled trial during early training , a significantly higher proportion of the biliary cannulations performed by trainees with EMS practice were successful and with faster cannulation time compared with those performed by trainees without such practice . The results provide objective evidence to support the continued evaluation of EMS practice to augment clinical training BACKGROUND Changes in medical practice have constrained the time available for education and the availability of patients for training . Computer-based simulators have been devised that can be used to achieve manual skills without patient contact . This study prospect ively compared , in a clinical setting , the efficacy of a computer-based simulator for training in upper endoscopy . METHODS Twenty-two fellows with no experience in endoscopy were r and omly assigned to two groups : one group underwent 10 hours of pre clinical training with a computer-based simulator , and the other did not . Each trainee performed upper endoscopy in 19 or 20 patients . Performance parameters evaluated included the following : esophageal intubation , procedure duration and completeness , and request for assistance . The performance of the trainees also was evaluated by the endoscopy instructor . RESULTS A total of 420 upper endoscopies were performed ; the computer pretrained group performed 212 and the non-pretrained group , 208 . The pretrained group performed more complete procedures ( 87.8 % vs. 70.0 % ; p < 0.0001 ) , required less assistance ( 41.3 % vs. 97.9 % ; p < 0.0001 ) , and the instructor assessed performance as " positive " more often for this group ( 86.8 % vs. 56.7 % ; p < 0.0001 ) . The length of procedures was comparable for the two groups . CONCLUSIONS The computer-based simulator is effective in providing novice trainees with the skills needed for identification of anatomical l and marks and basic endoscopic maneuvers , and in reducing the need for assistance by instructors Background . The NOSCAR white paper lists training as an important step to the safe clinical application of natural orifice translumenal endoscopic surgery ( NOTES ) . The aim of this r and omized controlled trial was to evaluate whether training novices in either a laparoscopic or endoscopic simulator curriculum would affect performance in a NOTES simulator task . Methods . A total of 30 third-year medical undergraduates were recruited . They were r and omized to 3 groups : no training ( control ; n = 10 ) , endoscopy training on a vali date d colonoscopy simulator protocol ( n = 10 ) , and training on a vali date d laparoscopy simulator curriculum ( n = 10 ) . All participants subsequently completed a simulated NOTES task , consisting of 7 steps , on the ELITE ( endoscopic-laparoscopic interdisciplinary training entity ) model . Performance was assessed as time taken to complete individual steps , overall task time , and number of errors . Results . The endoscopy group was significantly faster than the control group at accessing the peritoneal cavity through the gastric incision ( median 27 vs 78 s ; P = .015 ) , applying diathermy to the base of the appendix ( median 103.5 vs 173 s ; P = .014 ) , and navigating to the gallbladder ( median 76 vs 169.5 s ; P = .049 ) . Endoscopy participants completed the full NOTES procedure in a shorter time than the laparoscopy group ( median 863 vs 2074 s ; P < .001 ) . Conclusion . This study highlights the importance of endoscopic training for a simulated NOTES task that involves both navigation and resection with operative maneuvers . Although laparoscopic training confers some benefit for operative steps such as applying diathermy to the gallbladder fossa , this was not as beneficial as training in endoscopy BACKGROUND New Residency Review Committee requirements in general surgery require 50 colonoscopies . Simulators have been widely suggested to help prepare residents for live clinical experience . We assessed a computer-based colonoscopy simulator for effective transfer of skills to live patients . METHODS A r and omized controlled trial included general surgery and internal medicine residents with limited endoscopic experience . Following a pretest , the treatment group ( n = 12 ) practice d on the simulator , while controls ( n = 12 ) received no additional training . Both groups then performed a colonoscopy on a live patient . Technical ability was evaluated by expert endoscopists using previously vali date d assessment instruments . RESULTS In the live patient setting , the treatment group scored significantly higher global ratings than controls ( t(22 ) = 1.84 , P = .04 ) . Only 2 of the 8 computer-based performance metrics correlated significantly with previously vali date d global ratings of performance . CONCLUSIONS Residents trained on a colonoscopy simulator prior to their first patient-based colonoscopy performed significantly better in the clinical setting than controls , demonstrating skill transfer to live patients . The simulator 's performance metrics showed limited concurrent validity , suggesting the need for further refinement BACKGROUND The objective benefit of a training using the compact Erlangen Active Simulator for Interventional Endoscopy-simulator was demonstrated in two prospect i ve educational trials ( New York , France ) . The present study analysed whether endoscopic novices are able to reach a comparable level of endoscopic skills as in the above-described projects . METHODS Twenty-seven endoscopic novices ( medical students , first year residents ) were enrolled in this prospect i ve , r and omised trial . The compact Erlangen Active Simulator for Interventional Endoscopy-simulator with an upper GI-organ package and blood perfusion system was used as a training tool . Basic evaluation of endoscopic skills was performed after a practical and theoretical course in diagnostic upper GI endoscopy followed by a stratified r and omisation according to the rating in endoscopic skills into intensive ( n=14 ) and control group ( n=13 ) . The intensive group was trained 12 times every second week over 7 months in 4 endoscopic disciplines ( manual skills , injection therapy , haemoclip , b and ligation ) by skilled endoscopist ( three trainees/simulator ) . Assessment was performed ( single steps/overall ) using an analogue scale from 1 to 10 ( 1=worst , 10=optimal performance ) by expert tutors . The control group was not trained . Blinded final evaluation of all participants was performed in January 2003 . RESULTS We observed in all techniques applied a significant improvement of endoscopic skills and of the performance time in the intensive group compared to the control group ( p<0.001 ) . The comparison with the previous projects showed that the intensively trained novices achieved comparable levels of performance to the GI fellows in the New York and France Project ( at least 80 % of the median score in three out of four techniques ) . CONCLUSION Endoscopic novices acquired notable skills in interventional endoscopy in the simulator by an intensive , periodical training using the compactEASIE BACKGROUND AND STUDY AIMS Preliminary data suggested that simulation practice using an endoscopic retro grade cholangiopancreatography ( ERCP ) mechanical simulator ( EMS ) improved trainees ' skill . The aims of the current study were to confirm the impact of coached EMS practice at the beginning of ERCP training and to investigate whether subsequent uncoached EMS practice provides additional benefit . METHODS Trainees entering ERCP training in 2008 ( n = 8) and 2009 ( n = 8) at two referral medical centers were r and omized to receive a coached EMS practice either with ( 2009 ) or without ( 2008 ) subsequent uncoached practice s or only routine training ( controls ) . The outcome measures were successful deep biliary cannulation by the trainee and overall performance score as rated by blinded trainers , during the subsequent 3 months of clinical practice . RESULTS Trainees undergoing single and multiple EMS practice s were more likely than controls to achieve successful biliary cannulation ( single : adjusted odds ratio [ aOR ] 2.89 , 95 % confidence interval [ CI ] 2.21 - 3.80 [ P < 0.001 ] ; multiple : 3.09 , 95 % CI 1.13 - 8.46 [ P = 0.028 ] ) and to have superior overall performance scores ( aOR 3.29 , 95 % CI 1.37 - 7.91 [ P = 0.008 ] and 6.92 , 95 % CI 3.77 - 12.69 [ P < 0.001 ] , respectively ) . The benefit of single and multiple EMS practice s on overall performance score remained significant after adjustment for success or failure of deep biliary cannulation ( aOR 2.98 , 95 % CI 1.38 - 6.43 [ P = 0.005 ] and 6.09 , 95 % CI 2.40 - 15.45 [ P < 0.001 ] , respectively ) . The benefits of single vs. multiple EMS practice s were not statistically different . CONCLUSIONS Coached simulation using EMS improved novice trainees ' success of biliary cannulation and overall ERCP performance . Additional uncoached practice s did not appear to provide further benefit . Trainees should undergo a coached EMS practice at the beginning of ERCP training BACKGROUND AND AIM Computer-based endoscopic simulators have been developed in recent years , and their usefulness has been reported . However , there is no blinded prospect i ve r and omized controlled study on esophagogastroduodenoscopy ( EGD ) training using virtual reality simulators . The present study aim ed to assess the effectiveness of a computer-based simulator for basic training in EGD . METHODS The GI-Mentor II simulator was used . The subjects were 20 hospital medical residents . After receiving an explanation regarding the fundamentals of endoscopy , 10 trainees were each r and omized into a simulator group and a non-simulator group . The simulator group received 5 h of training with the GI-Mentor II plus bedside training , while the non-simulator group received bedside training . Subsequently , each subject performed endoscopy twice for assessment . Performance was evaluated according to a five- grade scale for a total of 11 items . RESULTS The score was significantly higher in the skills required for insertion into the esophagus , passing from the esophagogastric junction ( EGJ ) to the antrum , passing through the pylorus , and examination of the duodenal bulb and the fornix . CONCLUSIONS The performance of endoscopy was improved by 5 h of simulator training . The simulator was more effective with regard to the items related to manipulation skills . Computer-based simulator training in EGD is useful for beginners OBJECTIVES : Computer-based colonoscopy simulation ( CBCS ) is being utilized in endoscopy training without supporting evidence that it improves patient-based colonoscopy performance . The goal of this pilot study was to determine if CBCS training improves gastroenterology ( GI ) fellows ' patient-based colonoscopy skills . METHODS : Competency at colonoscopy among 4 novice GI fellows who completed a 6-h CBCS curriculum was compared with 4 novice fellows who were not CBCS-trained . Measurements of competency were rendered by supervising faculty by recording “ insertion time,”“depth of unassisted insertion,”“independent procedure completion,”“ability to identify endoscopic l and marks,”“inserts in a safe manner,”“adequately visualizes mucosa on withdrawal , ” and “ responds appropriately to patient discomfort ” with each colonoscopy . RESULTS : Simulator-trained fellows outperformed traditionally trained fellows during their initial 15 colonoscopies in all performance aspects except “ insertion time ” ( pp < 0.05 ) . Simulator-trained fellows inserted the endoscope significantly further and reached the cecum independently nearly twice as often during this early training period . Three parameters ( “ depth of insertion,”“independent completion , ” and “ ability to identify l and marks ” ) demonstrated a continued advantage out to 30 colonoscopies . Beyond 30 procedures , there was no difference in the performance of the two groups . CONCLUSION : In this pilot study , a 6-h CBCS curriculum provides an early training advantage by enhancing competency at the early stages of patient-based colonoscopy . These advantages are negligible after approximately 30 patient-based procedures . CBCS-enhanced training may allow faculty to be more efficient with their colonoscopy practice Background : Flexible sigmoidoscopy , a core skill for the primary care physician , requires learned h and -eye skills that can be difficult to master during residency training . With recent advances in virtual reality simulation technology , simulated flexible sigmoidoscopes are available to family medicine residents for training before their initial and subsequent live patient examinations . The purpose of the study was to determine whether a virtual reality flexible sigmoidoscope simulator would improve the h and -eye skills and various performance parameters in a live patient . Methods : Residents were assigned to a control ( n = 5 ) or experimental group ( n = 5 ) in which the experimental group trained on a virtual reality sigmoidoscopy simulator before their first sigmoidoscopies on live patient volunteers . After the initial live patient sigmoidoscopies , both control and experimental groups trained on the simulator so that it was possible to evaluate presimulator and postsimulator training effects on live patient performance and to compare speed and skill between the groups at different levels of training . Results : Training on the virtual reality simulator produced substantial improvements in examination times and h and -eye skill measures . After 6 to 10 hours of training on the simulator , the experimental group achieved significantly faster insertion times to 30 cm ( 119 versus 357 sec , P = 0.03 ) , 40 cm ( 211 versus 518 sec , P = 0.03 ) , and a shorter mean length of examination ( 323 versus 654 sec , P = 0.01 ) . There was also significant improvement of h and -eye skill measures of the experimental group in directional errors ( 1.6 versus . 8.6 , P < 0.01 ) , percentage of colon visualized ( 79 versus 45 percent , P = 0.02 ) , and viewing quality of examination when compared with the control group 's initial performance on live patients . Resident survey findings after the study confirmed the trainee 's perception of the benefit of the simulator training . Conclusions : This study shows the value of virtual reality simulator training for accelerating the development of the h and -eye skills to perform adequate sigmoidoscopy Objective : To develop and vali date an ex vivo comprehensive curriculum for a basic laparoscopic procedure . Background : Although simulators have been well vali date d as tools to teach technical skills , their integration into comprehensive curricula is lacking . Moreover , neither the effect of ex vivo training on learning curves in the operating room ( OR ) , nor the effect on nontechnical proficiency has been investigated . Methods : This r and omized single-blinded prospect i ve trial allocated 20 surgical trainees to a structured training and assessment curriculum ( STAC ) group or conventional residency training . The STAC consisted of case-based learning , proficiency-based virtual reality training , laparoscopic box training , and OR participation . After completion of the intervention , all participants performed 5 sequential laparoscopic cholecystectomies in the OR . The primary outcome measure was the difference in technical performance between the 2 groups during the first laparoscopic cholecystectomy . Secondary outcome measures included differences with respect to learning curves in the OR , technical proficiency of each sequential laparoscopic cholecystectomy , and nontechnical skills . Results : Residents in the STAC group outperformed residents in the conventional group in the first ( P = 0.004 ) , second ( P = 0.036 ) , third ( P = 0.021 ) , and fourth ( P = 0.023 ) laparoscopic cholecystectomies . The conventional group demonstrated a significant learning curve in the OR ( P = 0.015 ) in contrast to the STAC group ( P = 0.032 ) . Residents in the STAC group also had significantly higher nontechnical skills ( P = 0.027 ) . Conclusions : Participating in the STAC shifted the learning curve for a basic laparoscopic procedure from the operating room into the simulation laboratory . STAC-trained residents had superior technical proficiency in the OR and nontechnical skills compared with conventionally trained residents . ( The study registration ID is NCT01560494 . BACKGROUND AND STUDY AIMS Clinical investigation using endoscopy simulators is now possible due to recent advances in virtual reality technology . A prospect i ve r and omized trial was conducted to compare the exclusive use of a virtual reality endoscopy simulator with bedside teaching for training in sigmoidoscopy . MATERIAL S AND METHODS Internal medicine residents were r and omly assigned to training exclusively using a virtual reality simulator ( group 1 ) or via bedside teaching ( group 2 ) . Residents were then observed performing five sigmoidoscopic procedures in asymptomatic patients referred for colorectal cancer screening . Endoscopic examinations were evaluated for procedure duration , completion , ability to perform retroflexion , and level of patient comfort/discomfort . Each examination was scored from 1 ( inability to insert the endoscope beyond the rectum ) to 5 ( able to complete the entire examination independently in less than 20 min ) . RESULTS Sixty-six sigmoidoscopic examinations were completed by nine residents in group 1 ( simulator-trained group ) and seven residents in group 2 ( traditional teaching group ) . Participants in group 1 had more difficulty with initial endoscope insertion and negotiation of the rectosigmoid junction ( mean score + /- SEM 2.9 + /- 0.2 ) than those in group 2 ( 3.8 + /- 0.2 ) ( P < 0.001 ) . The splenic flexure was reached independently in 10 of 34 examinations ( 29 % ) in group 1 , compared with 23 of 32 examinations ( 72 % ) in group 2 ( P = 0.001 ) . Retroflexion was successfully performed by 19 of 34 ( 56 % ) in group 1 compared to 27 of 32 ( 84 % ) in group 2 ( P = 0.02 ) . The average procedure time , patient satisfaction , and discomfort associated with the procedure did not differ statistically between the two groups . CONCLUSIONS The use of a state-of-the-art virtual reality-based endoscopy simulator is inferior to traditional bedside teaching techniques when used exclusively for training medical residents to perform sigmoidoscopy Background The aim of this study was to analyze the learning curve for the GI Mentor II endoscope trainer and to determine whether psychomotor training can contribute to an improvement in the performance of virtual colonoscopy . Methods To analyze the learning curve , 28 subjects were divided into three groups on the basis of their experience with gastrointestinal ( GI ) endoscopy : experienced surgeons ( group 1 , performed > 200 endoscopic procedures , ( n = 8) ) residents ( group 2 , performed < 50 endoscopic procedures , ( n = 10 ) ) ; and medical students ( group 3 , never performed GI endoscopy , ( n = 10 ) ) . The participants were tested on the GI Mentor II virtual reality simulator 10 consecutive times . Assessment of the learning curve was based on the following three parameters : time used , number of punctured balloons , and number of wall collisions . In the second part of the study , 20 subjects who had never performed GI endoscopy were included . After performing a virtual colonoscopy , they were r and omized to a group that received psychomotor training and a control group . Finally , all subjects performed a virtual colonoscopy . Assessment of endoscopic skills during the colonoscopy was based on nine parameters dealing with psychomotor skills . Results The learning curve for time expended reached a plateau after the second repetition for group 1 ( Friedman ’s test , p < 0.05 ) , after the fifth repetition for group 2 ( p < 0.05 ) , and after the seventh repetition for group 3 ( p < 0.05 ) . Experienced surgeons did not improve their scores for regarding number of balloons punctured or number of wall collisions ( p > 0.05 ) , indicating the absence of a learning curve for these parameters . Group 2 improved their scores up to the fourth and fifth repetitions , respectively ( p < 0.05 ) , and group 3 up to the fifth and seventh repetitions , respectively ( p < 0.05 ) . Experienced surgeons achieved the best performance , followed by group 2 and then group 3 . The surgeons who had received psychomotor training performed the second virtual colonoscopy significantly faster than the control group ( Mann-Whitney test , p < 0.001 ) and made significantly greater improvement in all other parameters as well . Conclusions There were different learning curves for surgeons depending on their endoscopic background . The familiarization rate on the simulator was proportional to the endoscopic experience of the surgeons . Psychomotor training had a significant effect on the performance of a simulated colonoscopy BACKGROUND The Erlangen Active Simulator for Interventional Endoscopy ( EASIE ) was introduced in 1997 for interventional endoscopy training . compactEASIE developed in 1998 is a modified , light-weight version of the original model . Objective evidence of the benefits of training with these models is limited . A r and omized controlled study , therefore , was conducted to compare the effects of intensive 7-month , h and s-on training in hemostatic techniques by using the compactEASIE model ( in addition to clinical endoscopic training ) vs. pure clinical training in endoscopic hemostatic methods . METHODS Thirty-seven fellows in gastroenterology in New York City area training programs were enrolled . Baseline skills were assessed on the simulator for the following techniques : manual skills , injection and electrocoagulation , hemoclip application , and variceal ligation . Twenty-eight fellows were then r and omized into two comparable groups . Those r and omized to Group A received purely clinical training in endoscopic hemostatic techniques at their hospitals . Those in Group B , in addition , were trained by experienced tutors in 3 full-day hemostasis workshops over 7 months . Both groups underwent a final evaluation on the compactEASIE simulator conducted by their tutors and additional evaluators who were blinded to the method of training . Initial and final evaluation scores were compared for each group and between groups . Outcomes of actual clinical hemostatic procedures performed during the study period also were analyzed . RESULTS Ten of 14 fellows r and omized to Group A ( st and ard training ) and 13 of 14 in Group B ( intensive training ) returned for the final evaluation . For Group B , scores for all techniques were significantly improved . In Group A , a significant improvement was noted for variceal ligation alone . CONCLUSIONS compactEASIE simulator training ( 3 sessions over 7 months ) , together with clinical endoscopic training result ed in objective improvement in the performance by fellows of all 4 endoscopic hemostatic techniques , whereas significant improvement was noted for variceal ligation alone for fellows who had st and ard clinical training . In clinical practice , fellows who had intensive simulator/ clinical training had a significantly higher success rate and a nonsignificant reduction in the frequency of occurrence of complications BACKGROUND Skills in gastrointestinal endoscopy mainly depend on experience and practice . Patients upon whom trainees perform their first endoscopic examinations are likely to suffer more discomfort and prolonged procedures . Training on endoscopy simulators may reduce the time required to reach competency in patient endoscopy . PATIENTS AND METHODS Residents in internal medicine without experience of endoscopy were r and omized to a group who trained on a simulator before conventional training ( group S ) or one that received conventional training only ( group C ) before starting upper gastrointestinal endoscopy in patients . After endoscopy , discomfort and pain were evaluated by patients , who were blind to the beginners ' training status . Results in terms of time , technique ( intubation , pyloric passage , J-maneuver ) , and diagnosis of pathological entities were evaluated by experts . RESULTS From 2003 to 2007 , 28 residents were enrolled . Comparing group S with group C in their first ten endoscopic examinations in patients , time taken to reach the duodenum ( 239 seconds ( range 50 - 620 ) vs. 310 seconds ( 110 - 720 ; P < 0.0001 ) and technical accuracy ( P < 0.02 ) were significantly better in group S. Diagnostic accuracy did not differ between the groups . Fourteen residents ( 7 simulator-trained , 7 not simulator-trained ) continued endoscopy training . After 60 endoscopic examinations , investigation time was still shorter in group S. Technical and diagnostic accuracy improved during on-patient training in both groups ; here differences between groups were no longer observable . There were no significant differences in discomfort and pain scores between the groups after 10 and after 60 endoscopies . Discomfort and pain were higher than for endoscopy performed by experts . CONCLUSION This r and omized controlled trial shows that virtual simulator training significantly affects technical accuracy in the early and mid-term stages of endoscopic training . It helps reduce the time needed to reach technical competency , but clinical ly the effect is limited . Simulator training could be useful in an endoscopy training curriculum but can not replace on-patient training OBJECTIVE Computer-based colonoscopy simulators ( CBCS ) have been developed and are being introduced into the training environment . The ability of these simulators to replicate the dimensions of patient-based diagnostic colonoscopy is good . However , the benefit of simulators to either learners or their patients has not yet been established . We describe a process by which a CBCS curriculum and CBCS-based performance criteria were established for first-year gastroenterology fellows at the Mayo Clinic in Rochester , Minnesota . DESCRIPTION We used a commercially available CBCS ( AccuTouch Endoscopy Simulator , Immersion Medical , Gaithersburg , MD ) , which consists of a specialized colonoscope that is inserted into a computer-based module with a screen showing the colonic lumen of a virtual patient . A tutorial and six cases of varying complexity are available on the CBCS . Performance variables that are measured by the simulator include the time to complete the procedure , the distance that the scope was advanced , the degree to which the mucosa was adequately visualized , the possible complications such as colonic perforation , and the level of pain experienced by the simulated patient . To begin , we established ideal performance st and ards by measuring the above variables for ten " expert " faculty colonscopists who completed two cases on the CBCS . Next , we measured CBCS performance st and ards for five partially trained colonoscopists . Finally , two non-physician gastrointestinal assistants , without prior endoscopic training , were asked to practice on the simulator to determine the time and procedure frequency required to improve their CBCS proficiency . By calculating average performance st and ards within each of these three groups , we were able to estimate the number of CBCS cases and minimal performance st and ards for new trainees . Based on the learning curves for novice colonoscopists as well as the performances of partially trained and expert colonoscopists , we speculated that if CBCS training were to be beneficial , the benefit would most likely occur at the early stages of training . The curriculum we developed consists of viewing a one-hour , multimedia tutorial , which describes the procedure and various colonoscopy techniques . This is followed by nine hours of h and s-on CBCS experience , during which time the trainee will complete approximately 25 CBCS colonoscopies . Before advancing to live-patient colonoscopies , the trainee must meet certain performance st and ards on specific CBCS cases . These st and ards include the ability to view the entire colon in less than 15 minutes with minimal pain and no complications . DISCUSSION If effective , this new colonoscopy training curriculum should result in improved competency at patient-based colonoscopy , particularly in the early stages of training . To address this question , first-year gastroenterology fellows at Mayo Clinic have been r and omized into two groups : ( 1 ) a group that experiences a tutorial with h and s-on CBCS curriculum and ( 2 ) a group that experiences a tutorial only . Their performances at patient-based colonoscopy as well as surveys of patient satisfaction will be measured and analyzed to determine what , if any , benefit is provided by CBCS Background Recently , virtual reality computer simulators have been used to enhance traditional endoscopy teaching . Previous studies have demonstrated construct validity of these systems and transfer of virtual skills to the operating room . However , to date no simulator-training curricula have been design ed and there is very little evidence on the impact of external feedback on acquisition of endoscopic skills . The aim of the present study was to assess the impact of external feedback on the learning curves on a VR colonoscopy simulator using inexperienced trainees . Material s and methods 22 trainees , without colonoscopy experience were r and omised to a group which received structured feedback provided by an experienced supervisor and a controlled group . All participants performed 15 repetitions of task 3 from the Introduction colonoscopy module of the Accu Touch Endoscopy simulator . Retention/transfer tests on simulator were performed 4–6 weeks after the last repetition . The proficiency levels were based on the performance of eight experienced colonoscopists . Results All subjects were able to complete the procedure on the simulator . There were no perforations in the feedback group versus seven in the non-feedback group . Subjects in the feedback group reached expert proficiency levels in percentage of mucosa visualised and time to reach the caecum significantly faster compared with the control group . None of the groups demonstrated significant degradation of performance in simulator retention/transfer tests . Conclusion Concurrent feedback given by supervisor concur an advantage in acquisition of basic colonoscopy skills and achieving of proficiency level as compared to independent training BACKGROUND The Olympus colonoscopy simulator provides a high-fidelity training platform design ed to develop knowledge and skills in colonoscopy . It has the potential to shorten the learning process to competency . OBJECTIVE To investigate the efficacy of the simulator in training novices in colonoscopy by comparing training outcomes from simulator training with those of st and ard patient-based training . DESIGN Multinational , multicenter , single-blind , r and omized , controlled trial . SETTING Four academic endoscopy centers in the United Kingdom , Italy , and The Netherl and s. PARTICIPANTS AND INTERVENTION This study included 36 novice colonoscopists who were r and omized to 16 hours of simulator training ( subjects ) or patient-based training ( controls ) . Participants completed 3 simulator cases before and after training . Three live cases were assessed after training by blinded experts . MAIN OUTCOME MEASUREMENTS Automatically recorded performance metrics for the simulator cases and blinded expert assessment of live cases using Direct Observation of Procedural Skills and Global Score sheets . RESULTS Simulator training significantly improved performance on simulated cases compared with patient-based training . Subjects had higher completion rates ( P=.001 ) and shorter completion times ( P < .001 ) and demonstrated superior technical skill ( reduced simulated pain scores , correct use of abdominal pressure , and loop management ) . On live colonoscopy , there were no significant differences between the 2 groups . LIMITATIONS Assessment tools for live colonoscopies may lack sensitivity to discriminate between the skills of relative novices . CONCLUSION Performance of novices trained on the colonoscopy simulator matched the performance of those with st and ard patient-based colonoscopy training , and novices in the simulator group demonstrated superior technical skills on simulated cases . The simulator should be considered as a tool for developing knowledge and skills prior to clinical practice BACKGROUND Training simulators have been used for decades with success ; however , a st and ardized educational strategy for diagnostic EGD is still lacking . OBJECTIVE Development of a training strategy for diagnostic upper endoscopy . STUDY DESIGN Prospect i ve , r and omized trial . SETTING S A total of 28 medical and surgical residents without endoscopic experience were enrolled . Basic skills evaluations were performed following a structured program involving theoretical lectures and a h and s-on course in diagnostic EGD . Subsequently , stratified r and omization to clinical plus simulator training ( group 1 , n = 10 ) , clinical training only ( group 2 , n = 9 ) , or simulator training only ( group 3 , n = 9 ) was performed . Ten sessions of simulator training were conducted for groups 1 and 3 during the 4-month program . Group 2 underwent st and ard training in endoscopy without supplemental simulator training . The final evaluation was performed on the simulator and by observation of 3 clinical cases . Skills and procedural times were recorded by blinded and unblinded evaluators . MAIN OUTCOME MEASUREMENTS Time to reach the duodenum , pylorus , or esophagus . RESULTS All trainees demonstrated a significant reduction in procedure time during a simple manual skills test ( P < .05 ) and significantly better skills scores ( P = .006 , P = .042 and P = .017 ) in the simulator independent of the training strategy . Group 1 showed shorter times to intubate the esophagus ( 61 ± 26 seconds vs 85 ± 30 seconds and 95 ± 36 seconds ) and the pylorus ( 183 ± 65 seconds vs 207 ± 61 seconds and 247 ± 66 seconds ) during the clinical evaluation . Blinded assessment of EGD skills showed significantly better results for group 1 compared with group 3 . Blinded and unblinded evaluations were not statistically different . LIMITATIONS Small sample size . CONCLUSIONS Structured simulator training supplementing clinical training in upper endoscopy appears to be superior to clinical training alone . Simulator training alone does not seem to be sufficient to improve endoscopic skills Purpose To evaluate the effectiveness of a novel , simulation-based educational model rooted in scaffolding theory that capitalizes on a systematic progressive sequence of simulators that increase in realism ( i.e. , fidelity ) and information content . Method Forty-five medical students were r and omly assigned to practice intravenous catheterization using high-fidelity training , low-fidelity training , or progressive training from low to mid to high fidelity . One week later , participants completed a transfer test on a st and ardized patient simulation . Blinded expert raters assessed participants ' global clinical performance , communication , procedure documentation , and technical skills on the transfer test . Participants ' management of the re sources available during practice was also recorded . Data were analyzed using multivariate analysis of variance . The study was conducted in fall 2008 at the University of Toronto . Results The high-fidelity group scored higher ( P < .05 ) than the low-fidelity group on all measures except procedure documentation . The progressive group scored higher ( P < .05 ) than other groups for documentation and global clinical performance and was equivalent to the high-fidelity group for communication and technical skills . Total practice time was greatest for the progressive group ; however , this group required little practice time on the re source -intensive high-fidelity simulator . Conclusions Allowing students to progress in their practice on simulators of increasing fidelity led to superior transfer of a broad range of clinical skills . Further , this progressive group was re source -efficient , as participants concentrated on lower fidelity and lower re source -intensive simulators . It is suggested that clinical training curricula incorporate exposure to multiple simulators to maximize educational benefit and potentially save educator time 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 ( enrollment , 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 BACKGROUND Comfort during colonoscopy is a critical component of safety and quality . OBJECTIVE To develop and vali date the Nurse-Assessed Patient Comfort Score ( NAPCOMS ) . DESIGN Prospect i ve scale validation . SETTING Colorectal cancer screening centers in the United Kingdom and Canada . PATIENTS A total of 300 consecutive patients undergoing colonoscopy at participating colorectal cancer screening centers . INTERVENTION The NAPCOMS was developed by using a modified Delphi process . During colonoscopy , two endoscopy room nurses independently observed and rated patient comfort and tolerability by using NAPCOMS . In addition , endoscopists reported global comfort scores and patients ' reported global comfort by using visual 4-point Likert and National Health Service-United Kingdom Global Rating Scales . MAIN OUTCOME MEASUREMENTS Reliability and validity of NAPCOMS was measured by using intraclass correlations ( ICC ) between nurse ratings of colonoscopies and between NAPCOMS , endoscopist ratings , and patient ratings of global comfort . RESULTS The ICC for the overall NAPCOMS was 0.84 ( 95 % confidence interval [ CI ] , 0.80 - 0.87 ) . There was high agreement between the NAPCOMS and endoscopist ratings of comfort ( ICC = 0.77 ; 95 % CI , 0.72 - 0.81 ) , moderate agreement between the NAPCOMS and patient ratings ( ICC = 0.61 ; 95 % CI , 0.53 - 0.67 ) , and moderate agreement between the endoscopist and patient ratings ( ICC = 0.52 ; 95 % CI , 0.43 - 0.60 ) . LIMITATIONS NAPCOMS was vali date d in out patients who received colonoscopy with minimal to moderate sedation as part of a screening and surveillance program , so performance among in patients or those requiring deep sedation was not tested . CONCLUSION NAPCOMS is a reliable and valid tool for assessing patient comfort in the setting of outpatient colonoscopy performed with minimal to moderate sedation |
11,730 | 30,324,342 | Conclusions Despite substantial heterogeneity , we found evidence to support the hypothesis that vitamin D influences the composition of the gastrointestinal microbiome . | Purpose Variation in the human microbiome has been linked with a variety of physiological functions , including immune regulation and metabolism and bio synthesis of vitamins , hormones , and neurotransmitters .
Evidence for extraskeletal effects of vitamin D has been accruing and it has been suggested that the effect of vitamin D on health is partially mediated through the microbiome .
We aim ed to critically evaluate the evidence linking vitamin D and the gastrointestinal microbiome . | Context Disruption of gut microbiota may exacerbate severity of cystic fibrosis ( CF ) . Vitamin D deficiency is a common comorbidity in patients with CF that may influence composition of the gut microbiota . Objectives Compare microbiota of vitamin D-sufficient and -insufficient CF patients and assess impact of a weekly high-dose vitamin D3 bolus regimen on gut and airway microbiome in adults with CF and vitamin D insufficiency ( 25-hydroxyvitamin D < 30 ng/mL ) . Design Forty-one subjects with CF were classified into two groups : vitamin D insufficient ( n = 23 ) and vitamin D sufficient ( n = 18 ) . Subjects with vitamin D insufficiency were r and omized to receive 50,000 IU of oral vitamin D3 or placebo weekly for 12 weeks . Sputum and stool sample s were obtained pre- and postintervention and 16S ribosomal RNA genes sequenced using Illumina MiSeq technology . Results Gut microbiota differed significantly based on vitamin D status with Gammaproteobacteria , which contain numerous , potentially pathogenic species enriched in the vitamin D-insufficient group . Principal coordinates analysis showed differential gut microbiota composition within the vitamin D-insufficient patients following 12 weeks treatment with placebo or vitamin D3 ( permutation multivariate analysis of variance = 0.024 ) , with Lactococcus significantly enriched in subjects treated with vitamin D3 , whereas Veillonella and Erysipelotrichaceae were significantly enriched in patients treated with placebo . Conclusion This exploratory study suggests that vitamin D insufficiency is associated with alterations in microbiota composition that may promote inflammation and that supplementation with vitamin D has the potential to impact microbiota composition . Additional studies to determine the impact of vitamin D on microbiota benefit clinical outcomes in CF are warranted The importance of gut microbiota in pathogenesis of diabetes remains unknown . This study investigated the relationship between microbiota and metabolic markers in African American men ( AAM ) with prediabetes and hypovitaminosis D. The study was ancillary to a r and omized trial of vitamin D supplementation with weekly ergocalciferol ( 50,000 IU ) conducted in AAM veterans over 12 months ( D Intervention in Veterans Affairs ) . Glycemic groups ( Gr ) were characterized based on changes in oral glucose tolerance between baseline and exit . Subjects with stable normal glucose tolerance were assigned to Gr-1 and those with stable prediabetes ( impaired glucose tolerance and impaired fasting glucose ) to Gr-2 . Microbiota composition was analyzed in stool collected at the exit ( n = 115 ) and compared between Gr-1 and Gr-2 , as well as between the lowest and highest quartiles of dietary intake of energy and fat , hemoglobin A1c , and serum 25-hydroxyvitamin D ( 25[OH]D ) level . Differences between Gr-1 and Gr-2 included the Bacteroidetes/Firmicutes and Bacteroidales/Clostridia ratios and differences in genera such as Ruminococcus and Dialister . Changes in specific taxa associated with the lowest and highest quartiles of 25(OH)D ( eg , Ruminococcus , Roseburia , Blautia , Dorea ) were clearly distinct from those of dietary intake ( eg , Bacteroides , Bacteroides/Prevotella ratio ) or A1c ( eg , Faecalibacterium , Catenibacterium , Streptococcus ) . These findings suggest a novel interaction between microbiota and vitamin D and a role for microbiota in early stages of diabetes development . Although results suggest that specific taxa are associated with glycemic stability over time , a causative relationship between microbiota makeup and dysglycemia is still to be demonstrated Vitamin D has immunomodulatory properties giving it the potential to affect microbial colonization of the intestinal tract . We investigated whether maternal vitamin D supplemention , maternal plasma 25-hydroxyvitamin D concentration , or direct supplementation of the infant influences key bacterial taxa within microbiota of one month old infants . Infant and maternal vitamin D supplement use was ascertained via question naires . Maternal plasma 25-hydroxyvitamin D was determined at approximately the 36th week of pregnancy . In 913 one month old infants in the prospect i ve KOALA Birth Cohort Study , fecal Bifidobacterium spp . , Escherichia coli , Clostridium difficile , Bacteroides fragilis group , Lactobacillus spp . and total bacteria were quantified with real-time polymerase chain reaction assays targeting 16S rRNA gene sequences . The association between vitamin D exposure and prevalence or abundance of a specific bacterial group or species was analyzed using logistic or linear regression , respectively . There was a statistically significant negative linear trend between counts of Bifidobacterium spp . and levels of maternal vitamin D supplementation and maternal 25-hydroxyvitamin D quintiles , respectively . In addition , a positive linear trend between quintile groups and B. fragilis group counts was observed . Lower counts of C. difficile were associated with vitamin D supplementation of breast fed infants whose mothers were more likely to adhere to an alternative lifestyle in terms of , e.g. , dietary habits . These data suggest that vitamin D influences the abundance of several key bacterial taxa within the infant microbiota . Given that intestinal microbiotic homeostasis may be an important factor in the prevention of immune mediated diseases and that vitamin D status is a modifiable factor , further investigation of the impact of postnatal vitamin D supplementation should be conducted in older infants Background : The gut microbiome in infancy influences immune system maturation , and may have an important impact on allergic disease risk . Objective : We sought to determine how prenatal and early life factors impact the gut microbiome in a relatively large , ethnically diverse study population of infants at age 3 to 6 months , who were enrolled in Vitamin D Antenatal Asthma Reduction Trial , a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring . Methods : We performed 16S rRNA gene sequencing on 333 infants ' stool sample s. Microbial diversity was computed using the Shannon index . Factor analysis applied to the top 25 most abundant taxa revealed 4 underlying bacterial coabundance groups ; the first dominated by Firmicutes ( Lachnospiraceae/Clostridiales ) , the second by Proteobacteria ( Klebsiella/Enterobacter ) , the third by Bacteriodetes , and the fourth by Veillonella . Scores for coabundance groups were used as outcomes in regression models , with prenatal/birth and demographic characteristics as independent predictors . Multivariate analysis , using all microbial community members , was also conducted . Results : White race/ethnicity was associated with lower diversity but higher Bacteroidetes coabundance scores . C‐section birth was associated with higher diversity , but decreased Bacteroidetes coabundance scores . Firmicutes scores were higher for infants born by C‐section . Breast‐fed infants had lower proportions of Clostridiales . Cord blood vitamin D was linked to increased Lachnobacterium , but decreased Lactococcus . Conclusions : The findings presented here suggest that race , mode of delivery , breast‐feeding , and cord blood vitamin D levels are associated with infant gut microbiome composition , with possible long‐term implication s for immune system modulation and asthma/allergic disease incidence |
11,731 | 30,177,784 | Cognitive behavioral therapy , relaxation therapy , multi-component psychological therapy , hypnotherapy , and dynamic psychotherapy were all beneficial when data from two or more RCTs were pooled .
: Antidepressants are efficacious in reducing symptoms in IBS patients . | OBJECTIVES : Irritable bowel syndrome ( IBS ) is a chronic functional bowel disorder that is thought to be due to a disorder of brain – gut function .
Drugs acting central ly , such as antidepressants , and psychological therapies may , therefore , be effective . | The aim of this study was to investigate if cognitive behavior therapy ( CBT ) based on exposure and mindfulness exercises delivered via the Internet would be effective in treating participants with irritable bowel syndrome ( IBS ) . Participants were recruited through self-referral . Eighty-six participants were included in the study and r and omized to treatment or control condition ( an online discussion forum ) . One participant was excluded after r and omization . The main outcome measure was IBS-symptom severity and secondary measures included IBS-related quality of life , GI-specific anxiety , depression and general functioning . Participants were assessed at pre-treatment , post-treatment and 3 month follow-up ( treatment condition only ) . Four participants ( 5 % of total sample ) in the treatment condition did not participate in post-treatment assessment . Participants in the treatment condition reported a 42 % decrease and participants in the control group reported a 12 % increase in primary IBS-symptoms . Compared to the control condition , participants in the treatment group improved on all secondary outcome measures with a large between group effect size on quality of life ( Cohen 's d = 1.21 ) . We conclude that CBT-based on exposure and mindfulness delivered via the Internet can be effective in treating IBS- patients , alleviating the total burden of symptoms and increasing quality of life Twenty patients with irritable bowel syndrome ( IBS ) were r and omly assigned either to intensive , individualized cognitive therapy ( 10 sessions over 8 weeks ) or to 8 weeks of daily gastrointestinal ( GI ) symptom monitoring . Pre- to posttreatment evaluations showed significantly ( p = .005 ) greater GI symptom reduction for those receiving cognitive therapy than for those in symptom monitoring . At posttreatment , 80 % of the cognitive therapy group showed clinical ly significant improvement , whereas only 10 % of the monitoring group showed this . Results held up well at a 3-month follow-up . Within the cognitive therapy group , GI symptom reductions correlated significantly with increases in positive and reductions in negative automatic thoughts OBJECTIVES : Psychological treatments are considered to be useful in the irritable bowel syndrome ( IBS ) , although the evidence is based on small , often flawed trials . Although cognitive behavior therapy ( CBT ) and relaxation therapy have both been promising , we hypothesized that CBT would be superior to relaxation and st and ard care alone in IBS patients . The objective of this study was to test this assumption by comparing the effects of cognitive behavior therapy with relaxation therapy and routine clinical care alone in individuals with IBS . METHODS : Patients ( n = 105 ) with Rome I criteria for IBS were recruited from advertisement ( n = 51 ) and outpatient clinics ( n = 54 ) ; those patients with resistant IBS were not included . A r and omized controlled trial with three arms ( st and ard care for all groups plus either CBT or relaxation ) for 8 wk was conducted , which applied blinded outcome assessment s using vali date d measures with 1 yr of follow-up . The primary outcome for this study was bowel symptom severity . RESULTS : Of 105 patients at the commencement of treatment , the mean bowel symptom frequency score for the whole sample was 21.1 and at the end of treatment had fallen to 18.1 ; this persisted at the 52-wk follow-up , with a significant linear trend for scores to change over time ( F= 39.57 p < 0.001 ) . However , there were no significant differences among the three treatment conditions . Significant changes over time were found for physical functioning ( F= 4.37 , p < 0.001 ) , pain ( F= 3.12 , p < 0.05 ) , general health ( F= 2.71 , p < 0.05 ) , vitality ( F= 2.94 , p < 0.05 ) , and the social functioning scales on the Medical Outcomes Study Short Form 36 ( F= 4.08 , p < 0.05 ) ; however , all three arms showed similar improvement . There were significant reductions in anxiety , depression , and locus of control scales , but no significant differences among the treatment groups were detected . CONCLUSION : Cognitive behavior and relaxation therapy seem not to be superior to st and ard care alone in IBS CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice . Behavioral and pharmacological therapies each appear modestly effective , but data are lacking on their separate and combined effects . OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies , singly and combined , for chronic tension-type headaches . DESIGN AND SETTING R and omized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio . PARTICIPANTS Two hundred three adults ( mean age , 37 years ; 76 % women ) with diagnosis of chronic tension-type headaches ( mean , 26 headache d/mo ) . INTERVENTIONS Participants were r and omly assigned to receive tricyclic antidepressant ( amitriptyline hydrochloride , up to 100 mg/d , or nortriptyline hydrochloride , up to 75 mg/d ) medication ( n = 53 ) , placebo ( n = 48 ) , stress management ( eg , relaxation , cognitive coping ) therapy ( 3 sessions and 2 telephone contacts ) plus placebo ( n = 49 ) , or stress management therapy plus antidepressant medication ( n = 53 ) . MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings ( 0 - 10 scale ) recorded by participants in a daily diary 4 times per day ; number of days per month with at least moderate pain ( pain rating > /=5 ) , analgesic medication use , and Headache Disability Inventory scores , compared by intervention group . RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity , analgesic medication use , and headache-related disability than placebo , but antidepressant medication yielded more rapid improvements in headache activity . Combined therapy was more likely to produce clinical ly significant ( > /=50 % ) reductions in headache index scores ( 64 % of participants ) than antidepressant medication ( 38 % of participants ; P = .006 ) , stress management therapy ( 35 % ; P = .003 ) , or placebo ( 29 % ; P = .001 ) . On other measures the combined therapy and its 2 component therapies produced similar outcomes . CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches . Combined therapy may improve outcome relative to monotherapy Study Design . A 14-week , r and omized , double-blind , multicenter , placebo-controlled study of Japanese patients with chronic low back pain ( CLBP ) who were r and omized to either duloxetine 60 mg once daily or placebo . Objective . This study aim ed to assess the efficacy and safety of duloxetine monotherapy in Japanese patients with CLBP . Summary of Background Data . In Japan , duloxetine is approved for the treatment of depression , diabetic neuropathic pain , and pain associated with fibromyalgia ; however , no clinical study of duloxetine has been conducted for CLBP . Methods . The primary efficacy measure was the change in the Brief Pain Inventory ( BPI ) average pain score from baseline to Week 14 . Secondary efficacy measures included BPI pain ( worst pain , least pain , pain right now ) , Patient 's Global Impression of Improvement , Clinical Global Impressions of Severity , and Rol and -Morris Disability Question naire , among other measures , and safety and tolerability . Results . In total , 458 patients were r and omized to receive either duloxetine ( n = 232 ) or placebo ( n = 226 ) . The BPI average pain score improved significantly in the duloxetine group compared with that in the placebo group at Week 14 [ −2.43 ± 0.11 vs. −1.96 ± 0.11 , respectively ; between-group difference ( 95 % confidence interval ) , − 0.46 [ −0.77 to−0.16 ] ; P = 0.0026 ] . The duloxetine group showed significant improvement in many secondary measures compared with the placebo group , including BPI pain ( least pain , pain right now ) ( between-group difference : −1.69 ± 0.10 , P = 0.0009 ; −2.42 ± 0.12 , P P = 0.0230 , respectively ) , Patient 's Global Impression of Improvement ( 2.46 ± 0.07 , P = 0.0026 ) , Clinical Global Impressions of Severity ( −1.46 ± 0.06 , P = 0.0019 ) , and Rol and -Morris Disability Question naire ( −3.86 ± 0.22 , P = 0.0439 ) . Adverse events occurring at a significantly higher incidence in the duloxetine group were somnolence , constipation , nausea , dizziness , and dry mouth , most of which were mild or moderate in severity and were resolved or improved . Conclusion . Duloxetine 60 mg was effective and well tolerated in Japanese CLBP patients . Level of Evidence : BACKGROUND Recent guidelines for the treatment of irritable bowel syndrome ( IBS ) emphasize the need for research to facilitate home-based self-management for these patients in primary care . The aim of the current study was to test the efficacy of a manualized cognitive behavioural therapy (CBT)-based self-management programme for IBS in a pilot r and omized controlled trial ( RCT ) . METHOD Sixty-four primary -care patients meeting Rome criteria for IBS were r and omized into either self-management plus treatment as usual ( TAU ) ( n=31 ) or a TAU control condition ( n=33 ) . The self-management condition included a structured 7-week manualized programme that was self-administered in conjunction with a 1-hour face-to-face therapy session and two 1-hour telephone sessions . The primary outcome measures were the Subject 's Global Assessment ( SGA ) of Relief and the Irritable Bowel Syndrome Severity Scoring System ( IBS-SSS ) assessed at baseline , end of treatment ( 2 months ) , and 3 and 6 months post-treatment . RESULTS Analysis was by intention-to-treat . Twenty-three ( 76.7 % ) of the self-management group rated themselves as experiencing symptom relief across all three time periods compared to seven ( 21.2 % ) of the TAU controls [ odds ratio ( OR ) 12.2 , 95 % confidence interval ( CI ) 3.72 - 40.1 ] . At 8 months , 25 ( 83 % ) of the self-management group showed a clinical ly significant change on the IBS-SSS compared to 16 ( 49 % ) of the control group ( OR 5.3 , 95 % CI 1.64 - 17.26 ) . CONCLUSIONS This study provides preliminary evidence that CBT-based self-management in the form of a structured manual and minimal therapist contact is an effective and acceptable form of treatment for primary -care IBS patients OBJECTIVES : Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome ( IBS ) . However , r and omized , controlled studies are rare and few have been performed outside highly specialized research centers . The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical setting s outside the traditional research units . METHODS : The study population included IBS patients refractory to st and ard management . In study 1 , patients were r and omized to receive gut-directed hypnotherapy ( 12 sessions , 1 h/week ) in psychology private practice s or supportive therapy , whereas patients were r and omized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2 . Gastrointestinal symptom severity and quality of life were evaluated at baseline , at 3 months follow-up and after 1 year . RESULTS : We r and omized 138 IBS patients refractory to st and ard management , 90 in study 1 and 48 in study 2 . In both the studies , IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups ( P<0.05 ) , but not in the control groups ( ns ) . In study 1 , a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group ( P<0.05 ) , and a trend in the same direction was seen in study 2 ( P=0.17 ) . The results seen at 3 months were sustained up to 1 year . CONCLUSIONS : Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS , but the effectiveness is lower when the therapy is given outside the highly specialized research centers Background Irritable bowel syndrome is the most common disorder diagnosed by gastroenterologists . Although several r and omized‐controlled trials have assessed the therapeutic role of antidepressant drugs , there is insufficient evidence to support their use One hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy , relaxation , and st and ard medical treatment compared with st and ard medical treatment alone . Patients were only selected if their symptoms had not improved with st and ard medical treatment over the previous 6 months . At 3 months , the treatment group showed significantly greater improvement than the controls on both gastroenterologists ' and patients ' ratings of diarrhea and abdominal pain , but constipation changed little . Good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress , whereas those with constant abdominal pain were helped little by this treatment . This study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to st and ard medical treatment BACKGROUND Irritable bowel syndrome ( IBS ) is a chronic and debilitating medical condition with few efficacious pharmacological or psychosocial treatment options available . Evidence suggests that visceral anxiety may be implicated in IBS onset and severity . Thus , cognitive-behavioral treatment ( CBT ) that targets visceral anxiety may alleviate IBS symptoms . METHODS The current study examined the efficacy of a CBT protocol for the treatment of IBS which directly targeted visceral sensations . Participants ( N = 110 ) were r and omized to receive 10 sessions of either : ( a ) CBT with interoceptive exposure ( IE ) to visceral sensations ; ( b ) stress management ( SM ) ; or ( c ) an attention control ( AC ) , and were assessed at baseline , mid-treatment , post-treatment , and follow-up sessions . RESULTS Consistent with hypotheses , the IE group outperformed AC on several indices of outcome , and outperformed SM in some domains . No differences were observed between SM and AC . The results suggest that IE may be a particularly efficacious treatment for IBS . CONCLUSIONS Implication s for research and clinical practice are discussed Antidepressants are used in irritable bowel syndrome ( IBS ) and may have effects on the gut independent of improving mood . We have investigated the actions of a tricyclic antidepressant on small intestinal motor function in eight healthy volunteers and in six patients with diarrhea-predominant IBS . Fasting ambulatory motility was recorded from six small intestinal sites for 16–18 hr while on no drug ( baseline ) and while taking imipramine for five days . Orocecal transit time ( OCTT ) was measured by lactulose hydrogen breath test , during baseline and imipramine administration . Imipramine did not alter migrating motor complex periodicity , but slowed jejunal phase III propagation velocity in controls from 7.5±1.1 to 3.6±0.5 cm/min ( P<0.01 ) and in IBS from 7.8±0.6 to 4.4±0.5 cm/min ( P<0.0001 ) . Phase III duration at each site was increased , and total recorded phase III was greater during imipramine than baseline studies . Imipramine increased the amplitude of phase III contractions . There was no effect of imipramine on non-phase-III motility index or discrete clustered contractions . Imipramine prolonged OCTT from 73±6 min to 97±8 min in controls ( P<0.05 ) and from 61±9 min to 89±8 min in IBS ( P<0.05 ) . Although OCTT was shorter in this IBS group , no motility differences were seen between controls and IBS . This demonstration that a tricyclic antidepressant can modify small intestinal motor function in health and in IBS supports the view that these drugs may have therapeutic actions in IBS unrelated to mood improvement Objective Postpr and ial symptoms in irritable bowel syndrome are common and relate to an exaggerated motor and sensory component of the gastrocolonic response . We investigated whether this response can be affected by hypnotherapy . Methods We included 28 patients with irritable bowel syndrome refractory to other treatments . They were r and omized to receive gut-directed hypnotherapy 1 hour per week for 12 weeks ( N = 14 ) or were provided with supportive therapy ( control group ; N = 14 ) . Before r and omization and after 3 months , all patients underwent a colonic distension trial before and after a 1-hour duodenal lipid infusion . Colonic sensory thresholds and tonic and phasic motor activity were assessed . Results Before r and omization , reduced thresholds after vs. before lipid infusion were seen in both groups for all studied sensations . At 3 months , the colonic sensitivity before duodenal lipids did not differ between groups . Controls reduced their thresholds after duodenal lipids for gas ( 22 ± 1.7 mm Hg vs. 16 ± 1.6 mm Hg , p < .01 ) , discomfort ( 29 ± 2.9 mm Hg vs. 22 ± 2.6 mm Hg , p < .01 ) , and pain ( 33 ± 2.7 mm Hg vs. 26 ± 3.3 mm Hg , p < .01 ) , whereas the hypnotherapy group reduced their thresholds after lipids only for pain ( 35 ± 4.0 mm Hg vs. 29 ± 4.7 mm Hg , p < .01 ) . The colonic balloon volumes and tone response at r and omization were similar in both groups . At 3 months , baseline balloon volumes were lower in the hypnotherapy group than in controls ( 83 ± 14 ml vs. 141 ± 15 ml , p < .01 ) . In the control group , reduced balloon volumes during lipid infusion were seen ( 141 ± 15 ml vs. 111 ± 19 ml , p < .05 ) , but not after hypnotherapy ( 83 ± 14 ml vs. 80 ± 16 ml , p > .20 ) . Conclusion Hypnotherapy reduces the sensory and motor component of the gastrocolonic response in patients with irritable bowel syndrome . These effects may be involved in the clinical efficacy of hypnotherapy in IBS This study evaluated the effects of serotonergic psychoactive agents on gastrointestinal functions in healthy human subjects . Participants received one of four regimens in a r and omized , double-blind manner : buspirone , a 5-HT(1A ) receptor agonist ( 10 mg twice daily ) ; paroxetine , a selective serotonin reuptake inhibitor ( 20 mg daily ) ; venlafaxine-XR , a selective serotonin and norepinephrine reuptake inhibitor ( 75 mg daily ) ; or placebo for 11 days . Physiological testing performed on days 8 - 11 included scintigraphic assessment of gastrointestinal and colonic transit , the nutrient drink test , and assessment of the postpr and ial change in gastric volume . Fifty-one healthy adults ( 40 females , 11 males ) participated in this study . No effects on gastric emptying or colonic transit were identified with any agent . Small bowel transit of a solid meal was accelerated by paroxetine . Buspirone decreased postpr and ial aggregate symptom and nausea scores . Venlafaxine-XR increased the postpr and ial change in gastric volume . Buspirone , paroxetine , and venlafaxine-XR affect upper gastrointestinal functions in healthy humans . These data support the need for clinical and physiological studies of these agents in functional gastrointestinal disorders Introduction Irritable bowel syndrome ( IBS ) affects 10–22 % of the UK population , with Engl and 's annual National Health Service ( NHS ) costs amounting to more than £ 200 million . Abdominal pain , bloating and altered bowel habit affect quality of life , social functioning and time off work . Current treatment relies on a positive diagnosis , reassurance , lifestyle advice and drug therapies , but many people suffer ongoing symptoms . Cognitive behaviour therapy ( CBT ) and self-management can be helpful , but availability is limited . Methods and analysis To determine the clinical - and cost-effectiveness of therapist delivered cognitive behavioural therapy ( TCBT ) and web-based CBT self-management ( WBCBT ) in IBS , 495 participants with refractory IBS will be r and omised to TCBT plus treatment as usual ( TAU ) ; WBCBT plus TAU ; or TAU alone . The two CBT programmes have similar content . However , TCBT consists of six , 60 min telephone CBT sessions with a therapist over 9 weeks , at home , and two ‘ booster ’ 1 hour follow-up phone calls at 4 and 8 months ( 8 h therapist contact time ) . WBCBT consists of access to a previously developed and piloted WBCBT management programme ( Regul8 ) and three 30 min therapist telephone sessions over 9 weeks , at home , and two ‘ booster ’ 30 min follow-up phone calls at 4 and 8 months ( 2½ h therapist contact time ) . Clinical effectiveness will be assessed by examining the difference between arms in the IBS Symptom Severity Score ( IBS SSS ) and Work and Social Adjustment Scale ( WASAS ) at 12 months from r and omisation . Cost-effectiveness will combine measures of re source use with the IBS SSS at 12 months and quality -adjusted life years . Ethics and dissemination This trial has full ethical approval . It will be disseminated via peer review ed publications and conference presentations . The results will enable clinicians , patients and health service planners to make informed decisions regarding the management of IBS with CBT . Trial registration number IS RCT N44427879 OBJECTIVES : This prospect i ve , r and omized controlled trial explored the feasibility and efficacy of a group program of mindfulness training , a cognitive-behavioral technique , for women with irritable bowel syndrome ( IBS ) . The technique involves training in intentionally attending to present-moment experience and non-judgmental awareness of body sensations and emotions . METHODS : Seventy-five female IBS patients were r and omly assigned to eight weekly and one half-day intensive sessions of either mindfulness group ( MG ) training or a support group ( SG ) . Participants completed the IBS severity scale ( primary outcome ) , IBS- quality of life , brief symptom inventory-18 , visceral sensitivity index , treatment credibility scale , and five-facet mindfulness question naire before and after treatment and at 3-month follow-up . RESULTS : Women in the MG showed greater reductions in IBS symptom severity immediately after training ( 26.4 % vs. 6.2 % reduction ; P=0.006 ) and at 3-month follow-up ( 38.2 % vs. 11.8 % ; P=0.001 ) relative to SG . Changes in quality of life , psychological distress , and visceral anxiety were not significantly different between groups immediately after treatment , but evidence d significantly greater improvements in the MG than in the SG at the 3-month follow-up . Mindfulness scores increased significantly more in the MG after treatment , confirming effective learning of mindfulness skills . Participants ’ ratings of the credibility of their assigned interventions , measured after the first group session , were not different between groups . CONCLUSIONS : This r and omized controlled trial demonstrated that mindfulness training has a substantial therapeutic effect on bowel symptom severity , improves health-related quality of life , and reduces distress . The beneficial effects persist for at least 3 months after group training Background The efficacy of antidepressants in irritable bowel syndrome ( IBS ) is controversial . No trials have directly compared a tricyclic with a selective serotonin reuptake inhibitor . Our aim was to determine whether imipramine and citalopram are efficacious in IBS . Methods This was a r and omized , double-blind , placebo-controlled , parallel group pilot trial with imipramine ( 50 mg ) and citalopram ( 40 mg ) . Results Of 51 IBS patients r and omized , baseline characteristics were comparable among the treatment arms ; the majority was diarrhea-predominant . Adequate relief of IBS symptoms ( primary endpoint ) was similar for each treatment arm . Improvements in bowel symptom severity rating for interference ( P = 0.05 ) and distress ( P = 0.02 ) were greater with imipramine versus placebo , but improvements in abdominal pain were not . There was a greater improvement in depression score ( P = 0.08 ) and in the SF-36 Mental Component Score ( P = 0.07 ) , with imipramine . Citalopram was not superior to placebo . Approximately 20 % of the variance in scores was explained by treatment differences for abdominal pain , bowel symptom severity disability , depression and the mental component of the SF-36 . Conclusion Neither imipramine nor citalopram significantly improved global IBS endpoints over placebo BACKGROUND & AIMS Given the limitations of conventional therapies and restrictions imposed on newer pharmacologic agents , there is an urgent need to develop efficacious and efficient treatments that teach patients behavioral self-management skills for relieving irritable bowel syndrome ( IBS ) symptoms and associated problems . METHODS Seventy-five Rome II diagnosed IBS patients ( 86 % female ) without comorbid gastrointestinal disease were recruited from local physicians and the community and r and omized to either 2 versions of cognitive behavior therapy ( CBT ) ( 10-session , therapist-administered CBT vs 4-session , patient-administered CBT ) or a wait list control ( WLC ) that controlled for threats to internal validity . Final assessment occurred 2 weeks after the 10-week treatment phase ended . Outcome measures included adequate relief from pain and bowel symptoms , global improvement of IBS symptoms ( CGI-Improvement Scale ) , IBS symptom severity scale ( IBS SSS ) , quality of life ( IBSQOL ) , psychological distress ( Brief Symptom Inventory ) , and patient satisfaction ( Client Satisfaction Scale ) . RESULTS At week 12 , both CBT versions were significantly ( P < .05 ) superior to WLC in the percentage of participants reporting adequate relief ( eg , minimal contact CBT , 72 % ; st and ard CBT , 60.9 % ; WLC , 7.4 % ) and improvement of symptoms . CBT-treated patients reported significantly improved quality of life and IBS symptom severity but not psychological distress relative to WLC patients ( P < .0001 ) . CONCLUSIONS Data from this pilot study lend preliminary empirical support to a brief patient-administered CBT regimen capable of providing short-term relief from IBS symptoms largely unresponsive to conventional therapies Previous research from the United Kingdom has shown hypnotherapy to be effective in the treatment of irritable bowel syndrome ( IBS ) . The current study provides a systematic replication of this work in the United States . Six matched pairs of IBS patients were r and omly assigned to either a gut-directed hypnotherapy ( n=6 ) or to a symptom monitoring wait-list control condition ( n=6 ) in a multiple baseline across subjects design . Those assigned to the control condition were later crossed over to the treatment condition . Subjects were matched on concurrent psychiatric diagnoses , susceptibility to hypnosis , and various demographic features . On a composite measure of primary IBS symptoms , treatment was superior ( p=.016 ) to symptom monitoring . Results from the entire treated sample ( n=11 ; one subject was removed from analysis ) indicate that the individual symptoms of abdominal pain , constipation , and flatulence improved significantly . State and trait anxiety scores were also seen to decrease significantly . Results at the 2-month follow-up point indicated good maintenance of treatment gains . No significant correlation was found between initial susceptibility to hypnosis and treatment gain . A positive relationship was found between the incidence of psychiatric diagnosis and overall level of improvement Despite the accumulation of efficacy data for cognitive-behavioral treatment of Irritable Bowel Syndrome ( IBS ) , efforts to investigate methods for increasing access to psychological treatments are in their infancy . The current study examined the efficacy of self-administered treatment in comparison to a wait list control . Twenty-eight participants monitored gastrointestinal ( GI ) symptoms and completed measures of quality of life ( QOL ) and psychological distress prior to r and omized assignment to self-help treatment or wait list . Wait listed participants later received treatment . A 3 month post-treatment follow-up was included . Seven participants completed immediate treatment ; nine the wait list . The self-help treatment significantly decreased composite GI symptom scores in comparison to the wait list , but did not lead to significant improvements in QOL or distress . In the entire treated sample , including wait list crossovers , analyses showed significant improvement in abdominal pain , average GI symptoms , and perceived health and well-being . Interpretation of these results should be considered in the context of several limitations , including small sample size , brief baseline symptom monitoring , and high drop out rate . Despite these limitations , this study is an important first step in empirically validating low-cost , self-administered treatments as a first line psychological intervention for IBS Thirty-four patients with irritable bowel syndrome were r and omly assigned to 1 of 3 treatment conditions : individualized cognitive treatment ( CT ) , self-help support group ( SG ) , or symptom-monitoring waiting-list control ( WL ) . Each of the 3 conditions lasted approximately 8 weeks . Pre- to posttreatment analyses revealed significantly greater reductions in both individual gastrointestinal ( GI ) symptoms and in a composite index for GI symptom change for the CT condition than for the SG or WL conditions . When compared with the SG and WL conditions , the CT condition also showed significant improvement on psychological measures of depression and anxiety . At 3-month follow-up , the results for the CT condition were maintained and revealed further numerical improvements Background Irritable bowel syndrome ( IBS ) is a functional disorder of the lower gastrointestinal ( GI ) tract affected by stress , which may benefit from a biopsychosocial treatment approach such as mindfulness-based stress reduction ( MBSR ) . Purpose A treatment as usual ( TAU ) wait-list controlled trial was conducted in Calgary , Canada to investigate the impact of MBSR on IBS symptoms . It was hypothesized that MBSR patients would experience greater reduction in overall IBS symptom severity and self-reported symptoms of stress relative to control patients . Method Ninety patients diagnosed with IBS using the Rome III criteria were r and omized to either an immediate MBSR program ( n = 43 ) or to wait for the next available program ( n = 47 ) . Patients completed IBS symptom severity , stress , mood , quality of life ( QOL ) , and spirituality scales pre- and post-intervention or waiting period and at 6-month follow-up . Intent-to-treat linear mixed model analyses for repeated measures were conducted , followed by completers analyses . Results While both groups exhibited a decrease in IBS symptom severity scores over time , the improvement in the MBSR group was greater than the controls and was clinical ly meaningful , with symptom severity decreasing from constantly to occasionally present . Pre- to post-intervention dropout rates of 44 and 23 % for the MBSR and control groups , respectively , were observed . At 6-month follow-up , the MBSR group maintained a clinical ly meaningful improvement in overall IBS symptoms compared to the wait-list group , who also improved marginally , result ing in no statistically significant differences between groups at follow-up . Improvements in overall mood , QOL , and spirituality were observed for both groups over time . Conclusions The results of this trial provide preliminary evidence for the feasibility and efficacy of a mindfulness intervention for the reduction of IBS symptom severity and symptoms of stress and the maintenance of these improvements at 6 months post-intervention . Attention and self-monitoring and /or anticipation of MBSR participation may account for smaller improvements observed in TAU patients We report two controlled comparisons of a previously vali date d multicomponent ( relaxation , thermal biofeedback , and cognitive therapy ) treatment for irritable bowel syndrome ( IBS ) to an ostensible attention-placebo control ( pseudo-meditation and EEG alpha suppression biofeedback ) and to a symptom-monitoring control . In Study 1 ( n = 10 per condition ) there were nonsignificant trends for the multicomponent treatment to be superior to the attention-placebo condition . In Study 2 ( n = 30 per condition ) , we found no advantage for the multicomponent treatment over the attention-placebo condition . Subjects in both treatment conditions showed significant reductions in GI symptoms , as measured by daily symptom diaries , and significant reductions in trait anxiety and depression . The GI symptom reductions held up over a 6 month follow-up . Possible explanations for the results are explored AIM To study the efficacy of low-dose imipramine in relieving symptoms associated with the irritable bowel syndrome ( IBS ) . METHODS A r and omized , double-blind trial of 25 mg imipramine vs matched placebo for 12 wk was performed . Doubling the dose was allowed once at week 2 in case of an unsatisfactory early response . Primary efficacy variables were subjective global symptom relief and quality of life ( QoL ) using SF-36 at week 12 . RESULTS One hundred and seven patients were enrolled by advertisement or referral by general practitioners and 56 ( 31 imipramine : 25 placebo ) completed the 16-wk study . Baseline characteristics were comparable . A high overall dropout rate was noted in the imipramine and placebo arms ( 47.5 % vs 47.9 % , P > 0.05 ) , a mean of 25.0 and 37.4 d from enrollment , respectively ( P < 0.05 ) . At the end of 12 wk , there was a significant difference in global symptom relief with imipramine over placebo ( per- protocol : 80.6 % vs 48.0 % , P = 0.01 ) and a trend on intent-to-treat ( ITT ) analysis ( 42.4 % vs 25.0 % , P = 0.06 ) . This improvement was evident early and persisted to week 16 ( P = 0.024 and 0.053 by per- protocol and ITT analyses , respectively ) . Mean cumulative and component-specific SF-36 scores improved in the imipramine group only ( per- protocol , P < 0.01 ) . Drug-related adverse events leading to patient dropout were more common in the imipramine group ( 25.4 % vs 12.5 % , P > 0.05 ) . CONCLUSION Imipramine may be effective in the treatment of IBS patients and is associated with improved QoL. Careful patient selection , initiation of a low dose with gradual escalation and monitoring for side effects may result in an improved therapeutic response OBJECTIVES : Gut-directed hypnotherapy ( GHT ) in individual sessions is highly effective in the treatment of irritable bowel syndrome ( IBS ) . This study aim ed to assess the long-term effect of GHT in group sessions for refractory IBS . METHODS : A total of 164 patients with IBS ( Rome-III- criteria ) were screened , and 100 refractory to usual treatment were r and omized 1:1 either to supportive talks with medical treatment ( SMT ) or to SMT with GHT ( 10 weekly sessions within 12 weeks ) . The primary end point was a clinical ly important improvement on several dimensions of daily life ( assessed by IBS impact scale ) after treatment and 12-month follow-up . The secondary end point was improvement in general quality of life ( QOL ; Medical Outcome Study Short-Form-36 ) , psychological status ( Hospital Anxiety Depression Scale ) and reduction of single IBS symptoms . Analysis was by intention to treat . RESULTS : A total of 90 patients received allocated intervention . After treatment , 28 ( 60.8 % ) out of 46 GHT patients and 18 ( 40.9 % ) out of 44 SMTs improved ( absolute difference 20.0 % ; 95 % confidence interval ( CI ) : 0–40.2 % ; P=0.046 ) ; over 15 months , 54.3 % of GHT patients and 25.0 % of controls improved ( absolute difference 29.4 % ; 95 % CI 10.1–48.6 % ; P=0.004 ) . GHT with SMT improved physical and psychological well being significantly more than SMT alone ( P<0.001 ) . Gender , age , disease duration and IBS type did not have an influence on the long-term success of GHT . CONCLUSIONS : GHT improves IBS-related QOL , is superior to SMT alone , and shows a long-term effect even in refractory IBS Background : Irritable bowel syndrome has been treated with selective serotonin reuptake inhibitors but there is not enough evidence from controlled trials to prove their effectiveness BACKGROUND & AIMS Studies of antidepressants and psychological treatments in functional bowel disorders ( FBD ) are method ologically limited . The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy ( CBT ) against education ( EDU ) and desipramine ( DES ) against placebo ( PLA ) in female patients with moderate to severe FBD ( irritable bowel syndrome , functional abdominal pain , painful constipation , and unspecified FBD ) . We also evaluated the amenability of clinical ly meaningful subgroups to these treatments . METHODS This r and omized , comparator-controlled , multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD . Participants received psychological ( CBT vs. EDU ) or antidepressant ( DES vs. PLA ) treatment for 12 weeks . Clinical , physiologic , and psychosocial assessment s were performed before and at the end of treatment . RESULTS The intention-to-treat analysis showed CBT as significantly more effective than EDU ( P = 0.0001 ; responder rate , 70 % CBT vs. 37 % EDU ; number needed to treat [ NNT ] , 3.1 ) . DES did not show significant benefit over PLA in the intention-to-treat analysis ( P = 0.16 ; responder rate , 60 % DES vs. 47 % PLA ; NNT , 8.1 ) but did show a statistically significant benefit in the per- protocol analysis ( P = 0.01 ; responder rate , 73 % DES vs. 49 % PLA ; NNT , 5.2 ) , especially when participants with nondetectable blood levels of DES were excluded ( P = 0.002 ) . Improvement was best gauged by satisfaction with treatment . Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms , abuse history , no depression , and diarrhea-predominant symptoms ; CBT was beneficial over EDU for all subgroups except for depression . CONCLUSIONS For female patients with moderate to severe FBD , CBT is effective and DES may be effective when taken adequately . Certain clinical subgroups are more or less amenable to these treatments While cognitive-behavioral therapy for IBS is quite effective , the limited availability of competent therapists and lack of access to treatment remain problematic . This paper reports on a small , r and omized , controlled trial of a five week internet based cognitive-behavioral intervention for IBS with limited therapist feedback via e-mail . Fifty-four IBS patients were recruited via the internet and r and omly assigned to either immediate treatment or a wait-list control group . Thirty-one subjects completed the post-treatment assessment . 77 % of treatment completers also completed a 3-month follow-up assessment . Treatment completers experienced statistically and clinical ly significant declines in IBS symptoms and improvements in quality of life . Those gains were substantially maintained at follow-up . Treatment efficacy was partially mediated by reductions in the tendency to catastrophize the social and occupational implication s of symptoms , suggesting that catastrophizing may be an important target for treatment BACKGROUND & AIMS A r and omized clinical trial was used to test the effectiveness of an 8-session multicomponent program ( Comprehensive ) compared to a Brief ( single session ) version and Usual Care for women with irritable bowel syndrome . METHODS Menstruating women , ages 18 - 48 years , were recruited from a health maintenance organization as well as community advertisements . Psychiatric nurse practitioners delivered both programs . The primary outcomes were improved symptoms , psychological distress , health-related quality of life , and indicators of stress-related hormones . Outcome indicators were measured at 3 points : ( 1 ) immediately after the Comprehensive program or 9 weeks after entry into the Usual Care and Brief Self-Management groups , ( 2 ) at 6 months , and ( 3 ) at 12 months . RESULTS Compared to Usual Care , women in the Comprehensive program had reduced gastrointestinal symptoms , psychological distress indicators , interruptions in activities because of symptoms , and enhanced quality of life that persisted at the 12-month follow-up evaluation . Women in the Brief group also demonstrated statistically significant improvements in quality of life and smaller nonsignificant improvements in other outcome variables than observed in the Comprehensive group . There were no group differences in urine catecholamines and cortisol levels . CONCLUSIONS A comprehensive self-management program is an important therapy approach for women with irritable bowel syndrome . The Brief 1-session version is also moderately helpful for some women with IBS BACKGROUND & AIMS Psychotherapy and antidepressants are effective in patients with severe irritable bowel syndrome ( IBS ) , but the cost-effectiveness of either treatment in routine practice has not been established . METHODS Patients with severe IBS were r and omly allocated to receive 8 sessions of individual psychotherapy , 20 mg daily of the specific serotonin reuptake inhibitor ( SSRI ) antidepressant , paroxetine , or routine care by a gastroenterologist and general practitioner . Primary outcome measures of abdominal pain , health-related quality of life , and health care costs were determined after 3 months of treatment and 1 year later . RESULTS A total of 257 subjects ( 81 % response rate ) from 7 hospitals were recruited ; 59 of 85 patients ( 69 % ) r and omized to psychotherapy and 43 of 86 ( 50 % ) of the paroxetine group completed the full course of treatment . Both psychotherapy and paroxetine were superior to treatment as usual in improving the physical aspects of health-related quality of life ( SF-36 physical component score improvement , 5.2 [ SEM , 1.26 ] , 5.8 [ SEM , 1.0 ] , and -0.3 [ SEM , 1.17 ] ; P < 0.001 ) , but there was no difference in the psychological component . During the follow-up year , psychotherapy but not paroxetine was associated with a significant reduction in health care costs compared with treatment as usual ( psychotherapy , $ 976 [ SD , $ 984 ] ; paroxetine , $ 1252 [ SD , $ 1616 ] ; and treatment as usual , $ 1663 [ SD , $ 3177 ] ) . CONCLUSIONS For patients with severe IBS , both psychotherapy and paroxetine improve health-related quality of life at no additional cost BACKGROUND & AIMS Although widely prescribed , the evidence for the use of antidepressants for the treatment of irritable bowel syndrome ( IBS ) is limited . In this study , we hypothesized that fluoxetine ( Prozac ) , a selective serotonin reuptake inhibitor , has visceral analgesic properties , leading to increased sensory thresholds during rectal distention and improvement of symptoms , in particular in IBS patients with visceral hypersensitivity . METHODS Forty non-depressed IBS patients underwent a rectal barostat study to assess the sensitivity to rectal distention before and after 6 weeks of treatment with fluoxetine 20 mg or placebo . Abdominal pain scores , individual gastrointestinal symptoms , global symptom relief , and psychologic symptoms were assessed before and after the intervention . RESULTS At baseline , 21 of 40 patients showed hypersensitivity to rectal distention . Fluoxetine did not significantly alter the threshold for discomfort/pain relative to placebo , either in hypersensitive ( 19 + /- 3 vs. 22 + /- 2 mm Hg above MDP ) or in normosensitive ( 34 + /- 2 vs. 39 + /- 4 mm Hg above MDP ) IBS patients . Overall , 53 % of fluoxetine-treated patients and 76 % of placebo-treated patients reported significant abdominal pain scores after 6 weeks ( not significant ) . In contrast , in hypersensitive patients only , fluoxetine significantly reduced the number of patients reporting significant abdominal pain . Gastrointestinal symptoms , global symptom relief , and psychologic symptoms were not altered . CONCLUSIONS Fluoxetine does not change rectal sensitivity in IBS patients . Possible beneficial effects on pain perception need to be confirmed in larger trials BACKGROUND Irritable bowel syndrome ( IBS ) is a functional gastrointestinal ( GI ) disease that causes significant impairment in quality of life and accounts for $ 8 billion per year to the healthcare system and loss of productivity in the workplace . OBJECTIVE The authors examined the efficacy and safety of paroxetine controlled-release ( paroxetine-CR ) in patients with IBS . METHOD Seventy-two patients with IBS participated in a 12-week , double-blind , r and omized , placebo-controlled study of paroxetine-CR ( 12.5 mg-50 mg/day ) . Efficacy was measured by Composite Pain Scores ( primary outcome ) and the Clinical Global Impression-Improvement ( CGI-I ) and Severity ( CGI-S ) ratings . RESULTS In intent-to-treat analyses , there were no significant differences between paroxetine-CR ( N=36 ) and placebo ( N=36 ) on reduction in Composite Pain Scores , although the proportion of responders on CGI-I was significantly higher in the paroxetine-CR group . The treatment was well tolerated . CONCLUSION The study did not demonstrate a statistically significant benefit for paroxetine-CR over placebo on the primary outcome measure , although there was improvement in secondary outcome measures . Overall , paroxetine-CR seems to have potential benefit in IBS . Studies with adequate sample s may clarify the role of paroxetine-CR in IBS After organic disease had been excluded as far as possible by clinical examination , including laboratory tests , analysis of faeces , and X-ray examination or endoscopy of the upper and lower gastrointestinal tract , 61 patients were given either 50 mg trimipramine at bedtime or identically looking coded placebo in a prospect i ve study for 4 weeks . The complaints were grade d on an analogue scale by both the patients and the physicians . The results showed that the complaint scores were significantly reduced to about half in the placebo group . In the group treated with trimipramine a significantly greater reduction was found for the scores of vomiting , sleeplessness , depression , and for the mucus content of stools . The scores for tiredness during treatment had decreased less in the group receiving trimipramine than in the one receiving placebo . These improvements occurred already during the first week of treatment . No adverse side effect was recorded OBJECTIVE : The purpose of the trial was to determine whether a high-fiber diet ( HFD ) alone or in combination with paroxetine or placebo was effective treatment for patients with irritable bowel syndrome ( IBS ) . METHODS : Design : Trial of HFD alone ( Group 1 ) followed by a r and omized , double-blind trial of HFD with paroxetine or placebo ( Group 2 ) . Setting : Gastroenterology office in a 524-bed university-affiliated community hospital in Pittsburgh . Patients : Men and women , aged 18–65 yr , previously diagnosed with IBS but otherwise healthy . Intervention : Institution of HFD in 98 participants consuming low- or average-fiber diets . Allocation of paroxetine to 38 and placebo to 43 symptomatic participants consuming HFDs . Measurements : Overall well-being , abdominal pain , and abdominal bloating ( Groups 1 and 2 ) ; food avoidance , work functioning , and social functioning ( Group 2 ) . RESULTS : In Group 1 , overall well-being improved in 26 % patients , and abdominal pain and bloating decreased in 22 % and 26 % patients , respectively , with an HFD . In Group 2 , overall well-being improved more with paroxetine than with placebo ( 63.3%vs 26.3 % ; p= 0.01 ) , but abdominal pain , bloating , and social functioning did not . With paroxetine , food avoidance decreased ( p = 0.03 ) and work functioning was marginally better ( p = 0.08 ) . Before unblinding , more paroxetine recipients than placebo recipients wanted to continue their study medication ( 84%vs 37 % ; p < 0.001 ) . CONCLUSIONS : The difference in overall well-being found in our paroxetine/placebo trial is greater than that found in previously published drug/placebo trials for IBS . Moreover , the difference in well-being applied to nondepressed recipients of paroxetine Background and aims : Irritable bowel syndrome ( IBS ) is a disorder of intestinal hypersensitivity and altered motility , exacerbated by stress . Functional magnetic resonance imaging ( fMRI ) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex ( ACC ) , an area relevant to pain and emotions . Tricyclic antidepressants are effective for IBS . The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits . Secondary aims were to identify other brain regions altered by amitriptyline , and to determine if reductions in cerebral activation are greater during mental stress . Methods : Nineteen women with painful IBS were r and omised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout . Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI . Distensions were performed alternately during auditory stress and relaxing music . Results : Rectal pain induced significant activation of the perigenual ACC , right insula , and right prefrontal cortex . Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex , but only during stress . Conclusions : The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual ( limbic ) anterior cingulated cortex and parietal association cortex . These reductions are only seen during stress . Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS UNLABELLED This r and omized , double-blind , placebo-controlled study assessed efficacy and safety of duloxetine in patients with chronic low back pain ( CLBP ) . Adults ( n = 401 ) with a nonneuropathic CLBP and average pain intensity of ≥ 4 on an 11-point numerical scale ( Brief Pain Inventory [ BPI ] ) were treated with either duloxetine 60 mg once daily or placebo for 12 weeks . The primary measure was BPI average pain . Secondary endpoints included Patient 's Global Impressions of Improvement ( PGI-I ) , Rol and Morris Disability Question naire ( RMDQ-24 ) , BPI-Severity ( BPI-S ) , BPI-Interference ( BPI-I ) , and response rates ( either ≥ 30 % or ≥ 50 % BPI average pain reduction at endpoint ) . Health outcomes included Short Form-36 , European Quality of Life-5 Dimensions , and the Work Productivity and Activity Impairment question naire . Safety and tolerability were assessed . Compared with placebo-treated patients , duloxetine-treated patients reported a significantly greater reduction in BPI average pain ( P ≤ .001 ) . Similarly , duloxetine-treated patients reported significantly greater improvements in PGI-I , BPI-S , BPI-I , 50 % response rates , and some health outcomes . The RMDQ and 30 % response rate showed numerical improvements with duloxetine treatment . Significantly more patients in the duloxetine group ( 15.2 % ) than patients in the placebo group ( 5.4 % ) discontinued because of adverse events ( P = .002 ) . Nausea and dry mouth were the most common treatment-emergent adverse events with rates significantly higher in duloxetine-treated patients . PERSPECTIVE This study provides clinical evidence of the efficacy and safety of duloxetine at a fixed dose of 60 mg once daily in the treatment of chronic low back pain ( CLBP ) . As of December 2009 , duloxetine has not received regulatory approval for the treatment of CLBP Autogenic training ( AT ) is a useful and comprehensive relaxation technique . However , no studies have investigated the effects of AT on irritable bowel syndrome ( IBS ) . In this study we tested the hypothesis that AT improves symptoms of IBS . Twenty-one patients with IBS were r and omly assigned to AT ( n = 11 , 5 male , 6 female ) or control therapy ( n = 10 , 5 male , 5 female ) . AT patients were trained intensively , while the control therapy consisted of discussion s about patients ’ meal habits and life styles . All patients answered a question related to adequate relief ( AR ) of IBS symptoms and four question naires : Self-induced IBS Question naire ( SIBSQ ) , Self-reported Depression Scale ( SDS ) , State-Trait Anxiety Inventory ( STAI ) , and Medical Outcome Short Form 36 Health Survey ( SF-36 ) . The proportion of AR in the last AT session in the AT group ( 9/11 , 81.8 % ) was significantly higher than that in the controls ( 3/10 , 30.0 % , Chi-square test , p = 0.048 ) . Two subscales of the SF-36 , i.e. , social functioning and bodily pain , were significantly improved in the AT group ( p < 0.05 ) as compared to the control group . Role emotional ( p = 0.051 ) and general health ( p = 0.068 ) showed a tendency for improvement in the AT group . AT may be useful in the treatment of IBS by enhancing self-control Gut‐directed hypnotherapy can reduce IBS symptoms , but the mechanisms underlying this therapeutic effect remain unknown BACKGROUND Irritable bowel syndrome ( IBS ) is commonly thought to be associated with psychologic distress . However , in some studies only persons who had sought medical care for IBS ( IBS patients ) showed an increased frequency of psychiatric symptoms , and non patients did not differ significantly from normal subjects . Our aims were 1 ) to estimate the prevalence of IBS in the population aged 18 - 45 years , 2 ) to find the proportion seeking medical care for IBS , and 3 ) to compare IBS subjects with normals , and IBS patients with IBS non patients with regard to mental health . METHODS Question naires on IBS symptoms and the General Health Question naire ( GHQ ) were mailed to 5000 r and omly sample d persons aged 18 - 45 years . The response rate was 58 % . RESULTS IBS was found in 7.4 % of the men and 13.3 % of the women . Those who had sought medical attention had more severe symptoms . The Likert mean score on the GHQ was 4.7 ( 95 % confidence interval , 4.4 - 5.0 ) points higher for the IBS group than for normals ( P < 0.001 ) . There was no difference in GHQ scores between IBS patients and non patients . CONCLUSIONS The results indicate that IBS per se is associated with more psychiatric distress , regardless of medical care-seeking . Seeking medical care is associated with more severe IBS symptoms 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 BACKGROUND Current clinical guidelines identify several psychological treatments for irritable bowel syndrome ( IBS ) . IBS patients , however , have elevated trauma , life stress , relationship conflicts , and emotional avoidance , which few therapies directly target . We tested the effects of emotional awareness and expression training ( EAET ) compared to an evidence -based comparison condition-relaxation training- and a waitlist control condition . METHODS Adults with IBS ( N=106 ; 80 % female , Mean age=36 years ) were r and omized to EAET , relaxation training , or waitlist control . Both EAET and relaxation training were administered in three , weekly , 50-minute , individual sessions . All patients completed the IBS Symptom Severity Scale ( primary outcome ) , IBS Quality of Life , and Brief Symptom Inventory ( anxiety , depressive , and hostility symptoms ) at pretreatment and at 2 weeks posttreatment and 10 weeks follow-up ( primary endpoint ) . KEY RESULTS Compared to waitlist controls , EAET , but not relaxation training , significantly reduced IBS symptom severity at 10-week follow-up . Both EAET and relaxation training improved quality of life at follow-up . Finally , EAET did not reduce psychological symptoms , whereas relaxation training reduced depressive symptoms at follow-up ( and anxiety symptoms at posttreatment ) . CONCLUSIONS & INFERENCES Brief emotional awareness and expression training that targeted trauma and emotional conflicts reduced somatic symptoms and improved quality of life in patients with IBS . This emotion-focused approach may be considered an additional treatment option for IBS , although research should compare EAET to a full cognitive-behavioral protocol and determine which patients are best suited for each approach . Registered at clinical trials.gov ( NCT01886027 ) Abstract Objective To assess the efficacy of cognitive behaviour therapy delivered in primary care for treating irritable bowel syndrome . Design R and omised controlled trial . Setting 10 general practice s in London . Participants 149 patients with moderate or severe irritable bowel syndrome resistant to the antispasmodic mebeverine . Interventions Cognitive behaviour therapy delivered by trained primary care nurses plus 270 mg mebeverine taken thrice daily compared with mebeverine treatment alone . Main outcome measures Primary measures were patients ' scores on the irritable bowel syndrome symptom severity scale . Secondary measures were scores on the work and social adjustment scale and the hospital anxiety and depression scale . Results Of 334 referred patients , 72 were r and omised to mebeverine plus cognitive behaviour therapy and 77 to mebeverine alone . Cognitive behaviour therapy had considerable initial benefit on symptom severity compared with mebeverine alone , with a mean reduction in score of 68 points ( 95 % confidence interval 103 to 33 ) , with the benefit persisting at three months and six months after therapy ( mean reductions 71 points ( 109 to 32 ) and 11 points ( 20 to 3 ) ) but not later . Cognitive behaviour therapy also showed significant benefit on the work and social adjustment scale that was still present 12 months after therapy ( mean reduction 2.8 points ( 5.2 to 0.4 ) ) , but had an inconsistent effect on the hospital anxiety and depression scale . Conclusion Cognitive behaviour therapy delivered by primary care nurses offered additional benefit over mebeverine alone up to six months , although the effect had waned by 12 months . Such therapy may be useful for certain patients with irritable bowel syndrome in primary care BACKGROUND Functional somatic syndromes , including chronic fatigue syndrome or irritable bowel syndrome , often co-exist . Treatment guidelines supported by high quality evidence exist for most functional somatic syndromes , but are lacking for multiple comorbid functional somatic syndromes . We aim ed to assess the effect of the tricyclic antidepressant , imipramine , in patients with multiple functional somatic syndromes defined by the criteria for multiorgan bodily distress syndrome , a unifying diagnosis that encompasses most functional somatic syndromes and somatoform disorders . METHODS In this single-centre , double-blind , r and omised trial done in a Danish university hospital setting , participants were patients consecutively referred ( age 20 - 50 years ) fulfilling criteria for multiorgan bodily distress syndrome with no concurrent comorbid depression or anxiety disorder . Participants were r and omly assigned ( 1:1 ) to receive either 10 weeks of low-dose imipramine or placebo ( oral daily doses of 25 - 75 mg ) . The hospital pharmacy h and led r and omisation ( computer-generated ) and masking , providing sequentially numbered packs of study drug that were given serially to the participants . All others involved were masked to allocation . Primary outcome was patient-rated overall health improvement on a 5-point clinical global improvement scale . Improvement was defined as patients responding " better " or " much better " as opposed to " unchanged " and " worse " or " much worse " when rating their overall health status after 10 weeks of minimum 25 mg study drug . Analyses included patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01518634 . FINDINGS Between Jan 30 , 2012 , and Nov 24 , 2014 , 138 patients were r and omly assigned ; 70 to receive imipramine and 68 to receive placebo . The study was completed on May 1 , 2015 . 125 patients received at least one dose of study drug : 65 received imipramine and 60 received placebo . Treatment was terminated prematurely for eight ( 12 % ) patients receiving imipramine and seven ( 12 % ) patients receiving placebo . Data were missing for two ( 3 % ) patients receiving imipramine and three ( 5 % ) patients receiving placebo . Of the 120 patients ( 96 % ) who provided primary outcome data , 33 ( 53 % ) receiving imipramine reported their overall health status as " better " or " much better " compared with 14 patients ( 25 % ) receiving placebo . The improvement after imipramine was significantly greater than after placebo ( odds ratio 3·3 [ 95 % CI 1·6 - 6·8 ] ; p=0·001 ) . Number needed to treat was 3·6 ( 95 % CI 2·3 - 8·9 ) . Analysis of the worst-case scenario for patients with missing outcome did not change the interpretation of the results . 32 patients ( 49 % ) receiving imipramine and 10 patients ( 17 % ) receiving placebo had at least one adverse event of moderate intensity ( p=0·0001 ) ; eight patients ( 12 % ) receiving imipramine and three patients ( 5 % ) receiving placebo had at least one adverse event of severe intensity ( p=0·1496 ) . One patient ( 1 % ) receiving placebo experienced a serious adverse event ( a subdural haematoma sustained after an accident ) . Adverse events caused dropout in four patients ( 6 % ) receiving imipramine and three patients ( 5 % ) receiving placebo . INTERPRETATION Imipramine treatment compared with placebo significantly improved overall health in patients with multiple functional somatic syndromes when both treatments were supported by regular contacts with clinicians . Adverse events were more common in the imipramine group , but only rarely led to discontinuation of treatment . FUNDING The Danish Foundation , Trygfonden Abstract Numerous attempts have been made to relate specific emotional conflicts to colonic symptoms in the irritable colon syndrome . Depression has been described as an accompaniment of the illness . This paper investigates the relationship between irritable colon and depression using self-rating symptom scales and the Zung Self-Rating Depression Scale . Thirty-one subjects were followed for two months in a double-blind study employing a tricyclic antidepressant and an inactive placebo . The study demonstrates the frequency of depression in patients with the syndrome ; it shows a clearly positive treatment effect with placebo alone for both depressive symptoms and gastrointestinal complaints , and suggests that tricyclic antidepressant therapy results in moderately greater improvement in symptoms than does treatment with placebo alone Thirty-five patients with irritable bowel syndrome were r and omized to receive treatment in a stress management programme or conventional therapy which included the antispasmodic Colpermin . The stress management programme involved a median of six 40-min sessions with a physiotherapist during which patients were helped to underst and the nature of their symptoms , their relationship to stress and were taught relaxation exercises . Two thirds of those in the stress management programme found the programme effective in relieving symptoms and experienced fewer attacks of less severity . This benefit was maintained for at least 12 months . Few of those given conventional management had any benefit . A stress management programme would appear to be of value for patients with irritable bowel syndrome BACKGROUND Duloxetine has demonstrated analgesic effect in chronic pain states . This study assesses the efficacy of duloxetine in chronic low back pain ( CLBP ) . METHODS Adult patients with non-radicular CLBP entered this 13-week , double-blind , r and omized study comparing duloxetine 20 , 60 or 120 mg once daily with placebo . The primary measure was comparison of duloxetine 60 mg with placebo on weekly mean 24-h average pain . Secondary measures included Rol and -Morris Disability Question naire ( RMDQ-24 ) , Patient 's Global Impressions of Improvement ( PGI-I ) , Brief Pain Inventory ( BPI ) , safety and tolerability . RESULTS Four hundred four patients were enrolled , 267 completed . No significant differences existed between any dose of duloxetine and placebo on reduction in weekly mean 24-h average pain at end-point . Duloxetine 60 mg was superior to placebo from weeks 3 - 11 in relieving pain , but not at weeks 12 - 13 . Duloxetine 60 mg demonstrated significant improvement on PGI-I , RMDQ-24 , BPI-average pain and BPI-average interference . Significantly more patients taking duloxetine 120 mg ( 24.1 % ) discontinued because of adverse events , versus placebo ( 8.5 % ) . CONCLUSIONS Duloxetine was superior to placebo on the primary objective from weeks 3 - 11 , but superiority was not maintained at end-point . Duloxetine was superior to placebo on many secondary measures , and was well-tolerated |
11,732 | 28,181,696 | Characteristics associated with positive results for caregivers were a high intensity of case management and programs specifically addressed to dementia patients .
Despite the numerous method ological challenges in the assessment of such complex social interventions , our results show that case management programs can be beneficial for caregivers of dementia patients and that positive results for patients are achieved without increasing caregivers ' burden .
Copyright © 2017 John Wiley & Sons , | OBJECTIVE Informal caregivers are deeply involved in the case management process .
However , little is known about the consequences of such programs for informal caregivers .
This systematic literature review , reported according to the Preferred Reporting Items for Systematic Review s and Meta-Analyses statement , addressed the consequences of clinical case management programs , whether positive or negative , for caregivers of frail older persons or persons with dementia . | AIM This paper reports a study to examine the effectiveness of a 6-month dementia care programme for Chinese families living with and caring for a relative with dementia , compared with routine family support services in Hong Kong . BACKGROUND Recognizing the adverse psychosocial health effects inherent in dementia care , different psychosocial interventions provided preliminary evidence of their effectiveness in improving family members ' knowledge and skills in caregiving and delaying dementia sufferers ' illness deterioration and institutionalization . Little is known about the effects of such interventions for family caregivers ' psychosocial health conditions , particularly in non-Western population s. METHODS A r and omized controlled trial was conducted with 92 Chinese families of a relative with dementia in two dementia care centres in Hong Kong . They were r and omly selected from a dementia client list and then r and omly assigned to receive either the dementia family care programme ( n=46 ) , or routine care only ( n=46 ) . Clients ' symptoms and institutionalization , and caregivers ' quality of life , burden and social support at recruitment , 1 week , and 12 and 18 months following intervention were measured and compared between the study groups using repeated measures MANOVAS followed by Helmert 's contrast tests . Data was collected over a period of 24 months , between September 2007 and August 2009 . RESULTS Results of the MANOVAS and contrast tests indicated that at 18-month follow-up , participants in the family programme reported significantly greater improvements in clients ' symptoms and institutionalization rates , and caregivers ' quality of life and burden , when compared with their counterparts in the routine care group . CONCLUSION These findings provide evidence that the dementia care family programme can improve the psychosocial functioning of both clients with dementia and their family caregivers in a Chinese population . Further research is recommended to investigate whether this intervention can also apply to families with different socio-economic background s and across cultures 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 BACKGROUND It is believed that timely recognition and diagnosis of dementia is a pre-condition for improving care for both older adults with dementia and their informal caregivers . However , diagnosing dementia often occurs late in the disease . This means that a significant number of patients with early symptoms of dementia and their informal caregivers may lack appropriate care . OBJECTIVES To compare the effects of case management and usual care among community-dwelling older adults with early symptoms of dementia and their primary informal caregivers . DESIGN R and omized controlled trial with measurements at baseline and after 6 and 12 months . SETTING Primary care in West-Friesl and , the Netherl and s. PARTICIPANTS 99 pairs of community-dwelling older adults with dementia symptoms ( defined as abnormal screening for symptoms of dementia ) and their primary informal caregivers . INTERVENTION 12 months of case management by district nurses for both older adults and informal caregivers versus usual care . MEASUREMENTS PRIMARY OUTCOME informal caregiver 's sense of competence . SECONDARY OUTCOMES caregiver 's quality of life , depressive symptoms , and burden , and patient 's quality of life . Process measurements : intervention fidelity and caregiver 's satisfaction with the quality of case management . RESULTS Linear mixed model analyses showed no statistically significant and clinical ly relevant differences over time between the two groups . The process evaluation revealed that intervention fidelity could have been better . Meanwhile , informal caregivers were satisfied with the quality of case management . CONCLUSION This study shows no benefits of case management for older adults with dementia symptoms and their primary informal caregivers . One possible explanation is that case management , which has been recommended among diagnosed dementia patients , may not be beneficial if offered too early . However , on the other h and , it is possible that : ( 1 ) case management will be effective in this group if more fully implemented and adapted or aim ed at informal caregivers who experience more severe distress and problems ; ( 2 ) case management is beneficial but that it is not seen in the timeframe studied ; ( 3 ) case management might have undetected small benefits . This has to be established . Trial registration ISCRTN83135728 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 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 BACKGROUND Care for elderly persons with disabilities is usually characterized by fragmentation , often leading to more intrusive and expensive forms of care such as hospitalization and institutionalization . There has been increasing interest in the ability of integrated models to improve health , satisfaction , and service utilization outcomes . METHODS A program of integrated care for vulnerable community-dwelling elderly persons ( SIPA [ French acronym for System of Integrated Care for Older Persons ] ) was compared to usual care with a r and omized control trial . SIPA offered community-based care with local agencies responsible for the full range and coordination of community and institutional ( acute and long-term ) health and social services . Primary outcomes were utilization and public costs of institutional and community care . Secondary outcomes included health status , satisfaction with care , caregiver burden , and out-of-pocket expenses . RESULTS Accessibility was increased for health and social home care with increased intensification of home health care . There was a 50 % reduction in hospital alternate level inpatient stays ( " bed blockers " ) but no significant differences in utilization and costs of emergency department , hospital acute inpatient , and nursing home stays . For all study participants , average community costs per person were C dollar 3390 higher in the SIPA group but institutional costs were C dollar 3770 lower with , as hypothesized , no difference in total overall costs per person in the two groups . Satisfaction was increased for SIPA caregivers with no increase in caregiver burden or out-of-pocket costs . As expected , there was no difference in health outcomes . CONCLUSIONS Integrated systems appear to be feasible and have the potential to reduce hospital and nursing home utilization without increasing costs Background Dem and for home care services has increased considerably , along with the growing complexity of cases and variability among re sources and providers . Design ing services that guarantee co-ordination and integration for providers and levels of care is of paramount importance . The aim of this study is to determine the effectiveness of a new case-management based , home care delivery model which has been implemented in And alusia ( Spain ) . Methods Quasi-experimental , controlled , non-r and omised , multi-centre study on the population receiving home care services comparing the outcomes of the new model , which included nurse-led case management , versus the conventional one . Primary endpoints : functional status , satisfaction and use of healthcare re sources . Secondary endpoints : recruitment and caregiver burden , mortality , institutionalisation , quality of life and family function . Analyses were performed at base-line , and at two , six and twelve months . A bivariate analysis was conducted with the Student 's t-test , Mann-Whitney 's U , and the chi squared test . Kaplan-Meier and log-rank tests were performed to compare survival and institutionalisation . A multivariate analysis was performed to pinpoint factors that impact on improvement of functional ability . Results Base-line differences in functional capacity – significantly lower in the intervention group ( RR : 1.52 95%CI : 1.05–2.21 ; p = 0.0016 ) – disappeared at six months ( RR : 1.31 95%CI : 0.87–1.98 ; p = 0.178 ) . At six months , caregiver burden showed a slight reduction in the intervention group , whereas it increased notably in the control group ( base-line Zarit Test : 57.06 95%CI : 54.77–59.34 vs. 60.50 95%CI : 53.63–67.37 ; p = 0.264 ) , ( Zarit Test at six months : 53.79 95%CI : 49.67–57.92 vs. 66.26 95%CI : 60.66–71.86 p = 0.002 ) . Patients in the intervention group received more physiotherapy ( 7.92 CI95 % : 5.22–10.62 vs. 3.24 95%CI : 1.37–5.310 ; p = 0.0001 ) and , on average , required fewer home care visits ( 9.40 95%CI : 7.89–10.92 vs.11.30 95%CI : 9.10–14.54 ) . No differences were found in terms of frequency of visits to A&E or hospital re-admissions . Furthermore , patients in the control group perceived higher levels of satisfaction ( 16.88 ; 95%CI : 16.32–17.43 ; range : 0–21 , vs. 14.65 95%CI : 13.61–15.68 ; p = 0,001 ) . Conclusion A home care service model that includes nurse-led case management streamlines access to healthcare services and re sources , while impacting positively on patients ' functional ability and caregiver burden , with increased levels of satisfaction . Trial registration IS RCT Background The ' Hawthorne Effect ' may be an important factor affecting the generalisability of clinical research to routine practice , but has been little studied . Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge , no attempt has been made to quantify them . Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia . Methods Participants in a dementia trial were r and omised to intensive follow-up ( with comprehensive assessment visits at baseline and two , four and six months post r and omisation ) or minimal follow-up ( with an abbreviated assessment at baseline and a full assessment at six months ) . Our primary outcomes were cognitive functioning ( ADAS-Cog ) and participant and carer-rated quality of life ( QOL-AD ) . Results We recruited 176 participants , mainly through general practice s. The main analysis was based on Intention to treat ( ITT ) , with available data . In the ANCOVA model with baseline score as a co-variate , follow-up group had a significant effect on outcome at six months on the ADAS-Cog score ( n = 140 ; mean difference = -2.018 ; 95%CI -3.914 , -0.121 ; p = 0.037 favouring the intensive follow-up group ) , and on participant-rated quality of life score ( n = 142 ; mean difference = -1.382 ; 95%CI -2.642 , -0.122 ; p = 0.032 favouring minimal follow-up group ) . There was no significant difference on carer quality of life . Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia result ed in a better outcome than minimal follow-up , as measured by their cognitive functioning . Trial registration Current controlled trials : IS RCT Background Controlled clinical trials of health care interventions are either explanatory or pragmatic . Explanatory trials test whether an intervention is efficacious ; that is , whether it can have a beneficial effect in an ideal situation . Pragmatic trials measure effectiveness ; they measure the degree of beneficial effect in real clinical practice . In pragmatic trials , a balance between external validity ( generalizability of the results ) and internal validity ( reliability or accuracy of the results ) needs to be achieved . The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention . The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized . However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability . We are conducting two pragmatic r and omized controlled trials on interventions in the management of hypertension in primary care . We describe the design of the trials and the steps taken to deal with the competing dem and s of external and internal validity . Discussion External validity is maximized by having few exclusion criteria and by allowing flexibility in the interpretation of the intervention and in management decisions . Internal validity is maximized by decreasing contamination bias through cluster r and omization , and decreasing observer and assessment bias , in these non-blinded trials , through baseline data collection prior to r and omization , automating the outcomes assessment with 24 hour ambulatory blood pressure monitors , and blinding the data analysis . Summary Clinical trials conducted in community practice s present investigators with difficult method ological choices related to maintaining a balance between internal validity ( reliability of the results ) and external validity ( generalizability ) . The attempt to achieve method ological purity can result in clinical ly meaningless results , while attempting to achieve full generalizability can result in invalid and unreliable results . Achieving a creative tension between the two is crucial Background This study explored the effects of an integrated care model aim ed at the frail elderly on the perceived health , objective burden , subjective burden and quality of life of informal caregivers . Methods A quasi-experimental design with before/after measurement ( with question naires ) and a control group was used . The analysis encompassed within and between groups analyses and regression analyses with baseline measurements , control variables ( gender , age , co-residence with care receiver , income , education , having a life partner , employment and the duration of caregiving ) and the intervention as independent variables . Results The intervention significantly contributed to the reduction of subjective burden and significantly contributed to the increased likelihood that informal caregivers assumed household tasks . No effects were observed on perceived , health , time investment and quality of life . Conclusions This study implies that integrated care models aim ed at the frail elderly can benefit informal caregivers and that such interventions can be implemented without dem and ing additional time investments from informal caregivers . Recommendations for future interventions and research are provided . Trial registration Current Controlled Trials IS RCT N05748494 . Registration date : 14/03/2013 OBJECTIVES To determine the effect of a primary care-based care management initiative on residential care placement and death in a population of frail older adults referred for needs assessment in New Zeal and . DESIGN R and omized controlled trial with follow-up at 3 , 6 , 12 , 18 , and 24 months for residential care placement and mortality . SETTING Fifty-five family physician practice s in New Zeal and that established a care management initiative for older adults assessed as being at high risk of residential care placement in 2004 to 2006 . PARTICIPANTS Three hundred fifty-one individuals ( 243 female , 108 male ) aged 65 and older ( mean 81 ) who were assessed as being at risk of permanent residential care placement . INTERVENTIONS The care management program ( Coordinator of Services for Elderly ) consisted of a nominated health professional care manager geographically aligned to family physicians housed with the family physician or located nearby . MEASUREMENTS Rates of permanent residential care placement and mortality . RESULTS The risk of permanent residential care placement or death was 0.36 for usual care ( control group ) and 0.26 for the care management initiative , a 10.2 % absolute risk reduction , with the majority of the risk reduction seen in residential care placement ( control group 0.25 , intervention group 0.16 ) . CONCLUSION A family physician-aligned community care management approach reduces frail older adults ' risk of mortality and permanent residential care placement Context Dementia is an incurable chronic disease , but assistance to caregivers can reduce the severity of patients ' symptoms and delay institutionalization . Because this assistance requires provision of multiple health care and social services , patients and caregivers might benefit from a coordinated system of care . Contribution The investigators r and omly assigned patients with dementia and their caregivers to usual care or to a coordinated system of care . In the coordinated system , care managers regularly assessed patient and caregiver pairs and coordinated guideline -recommended provision of services by health care providers and community agencies using computerized information systems . The study found that pairs cared for in the coordinated system received higher- quality health care and more needed assistance than those who received usual care . Caution s The study focused on a relatively homogeneous population of white , well-educated , otherwise healthy , noninstitutionalized patients with health insurance . The findings might not apply to other population s. Implication s The quality of care for patients with dementia and their caregivers can be improved with a model of care in which services provided by the health system and community agencies are coordinated by a care manager . The Editors Dementia has enormous health and financial consequences for affected individuals , their family caregivers , and society ( 15 ) . Although most dementia is currently neither preventable nor reversible , existing practice guidelines reflect evidence from r and omized , controlled trials that caregiver assistance and support can delay institutionalization ( 68 ) , and nonpharmacologic management of problem behaviors and depression can reduce symptom severity and improve patient health ( 9 , 10 ) . Yet , adherence to published dementia care guidelines ( 1114 ) is poor ( 15 ) , including inappropriate use of psychoactive medications for initial management of agitation ( 16 ) ; low referral rates to community agencies ( 17 , 18 ) ; and underdetection of elder abuse , for which cognitive impairment is a risk factor ( 19 ) , and of depression ( 20 ) , a common comorbid condition ( 21 ) . There are few controlled trials of improvement interventions for dementia care . An opinion leader intervention improved neurologists ' reported adherence to dementia care guidelines ( 18 ) , and a recent trial using advanced practice nurses within primary care improved care quality ( 22 ) ; other trials reported limited impacts ( 23 , 24 ) . All studies were conducted primarily within or outside of health care delivery systems ; to date , trials of comprehensive , guideline -based dementia care interventions that incorporate all chronic care model components , including substantive collaboration between health systems and community agencies ( 25 , 26 ) , have not been reported . Yet , this would seem to be a well-suited approach because of the multifaceted nature of dementia care management and the need for coordinated efforts across health care delivery systems and community agencies to provide recommended medical , behavioral , and social services and support . To address gaps in care quality for persons with dementia , we design ed and tested a guideline -based , comprehensive dementia care management intervention in a clinic-level , cluster r and omized , controlled trial ( 27 ) . Intervention components were based on the chronic care model and emphasized linkages with community re sources and multiagency coordination ( 25 , 26 , 28 ) . Key components included dementia care managers , formal procedures for communication within and between organizations and agencies , Internet-based care management , collaborative care planning with caregivers , caregiver self-management support , ongoing follow-up , and provider education . We hypothesized that patient and caregiver dyads in intervention clinics would receive care in higher accordance with guidelines ; receive more community re sources and services ; have fewer unmet caregiving assistance needs ; and have better patient and caregiver health and caregiving quality , social support , and perceived care quality than dyads receiving usual care . Methods The institutional review boards of the University of California , Los Angeles , and all participating health care organizations approved the study procedures . All enrolled patient and caregiver dyads provided written informed consent . Three health care organizations ( Kaiser Permanente San Diego , Scripps Clinic , University of California , San Diego , Healthcare ) and 3 community agencies ( Alzheimer 's AssociationSan Diego Chapter , Southern Caregiver Re source Center , Meals on WheelsGreater San Diego ) providing services for persons with dementia and their informal caregivers in the San Diego metropolitan area participated . Private group practice , academic group practice , and health maintenance organization practice types were represented by the 3 health care organizations . Study Participants The study included 18 clinics from the participating health care organizations ( 4 to 8 per organization ) ( Table 1 ) . The inclusion criterion was that these be primary care clinics . Table 1 . Characteristics of Participating Health Care Organizations * Patients with dementia who were age 65 years or older and receiving Medicare were identified by querying health care organization administrative data bases for occurrence during the previous year of a dementia diagnosis code ( 29 ) at an outpatient visit or hospitalization or a cholinesterase inhibitor prescription . Patient lists were grouped by primary provider and were circulated to those providers for confirmation of dementia diagnosis and identification of additional potential participants from his or her practice ( generating < 5 % of the sample ) . Patients had to have an informal caregiver ( age 18 years ) . Patients were recruited by mail with English- and Spanish- language letters from their physician and an opt-out postcard , followed by up to 3 mailings of a patient consent or assent form ( depending on the physician 's design ation of the patient 's ability to provide consent ) , a caregiver consent form ( containing a proxy consent for the patient if he or she was judged unable to provide consent ) , and a baseline caregiver survey . R and omization was conducted at the clinic level , based on the clinic-focused design of the care management intervention . Within each health care organization , we paired clinics by patient volume ; within each pair , we r and omly assigned 1 clinic to the intervention and the other clinic to usual care using a computerized r and om-number generator operated by a study statistician . Participants were unaware of clinic r and omization status at enrollment and at completion of the baseline survey and were not reminded of r and omization status at follow-up . Intervention A steering committee that included a physician from each health care organization , a leader from each community agency , a community caregiver , and investigators used a formal method ( 30 ) to identify 23 existing dementia guideline recommendations as care goals ( 11 , 12 , 14 ) . They also design ed a structured assessment , algorithms linking specific care management actions to assessment results , and interorganization care coordination and referral protocol s. A key intervention element was health care organization and community agencybased dementia care managers ( primarily social workers ) who received formal training and used an Internet-based care management software system for care planning and coordination ( 25 , 26 , 28 ) . Every enrolled patient and caregiver dyad in the intervention group was assigned 1 health care organization care manager , who contacted them to schedule a structured home assessment . Assessment responses were entered into the software system , generating a preliminary problem list and guides to care-plan actions . The care manager collaborated with the caregiver to prioritize problem areas ; teach problem-solving skills ; initiate care plan actions ; and send an assessment summary , a problem list , and selected recommendations to the patient 's primary care physician and other design ated providers . A menu of potential care plan actions ( for example , referral for respite care services ) was documented in a comprehensive care management manual . The care management protocol included ongoing follow-up , usually by telephone , with frequency based on need and a formal in-home re assessment every 6 months to assess the need for major care-plan revisions . The software system had a feature to enable efficient tracking of multiple cases and tasks . Referrals to a particular community agency were guided by flagged problem areas . With patient and caregiver consent , referrals were communicated through the software system to that agency , whose design ated care manager subsequently received system access to the assessment , problem list , and care plan . Each dyad could have 1 or more community agency care managers . Care managers from the health care organizations and community agencies received the same formal education and training program , which was conducted jointly , and met monthly to refine care coordination procedures . Care management began within a month after enrollment of the first dyads and was active throughout the study follow-up unless a case was closed , for example , because a patient moved out of the study area and no longer was enrolled in the health care organization . At each intervention clinic , more than 90 minutes of st and ardized , interactive seminars ( in up to 5 sessions ) on relevant care issues , including evaluation of acute behavioral changes , depression management , and determination of decision-making capacity ( 31 ) , were offered to primary care providers . Selected intervention tools and documents with more detailed descriptions can be accessed at www.adc.ucla.edu/access/access.swf . Patients , caregivers , and providers in the usual care group were not offered study interventions . Outcome Measures Primary Outcome The study 's primary outcome was BACKGROUND : Following the lead of evidence -based medicine , practice based on effectiveness research has become the new gold st and ard of contemporary public policy . Studies of this sort are increasingly dem and ed to evaluate services provided by mental health , social services and criminal justice systems . AIMS : The paper questions whether the simple r and omized controlled trial ( RCT ) paradigm as applied in clinical trials can be used " off the rack " to evaluate socially complex service ( SCS ) interventions . These are services that are characterized by complex , diverse and non-st and ardized staffing arrangements ; ambiguous protocol s ; hard-to-define study sample s and unevenly motivated subjects and dependence on broader social environments . The difficulty of ensuring precise protocol s , equivalent groups ( tied to a meaningful target population ) and neutral and equivalent trial environments under real world conditions are explored , as are the implication s of not achieving st and ardization and equivalence . METHODS : Limitations of effectiveness research as a research tool and information source are examined by comparing the assumptions underpinning the simple RCT to the characteristics of SCS interventions , as illustrated by programs targeted to mentally disordered offenders in Britain . RESULTS : SCSs violate the assumptions underpinning the simple RCT model in ways that draw into sharp question the validity , reliability and generalizability of inferences of SCS trials . DISCUSSION : The RCT is not a panacea . Effectiveness research of SCS interventions that is based on the RCT model is unlikely to yield valid , reliable and generalizable inferences without becoming more complex in design and more sensitive to issues of selection bias , unmeasured variables and endogeneity . Ten recommendations are offered for stylizing the RCT design to the characteristics of socially complex services . IMPLICATION S : It remains an empirical issue whether RCT -based services effectiveness research can inform mental health policy . Without major design innovations , it is more likely that the information generated by this research will have limited practical use , especially if the RCT model is unable to control for the effect of social complexity and the interaction between social complexity and dynamic systemic change . Scientific evaluations of services make clinical and economic sense so long as they are design ed to meet the challenges of the services of which they promise greater knowledge OBJECTIVES To evaluate the impact of a coordination-type integrated service delivery ( ISD ) model on health , satisfaction , empowerment , and services utilization of frail older people . METHODS Program of Research to Integrate Services for the Maintenance of Autonomy ( PRISMA ) is a population -based , quasi-experimental study with three experimental and three comparison areas . From a r and om selection of people 75 years or older , 1,501 persons identified at risk of functional decline were recruited ( 728 experimental and 773 comparison ) . Participants were measured over 4 years for disabilities ( Functional Autonomy Measurement System ) , unmet needs , satisfaction with services , and empowerment . Information on utilization of health and social services was collected by bimonthly telephone question naires . RESULTS Over the last 2 years ( when the implementation rate was over 70 % ) , there were 62 fewer cases of functional decline per 1,000 individuals in the experimental group . In the fourth year of the study , the annual incidence of functional decline was lower by 137 cases per 1,000 in the experimental group , whereas the prevalence of unmet needs in the comparison region was nearly double the prevalence observed in the experimental region . Satisfaction and empowerment were significantly higher in the experimental group . For health services utilization , a lower number of visits to emergency rooms and hospitalizations than expected was observed in the experimental cohort . CONCLUSION The PRISMA model improves the efficacy of the health care system for frail older people OBJECTIVES This study tested the effectiveness of a dementia care management program for Chinese families of relatives with dementia on caregivers ' and patients ' health outcomes over a 12-month follow-up period . METHODS The dementia care management program is an educational and supportive group for caregivers that lasts six months . A controlled trial was conducted with 88 primary caregivers of persons with dementia in two dementia care centers in Hong Kong . Family members were assigned r and omly to either the dementia care program or st and ard care . The two groups were compared for patients ' symptoms and institutionalization rates and caregivers ' quality of life , burden , and social support upon recruitment and six and 12 months after group assignment . RESULTS Over the 12-month follow-up period , patients with family members in the dementia care program showed significantly greater improvements in symptoms and institutionalization rates and their caregivers reported significantly greater improvements in quality of life and burden compared with the control group . CONCLUSIONS The findings provide evidence that the dementia care management program can improve the psychosocial functioning of Chinese persons with dementia and their caregivers BACKGROUND The Guided Care Program for Families and Friends ( GCPFF ) is one component of " Guided Care " ( GC ) , a model of primary care for chronically ill older adults that is facilitated by a registered nurse who has completed a supplemental educational curriculum . METHODS The GCPFF melds support for family caregivers with the delivery of coordinated and comprehensive chronic care and seeks to improve the health and well-being of both patients and their family caregivers . The GCPFF encompasses ( a ) an initial meeting between the nurse and the patient 's primary caregiver , ( b ) education and referral to community re sources , ( c ) ongoing " coaching , " ( d ) a six-session group Caregiver Workshop , and ( e ) monthly Support Group meetings , all facilitated by the patient 's GC nurse . RESULTS A cluster-r and omized controlled trial of GC is underway in 14 primary care physician teams . Of 904 consented patients , 450 ( 49.8 % ) identified a primary caregiver ; 308 caregivers met eligibility criteria , consented to participate , and completed a baseline interview . At 6-month follow-up , intervention group caregivers ' mean Center for Epidemiological Studies Depression ( CESD ) and Caregiver Strain Index ( CSI ) scores were respectively 0.97 points ( p = .14 ) and 1.14 points ( p = .06 ) lower than control group caregivers ' . Among caregivers who provided more than 14 hours of weekly assistance at baseline , intervention group caregivers ' mean CESD and CSI scores were respectively 1.23 points ( p = .20 ) and 1.83 points ( p = .04 ) lower than control group caregivers ' . CONCLUSIONS The GCPFF may benefit family caregivers of chronically ill older adults . Outcomes will continue to be monitored at 18-months follow-up OBJECTIVE To evaluate a case management ( CM ) model for people with mild dementia , whereby re sources within the family and in the community were mobilized and optimally used . METHOD Community dwelling psychiatric and geriatrics out patients with mild dementia were r and omized to receive CM by a trained occupational therapist for 4 months ( CM group , N = 59 ) or usual care only ( control group , N = 43 ) . Primary outcome indicators included the Zarit Burden Scale ( ZBI ) , General Health Question naire ( GHQ ) , and Personal Well-Being Index for Adult ( PWI-A ) of the family caregivers . Secondary outcome indicators included the Mini-Mental State Examination ( MMSE ) , Neuropsychiatric Inventory ( NPI ) , Cornell Scale for Depression in Dementia ( CSDD ) , and Personal Well-Being Index for Intellectually Disabled ( PWI-ID ) of the demented subjects as measured at fourth and twelfth months . RESULT CSDDis reduced in the CM group at fourth month , but not at twelfth month . The changes in outcome variables of persons with dementia did not differ between the groups ( Mann-Whitney U-test , p > 0.05 ) . At follow-up , CM group used more day care and domestic helpers than control group ( chi ( 2 ) , p > 0.05 ) . CONCLUSION Case management for Chinese persons with mild dementia out patients did not show significant effects in reducing caregiver burden , but encouraged family caregivers to seek external support STUDY QUESTION Does improved access to community-based care reduce perceived burden and reported levels of depression among primary caregivers of people with dementia ? DATA SOURCES Baseline and periodic caregiver interviews with participants in the Medicare Alzheimer 's Disease Demonstration . Client and caregiver attributes and caregiver outcomes such as depression and burden scores were among the measures . STUDY DESIGN Applicants to the demonstration ( all voluntary ) were r and omly assigned into treatment and control groups . Treatment group cases were eligible for case management and for up to $ 699 per month in community care benefits . ( The actual monthly entitlement varied among the eight demonstration communities due to regional cost differences and inflation adjustments over the four-year demonstration period . ) DATA COLLECTION A total of 5,307 eligible individuals received a baseline assessment at the time of application to the demonstration and at least one semi-annual re assessment . Clients and their caregivers were periodically reassessed producing a total of 20,707 observations . PRINCIPAL FINDINGS Persons in the treatment group had a high exposure to case management and a greater likelihood of community service use relative to those in the control group . Treatment group membership was associated with statistically significant , but very small reductions in caregiver burden ( in four of eight sites ) and depression ( three of eight sites ) over a 36-month tracking period . These findings are not sustained with all cases combined , or among a higher-re source demonstration model considered separately . CONCLUSIONS Both the fact that these programmatic differences did not translate into substantial treatment group reductions in caregiver burden or depression , and the consistency of these findings with those of prior case management evaluations suggest the need to reformulate this programmatic intervention into areas not previously tested : 24-hour care , crisis intervention , coordination with primary care , or chronic disease management OBJECTIVES The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . INCLUSION CRITERIA Types of participants Adult caregivers who provide support for people with dementia living in the community ( non-institutional care).Types of interventions Interventions design ed to support caregivers in their role such as skills training , education to assist in caring for a person living with dementia and support groups/programs . Interventions of formal approaches to care design ed to support caregivers in their role , care planning , case management and specially design ated members of the healthcare team - for example dementia nurse specialist or volunteers trained in caring for someone with dementia . Types of studies This review considered any meta-analyses , systematic review s , r and omised control trials , quasi-experimental studies , cohort studies , case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . SEARCH STRATEGY The search sought to identify published studies from 2000 to 2005 through the use of electronic data bases . Only studies in English were considered for inclusion . The initial search was conducted of the data bases , CINAHL , MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group . A second more extensive search was then conducted using the appropriate Medical Subject Headings ( MeSH ) and keywords for other available data bases . Finally , h and search ing of reference lists of articles retrieved and of core dementia , geriatric and psycho geriatric journals was undertaken . ASSESSMENT OF QUALITY Method ological quality of each of the articles was assessed by two independent review ers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Review s and Dissemination . DATA COLLECTION AND ANALYSIS St and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each included study reported in the meta- analysis . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software from the Cochrane Collaboration . Heterogeneity between combined studies was tested using st and ard chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . RESULTS A comprehensive search of relevant data bases , h and search ing and cross referencing found 685 articles that were assessed for relevance to the review . Eighty-five papers appeared to meet the inclusion criteria based on title and abstract , and the full paper was retrieved . Of the 85 full papers review ed , 40 were accepted for inclusion , three were systematic review s , three were meta- analysis , and the remaining 34 were r and omised controlled trials . For the r and omised controlled trials that were able to be included in a meta- analysis , st and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . The results are discussed in two main sections . Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression , health , subjective well-being , self-efficacy and burden . Secondly , results are reported by main outcome category . For each of these sections , meta- analysis was conducted where it was possible ; otherwise , a narrative summary describes the findings . EFFECTIVENESS OF INTERVENTION TYPE Four categories of intervention were included in the review - psycho-educational , support , multi-component and other . Psycho-educational Thirteen studies used psycho-educational interventions , and all but one showed positive results across a range of outcomes . Eight studies were entered in a meta- analysis . No significant impact of psycho-educational interventions was found for the outcome categories of subjective well-being , self-efficacy or health . However , small but significant results were found for the categories of depression and burden . Support Seven studies discussed support only interventions and two of these showed significant results . These two studies were suitable for meta- analysis and demonstrated a small but significant improvement on caregiver burden . Multi-component Twelve of the studies report multi-component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self-efficacy , depression , subjective well-being and burden . Unfortunately because of the heterogeneity of study design s and outcome measures , no meta- analysis was possible . Other interventions Other interventions included the use of exercise or nutrition which result ed in improvements in psychological distress and health benefits . Case management and a computer aided support intervention provided mixed results . One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour . EFFECTIVENESS OF INTERVENTIONS USING SPECIFIC OUTCOME CATEGORIES In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies . In particular the impact of interventions on caregiver depression was available for meta- analysis from eight studies . This indicated that multi-component and psycho-educational interventions showed a small but significant positive effect on caregiver depression . Five studies using the outcome category of caregiver burden were entered into a meta- analysis and findings indicated that there were no significant effects of any of interventions . No meta- analysis was possible for the outcome categories of health , self-efficacy or subjective well-being . IMPLICATION S FOR PRACTICE From this review there is evidence to support the use of well- design ed psycho-educational or multi-component interventions for caregivers of people with dementia who live in the community . Factors that appear to positively contribute to effective interventions are those which : Factors which do not appear to have benefit in interventions are those which |
11,733 | 22,535,147 | Overall considered , these results support the hypothesis of a primary visual cortex hyper-excitability in MA , providing not enough evidence for MwA. A significant statistical heterogeneity reflects clinical and method ological differences across studies , and higher temporal variabilities among PT measurements over time , related to unstable excitability levels . | null | null |
11,734 | 25,869,992 | The prevalence of polypharmacy in LTCFs is high , varying widely between facilities , geographical locations and the definitions used . | OBJECTIVE The objective of the study was to investigate the prevalence of , and factors associated with , polypharmacy in long-term care facilities ( LTCFs ) . | INTRODUCTION At present , 7.2 % of the population in Singapore is in the geriatric age group , which will increase to 18.4 % in the year 2030 . The frailest segment of the geriatric population live in nursing homes . They suffer from multiple co-morbidities requiring multiple medication use . Polypharmacy and inappropriate medication use have been considered as quality indicators for nursing home care . As no data of these indicators are available in Singapore , this study was planned to assess the prevalence of polypharmacy and inappropriate medication use in Singapore nursing homes . MATERIAL S AND METHODS A total of 454 residents in the geriatric age group residing in 3 r and omly selected nursing homes were involved in the study . Case notes were review ed for demographic information , clinical history and medication use . The data were analysed for polypharmacy ( 5 or more medication orders ) and inappropriate medication use ( based on established criteria ) . RESULTS Residents were on an average of 5.32 medications . Polypharmacy and inappropriate medication use were seen in 266 ( 58.6 % ) and 318 ( 70.0 % ) residents , respectively . There was significant association between polypharmacy and inappropriate medication use [ P < 0.001 , chi2 = 82.56 at 95 % confidence interval ( CI ) ] . The most common medication-related problems were the use of medication without proper indication ( n = 302 ) , significant potential for adverse drug reactions ( n = 281 ) and drug interactions ( n = 141 ) . CONCLUSION The prevalence of polypharmacy and inappropriate medication use is high in Singapore nursing homes . Current practice of medication use in the nursing homes may lead to significant adverse drug reactions and drug interactions . A multidisciplinary approach involving geriatricians , nursing home physicians , nurses and pharmacists may potentially reduce polypharmacy and inappropriate medication use in Singapore nursing homes Background Nursing home residents are mainly older people with multiple diseases and taking multiple medications . The quality use of medication and its association with health related quality of life ( HRQoL ) have not been reported in Malaysia . This study aims to investigate the association between the use of potentially inappropriate medications ( PIMs ) and the changes observed in the HRQoL among older nursing home residents . Methods A prospect i ve follow up study was conducted at four nongovernmental organization nursing homes in Penang , Malaysia . Older residents ( ≥65 years old ) taking at least one prescribed medication were included . Residents with PIMs were identified by using Screening Tool of Older Person ’s potentially inappropriate Prescriptions ( STOPP ) criteria . HRQoL was assessed using EuroQol-5 dimension ( EQ-5D ) and EuroQol-visual analog scale ( EQ-VAS ) at baseline and after a 3-month follow up . The association of PIMs with HRQoL was analyzed using Mann-Whitney U test . Results The median age of the 211 participants was 77 years ( interquartile range 72–82 years ) and the median number of prescription medicines was four ( interquartile range three to six ) . The prevalence of PIMs was 23.7 % and 18.6 % at baseline and 3 months later , respectively . The most commonly prescribed PIMs in decreasing order were first generation antihistamine , prescriptions of duplicate drug class , glibenclamide with type 2 diabetes mellitus , and anticholinergic to treat extrapyramidal side effects of neuroleptic medications . At baseline , there was no significant difference among residents with or without PIMs in each bracket of EQ-5D , EQ-5D index , or EQ-VAS scores . Comparison of the differences in the mean score index of EQ-5D between baseline and after 3 months also showed no statistically significant differences . Conclusion PIMs were found to be relatively common among older nursing home residents . However , no significant changes were observed in HRQoL among these residents . Further studies with a bigger sample size and longer follow up period are required to establish this association PURPOSE To develop a simple screen based on easily collectable measures to identify older people living in residential care facilities at high risk of falls . METHODS This prospect i ve study was conducted in seven residential care facilities in the U.K. Residents aged>60 years who were not bedbound or terminally ill participated . Demographics , medical history , medication use , cognition ( mini mental state examination ( MMSE ) ) , function ( Barthel , balance and sit-to-st and ability ) and behavior ( neuro-psychiatric inventory ( NPI ) and impulsivity ) were recorded at baseline . Falls and injuries were prospect ively recorded over 6 months . Data were analyzed for differences between fallers and non-fallers and significant variables entered into logistic regression analysis . RESULTS Two hundred and forty residents completed the study . In the follow-up period , 50 % fell ≥1 times . Fallers had worse function , cognition , behavior and balance and took more medications . Falling in the past year , walking frame and hypnotic/anxiolytic and anti-depressant medication use were also associated with increased likelihood of falling . Logistic regression identified MMSE<17 , impulsivity score ≥ 2 , st and ing balance score<6 , requiring a walking frame , falling in the previous year and use of antidepressants and hypnotics/anxiolytics as independent and significant predictors of falls . The area under the receiver operating curve ( ROC ) for this model was 0.79 ( 95 % CI 0.73 - 0.84 ) . CONCLUSIONS This tool comprising multi-factorial measures provides a simple way of quantifying the probability with which a care home resident will fall over a 6-month period . The tool may also assist in guiding the development and targeting of interventions to prevent falls in this group BACKGROUND In a prospect i ve study of nursing home residents , we found adverse drug events ( ADEs ) to be common , serious , and often preventable . To direct prevention efforts at high-risk residents , information is needed on resident-level risk factors . METHODS Case-control study nested within a prospect i ve study of ADEs among residents in 18 nursing homes . For each ADE , we r and omly selected a control from the same home . Data were abstract ed from medical records on functional status , medical conditions , and medication use . RESULTS Adverse drug events were identified in 410 nursing home residents . Independent risk factors included being a new resident ( odds ratio [ OR ] , 2.8 ; 95 % confidence interval [ CI ] , 1.5 - 5.2 ) and taking anti-infective medications ( OR , 4.0 ; CI , 2.5 - 6.2 ) , antipsychotics ( OR , 3.2 ; CI , 2.1 - 4.9 ) , or antidepressants ( OR , 1.5 ; CI , 1.1 - 2.3 ) . The number of regularly scheduled medications was associated with increased risk of ADEs ; the OR associated with taking 5 to 6 medications was 2.0 ( CI , 1.2 - 3.2 ) ; 7 to 8 medications , 2.8 ( CI , 1.7 - 4.7 ) ; and 9 or more , 3.3 ( CI , 1.9 - 5.6 ) . Taking supplements or nutrients was associated with lower risk ( OR , 0.42 ; CI , 0.27 - 0.63 ) . Preventable ADEs occurred in 226 residents . Independent risk factors included taking opioid medications ( OR , 6.6 ; CI , 2.3 - 19.3 ) , antipsychotics ( OR , 4.0 ; CI , 2.2 - 7.3 ) , anti-infectives ( OR , 3.0 ; CI , 1.6 - 5.8 ) , antiepileptics ( OR , 2.2 ; CI , 1.1 - 4.5 ) , or antidepressants ( OR , 2.0 ; CI , 1.1 - 3.5 ) . Scores of 5 or higher on the Charlson Comorbidity Index were associated with increased risk of ADEs ( OR , 2.6 ; CI , 1.1 - 6.0 ) . The number of regularly scheduled medications was also a risk factor : the OR for 7 to 8 medications was 3.2 ( CI , 1.4 - 6.9 ) and for 9 or more , 2.9 ( CI , 1.3 - 6.8 ) . Residents taking nutrients or supplements were at lower risk ( OR , 0.27 ; CI , 0.14 - 0.50 ) . CONCLUSIONS It is possible to identify nursing home residents at high risk of having an ADE . Particular attention should be directed at new residents , those with multiple medical conditions , those taking multiple medications , and those taking psychoactive medications , opioids , or anti-infective drugs Objective : To study changes in drug use after admission to Dutch nursing homes . Setting . Six nursing homes near the city of Nijmegen , The Netherl and s. Design . Prospect i ve longitudinal study . Methods . All patients who had been newly admitted to the nursing home were included in the study . Age , gender , residence of the patients before admission , and indication were registered . All prescriptions were registered with start‐ date and end‐ date . The nomenclature and subcategory definitions used were those of the World Health Organisation Nordic Anatomical Therapeutic Chemical classification index ( ATC ) codes . Patients had a follow‐up of six weeks . Results . There was a minor , but statistically significant , increase in the mean number of drugs from 5.6 on admission to 5.8 six weeks later . Patients referred from a hospital and patients with a somatic indication were prescribed the highest number of drugs . On admission 5.5 % of the patients were not on medication at all , 48%were using 1‐2 drugs , and 46 % had been prescribed 6 or more drugs . Six weeks after admission , a significant increase in drug use was found in drugs for the nervous system , and drugs for the sensory organs . Conclusion . Increase in drug use does not necessarily have to reflect bad prescribing practice s. However , in this frail population , continuous drug review is needed to guarantee quality of prescribing and reduce unnecessary polypharmacy OBJECTIVES To evaluate the association between the Drug Burden Index ( DBI ) , a measure of a person 's total exposure to anticholinergic and sedative medications that includes principles of dose-response and maximal effect and is associated with impaired physical function in community-dwelling older people , and falls in residents of residential aged care facilities ( RACFs ) . DESIGN Data were drawn from participants in a r and omized controlled trial that investigated falls and fractures . SETTING RACFs in Sydney , Australia . PARTICIPANTS Study participants ( N=602 ; 70.9 % female ) were recruited from 51 RACFs . Mean age was 85.7 ± 6.4 , and mean DBI was 0.60 ± 0.66 . MEASUREMENTS Medication history was obtained on each participant . Drugs were classified as anticholinergic or sedative and a DBI was calculated . Falls were measured over a 12-month period . Comorbidity , cognitive impairment ( Mini-Mental State Examination ) and depression ( Geriatric Depression Scale ) were determined . RESULTS There were 998 falls in 330 individuals during a follow-up period of 574.2 person-years , equating to an average rate of 1.74 falls per person-year . The univariate negative binomial regression model for falls showed incidence rate ratios of 1.69 ( 95 % confidence interval (CI)=1.22 - 2.34 ) for low DBI ( < 1 ) and 2.11 ( 95 % CI=1.47 - 3.04 ) for high DBI ( ≥1 ) when compared with those who had a DBI of 0 . After adjusting for age , sex , history of falling , cognitive impairment , depression , use of a walking aid , comorbidities , polypharmacy , and incontinence , incident rate ratios of 1.61 ( 95 % CI=1.17 - 2.23 ) for low DBI and 1.90 ( 95 % CI=1.30 - 2.78 ) for high DBI were obtained . CONCLUSION DBI is significantly and independently associated with falls in older people living in RACFs . Interventional studies design ed for this population are needed to determine whether reducing DBI , through dose reduction or cessation of anticholinergic and sedative drugs , can prevent falls OBJECTIVES To evaluate the feasibility of developing consensus recommendations for appropriate prescribing for patients with advanced dementia using a new conceptual framework and to determine the frequency of inappropriate medication use based on these recommendations in a small sample of patients with advanced dementia . DESIGN Medication data were obtained using chart review . Recommendations for appropriate prescribing were achieved using a modified Delphi consensus panel . SETTING Three long-term care facilities . PARTICIPANTS Thirty-four patients with advanced dementia enrolled in the Palliative Excellence in Alzheimer Care Efforts Program were selected to evaluate medication use . Twelve geriatricians at the University of Chicago participated in the modified Delphi consensus panel . MEASUREMENTS Prescription and over-the-counter medications were recorded for the 34 patients . Following the modified Delphi process , medications were characterized into one of four categories for use in palliative care patients with advanced dementia : never appropriate , rarely appropriate , sometimes appropriate , or always appropriate . RESULTS Patients were taking an average of 6.5 medications at enrollment . Six patients were taking 10 or more medications daily . Consensus was reached ranking the appropriateness of 69 of 81 medication classes for patients with advanced dementia . Overall , 5 % of the 221 medications prescribed at enrollment were considered to be never appropriate , and 10 of 34 patients ( 29 % ) had been taking a medication considered to be never appropriate . CONCLUSION Based on these preliminary findings , consensus criteria for prescribing in advanced dementia are needed to decrease polypharmacy and reduce the use of medications that are of minimal benefit or high risk BACKGROUND Chronic Kidney Disease ( CKD ) and its progression are associated with multiple risk factors . CKD is prevalent in nursing homes residents , but factors related to CKD in this setting have not been defined . METHODS A cross-sectional study was conducted ( n=103 ) . Data was abstract ed using st and ardized forms and analyzed ( SAS 9.2 ) . Chi square and t-test statistics were used to compare proportions and means ; correlation coefficients were used to describe associations . Logistic models were fit to the data to determine multivariate associations . Modification of Diet in Renal Disease ( MDRD ) formula was used to estimate GFR . CKD was defined according to established st and ards . A cutoff point of 60 was chosen for further analysis . RESULTS Twenty-three percent of subjects had CKD . Mean age for eGFR < 60 was 70.8 + /- 13 and for eGFR > 60 was 61.7 + /-14 . Frequent co-morbidities were hypertension ( 75 % ) , GERD ( 40 % ) , obesity ( 39 % ) , dyslipidemia ( 35 % ) , depression ( 34 % ) , anemia ( 32 % ) , and diabetes ( 32 % ) . CONCLUSIONS Our population is unique in terms of its age and reasons for nursing home admission . Factors associated with CKD in our study include age > 65 years old , being male , having a positive history of cardiovascular disease ( including congestive heart failure and coronary artery disease , ) anemia , polypharmacy , and being obese ( BMI > 30 ) . Further analysis showed that age and anemia are the strongest factors associated with CKD in our population . Management targeted at CKD risk factor reduction may play a vital role in controlling the magnitude of this disease . Prospect i ve studies to investigate the relationship between gender , a BMI greater than 30 , cardiovascular disease , and CKD and its complications are warranted |
11,735 | 25,247,310 | Conclusion : In the available studies , FG did not consistently have a positive influence on the healing of gastrointestinal anastomoses .
It is consequently plausible that the positive effect of FG sealing of gastrointestinal anastomoses , if there is any , may be due to a mechanical sealing effect rather than due to improved healing per se | Background / Aim : Anastomotic leakage remains a frequent and serious complication in gastrointestinal surgery .
In order to reduce its incidence , several clinical and experimental studies on anastomotic sealing have been performed .
In a number of these studies , the sealing material has been fibrin glue ( FG ) , and the results in individual studies have been varying .
The positive effect of anastomotic sealing with FG might be due to the mechanical/physical properties , the increased healing of the anastomoses or both .
The aim of this systematic review was to evaluate the existing evidence on the healing effects of FG on gastrointestinal anastomoses . | Background : Excluding pulmonary embolism , anastomotic leak is the leading cause of death and major morbidity in patients undergoing open or laparoscopic gastric bypass operations . We observed a number of these leaks ( 11 out of 1,120 MicropouchSM gastric bypass [ MGB ] patients ; 0.9 % ) . The majority ( 80 % ) required emergency laparotomy and drainage , massive fluid resuscitation , and aggressive nutritional support . Therefore , we design ed a 2-year , prospect i ve study to determine the therapeutic efficacy of vapor-heated fibrin sealant to prevent anastomotic leaks at the gastro-jejunostomy ( GJS ) site . Methods : Between April , 2000 and March , 2002 , 738 patients underwent a primary ( n=671 ) or revisionary ( n=67 ) MGB procedure . The gastric reservoir was limited to the cardia of the stomach . Vapor-heated fibrin glue 1 cc was applied circumferentially to a 12-mm , non-b and ed GJS anastomosis . Once activated , fibrin sealant polymerized into a soft , closely adherent gel . No omental patch was used to cover the fibrin-sealed anastomosis . Results : Of 738 patients , 2 required emergency laparotomy for leaks and 2 for adhesive b and s that contributed to a distal small bowel obstruction . There were no anastomotic leaks at the fibrin-sealed GJS sites . No gastro-gastric or gastro-enteric fistulas were recorded . Conclusion . Fibrin sealant applied to the GJS site appears to have eliminated anastomotic leaks in our MicropouchSM gastric bypass patients . These results suggest that fibrin glue application may contribute to " leak prophylaxis " in patients undergoing open Rouxen-Y gastric bypass . Glue placements may also benefit patients undergoing a laparoscopic Roux-en-Y procedure , wherein anastomotic leaks have been reported early in the learning curve PURPOSE : The aim of this study was to investigate the role of omentoplasty , by means of intact omentum , in preventing anastomotic leakages after rectal resection . METHODS : Between 1992 and 1997 a total of 112 patients ( 64 males ) with a mean age of 64.7 ( range , 39–83 ) years were r and omly assigned to undergo omentoplasty ( Group A ) or not ( Group B ) to reinforce the colorectal anastomosis after anterior resection for rectal cancer . The primary end point was anastomotic leakage ; the secondary end point included morbility and mortality related to omentoplasty . RESULTS : The two groups were comparable in terms of preoperative and intraoperative characteristics . Staple-ring disruption at plain abdominal radiographs was detected in seven instances in Group A and in ten in Group B patients ( P = not significant ) . Two leakages were evident clinical ly in Group A and seven in Group B ( P<0.05 ) . Three leaks were documented radiologically in Group A and eight in Group B ( P = not significant ) . No complications related to omentoplasty were observed in Group A. There were two repeat operations for anastomotic leakage in Group B. At follow-up , one stricture developed in Group A and three in Group B ( P = not significant ) CONCLUSIONS : Despite a similar incidence of staple-ring defects , a strikingly lower rate of clinical ly and radiologically detected leaks developed in patients su bmi tted to omentoplasty . Although not affecting the incidence of anastomotic disruption , omentoplasty seems to contain the severity of anastomotic leakage BACKGROUND Despite improved surgical techniques , anastomotic leakage remains as a serious complication in colorectal surgery , producing increased morbidity and mortality . This prospect i ve study was initiated to test the hypothesis that preexisting disorders in the extracellular matrix ( ECM ) may be a factor influencing the onset of anastomotic wound healing complications . METHODS In this prospect i ve study of 119 patients with colorectal anastomoses , 30 clinical parameters with possible influence on anastomotic complications were evaluated . From all patients , sample s of macroscopically intact colonic tissue were obtained at the index operation . Crosspolarization microscopy was performed to analyze the collagen type I/III ratio , and immunohistochemical studies were done to determine the expression of matrix metalloproteinase ( MMP ) 1 , 2 , 9 , and 13 . The patients with uncomplicated postoperative healing were compared with those developing anastomotic leakage . RESULTS Patients with impaired anastomotic healing exhibited a significantly lower collagen type I/III ratio compared with the controls . Significantly higher expression of MMP-1 and MMP-2 in the mucosal layers and of MMP-2 and MMP-9 in the submucosal layers was found in the normal bowel wall of the leakage group . These findings were statistically independent from the clinical parameters . CONCLUSION The present study confirms the hypothesis that disturbances of the ECM play a role in the pathogenesis of anastomotic leakage after large bowel surgery A left-sided colon obstruction was produced with a polypropylene sling in 65 rats . Colon resection and primary anastomosis were performed three days later . The animals were then r and omly allocated to the FG ( fibrin glue ) group receiving sealing of the anastomosis with 0.4 ml of fibrin glue ( Beriplast R ) , or to the NG ( non-glue ) group . The anastomoses were assessed 30 min , two days and four days later . Adhesion formation was similar in both groups . The number of macroscopic or radiological leakages did not differ either . At 30 min the mean bursting pressure was 74.6 + /- 8.6 ( SD ) mmHg in the FG group and 58.3 + /- 21.6 mmHg in NG ( non-glue ) group ( p less than 0.05 , Mann-Whitney test ) . Later on the strength of the anastomoses was equal in both groups . We conclude that the initial sealing of weak points in the anastomoses was beneficial but the inherent strength per se could not be enhanced Purpose To investigate whether a collagen fleece kept in place by fibrin glue might seal off a colorectal anastomosis , provide reinforcement , and subsequently improve anastomotic healing . Methods Wistar rats underwent a 1-cm left-sided colonic resection followed by a 4-suture end-to-end anastomosis . They were then r and omly assigned to one of three treatment groups : no additional intervention ( control , n = 20 ) , the anastomosis covered with fibrin glue ( fibrin glue , n = 20 ) , the anastomosis covered with a collagen fleece , kept in place with fibrin glue ( collagen fleece , n = 21 ) . At either 3 or 7 days follow-up , anastomotic bursting pressure was measured and tissue was obtained for histology and collagen content assessment after which animals were sacrificed . Results Three rats in the control ( 15 % ) , three in the fibrin glue ( 15 % ) , and one in the collagen group ( 4.8 % ) died due to anastomotic complications ( P = 0.497 ) . Anastomotic bursting pressures were not significantly different between groups at 3 and 7 days follow-up ( P = 0.659 and P = 0.427 , respectively ) . However , bowel obstructions occurred significantly more often in the collagen group compared to the control group ( 14/21 vs. 3/20 , P = 0.003 ) . Collagen contents were not different between groups , but histology showed a more severe inflammation in the collagen group compared to the other groups at both 3 and 7 days follow-up . Conclusions A collagen fleece kept in place by fibrin glue does not improve healing of colonic anastomoses in rats . Moreover , this technique induces significantly more bowel obstructions in rats , warranting further study before being translated to a clinical setting Objective The aim of this study was to characterize a successful approach for the management of infants with long-gap esophageal atresia ( EA ) with tracheoesophageal fistula ( TEF ) . The goal was to preserve the native esophagus and minimize the incidence of esophageal anastomotic leaks using fibrin glue as a sealant over the esophageal anastomosis . Method A total of 52 patients were evaluated in this study . Only patients in whom , gap between the two ends of the esophagus was ≥ 2 cm were selected during January 2005 to January 2007 . Patients were divided in two groups on the basis of block r and omization . Group A comprised the patients in whom fibrin sealant was used as reinforcement on a primary end-to-end esophageal anastomosis ; in group B , fibrin glue was not used . The two groups were compared in terms of esophageal anastomotic leak ( EL ) , postoperative esophageal stricture ( ES ) , and mortality . The statistical analysis was done using Fisher ’s exact test and the chi-squared test . Result The number of anastomotic leaks in group A ( glue group ) was about one-fifth that in group B ( no glue group ) . The incidence of ES was almost twice as high in group B as in group A. The mortality rate was almost threefold higher in group B ( no-glue group ) . The higher incidence of EL and ES in group B compared to group A was statistically significant . Conclusion Thus , fibrin glue when used as an adjunct to esophageal anastomosis for primary repair of long-gap EA with TEF appears safe in the clinical setting and may lower the chances of esophageal leak and anastomosis-site strictures . Hence , it can diminish the mortality and morbidity of these patients Abstract Background After colon resection for colonic cancer , the administration of antineoplastic agents may prolong survival by killing residual cancer calls and preventing metastasis , but may also slow anastomotic healing . This study was design ed to determine the effects of 5-fluorouracil ( 5-FU ) and leucovorin ( LEV ) , injected intraperitoneally , on the healing of colonic anastomoses with or without fibrin glue ( FG ) covering . Methods Sixty rats were r and omized to one of four groups . After resection of a transverse colon segment , an end-to-end sutured anastomosis was performed . Rats in the 5-FU+LEV and the 5- FU+LEV+FG groups received 5-FU+LEV intraperitoneally . The colonic anastomoses of the rats in the FG group and in the 5-FU+LEV+FG group were covered with fibrin glue . All rats were killed on postoperative day 8 . Bursting pressure measurements were recorded and the anastomoses were examined macroscopically and histologically . Results The leakage rate of the anastomoses was significantly different among groups . Specifically , the leakage rate was significantly higher in the 5-FU+LEV group ( 40 % ) than in the FG and in the 5-FU+LEV+FG groups where there were no leakages ( p=0.017 ) . The mean adhesion formation score was significantly higher in rats of the 5-FU+LEV group , compared to the control ( p=0.023 ) , the FG ( p=0.006 ) and the 5-FU+LEV+FG ( p=0.006 ) groups . Bursting pressures were significantly lower in the 5-FU+LEV group than in the other groups ( p<0.001 ) . Also , bursting pressures were significantly lower in the control group compared to the FG and 5-FU+LEV+FG groups ( p<0.001 ) . Rats in the 5-FU+LEV+FG group had significantly greater neoangiogenesis and fibroblast activity than those in the 5-FU+LEV group ( p=0.025 ) . Conclusion The early intraperitoneal postoperative administration of 5-fluorouracil plus leucovorin impaired colonic wound healing . However , the application of fibrin glue prevented the deleterious effect of chemotherapy OBJECTIVE To investigate the role of omentoplasty ( OP ) in the prevention of anastomotic leakage after colonic or rectal resection . SUMMARY BACKGROUND DATA It has been proposed that OP -- wrapping the omentum around the colonic or rectal anastomosis -- reinforces intestinal sutures with the expectation of lowering the rate of anastomotic leakage . However , there are no prospect i ve , r and omized trials to date to prove this . METHODS Between September 1989 and March 1994 , a total of 705 patients ( 347 males and 358 females ) with a mean age of 66 + /- 15 years ( range , 15 - 101 ) originating from 20 centers were r and omized to undergo either OP ( n = 341 ) or not ( NO , n = 364 ) to reinforce the colonic anastomosis after colectomy . Patients had carcinoma , benign tumor , colonic Crohn 's disease , diverticular disease of the sigmoid colon , or another affliction located anywhere from the right colon to and including the midrectum . Patients undergoing emergency surgery were not included . R and om allotment took place once the resection and anastomosis had been performed , the surgeon had tested the anastomosis for airtightness , and the omental flap was deemed feasible . Patients were divided into four strata : ileo- or colocolonic anastomosis , supraperitoneal ileo- or colorectal anastomosis , infraperitoneal ileo- or colorectal anastomosis , and ileo- or coloanal anastomosis . The primary end point was anastomotic leakage . Secondary end points included intra- and extraabdominal related morbidity and mortality . Severity of anastomotic leakage was based on the rate of repeat operations and related deaths . RESULTS Both groups were comparable in terms of preoperative characteristics . Intraoperative findings were similar , except that there were significantly more septic operations and abdominal drainage performed in the NO group ( p < 0.05 and p < 0.01 , respectively ) . Thirty-five patients ( 4.9 % ) had postoperative anastomotic leakage , 16 in the OP group ( 4.7 % ) and 19 in the NO group ( 5.2 % ) . There were 32 deaths ( 4.5 % ) , 17 ( 4.9 % ) in the OP group and 15 ( 4.2 % ) in the NO group . Five patients with anastomotic leakage died ( 0.8 % ) , 2 of whom had OP . There were 37 repeat operations ( 30 % ) , 12 ( 6 in each group ) for anastomotic leakage . Repeat operation was associated with fatal outcome in 14 % of cases . The rate of these and the other intra- and extraabdominal complications did not differ significantly between the two groups . CONCLUSION OP to reinforce colorectal anastomosis decreases neither the rate nor the severity of anastomotic failure Background The adoption of advanced laparoscopic techniques for complex surgical procedures has raised the concern that the leak rate might be higher than for open surgery , particularly in the surgeon 's early experience or in difficult cases . In this study , the sealing effect of fibrin glue on leaking gastrointestinal anastomoses was evaluated in an experimental swine model . Methods A st and ardized gastrojejunostomy was performed on 20 female pigs ( mean weight , 47.7 ± 5.7 kg ) . A leak was created on the anterior surface of the anastomosis . The animals were r and omized to either fibrin glue or no treatment of the leak . Clinical conditions and vital signs , including body temperature , heart rate and , respiratory rate , were collected three times a day . Preoperative and postoperative complete and differential blood count and lactate dehydrogenase levels were determined . Postmortem analysis was performed when the animals were killed . Results Clinical signs of peritonitis developed in the control animals by the second or third postoperative day . Findings that confirmed the presence of an anastomotic leak at the postmortem examination were the presence of food or gastrojejunal juices in the abdominal cavity , a localized abscess , or a positive air leak test . Fibrin glue treatment prevented the development of peritonitis in all the animals . Complete sealing of the leak was observed on postoperative day 7 in all treated animals , except one in which an asymptomatic contained leak developed . The postoperative total white blood count was significantly increased in the untreated group ( 24.69 ± 5.5 vs 12.74 ± 3.7 103/ul p < 0.001 , paired t-test ) , as compared with the treated group ( 15 . 55 ± 2.4 vs 14.89 ± 2.7 103/ul ; p = 0.24 ) . Conclusion In this study , fibrin glue showed reproducible sealing effects on leaking gastrojejunal anastomoses . Fibrin glue application may be a valuable approach for the treatment of gastrointestinal anastomotic leaks Background It has been well established that the immediate postoperative intraperitoneal administration of chemotherapeutic agents such as 5-fluorouracil ( 5-FU ) after curative colon resection for colon cancer destroys disseminated cancer cells and inhibits micrometastases but also inhibits anastomotic healing . On the other h and , the application of fibrin glue constitutes a physical barrier around the anastomosis and may prevent anastomotic leakage . The purpose of this experimental study was to determine the effect of 5-FU plus interferon (IFN)-α-2a on the integrity of colonic anastomoses covered with fibrin glue when injected intraperitoneally immediately after colon resection . Material s and Methods Sixty rats were r and omized to one of four groups . After resection of a 1-cm segment of the transverse colon , an end-to-end sutured anastomosis was performed . Rats of the control and the fibrin glue groups were injected with 6 ml of 0.9 % sodium chloride ( NaCl ) solution intraperitoneally . Rats in the 5-FU + IFN and the 5-FU + IFN + fibrin glue groups received 5-FU plus IFN intraperitoneally . The colonic anastomoses of the rats in the fibrin glue and in the 5-FU + IFN + fibrin glue groups were covered with fibrin glue . All rats were sacrificed on the 8th postoperative day , and the anastomoses were examined macroscopically . The bursting pressure measurements were recorded , and the anastomoses were grade d histologically . Results Only the 5-FU + IFN group had anastomoses rupture , and the rupture rate ( 33 % ) in this group was significantly greater than in the other groups , where there were no ruptures ( P = 0.015 ) . The adhesion formations score was , on average , significantly higher in rats of the 5-FU + IFN group compared with the control group ( P = 0.006 ) and the 5-FU + IFN + fibrin glue group ( P = 0.010 ) . Bursting pressures were significantly lower in the control group when compared to the fibrin glue and 5-FU + IFN + fibrin glue group ( P < 0.001 ) . Rats in the 5-FU + IFN + fibrin glue group developed significantly more marked neoangiogenesis than rats in the other groups . Inflammatory cell infiltration , collagen deposition , and fibroblast activity did not differ significantly among the four groups ( P = 0.856 , P = 0.192 and P = 0.243 , respectively ) . Conclusion The immediate postoperative intraperitoneal administration of 5-FU plus IFN impairs colonic healing . However , when the colonic anastomoses were covered with fibrin glue , the injection of 5-FU plus IFN had no adverse effects on the integrity of the anastomoses The impact of anastomotic leakage on long-term outcomes after curative surgery for colorectal cancer has not been well documented . This study aim ed to investigate the effect of anastomotic leakage on survival and tumor recurrence in patients who underwent curative resection for colorectal cancer . Prospect ively collected data of the 1,580 patients ( 904 men ) of a median age of 70 years ( range : 24–94 ) , who underwent potentially curative resection for colorectal cancer between 1996 and 2004 , were review ed . Cancer-specific survival and disease recurrence were analyzed using Kaplan Meier method , and variables were compared with log rank test . Cox regression model was used in multivariate analysis . The cancer was situated in the colon and the rectum in 933 and 647 patients , respectively . Anastomotic leakage occurred in 60 patients ( clinical leakage : n = 48 ; radiological leak : n = 12 ) . The leakage rate was significantly higher in patients with surgery for rectal cancer ( 6.3 vs 2.0 % , p < 0.001 ) . The 5-year cancer-specific survivals were 56.9 % in those with leakage and 75.9 % in those without leakage ( p = 0.012 ) . The 5-year systemic recurrence rates were 48.4 and 22.6 % in patients with and without anastomotic leak , respectively ( p = 0.001 ) , whereas the 5-year local recurrence rates were 12.9 and 5.7 % , respectively ( p = 0.009 ) . Anastomotic leakage remained an independent factor associated with a worse cancer-specific survival ( p = 0.043 , hazard ratio : 1.63 , 95 % CI : 1.02–2.60 ) and a higher systemic recurrence rate ( hazard ratio : 1.94 , 95 % CI : 1.23–3.06 , p = 0.004 ) on multivariate analysis . In rectal cancer , anastomotic leakage was an independent factor for a higher local recurrence rate ( hazard ratio : 2.55 , 95 % CI : 1.07–6.06 , p = 0.034 ) . In conclusion , anastomotic leakage is associated with a poor survival and a higher tumor recurrence rate after curative resection of colorectal cancer . Efforts should be undertaken to avoid this complication to improve the long-term outcome Purpose Experimental and clinical studies on the sealing of colorectal anastomoses in order to reduce the rate of leakage have previously been performed with divergent results . However , comparatively few studies have been performed on anastomotic healing using a fibrin glue-coated patch . The aim of this experimental basic scientific study in mice was to investigate the effect of fibrin glue-coated collagen patches on the healing process of colonic anastomoses in situations of adverse healing process ( technical deficiency and peritonitis ) . Methods Colonic anastomoses were carried out in 206 mice and r and omized into six groups ( I : complete anastomoses , II : sealed complete anastomoses , III : incomplete anastomoses , IV : sealed incomplete anastomoses , V : complete anastomoses in the presence of bacterial peritonitis , VI : sealed complete anastomoses in the presence of bacterial peritonitis ) . Tissues from the anastomoses were removed and used for functional , histochemical , molecular , and biochemical investigations . Results The evaluation of postoperative course data revealed the beneficial effect of additional sealing with a fixed combination of collagen matrix-bound coagulation factors I and IIa ( Tachosil ® , Nycomed Austria , Linz ) in high-risk experimental anastomotic healing . Sealing incomplete anastomoses result ed in significantly lower lethality and leakage rates , as well as significantly higher bursting pressure values and histopathologic scores . Collagen 1 and 3 expressions and hydroxyproline concentrations are greatly increased with additional sealing in all high-risk anastomoses . Conclusions In our current model , we demonstrate that additionally sealing high-risk experimental colonic anastomoses provides a positive effect on the healing process . The effect on the molecular level in particular seems to be essential and requires further experimental studies to evaluate the mechanism BACKGROUND Anastomotic leakage is a feared complication after esophagectomy . The purpose of this study was to investigate whether the use of a fibrin-thrombin coated collagen patch ( TachoSil ; Nycomed , Zurich , Switzerl and ) , applied as a sealant , would strengthen the esophagogastric anastomosis and stimulate anastomotic healing in a rat model . METHODS H and sewn , end-to-side esophagogastric anastomoses were performed in 54 rats . Animals were r and omized for an unsealed or sealed anastomosis . Rats were sacrificed on postoperative d 0 , 3 , 5 , and 7 . Primary parameter was bursting pressure . Secondary outcomes were complications , weight , and immunohistochemical staining for collagen formation and fibroblast activity . RESULTS Bursting pressure at d 0 and 3 was significantly increased when a sealant was used ( 55.1 ± 4.6 mmHg versus 102.4 ± 7.3 mmHg , P < 0.010 ; and 19.7 ± 3.3 mmHg versus 34.6 ± 4.9 mmHg , P < 0.050 respectively ) . There was no difference in bursting pressure at d 5 and 7 between unsealed and sealed anastomoses ( 60.9 ± 18.2 mmHg versus 53.4 ± 6.6 mmHg , P = 0.690 ; and 118.8 ± 20.2 mmHg versus 97.2 ± 8.3 mmHg , P = 0.374 respectively ) . Application of sealant independently influenced bursting pressure ( P < 0.010 ) . Increased fibroblastic activity was noticed at d 7 in sealed anastomoses ( P < 0.050 ) . There were no differences in weight gain between groups . CONCLUSIONS Additional sealing of the anastomosis increased anastomotic strength during early postoperative recovery when anastomotic strength is at its weakest . The findings indicate that sealing of the anastomosis has the potential to prevent leakage after esophagectomy in humans Background The aim of the study was to compare the degree of healing and air tightness of h and -sewn colonic anastomoses provided by different biological glues . Methods Thirty colonic anastomoses were fashioned in ten rabbits , at 5 , 10 , 15 cm from the ileocecal valve , with 4/0 PDS running sutures . Each suture was r and omized to treatment with fibrin sealant ( Tissucol ® ) , a synthetic glue ( Coseal ® ) , or nothing ( control ) . After 15 days , the rabbits were killed and the anastomoses examined for their integrity and resistance to bursting . The van der Hamm scale was used to evaluate postoperative adhesions . A blind histological evaluation of the newly formed tissue was made ( Ehrlich – Hunt scale ) . Results Two rabbits developed an intraabdominal abscess , one in the control anastomosis group without glue . Postoperative adhesions were present in all animals . Median anastomosis bursting pressures were 0.9 atm in all three groups : Tissucol , Coseal , and control . Pressure values were 0.9 , 1.0 , and 0.9 atm in the three different proximodistal sites , respectively . A trend toward an increased resistance was observed in the glued anastomosis , although this was not significant . Lymphocyte infiltration , fibroblast activity , blood vessel density , and collagen deposition were lower in controls . Anastomoses treated with Tissucol had the highest lymphocyte infiltration level . The Coseal group developed the highest rates of fibroblast activity , collagen deposition , and blood vessel neogenesis . Conclusion The use of biological glues did not result in a statistically significantly increased bursting resistance . Histological evaluation demonstrated more intense tissue neoformation in the glue groups , particularly in the Coseal group . The role of biological glues in decreasing the leakage rate of intestinal anastomoses is uncertain , and larger trials using different protective agents are warranted BACKGROUND / AIMS Anastomotic leakage is a major cause of mortality in colorectal surgery . Several methods have been evaluated in order to prevent anastomotic leakage . To decrease the rate and severity of anastomotic leakage , omentoplasty ( OP ) has been proposed by several authors on the basis of experimental and clinical studies . A prospect i ve , r and omized trial was design ed to study the influence of omentoplasty on anastomotic leakage after colorectal resection . METHODOLOGY One hundred and twenty-six patients undergoing elective or emergency surgery for malignancy , benign tumor , diverticular disease and other were r and omly assigned to omentoplasty ( OP group ) or not ( NO group ) . The primary end point was the rate of clinical and radiological anastomotic leakage . Both groups were comparable in terms of demographic data , preoperative characteristics and intraoperative findings . RESULTS Eighteen patients ( 14.3 % ) had anastomotic leakage , 4 ( 6.4 % ) in the OP group and 14 ( 21.9 % ) in the NO group . Significant differences ( P<0.05 ) between the two groups were also found in terms of repeat operation ( 3.2 % vs. 14.1 % ) and deaths ( 3.2 vs. 7.8 % ) . Other factors associated with anastomotic leakage were the distal site of anastomosis ( < 5 cm from anal verge ) and the emergency . CONCLUSIONS Omental wrap , with its mechanical and biological properties , seems to be effective in lowering the rate and the severity of anastomotic leakage after colorectal surgery BACKGROUND Anastomotic leak after laparoscopic gastric bypass ( GBP ) can result in significant morbidity , mortality , and consumption of healthcare re sources . Fibrin sealant has been used clinical ly in the prevention of leak ; however , its efficacy has not been clearly demonstrated . The aims of this study were to ( 1 ) develop an iatrogenic leak model in swine , ( 2 ) examine the efficacy of fibrin sealant in sealing iatrogenic anastomotic leak , and ( 3 ) review our experience with the use of fibrin sealant in 66 patients who underwent laparoscopic GBP . METHODS This study was performed in three phases . In phase 1 , laparoscopic gastrojejunostomy was performed in adult swine with iatrogenic disruption of the anastomotic staple line . The size of disruption was sequentially increased ( 6- to 12-F opening ) until a leak model was developed . In phase 2 , 16 animals underwent laparoscopic gastrojejunostomy with a 12-F disruption of the anastomosis ; 10 animals ( study group ) had fibrin sealant ( Tisseel VH ) applied on the disrupted anastomosis and 6 animals ( control group ) did not receive fibrin sealant . Animals were sacrificed on postoperative day 5 or earlier if peritonitis developed and were examined for sealing of the anastomotic disruption and the presence of intraabdominal abscess . In phase 3 , the outcome of 66 consecutive patients who underwent laparoscopic GBP with fibrin sealant applied at the gastrojejunostomy was review ed . RESULTS In phase 1 , an anastomotic leak model was developed with a 12-F disruption of the staple line . In phase 2 , two control animals required early sacrifice for bile peritonitis ; three control animals had intraabdominal abscess discovered at sacrifice and one animal did not have any evidence of intraabdominal abscess or leak . Of the 10 animals in the study group , all survived until sacrifice and none of these animals had evidence of intraabdominal abscess or persistent leak . Therefore , 83 % of animals in the control group developed either leak or abscess compared to 0 % in the study group ( P < 0.01 , Fisher 's exact test ) . Clinical ly , no leak or intraabdominal abscess developed in 66 patients who underwent laparoscopic GBP with the use of fibrin sealant . CONCLUSIONS An anastomotic leak model was developed in swine with disruption of the stapled gastrojejunostomy to a 12-F opening . The use of fibrin sealant significantly reduces leak and abscess complication . Our results support the tissue sealing property of fibrin sealant and its use on high-risk gastrointestinal anastomosis Purpose : Anastomotic leaks are among the most dreaded complications after colorectal surgery . However , problems with definitions and the retrospective nature of previous analyses have been major limitations . We sought to use a prospect i ve data base to define the true incidence and presentation of anastomotic leakage after intestinal anastomosis . Methods : A prospect i ve data base of two colorectal surgeons was review ed over a 10-year period ( 1995–2004 ) . The incidence of leak by surgical site , timing of diagnosis , method of detection , and treatment was noted . Complications were entered prospect ively by a nurse practitioner directly involved in patient care . St and ardized criteria for diagnosis were used . A logistic regression model was used to discriminate statistical variation . Results : A total of 1223 patients underwent resection and anastomosis during the study period . Mean age was 59.1 years . Leaks occurred in 33 patients ( 2.7 % ) . Diagnosis was made a mean of 12.7 days postoperatively , including four beyond 30 days ( 12.1 % ) . There was no difference in leak rate by surgeon ( 3.6 % vs. 2.2 % ; P = 0.08 ) . The leak rate was similar by surgical site except for a markedly increased leak rate with ileorectal anastomosis ( P = 0.001 ) . Twelve leaks were diagnosed clinical ly versus 21 radiographically . Contrast enema correctly identified only 4 of 10 leaks , whereas CT correctly identified 17 of 19 . A total of 14 of 33 ( 42 % ) patients had their leak diagnosed only after readmission . Fifteen patients required fecal diversion , whereas 18 could be managed nonoperatively . Conclusions : Anastomotic leaks are frequently diagnosed late in the postoperative period and often after initial hospital discharge , highlighting the importance of prospect i ve data entry and adequate follow-up . CT scan is the preferred diagnostic modality when imaging is required . More than half of leaks can be managed without fecal diversion INTRODUCTION Anastomotic leakage is a major complication of colorectal surgery causing a significant increase in 30-day mortality . The long-term prognosis of anastomotic leakage is poorly documented . This study was design ed to assess whether anastomotic leakage affects five-year survival and local recurrence . METHODS A total of 5,173 patients were recruited to the Wessex Colorectal Cancer Audit during the period September 1991 to August 1995 ( prospect i ve data , 5-year follow-up ) . The effect of anastomotic leakage on five-year survival and local recurrence was analyzed using Kaplan-Meier curves and the log-rank test . RESULTS A total of 1,834 patients underwent a curative resection with an anastomosis ( anastomotic leak = 71 ; 3.9 percent ) : 30-day mortality : 18.3 percent in the leak group , and 3.5 percent in the nonleak group ( P < 0.001 ) ; local recurrence : 19 percent in the leak group , and 9.8 percent in the nonleak group ( P = 0.018 ) . A total of 1,201 patients underwent colonic anastomosis ( anastomotic leak = 31 ; 2.6 percent ) . There was no significant difference in local recurrence or five-year survival between the leak and nonleak groups . A total of 633 patients underwent rectal anastomosis ( anastomotic leakage = 40 ; 6.3 percent ) : 30-day mortality : 10 percent in the leak group , and 2 percent in the nonleak group ( P = 0.014 ) ; cumulative five-year estimate of local recurrence : 25.1 ( 95 percent confidence interval , 9.6–40.5 ) percent in the leak group , and 10.4 ( 95 percent confidence interval , 7.7–13 ) percent in the nonleak group ( P = 0.007 ) . Cumulative five-year estimate of overall survival : 52.8 ( 95 percent confidence interval , 36.1–69.4 ) percent in the leak group , and 63.9 ( 95 percent confidence interval , 59.9–67.9 ) percent in the nonleak group ( P = 0.19 ) . CONCLUSIONS After rectal anastomosis , an anastomotic leak is associated with a significant increase in local recurrence Background Most likely because of low statistical power , no previous studies have shown any significant association between long-term survival and anastomotic leakage in patients who have undergone gastroesophageal cancer resection . Material and methods The present study included , prospect ively and consecutively , nationwide collected patients who underwent gastroesophageal cancer resection between 2003 and 2011 in Denmark . The operation was carried out as an Ivor Lewis procedure . Only patients with intrathoracic anastomosis were included in the analysis . Results From 2003 to 2011 , 1,296 patients underwent gastroesophageal resection , and 128 ( 9.9 % ) of these experienced anastomotic leakage . The overall 5-year survival rates in patients with and without anastomotic leakage were 20 and 35 % ( P < 0.0001 ) , respectively . After exclusion of 4 weeks mortality , the 5-year survival rate in patients with leakage was 22 % compared to 36 % in patients without anastomotic leakage ( P < 0.001 ) . After exclusion of 8 weeks mortality , the 5-year survival rate was 23 % in patients with leakage and 36 % in those without ( P = 0.009 ) . The corresponding median time of survival was 74 versus 128 , 87 versus 138 , and 95 versus 138 weeks , respectively . The overall hazard ratios of death after anastomotic leakage , unadjusted , and after adjusting for potentially confounding factors , were 1.59 ( 1.27–1.99 ) and 1.45 ( 1.14–1.84 ) . The unadjusted and adjusted odds ratios after exclusion of 4 weeks mortality were 1.51 ( 1.19–1.90 ) and 1.41 ( 1.10–1.81 ) . After exclusion of 8 weeks mortality the odds ratios were 1.38 ( 1.08–1.77 ) and 1.32 ( 1.02–1.71 ) . Conclusions This nationwide study confirms that patients experiencing anastomotic leakage after gastroesophageal cancer resection have a significantly lower long-term survival , even following full recovery after the leakage Leakage from a colonic anastomosis remains a major complication of surgery for colon emergencies and is associated with a significant increase in postoperative hospital stay and mortality rate . The purpose of our study was to investigate whether fibrin sealant , a well known tissue adhesive , will augment healing of bowel anastomosis in an experimental peritonitis model . Forty-eight male Sprague-Dawley rats were r and omized into four groups . All rats underwent conventional sutured colo-colic anastomosis . The rats in group 3 and 4 had been exposed peritonitis before that procedure . In groups 2 and 4 fibrin sealant was added to the suture line . The measurements of bursting pressure and histopathological evaluations of suture lines revealed that peritonitis was deleterious to healing of colonic anastomosis . It was also seen that fibrin sealant augments healing of colonic anastomosis both in normal and peritonitis models Abstract . Background : This study was aim ed at examining whether the addition of fibrin glue to a sutured colonic anastomosis improves its healing or not . Methods : We studied the effect of adding fibrin glue on a sutured colonic anastomosis . Thirty-six Wistar rats were r and omized into two groups of 18 rats each . A sutured anastomosis was performed in all rats . Fibrin glue was applied around the anastomosis of the rats of group B. Rats were sacrificed on the eighth postoperative day . Results : The rate of anastomotic leakage was found not to be significantly different between the two groups . The mean bursting pressure of the colonic anastomoses was significantly higher in group B ( fibrin-treated ) than in group A. Conclusion : Fibrin glue application around a sutured anastomosis provides a safer anastomosis which is stronger than the sutured one Because bowel and omental adhesions offer some protection when an anastomosis leaks , the effect of a fibrin glue on the leak rate was determined in a prospect i ve animal study . EEA stapled anastomoses of the rectum were evaluated in dogs with respect to mortality , postmortem leak rate , adhesions , and the accuracy of barium enema done just before the animals were killed 7 days postoperatively . There was a reduction in fatal , free , and confined leaks which did not reach statistical significance . Adhesions were reduced . There were no false-positive barium enemas but a 7 percent incidence of false-negative results . The clinical management of a suspected anastomotic leak is discussed Background Anastomotic dehiscence is the most severe surgical complication after large bowel resection . This study was design ed to assess the incidence , to observe the consequences , and to identify the risk factors associated with anastomotic leakage after colorectal surgery . Material s and methods All procedures involving anastomoses of the colon or the rectum , which were performed between November 2002 and February 2006 in a single institution , were prospect ively entered into a computerized data base . Results One thous and eighteen colorectal resections and 811 anastomoses were performed over this 40-month period . The most frequent procedures were sigmoid ( 276 ) and right colectomies ( 217 ) . The overall anastomotic leak rate was 3.8 % . The mortality rate associated with anastomotic leak was 12.9 % . In univariate analysis , the following parameters were associated with an increased risk for anastomotic dehiscence : ( 1 ) ASA score ≥ 3 ( p = 0.004 ) , ( 2 ) prolonged ( > 3 h ) operative time ( p = 0.02 ) , ( 3 ) rectal location of the disease ( p < 0.001 ) , ( 4 ) and a body mass index > 25 ( p = 0.04 ) . In multivariate analysis , ASA score ≥ 3 ( OR = 2.5 ; 95 % CI 1.5–4.3 , p < 0.001 ) , operative time > 3 h [ OR = 3.0 ; 95 % CI 1.1–8.0 , p = 0.02 ) , and rectal location of the disease ( OR = 3.75 ; 95 % CI 1.5–9.0 ( vs left colon ) , p = 0.003 ; OR = 7.69 ; 95 % CI 2.2–27.3 ( vs right colon ) , p = 0.001 ] were factors significantly associated with a higher risk of anastomotic dehiscence . Conclusions Three risk factors for anastomotic leak have been identified , one is patient-related ( ASA score ) , one is disease-related ( rectal location ) , the third being surgery-related ( prolonged operative time ) . These factors should be considered in perioperative decision-making regarding defunctioning stoma formation Despite substantial improvements in perioperative mortality , complications , and specifically the development of a pancreatic fistula , remain a common occurrence after pancreaticoduodenectomy . It was the objective of this study to evaluate the role of fibrin glue sealant as an adjunct to decrease the rate of pancreatic fistula after pancreaticoduodenectomy . One hundred twenty-five patients were r and omized after pancreaticoduodenal resection only if , in the opinion of the surgeon , the pancreaticojejunal anastomosis was at high risk for development of a pancreatic anastomotic leak . After completion of the pancreaticojejunal anastomosis , the patients were r and omized to topical application of fibrin glue sealant to the surface of the anastomosis or no such application . The primary postoperative end points in this study were pancreatic fistula , total complications , death , and length of hospital stay . A total of 59 patients were r and omized to the fibrin glue arm , whereas 66 patients were r and omized to the control arm and did not receive fibrin glue application . The pancreatic fistula rate in the fibrin glue arm of the study was 26 % vs. 30 % in the control group ( p = not significant [ NS ] ) . The mean length of postoperative stay for all patients r and omized was similar ( fibrin glue = 12.2 days , control = 13.6 days ) and the mean length of stay for patients in whom pancreatic fistula developed was also not different ( fibrin glue = 18.9 days , control = 21.7 days ) . There were no differences with respect to total complications or specific complications such as postoperative bleeding , infection , or delayed gastric emptying . These data demonstrate that the topical application of fibrin glue sealant to the surface of the pancreatic anastomosis in this patient population undergoing high-risk pancreaticojejunal anastomosis did not reduce the incidence of pancreatic fistula or total complications after pancreaticodudodenectomy . There seems to be no benefit regarding the use of this substance in this setting Background Published interim results have shown that fibrin sealant ( Tissucol ® /Tisseel ® Baxter AG , Vienna , Austria ) may be effective in preventing anastomotic leaks and internal hernias following laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) . We report the final results of a multicenter , r and omized clinical trial evaluating the use of fibrin sealant in LRYGBP . Methods Between January 2004 and December 2005 , 340 patients aged 21–65 years with a body mass index ( BMI ) of 40–59 kg/m2 undergoing LRYGBP were r and omized ( 1:1 ) to two treatment groups : fibrin sealant group ( applied to gastrojejunal and jejunojejunal anastomoses and over mesenteric openings ) , and control group ( no fibrin sealant ; suture of the mesenteric openings ) . Operative time , early and late complications , re interventions , time to oral diet initiation , and length of stay were assessed . Results Overall , 320 patients were included into the study : 160 in the control group and 160 in the fibrin sealant group . All patients completed follow-up assessment s at 6 and 12 months , and 60.9 % completed assessment s at 24 months . There were no significant differences between groups with respect to demographics , operative time , oral diet initiation , hospital stay , and BMI reduction at 6 , 12 , and 24 months . The incidence of anastomotic leak was numerically , but not significantly , greater in the control group . The overall reintervention rate for specific early complications ( < 30 days ) was significantly higher in the control group ( p = 0.016 ) . No deaths or conversions to open laparotomy occurred . Conclusion The use of fibrin sealant in laparoscopic RYGBP may be beneficial in reducing the reintervention rate for major perioperative ( < 30 days ) complications . Larger studies are needed Adult Wistar rats were used to investigate the ability of an omental wrap to limit leakage from compromised intestinal anastomoses . Under ketamine anesthesia , a section of small bowel was divided and then reanastomosed using a “ control ” anastomosis , a “ deficient ” anastomosis , or an “ ischemic ” anastomosis , plus or minus the addition of a wrap of omentum . Initially 10 rats were r and omly assigned to each group . Nineteen of the 20 rats with unwrapped compromised anastomoses died within six weeks , compared with five deaths in the rats protected by an omental wrap ( Fisher 's exact test;P < 0.01 ) . The experiment was then repeated with a sample of rats from each anastomotic group being sacrificed for histologic examination on days 2 to 7 , 10 , 14 , and 42 . At the time of sacrifice a dye was injected into the omental vasculature to determine its contribution to the healing anastomosis . An anastomosis could be demonstrated between omental and bowel wall vessels by the third postoperative day . At one week the infa rct ed bowel edges were being resorbed and the omentum formed a fibrotic cylinder aligning the separated ends of bowel wall . At six weeks the scar became more contracted and the bowel mucosa had started to grow onto its luminal surface . It is concluded from this study that the omental wrap is protective to a compromised anastomosis by providing a biologically viable plug to prevent early leakage and a source of granulation tissue and neovasculature for later wound repair Many surgeons are reluctant to construct a bowel anastomosis with irradiated intestine . Previous studies have demonstrated diminished tensile strength of rat small bowel anastomoses that have been irradiated intraoperatively . To determine whether fibrin glue , a known tissue adhesive , improves the healing of these anastomoses , 69 male Sprague-Dawley rats were r and omized into three anastomotic groups : Group 1 , sutured ileal anastomosis without radiation or fibrin glue ; Group 2 , irradiated sutured ileal anastomosis without fibrin glue ; and Group 3 , irradiated ileal anastomosis with fibrin glue added to the suture line . Groups 2 and 3 received a single dose of 2,000 R intraoperatively . At seven days , the rats were sacrificed and the anastomotic segment was tested for breaking ( tensile ) strength . Anastomotic collagen content was evaluated using a hydroxyproline assay . Tensile strength results demonstrated that Group 2 was significantly weaker than Groups 1 and 3 ( P=0.001 ) and that the hydroxyproline content of Group 3 was significantly greater than that of Group 2 ( P=0.015 ) . These results show that the addition of fibrin glue to an intraoperatively irradiated small bowel anastomosis improves healing , as demonstrated by both tensile strength and hydroxyproline content studies 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 Objective : The aim of this study was to determine whether anastomotic leakage has an independent association with overall survival and cancer-specific survival . Summary Background Data : There are many known prognostic indicators following surgery for colorectal cancer ( CRC ) . However , the impact of anastomotic leakage has not been adequately assessed . Methods : Consecutive patients undergoing resection between 1971 and 1999 were recorded prospect ively in the Concord Hospital CRC data base . Total anastomotic leakage was defined as any leak , whether local , general , or radiologically diagnosed . Patients were followed until death or to December 31 , 2002 . The association between anastomotic leakage and both overall survival and cancer-specific survival was examined by proportional hazards regression with adjustment for other patient and tumor characteristics influencing survival . Confidence intervals ( CI ) were set at the 95 % level . Results : From an initial 2980 patients , 1722 remained after exclusions . The total leak rate was 5.1 % ( CI 4.1–6.2 % ) . In patients with a leak , the 5-year overall survival rate was 44.3 % ( CI 33.5–54.6 % ) compared to 64.0 % ( CI 61.5–66.3 % ) in those without leak . In proportional hazards regression – after adjustment for age , gender , urgent resection , site , size , stage , grade , venous invasion , apical node metastasis and serosal surface involvement – anastomotic leakage had an independent negative association with overall survival ( hazard ratio [ HR ] 1.6 , CI 1.2–2.0 ) and cancer-specific survival ( HR 1.8 , CI 1.2–2.6 ) . Conclusion : Apart from its immediate clinical consequences , anastomotic leakage also has an independent negative association with survival Sealing of anastomoses has previously been tested with several methods , including sealing with liquid fibrin glue . Sealing with a collagen patch coated with fibrin glue components has never been systematic ally examined . The aim of the present study was to determine the safety of sealing gastrointestinal anastomoses with a collagen patch coated with fibrin glue . The study is a prospect i ve , experimental animal study comparing sealed and unsealed gastrointestinal anastomoses . Laparotomy was performed in 11 pigs under general anesthesia . In each pig two anastomoses were performed on the small intestine . One of the anastomoses was sealed with a collagen patch coated with fibrin glue components ( TachoSil ® ) . The other anastomosis contained no sealing . The pigs were observed for 1 to 6 weeks . The observation period was followed by in vivo examination under general anesthesia and included observation for anastomotic leakage , signs of present or former peritonitis , abscess , adhesions to the anastomoses , and signs of intestinal obstruction . In addition , the anastomotic diameter was measured with barium and radiography . Finally , bursting pressure was measured in each segment . After the pigs were sacrificed , the bowel segments were microscopically examined . There were no differences between the sealed and the unsealed anastomoses with respect to abdominal pathology , in vivo bursting pressure , or degree of stenosis . The collagen fleeces were in situ in all anastomoses . Microscopically , we found no difference in healing or signs of infection Purpose : The aim of this experimental study was to investigate whether covering the colonic anastomoses with fibrin glue can protect the colonic healing from the adverse effects of 5-fluorouracil ( 5-FU ) , when it is injected intraperitoneally immediately after colon resection . Methods : Sixty-four rats were r and omized to one of four groups . After resection of a 1-cm segment of the transverse colon , an end-to-end sutured anastomosis was performed . Rats of the control group and the fibrin glue group were injected with 6 ml of solution 0.9 percent NaCl intraperitoneally . Rats in the 5-FU and the 5-FU + fibrin glue groups received 5-FU intraperitoneally . The colonic anastomoses of the rats in the fibrin glue group and in the 5-FU + fibrin glue group were covered with fibrin glue . All rats were killed on the 8th postoperative day and the anastomoses were examined macroscopically . The bursting pressure measurements were recorded and the anastomoses were grade d histologically . Results : The leakage rate of the anastomoses was significantly higher in the rats of the 5-FU group than in those of the fibrin glue group and those of the 5-FU + fibrin glue group ( 37.5 percent vs. 0 percent , P = 0.020 ) . The adhesion formation score was significantly higher in rats of the 5-FU group than in the other groups . Bursting pressures were also significantly lower in the 5-FUgroup than in the other groups ( P < 0.001 ) . Rats in the 5-FU + fibrin glue group developed significantly more marked neoagiogenesis than rats in the other groups . Rats in the 5-FU + fibrin glue group also presented significantly more fibroblast activity than those in the 5-FU group . ( P = 0.004 ) Conclusions : The immediate postoperative , intraperitoneal administration of 5-FU inhibited wound healing . However , when the colonic anastomoses were covered with fibrin glue , the injection of 5-FU had no adverse effects on the healing of the Abstract Background The aim of this study was to evaluate the effect of absorbable fibrin-collagen patch ( FCP ) during early colonic anastomotic healing in rats . Methods Prepubertal Wistar albino rats were r and omly divided into 6 groups of 6 rats each . Colon was transected and then anastomosed with sutures ( Group A ) , sutures+FCP ( TachoComb ; Nycomed , Austria ) ( Group AT ) or only FCP ( Group T ) . Rats were sacrificed either 3 or 7 days after the anastomosis . Anastomoses were evaluated for perianastomotic adhesion formation , bursting pressures and histological features . Results Perianastomotic adhesion formation was significant in Groups AT and T. Bursting pressures were in higher group AT than in Group A on postoperative day 3 and lower on day 7 ( p<0.05 ) . Histological examinations revealed an increase in inflammatory cells in Group T on day 3 and decreased wound healing in Group AT when compared to Group A on day 7 ( p<0.05 ) . Conclusions In the early period of anastomotic healing , FCP supports anastomotic integrity . However , it also causes an inflammatory reaction which may increase the time necessary for healing process . Thus , the use of this bio material should be preferred in only selective clinical cases with a careful follow-up PURPOSE : This study was design ed to analyze the impact of anastomotic leak and intra-abdominal abscess on cancer recurrence and survival in patients who underwent resection for colorectal cancer . METHODS : Data for patients who underwent resection for colon or rectal cancer were retrieved from a prospect i ve colorectal cancer data base . Patients with inflammatory bowel disease , familial adenomatous polyposis , hereditary nonpolyposis colorectal cancer , palliative resection , or perioperative mortality were excluded . Patients with postoperative anastomotic leak or intra-abdominal abscess were matched at a 1:2 ratio to patients from the same data base who had no leak or abscess . Matched characteristics were age , gender , cancer stage , tumor histology , and operation occurring within three years of each other . Survival and cancer recurrence at five-year follow-up were evaluated with the Kaplan-Meier method and log rank test . RESULTS : In patients with colon cancer , comparison of the 59 patients with a leak or an abscess with 118 matched controls showed no differences in demographic or treatment characteristics , recurrence , or mortality . In patients with rectal cancer , comparison of the 97 patients with a leak or an abscess with 194 matched controls showed that at five-year follow-up the complication group had higher rates of overall mortality ( 46.8 vs. 28.9 , P < 0.01 ) , cancer-specific mortality ( 28.7 percent vs. 18.0 percent , P = 0.03 ) , overall recurrence ( 28.6 vs. 15.7 , P = 0.01 ) and local recurrence ( 11.0 percent vs. 5.0 percent , P = 0.04 ) . CONCLUSION : Anastomotic leak and intra-abdominal abscess were not associated with worsened 5-year survival or recurrence in patients who underwent resection for colon cancer . However , these complications were associated with increased overall and cancer-specific mortality and increased overall and local recurrence in patients who underwent resection for rectal cancer The effect of fibrin glue sealing on sutured colonic anastomoses was studied using a ' high-risk ' colon anastomosis model in the rat . Animals ( n = 104 ) were r and omized to have their sutured anastomosis sealed with fibrin glue or left untreated . They were assessed clinical ly until they were killed on the fourth day after surgery when contrast radiology , detailed post-mortem examination , anastomotic bursting pressure ( ABP ) and assessment of adhesion formation were performed . The clinical outcome was worse in the glued group ( toxic or death from sepsis : 18 versus seven in the non-glued group ; P = 0.0354 ) , which also showed a significantly higher moderate to major leak rate ( 17 versus two in the non-glued group ; P = 0.0009 ) . The median ABP was significantly higher in the glued anastomosis group ( 96 versus 68 cmH2O in the non-glued group ; P = 0.0367 ) . Excessive perianastomotic adhesion formation was significantly greater in the glued group . Microscopic examination showed an extremely intense inflammatory reaction in the glued anastomoses compared with that in the untreated group . These results indicate that sealing of a sutured anastomosis with fibrin glue containing an antiproteinase impairs healing the of anastomotic wound , probably by resisting the ingrowth of vascular granulation tissue during the early stages of repair A prospect i ve r and omized study was conducted on 100 patients operated upon for oesophageal diseases to evaluate the usefulness of fibrin glue in reinforcing oesophageal anastomoses . The anastomoses were located in the neck , the chest or the lower mediastinum . The operative mortality rate , the number and severity of fistulae and the incidence of anastomotic stenosis were studied . This series was insufficient to demonstrate that fibrin glue was effective in this type of surgery Background Results are conflicting and no population -based studies are available regarding the postoperative mortality after intrathoracic anastomotic leakage . The current study addressed the unselected and independent fatality rate of intrathoracic esophageal anastomotic leaks after resection for cancer . Methods A prospect i ve , nationwide study was conducted in Sweden in April 2001 through December 2005 . Details concerning patient and tumor characteristics , surgical procedures , postoperative anastomotic leakage , and mortality were collected prospect ively . Logistic regression was performed to estimate odds ratios ( ORs ) and 95 % confidence intervals ( 95 % CIs ) , adjusted for age , tumor stage , comorbidity , and hospital volume . Results Among 559 resected patients with an intrathoracic anastomosis , 44 patients ( 7.9 % ) sustained an anastomotic leak within 30 days of surgery . Of these , 8 patients ( 18.2 % ) died within 90 days of surgery , compared with 32 of the 515 patients without leakage ( 6.2 % ) ( P = .003 ) . The adjusted OR of postoperative death following intrathoracic anastomotic leakage was increased 3-fold compared with those without such a complication ( OR 3.0 , 95 % CI 1.2–7.2 ) . Conclusion Intrathoracic anastomotic leakage after esophageal resection for cancer remains a major risk factor for short-term postoperative death in an unselected , population -based setting BACKGROUND The aim of this study was to evaluate whether the use of fibrin glue as a sealant over an anastomosis is a risk factor for anastomotic leakage after laparoscopic rectal cancer surgery . METHODS Prospect i ve data were collected from 223 patients with rectal cancer who underwent laparoscopic resection without defunctioning stoma . RESULTS A total of 104 patients underwent laparoscopic rectal resection , followed by the application of fibrin glue over the stapled anastomosis , while 119 underwent surgery alone . No difference in clinical ly significant leakage was observed between the fibrin and the nonfibrin groups ( 5.8 % vs 10.9 % , P = .169 ) . In multivariate analysis , extraperitoneal tumor location and operation duration > 220 minutes were independently associated with anastomotic leakage . CONCLUSIONS Significant predictors of anastomotic leakage include extraperitoneal tumor location and operation length > 220 minutes . Fibrin glue application over the stapled anastomosis was not found to be significantly associated with anastomotic leakage |
11,736 | 11,074,906 | Furthermore , the risk for a catastrophic gastrointestinal event in elderly patients taking NSAIDs is dose dependent ( 18 ) .
Celecoxib has been found to be more effective than placebo and as effective as naproxen for symptoms in patients with hip or knee osteoarthritis ( 27 - 29 ) .
Rofecoxib has also been found to be more effective than placebo and is comparable in efficacy to both ibuprofen and diclofenac in patients with hip or knee osteoarthritis ( 30 , 31 ) .
A further advantage of COX-2specific inhibitors with respect to upper gastrointestinal bleeding is that celecoxib and rofecoxib do not have a clinical ly significant effect on platelet aggregation or bleeding time .
In addition , at doses recommended for treatment of osteoarthritis , these drugs appear to be better tolerated than comparator nonselective NSAIDs , with a lower incidence of dyspepsia and other gastrointestinal side effects .
As with nonselective NSAIDs , however , COX-2specific inhibitors can cause renal toxicity .
Histamine-2 blockers in usual doses , however , have not been found to be as effective as misoprostol ( 36 ) , whereas omeprazole ( 20 mg/d or 40 mg/d ) was as effective as misoprostol ( 200 g twice daily ) in treatment of existing ulcers and was better tolerated and associated with a lower rate of relapse ( 37 ) . | There is no known cure for osteoarthritis , and the goal of contemporary management of the patient with osteoarthritis remains control of pain and improvement in function and health-related quality of life with avoidance , if possible , of therapeutic toxicity .
Recent studies have demonstrated the potential of treatments ranging from newly approved oral medications to nutriceuticals , patient education interventions , and surgery .
Increasingly , appropriate treatment of osteoarthritis combines one or more oral agents with exercise and other biomechanical techniques .
Systemic and Topical Treatments Dr. Marc C. Hochberg ( University of Maryl and School of Medicine , Baltimore , Maryl and ) , Dr. Timothy McAlindon ( Boston University School of Medicine , Boston , Massachusetts ) , and Dr. David T. Felson ( Boston University School of Medicine ) : Drug therapy for pain management is most effective when combined with nonpharmacologic strategies ( 1 , 2 ) .
In 1995 , the American College of Rheumatology issued guidelines for the medical management of osteoarthritis of the hip and knee ( 2 , 3 ) .
Systemic Treatments Nonopioid Analgesics For many patients with osteoarthritis , the relief of mild to moderate joint pain afforded by the simple analgesic acetaminophen is comparable to that achieved with a nonsteroidal anti-inflammatory drug ( NSAID ) ( 7 , 8) .
Accordingly , although acetaminophen fails to adequately relieve pain in many patients , it merits a trial as initial therapy on the basis of its overall cost , efficacy , and toxicity profile ( 9 , 10 ) .
The daily dose of acetaminophen should not exceed 4 g. Although it is one of the safest analgesics , acetaminophen can be associated with clinical ly important adverse events , such as prolongation of the half-life of warfarin ( 11 ) .
At therapeutic doses acetaminophen rarely causes hepatic toxicity , but it should be used cautiously in patients with existing liver disease and avoided in patients with chronic alcohol abuse because of known increased risk in these patients ( 12 - 14 ) .
Tramadol , a central ly acting oral analgesic , is a synthetic opioid agonist that inhibits reuptake of norepinephrine and serotonin .
Although numerous studies have examined use of tramadol to treat general pain , few controlled studies have examined its use in osteoarthritis .
The efficacy of tramadol has been found to be comparable to that of ibuprofen in patients with hip and knee osteoarthritis ( 16 ) , and it is useful as adjunctive therapy in patients with osteoarthritis whose symptoms were inadequately controlled with NSAIDs ( 17 ) .
Daily doses of tramadol have generally been in the range of 200 to 300 mg given in four divided doses .
Side effects are common and include nausea , constipation , and drowsiness .
Despite the opioid pharmacology of tramadol , a comprehensive surveillance program has failed to demonstrate significant abuse , and tramadol remains an unscheduled agent .
Seizures have been reported as a rare side effect , either at doses above the recommended range or at doses within the recommended range in patients with a history of epilepsy and those taking concomitant medications that lower the seizure threshold .
Risk factors for upper gastrointestinal bleeding in patients treated with NSAIDs include age 65 years or older , history of peptic ulcer disease or previous upper gastrointestinal bleeding , concomitant use of oral corticosteroids or anticoagulants , and possibly smoking and alcohol consumption ( 21 - 23 ) .
Risk factors for reversible renal failure in patients with intrinsic renal disease who are treated with NSAIDs include age 65 years or older , hypertension or congestive heart failure , and concomitant use of diuretics and angiotensin-converting enzyme inhibitors ( 24 ) .
Additional considerations involved in a practitioner 's decision to treat an individual patient with osteoarthritis include existing comorbid conditions and concomitant therapy , as well as the side effects and costs of specific treatments .
Endoscopic studies have shown that celecoxib and rofecoxib are associated with an incidence of gastroduodenal ulcers lower than that of comparator NSAIDs and similar to that of placebo ( 25 ) .
These data suggest an advantageous safety profile compared with nonselective NSAIDs , especially for treatment of high-risk patients ( 21 - 23 ) .
However , no large long-term studies have been published that were design ed to demonstrate differences between COX-2specific inhibitors and nonselective NSAIDs with respect to major gastrointestinal clinical outcomes ; such studies are in progress .
Side effects , particularly diarrhea and flatulence , may occur with this agent in a dose-dependent manner ( 33 ) .
Alternative approaches to prophylaxis with misoprostol include use of omeprazole or high-dose famotidine , both of which have been shown in carefully conducted endoscopy studies to be effective in treating and preventing NSAID-induced gastropathy ( 34 - 37 ) . | OBJECTIVE We previously reported that monthly telephone contact by lay personnel , to promote self-care for patients with osteoarthritis ( OA ) , was associated with improved joint pain and physical function after 1 year of followup . The present study was a secondary analysis to determine whether improvement was contingent on intensified medical treatment . METHODS We reanalyzed control/treatment group differences in all 40 subjects with radiographically confirmed knee OA who had had no changes in antirheumatic drug therapy or institution of physical therapy during the period of observation . RESULTS Group differences in measured pain remained significant ( effect size [ ES ] = 0.65 SD , P less than 0.01 ) . The same trend was observed for physical function ( ES = 0.53 SD , P not significant ) . CONCLUSION The findings in this re analysis suggest that periodic telephone support interventions are effective enough to be regarded as an adjunctive treatment for OA OBJECTIVE The purpose of this study was to investigate the efficacy of acupuncture as an adjunctive therapy to st and ard care for the relief of pain and dysfunction in elderly patients with osteoarthritis ( OA ) of the knee . METHODS Seventy-three patients with symptomatic OA of the knee were r and omly assigned to treatment ( acupuncture ) or st and ard care ( control ) . Analysis was performed on last score carried forward to account for patients who dropped out before completion . Patients self-scored Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and Lequesne indices at baseline and at 4 , 8 and 12 weeks . Patients in the control group were offered acupuncture treatment after 12 weeks . The data for these patients are pooled with those from the original acupuncture group for within-group analysis . RESULTS Patients r and omized to acupuncture improved on both WOMAC and Lequesne indices compared to those who received st and ard treatment alone . Significant differences on total WOMAC Scale were seen at 4 and 8 weeks . There appears to be a slight decline in effect at 4 weeks after cessation of treatment ( 12 weeks after first treatment ) . No adverse effects of acupuncture were reported . CONCLUSION These data suggest that acupuncture is an effective and safe adjunctive therapy to conventional care for patients with OA of the knee OBJECTIVE To evaluate the cost-effectiveness of telephone intervention for patients with osteoarthritis . METHODS R and omized , controlled trial . RESULTS The intervention did not significantly increase health care costs . The annual costs for a 1-unit improvement in physical functioning and in pain , as measured by the Arthritis Impact Measurement Scales , were $ 70.86 and $ 31.00 , respectively . CONCLUSION Telephone contact is a potentially cost-effective intervention in osteoarthritis OBJECTIVE The effects of treatment counseling or symptom monitoring telephone intervention strategies on the health outcomes of patients with rheumatoid arthritis ( RA ) or osteoarthritis ( OA ) , compared with usual care , were assessed . METHODS A 3-group , r and omized , controlled 9-month trial was conducted incorporating 405 patients with RA or OA and using the Arthritis Impact Measurement Scales ( AIMS 2 ) as the outcome measure . RESULTS Analyses of covariance showed that the AIMS 2 total health status of the treatment counseling group ( effect size = 33 , P < 0.01 ) , but not the symptom monitoring group ( effect size = 0.21 , P = 0.10 ) , was significantly improved , compared with usual care , for both RA and OA patients . The specific types of benefits differed significantly between RA and OA patients . The mean number of medical visits by OA patients in the treatment counseling group was also significantly reduced ( P < 0.01 ) . CONCLUSION Telephone contact using the treatment counseling strategy produced significant , but different , health status benefits for RA and OA patients . The symptom monitoring strategy produced modest benefits Approximately 14 million patients in the United States regularly take nonsteroidal anti-inflammatory drugs(NSAIDs ) for various types of arthritis [ 1 ] for relief of pain , stiffness , and other symptoms . However , these benefits are obtained at a price . Use of NSAIDs is associated with various gastrointestinal side effects . Minor side effects such as nausea , dyspepsia , anorexia , abdominal pain , flatulence , and diarrhea may affect 10 % to 60 % of patients [ 2 ] . Symptomatic ulcers and potentially life-threatening ulcer complications such as upper gastrointestinal bleeding , perforation , and gastric outlet obstruction are reported in 2 % to 4 % of patients who take NSAIDs for a year [ 3 ] . The chance of hospitalization or death from a gastrointestinal adverse event is 1.3 % to 1.6 % per year in patients with rheumatoid arthritis [ 4 ] . These infrequent but potentially serious gastrointestinal side effects of NSAIDs have become a major health care problem because of the many patients at risk [ 5 ] . General physicians and rheumatologists caring for patients with symptoms of chronic arthritis may be reluctant to ab and on using NSAIDs , which help most of these patients , in order to protect the few who may develop serious complications from use of these drugs . On the other h and , gastroenterologists see fewer patients for arthritis but many with serious gastrointestinal complications . Life-threatening events such as perforation or serious hemorrhage from NSAID-induced ulcers , which often develop with little or no warning [ 6 ] , are a real problem because of the many patients at risk . Various agents have been used in attempts to reduce the incidence of NSAID-induced gastrointestinal lesions . In one endoscopic study , cimetidine at a dose of 300 mg four times a day showed no benefit in healing NSAID-related lesions compared with placebo , and 400 mg at bedtime provided no benefit in preventing these lesions compared with placebo [ 7 ] . Antacids ( magnesium-aluminum hydroxide , 10 to 20 mL as needed to a dose as high as 60 mL daily ) and sucralfate have recently been reported to reduce dyspeptic symptoms in arthritic patients receiving NSAIDs in whom gastropathic lesions ( but not ulcers ) were shown endoscopically [ 8 , 9 ] . The surface-active antiulcer drug sucralfate was ineffective in preventing ulcers in persons receiving NSAIDs [ 10 , 11 ] , and the histamine-2-receptor antagonist ranitidine did not prevent gastric ulcers but did reduce the frequency of duodenal ulcers [ 12 , 13 ] . Results of preliminary studies indicate that the effects of omeprazole parallel those of ranitidine [ 14 ] . A recent study [ 15 ] in achlorhydric patients showed that NSAID-induced ulcers develop in the absence of gastric acid . In contrast , several clinical trials have shown that the incidence of endoscopically visible erosions and ulcers associated with NSAID use can be reduced by cotherapy with the synthetic prostagl and in misoprostol [ 16 - 19 ] . However , it was not proved that preventing endoscopic lesions would prevent clinical ly serious complications of NSAID-induced gastrointestinal ulcers [ 20 ] . Our objective was to determine whether concurrent therapy with misoprostol reduces the incidence of serious upper gastrointestinal complications in older patients with chronic rheumatoid arthritis who are taking NSAIDs . Because most patients taking NSAIDs do not routinely have endoscopy , we investigated the incidence of these complications during clinical care as actually practice d. A second goal was to better define which patients were at increased risk for development of serious NSAID-induced upper gastrointestinal complications . Methods Patients Ambulatory patients at least 52 years of age who had chronic rheumatoid arthritis , defined by American College of Rheumatology criteria [ 21 ] , and who were expected to be taking 1 of 10 specified NSAIDs at predefined minimum doses for 6 months were sought from practice s of family medicine , internal medicine , or rheumatology . Of these practice s , 661 in the United States and 3 in Canada enrolled at least one patient between July 1991 and August 1993 . For all patients , a medical history was elicited , a physical examination was done , and a modified Health Assessment Question naire that included eight items on activities of daily living was administered [ 22 ] . Patients were excluded if they had had active peptic ulcer disease within 30 days of study enrollment ; were taking or expected to need antiulcer medication ( histamine-2 blockers , sucralfate , omeprazole ) or any experimental medication during the study ; had the Zollinger-Ellison syndrome , pyloric or duodenal obstruction , previous gastric resection or vagotomy , gastroesophageal reflux disease , varices , or cirrhosis ; had a history of inflammatory bowel disease , upper gastrointestinal tract malignancies , hepatitis , alcoholism , or bleeding diathesis ; were estimated to have a life expectancy of less than 8 months or had do-not-resuscitate status ; were women of child-bearing potential ; or could not tolerate misoprostol or any prostagl and in . The following were the minimum NSAID doses ( mg/d ) allowed : aspirin , 2000 ; diclofenac , 100 ; flurbiprofen , 200 ; ibuprofen , 1200 ; indomethacin , 75 ; ketoprofen , 150 ; naproxen , 750 ; piroxicam , 20 ; sulindac , 200 ; or tolmetin , 1200 . Patients were allowed to receive more than one NSAID . Intervention Eligible patients were r and omly assigned to receive either misoprostol or placebo in the form of 200- micrograms tablets from coded bottles supplied by the manufacturer . Patients were r and omly assigned in blocks of four , so that in each block , half the patients would receive misoprostol and half would receive placebo . Because blocks were assigned to investigators , patients were r and omly assigned within the individual centers . Investigators were not informed about the r and omization procedure but were told only that the study was r and omized and double-blind . Patients were instructed to begin taking half a tablet with meals and at bedtime each day for 10 days and then , if the drug was tolerated , to increase the dose to a whole tablet four times a day for the rest of the study . If the drug was not tolerated , the patients were instructed to reduce the dose back to half a tablet four times a day . Patients could continue therapy with arthritis disease-modifying agents ( such as gold or corticosteroids ) and were allowed to take antacids that did not contain magnesium . Patients purchased their own arthritis medications or antacids and reported their consumption when seen monthly for examination and counts of study medication tablets . Physicians were instructed to watch closely for clinical signs of gastrointestinal bleeding or other possible gastrointestinal complications , to inquire about symptoms , and to investigate suspicious episodes by appropriate clinical procedures . Outcome Measures All suspicious events , regardless of presumed cause , were to be reported , along with all available patient data , to the study medical officer ( HWD ) and then to an external review committee . This committee consisted of a gastroenterologist ( FS ) , a rheumatologist ( Kenneth Br and t , MD , Indiana University ) , and an epidemiologist ( Marie Griffin , MD , MPH , V and erbilt University ) . The committee determined , without unblinding the r and omization code , whether the patient had upper gastrointestinal bleeding ; other ulcer complications ; or a problem such as hemorrhoids , diverticulitis , colon polyps , or cancer . It developed definitions of what were considered to be complications related to NSAID use and categories of such complications . The committee reached consensus and assigned such events to one of the following categories of definite upper gastrointestinal complications : 1 . perforated ulcer , proved at surgery ; 2 . gastric outlet obstruction caused by proven ulceration and stricture , proved by endoscopy ; 3 . hematemesis , with endoscopically proven gastric or duodenal ulceration or erosion ; 4 . active or recent visualized bleeding from endoscopically proven ulceration or erosion ; 5 . melena , with endoscopically proven ulceration or erosion ; 6 . heme-positive stool , with endoscopically proven ulceration or erosion , plus either a ) a decrease in hematocrit of at least 0.05 or b ) orthostatic change in the pulse rate ( from sitting to st and ing ) of at least 20 beats per minute or decrease in systolic blood pressure of at least 20 mm Hg and a decrease in diastolic blood pressure of 10 mm Hg ; 7 . hematemesis , without endoscopically proven ulceration or erosion ; and 8 . melena , with heme-positive stool and without endoscopically proven ulceration or erosion . The committee also defined categories of events not involving clinical ly significant bleeding : 9 . report of melena with no other data ; 10 . heme-positive stools , with endoscopically proven ulceration or erosion and without active bleeding ; and 11 . report of melena and heme-negative stools when the stools were tested . Sample Size Calculation and Statistical Methods The placebo group was expected to have an incidence of serious NSAID-induced upper gastrointestinal complications of about 2 % per year or about 1 % during the 6-month study period . We estimated that the misoprostol group might have 40 % to 50 % fewer complications and that 60 % to 70 % of patients would complete the study . Given an less than 0.05 and power greater than 0.80 , we planned in the protocol to assess the number of such complications observed , without unblinding the study , after 7500 patients had been followed . We did this to confirm the incidence assumptions and adjust the study size if necessary . We used the Fisher exact test to compare occurrence of events in the treatment groups . To identify risk factors , we evaluated the relation between the occurrence of serious upper gastrointestinal complications and patient characteristics using logistic regression . Supplementary time-to-event analyses were done using the log-rank test and Kaplan-Meier curves . The study was supported by a grant from G.D. Searle & Co. Data 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 OBJECTIVES This analysis evaluated the clinical and demographic risk factors for a suspected , serious nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal ( GI ) complication in everyday clinical practice and calculated the risk reduction associated with misoprostol therapy in these " at-risk " patients . METHODS Using logistic regression analysis , the data set from a r and omized , parallel , placebo-controlled trial of misoprostol in 8,843 rheumatoid arthritis patients taking NSAIDs ( the Misoprostol Ulcer Complications Outcomes Safety Assessment trial ) was modeled to identify risk factors for GI adverse events . The dependent variable was defined as a " suspected serious GI complication , " and the independent variables included demographic features , level of functional disability , presence of co-morbid diseases , use of certain drugs , and treatment arm . RESULTS Two hundred forty-two suspected serious GI complications were observed ; 102 occurred in the misoprostol treatment group ( risk : 2.32 % ) and 140 in the placebo group ( risk : 3.15 % ) . Overall risk reduction due to misoprostol therapy was 26.6 % ( confidence interval 5.5%-42.9 % , P < .05 ) . However , in patient groups with identified risk factors , misoprostol use decreased the risk for an adverse GI event by 38.3%-87.3 % . Specifically , those who benefitted significantly from therapy with misoprostol were patients with a history of peptic ulcer disease ( risk reduction 52.4 % ) , history of previous GI bleeding ( risk reduction 50 % ) , history of significant cardiovascular disease ( risk reduction 38.3 % ) , significant functional disability ( risk reduction 87.2 % ) , and patients whose symptoms required concomitant antacid use ( risk reduction 48.3 % ) . CONCLUSION We conclude that in everyday practice , patients who require chronic NSAID therapy and who have specific clinical risk factors may benefit from misoprostol co-therapy Behavioral and health status outcomes of an unreinforced , self-help education program for arthritis patients taught by lay persons were examined in 2 ways : a 4-month r and omized experiment and a 20-month longitudinal study . At 4 months , experimental subjects significantly exceeded control subjects in knowledge , recommended behaviors , and in lessened pain . These changes remained significant at 20 months . The course was inexpensive and well-accepted by patients , physicians , and other health professionals BACKGROUND The optimal short-term , symptomatic therapy for osteoarthritis of the knee has not been fully determined . Accordingly , we compared the efficacy of a nonsteroidal antiinflammatory drug , ibuprofen , given in either an antiinflammatory dose ( high dose ) or an analgesic dose ( low dose ) , with that of acetaminophen , a pure analgesic . METHODS In a r and omized , double-blind trial , 184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200 mg of ibuprofen per day or 4000 mg of acetaminophen per day . They were evaluated after a washout period of three to seven days before the beginning of the study , and again after four weeks of treatment . The major measures of outcome included scores on the pain and disability scales of the Stanford Health Assessment Question naire ( range of possible scores , 0 to 3 ) , scores on the visual-analogue scales for pain at rest and pain while walking , the time needed to walk 50 ft ( 15 m ) , and the physician 's global assessment of the patient 's arthritis . RESULTS Seventy-eight percent of the patients completed four weeks of therapy . No significant differences were noted among the three treatment groups with respect to failure to complete the trial because of noncompliance or adverse events . All three groups had improvement in all major outcome variables , and the groups did not differ significantly in the magnitude of improvement in most variables . The mean improvement ( change ) in the scores on the pain scale of the Health Assessment Question naire was 0.33 with acetaminophen ( 95 percent confidence interval , 0.14 to 0.52 ) , 0.30 with the low dose of ibuprofen ( 95 percent confidence interval , 0.09 to 0.51 ) , and 0.35 with the high dose of ibuprofen ( 95 percent confidence interval , 0.13 to 0.57 ) . Side effects were minor and similar in all three groups . CONCLUSIONS In short-term , symptomatic treatment of osteoarthritis of the knee , the efficacy of acetaminophen was similar to that of ibuprofen , whether the latter was administered in an analgesic or an antiinflammatory dose OBJECTIVE To compare the relative safety and efficacy of naproxen and acetaminophen in the treatment of osteoarthritis ( OA ) of the knee . The major outcome measures were radiographic progression and withdrawal from the trial due to lack of efficacy . METHODS One hundred seventy-eight patients with OA of the knee were enrolled in a 2-year prospect i ve , controlled , double-blind multicenter trial and were r and omly assigned to receive acetaminophen ( ACT ) or naproxen ( NPX ) treatment . RESULTS After 6 weeks of treatment , modest improvement in pain on motion and in physician 's global assessment was seen in both the ACT and the NPX groups , and the NPX group also had modest improvement in pain at rest and in 50-foot walk time . Sixty-two patients completed the 2-year study . Among these patients , radiographic progression was similar in the 2 treatment groups . Withdrawal from the trial due to lack of drug efficacy was slightly more frequent among patients in the ACT group ( 22 % versus 16 % ) , but withdrawal due to adverse drug effects was slightly more common in the NPX group ( 23 % versus 18 % ) . CONCLUSION The efficacy of ACT treatment and NPX treatment was similar , although it was slightly better for NPX . The toxicity rate was slightly lower with ACT . However , the high rate of withdrawal in both treatment groups suggests that neither is satisfactory for the treatment of OA Osteoarthritis of the knee is the most common cause of chronic disability among older persons in the United States [ 1 ] . In persons with symptomatic osteoarthritis of the knee , quadriceps muscle weakness is common and is widely believed to result from disuse atrophy secondary to joint pain . Although exercises to strengthen the quadriceps may relieve joint pain in persons with osteoarthritis of the knee [ 2 - 6 ] , the role of periarticular muscle weakness in the pathogenesis of joint pain and disability in these persons is poorly understood . The basis for the beneficial effect of strengthening exercises is unclear , and the duration of the improvement has not been studied . Furthermore , the possibility that muscle weakness is an etiologic factor underlying the pathologic changes of osteoarthritis has seldom been considered . Elucidation of the role of muscle weakness in osteoarthritis is particularly important given our growing underst and ing of safe and effective methods for increasing strength in elderly persons [ 7 , 8 ] . A substantial proportion of persons who have radiographic evidence of osteoarthritis of the knee have no joint pain [ 9 ] . Because asymptomatic persons with radiographic changes seldom seek medical attention for osteoarthritis , muscle weakness has not been studied previously in this group . Thus , it is not known whether quadriceps weakness precedes or follows joint pain or ( if it follows joint pain ) whether it is mediated by disuse atrophy or by physiologic mechanisms that may inhibit muscle contraction [ 10 ] . To address this issue , we studied the relation among lower-extremity muscle strength , lower-extremity lean tissue mass , and osteoarthritis of the knee in men and women 65 years of age and older . Methods Study Group To obtain a sample of elderly persons living in the community , we conducted brief telephone interviews with residents of households in central Indiana . Potential participants were selected through modified r and om-digit dialing to increase the sample d proportion of persons 65 years of age and older . Persons were eligible if they met the minimal criteria for participation : They were willing and able to provide informed consent and to undergo the necessary strength assessment s and other evaluations . Persons were excluded if they had had amputations of both lower extremities , had undergone total knee arthroplasty , or had recently had a cerebrovascular accident or myocardial infa rct ion . A total of 462 persons ( approximately 55 % of all who were eligible ) agreed to participate and completed the following evaluations . Evaluations Radiography of the Knee St and ing anteroposterior and lateral radiographs of both knees of each study participant were obtained , and the severity of osteoarthritis in the tibiofemoral compartment was grade d by a musculoskeletal radiologist according to the criteria of Kellgren and Lawrence . Similar criteria , based on the presence of osteophytes and joint space narrowing , were used for the patellofemoral compartment [ 11 ] . The radiologist was blinded to the clinical status and characteristics of all patients . A participant had to have a Kellgren and Lawrence grade of 2 or more in either knee to be classified as having osteoarthritis . Knee Pain and Function The Western Ontario and McMaster Universities Arthritis Index was used to evaluate knee pain and function [ 12 ] . This index assesses the severity of knee pain during 5 activities or situations ( walking on a flat surface , going up or down stairs , at night while in bed , sitting or lying , and st and ing upright ) and the severity of impairment of lower-extremity function during 17 activities . Pain and functional impairment were assessed in each knee separately . Responses to each question about the severity of knee pain and level of impairment were recorded on a categorical scale as none , mild , moderate , severe , or extreme . Each category was assigned a corresponding numeric score from 1 to 5 ( 5 = extreme ) . Hence , the range on the pain scale was 5 to 25 and the range on the physical impairment scale was 17 to 85 ( 85 = greatest functional limitation ) . For the purpose s of analysis , participants who rated the severity of their knee pain as moderate or greater ( 3 ) with any of the 5 activities on more than half of the days in the month preceding the evaluation were considered to have knee pain . Thus , pain in the more distant past that had resolved was not included . Participants were also question ed about current and previous regular ( 5 times per week ) or occasional use of over-the-counter and prescription analgesics and nonsteroidal anti-inflammatory drugs ( NSAIDs ) in the past year . Lower-Extremity Muscle Strength The strength of each leg was evaluated by using an isokinetic dynamometer ( KIN-COM 500H , Chattecx Corp. , Hixson , Tennessee ) . Peak torque was recorded in both the concentric ( contractions during muscle shortening ) and eccentric ( contractions during muscle lengthening ) modes . Participants were allowed several submaximal or maximal practice efforts to familiarize themselves with the operation of the dynamometer . Once formal testing began , the best of three maximal efforts was recorded for flexion and extension at both 60 degrees per second and 120 degrees per second . Aborted efforts were repeated in order to obtain the best possible representation of strength for each participant . Concentric and eccentric testing yielded similar results , but because of greater variability in eccentric testing , only the concentric test results are shown . Lower-Extremity Lean Tissue Mass Total-body dual-energy x-ray absorptiometry was done in all participants by using a Lunar-DPX-L instrument ( Lunar Corp. , Madison , Wisconsin ) . Results were analyzed for total and regional body composition , including body fat , mineral , and lean components ( lean components were components other than fat or mineral ) . The right and left lower extremities were analyzed separately . The lower extremity was defined as all tissue below a diagonal line drawn outward and upward from the groin area through the femoral neck . Statistical Analysis Participants were divided into four groups on the basis of presence or absence of radiographic evidence of osteoarthritis of the knee and presence or absence of knee pain , as defined above . Men and women were compared by using the t-test . Comparisons of Arthritis Index pain and functional impairment scores were done by using nonparametric approaches . For analyses of continuous data involving more than two groups of participants ( for example , osteoarthritis with or without knee pain ) , analysis of variance was used to determine whether an overall difference was present . The Fisher protected least-significant-difference procedure was used for pairwise comparisons . Comparisons within participants ( for example , comparison of the two legs in a person with unilateral osteoarthritis of the knee ) were done by using paired t-tests . Regression models were constructed with the generalized estimating equations approach of Zeger and Liang [ 13 ] . This approach inflates the st and ard errors to adjust for correlations in both independent variables ( such as strength ) and dependent variables ( such as radiographic grade ) within participants . Statistically significant differences ( P < 0.05 ) in the above analyses are specifically noted below . Results The characteristics of the 462 men and women in the cohort are shown in Table 1 . As expected , men were taller , were heavier , and had greater lower-extremity strength and lean tissue mass in the lower extremities compared with women ( P < 0.001 for all comparisons ) . Table 1 . Age , Height , Weight , and Lower-Extremity Strength and Lean Tissue Mass * One hundred forty-five participants ( 31 % ; 33 % of the women and 30 % of the men ) had radiographic evidence of osteoarthritis involving the tibiofemoral compartment , the patellofemoral compartment , or both . In 62 participants ( 43 % ) , the radiographic changes were unilateral . Table 2 shows the association between osteoarthritis and obesity [ 14 - 16 ] . Women in the cohort who had osteoarthritis were approximately 15 % heavier than women with normal radiographs and no knee pain . Men with osteoarthritis were also slightly heavier than men without osteoarthritis . Table 2 . Body Weight and Summed Arthritis Index Scores for Recent Pain and Function in the Left Knee in Participants with and without Radiographic Evidence of Osteoarthritis * Among those with radiographic evidence of tibiofemoral osteoarthritis , women were slightly more likely than men to report knee pain ( P = 0.10 ; Table 3 ) . Table 3 . Radiography and Recent Pain in the Left Knee Table 2 also shows the mean summed and the distribution of scores for left knee pain and functional impairment ( data for the right knee were similar ) . Among men and women with radiographic evidence of osteoarthritis who reported having knee pain , the mean summed pain score for the knee with osteoarthritis was approximately 12 ( median score , 2 of 5 ) . In comparison , the mean pain score of participants who reported knee pain but did not have radiographic evidence of osteoarthritis in the painful knee was approximately 10 ( median score , 2 of 5)-only slightly lower than the mean pain score of participants with radiographic changes . Consistent with their relatively low pain scores , these community-dwelling participants with osteoarthritis reported moderately low use of NSAIDs ( Table 4 ) . Table 4 . Participants Reporting Regular Current or Previous Use of Analgesics and Nonsteroidal Anti-inflammatory Drugs Related to the Presence of Radiographic Evidence of Osteoarthritis of the Knee and Recent Knee Pain * Arthritis Index scores for functional impairment paralleled those for pain ( Table 2 ) . Participants with osteoarthritis had the greatest functional impairment ( P < 0.001 for the comparison with patients who did not have pain or radiographic evidence of osteoarthritis ) . Functional impairment in participants who had pain but no radiographic evidence of OBJECTIVE To evaluate the relative risk for peptic ulcer disease that is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs . DESIGN Nested case-control study . SETTING Tennessee Medicaid program . PARTICIPANTS Medicaid enrollees 65 years of age or older were included in the study . The 1415 case patients had been hospitalized for confirmed peptic ulcer disease at some point from 1984 through 1986 . The 7063 control persons represented a stratified r and om sample of other Medicaid enrollees . MEASUREMENTS AND MAIN RESULTS The estimated relative risk for the development of peptic ulcer disease among current users of nonaspirin nonsteroidal anti-inflammatory drugs , compared with that among nonusers , was 4.1 ( 95 % CI , 3.5 to 4.7 ) . For current users , the risk increased with increasing dose , from a relative risk of 2.8 ( CI , 1.8 to 4.3 ) for the lowest to a relative risk of 8.0 ( CI , 4.4 to 14.8 ) for the highest dose category . The risk was greatest in the first month of use ( relative risk , 7.2 ; CI , 4.9 to 10.5 ) . If the association is fully causal , 29 % of peptic ulcers in the study sample result ed from the use of these drugs , and the excess risk associated with such use was 17.4 hospitalizations for ulcer disease per 1000 person-years of exposure . CONCLUSIONS These data support other findings indicating that a clinical ly significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs . The data show that this risk increases with dose and recency of use and that use of these drugs may be responsible for a large proportion of peptic ulcer disease among elderly persons Other members of the guideline development and project groups are listed in the Appendix This guideline addresses the appropriate use of non-steroidal anti-inflammatory drugs in the primary care treatment of patients with joint pain believed to be caused by degenerative arthritis . It does not consider therapies other than drug treatment . General practitioners must use their professional knowledge and judgement when applying guideline recommendations to the management of individual patients . They should note the information , contraindications , interactions , and side effects contained in the British National Formulary.1 This is a summary of the full version of the guideline .2 In this article , the statements accompanied by categories of evidence ( cited as Ia , Ib , IIa , IIb , III , and IV ) and recommendations classified according to their strength ( A , B , C , or D ) are as described previously and are summarised in the box.3 # # # Summary points The methods used to develop the guideline have been described previously.3Briefly , we search ed the electronic data bases Medline and Embase , using a combination of subject heading and free text terms aim ed at locating systematic review s , meta-analyses , r and omised trials , quality of life studies , and economic studies . The search was backed up by the expert knowledge and experience of group members . # # # Strength of Forty-four patients with chronic cervical osteoarthritis took part in this study . Patients were treated with acupuncture , sham-acupuncture , diazepam or placebo-diazepam in r and omized order . Pain was rated on visual analogue scales before , during , and after treatment . Two scales were separately used to rate the intensity ( sensory component ) and the unpleasantness ( affective component ) of pain . The results analyzed from these trials show that diazepam , placebo-diazepam , acupuncture and sham-acupuncture have a more pronounced effect on the affective than on the sensory component of pain . Acupuncture was significantly more effective than placebo-diazepam ( p less than 0.05 ) , but not significantly more effective than diazepam or sham-acupuncture OBJECTIVE The purpose of this study was to determine whether acupuncture was more effective than sham acupuncture in the reduction of pain in persons with osteoarthritis ( OA ) of the knee . METHODS Forty subjects ( 20 men , 20 women ) with radiographic evidence of OA of the knee were stratified by gender and r and omly assigned to either the experimental ( real acupuncture ) or control ( sham acupuncture ) groups . Subjects were treated three times per week for 3 weeks and evaluated at three test sessions . Outcome measures were : 1 ) the Pain Rating Index of the McGill Pain Question naire , 2 ) the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index , and 3 ) pain threshold at four sites at the knee . RESULTS The analyses of variance showed that both real and sham acupuncture significantly reduced pain , stiffness , and physical disability in the OA knee , but that there were no significant differences between groups . CONCLUSIONS Acupuncture is not more effective than sham acupuncture in the treatment of OA pain BACKGROUND Acid suppression with famotidine , a histamine H2-receptor antagonist , provides protection against gastric injury in normal subjects receiving short courses of aspirin or naproxen . The efficacy of famotidine in preventing peptic ulcers in patients receiving long-term therapy with nonsteroidal antiinflammatory drugs ( NSAIDs ) is not known . METHODS We studied the efficacy of two doses of famotidine ( 20 mg and 40 mg , each given orally twice daily ) , as compared with placebo , in preventing peptic ulcers in 285 patients without peptic ulcers who were receiving long-term NSAID therapy for rheumatoid arthritis ( 82 percent ) or osteoarthritis ( 18 percent ) . The patients were evaluated clinical ly and by endoscopy at base line and after 4 , 12 , and 24 weeks of treatment . The evaluators were unaware of the treatment assignment . The primary end point was the cumulative incidence of gastric or duodenal ulceration at 24 weeks . RESULTS The cumulative incidence of gastric ulcers was 20 percent in the placebo group , 13 percent in the group of patients receiving 20 mg of famotidine twice daily ( P = 0.24 for the comparison with placebo ) , and 8 percent in the group receiving 40 mg of famotidine twice daily ( P = 0.03 for the comparison with placebo ) . The proportion of patients in whom duodenal ulcers developed was significantly lower with both doses of famotidine than with placebo ( 13 percent in the placebo group , 4 percent in the low-dose famotidine group [ P = 0.04 ] , and 2 percent in the high-dose famotidine group [ P = 0.01 ] ) . Both doses of famotidine were well tolerated . CONCLUSIONS Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy Forty patients , r and omly assigned to an experimental and a control group , participated in a double-blind study to assess the effectiveness of acupuncture in reducing chronic pain associated with osteoarthritis . The experimental group received treatment at st and ard acupuncture points , and the control group at placebo points . Analysis before and after treatment showed a significant ( P less than 0.05 ) improvement in tenderness and subjective report of pain in both groups as evaluated by two independent observers and in activity by one observer . Comparison of responses to treatment between the two groups showed no significant ( P greater than 0.05 ) difference . Thus , both experimental and control groups showed a reduction in pain after the treatments . These results may reflect the natural course of illness , and various attitudinal and social factors OBJECTIVE To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis . SETTING AND DESIGN A r and omized , single-blind clinical trial lasting 18 months conducted at 2 academic medical centers . PARTICIPANTS A total of 439 community-dwelling adults , aged 60 years or older , with radiographically evident knee osteoarthritis , pain , and self-reported physical disability . INTERVENTIONS An aerobic exercise program , a resistance exercise program , and a health education program . MAIN OUTCOME MEASURES The primary outcome was self-reported disability score ( range , 1 - 5 ) . The secondary outcomes were knee pain score ( range , 1 - 6 ) , performance measures of physical function , x-ray score , aerobic capacity , and knee muscle strength . RESULTS A total of 365 ( 83 % ) participants completed the trial . Overall compliance with the exercise prescription was 68 % in the aerobic training group and 70 % in the resistance training group . Postr and omization , participants in the aerobic exercise group had a 10 % lower adjusted mean ( + /- SE ) score on the physical disability question naire ( 1.71 + /- 0.03 vs 1.90 + /- 0.04 units ; P<.001 ) , a 12 % lower score on the knee pain question naire ( 2.1 + /- 0.05 vs 2.4 + /- 0.05 units ; P=.001 ) , and performed better ( mean [ + /- SE ] ) on the 6-minute walk test ( 1507 + /- 16 vs 1349 + /- 16 ft ; P<.001 ) , mean ( + /-SE ) time to climb and descend stairs ( 12.7 + /- 0.4 vs 13.9 + /- 0.4 seconds ; P=.05 ) , time to lift and carry 10 pounds ( 9.1 + /- 0.2 vs 10.0 + /- 0.1 seconds ; P<.001 ) , and mean ( + /-SE ) time to get in and out of a car ( 8.7 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P<.001 ) than the health education group . The resistance exercise group had an 8 % lower score on the physical disability question naire ( 1.74 + /- 0.04 vs 1.90 + /- 0.03 units ; P=.003 ) , 8 % lower pain score ( 2.2 + /- 0.06 vs 2.4 + /- 0.05 units ; P=.02 ) , greater distance on the 6-minute walk ( 1406 + /- 17 vs 1349 + /- 16 ft ; P=.02 ) , faster times on the lifting and carrying task ( 9.3 + /- 0.1 vs 10.0 + /- 0.16 seconds ; P=.001 ) , and the car task ( 9.0 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P=.003 ) than the health education group . There were no differences in x-ray scores between either exercise group and the health education group . CONCLUSIONS Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability , physical performance , and pain from participating in either an aerobic or a resistance exercise program . These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis OBJECTIVE To evaluate the effects of a spouse-assisted pain-coping skills training intervention on pain , psychological disability , physical disability , pain-coping , and pain behavior in patients with osteoarthritis ( OA ) of the knees . METHODS Eighty-eight OA patients with persistent knee pain were r and omly assigned to 1 of 3 conditions : 1 ) spouse-assisted pain-coping skills training , ( spouse-assisted CST ) , 2 ) a conventional CST intervention with no spouse involvement ( CST ) , or 3 ) an arthritis education-spousal support ( AE-SS ) control condition . All treatment was carried out in 10 weekly , 2-hour group sessions . RESULTS Data analysis revealed that at the completion of treatment , patients in the spouse-assisted CST condition had significantly lower levels of pain , psychological disability , and pain behavior , and higher scores on measures of coping attempts , marital adjustment , and self-efficacy than patients in the AE-SS control condition . Compared to patients in the AE-SS control condition , patients who received CST without spouse involvement had significantly higher post-treatment levels of self-efficacy and marital adjustment and showed a tendency toward lower levels of pain and psychological disability and higher scores on measures of coping attempts and ratings of the perceived effectiveness of pain-coping strategies . CONCLUSION These findings suggest that spouse-assisted CST has potential as a method for reducing pain and disability in OA patients Purpose : Acupuncture treatment of patients waiting for arthroplasty surgery . Methods : 29 patients with a total of 42 osteoarthritic knees were r and omized to two groups . Group A was treated while Group B served as a no‐treatment control group . After 9 weeks Group B was treated too . Analgesic consumption , pain and objective measurements were registered . All objective measures were done by investigators who were “ blinded ” as to Group A & B. In the second part of the study 17 patients ( 26 knees ) continued with treatments once a month . Registration of analgesic consumption , pain and objective measurements continued . Total study period 49 weeks . Results : Comparing Group A to B there was a significant reduction in pain , analgesic consumption and in most objective measures . In Group A + B combined there was an 80 % subjective improvement , and a significantly increased knee range movement – an increase mainly in the worst knees . Results were significantly better in those who had not been ill for a long time . In the second part of the study , it was shown that it was possible to maintain the improvements . Conclusions : Acupuncture can ease the discomfort while waiting for an operation and perhaps even serve as an alternative to surgery . Seven patients have responded so well that at present they do not want an operation . ( USD 9000 saved per operation ) OBJECTIVE Self-management courses in arthritis have been shown to improve outcomes and to decrease medical re source utilization . We studied the effectiveness of a mail-delivered arthritis self-management program with the potential for extending these effects more broadly . METHODS R and omized controlled trial of 375 program participants and 434 controls over a 6 month period . Baseline and 6 month data were analyzed for each group and between groups by paired 2 sample t test . The intervention consists of health assessment question naires at 3 month intervals , with computer processed recommendation letters and reports individualized to age , diagnosis , education level , disability , pain , medication , and other patient-specific variables . RESULTS At 6 months , outcomes of function ( 4.7 % ; 95 % confidence limits 2.7 , 6.7 ) , decreased pain ( 9 % ; 2.8 , 15.2 ) , global vitality ( 7 % ; 2.8 , 11.2 ) , and joint count ( 28 % ; 20 , 36 ) were improved in the program group compared with controls ( p < 0.01 ) . Exercise ( 35 % ; 26 , 44 ) and self-efficacy ( 14.7 % ; 9 , 20 ) were increased in the program group but not controls ( p < 0.001 ) . Doctor visits/year were decreased by 16 % ( 3 , 29 ) in the program group compared with controls ( p < 0.05 ) and days missed work or confined to home decreased by 52 % ( -3 , 107 ) in the program group compared with controls ( p = 0.06 ) . At one year , patients in the original program group continued to improve , and the control group , provided with the program in the second 6 months , showed improvement similar to the first 6 months of the original program group . CONCLUSION A mail-delivered arthritis self-management program can positively affect patient outcomes and can decrease medical re source utilization Worldwide , nonsteroidal anti-inflammatory drugs ( NSAIDs ) are prescribed more frequently than any other group of medications [ 1 ] . Unfortunately , NSAID use is almost invariably accompanied by some degree of injury to the gastroduodenal mucosa , manifested by fecal blood loss or discovered by upper gastrointestinal endoscopy [ 2 - 10 ] . Gastroduodenal mucosal damage induced by NSAIDs may lead to the development of gastric or duodenal ulcers , or both , with the attendant possibility of hemorrhage and perforation in some patients . Several studies [ 4 , 5 , 8 , 11 - 16 ] have shown that misoprostol , a synthetic analog of prostagl and in E1 , affords significant protection against NSAID-induced gastric and duodenal ulcers ; the drug has also been shown to reduce the incidence of ulcer complications [ 17 ] . However , the use of misoprostol at the currently recommended dosage of 200 g four times daily is associated with frequent side effects , which primarily affect the gastrointestinal tract . These side effects are generally mild but may lead to poor patient compliance . A lower dosage of misoprostol , such as 200 g twice or three times daily , might result in a lower incidence of adverse events ( and , hence , better compliance ) without adversely affecting efficacy . We sought to determine the effectiveness and tolerability of three different misoprostol regimens . Methods The study was a 12-week , r and omized , parallel , placebo-controlled , double-blind comparison of three regimens of misoprostol ( Cytotec , G.D. Searle & Co. , Chicago , Illinois ) and was done at 135 centers . A single study protocol was approved by the institutional review boards for all study sites . Informed consent was obtained from all patients . Patients qualifying for study entry had a clinical diagnosis of osteoarthritis , rheumatoid arthritis , psoriatic arthritis , ankylosing spondylitis , or the Reiter syndrome and were receiving NSAID therapy that was expected to continue uninterrupted for at least 3 additional months at a fixed dose . The following minimum daily NSAID dosages were required : ibuprofen , 1200 mg ; piroxicam , 20 mg ; naproxen , 750 mg ; sulindac , 200 mg ; tolmetin , 1200 mg ; indomethacin , 75 mg ; flurbiprofen , 200 mg ; ketoprofen , 150 mg ; or diclofenac , 150 mg . Qualifying patients had to be having upper gastrointestinal symptoms , such as pain , cramps , bloating , or heartburn . Before study entry , patients supplied a medical history and had a physical examination , upper gastrointestinal symptom assessment , routine laboratory tests , and upper gastrointestinal endoscopy . Patients with a gastric or duodenal mucosal defect 0.3 cm or less in diameter , a mucosal defect of any size with perceptible depth , or any esophageal erosions or ulcers were excluded from the study . Also excluded were patients who had had upper gastrointestinal surgery within 30 days of anticipated entry into the study and patients with upper gastrointestinal malignancy , pyloric obstruction , acute hepatitis , pancreatitis , inflammatory bowel disease , or a bleeding diathesis . Patients were assigned to their regimens according to a central ized , computer-generated r and omization schedule . Each center was assigned with one or more r and omization blocks of seven in sealed envelopes . Patients were assigned sequentially to receive one of four regimens : placebo four times daily ; 200 g of misoprostol twice daily plus placebo twice daily ; 200 g of misoprostol three times daily plus placebo once daily ; or 200 g of misoprostol four times daily . One patient was assigned to the group receiving misoprostol four times daily for every two patients assigned to the other groups . These assignment ratios were chosen in light of the known therapeutic effectiveness of four-times-daily dosing . They were calculated to demonstrate a reduction in the rate of gastric ulcer development from 13 % in the placebo group to 4 % in each of the active treatment arms ( twice daily , three times daily , and four times daily ) , and to show a similar reduction in duodenal ulcer development from 6.3 % to 1 % , with an overall error rate of 0.05 % and a power of 80 % . Blister cards of scored tablets were supplied by the sponsor and contained tablets of misoprostol , 200 g , or identical tablets composed of inert excipient . Labels on the blister packs indicated the breakfast , lunch , dinner , and bedtime doses . For the first 3 days of the study , patients were instructed to take one half of one tablet four times daily and to discard the other halves of the tablets . Subsequently , full tablets were taken . Patients who missed a dose were instructed to skip that dose . Each patient was provided with antacid tablets , 84 600 mg aluminum hydroxide ( Amphogel , Wyeth-Ayerst Laboratories , Philadelphia , Pennsylvania ) , and instructed to take as many as four tablets per day as required for relief of upper abdominal symptoms during the first 3 weeks of the study . Study medication dispensed at one visit was collected and inventoried at the next visit to ensure at least 60 % compliance in the dosing of misoprostol . Patients had endoscopic and upper gastrointestinal symptom evaluations after 4 , 8 , and 12 weeks of therapy . Endoscopic examinations included assessment of the gastric and duodenal mucosa . Patient Groups Analyzed Of the 1623 patients enrolled in the study , 1259 finished the trial . Of these , 1197 met major accession , study drug compliance , and endoscopic evaluation criteria and composed the evaluable group of patients . Primary analyses were done on this evaluable group . Confirmatory analyses were also done on the intention-to-treat group , which comprised patients who had received at least one dose of study medication . End Points A patient who developed an endoscopically confirmed gastric or duodenal ulcer ( 0.3 cm in diameter and with perceptible depth ) during the study was considered a prophylaxis failure . Statistical Analysis The baseline demographic characteristics of the study treatment groups were compared using either the Pearson chi-square test ( sex and race ) or the Kruskal-Wallis test ( age ) . To evaluate the efficacy of misoprostol therapy in the prevention of NSAID-induced gastric and duodenal ulcers , the following three pairwise comparisons were made : misoprostol twice daily compared with placebo , misoprostol three times daily compared with placebo , and misoprostol four times daily compared with placebo . In addition , comparisons of the incidence of NSAID-induced ulcers in the groups receiving misoprostol twice and three times daily with that in the group receiving misoprostol four times daily were done to determine evidence of similar effectiveness in the prevention of ulcers . Treatment-by-investigator interactions were assessed qualitatively . The dosage-response effect of misoprostol was determined by using a logistic regression analysis with ulcer occurrence as the dependent variable and dosage as the independent variable . The placebo group was not included for these analyses . Incidence rates for adverse events were calculated for body system , type of event , severity ( mild , moderate , and severe ) , and relation to study drug ( none , uncertain , and probable ) . Interregimen incidence rate comparisons were made using the unadjusted , two-tailed chi-square test . If chi-square assessment of incidence rates for the four regimens for an individual adverse event showed a statistically significant difference , incidence rates for the particular adverse event were further tested without the placebo group to distinguish differences among the three active treatment groups . Adverse events causing withdrawal from the study were compared across treatment groups using the Pearson chi-square test or the Fisher exact test . Dosage-response effect on adverse events was determined by using a logistic regression analysis with adverse event as the dependent variable and dosage as the independent variable . The statistical analysis was done by G.D. Searle & Co. Results Study Population The disposition and r and omization of patients entered into the study ( n = 1623 ) is presented in Table 1 . Five patients received no medication and were excluded from the intention-to-treat group . A total of 421 patients was excluded from the intention-to-treat group ( 359 were withdrawn before reaching an end point and 62 were excluded for other reasons ) , leaving 1197 patients in the evaluable group . Table 1 . Disposition of Patients Entered into the Study Demographic Characteristics Demographic data for the intention-to-treat group are shown in Table 2 . Neither the intention-to-treat group nor the evaluable groups differed significantly with respect to age , sex , race , NSAID use , type of arthritis , prevalence of smoking , or alcohol use . Table 2 . Demographic Characteristics of the Intention-to-Treat Group Gastric Ulcers Gastric ulcers ( evaluable for the gastric ulcer group ) were noted in 51 of 325 patients ( 15.7 % ) receiving placebo , in 29 of 358 patients ( 8.1 % ) receiving misoprostol twice daily , in 13 of 336 patients ( 3.9 % ) receiving misoprostol three times daily , and in 6 of 152 patients ( 4.0 % ) receiving misoprostol four times daily ( Table 3 ) . The incidence of gastric ulcers was significantly lower in groups receiving misoprostol twice daily ( difference , 7.6 % [ 95 % CI , 2.7 % to 12.5 % ] ; P = 0.002 ) , three times daily ( difference , 11.8 % [ CI , 7.4 % to 16.3 % ] ; P < 0.001 ) , and four times daily ( difference , 11.7 % [ CI , 6.7 % to 16.8 % ] ; P < 0.001 ) than in the group receiving placebo . Pairwise comparison showed no statistical difference between the group receiving misoprostol four times daily and the groups receiving it three times or twice daily . However , a significant difference ( difference , 4.2 % [ CI , 0.7 % to 7.7 % ] ; P = 0.02 ) was noted between the group receiving misoprostol twice daily and the group receiving it three times daily . A significant dose-response effect across treatment groups was noted ( P = 0.02 ) . Table 3 . Pairwise Comparison of Rates of Gastric Ulcer in the Evaluable-for-Gastric-Ulcer Group Duodenal Ulcers Duodenal OBJECTIVE To evaluate the efficacy of tramadol as adjunctive therapy in patients with musculoskeletal pain attributed to osteoarthritis ( OA ) who experienced breakthrough pain while taking a nonsteroidal antiinflammatory drug ( NSAID ) . METHODS This single center , parallel , placebo controlled , 2 phase study was conducted in adults who experienced breakthrough OA pain while undergoing stable NSAID therapy . In a 24 h open label phase , patients took 100 mg of tramadol followed by 50 mg every 6 h ( total 250 mg ) in addition to their daily NSAID regimen . Supplemental analgesics were prohibited . Patients who met entry criteria and were willing to continue therapy were r and omized to a 13 day double blind phase of adjunctive therapy with tramadol ( 50 - 100 mg every 4 - 6 h as needed for pain ) or placebo ; NSAID therapy was continued . The primary efficacy endpoint was the time to exit from the study because of therapeutic failure ( i.e. , insufficient pain relief or an inability to perform activities of daily living ) . RESULTS The time to exit from the study because of insufficient pain relief tended to be longer in the tramadol group ( 250 mg/day ) compared with the placebo group ( p = 0.066 ) . At the end of the double blind phase , pain at rest was significantly less severe in tramadol treated patients ( p = 0.046 ) . In addition , severity of pain on motion tended to be less severe in tramadol treated patients ( p = 0.059 ) . General severity of current pain and ability to perform activities of daily living were not significantly different with tramadol or placebo . Patients ' overall assessment of therapy ( p = 0.022 ) and investigator 's rating of global improvement ( p = 0.004 ) were significantly better with tramadol than with placebo . CONCLUSION Tramadol may have a role as adjunctive treatment for breakthrough pain in patients receiving NSAID therapy for musculoskeletal pain attributed to OA The neuropeptide substance P has been implicated in the pathogenesis of inflammation and pain in arthritis . In this double-blind r and omized study , 70 patients with osteoarthritis ( OA ) and 31 with rheumatoid arthritis ( RA ) received capsaicin ( a substance P depletor ) or placebo for four weeks . The patients were instructed to apply 0.025 % capsaicin cream or its vehicle ( placebo ) to painful knees four times daily . Pain relief was assessed using visual analog scales for pain and relief , a categorical pain scale , and physicians ' global evaluations . Most of the patients continued to receive concomitant arthritis medications . Significantly more relief of pain was reported by the capsaicin-treated patients than the placebo patients throughout the study ; after four weeks of capsaicin treatment , RA and OA patients demonstrated mean reductions in pain of 57 % and 33 % , respectively . These reductions in pain were statistically significant compared with those reported with placebo ( P = 0.003 and P = 0.033 , respectively ) . According to the global evaluations , 80 % of the capsaicin-treated patients experienced a reduction in pain after two weeks of treatment . Transient burning was felt at the sites of drug application by 23 of the 52 capsaicin-treated patients ; two patients withdrew from treatment because of this side effect . It is concluded that capsaicin cream is a safe and effective treatment for arthritis OBJECTIVE To investigate the efficacy and safety of SC-58635 ( celecoxib ) , an antiinflammatory and analgesic agent that acts by selective cyclooxygenase 2 ( COX-2 ) inhibition and is not expected to cause the typical gastrointestinal ( GI ) , renal , and platelet-related side effects associated with inhibition of the COX-1 enzyme . METHODS Four phase II trials were performed : a 2-week osteoarthritis efficacy trial , a 4-week rheumatoid arthritis efficacy trial , a 1-week endoscopic study of GI mucosal effects , and a 1-week study of effects on platelet function . RESULTS The 2 arthritis trials identified SC-58635 dosage levels that were consistently effective in treating the signs and symptoms of arthritis and were distinguished from placebo on st and ard arthritis scales . In the upper GI endoscopy study , 19 % of subjects receiving naproxen ( 6 of 32 ) developed gastric ulcers , whereas no ulcers occurred in subjects receiving SC-58635 or placebo . The study of platelet effects revealed no meaningful effect of SC-58635 on platelet aggregation or thromboxane B2 levels , whereas aspirin caused significant decreases in 2 of 3 platelet aggregation measures and thromboxane B2 levels . In all 4 trials , SC-58635 was well tolerated , with a safety profile similar to that of placebo . CONCLUSION SC-58635 achieves analgesic and antiinflammatory efficacy in arthritis through selective COX-2 inhibition , without showing any evidence of 2 of the toxic effects of COX-1 inhibition associated with nonsteroidal antiinflammatory drugs The cost-effectiveness of the Mallory Head ( Biomet , Warsaw , IN ) cemented versus noncemented total hip arthroplasty was determined as part of a r and omized trial . Costs were assessed during the first postoperative year . In-hospital re source use was determined using a chart review of 60 r and omly selected patients . Costs were determined using a fully allocated costing model . Outpatient re source use was determined using patient diaries , and appropriate costs were allocated for outpatient visits , admissions to hospital , and patient-borne costs . There was no difference in costs between the cemented and noncemented prostheses . The average cost of the initial hospitalization was $ 9,990 ( 1988 Canadian dollars ) , and outpatient costs during the first year were $ 1,137 ( total cost during the first year was $ 11,127 ) . The cost per quality adjusted life year was $ 27,139 during the first year and $ 8,031 during the first 3 years & NA ; Forty patients with chronic pain below the waist level not amenable to conventional medical and /or surgical treatment were r and omly assigned to one of two different methods of acupuncture , after study ing the underlying pain mechanisms using a Multidisciplinary Pain Clinic approach and the differential spinal block ( DSB ) . One group received acupuncture needling in the classical acupuncture points referred to as meridian loci needling ( MLN ) and the other group received tender area needling ( TAN ) with needles inserted in the dermatomal distribution of the painful areas . The responses between the two groups showed no significant difference . Results were then related to the predetermined somatopsychological basis of the individual 's pain problems as classified by the DSB . A group of patients in whom pain relief occurred upon subarachnoid injection of 0.25 % procaine followed by sympathetic blockade or 0.5 % procaine injection followed by hypalgesia without motor loss , also reported maximum subjective improvement in their pain level following acupuncture therapy performed at a later time . The other group of patients in whom pain persisted despite sensory and motor blockade ( 1 % procaine ) responded very poorly to acupuncture therapy . DSB was found to be complimentary to acupuncture therapy in that it facilitated patient selection for the therapy OBJECTIVE To determine whether experimentally developed social support and education about appropriate use of the health care system decrease health care costs without negatively affecting health status . METHOD Three hundred sixty-three health maintenance organization members with osteoarthritis were r and omly assigned to 1 of 3 intervention groups or to a control group . Health status and health care use were assessed upon entering the study , and after 1 year and 2 years . RESULTS A savings of $ 1,156/participant/year was obtained when health care costs of the experimental groups were compared with those of the control group . Production or implementation costs were least for the social support intervention . The nearly equal effects of the 3 interventions on health care costs make implementation costs the primary focus when deciding which intervention to use . CONCLUSION We believe that the social support treatment is the most cost-effective intervention A group of 120 patients with rheumatoid arthritis or osteoarthritis volunteered to be subjects for this study of aerobic versus nonaerobic exercise . Patients were stratified by diagnosis and r and omized into an exercise program of aerobic walking , aerobic aquatics , or nonaerobic range of motion ( controls ) . The retention rate for the 12-week program was 83 % . Exercise tolerance , disease-related measures , and self-reported health status were assessed . The aquatics and walking exercise groups showed significant improvement over the control group in aerobic capacity , 50-foot walking time , depression , anxiety , and physical activity after the 12-week exercise program . There were no significant between-group group differences in the change scores for flexibility , number of clinical ly active joints , duration of morning stiffness , or grip strength . Our findings document the feasibility and efficacy of conditioning exercise for people who have rheumatoid arthritis or osteoarthritis Abstract Objective : To test the hypothesis that medial taping of the patella reduces the symptoms of osteoarthritis of the knee when the patellofemoral joint is affected . Design : R and omised , single blind , crossover trial of three different forms of taping of the knee joint . Each tape ( medial , lateral , or neutral ) was applied for four days , with three days of no treatment between tape positions . Subjects : 14 patients with established , symptomatic osteoarthritis of the knee and both clinical and radiographic evidence of patellofemoral compartment disease . Main outcome measures : Daily visual analogue scale ratings for pain ; patients ' rating of change with each treatment ; and tape preference . Results - Medical taping of the patella was significantly better than the neutral or lateral taping for pain scores , symptom change , and patient preference . The medical tape result ed in a 25 % reduction in knee pain . Conclusion : Patella taping is a simple , safe , cheap way of providing short term pain relief in patients with osteoarthritis of the patellofemoral joint BACKGROUND Non-steroidal anti-inflammatory drugs ( NSAIDs ) are known to cause gastroduodenal lesions and dyspeptic symptoms . METHODS Patients with a history of dyspepsia or uncomplicated peptic ulcer disease and with a need for continuous NSAID treatment were r and omized to receive either 20 mg omeprazole once daily or placebo . Gastroduodenal ulcers , erosions , and dyspeptic symptoms were evaluated after 1 and 3 months . RESULTS During a 3-month study period 4.7 % ( 4 of 85 ) of omeprazole-treated patients developed peptic ulcer , compared with 16.7 % ( 15 of 90 ) of patients treated with placebo . This prophylactic effect of omeprazole was sustained independently of previous peptic ulcer history or Helicobacter pylori status . Development of dyspeptic symptoms requiring active treatment , either alone or in combination with ulcer(s ) or erosions , occurred in 15.3 % ( 15 of 85 ) of patients treated with omeprazole and 35.6 % of those who received placebo . CONCLUSIONS Omeprazole , 20 mg once daily , provides effective prophylactic therapy in patients at risk of developing NSAID-associated peptic ulcers or dyspeptic symptoms OBJECTIVES To determine 4-month and 1-year health-related outcomes of a 6-week , lay-led , and community-based arthritis self-management program for Spanish-speaking participants and to determine the role of self-efficacy in predicting health status for this population . METHODS Three hundred and thirty one subjects were r and omized to the program or to a 4-month wait list control group . One hundred ninety eight subjects continued in a 1-year longitudinal study . Data were collected via mailed question naires with telephone follow up . RESULTS At 4 months , treatment subjects , compared with controls , demonstrated positive changes in exercise , disability , pain , and self-efficacy ( P < 0.05 ) . At 1 year , compared with baseline , treatment subjects demonstrated improvements in exercise , general health , disability , pain , self-efficacy , and depression ( P < 0.05 ) . Baseline and 4-month changes in self-efficacy predicted health status at 1 year . CONCLUSIONS Spanish-speaking participants of an arthritis self-management program demonstrate short- and long-term benefits ( improved health behaviors , health status , and self-efficacy ) 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 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 |
11,737 | 25,059,197 | While there is abundant literature on the topic of AHR in sheep GINs , few studies have explicitly investigated the association between putative risk or protective factors and AHR . | BACKGROUND Anthelmintic drugs have been widely used in sheep as a cost-effective means for gastro-intestinal nematode ( GIN ) control .
However , growing anthelmintic resistance ( AHR ) has created a compelling need to identify evidence -based management recommendations that reduce the risk of further development and impact of AHR .
OBJECTIVE To identify , critically assess , and synthesize available data from primary research on factors associated with AHR in sheep . | Abstract AIM : To establish the prevalence of anthelmintic resistance in parasitic nematodes on sheep farms in New Zeal and . METHODS : A cross-sectional prevalence study was conducted , using a st and ardised faecal nematode egg count ( FEC ) reduction ( FECR ) test ( FECRT ) for ivermectin , at a full ( 0.2 mg/kg ) and half ( 0.1 mg/kg ) dose rate , and albendazole , levamisole and albendazole-levamisole in combination , on 60 lambs ( n=10 per group ) on farms selected from throughout New Zeal and . Farms that conformed with selection criteria were chosen at r and om ( n=80 ) or with a history of suspected resistance to macrocy- clic lactone ( ML ) anthelmintics ( n=32 ) . Resistance to an an- thelmintic was inferred when there was < 95 % reduction in FEC 7 - 10 days after treatment . Larval cultures were performed for all control groups and for treated groups for which resistance was evident . RESULTS : Of the farms r and omly selected , 36 % showed ≥95 % FECR for all anthelmintics tested ; resistance to ivermectin at 0.1 and 0.2 mg/kg liveweight was evident on 36 % and 25 % of these farms , respectively . Resistance to both ivermectin ( 0.2 mg/kg ) and levamisole was evident on 8/80 ( 10 % ) farms , to ivermectin and albendazole on 10/80 ( 13 % ) farms , and to iver- mectin , levamisole and albendazole on 6/80 ( 8 % ) farms . The prevalence of resistance to a half dose of ivermectin tended to be more prevalent on farms with a history of suspected ML resistance ( p=0.06 ) . Resistance to albendazole was seen across all the main parasite genera , and to levamisole in Nematodirus , Ostertagia (= Teladorsagia ) and Trichostrongylus species . Resistance to ivermectin was dominated by Ostertagia spp , although Cooperia , Nematodirus and Trichostrongylus species were also implicated . CONCLUSION : Anthelmintic resistance in parasitic nema-todes of sheep is common in New Zeal and . Not only was resistance to albendazole and levamisole common , but resistance to the ML , ivermectin , was at a higher prevalence than expected . Sheep farmers and advisors in New Zeal and need to re-evaluate the way they manage parasites , and more research is urgently needed if the steady decline in anthelmintic susceptibility is to be halted Abstract AIM : To test the theory that creating a reservoir of unselected worms by leaving a proportion of lambs in a flock untreated with anthelmintic , i.e. in refugia , will slow the development of anthelmintic resistance in nematode parasite population s. METHODS : Newly weaned Romney lambs ( n=180 ) were infected with two nematode parasite species , Teladorsagia ( = Ostertagia ) circumcincta and Trichostrongylus colubriformis . For each species , the challenge doses contained a mixture of infective larvae from benzimidazole-resistant and -susceptible isolates calculated to yield , from the combined population , a 95 % reduction in faecal nematode egg counts ( FEC ) following treatment with albendazole . Once the infections were patent , the lambs were divided into nine groups of 20 animals , and each group was allocated to one of three treatments . In Treatments 1 , 2 and 3 , 100 % , 90 % and 80 % of animals were treated with an anthelmintic , respectively . For treatments 2 and 3 , the heaviest animals remained untreated . Following treatment , each group was moved to its own previously prepared low-contamination pasture . Lambs grazed this pasture for 7 weeks before again being treated and moved to new low-contamination pastures ( Shift 1 and Shift 2 ) . The parasite population s on pasture result ing from the different treatments were subsequently sample d using tracer lambs , and worm eggs derived from these were used in both egg-hatch assays ( EHA ) and larval development assays ( LDA ) , to measure albendazole-resistance status . RESULTS : Treating all animals each time the groups were moved to new low-contamination pastures result ed in higher levels of albendazole resistance ( p<0.05 ) , measured using EHA and LDA , in subsequent parasite generations than when either 10 or 20 % of animals were left untreated . However , higher FEC in the tracer lambs grazed on pastures in Treatments 2 and 3 , compared with Treatment 1 , indicated an increased level of pasture contamination as a result of leaving some animals untreated . CONCLUSIONS : The results demonstrate that creating a reservoir of unselected parasites slows the development of anthelmintic resistance , and emphasises the risk of treating all animals prior to a shift on to low-contamination pasture . However , higher levels of pasture contamination , result ing from untreated animals , indicate the difficulty in managing both worm control and resistance Objective To investigate the effect of an additional review based on reporting guidelines such as STROBE and CONSORT on quality of manuscripts . Design Masked r and omised trial . Population Original research manuscripts su bmi tted to the Medicina Clínica journal from May 2008 to April 2009 and considered suitable for publication . Intervention Control group : conventional peer review s alone . Intervention group : conventional review plus an additional review looking for missing items from reporting guidelines . Outcomes Manuscript quality , assessed with a 5 point Likert scale ( primary : overall quality ; secondary : average quality of specific items in paper ) . Main analysis compared groups as allocated , after adjustment for baseline factors ( analysis of covariance ) ; sensitivity analysis compared groups as review ed . Adherence to review er suggestions assessed with Likert scale . Results Of 126 consecutive papers receiving conventional review , 34 were not suitable for publication . The remaining 92 papers were allocated to receive conventional review s alone ( n=41 ) or additional review s ( n=51 ) . Four papers assigned to the conventional review group deviated from protocol ; they received an additional review based on reporting guidelines . We saw an improvement in manuscript quality in favour of the additional review group ( comparison as allocated , 0.25 , 95 % confidence interval –0.05 to 0.54 ; as review ed , 0.33 , 0.03 to 0.63 ) . More papers with additional review s than with conventional review s alone improved from baseline ( 22 ( 43 % ) v eight ( 20 % ) , difference 23.6 % ( 3.2 % to 44.0 % ) , number needed to treat 4.2 ( from 2.3 to 31.2 ) , relative risk 2.21 ( 1.10 to 4.44 ) ) . Authors in the additional review group adhered more to suggestions from conventional review s than to those from additional review s ( average increase 0.43 Likert points ( 0.19 to 0.67 ) ) . Conclusions Additional review s based on reporting guidelines improve manuscript quality , although the observed effect was smaller than hypothesised and not definitively demonstrated . Authors adhere more to suggestions from conventional review s than to those from additional review s , showing difficulties in adhering to high method ological st and ards at the latest research phases . To boost paper quality and impact , authors should be aware of future requirements of reporting guidelines at the very beginning of their study . Trial registration and protocol Although registries do not include trials of peer review , the protocol design was su bmi tted to sponsored research projects ( Instituto de Salud Carlos III , PI081903 ) Abstract Fifty four r and omly selected farms , located throughout the North Isl and and the Nelson region of South Isl and , were surveyed for anthelmintic usage and for sheep nematodes resistant to anthelmintics . Information on anthelmintic usage was recorded on a st and ardized question naire . Most fanners had used both benzimidazole and non- benzimidazole broad spectrum drenches on their properties in previous years . Sheep were being drenched , on average , 7 times within their first year of life but much less frequently thereafter . Commercial interests played the dominant role in helping farmers formulate their drenching policies . On each farm 24 numbered ewe replacement lambs were sample d for faeces at the beginning of the trial to provide material for egg counts and larval cultures . The lambs were weighed and divided into three groups of eight . One group received thiabendazole ( TBZ ) at 66 mg/kg , the second levamisole ( LEV ) at 8mg/kg while the third remained untreated as controls . All were re sample d 4 to 10 da Forty-three r and omly selected farms located throughout South Isl and , excluding the Nelson region , were surveyed for anthelmintic usage and for sheep nematodes resistant to anthelmintics . Most farmers had used both benzimidazole and non-benzimidazole broad-spectrum drenches on their properties in previous years . Sheep were being drenched , on average , 5.6 times within their first year of life but much less frequently thereafter . Commercial interests played the dominant role in helping farmers formulate their drenching policies . On each farm 24 numbered ewe replacement lambs , born during the spring of 1980 , were sample d for faeces at the beginning of the trial to provide material for egg counts and larval cultures . The lambs were weighed and divided into three groups of eight . One group received thiabendazole ( TBZ ) at 66 mg/kg , the second levamisole ( LEV ) at 8 mg/kg while the third remained untreated as controls . All were re sample d 4 to 10 days later . On 32 ( 88 % ) of the 40 farms where drenching trials were successfully carried out during autumn 1981 , the faecal egg count depression ( FECD ) following treatment with either drench was 100 % . On one farm TBZ was less than 100 % effective as gauged by FECD . LEV proved to be less than 100 % effective on 7 farms . On one farm the FECD was less than 80 % , on 2 between 90 % and 95 % and on 4 between 95 % and 99 % OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required This survey was conducted on 252 farms r and omly distributed over all the sheep raising areas in Uruguay . The study involved farms with more than 600 sheep , which represented 80 % of the total sheep population of the country . Three anthelmintic groups were assessed , namely , benzimidazoles , levamisole and avermectins . Overall , the results showed 80 % of sheep flocks had benzimidazole resistance , 71 % had resistance to levamisole , and 1.2 % of flocks showed resistance to avermectins . Approximately 28 % of farms had resistance to one anthelmintic group , 64 % to two anthelmintic groups , and 1 % resistance to all three groups . Only 7.5 % of farms had no detectable levels of anthelmintic resistance . More than 80 % of farms had Trichostrongylus population s resistant to both benzimidazoles and levamisole . Resistance was recorded in all three anthelmintic groups for Haemonchus and resistance also occurred to benzimidazoles and levamisole in Ostertagia Abstract AIM : To examine the effect of an anthelmintic treatment to lambs , followed immediately by a shift onto pastures with differing levels of larval contamination , on the development of anthelmintic resistance , in order to support recommendations to farmers regarding drench- and -shift practice s for sustainable worm control . METHODS : Newly weaned Romney lambs ( n=72 ) were dosed with third-stage infective larvae ( L3 ) of two nematode parasite species , Teladorsagia ( = Ostertagia ) circumcincta and Trichostrongylus colubriformis , comprising benzimidazole-resistant and -susceptible isolates , calculated to yield , after treatment with albendazole , a 95 % reduction in faecal nematode egg count ( FEC ) . Once infections became patent ( Day 0 ) , lambs were r and omised into nine groups of eight animals , treated with albendazole at the manufacturer 's recommended dose rate , and moved to individual pastures each previously prepared to have one of three different levels of parasite larval infestation ( Treatment 1 = low contamination , Treatment 2 = medium contamination , and Treatment 3 = high contamination ) , and grazed on those pastures before receiving a second treatment with albendazole at Day 47 . Anthelmintic resistance status in each group of lambs was measured using FEC reduction ( FECR ) and egghatch assays ( EHA ) after the first anthelmintic treatment , and FECR after the second treatment . RESULTS : Egg-hatch assays demonstrated significant differences between treatments . The concentration of anthelmintic required to kill 50 % of the eggs ( LC50 ) for Treatment 1 , comprising the least contaminated pastures , was significantly higher than for Treatments 2 and 3 on Days 33 and 40 . Treatment 1 also had a significantly lower FECR at the final anthelmintic treatment , and significantly lower FEC than the other two treatments from Days 26 to 47 . CONCLUSIONS : The results demonstrated that the population s of T. circumcincta and T. colubriformis in lambs treated with anthelmintic had significantly higher levels of albendazole resistance at the end of the grazing period in lambs moved onto pastures with relatively low levels of parasite contamination than those moved onto pastures with relatively higher contamination , confirming drench- and -shift onto ‘ clean ’ pasture as a high-risk practice for the selection for anthelmintic resistance . While this does not necessarily preclude the use of this practice it does emphasise the importance of taking appropriate remedial action to minimise the risk Abstract AIM : To identify farm practice s associated with the presence of resistance to a macrocyclic lactone ( ML ) anthelmintic on sheep farms in New Zeal and . METHODS : A cross-sectional study was conducted to test for associations between the presence of resistance to an ML anthelmintic ( ivermectin ) and management practice s on sheep farms in New Zeal and . Selection of farms was both r and om ( n=80 ) and purposive ( n=32 ; being farms with a history of suspected ML resistance ) . Resistance was inferred from faecal nematode egg count ( FEC ) reduction ( FECR ) tests ( FECRTs ) when there was < 95 % reduction in FEC 7–10 days after treatment with a half dose of ivermectin ( 0.1 mg/kg ) . A logistic regression model was built to identify farm-level factors that were associated with the presence or absence of ML resistance . RESULTS : Of the 112 flock managers that were approached for interview , 103 ( 92 % ) returned useable question naires . The odds of ML resistance were increased : on farms that had used long-acting ML products in ewes as a pre-lambing treatment for ≥3 of the previous 5 years ( odds ratio ( OR ) = 7.2 ; 95 % confidence interval ( CI ) = 1.7–30.3 ) ; on farms where < 70 % of the total stock units mid-winter were from sheep ( OR=6.5 ; 95 % CI=1.6–25.6 ) ; on farms which over the year purchased ≥10 % of the number of sheep present mid-winter ( OR=7.1 ; 95 % CI=1.5–34.7 ) ; and on farms where the average wool diameter of the main flock was < 37 ( OR=4.1 ; 95 % CI=1.1–14.7 ) microns . The model provided a good fit to the data ( pseudo R2=0.64 ; Hosmer-Lemeshow statistic = 0.38 ) . CONCLUSIONS : Explanatory factors identified as associated with the presence of ML ( ivermectin ) resistance on farms included the use of long-acting anthelmintic formulations in ewes pre-lambing , sources of refugia of unselected parasites on the farm , breed of sheep and their requirements for anthelmintic treatments , and the importing of resistant parasites with purchased stock . The study provides support for controls that aim to provide refugia of susceptible worms and that minimise the risk of introduction of resistance through effective quarantine-drenching After reports of the apparent failure of monepantel to reduce the egg counts of goats on a farm in the lower North Isl and of New Zeal and , faecal egg count reduction tests were conducted in goats and lambs resident on the property , and a confirmatory , slaughter study was conducted using 12 sheep , source d elsewhere , that were grazed on the farm for approximately 5 weeks . In the egg count reduction test in goats , 8 animals were given monepantel at 3.9 mg/kg ( just over 1.5 × the sheep dose rate of 2.5mg/kg ) , whilst four received 7.7 mg/kg ( just over 3 × the sheep dose ) . In the egg count reduction test in sheep , 15 lambs were treated with 3.0mg/kg of monepantel . For the confirmatory study , the sheep were housed indoors for 2 weeks before half were treated with 2.9 mg/kg monepantel and the animals were killed for worm counts 9 days later . There was no evidence of efficacy in either egg count reduction test , or in the goats , the two dose rates used appeared equally ineffective . Likewise , there were no significant reductions in egg counts or worm burdens in the slaughter study . Monepantel was ineffective against at least two gastrointestinal nematode species , Teladorsagia circumcincta and Trichostrongylus colubriformis . These findings represent the first report from the field of resistance having developed to the anthelmintic monepantel with severe resistance developing in more than one species after being administered on 17 separate occasions to different stock classes and in less than 2 years of the product first being used on the farm in question The conduct of r and omized controlled trials in livestock with production , health , and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports . The objective of this project was to modify the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to reflect the unique aspects of reporting these livestock trials . A two-day consensus meeting was held on November 18 - 19 , 2008 in Chicago , Ill , United States of America , to achieve the objective . Prior to the meeting , a Web-based survey was conducted to identify issues for discussion . The 24 attendees were biostatisticians , epidemiologists , food-safety research ers , livestock production specialists , journal editors , assistant editors , and associate editors . Prior to the meeting , the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials . The consensus meeting result ed in the production of the REFLECT ( Reporting Guidelines for R and omized Control Trials ) statement for livestock and food safety ( LFS ) and 22-item checklist . Fourteen items were modified from the CONSORT checklist , and an additional sub-item was proposed to address challenge trials . The REFLECT statement proposes new terminology , more consistent with common usage in livestock production , to describe study subjects . Evidence was not always available to support modification to or inclusion of an item . The use of the REFLECT statement , which addresses issues unique to livestock trials , should improve the quality of reporting and design for trials reporting production , health , and food-safety outcomes |
11,738 | 27,669,500 | Three of which looked into muscular capacity and one looked into muscular activation patterns but none of the studies found strong evidence of how muscular capacity or muscular activation deficits are a risk factor for a primary non-contact ACL injury . | The aim of this systematic review was ( i ) to identify neuromuscular markers that have been predictive of a primary non-contact ACL injury , ( ii ) to assess whether proposed risk factors have been supported or refuted in the literature from cohort and case-control studies , and ( iii ) to reflect on the body of research that aims at developing field based tools to assess risk through an association with these risk factors . | Background Female athletes have a higher risk of anterior cruciate ligament injury than their male counterparts who play at similar levels in sports involving pivoting and l and ing . Hypothesis The competitive female basketball players who participated in a sports injury prevention training program would show better muscle strength and flexibility and improved biomechanical properties associated with anterior cruciate ligament injury than during the pretraining period and than posttraining parameters in a control group . Study Design Controlled laboratory study . Methods A total of 22 high school female basketball players were recruited and r and omly divided into 2 groups ( the experimental group and the control group , 11 participants each ) . The experimental group was instructed in the 6 parts of the sports injury prevention training program and performed it during the first 20 minutes of team practice for the next 8 weeks , while the control group performed their regular training program . Both groups were tested with a rebound-jump task before and after the 8-week period . A total of 21 reflective markers were placed in preassigned positions . In this controlled laboratory study , a 2-way analysis of variance ( 2 × 2 ) experimental design was used for the statistical analysis ( P < .05 ) using the experimental group and a testing session as within and between factors , respectively . Post hoc tests with Sidak correction were used when significant factor effects and /or interactions were observed . Results A comparison of the experimental group 's pretraining and posttraining results identified training effects on all strength parameters ( P = .004 to .043 ) and on knee flexion , which reflects increased flexibility ( P = .022 ) . The experimental group showed higher knee flexion angles ( P = .024 ) , greater interknee distances ( P = .004 ) , lower hamstring-quadriceps ratios ( P = .023 ) , and lower maximum knee extension torques ( P = .043 ) after training . In the control group , no statistical differences were observed between pretraining and posttraining findings ( P = .084 to .873 ) . At pretraining , no significant differences were observed between the 2 groups for any parameter ( P = .067 to .784 ) . However , a comparison of the 2 groups after training revealed that the experimental group had significantly higher knee flexion angles ( P = .023 ) , greater knee distances ( P = .005 ) , lower hamstring-quadriceps ratios ( P = .021 ) , lower maximum knee extension torques ( P = .124 ) , and higher maximum knee abduction torques ( P = .043 ) than the control group . Conclusion The sports injury prevention training program improved the strength and flexibility of the competitive female basketball players tested and biomechanical properties associated with anterior cruciate ligament injury as compared with pretraining parameters and with posttraining parameters in the control group . Clinical Relevance This injury prevention program could potentially modify the flexibility , strength , and biomechanical properties associated with ACL injury and lower the athlete 's risk for injury Background : The causes of noncontact anterior cruciate ligament injury remain an enigma . Purpose : To prospect ively evaluate risk factors for noncontact anterior cruciate ligament injuries in a large population of young athletic people . Study Design : Prospect i ve cohort study . Methods : In 1995 , 1198 new United States Military Academy cadets underwent detailed testing and many parameters were documented . During their 4-year tenure , all anterior cruciate ligament injuries that occurred were identified . Statistical analyses were used to identify the factors that may have predisposed the cadets to noncontact anterior cruciate ligament injuries . Results : Among the 895 cadets who completed the entire 4-year study , there were 24 noncontact anterior cruciate ligament tears ( 16 in men , 8 in women ) . Significant risk factors included small femoral notch width , generalized joint laxity , and , in women , higher than normal body mass index and KT-2000 arthrometer values that were 1 st and ard deviation or more above the mean . The presence of more than one of these risk factors greatly increased the relative risk of injury . All female cadets who had some combination of risk factors sustained noncontact anterior cruciate ligament injuries , indicating that some combinations of factors are especially perilous to the female knee . Conclusion : Several risk factors may predispose young athletes to noncontact anterior cruciate ligament injury CONTEXT Improving neuromuscular control of hamstrings muscles might have implication s for decreasing anterior cruciate ligament injuries in females . OBJECTIVE To examine the effects of a 6-week agility training program on quadriceps and hamstrings muscle activation , knee flexion angles , and peak vertical ground reaction force . DESIGN Prospect i ve , r and omized clinical research trial . SETTING Sports medicine research laboratory . PATIENTS OR OTHER PARTICIPANTS Thirty female intramural basketball players with no history of knee injury ( age = 21.07 + /- 2.82 years , height = 171.27 + /- 4.66 cm , mass = 66.36 + /- 7.41 kg ) . INTERVENTION(S ) Participants were assigned to an agility training group or a control group that did not participate in agility training . Participants in the agility training group trained 4 times per week for 6 weeks . MAIN OUTCOME MEASURE(S ) We used surface electromyography to assess muscle activation for the rectus femoris , vastus medialis oblique , medial hamstrings , and lateral hamstrings for 50 milliseconds before initial ground contact and while the foot was in contact with the ground during a side-step pivot maneuver . Knee flexion angles ( at initial ground contact , maximum knee flexion , knee flexion displacement ) and peak vertical ground reaction force also were assessed during this maneuver . RESULTS Participants in the training group increased medial hamstrings activation during ground contact after the 6-week agility training program . Both groups decreased their vastus medialis oblique muscle activation during ground contact . Knee flexion angles and peak vertical ground reaction force did not change for either group . CONCLUSIONS Agility training improved medial hamstrings activity in female intramural basketball players during a side-step pivot maneuver . Agility training that improves hamstrings activity might have implication s for reducing anterior cruciate ligament sprain injury associated with side-step pivots Background : Anterior cruciate ligament ( ACL ) injuries are immediately disabling , costly , take a significant amount of time to rehabilitate , and are associated with an increased risk of developing posttraumatic osteoarthritis of the knee . Specific multiplanar movement patterns of the lower extremity , such as those associated with the drop vertical jump ( DVJ ) test , have been shown to be associated with an increased risk of suffering noncontact ACL injuries . The L and ing Error Scoring System ( LESS ) has been developed as a tool that can be applied to identify individuals who display at-risk movement patterns during the DVJ . Hypothesis : An increase in LESS score is associated with an increased risk of noncontact ACL injury . Study Design : Case-control study ; Level of evidence , 3 . Methods : Over a 3-year interval , 5047 high school and college participants performed preseason DVJ tests that were recorded using commercial video cameras . All participants were followed for ACL injury during their sports season , and video data from injured participants and matched controls were then assessed with the LESS . Conditional logistic regression analysis was used to examine the association between LESS score and ACL injury risk in all participants as well as subgroups of female , male , high school , and college participants . Results : There was no relationship between the risk of suffering ACL injury and LESS score whether measured as a continuous or a categorical variable . This was the case for all participants combined ( odds ratio , 1.04 per unit increase in LESS score ; 95 % confidence interval , 0.80 - 1.35 ) as well as within each subgroup ( odds ratio range , 0.99 - 1.14 ) . Conclusion : The LESS did not predict ACL injury in our cohort of high school and college athletes CONTEXT Anterior tibial shear force and knee valgus moment increase anterior cruciate ligament ( ACL ) loading . Muscle coactivation of the quadriceps and hamstrings influences anterior tibial shear force and knee valgus moment , thus potentially influencing ACL loading and injury risk . Therefore , identifying exercises that facilitate balanced activation of the quadriceps and hamstrings might be beneficial in ACL injury rehabilitation and prevention . OBJECTIVE To quantify and compare quadriceps with hamstrings coactivation electromyographic ( EMG ) ratios during commonly used closed kinetic chain exercises . DESIGN Cross-sectional study . SETTING Research laboratory . PATIENTS OR OTHER PARTICIPANTS Twenty-seven healthy , physically active volunteers ( 12 men , 15 women ; age = 22.1 ± 3.1 years , height = 171.4 ± 10 cm , mass = 72.4 ± 16.7 kg ) . INTERVENTION(S ) Participants completed 9 separate closed chain therapeutic exercises in a r and omized order . MAIN OUTCOME MEASURE(S ) Surface electromyography quantified the activity level of the vastus medialis ( VM ) , vastus lateralis ( VL ) , medial hamstrings ( MH ) , and biceps femoris ( BF ) muscles . The quadriceps-to-hamstrings ( Q : H ) coactivation ratio was computed as the sum of average quadriceps ( VM , VL ) EMG amplitude divided by the sum of average hamstrings ( MH , BF ) EMG amplitude for each trial . We used repeated- measures analyses of variance to compare Q : H ratios and individual muscle contributions across exercises ( α = .05 ) , then used post hoc Tukey analyses . RESULTS We observed a main effect for exercise ( F(3,79 ) = 22.6 , P < .001 ) . The post hoc Tukey analyses revealed smaller Q : H ratios during the single-limb dead lift ( 2.87 ± 1.77 ) than the single-limb squat ( 5.52 ± 2.89 ) exercise . The largest Q : H ratios were observed during the transverse-lunge ( 7.78 ± 5.51 , P < .001 ) , lateral-lunge ( 9.30 ± 5.53 , P < .001 ) , and forward-lunge ( 9.70 ± 5.90 , P < .001 ) exercises . CONCLUSIONS The most balanced ( smallest ) coactivation ratios were observed during the single-limb dead-lift , lateral-hop , transverse-hop , and lateral b and -walk exercises . These exercises potentially could facilitate balanced activation in ACL rehabilitation and injury-prevention programs . They also could be used in postinjury rehabilitation programs in a safe and progressive manner BACKGROUND The purpose of this study was to determine whether current post-operative rehabilitation protocol s return the strength of the contralateral uninjured limb knee flexors and extensors after an anterior cruciate ligament ( ACL ) reconstruction to those of an uninjured control group . METHODS Subjects with a hamstring tendon ACL reconstruction ( n=12 ) were compared to an active control group ( n=30 ) . Comprehensive bilateral knee flexor and extensor isovelocity strength testing was performed ( five speeds , 5 - 95 degrees , concentric and eccentric contractions ) . FINDINGS After hamstring tendon ACL reconstruction and rehabilitation , bilateral strength normalization ( within 10 % of the contralateral limb ) is achieved by the knee extensors but not the knee flexors . When compared to the uninjured control group , large and statistically significant strength deficits were demonstrated in the knee extensors and knee flexors of both the anterior cruciate ligament reconstructed ( extensors 24.8 % ; flexors 26.8 % ) and the contralateral uninjured ( extensors 21 % ; flexors 13.5 % ) limbs . INTERPRETATION These findings suggest that improvement can be made in knee flexor rehabilitation after ACL reconstruction and limit the validity of the use of a contralateral leg as a rehabilitation endpoint or as a control in the ACL reconstructed population Objective : To determine the association of quadriceps and hamstrings strength to anterior cruciate ligament ( ACL ) injury risk in female athletes . The primary hypothesis was that there would be decreased knee flexor and increased knee extensor strength in female athletes who went on to ACL injured status ( FACL ) compared to uninjured female ( FC ) and male ( MC ) control subjects . Study Design : Matched case control . Setting : Institutional Biomechanics Laboratory . Participants : Prospect ively measured FACL ( n = 22 ) female athletes who subsequently suffered confirmed noncontact ACL ruptures ( 16 during soccer and 6 during basketball play ) were matched ( 1:4 ratio ) to female controls ( FC ; n = 88 ) using limb ( dominant or nondominant ) , pubertal status , sport , and nearest height and mass . In addition , male controls ( MC ) were matched ( 1:1 ratio ) to FACL to serve as a secondary comparative control . Assessment of Risk Factors : Isokinetic ( concentric ) knee extension/flexion strength ( 300 degrees/s ) . Results : FACL subjects had decreased hamstrings strength compared to MC ( 15 % ; 95 % CI , 1 to 27 % ; P = 0.04 ) . FC were not different from MC in hamstrings strength . Conversely , FACL subjects did not differ compared to the MC in quadriceps strength , and the FC demonstrated decreased quadriceps strength relative to MC ( 10 % ; 95 % CI , 3 to 18 % ; P = 0.01 ) . Conclusions : The results of this investigation indicate that female athletes who suffered ACL injury subsequent to strength testing had a combination of decreased hamstrings strength but not quadriceps strength compared to males . In direct contrast , female athletes who did not go on to ACL injury had decreased quadriceps strength and similar hamstrings strength compared to matched male athletes Objective : The purpose of this study was to evaluate and characterize the agonist-antagonist strength balance ( hamstring/quadriceps [ H/Q ] ratio and dynamic control ratio [ DCR ] ) about the knee specific to velocity , range of motion , and contraction type . We hypothesized that there would be systematic variation in the H/Q ratio and DCR based on knee joint angle , angular velocity , and contraction type . We also hypothesized that these ratios would be altered in the anterior cruciate ligament (ACL)-reconstructed group in favor of protecting the ACL graft ( relative knee flexor strength when strain on the ACL is the greatest ) . Design : Cross-sectional design . Setting : A tertiary care sport medicine clinic . Patients or Participants : Sixteen subjects more than 1 year after hamstring tendon ACL reconstruction were compared with 30 active uninjured control subjects . Interventions : Isokinetic strength testing was performed over 5 ° to 95 ° knee joint range of motion , 5 angular velocities ( 50 , 100 , 150 , 200 , 250 ° /s ) , for concentric and eccentric contractions . Main Outcome Measurements : Angle and velocity-matched H/Q ratio maps and DCR maps were produced for each group . Difference maps allowed quantification of the differences between the groups . Results : Angle and velocity-matched H/Q ratio maps demonstrated systematic variation based on joint angle , velocity , and contraction type for both the control ( H/Q , ~0–1.42 ; DCR , ~0–1.57 ) and the ACL-reconstructed group ( H/Q , ~0–1.33 ; DCR , ~0–1.35 ) . Difference maps demonstrate regional ( angle and velocity-specific ) alteration in the ratio between the ACL-reconstructed and control groups . Conclusions : Specific imbalances were demonstrated in the ACL-reconstructed group compared with control . In high knee flexion angles , the low H/Q ratio may represent a compromised ability of the hamstrings to stabilize the knee joint throughout the full range of motion . Near full knee extension shifts in favor of the knee flexors may represent an attempt to stabilize the knee at the angle of greatest ACL strain . These finding have implication s for graft donor site selection and postoperative rehabilitation as well as provide insight into the neuromuscular control of the knee STUDY DESIGN Controlled laboratory study . OBJECTIVES To determine whether gender differences in electromyographic ( EMG ) activity of hip-stabilizing muscles are present during single-leg l and ing . BACKGROUND Numerous factors may explain the greater rate of anterior cruciate ligament ( ACL ) injuries in female athletes . However , gender differences in hip muscle activity during dynamic events have not been well characterized . METHODS AND MEASURES Twenty-two Division I collegiate athletes ( 13 female , 9 male ) performed drop l and ings from 30.5- and 45.8-cm heights . Surface EMG was used to examine relative muscle activity from 200 milliseconds prior to initial contact to 250 milliseconds postcontact . Peak and mean values for each muscle ( gluteus maximus , gluteus medius , rectus femoris ) in each time epoch were analyzed using 2 x 2 ( group by height ) analyses of variance ( ANOVAs ) to determine significance . RESULTS Females demonstrated lower gluteus maximus peak ( mean + /- SD , 69.5 + /- 30.2 versus 98.0 + /- 33.4 percent maximum voluntary contraction [ % MVIC ] ; P= .019 ) and mean ( mean + /- SD , 37.5 + /- 15.6 versus 53.9 + /- 18.0 % MVIC ; P = .018 ) muscle activation during the postcontact phase of l and ing than males . Furthermore , females demonstrated greater peak rectus femoris activity during the precontact phase ( mean + /- SD , 33.6 + /- 18.5 versus 18.7 + /- 8.2 % MVIC ; P = .029 ) . A positive effect of drop height on relative activity of all muscles was observed during both phases ( P<.05 ) . CONCLUSIONS Females utilize different muscular activation patterns compared to males ( ie , decreased gluteus maximus and increased rectus femoris muscle activity ) during l and ing maneuvers . Decreased hip muscle activity and increased quadriceps activity may be important contributors to the increased susceptibility of female athletes to noncontact ACL injuries Background A high percentage of female athletes who sustain an anterior cruciate ligament ( ACL ) rupture suffer serious long-term consequences such as osteoarthritis and disability . Thus , identification of risk factors has high clinical relevance in the prevention of ACL rupture . Hypothesis Noninjured athletes with low knee flexor electromyography ( EMG ) preactivity and high knee extensor EMG preactivity during sidecutting are at increased risk of future ACL rupture . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods Fifty-five elite female athletes ( team h and ball and soccer ) aged 24 ± 5 years with no history of ACL injury were tested for EMG preactivity of vastus lateralis and medialis , rectus femoris , semitendinosus , and biceps femoris during a st and ardized side-cutting maneuver . The incidence of ACL ruptures was registered in the following 2 match seasons . Results During the subsequent 2 match seasons , 5 athletes sustained a confirmed noncontact ACL rupture . Before injury , all 5 players displayed a neuromuscular pattern that differed from the noninjured players , characterized by reduced EMG preactivity for the semitendinosus ( ST ) and elevated EMG preactivity for the vastus lateralis ( VL ) ( P < .01 ) . On the basis of these findings , a high-risk zone was defined as one st and ard deviation above the mean VL-ST difference . In our population , 5 of 10 subjects with a VL-ST difference in this zone sustained an ACL injury during the study period . Conclusion In the present study , currently noninjured female athletes with reduced EMG preactivity of the ST and increased EMG preactivity of the VL during side cutting were at increased risk of future noncontact ACL rupture . Our data indicate that a high-risk zone can be used to identify noninjured players at high risk of future ACL rupture . Consequently , individual preventive efforts can be introduced in time . However , large prospect i ve studies are needed to confirm this finding before definitive clinical recommendations can be made Context : Injuries to the anterior cruciate ligament ( ACL ) of the knee are immediately debilitating and can cause long-term consequences , including the early onset of osteoarthritis . It is important to have a comprehensive underst and ing of all possible risk factors for ACL injury to identify individuals who are at risk for future injuries and to provide an appropriate level of counseling and programs for prevention . Objective : This review , part 1 of a 2-part series , highlights what is known and still unknown regarding anatomic and neuromuscular risk factors for injury to the ACL from the current peer- review ed literature . Data Sources : Studies were identified from MEDLINE ( 1951–March 2011 ) using the MeSH terms anterior cruciate ligament , knee injury , and risk factors . The bibliographies of relevant articles and review s were cross-referenced to complete the search . Study Selection : Prognostic studies that utilized the case-control and prospect i ve cohort study design s to evaluate risk factors for ACL injury were included in this review . Results : A total of 50 case-control and prospect i ve cohort articles were included in the review , and 30 of these studies focused on neuromuscular and anatomic risk factors . Conclusions : Several anatomic and neuromuscular risk factors are associated with increased risk of suffering ACL injury — such as female sex and specific measures of bony geometry of the knee joint , including decreased intercondylar femoral notch size , decreased depth of concavity of the medial tibial plateau , increased slope of the tibial plateaus , and increased anterior-posterior knee laxity . These risk factors most likely act in combination to influence the risk of ACL injury ; however , multivariate risk models that consider all the aforementioned risk factors in combination have not been established to explore this interaction |
11,739 | 20,495,832 | Patients receiving PAL presented less nausea and vomiting regardless of the use of corticoids .
Conclusion PAL was more effective than the other 5-HT3R in preventing acute and delayed CINV in patients receiving MoHE treatments , regardless of the use of concomitant corticosteroids | Objective The objective of this work is to perform a systematic review and meta- analysis of all r and omized controlled trials comparing a single intravenous dose of palonosetron ( PAL ) 0.25 mg with other 5-HT3R in patients receiving moderately or highly emetogenic ( MoHE ) chemotherapy . | BACKGROUND This pivotal phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting ( CINV ) following highly emetogenic chemotherapy ( HEC ) . PATIENTS AND METHODS Patients were r and omized to a single intravenous dose of palonosetron 0.25 mg or 0.75 mg , or ondansetron 32 mg prior to HEC . Dexamethasone pre-treatment ( with stratification ) was used at investigator discretion . The primary efficacy endpoint was the proportion of patients with complete response ( CR ) during the first 24 h post-chemotherapy ( acute phase ) . RESULTS In the intent-to-treat analysis ( n = 667 ) , palonosetron 0.25 mg and 0.75 mg were at least as effective as ondansetron in preventing acute CINV ( 59.2 % , 65.5 % , and 57.0 % CR rates , respectively ) ; CR rates were slightly higher with palonosetron than ondansetron during the delayed ( 24 - 120 h ) and overall ( 0 - 120 h ) phases . Two thirds of patients ( n = 447 ) received concomitant dexamethasone . Patients pre-treated with palonosetron 0.25 mg plus dexamethasone had significantly higher CR rates than those receiving ondansetron plus dexamethasone during the delayed ( 42.0 % versus 28.6 % ) and overall ( 40.7 % versus 25.2 % ) phases . Palonosetron and ondansetron were well tolerated . CONCLUSIONS Single-dose palonosetron was as effective as ondansetron in preventing acute CINV following HEC , and with dexamethasone pre-treatment , its effectiveness was significantly increased over ondansetron throughout the 5-day post-chemotherapy period Although elderly patients have been reported to be less prone to chemotherapy-induced nausea and vomiting ( CINV ) , its management is complicated by a high frequency of comorbidities and polypharmacy and an increased risk of dehydration and impaired cognition . The comparative efficacy and tolerability of palonosetron and ondansetron/dolasetron were assessed in a retrospective post hoc analysis using pooled data from 171 elderly patients ( age > or = 65 years ) with cancer enrolled in two r and omized , double-blind , phase III clinical studies comparing single IV doses of these antiemetic agents given prior to receipt of moderately emetogenic chemotherapy . The complete response rate during the postchemotherapy period was significantly higher in the palonosetron group than in the ondansetron/dolasetron group in the 5 days following chemotherapy . The proportion of patients who were nausea-free on the problematic days 2 and 3 post chemotherapy and the time to treatment failure also significantly favored palonosetron . In this population that included patients with pre-existing comorbidities , palonosetron was well tolerated , with similar or fewer adverse events than the comparators . Comparisons in electrocardiogram parameters revealed that the mean postdose change from baseline in QTc interval was 3 ms for palonosetron 0.25 mg and 5 ms for ondansetron/dolasetron . In this retrospective analysis , palonosetron provided superior efficacy to ondansetron/dolasetron for the treatment of CINV in elderly patients receiving moderately emetogenic chemotherapy . Based on its safety profile , antiemetic control , and convenient dosing , palonosetron can be recommended for use in elderly patients with cancer receiving emetogenic chemotherapy BACKGROUND The localization of substance P in brain-stem regions associated with vomiting , and the results of studies in ferrets , led us to postulate that a neurokinin-1-receptor antagonist would be an antiemetic in patients receiving anticancer chemotherapy . METHODS In a multicenter , double-blind , placebo-controlled trial involving 159 patients who had not previously received cisplatin , we evaluated the prevention of acute emesis ( occurring within 24 hours ) and delayed emesis ( on days 2 to 5 ) after a single dose of cisplatin therapy ( 70 mg or more per square meter of body-surface area ) . Before receiving cisplatin , all the patients received granisetron ( 10 microg per kilogram of body weight intravenously ) and dexamethasone ( 20 mg orally ) . The patients were r and omly assigned to one of three treatments in addition to granisetron and dexamethasone : 400 mg of an oral trisubstituted morpholine acetal ( also known as L-754,030 ) before cisplatin and 300 mg on days 2 to 5 ( group 1 ) , 400 mg of L-754,030 before cisplatin and placebo on days 2 to 5 ( group 2 ) , or placebo before cisplatin and placebo on days 2 to 5 ( group 3 ) . Additional medication was available at any time to treat occurrences of vomiting or nausea . RESULTS In the acute-emesis phase , 93 percent of the patients in groups 1 and 2 combined and 67 percent of those in group 3 had no vomiting ( P<0.001 ) . In the delayed-emesis phase , 82 percent of the patients in group 1 , 78 percent of those in group 2 , and 33 percent of those in group 3 had no vomiting ( P<0.001 for the comparison between group 1 or 2 and group 3 ) . The median nausea score in the delayed-emesis phase was significantly lower in group 1 than in group 3 ( P=0.003 ) . No serious adverse events were attributed to L-754,030 . CONCLUSIONS The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin . Moreover , combining L-754,030 with granisetron plus dexamethasone improves the prevention of acute emesis Palonosetron , a highly selective and potent 5‐HT3 receptor antagonist with a strong binding affinity and a long plasma elimination half‐life ( approximately 40 hours ) , has shown efficacy in Phase II trials in preventing chemotherapy‐induced nausea and vomiting ( CINV ) result ing from highly emetogenic chemotherapy . The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that BACKGROUND Although currently available 5-hydroxytryptamine type 3 receptor ( 5-HT3 ) antagonists are effective , not all patients receiving these agents achieve adequate control of chemotherapy-induced nausea and vomiting ( CINV ) . Palonosetron , a potent and highly selective 5-HT3 antagonist with a strong affinity for 5-HT3 and a prolonged plasma elimination half-life , may provide a longer duration of action than other approved agents . PATIENTS AND METHODS One hundred and sixty-one patients were r and omly assigned to receive a single intravenous bolus dose of palonosetron ( 0.3 , 1 , 3 , 10 , 30 or 90 microg/kg ) before administration of highly emetogenic chemotherapy , with no pretreatment with corticosteroids . RESULTS The four highest doses of palonosetron were similarly effective during the first 24 h , producing clearly higher complete response ( CR ) ( no emesis , no rescue medication ) rates in the 3 , 10 , 30 and 90 microg/kg groups ( 46 % , 40 % , 50 % and 46 % , respectively ) than in the 0.3 - 1 microg/kg group ( 24 % ) of evaluable patients ( n = 148 ) . The 3 microg/kg dose was identified as the lowest effective dose . A single dose of palonosetron showed prolonged efficacy in preventing delayed emesis , with approximately one-third of patients who received palonosetron 10 or 30 microg/kg maintaining a CR throughout the 7-day period following chemotherapy administration . Dose-proportional increases in pharmacokinetic parameters and a long plasma half-life ( 43.7 - 128 h ) were observed . Palonosetron was well-tolerated , with no dose-response effect evident for the incidence or intensity of adverse events . CONCLUSIONS Palonosetron is an effective and well-tolerated agent for the prevention of CINV following highly emetogenic chemotherapy , with 3 and 10 microg/kg identified as the lowest effective palonosetron doses This study evaluated the safety and pharmacokinetics of consecutive multiple-day dosing of palonosetron . Sixteen healthy subjects received an intravenous bolus dose of palonosetron 0.25 mg ( n = 12 ) or placebo ( n = 4 ) daily for 3 consecutive days . Safety was evaluated throughout the study . Serial plasma sample s were collected on days 1 and 3 for pharmacokinetic determinations . Three days of dosing with palonosetron 0.25 mg was safe and well tolerated . There were no clinical ly significant changes from baseline in laboratory values , vital signs , physical examinations , or electrocardiogram intervals . Plasma palonosetron concentrations declined in a biphasic manner , measurable up to 168 hours after dosing on day 3 . Mean terminal phase elimination half-life after day 3 dosing was 42.8 hours . The 2.1-fold accumulation of palonosetron in plasma following 3 daily doses was predictable based on elimination half-life of approximately 40 hours , and the maximum plasma concentration remained below the maximum plasma concentration previously observed after a single , well-tolerated 0.75 mg intravenous bolus dose of palonosetron Purpose This clinical trial was conducted to evaluate the efficacy and safety of Palonosetron in preventing chemotherapy-induced vomiting ( CIV ) among the Chinese cancer patients . Patients and methods Two hundred and forty patients were scheduled to be enrolled and r and omized to receive a single intravenous dose of palonosetron 0.25 mg , or granisetron 3 mg , 30 min before receiving highly emetogenic chemotherapy . The primary efficacy endpoint was the complete response ( CR ) rate for acute CIV ( during the 0–24-h interval after chemotherapy ) . Secondary endpoints included the CR rates for delayed CIV ( more than 24 h after chemotherapy ) . Results Two hundred and eight patients were accrued and received study medication . CR rates for acute CIV were 82.69 % for palonosetron and 72.12 % for granisetron , which demonstrated that palonosetron was not inferior to granisetron in preventing acute CIV . Comparisons of CR rates for delayed CIV yielded no statistical difference between palonosetron and granisetron groups and did not reveal non-inferiority of palonosetron to granisetron . Adverse events were mostly mild to moderate , with quite low rates among the two groups . Conclusions A single dose ( 0.25 mg ) of palonosetron is not inferior to a single dose ( 3 mg ) of granisetron in preventing CIV and possesses an acceptable safety profile in the Chinese population ABSTRACT Background : Palonosetron is a second-generation 5-HT3 receptor antagonist with a prolonged duration of action and higher receptor binding affinity than first-generation agents ( ondansetron , granisetron , and dolasetron ) . Aprepitant is a selective antagonist of substance P/neurokinin 1 that augments the benefit of 5-HT3 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting . Methods : This r and omized , open-label , two-way , crossover trial was design ed to evaluate the effect of oral aprepitant on the pharmacokinetics and safety of a single intravenous ( IV ) dose of palonosetron in 12 healthy subjects . Treatment A consisted of a single IV bolus dose of palonosetron 0.25 mg on day 1 . Treatment B added oral aprepitant 125 mg on day 1 ( 30 minutes prior to palonosetron ) and 80 mg on days 2 and 3 . Blood for pharmacokinetic evaluations was collected through 168 hours after palonosetron administration on days 1 and 15 ; safety was monitored through day 22 . Results : Mean plasma concentration-time plots for palonosetron were virtually identical for palonosetron administered alone or with concomitant aprepitant . The ratio of geometric least-square mean values ( with : without aprepitant ) for Cmax was 98.6 % ( 90 % confidence interval [ CI ] : 61.8–157 % ) , and for AUC0–∞ the ratio was 101 % ( 90 % CI : 85.6–119 % ) . With and without aprepitant coadministration , respectively , mean plasma elimination half-life was 40 hours and 43 hours ( difference : –3.0 hours ; p = 0.348 ) , mean total body clearance was 130 mL/min and 136 mL/min ( difference : –5.6 mL/min ; p = 0.735 ) , and mean volume of distribution at steady-state was 410.9 L and 442.3 L ( difference : –31.4 L ; p = 0.463 ) . Palonosetron alone and the palonosetron/aprepitant regimen were well tolerated . Conclusion : These results indicate no significant differences in pharmacokinetic parameters for palonosetron between the two treatments , and suggest that palonosetron can be safely coadministered with aprepitant with no alterations in the expected safety profile and no dosage adjustment necessary 9627 Background : APF530 is a polymeric formulation of granisetron providing sustained drug release over 5 days . Two doses ( 5 and 10 mg ) of subcutaneous APF530 were evaluated in comparison to 0.25 mg intravenous palonosetron . Efficacy was evaluated in acute ( 0 - 24 hrs ) and delayed ( 24 - 120 hrs ) CINV among patients receiving moderate ( MEC ) or highly ( HEC ) emetogenic chemotherapy . METHODS R and omized , blinded patients ( n=1,395 ) were stratified into MEC or HEC according to Hesketh et al 1999 , and assigned to receive either dose of APF530 or palonosetron . Dexamethasone use was st and ardized based on the emetogenic strata . Patient diaries recorded emetic episodes , nausea and rescue medications over a 5-day period . Primary endpoint was Complete Response ( CR ) , defined as no emetic episodes and no rescue medication . Non-inferiority to palonosetron was declared if the lower bound of the CI for the difference was above -15 % . RESULTS APF530 was well tolerated . Adverse events were consistent with those previously reported for granisetron . For APF530 Tmax was observed about 24 hrs with sustained levels over 120 hrs . For MEC acute phase CR rates of 74.8 % ( n=214 ) , 76.9 % ( n=212 ) and 75.0 % ( n=208 ) were observed for 5 mg , 10 mg APF530 and palonosetron , respectively . Delayed phase CR rates of 51.4 % , 59.0 % and 57.7 % were observed for 5 mg , 10 mg APF530 and palonosetron , respectively . For HEC acute phase CR rates of 77.7 % ( n=229 ) , 81.3 % ( n=240 ) and 80.7 % ( n=238 ) were observed for 5 mg , 10 mg APF530 and palonosetron , respectively . Delayed phase CR rates of 64.6 % , 68.3 % and 66.4 % were observed for 5 mg , 10 mg APF530 and palonosetron , respectively . Efficacy was maintained with APF530 over multiple cycles ( up to 4 ) . CONCLUSIONS Both doses of APF530 were non-inferior to palonosetron with respect to CR during the acute phase following MEC and HEC . Only the higher dose of APF530 ( 10 mg granisetron ) was non-inferior to palonosetron during the delayed phase of MEC . Both doses of APF530 were comparable to the CR rates of palonosetron during the delayed phase of HEC . [ Table : see text ] Palonosetron ( Aloxi , Onicit ) is a selective 5-HT(3 ) receptor antagonist recently approved by the Food and Drug Administration for the prevention of acute and delayed chemotherapy-induced nausea and vomiting . This study was performed to determine the pharmacokinetics and assess the safety and tolerability of intravenous ( IV ) palonosetron in healthy U.S. and Japanese subjects . Subjects were administered a single IV dose of palonosetron , ranging from 0.3 to 90 microg/kg in either of two r and omized , double-blind , placebo-controlled , ascending-dose studies ( n = 80 and n = 32 , respectively ) . Serial blood sample s were obtained in both studies to evaluate the pharmacokinetics of palonosetron and its N-oxide metabolite , M9 . Intravenous palonosetron was well tolerated across a wide range of doses in both studies . The incidence and severity of adverse events ( AEs ) were similar between subjects receiving palonosetron and those receiving placebo , with no dose-dependent incidences . The most frequently reported AEs were headache , transient elevation of liver enzymes , and constipation . Systemic exposure ( AUC and C(max ) ) for palonosetron generally increased with increasing dose . Mean total body clearance , elimination half-life , and apparent volume of distribution ranged from 1.11 to 3.90 mL/min/kg , 33.7 to 54.1 hours , and 3.85 to 12.6 L/kg , respectively , in U.S. subjects and from 2.58 to 3.50 mL/min/kg , 30.8 to 36.8 hours , and 6.96 to 9.85 L/kg , respectively , in Japanese subjects . The pharmacokinetics of palonosetron appeared to be independent of dose , with no dose adjustment required in Japanese subjects . The plasma concentration profile of palonosetron , as represented by a half-life of approximately 40 hours , may provide a clinical advantage over other 5-HT(3 ) antagonists Aim of the present phase II non-r and omized study was to verify whether palonosetron might be able to prevent acute and especially delayed CINV for either HEC or MEC , starting from the second chemotherapy cycle , in patients who had failed to respond to a different antiemetic 5-HT(3 ) antagonist during the first cycle . Stratification factor was age < 65 years vs. > or = 65 years of patients included . Forty-seven cancer patients ( 23 elderly and 24 non-elderly ) scheduled to receive HEC or MEC regimens who had experienced CINV grade 3 - 4 during the first chemotherapy course and for whom the same course of chemotherapy regimen was further scheduled were enrolled . Complete response ( CR ) and complete control ( CC ) rates for the acute , delayed and overall phases of CINV were not significantly different between elderly and non-elderly patients . Palonosetron was safe : only grade 1 - 2 toxicities were observed with a peak of 12.9 % for asthenia with no significant difference between elderly and non-elderly patients . In conclusion , single dose palonosetron ( 250 microg ) should be considered a safe and effective second generation 5-HT(3 ) antagonist in the prevention of nausea and vomiting induced by HEC or MEC , irrespective of patients ' age BACKGROUND Although all first-generation 5-HT(3 ) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting ( CINV ) , effective prevention of delayed CINV has not yet been achieved . This study compared the efficacy and tolerability of palonosetron , a novel , second-generation 5-HT(3 ) receptor antagonist , with ondansetron . PATIENTS AND METHODS In this multicenter , r and omized , double-blind , stratified , phase III study , 570 adult cancer patients were r and omized to receive a single i.v . dose of palonosetron 0.25 mg , palonosetron 0.75 mg or ondansetron 32 mg , each administered 30 min before initiation of moderately emetogenic chemotherapy . The primary end point was the proportion of patients with no emetic episodes and no rescue medication [ complete response ( CR ) ] during the 24 h after chemotherapy administration ( acute period ) . Secondary end points included efficacy in treatment of delayed CINV ( < /=5 days post-chemotherapy ) and overall tolerability . RESULTS 563 patients were evaluable for efficacy . CR rates were significantly higher ( P < 0.01 ) for palonosetron 0.25 mg than ondansetron during the acute ( 0 - 24 h ) ( 81.0 % versus 68.6 % , respectively ) , delayed ( 24 - 120 h ) ( 74.1 % versus 55.1 % ) and overall ( 0 - 120 h ) ( 69.3 % versus 50.3 % ) periods . CR rates achieved with palonosetron 0.75 mg were numerically higher but not statistically different from ondansetron during all three time intervals . Both treatments were well tolerated . CONCLUSIONS A single i.v . dose of palonosetron 0.25 mg was significantly superior to i.v . ondansetron 32 mg in the prevention of acute and delayed CINV BACKGROUND Palonosetron is a second-generation 5-hydroxytryptamine 3 ( 5-HT(3))-receptor antagonist that has shown better efficacy than ondansetron and dolasetron in preventing chemotherapy-induced nausea and vomiting ( CINV ) in patients receiving moderately emetogenic chemotherapy , and similar efficacy to ondansetron in preventing CINV in patients receiving highly emetogenic chemotherapy . In this phase III , multicentre , r and omised , double-blind , double-dummy , stratified , parallel-group , active-comparator trial , we assessed the efficacy and safety of palonosetron versus granisetron for chemotherapy-induced nausea and vomiting , both of which were administered with dexamethasone in patients receiving highly emetogenic chemotherapy . METHODS Between July 5 , 2006 , and May 31 , 2007 , 1143 patients with cancer who were receiving highly emetogenic chemotherapy ( ie , cisplatin , or an anthracycline and cyclophosphamide combination [ AC/EC ] ) were recruited from 75 institutions in Japan , and r and omly assigned to either single-dose palonosetron ( 0.75 mg ) , or granisetron ( 40 microg/kg ) 30 min before chemotherapy on day 1 , both with dexamethasone ( 16 mg intravenously ) on day 1 followed by additional doses ( 8 mg intravenously for patients receiving cisplatin or 4 mg orally for patients receiving AC/EC ) on days 2 and 3 . A non-deterministic minimisation method with a stochastic-biased coin was applied to the r and omisation of patients . Covariates known to effect emetic risk , such as sex , age , and type of highly emetogenic chemotherapy , were used as stratification factors of minimisation to ensure balance between the treatment groups . Primary endpoints were the proportion of patients with a complete response ( defined as no emetic episodes and no rescue medication ) during the acute phase ( 0 - 24 h postchemotherapy ; non-inferiority comparison with granisetron ) and the proportion of patients with a complete response during the delayed phase ( 24 - 120 h postchemotherapy ; superiority comparison with granisetron ) . The non-inferiority margin was predefined in the study protocol as a 10 % difference between groups in the proportion of patients with complete response . The palonosetron dose of 0.75 mg was chosen on the basis of two dose-determining trials in Japanese patients . All patients who received study treatment and highly emetogenic chemotherapy were included in the efficacy analyses ( modified intention to treat ) . This trial is registered with Clinical Trials.gov , number NCT00359567 . FINDINGS 1114 patients were included in the efficacy analyses : 555 patients in the palonosetron group and 559 patients in the granisetron group . 418 of 555 patients ( 75.3 % ) in the palonosetron group had complete response during the acute phase compared with 410 of 559 patients ( 73.3 % ) in the granisetron group ( mean difference 2.9 % [ 95 % CI -2.70 to 7.27 ] ) . During the delayed phase , 315 of 555 patients ( 56.8 % ) had complete response in the palonosetron group compared with 249 of 559 patients ( 44.5 % ) in the granisetron group ( p<0.0001 ) . The main treatment-related adverse events were constipation ( 97 of 557 patients [ 17.4 % ] in the palonosetron group vs 88 of 562 [ 15.7 % ] in the granisetron group ) and raised concentrations of serum aminotransferases ( aspartate aminotransferase : 24 of 557 [ 4.3 % ] vs 34 of 562 [ 6.0 % ] ; alanine aminotransferase : 16 of 557 [ 2.9 % ] vs 33 of 562 [ 5.9 % ] ) ; no grade 4 main treatment-related adverse events were reported . INTERPRETATION When administered with dexamethasone before highly emetogenic chemotherapy , palonosetron exerts efficacy against chemotherapy-induced nausea and vomiting which is non-inferior to that of granisetron in the acute phase and better than that of granisetron in the delayed phase , with a comparable safety profile for the two treatments . FUNDING Taiho Pharmaceutical ( Tokyo , Japan ) BACKGROUND Emesis and nausea are common adverse effects of chemotherapy . Consequences include dehydration , acute renal failure , esophageal rupture , electrolyte imbalance and undernutrition , among others . First-generation 5-HT3 antagonists significantly reduce these symptoms but are expensive and require administration every 8 - 12h . Palonosetron , a second generation 5-HT3 antagonist has proven better results in adult population s. Other benefits include a one-dose administration with effect for up to 7 days and a lower treatment cost . No clinical studies have evaluated the safety and efficacy of palonosetron in children . METHODS Prior to every course , patients were r and omized to receive palonosetron or ondansetron . Patients or guardians recorded the number of emetic events and the intensity of nausea over a 7-day period . They also reported any possible adverse effects . Statistical analysis included chi(2 ) test , relative risk , and Student 's t test . RESULTS Fifty courses were analyzed for each group . There was a significant reduction in emesis on the first 3 days and in the intensity of nausea in the first four days in the palonosetron group . There was an increased risk of presenting emesis and nausea in the acute phase when treated with ondansetron . No adverse effects were reported . The cost of treatment was also reduced when using palonosetron . CONCLUSIONS Palonosetron is a safe and effective antiemetic treatment in children , as well as being cost effective BACKGROUND Despite widespread use of short-acting antagonists for the 5-hydroxytryptamine ( 5-HT ) receptor , about 50 % of patients given moderately emetogenic chemotherapy have delayed nausea . We aim ed to assess whether a 5-HT-receptor antagonist was more effective than was prochlorperazine for control of delayed nausea and delayed vomiting caused by doxorubicin . METHODS 691 patients who previously had not had chemotherapy and who were scheduled to receive doxorubicin were given a short-acting 5-HT-receptor antagonist and dexamethasone before doxorubicin ( day 1 ) , and were r and omly assigned to one of three regimens for days 2 and 3 : 10 mg prochlorperazine taken orally every 8 h ; any first-generation 5-HT-receptor antagonist ( except palonosetron ) taken as st and ard dose intravenously or orally ; or 10 mg prochlorperazine taken as needed . Nausea and vomiting were assessed by use of a home record . The primary endpoint was mean severity of delayed nausea . The secondary endpoint was quality of life . Analyses were done by intention to treat . FINDINGS 519 ( 77 % ) of the 671 evaluable patients had delayed nausea , with a mean severity of 3.33 ( 95 % CI 3.22 - 3.44 ) . 161 ( 71 % ) of 226 patients assigned prochlorperazine every 8 h reported delayed nausea ( mean severity 3.37 [ 3.16 - 3.58 ] ) , as did 179 ( 79 % ) of 226 patients assigned 5-HT-receptor antagonists ( 3.29 [ 3.09 - 3.48 ] ) and 179 ( 82 % ) of 219 patients assigned prochlorperazine as needed ( 3.33 [ 3.15 - 3.50 ] ) ; groups did not differ in mean severity ( p=0.853 , one-way ANOVA ) . Patients allocated prochlorperazine every 8 h had less delayed nausea than did those allocated 5-HT-receptor antagonists ( p=0.05 , t test ) and those allocated prochlorperazine as needed ( p=0.009 , t test ) . INTERPRETATION Short-acting 5-HT-receptor antagonists are no better than is prochlorperazine in control of delayed nausea caused by doxorubicin . Although fewer patients taking prochlorperazine report delayed nausea , the proportion was unacceptably high 8051 Background : Control of acute chemotherapy-induced nausea and vomiting ( A-CINV ) is a positive predictor of control of D-CINV . First-generation 5-HT3 receptor antagonists ( RA ) are highly effective in preventing A-CINV but less so in preventing D-CINV . PALO is a pharmacologically distinct 5-HT3 RA with a 30 + fold higher binding affinity , a 40 hr plasma half-life , and has greater efficacy than ondansetron ( OND ) and dolasetron ( DOL ) in preventing both A-CINV and D-CINV in patients receiving moderately emetogenic chemotherapy ( Aapro , ASCO ' 03 , Rubenstein ASCO ' 03 ) . METHODS Establishing whether this efficacy benefit in control of D-CINV is strictly a carryover effect from better control of A-CINV was analyzed using pooled data from 2 identically design ed phase III trials where 754 patients received either a single IV dose of 0.25 mg PALO or 32 mg OND ( study 1 ) or 100 mg DOL ( study 2 ) . Two methods for evaluating the carryover effect were conducted : evaluating control of D-CINV in all patients with or without A-CINV ( Grunberg , ASCO ' 03 ) and hierarchical models evaluating treatment effects adjusting for risk factors over time . RESULTS Of the 500 pts across all groups with no A-CINV , 376 ( 75 % ) had no D-CINV . Of these pts controlled for A-CINV , more pts ( 218/272 ; 80 % ) receiving PALO had no D-CINV compared with those receiving OND or DOL ( 158/228 ; 69 % ) [ P = 0.005 ] . A similar benefit was also seen among the 254 pts who did have A-CINV . 24/106 ( 23 % ) receiving PALO had no D-CINV while 18/148 ( 12 % ) receiving OND or DOL had no D-CINV [ P = 0.027 ] . CONCLUSIONS The same magnitude of improved prevention of D-CINV with PALO in patients with or without A-CINV provides evidence that this greater efficacy in preventing D-CINV is a true pharmacologic effect rather than carryover from better prevention of A-CINV . Complete results utilizing a hierarchical ( r and om-effects ) model accounting for risk factors and trial heterogeneity will also be presented . [ Table : see text ] PURPOSE To up date the 1999 American Society of Clinical Oncology guideline for antiemetics in oncology . UP DATE METHODOLOGY The Up date Committee completed a review and analysis of data published from 1998 thru February 2006 . The literature review focused on published r and omized controlled trials , and systematic review s and meta-analyses of published phase II and phase III r and omized controlled trials . RECOMMENDATIONS The three-drug combination of a 5-hydroxytryptamine-3 ( 5-HT(3 ) ) serotonin receptor antagonist , dexamethasone , and aprepitant is recommended before chemotherapy of high emetic risk . For persons receiving chemotherapy of high emetic risk , there is no group of patients for whom agents of lower therapeutic index are appropriate first-choice antiemetics . These agents should be reserved for patients intolerant of or refractory to 5-HT3 serotonin receptor antagonists , neurokinin-1 receptor antagonists , and dexamethasone . The three-drug combination of a 5-HT3 receptor serotonin antagonist , dexamethasone , and aprepitant is recommended for patients receiving an anthracycline and cyclophosphamide . For patients receiving other chemotherapy of moderate emetic risk , the Up date Committee continues to recommend the two-drug combination of a 5-HT3 receptor serotonin antagonist and dexamethasone . In all patients receiving cisplatin and all other agents of high emetic risk , the two-drug combination of dexamethasone and aprepitant is recommended for the prevention of delayed emesis . The Up date Committee no longer recommends the combination of a 5-HT3 serotonin receptor antagonist and dexamethasone for the prevention of delayed emesis after chemotherapeutic agents of high emetic risk . CONCLUSION The Up date Committee recommends that clinicians administer antiemetics while considering patients ' emetic risk categories and other characteristics |
11,740 | 27,809,960 | Conclusions Transactional sex is associated with HIV among women , whereas findings for men were inconclusive . | Introduction Young women aged 15 to 24 years in sub-Saharan Africa continue to be disproportionately affected by HIV .
A growing number of studies have suggested that the practice of transactional sex may in part explain women 's heightened risk , but evidence on the association between transactional sex and HIV has not yet been synthesized .
We set out to systematic ally review studies that assess the relationship between transactional sex and HIV among men and women in sub-Saharan Africa and to summarize the findings through a meta- analysis . | BACKGROUND This paper aims to describe factors associated with HIV sero-status in young , rural South African women and the relationship between intimate partner violence ( IPV ) and HIV . METHODS A total of 1295 sexually active female volunteers , aged 15 - 26 , from 70 villages were recruited to participate in a cluster r and omized controlled trial of an HIV behavioural intervention . The main measures were HIV sero-status , and IPV and sexual practice s measured using a question naire administered during baseline interviews . RESULTS About 12.4 % of women had HIV and 26.6 % had experienced more than one episode of physical or sexual IPV . After adjusting for age , HIV infection was associated with having three or more past year partners [ odds ratio ( OR ) 2.39 ; 95 % confidence interval ( 95 % CI ) 1.48 - 3.85 ] , sex in past 3 months ( OR 3.33 ; 95 % CI 1.87 - 5.94 ) , a partner three or more years older ( OR 1.69 ; 95 % CI 1.16 - 2.48 ) , and a more educated partner ( OR 1.91 ; 95 % CI 1.30 - 2.78 ) . IPV was associated with HIV in two-way analyses ( OR 1.56 ; 95 % CI 1.08 - 2.23 ) , but the effect was non-significant after adjusting for HIV risk behaviours . The experience of IPV was strongly associated with past year partner numbers , time of last sex , and partner 's education ; it was also marginally associated with partner age difference . Adverse experiences in childhood , including sexual abuse , increased the likelihood of having more past year partners ( OR 1.43 ; 95 % CI 1.21 - 1.69 ) . CONCLUSIONS IPV was strongly associated with most of the identified HIV risk factors . Our findings provide further evidence of links between IPV and HIV among women and the importance of joint prevention Objective To assess the impact of Stepping Stones , a HIV prevention programme , on incidence of HIV and herpes simplex type 2 ( HSV-2 ) and sexual behaviour . Design Cluster r and omised controlled trial . Setting 70 villages ( clusters ) in the Eastern Cape province of South Africa . Participants 1360 men and 1416 women aged 15 - 26 years , who were mostly attending schools . Intervention Stepping Stones , a 50 hour programme , aims to improve sexual health by using participatory learning approaches to build knowledge , risk awareness , and communication skills and to stimulate critical reflection . Villages were r and omised to receive either this or a three hour intervention on HIV and safer sex . Interviewers administered question naires at baseline and 12 and 24 months and blood was tested for HIV and HSV-2 . Main outcome measures Primary outcome measure : incidence of HIV . Other outcomes : incidence of HSV-2 , unwanted pregnancy , reported sexual practice s , depression , and substance misuse . Results There was no evidence that Stepping Stones lowered the incidence of HIV ( adjusted incidence rate ratio 0.95 , 95 % confidence interval 0.67 to 1.35 ) . The programme was associated with a reduction of about 33 % in the incidence of HSV-2 ( 0.67 , 0.46 to 0.97 ; P=0.036)—that is , Stepping Stones reduced the number of new HSV-2 infections over a two year period by 34.9 ( 1.6 to 68.2 ) per 1000 people exposed . Stepping Stones significantly improved a number of reported risk behaviours in men , with a lower proportion of men reporting perpetration of intimate partner violence across two years of follow-up and less transactional sex and problem drinking at 12 months . In women desired behaviour changes were not reported and those in the Stepping Stones programme reported more transactional sex at 12 months . Conclusion Stepping Stones did not reduce incidence of HIV but had an impact on several risk factors for HIV — notably , HSV-2 and perpetration of intimate partner violence . Trial Registration Clinical Trials NCT00332878 OBJECTIVE To describe factors associated with HIV infection in men aged 15 - 26 years . SETTING Rural Eastern Cape Province , South Africa . SAMPLE A total of 1277 sexually experienced Xhosa male volunteers from 70 villages participating in a cluster r and omized controlled trial of an HIV behavioural intervention . Xhosas circumcise during manhood initiation rituals . DESIGN Cross-sectional , analysis of the study 's baseline interviews . MAIN MEASURE HIV sero-status , sexual practice s measured with an interviewer-administered question naire . RESULTS About 2 % of the men were HIV positive . A logistic regression model showed HIV positivity to be associated with age ( OR 1.55 ; 95%CI 1.22 - 1.95 ) , having made a woman pregnant ( OR 2.93 ; 95 % CI 1.28 - 6.68 ) , having been circumcised ( OR 0.40 ; 95 % CI 0.16 - 0.98 ) , and having had sex with a man ( OR 3.61 ; 95 % CI 1.0 - 13.0 ) . CONCLUSIONS Our findings provide further evidence to suggest that circumcision is protective . There was much heterosexual risk taking among men but only pregnancy ( with its association with sexual frequency ) predicted HIV sero-positivity . Although relatively rare , same-sex sexual experiences were a risk factor . Male-male sexual contact is rarely assessed in HIV research in Africa and almost never addressed in general HIV prevention programming . Our findings suggest that it should be given more attention BACKGROUND Lack of education and an economic dependence on men are often suggested as important risk factors for HIV infection in women . We assessed the efficacy of a cash transfer programme to reduce the risk of sexually transmitted infections in young women . METHODS In this cluster r and omised trial , never-married women aged 13 - 22 years were recruited from 176 enumeration areas in the Zomba district of Malawi and r and omly assigned with computer-generated r and om numbers by enumeration area ( 1:1 ) to receive cash payments ( intervention group ) or nothing ( control group ) . Intervention enumeration areas were further r and omly assigned with computer-generated r and om numbers to conditional ( school attendance required to receive payment ) and unconditional ( no requirements to receive payment ) groups . Participants in both intervention groups were r and omly assigned by a lottery to receive monthly payments ranging from US$ 1 to $ 5 , while their parents were independently assigned with computer-generated r and om numbers to receive $ 4 - 10 . Behavioural risk assessment s were done at baseline and 12 months ; serology was tested at 18 months . Participants were not masked to treatment status but counsellors doing the serologic testing were . The primary outcomes were prevalence of HIV and herpes simplex virus 2 ( HSV-2 ) at 18 months and were assessed by intention-to-treat analyses . The trial is registered , number NCT01333826 . FINDINGS 88 enumeration areas were assigned to receive the intervention and 88 as controls . For the 1289 individuals enrolled in school at baseline with complete interview and biomarker data , weighted HIV prevalence at 18 month follow-up was 1·2 % ( seven of 490 participants ) in the combined intervention group versus 3·0 % ( 17 of 799 participants ) in the control group ( adjusted odds ratio [ OR ] 0·36 , 95 % CI 0·14 - 0·91 ) ; weighted HSV-2 prevalence was 0·7 % ( five of 488 participants ) versus 3·0 % ( 27 of 796 participants ; adjusted OR 0·24 , 0·09 - 0·65 ) . In the intervention group , we noted no difference between conditional versus unconditional intervention groups for weighted HIV prevalence ( 3/235 [ 1 % ] vs 4/255 [ 2 % ] ) or weighted HSV-2 prevalence ( 4/233 [ 1 % ] vs 1/255 [ < 1 % ] ) . For individuals who had already dropped out of school at baseline , we detected no significant difference between intervention and control groups for weighted HIV prevalence ( 23/210 [ 10 % ] vs 17/207 [ 8 % ] ) or weighted HSV-2 prevalence ( 17/211 [ 8 % ] vs 17/208 [ 8 % ] ) . INTERPRETATION Cash transfer programmes can reduce HIV and HSV-2 infections in adolescent schoolgirls in low-income setting s. Structural interventions that do not directly target sexual behaviour change can be important components of HIV prevention strategies . FUNDING Global Development Network , Bill & Melinda Gates Foundation , National Bureau of Economic Research Africa Project , World Bank 's Research Support Budget , and several World Bank trust funds ( Gender Action Plan , Knowledge for Change Program , and Spanish Impact Evaluation fund ) Background : Incidence data from prospect i ve cohort studies using rigorous laboratory methods are important in design ing and evaluating HIV vaccine and therapeutic clinical trials and health care programs . We report 36-month HIV-1 incidence rates and demographic and psychosocial risks from the Kericho cohort in rural Kenya 's southern Rift Valley Province . Methods : Thirty-six month , prospect i ve , closed , observational cohort study of adult plantation workers and dependents followed biannually . HIV-1 incidence rates per 100 person-years ( py ) were calculated , and Cox regression analyses were used to estimate hazards ratios ( HR ) associated with seroconversion . Results : Two thous and four hundred volunteers ( mean age ± SD = 30.1 ± 8.5 years ; 36.5 % women ) participated . Twenty-nine new HIV cases were identified in year 1 of follow-up , which increased to cumulative totals of 49 and 63 cases in years 2 and 3 , respectively . The corresponding 1- , 2- , and 3-year incidence rates were 1.41 [ 95 % confidence interval ( CI ) = 0.95 - 2.02 ] , 1.16 ( 95 % CI = 0.86 - 1.54 ) , and 1.00 ( 95 % CI = 0.77 - 1.28 ) per 100 py . Risk factors associated with HIV seroconversion included the following : of the Luo tribe ( HR = 3.31 ; 95 % CI = 1.65 - 6.63 ) , marriage more than once ( HR = 2.83 ; 95 % CI = 1.20 - 6.69 ) , self-reported male circumcision ( HR = 0.32 ; 95 % CI = 0.17 - 0.60 ) , history of sexually transmitted infection ( HR = 2.40 ; 95 % CI = 1.09 - 5.26 ) , history of substance abuse during sex ( HR = 2.44 ; 95 % CI = 1.16 - 5.13 ) , and history of transactional sex ( HR = 3.30 ; 95 % CI = 1.79 - 6.09 ) . Conclusions : HIV-1 incidence rates were relatively low in adult plantation workers and dependents in rural Kenya . Cohorts including higher risk population s ( eg , commercial sex workers ) warrant consideration for regional HIV preventive vaccine trials . Even low incidence , well-described cohorts generate valuable epidemiological clinical trial data Objective : To identify and describe population s at risk for HIV in 3 clinical research centers in Kenya and South Africa . Design : Prospect i ve cohort study . Methods : Volunteers reporting recent sexual activity , multiple partners , transactional sex , sex with an HIV-positive partner , or , if male , sex with men ( MSM ; in Kenya only ) were enrolled . Sexually active minors were enrolled in South Africa only . Risk behavior , HIV testing , and clinical data were obtained at follow-up visits . Results : From 2005 to 2008 , 3023 volunteers were screened , 2113 enrolled , and 1834 contributed data on HIV incidence . MSM had the highest HIV incidence rate of 6.8 cases per 100 person-years [ 95 % confidence interval ( CI ) : 4.9 to 9.2 ] followed by women in Kilifi and Cape Town ( 2.7 cases per 100 person-years , 95 % CI : 1.7 to 4.2 ) . No seroconversions were observed in Nairobi women or men in Nairobi or Cape Town who were not MSM . In 327 MSM , predictors of HIV acquisition included report of genital ulcer ( Hazard Ratio : 4.5 , 95 % CI : 1.7 to 11.6 ) , not completing secondary school education ( HR : 3.4 , 95 % CI : 1.6 to 7.2 ) and reporting receptive anal intercourse ( HR : 8.2 , 95 % CI : 2.7 to 25.0 ) . Paying for sex was inversely associated with HIV infection ( HR : 0.2 , 95 % CI : 0.04 to 0.8 ) . 279 ( 13.0 % ) volunteers did not return after the first visit ; subsequent attrition rates ranged from 10.4 to 21.8 volunteers per 100 person-years across clinical research centers . Conclusions : Finding , enrolling , and retaining risk population s for HIV prevention trials is challenging in Africa . African MSM are not frequently engaged for research , have high HIV incidence , need urgent risk reduction counseling , and may represent a suitable population for future HIV prevention trials Objectives To examine risk factors for HIV-1 infection in three geographic strata ( main road trading centers that service local and international traffic , small trading villages on secondary dirt roads that serve as foci for local communications , and agricultural villages off main and secondary roads ) in Rakai District , Ug and a. Design and methods Serological , sociodemographic , knowledge/hehaviors and health survey conducted in 21 r and omly selected community clusters ; complete data were collected for 1292 consenting adults . Results Fifteen per cent of the men and 24 % of the women were HIV-1-positive . On univariate analysis , several sociodemographic and behavioral factors were significantly associated with risk of HIV infection , including age , place of residence , travel , occupation , marital status , number of sex partners , sex for money or gifts , history of sexually transmitted disease ( STD ) , and history of injections . On multivariate analysis , age , residence and number of sex partners remained significantly associated with HIV infection in both sexes ; a history of STD and not having been circumcised were significant in men . There was a significant interaction between place of residence and reported number of sex partners : for any given level of sexual activity , the risk of HIV infection was markedly increased if the background community prevalence was high . ConclusionS exual transmission appears to be the primary behavioral risk factor for infection , but the risks associated with this factor vary substantially between the three geographic strata . These data can be used to design targeted interventions Objectives : To examine associations between the perpetration of intimate partner violence and HIV risk behaviour among young men in rural South Africa . Design : An analysis of baseline data from men enrolling in a r and omized controlled trial of the behavioural intervention , Stepping Stones . Methods : Structured interviews with 1275 sexually experienced men aged 15–26 years from 70 villages in the rural Eastern Cape . Participants were asked about the type , frequency , and timing of violence against female partners , as well as a range of questions about HIV risk behaviours . Results : A total of 31.8 % of men reported the perpetration of physical or sexual violence against female main partners . Perpetration was correlated with higher numbers of past year and lifetime sexual partners , more recent intercourse , and a greater likelihood of reporting casual sex partners , problematic substance use , sexual assault of non-partners , and transactional sex . Men who reported both physical and sexual violence against a partner , perpetration both before and within the past 12 months , or more than one episode of perpetration reported significantly higher levels of HIV risk behaviour than men who reported less severe or less frequent perpetration of violence . Conclusion : Young men who perpetrate partner violence engage in significantly higher levels of HIV risk behaviour than non-perpetrators , and more severe violence is associated with higher levels of risky behaviour . HIV prevention interventions must explicitly address the links between the perpetration of intimate partner violence and HIV risk behaviour among men , as well as the underlying gender and power dynamics that contribute to both Objectives : To investigate sexual practice s and risk factors for prevalent HIV infection among young men in Kisumu , Kenya . Goal : The goal of this study was to identify behaviors associated with HIV in Kisumu to maximize the effectiveness of future prevention programs . Study Design : Lifetime sexual histories were collected from a nested sample of 1337 uncircumcised participants within the context of a r and omized controlled trial of male circumcision to reduce HIV incidence . Results : Sixty-five men ( 5 % ) tested positive for HIV . Multiple logistic regression revealed the following independent predictors of HIV : older age , less education , being married , being Catholic , > 4 lifetime sex partners , prior treatment for an STI , sex during partner 's menstruation , ever practicing bloodletting , and receipt of a medical injection in the last 6 months . Prior HIV testing and postcoital cleansing were protective . Conclusions : This analysis confirms the importance of established risk factors for HIV and identifies practice s that warrant further investigation |
11,741 | 22,859,322 | The evidence found in our review does not support differences in efficacy of topical agents to reduce sepsis and /or local infections in burn patients | Topical agents are widely used in the care of burn patients ; however the efficacy to prevent local infections and /or sepsis has not been clearly established in studies with a high level of evidence .
This systematic review was conducted to assess the comparative efficacy among different topical agents . | Sixty patients with moderate and severe burns were r and omly assigned to receive topical silver sulfadiazine ( SSD ) alone ( n=30 ) or SSD combined with cerium nitrate ( SSD-CN ) ( n=30 ) . There were four deaths in the SSD group and one in the SSD-CN group ; more patients with higher risk severity survived in the SSD-CN group . Wound infection did not differ significantly between the groups . The rate of re-epithelialization of partial thickness burns was faster by 8 days in the SSD-CN group . The relatively dry shell-like eschar of the SSD-CN-treated burn allowed planned excisions with immediate autologous grafting and the tissue beneath was ready to accept grafting 11 days earlier than in the SSD group ( p=0.03 ) . This result ed in a significantly shorter hospital stay for those in the SSD-CN group than in the SSD group ( 23.3 vs. 30.7 days ; p=0.03 ) with consequent cost savings . A higher incidence of transient stinging pain was reported with application of SSD-CN , but this was effectively managed with analgesics where necessary . The results of this study confirm the greater efficacy of SSD-CN in the treatment of burns patients Burn injury is associated with a high incidence of death and disability ; yet , its management remains problematic and costly . We conducted this clinical study to evaluate the efficacy of honey in the treatment of superficial and partial-thickness burns covering less than 40 % of body surface area and compared its results with those of silver sulphadiazine ( SSD ) . In this r and omised comparative clinical trial , carried out Burn Center of POF Hospital , Wah Cantt , Pakistan , from May 2007 to February 2008 , 150 patients of all ages having similar types of superficial and partial-thickness burns at two sites on different parts of body were included . Each patient had one burn site treated with honey and one treated with topical SSD , r and omly . The rate of re-epithelialization and healing of superficial and partial-thickness burns was significantly faster in the sites treated with honey than in the sites treated with SSD ( 13·47 ± 4·06 versus 15·62 ± 4·40 days , respectively : P < 0·0001 ) . The site treated with honey healed completely in less than 21 days versus 24 days for the site treated with SSD . Six patients had positive culture for Pseudomonas aeroginsa in honey-treated site , whereas 27 patients had positive culture in SSD-treated site . The results clearly showed greater efficacy of honey over SSD cream for treating superficial and partial-thickness burns The present paper reports the results of clinical and laboratory tests carried out on two homogeneous groups of ten burn patients subjected to local therapy , either with isotonic chloroxidating solution Amuchina * or with 1 % silver sulfadiazine cream at the Burns Centre of the Pisa University Dermatological Clinic . The local systemic behaviour of the patients examined was evaluated for the containment of septic complications at the burn site . In the group subjected to treatment with chloroxidating solution , sepsis appeared to have a lower incidence in the evolution of dermatitis in the phase of escharolysis , in the formation of granulation tissue , and in the attachment of cutaneous grafts . The systemic involvement ( temperature curve , etc . ) appeared to be more marked for some patients treated with silver sulfadiazine in response to septic aggression of the burn wounds . On the basis of data referring to the development of the wound granulation and the temperature curve , as well as the microbial presence and the subjective tolerance of the medication , the comparison was favourable , making all necessary allowances , to topical treatment with electrolytic chloroxidating solution ; other comparative data were at the limit of significance OBJECTIVE To evaluate the therapeutic effect of silver nitrate ointment on partial-thickness burn wounds , and observe its side-effects . METHODS Multi-center , r and omized , positive drug paralleled self-controlled trial was carried out . Eighty patients with superficial partial-thickness burns , and 40 with deep-partial thickness burns were r and omized into AgNO3 group and SD-Ag group according to drug topically applied to the wounds . The wound healing time , wound healing rate and bacterial culture of the wound , the effect and safety of the drug , as well as drug irritation to the wounds were studied in these two groups . RESULTS For the patients with superficial partial-thickness burn wounds , the wound healing time in silver nitrate group was ( 9.5 + /- 2.7 ) days , which was obviously shorter than that in SD-Ag group [ ( 10.8 + /- 3.4 ) days , P < 0.01 ] . The wound healing rate in silver nitrate group on 7 post-burn day ( PBD ) was ( 77.9 + /- 20.5)% , which was obviously higher than that in SD-Ag group [ ( 67.3 + /- 22.6 ) % , P < 0.01 ] . For those with deep-partial thickness burn wounds , the wound healing time in silver nitrate group was ( 21.5 + /- 4.8 ) days , which was evidently shorter than that in SD-Ag group [ ( 23.3 + /- 6.4 ) days , P < 0.01 ] . The wound healing rate in silver nitrate group on 20 PBD was ( 86.6 + /- 15.9)% , which was evidently higher than that in SD-Ag group [ ( 78.5 + /- 17.7)% , P < 0.01 ] . Silver nitrate ointment has the same antibacterial effect as 1 % SD-Ag cream , but it was less painful when applied to the open wounds . CONCLUSION Silver nitrate ointment is an effective and safe medicament for the clinical management of partial-thickness burn wounds Due to the limited re sources for the management of burns in most regions of Africa there is a significant role for many aspects of traditional African medicine . The active component of many traditional preparations is often of plant origin and more than 25 plants have been described as useful in relations to burns and wound healing . Carica papaya is currently used in The Gambia at the Royal Victoria Hospital , Banjul in the Paediatric Unit as the major component of burns dressings , where it is well tolerated by the children . Cheap and widely available , the pulp of the papaya fruit is mashed and applied daily to full thickness and infected burns . It appears to be effective in desloughing necrotic tissue , preventing burn wound infection , and providing a granulating wound suitable for the application of a split thickness skin graft . Possible mechanisms of action include the activity of proteolytic enzymes chymopapain and papain , as well as an antimicrobial activity , although further studies are required We prospect ively studied 52 consecutive patients who were treated by early tangential excision and grafting following thermal injury . The usefulness of two topical antimicrobial agents—0.5 % silver nitrate ( Ag ) and neomycin ( 1 gm/liter ) plus bacitracin ( 50,000 units/liter ) (NB)—was compared with the effectiveness of Ringer 's lactate ( RL ) for prevention of autogenous skin-graft loss due to infection . Graft loss of 10 percent or more occurred in 17 patients ( 33 percent)—due to infection in 16 . Skin-graft loss was a minor problem in patients with less than 20 percent total body surface area ( TBSA ) burn ( Ag : 0 of 6 , NB : 1 of 6 , RL : 1 of 5 ) . The use of either antimicrobial ( Ag or NB ) result ed in less graft loss ( 1 of 14 ) than RL ( 4 of 6 ; p < 0.05 ) in the 20 to 40 percent TBSA burn group . Large burns ( > 40 percent ) had a very high incidence of at least 10 percent graft loss ( 67 percent ) regardless of treatment . Infection in the area of graft loss was caused by antibiotic-resistant organisms or yeast in 50 percent of the Ringer 's lactate group and the entire neomycin plus bacitracin group . No graft infections were caused by resistant organisms or yeast in the silver nitrate group . This study demonstrates that topical antimicrobial agents reduce infection-related skin-graft loss in patients with medium-sized ( 20 to 40 percent TBSA ) burns and that neomycin plus bacitracin is associated with rapid emergence of drug-resistant organisms whereas silver nitrate is not |
11,742 | 18,415,952 | This meta- analysis suggests that late revascularization of an occluded IRA may improve left ventricular systolic function and remodeling , supporting the " open artery hypothesis . " | BACKGROUND Late percutaneous coronary intervention ( PCI ) of a totally occluded infa rct -related artery ( IRA ) in stable patients is currently not recommended based on the lack of clear clinical benefits in r and omized controlled trials .
We sought to perform a systematic review and meta- analysis of r and omized controlled trials comparing PCI with optimal medical therapy in patients with IRA occlusion more than 12 hr after onset of acute myocardial infa rct ion ( AMI ) , focusing on left ventricular function and remodeling . | BACKGROUND Although the short-term and long-term beneficial effects of early coronary revascularization by primary PTCA or thrombolytic therapy have been established for acute myocardial infa rct ion , thrombolytic therapy > 24 hours after the onset of acute myocardial infa rct ion has not been shown to improve clinical outcome . The purpose of this study was to assess the effect of late revascularization by primary PTCA over a 5-year period . METHODS AND RESULTS Eighty-three patients with initial Q-wave anterior myocardial infa rct ion > 24 hours after onset were r and omized into a PTCA group ( n=44 ) and a no-PTCA group ( n=39 ) . Long-term follow-up was conducted with regard to end points , which included cardiac death , nonfatal recurrence of myocardial infa rct ion , and development of congestive heart failure . Left ventricular ejection fraction and regional wall motion at 6 months after myocardial infa rct ion were similar in the 2 groups . Left ventricular end-diastolic and end-systolic volume indexes were significantly smaller in the PTCA group than in the no-PTCA group ( P<0.0001 ) . With cardiac events as end points , a 5-year Kaplan-Meier event-free survival analysis revealed that the no-PTCA group had a worse prognosis than the PTCA group ( P<0.0001 ) . Patency of the infa rct -related artery , left ventricular ejection fraction , end-diastolic volume index , and end-systolic volume index were significantly associated with cardiac events by a Cox proportional hazards analysis ( hazard ratios 0.120 , 0.845 , 1.065 , and 1.164 , respectively ) . CONCLUSIONS In initial Q-wave anterior myocardial infa rct ion , we conclude that even with late reperfusion , PTCA had beneficial effects on cardiac events over the 5-year period after myocardial infa rct ion , with the prevention of left ventricular dilation after myocardial infa rct ion being a possible mechanism Background After thrombolytic therapy for patients with acute myocardial infa rct ion ( MI ) , percutaneous transluminal coronary angioplasty ( PTCA ) is frequently performed because of the presence of a “ significant ” infa rct vessel stenosis demonstrated at predischarge coronary angiography . Several studies have shown PTCA performed early after thrombolysis to be unnecessary or even harmful . However , PTCA in these trials was generally performed 1–3 days after MI , when the milieu in the infa rct artery may be unsuited for PTCA , and the incidence of major ischemic complications was high . To date , no trial has assessed whether delayed PTCA ( 4–14 days ) should be performed in patients without evidence of ischemia on stress testing . Methods and Results To test the hypothesis that delayed PTCA might provide clinical benefit compared with medical therapy alone , 87 patients treated within 6 hours of chest pain onset with thrombolytic therapy and with negative functional test were r and omized between PTCA to be performed 4–14 days after MI versus no PTCA . Both groups received medical therapy . Patients with postinfa rct angina or prior Q wave infa rct ion in the infa rct distribution were excluded . The primary study end point was increase in left ventricular ejection fraction with exercise measured by radionuclide studies 6 weeks after MI , a parameter known from other studies to correlate inversely with future ischemic events . Clinical outcome was also monitored for 12 months . There were no differences between the study groups for any prer and omization variable recorded . Mean age was 57± 10 years , 84 % of patients were male , 21 % had prior MI , 36 % had anterior MI , 7 % had multivessel disease , and the infa rct stenosis measured 70±17 % before r and omization . PTCA was successful in 38 of 42 patients ( 88 % ) but result ed in non-Q wave MI due to acute closure of the treated site in three of 42 ( 9.5 % ) . There was no difference in 6-week resting ejection fraction or increase in ejection fraction with exercise between the two groups ( 47±12 % and 6±8 % , respectively , in the PICA group ; 49±10 % and 5±9%o in the no-PTCA group ; p = NS for both . ) There were no deaths in either group . Actuarial 12-month infa rct -free survival was 97.8 % in the no-PTCA group and 90.5 % in the PTCA group ( p=0.07 ) . Conclusions There was no functional or clinical benefit from routine late PTCA after MI treated with thrombolytic therapy in this relatively low-risk cohort of patients . These data strongly suggest that patients with an uncomplicated MI after thrombolytic therapy , even if they have a “ significant ” residual stenosis of the infa rct vessel , should be treated medically if they are without evidence of ischemia on stress testing before hospital discharge Background Experimental and observational clinical studies of acute coronary occlusion have suggested that late reperfusion prevents infa rct expansion and facilitates myocardial healing . The purpose of this trial was to assess whether infa rct vessel patency could be achieved in late-entry patients and what benefit , if any , can be demonstrated . Methods and Results In a double-blind fashion , 197 patients with 6 to 24 hours of symptoms and ECG ST elevation were r and omly assigned to tissue-type plasminogen activator ( 100 mg over 2 hours ) or placebo . Coronary angiography within 24 hours was used to determine infa rct vessel patency status . Patients with infa rct -related occluded arteries were then eligible for a second r and omization to either angioplasty ( 34 patients ) or no angioplasty ( 37 patients ) . Ventricular function and cavity size were reassessed at 1 month by gated blood pool scintigraphy and at 6 months by repeat cardiac catheterization . The primary end point , infa rct vessel patency , was 65 % for plasminogen activator patients compared with 27 % in the placebo group ( p<0.0001 ) . There were no differences between these groups in ejection fraction or infa rct zone regional wall motion at 1 or 6 months . At 6 months , infa rct vessel patency was 59 % in both groups . In the placebo group , there was a significant increase in end-diastolic volume from acute phase of 127 ml to 159 ml at 6-month follow-up ( p=0.006 ) but no increase in cavity size for the plasminogen activator group patients . Coronary angioplasty was associated with an initial 81 % recanalization success and improved ventricular function at 1 month , but by late follow-up no advantage could be demonstrated for this procedure , and there was a 38 % spontaneous recanalization rate in the patients assigned to no angioplasty . Conclusions The study demonstrates that it is possible to achieve infa rct vessel recanalization in the majority of late-entry patients with either thrombolytic therapy or angioplasty . Thrombolytic intervention had a favorable effect on prevention of cavity dilatation and left ventricular remodeling , but there are no late benefits on systolic function after thrombolysis or coronary angioplasty . The conclusions concerning overall potential benefit of applying late reperfusion therapy will require data from large-scale trials design ed to assess mortality reduction For nearly a decade , it has been appreciated that 1 ) thrombotic occlusion of an epicardial coronary artery is usually the proximate cause of acute myocardial infa rct ion ; 2 ) after sudden and sustained total occlusion of such a vessel , the course of myocardial necrosis is generally rapid and relentless ( in most cases , the process is completed within 3 or 4 hours of the coronary occlusion , in 6 hours at a maximum ) ; 3 ) infa rct size is a critical determinant of left ventricular function ; and 4 ) left ventricular function , in turn , is the most important determinant of early ( in-hospital ) and long-term ( postdischarge ) survival . Major efforts have been devoted to the development of techniques design ed to interfere with the sequence of events summarized above . Considerable attention has been directed to achieving timely reperfusion of occluded coronary arteries to interrupt the infa rct ion with the hope that the result ant limitation of infa rct size will improve ventricular function and thereby patient survival.1 Many techniques to achieve reperfusion have been used , including emergency coronary artery bypass surgery , emergency percutaneous transluminal coronary angioplasty ( PTCA ) , and the intracoronary and intravenous administration of a variety of thrombolytic agents ; the last of these approaches is particularly attractive because its simplicity makes it applicable to a large proportion of patients with acute myocardial infa rct ion . In some instances , combinations of these techniques , such as intravenous thrombolytic therapy followed by PTCA , have been used . These efforts to treat acute myocardial infa rct ion have been notably successful , as reflected in an improvement in survival noted in controlled r and omized trials.2 - 6 Also , the absolute mortality rates achieved in some recent trials of reperfusion therapy ( 3 - 5 % ) are far lower than those noted The TAMI-6 trial has demonstrated that coronary reperfusion > 6h after onset ( ie , late reperfusion ) in patients with acute myocardial infa rct ion ( AMI ) does not improve left ventricular ( LV ) function during the chronic phase of infa rct ion . However , the low patency rate ( only 60 % ) of the infa rct -related artery ( IRA ) during the chronic phase in the TAMI-6 trial raises a new hypothesis that late reperfusion with a higher patency rate may improve LV function during the chronic phase . Forty-four patients with AMI , who were admitted to hospital 6 - 24h after the symptom onset and in whom emergency coronary angiography revealed a total occlusion of the IRA , were r and omly assigned to either the late reperfusion group ( n=22 ) or the non-reperfusion group ( n=22 ) . The initial success rate of reperfusion therapy in the late reperfusion group was 86 % and the chronic patency rate of the IRA was 91 % . The improvements in ejection fraction and chord shortening in the infa rct region from the acute phase to the chronic phase were significantly greater in the late reperfusion group than in the non-reperfusion group . Late reperfusion with a high patency rate of the IRA significantly improves LV global and regional function in patients with AMI Background —A recent l and mark report has demonstrated that plasma B-type natriuretic peptide ( BNP ) measured in acute coronary syndromes independently predicts mortality , heart failure , and new myocardial infa rct ion . After acute cardiac injury , left ventricular ejection fraction ( LVEF ) is also of prognostic significance and plays a major role in determining the therapeutic response . Methods and Results —The present report is the first from a substantial ( n=666 ) cohort of patients with acute myocardial infa rct ion to test the prognostic utility of concurrent measurements of BNP , amino-terminal BNP ( N-BNP ) , norepinephrine , and radionuclide LVEF . The B-type peptides and LVEF were predictors of death , heart failure , and new myocardial infa rct ion ( all P < 0.001 ) independent of patient age , gender , previous myocardial infa rct ion , antecedent hypertension or diabetes , previous heart failure , plasma norepinephrine , creatinine , cholesterol , drug therapy , and coronary revascularization procedures . The combination of N-BNP ( or BNP ) with LVEF substantially improved risk stratification beyond that provided by either alone . Elevated N-BNP ( or BNP ) predicted new myocardial infa rct ion only in patients with LVEF < 40 % . LVEF < 40 % coupled to N-BNP over the group median conferred substantial 3-year risks of death , heart failure , and new myocardial infa rct ion of 37 % , 18 % , and 26 % , respectively . N-BNP and BNP were equivalent prognostic markers for these clinical outcomes . Conclusions —Plasma N-BNP ( or BNP ) and LVEF are complementary independent predictors of major adverse events on follow-up after myocardial infa rct ion . Combined measurement provides risk stratification substantially better than that provided by either alone Experimental and clinical studies have suggested that late opening of an infa rct -related artery ( IRA ) after myocardial infa rct ion ( MI ) could improve clinical outcome . However , the suggestive observational data are limited by selection biases . Indeed , most small r and omized studies have not demonstrated benefit . Thus , there is no recommendation for routine late opening of the IRA in current national guidelines for management of stable post-MI patients . The OAT is design ed to test the hypothesis that opening a totally occluded IRA 3 to 28 days after MI in high-risk asymptomatic patients will improve clinical outcome and be cost-effective . The primary end point is the first occurrence of recurrent MI , hospitalization/treatment of New York Heart Association class IV congestive heart failure , or death . Trial background , design , and preliminary baseline characteristics of 2027 r and omized patients are presented . Eligible patients are r and omly assigned in equal proportions to optimal evidence -based medical care or optimal care plus late opening of the IRA using percutaneous coronary intervention of the occluded IRA . Treatment groups will be compared using intent-to-treat analysis . The results of OAT should have broad clinical impact by defining an evidence -based approach to the asymptomatic , high-risk , post-MI patient with an occluded IRA . If the efficacy and cost-effectiveness of percutaneous coronary intervention are established , then a policy of routinely seeking and opening persistently occluded IRAs could be advocated . If not , this strategy should be avoided in this large subgroup of post-MI patients OBJECTIVE We sought to conduct a r and omized trial comparing late revascularization with conservative therapy in symptom-free patients after acute myocardial infa rct ion ( AMI ) . BACKGROUND In the absence of ischemia , the benefits of reperfusion late after AMI remain controversial . However , the possibility exists that an open infa rct related artery benefits healing post AMI . METHODS Of 223 patients enrolled with Q-wave anterior AMI , 66 with isolated persistent occlusion of the left anterior descending coronary artery ( LAD ) were r and omized to the following treatments : 1 ) medical therapy ( closed artery group ; n = 34 ) or 2 ) late intervention and stent to the LAD + medical therapy ( open artery group ; n = 32 ) . The study was powered to compare left ventricular ( LV ) end-systolic volume between the two groups 12 months post AMI . RESULTS Late intervention 26 + /- 18 days post AMI result ed in significantly greater LV end-systolic and end-diastolic volumes at 12 months than medical therapy alone ( 106.6 + /- 37.5 ml vs. 79.7 + /- 34.4 ml , p < 0.01 and 162.0 + /- 51.4 ml vs. 130.1 + /- 46.1 ml , p < 0.01 , respectively ) . Exercise duration and peak workload significantly increased in both groups from 6 weeks to 12 months post AMI , although absolute values were greater in the open artery group . Quality of life scores tended to deteriorate during this time interval in the closed artery patients but remained unchanged in the open artery patients . Coronary angiography at 1 year documented a low incidence of intergroup cross-over ( spontaneous recanalization in 19 % and closure in 11 % ) . CONCLUSIONS In the present study , recanalization of occluded infa rct -related arteries in symptom-free patients approximately 1 month post AMI had an adverse effect on remodeling but tended to increase exercise tolerance and improve quality of life Background —Percutaneous transluminal coronary angioplasty of the infa rct -related artery in stable survivors of acute myocardial infa rct ion is often performed , even in patients without any symptoms or residual ischemia . Despite the lack of r and omized studies , it is widely believed that this intervention will improve the clinical outcome of these patients . Methods and Results —Three hundred patients with single vessel disease of the infa rct vessel and no or minor angina pectoris in the subacute phase ( 1 to 6 weeks ) after an acute myocardial infa rct ion were r and omized to angioplasty ( n=149 ) or medical therapy ( n=151 ) . Primary end point was the survival free of reinfa rct ion , (re)intervention , coronary artery bypass surgery , or readmission for severe angina pectoris at 1 year . The event-free survival at 1 year was 82 % in the medical group and 90 % in the angioplasty group ( P = 0.06 ) . This difference was mainly driven by the difference in the need for ( re ) interventions ( 20 versus 8 , P = 0.03 ) . At long-term follow-up ( mean , 56 months ) , survival was 89 % and 96 % ( P = 0.02 ) . Survival free of reinfa rct ion , (re)intervention , or coronary artery bypass surgery was 66 % and 80 % in the medically and interventionally treated patients , respectively ( P = 0.05 ) . The use of nitrates was significantly lower in the angioplasty group , both at 1 year ( 38 % versus 67 % , P = 0.001 ) and at long-term follow-up ( 36 % versus 55 % , P = 0.006 ) . Conclusions —Percutaneous revascularization of the infa rct -related coronary artery in stable patients with single vessel disease improves clinical outcome at long-term follow-up and reduces the use of nitrates . The results of our study should be reproduced in a confirmatory study with a larger sample size before percutaneous coronary intervention in this low-risk patient subgroup , after myocardial infa rct ion can be recommended as routine treatment in clinical practice OBJECTIVE To assess the safety and feasibility of acute transport followed by rescue percutaneous transluminal coronary angioplasty ( PTCA ) or primary PTCA in patients with acute myocardial infa rct ion initially admitted to a hospital without PTCA facilities . DESIGN In a multicentre r and omised open trial , three regimens of treatment of acute large myocardial infa rct ion were compared for patients admitted to hospitals without angioplasty facilities : thrombolytic treatment with alteplase ( 75 patients ) , alteplase followed by transfer to the PTCA centre and ( if indicated ) rescue PTCA ( 74 patients ) , or transfer for primary PTCA ( 75 patients ) . RESULTS Between 1995 and 1997 224 patients were included . Baseline characteristics were distributed evenly . Transport to the PTCA centre was without severe complications in all patients . Mean ( SD ) delay from onset of symptoms to r and omisation was 130 ( 75 ) minutes and from r and omisation to angiography 90 ( 25 ) minutes . Death or recurrent infa rct ion within 42 days occurred in 12 patients in the thrombolysis group , in 10 patients in the rescue PTCA group , and in six patients in the primary PTCA group . These differences were not significant . CONCLUSIONS Acute transfer for rescue PTCA or primary PTCA in patients with extensive myocardial infa rct ion is feasible and safe . Efficacy of rescue PTCA or primary PTCA in this setting will have to be tested in larger series before this approach can be implemented as “ routine treatment ” for patients with extensive myocardial infa rct ion Objective : To investigate the influence of infa rct zone viability on remodelling after late recanalisation of an occluded infa rct related artery . Methods : A subgroup of 26 volunteers from TOAT ( the open artery trial ) underwent dobutamine stress cardiovascular magnetic resonance at baseline to assess the amount of viable myocardium present with follow up to assess remodelling at one year . TOAT studied patients with left ventricular dysfunction after anterior myocardial infa rct ion ( MI ) associated with isolated proximal occlusion of the left anterior descending coronary artery with r and omisation to percutaneous coronary intervention ( PCI ) with stent at 3.6 weeks after MI ( PCI group ) or to medical treatment alone ( medical group ) . Results : In the PCI group there was a significant relation between the number of viable segments within the infa rct zone and improvement in end systolic volume index ( −7.7 ml/m2 , p = 0.02 ) and increased ejection fraction ( 4.1 % , p = 0.03 ) . The relation between viability and improvements in end diastolic volume index ( −8.8 ml/m2 , p = 0.08 ) and mass index ( −6.3 g/m2 , p = 0.01 ) did not reach significance ( p = 0.27 and p = 0.8 , respectively ) . In the medical group , there was no significant relation between the number of viable segments in the infa rct zone and the subsequent changes in end diastolic ( p = 0.84 ) and end systolic volume indices ( p = 0.34 ) , ejection fraction ( p = 0.1 ) , and mass index ( p = 0.24 ) . Conclusion : The extent of viable myocardium in the infa rct zone is related to improvements in left ventricular remodelling in patients who undergo late recanalisation of an occluded infa rct related artery One thous and fifty-one consecutive patients who had acute myocardial infa rct ion were classified into 3 risk groups by 4 echocardiographic risk assessment s : left ventricular ejection fraction , left ventricular filling pattern , estimated systolic pulmonary artery pressure , and mitral regurgitation , with 30-day mortality rates of 13.7 % , 3.8 % , and 1 % , respectively ( p < 0.001 ) . Independent echocardiographic and clinical predictors of 30-day mortality included age ( 10 years , hazard ratio [ HR ] 1.30 , 95 % confidence interval [ CI ] 0.91 to 1.89 ) , female gender ( HR 2.12 , 95 % CI 0.94 to 4.74 ) , Killip 's class > or = II on admission ( HR 3.09 , 95 % CI 1.38 to 7.11 ) , group 2 ( moderate ) risk ( HR 2.89 , 95 % CI 1.07 to 8.56 ) , and group 1 ( high ) risk ( HR 8.16 , 95 % CI 2.95 to 25.23 ) BACKGROUND When used in the setting of acute myocardial infa rct ion , intravenous thrombolytic agents fail to achieve early infa rct artery patency in 15 % to 50 % of patients . We tested the hypothesis that immediate balloon angioplasty applied to patients with failed early reperfusion would improve left ventricular function and clinical outcome at 30 days compared with conservative management alone . METHODS AND RESULTS One hundred fifty-one patients with first anterior wall infa rct ion treated with any accepted intravenous thrombolytic regimen and angiographically demonstrated to have an occluded infa rct vessel within 8 hours of chest pain onset were r and omized to aspirin , heparin , and coronary vasodilators ( conservative therapy ) or to this therapy and balloon angioplasty supplemented by further thrombolytic therapy as needed . Left ventricular function was assessed using multiple-gated equilibrium radionuclide technique to determine ejection fraction , and adverse clinical outcome was assessed evaluating death , ventricular tachycardia , and class III or IV heart failure at 30 days . Seventy-three patients were r and omized to conservative therapy and 78 to angioplasty . The two groups were well balanced for patient age ( 59 + /- 11 years ) , sex ( 82 % were male ) , and time to r and omization ( 4.5 + /- 1.9 hours ) . Angioplasty was technically successful in 72 of 78 r and omized patients ( 92 % ) . Two patients r and omized to conservative therapy crossed over to angioplasty within 72 hours . Resting 30-day ejection fraction was 40 + /- 11 % in the angioplasty group and 39 + /- 12 % in the conservative group ( P = .49 ) , but ejection fraction with exercise was 43 + /- 15 % and 38 + /- 13 % for the angioplasty and conservatively treated groups , respectively ( P = .04 ) . Adverse clinical outcomes included death in 5 % and 10 % ( P = .18 ) , severe heart failure in 1 % and 7 % ( P = .11 ) , and either death or severe heart failure in 6 % and 17 % ( P = .05 ) of the angioplasty and conservatively managed groups , respectively . CONCLUSIONS When applied to patients with first anterior infa rct ion , rescue angioplasty appears to be useful in the prevention of death or severe heart failure , with improvement in exercise , but not resting , ejection fraction . This strategy deserves further study and highlights the potential advantage of early mechanical restoration of infa rct vessel patency when thrombolytic therapy has failed The effect of late percutaneous transluminal coronary angioplasty ( PTCA ) of an occluded infa rct -related artery on left ventricular ejection fraction was studied in patients with a recent , first Q-wave myocardial infa rct ion in a prospect i ve , r and omized study . Forty-four patients ( 31 men and 13 women , mean age 58 + /- 12 years ) with an occluded infa rct -related coronary artery were r and omized to PTCA ( n = 25 ) or no PTCA ( n = 19 ) . Patients received acetylsalicylic acid , a beta blocker and an angiotensin-converting enzyme inhibitor unless contraindicated . Left ventricular ejection fraction was determined at baseline and 4 months . Coronary angiography was repeated at 4 months . Baseline ejection fraction measured 20 + /- 12 days after myocardial infa rct ion was 45 + /- 12 % in both groups . PTCA was performed 21 + /- 13 days after the event . The primary PTCA success rate was 72 % . One patient in each group died before angiographic follow-up , which was completed in 37 of the remaining 42 patients ( 88 % ; 21 with and 16 without PTCA ) . At 4 months , the infa rct -related artery was patent in 43 % of PTCA patients and in 19 % of no PTCA patients ( p = NS ) . Reocclusion occurred in 40 % of patients after successful PTCA . Secondary analyses showed that the change in left ventricular ejection fraction was significantly greater in patients with a patent infa rct -related artery ( + 9.4 + /- 6.2 % ) than in those with an occluded artery ( + 1.6 + /- 8.8 % ; p = 0.0096 ) . Baseline ejection fraction also independently predicted improvement in left ventricular ejection fraction ( p = 0.0001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Background — In the present study , we sought to determine whether opening a persistently occluded infa rct -related artery ( IRA ) by percutaneous coronary intervention ( PCI ) in patients beyond the acute phase of myocardial infa rct ion ( MI ) improves patency and indices of left ventricular ( LV ) size and function . Methods and Results — Between May 2000 and July 2005 , 381 patients with an occluded native IRA 3 to 28 days after MI ( median 10 days ) were r and omized to PCI with stenting ( PCI ) or optimal medical therapy alone . Repeat coronary and LV angiography was performed 1 year after r and omization ( n=332 , 87 % ) . Co primary end points were IRA patency and change in LV ejection fraction . Secondary end points included change in LV end-systolic and end-diastolic volume indices and wall motion . PCI was successful in 92 % . At 1 year , 83 % of PCI versus 25 % of medical therapy – only patients had a patent IRA ( P<0.001 ) . LV ejection fraction increased significantly ( P<0.001 ) in both groups , with no between-group difference : PCI 4.2±8.9 ( n=150 ) versus medical therapy 3.5±8.2 ( n=136 ; P=0.47 ) . Median change ( interquartile range ) in LV end-systolic volume index was −0.5 ( −9.3 to 5.0 ) versus 1.0 ( −5.7 to 7.3 ) mL/m2 ( P=0.10 ) , whereas median change ( interquartile range ) in LV end-diastolic volume index was 3.2 ( −8.2 to 13.3 ) versus 5.3 ( −4.6 to 23.2 ) mL/m2 ( P=0.07 ) in the PCI ( n=86 ) and medical therapy – only ( n=76 ) groups , respectively . Conclusions — PCI with stenting of a persistently occluded IRA in the subacute phase after MI effectively maintains long-term patency but has no effect on LV ejection fraction . On the basis of these findings and the lack of clinical benefit in the main Occluded Artery Trial , routine PCI is not recommended for stable patients with a persistently occluded IRA after MI Background Although percutaneous coronary intervention ( PCI ) is becoming the st and ard therapy in ST-segment elevation myocardial infa rct ion ( STEMI ) , to date most patients , even in developed countries , are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all . In the post-lysis period these patients are at high risk for recurrent ischemic events . Early identification of these patients is m and atory as this subgroup could possibly benefit from an angioplasty of the infa rct -related artery . Since viability seems to be related to ischemic adverse events , we initiated a clinical trial to investigate the benefits of PCI with stenting of the infa rct -related artery in patients with viability detected early after acute myocardial infa rct ion . Methods The VIAMI- study is design ed as a prospect i ve , multicenter , r and omized , controlled clinical trial . Patients who are hospitalized with an acute myocardial infa rct ion and who did not have primary or rescue PCI , undergo viability testing by low-dose dobutamine echocardiography ( LDDE ) within 3 days of admission . Consequently , patients with demonstrated viability are r and omized to an invasive or conservative strategy . In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infa rct -related coronary artery and concomitant use of abciximab . In the conservative group an ischemia-guided approach is adopted ( st and ard optimal care).The primary end point is the composite of death from any cause , reinfa rct ion and unstable angina during a follow-up period of three years . Conclusion The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infa rct -related coronary artery with stenting and concomitant use of abciximab results in a clinical ly important risk reduction of future cardiac events in patients with viability in the infa rct -area , detected early after myocardial infa rct ion CONTEXT The effect of a percutaneous coronary intervention ( PCI ) on the long-term prognosis of patients with silent ischemia after a myocardial infa rct ion ( MI ) is not known . OBJECTIVE To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI . DESIGN , SETTING , AND PARTICIPANTS R and omized , unblinded , controlled trial ( Swiss Interventional Study on Silent Ischemia Type II [ SWISSI II ] ) conducted from May 2 , 1991 , to February 25 , 1997 , at 3 public hospitals in Switzerl and of 201 patients with a recent MI , silent myocardial ischemia verified by stress imaging , and 1- or 2-vessel coronary artery disease . Follow-up ended on May 23 , 2006 . INTERVENTIONS Percutaneous coronary intervention aim ed at full revascularization ( n = 96 ) or intensive anti-ischemic drug therapy ( n = 105 ) . All patients received 100 mg/d of aspirin and a statin . MAIN OUTCOME MEASURES Survival free of major adverse cardiac events defined as cardiac death , nonfatal MI , and /or symptom-driven revascularization . Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up . RESULTS During a mean ( SD ) follow-up of 10.2 ( 2.6 ) years , 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group ( adjusted hazard ratio , 0.33 ; 95 % confidence interval , 0.20 - 0.55 ; P<.001 ) , which corresponds to an absolute event reduction of 6.3 % per year ( 95 % confidence interval , 3.7%-8.9 % ; P<.001 ) . Patients in the PCI group had lower rates of ischemia ( 11.6 % vs 28.9 % in patients in the drug therapy group at final follow-up ; P = .03 ) despite fewer drugs . Left ventricular ejection fraction remained preserved in PCI patients ( mean [ SD ] of 53.9 % [ 9.9 % ] at baseline to 55.6 % [ 8.1 % ] at final follow-up ) and decreased significantly ( P<.001 ) in drug therapy patients ( mean [ SD ] of 59.7 % [ 11.8 % ] at baseline to 48.8 % [ 7.9 % ] at final follow-up ) . CONCLUSION Among patients with recent MI , silent myocardial ischemia verified by stress imaging , and 1- or 2-vessel coronary artery disease , PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00387231 AIMS To assess the recanalization effects of post-myocardial infa rct ion ( MI ) on left ventricular ( LV ) remodelling and contractility in relation to conservative therapy . METHODS AND RESULTS Thirty-six patients with occluded infa rct -related artery between 12 h and 14 days post-anterior MI were r and omized to percutaneous coronary intervention ( PCI group ) or conservative therapy ( no-PCI group ) . Magnetic resonance imaging was performed at enrollment and after 6 months . The left ventricle was divided into infa rct , adjacent , and remote segments . There was no difference in relation to LV volume between groups at the 6 month follow-up . Change in LV ejection fraction was favourable to the PCI group : 5.00 % vs. -0.76 % , P=0.012 . Change in circumferential shortening ( Ecc ) of the remote segments in the PCI group was significantly better than in the no-PCI group : -1.67+/-6.30 % vs. 0.29+/-6.02 % , P<0.001 . Infa rct size and LV mass were similar between groups . CONCLUSIONS Late recanalization improved LV ejection fraction and myocardial contractility in late follow-up , but did not change the ventricular volumes . Improvement in the left ventricle global and regional contractility may benefit the long-term outcome in post-MI patients with sustained patency of the infa rct -related artery BACKGROUND The appropriate treatment for patients in whom reperfusion fails to occur after thrombolytic therapy for acute myocardial infa rct ion remains unclear . There are few data comparing emergency percutaneous coronary intervention ( rescue PCI ) with conservative care in such patients , and none comparing rescue PCI with repeated thrombolysis . METHODS We conducted a multicenter trial in the United Kingdom involving 427 patients with ST-segment elevation myocardial infa rct ion in whom reperfusion failed to occur ( less than 50 percent ST-segment resolution ) within 90 minutes after thrombolytic treatment . The patients were r and omly assigned to repeated thrombolysis ( 142 patients ) , conservative treatment ( 141 patients ) , or rescue PCI ( 144 patients ) . The primary end point was a composite of death , reinfa rct ion , stroke , or severe heart failure within six months . RESULTS The rate of event-free survival among patients treated with rescue PCI was 84.6 percent , as compared with 70.1 percent among those receiving conservative therapy and 68.7 percent among those undergoing repeated thrombolysis ( overall P=0.004 ) . The adjusted hazard ratio for the occurrence of the primary end point for repeated thrombolysis versus conservative therapy was 1.09 ( 95 percent confidence interval , 0.71 to 1.67 ; P=0.69 ) , as compared with adjusted hazard ratios of 0.43 ( 95 percent confidence interval , 0.26 to 0.72 ; P=0.001 ) for rescue PCI versus repeated thrombolysis and 0.47 ( 95 percent confidence interval , 0.28 to 0.79 ; P=0.004 ) for rescue PCI versus conservative therapy . There were no significant differences in mortality from all causes . Nonfatal bleeding , mostly at the sheath-insertion site , was more common with rescue PCI . At six months , 86.2 percent of the rescue-PCI group were free from revascularization , as compared with 77.6 percent of the conservative-therapy group and 74.4 percent of the repeated-thrombolysis group ( overall P=0.05 ) . CONCLUSIONS Event-free survival after failed thrombolytic therapy was significantly higher with rescue PCI than with repeated thrombolysis or conservative treatment . Rescue PCI should be considered for patients in whom reperfusion fails to occur after thrombolytic therapy OBJECTIVES We sought to compare emergency coronary angiography with or without rescue percutaneous coronary intervention ( PCI ) with conservative treatment in patients with failed fibrinolysis complicating ST-segment elevation myocardial infa rct ion ( STEMI ) . BACKGROUND Most patients with STEMI receive fibrinolytic therapy and aspirin . The management of failed fibrinolysis is unclear . METHODS A total of 307 patients with STEMI and failed fibrinolysis were r and omized to emergency coronary angiography with or without rescue PCI or conservative treatment . RESULTS Thirty-day all-cause mortality was similar in the rescue and conservative groups ( 9.8 % vs. 11 % , p = 0.7 , risk difference [ RD ] 1.2 % , 95 % confidence interval [ CI ] -5.8 to 8.3 ) . The composite secondary end point of death/re-infa rct ion/stroke/subsequent revascularization/heart failure occurred less frequently in the rescue group ( 37.3 % vs. 50 % , p = 0.02 , RD 12.7 % , 95 % CI 1.6 to 23.5 ) , driven by less subsequent revascularization ( 6.5 % vs. 20.1 % , p < 0.01 , RD 13.6 % , 95 % CI 6.2 to 21.4 ) . Re-infa rct ion and clinical heart failure were less common in the rescue group ( 7.2 % vs. 10.4 % , p = 0.3 , RD 3.2 % , 95 % CI -3.3 to 9.9 ; and 24.2 % vs. 29.2 % , p = 0.3 , RD 5.7 % , 95 % CI -4.3 to 15.6 , respectively ) . Strokes and transfusions were more common in the rescue group ( 4.6 % vs. 0.6 % , p = 0.03 , RD 3.9 % , 95 % CI 0.5 to 8.6 ; and 11.1 % vs. 1.3 % , p < 0.001 , RD 9.8 % , 95 % CI 4.9 to 19.9 , respectively ) . Left ventricular function at 30 days was the same in the two groups . CONCLUSIONS Rescue angioplasty did not improve survival by 30 days , but improved event-free survival , almost completely due to a reduction in subsequent revascularization . Rescue angioplasty was associated with more strokes and more transfusions and did not result in preservation of left ventricular systolic function at 30 days Although both the European Cooperative Study Group and the Thrombolysis in Myocardial Infa rct ion IIB trial indicated that angiography and angioplasty as routine measures after thrombolytic treatment do not improve clinical outcome in patients with acute myocardial infa rct ion , the potential benefit of angioplasty may have been negated by the fact that the procedure was performed too soon ( less than 32 hours ) after admission . A similar study was design ed in which delayed invasive treatment was compared with conservative treatment in 201 patients with acute myocardial infa rct ion given recombinant tissue-type plasminogen activator . The 97 patients r and omized to the invasive group underwent routine coronary angiography and angioplasty 5 + /- 2 days after thrombolytic therapy , whereas the 104 patients r and omized to the conservative group underwent angiography only for recurrent postinfa rct ion angina or exercise-induced ischemia . Baseline characteristics of both groups were similar . In the invasive group , 92 patients underwent angiography , 49 angioplasty and 11 coronary artery bypass surgery . In the conservative group , 40 patients experienced early ischemia , 39 underwent angiography , 20 angioplasty and 4 coronary artery bypass surgery . Reinfa rct ion rate and preservation of left ventricular function at discharge or 8 weeks after discharge did not differ in the 2 groups . Total mortality after a mean follow-up of 10 months was 8 of 97 in the invasive and 4 of 104 in the conservative groups ( p = 0.15 ) . However , if only patients who died after the timing of the scheduled protocol catheterization in the invasive arm were included , mortality was 5 of 94 and 0 of 100 in the invasive and conservative treatment groups , respectively ( p = 0.02 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Rescue percutaneous transluminal coronary angioplasty ( PTCA ) has been used to establish reperfusion after failed thrombolysis , and the goal of this study was to examine the angiographic and clinical outcomes after rescue PTCA performed for an occluded artery 90 minutes after thrombolysis . Four hundred two patients with acute myocardial infa rct ion were r and omized to receive either anistreplase ( APSAC ) , recombinant tissue plasminogen activator , or their combination in the Thrombolysis in Myocardial Infa rct ion ( TIMI ) 4 trial . The angiographic and clinical outcomes of patients with a patent artery 90 minutes after thrombolysis were compared with those of patients with an occluded artery treated in a nonr and omized fashion with either rescue or no rescue PTCA . At 90 minutes , the number of frames required to opacify st and ard l and marks ( corrected TIMI frame count ) was significantly lower ( i.e. , flow was faster ) after successful rescue PTCA ( 27 + /- 11 ) than that in patent arteries after successful thrombolysis ( 39 + /- 20 , p < 0.001 ) , and the incidence of TIMI grade 3 flow was correspondingly higher after successful rescue PTCA ( 87 % vs 65 % , p = 0.002 ) . In-hospital adverse outcomes ( death , recurrent acute myocardial infa rct ion , severe congestive heart failure , cardiogenic shock or an ejection fraction < 40 % ) occurred in 29 % of successful rescue PTCAs and in 83 % of failed rescue PTCAs ( p = 0.01 ) . Among all patients in whom rescue PTCA was performed ( successes and failures combined ) , 35 % of patients experienced an adverse outcome , which was the same as the 35 % incidence observed in patients not undergoing rescue PTCA ( p = NS ) and tended to be higher than the 23 % incidence observed in patients with patent arteries ( p = 0.07 ) . Although successful rescue PTCA for an occluded artery at 90 minutes results in restoration of flow that is superior to that of successful thrombolysis , the incidence of adverse events for the strategy of rescue PTCA as a whole was the same as that of undertaking no PTCA |
11,743 | 26,371,211 | Surprisingly , TOTAL showed no difference in the primary efficacy outcome between the two approaches , but a significant increase in stroke .
Thus thrombectomy is associated with an increase in stroke , but , based on a meta- analysis of all trials , possibly with a trend towards reduced mortality .
Endovascular therapy significantly improved the rate of functional independence compared with fibrinolysis alone | Acute ischaemic stroke ranks high in morbidity and mortality statistics worldwide .
Unfortunately , even today , only a minority of patients receive interventional treatment .
Recent advances in imaging , mechanical thrombectomy , and logistics demonstrated a better outcome in stroke patients managed invasively .
This issue begins with a timely Current Opinion article entitled ‘ Ischaemic stroke and ST-segment elevation myocardial infa rct ion : fast-track single-stop approach ’ by Peter Lanzer from the Health Care Center in Bitterfeld , Germany .
In it , the authors propose a streamlined fast-track single-stop approach to treat patients with ischaemic stroke based on modified ST-segment elevation myocardial infa rct ion ( STEMI ) logistics to improve further the outcome of this devastating condition .
In addition to atrial fibrillation , atrial flutter is also a potential cause of stroke .
Since its first description about a century ago , our underst and ing of atrial flutter circuits has evolved considerably .
One atrial flutter circuit can have variable ECG manifestations , depending on the presence of a pre-existing atrial lesion or an altered atrial substrate .
Conversely , different right-sided or even left-sided atrial circuits including different mechanisms , for instance macro reentrant , micro re-entrant , or focal circuits , can present with a very a similar surface ECG .
The development of efficient high-resolution electroanatomical mapping systems has improved our knowledge about atrial flutter , as well as facilitated its treatment with radiofrequency catheter ablation .
Although stroke was commonly associated with myocardial infa rct ion in the past , particularly in patients with severe left ventricular dysfunction and thrombus formation after the event , this complication has become quite rare with modern early reperfusion .
Primary percutaneous intervention ( PCI ) aims to re-establish normal coronary perfusion as soon as possible .
To that end , many operators routinely use thrombectomy catheters to reduce thrombus load .
Although primary PCIs are state-of-the-art in the management of acute coronary syndromes , evidence from r and omized controlled trials on the possible benefits of endovascular therapy for acute ischaemic stroke showed conflicting results .
In another FAST TRACK paper entitled ‘ Endovascular therapy for acute ischaemic stroke : a systematic review and meta- analysis of r and omized trials ’ Partha Sardar and colleagues from the University of Utah Health Science Center in Salt Lake City analysed clinical outcomes of intravenous fibrinolysis alone compared with intravenous fibrinolysis plus endovascular therapy in acute ischaemic stroke . | AIMS Patients with atrial flutter are believed to be at lower risk of thromboembolism than patients with atrial fibrillation . However , the incidence of atrial thrombi and the need for anticoagulation in patients with atrial flutter is not well established . METHODS AND RESULTS A prospect i ve observational multicentre study was undertaken to assess the frequency of atrial thrombi and spontaneous echocontrast and the prevalence for aortic complex atherosclerotic lesions in a cohort of unselected patients with atrial flutter . We evaluated 134 patients ( 102 male , aged 70+/-9 years ) ; exclusion criteria were history of atrial fibrillation , rheumatic mitral valve disease and mitral mechanical prosthesis . The median of atrial flutter duration was 33 days . Twelve patients had been taking warfarin for more than 7 days . One hundred and twenty-four patients ( 94 % ) underwent a transoesophageal echocardiogram , which revealed left atrial appendage thrombi in two patients ( 1.6 % ) and right atrial thrombi in one patient ( 1 % ) . At least moderate left atrial echocontrast was found in 16/124 patients ( 13 % ) . Complex atherosclerotic aortic plaques were detected in 10 patients ( 8 % ) . Atrial flutter conversion was attempted in 93/134 patients ( 69 % ) . At the 1-month follow-up , two patients experienced a thromboembolic event following restoration of sinus rhythm . CONCLUSIONS Atrial thrombi and echocontrast , and complex aortic atherosclerotic plaques are relatively uncommon in patients with atrial flutter . Post-cardioversion embolism was observed in two patients in our study population ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American – Australian – African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association AND ROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled , double-blind , parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d . for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid ( ASA ) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospect i ve , r and omized , double-blind , Active-controlled , superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die ( twice daily ) b.p.m . : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension , Age ≥75 ( doubled ) , Diabetes , Stroke (doubled)-Vascular disease , Age 65–74 , Sex category ( female ) CHADS2 : Congestive heart failure , Hypertension , Age ≥75 , Diabetes , Stroke ( doubled ) CI : confidence interval CRAFT : Controlled R and omized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : R and omized Double blind trIal to evaluate efficacy and safety of drOnedarone ( 400 mg b.i.d . ) vs . amiodaroNe ( 600 mg q.d . for 28 daYS , then 200 mg qd thereafter ) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v . : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d . : omni die ( every day ) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of st and ard therapy PCI : percutaneous coronary intervention PREVAIL : Prospect i ve R and omized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : R and omized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d . : ter in die ( three times daily ) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition , taking into account the impact on AIMS We investigated the temporal changes in circulating levels of markers of extracellular cardiac matrix ( ECCM ) turnover and their relationship with infa rct size ( IS ) , ejection fraction ( EF ) , and left ventricular ( LV ) volumes , determined by serial cardiac magnetic resonance ( CMR ) imaging in patients with first-time ST-elevation myocardial infa rct ion ( STEMI ) . METHODS AND RESULTS Forty-two patients with a first-time STEMI , successfully revascularized by primary percutaneous coronary intervention ( pPCI ) had serum sample s taken prior to pPCI , 2 , 7 days , 2 months , and 1 year following STEMI for the analysis of the markers of collagen synthesis , and collagen degradation . Late enhancement and cine CMR was performed on Days 2 , 7 , 2 months , and 1-year post-STEMI . There was a significant increase in type I collagen degradation following STEMI that was not accompanied by an increase in collagen type I synthesis until 2 months and 1 year . In contrast to the delay in type I collagen synthesis , there was an immediate increase in type III collagen synthesis that was sustained for 1 year . N-terminal procollagen type I levels assessed prior to pPCI were predictive of adverse LV remodelling at all CMR time-points . CONCLUSIONS Our findings indicate a net type I collagen breakdown in the first week following STEMI compensated by an early increase in collagen type III synthesis . There is an increase in both type I and III collagen synthesis markers at 2 months and 1 year , indicating a persistent increase in collagen turnover even in these apparently successfully treated patients AIMS Primary percutaneous coronary intervention ( PCI ) is the preferred treatment for ST-elevation myocardial infa rct ion ( STEMI ) . The distance to primary PCI centres and the inherent time delay in delivering primary PCI , however , limit widespread use of this treatment . This study aim ed to evaluate the impact of pre-hospital diagnosis on time from emergency medical services contact to balloon inflation ( system delay ) in an unselected cohort of patients with STEMI recruited from a large geographical area comprising both urban and rural districts . METHODS AND RESULTS From February 2004 until January 2007 , data on pre-hospital timing and transport distance were prospect ively recorded . Patients were divided into groups depending on achievement of pre-hospital diagnosis and /or direct referral to a primary PCI centre . Seven hundred and fifty-nine consecutive STEMI patients were included . In patients with a pre-hospital diagnosis and direct referral , the system delay was 92 vs. 153 min in patients without pre-hospital diagnosis ( P < 0.001 ) . Patients from rural areas were transported a median of 30 km longer than patients from urban areas ; however , this prolonged the system delay by only 9 min . CONCLUSION Pre-hospital electrocardiographic ( ECG ) diagnosis and direct referral for primary PCI enables STEMI patients living far from a PCI centre to achieve a system delay comparable with patients living in close vicinity of a PCI centre AIMS TOTAL ( N = 10 732 ) , a r and omized trial of routine manual thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infa rct ion , showed no difference in the primary efficacy outcome but a significant increase in stroke . We sought to underst and these findings . METHODS AND RESULTS A detailed analysis of stroke timing , stroke severity , and stroke subtype was performed . Strokes were adjudicated by neurologists blinded to treatment assignment . Stroke within 30 days , the primary safety outcome , was increased [ 33 ( 0.7 % ) vs. 16 ( 0.3 % ) , hazard ratio ( HR ) 2.06 ; 95 % confidence interval ( CI ) 1.13 - 3.75 ] . The difference in stroke was apparent within 48 h [ 15 ( 0.3 % ) vs. 5 ( 0.1 % ) , HR 3.00 ; 95 % CI 1.09 - 8.25 ] . There was an increase in strokes within 180 days with minor or no disability ( Rankin 0 - 2 ) [ 18 ( 0.4 % ) vs. 13 ( 0.3 % ) HR 1.38 ; 95 % CI 0.68 - 2.82 ] and in strokes with major disability or fatal ( Rankin 3 - 6 ) [ 35 ( 0.7 % ) vs. 13 ( 0.3 % ) , HR 2.69 ; 95 % CI 1.42 - 5.08 ] . Most of the absolute difference was due to an increase in ischaemic strokes within 180 days [ 37 ( 0.7 % ) vs. 21 ( 0.4 % ) , HR 1.71 ; 95 % CI 1.03 - 3.00 ] , but there was also an increase in haemorrhagic strokes [ 10 ( 0.2 % ) vs. 2 ( 0.04 % ) , HR 4.98 ; 95 % CI 1.09 - 22.7 ] . Patients that had a stroke had a mortality of 30.8 % within 180 days vs. 3.4 % without a stroke ( P < 0.001 ) . A meta- analysis of r and omized trials ( N = 21 173 ) showed an increase in risk of stroke ( odds ratio 1.59 ; 95 % CI 1.11 - 2.27 ) but a trend towards reduction in mortality odds ratio ( odds ratio 0.87 ; 95 % CI 0.76 - 1.00 ) . CONCLUSION Thrombectomy was associated with a significant increase in stroke . Based on these findings , future trials must carefully collect stroke to determine safety in addition to efficacy The prevalence of left ventricular ( LV ) thrombosis and incidence of arterial embolism after acute anterior myocardial infa rct ion ( AAMI ) treated with streptokinase 1.5 x 10(6 ) IU intravenously was studied in 136 patients enrolled consecutively in five cardiological centres . Adjunctive antithrombotic therapy was administered according to the routine of each centre . Thrombus formation was studied by two-dimensional echocardiography , and events of arterial embolism recorded . LV thrombosis was found in 37 ( 27.2 % ) of the patients . In a subgroup of 53 patients receiving post-thrombolytic therapy with acetylsalicylic acid only , a thrombus developed in 14 ( 26.4 % ) . The thrombus prevalence among patients given high-dose heparin was significantly lower than among those receiving either low-dose heparin or no heparin ( 4/30 vs 33/106 , P = 0.045 ) . Logistic regression analysis suggested that severe LV wall motion abnormality ( P < 0.001 ) and avoidance of treatment with high-dose heparin ( P = 0.023 ) were independent predictors of LV thrombus formation . Only one patient ( 0.7 % ) suffered arterial embolism ( ischaemic stroke ) . In conclusion , LV thrombosis is frequent after thrombolytic therapy for AAMI , and impaired LV wall motion represents an independent predisposing factor . Low-dose heparin and acetylsalicylic acid seem less effective for LV thrombus prophylaxis than high-dose heparin . The incidence of arterial embolism is low |
11,744 | 24,771,460 | AUTHORS ' CONCLUSIONS This up date d Cochrane review supports the conclusions of the previous version of this review that , compared with no exercise control , exercise-based rehabilitation does not increase or decrease the risk of all-cause mortality in the short term ( up to 12-months ' follow-up ) but reduces the risk of hospital admissions and confers important improvements in health-related quality of life .
This up date provides further evidence that exercise training may reduce mortality in the longer term and that the benefits of exercise training on appear to be consistent across participant characteristics including age , gender and HF severity . | BACKGROUND Previous systematic review s and meta-analyses consistently show the positive effect of exercise-based rehabilitation for heart failure ( HF ) on exercise capacity ; however , the direction and magnitude of effects on health-related quality of life , mortality and hospital admissions in HF remain less certain .
This is an up date of a Cochrane systematic review previously published in 2010 .
OBJECTIVES To determine the effectiveness of exercise-based rehabilitation on the mortality , hospitalisation admissions , morbidity and health-related quality of life for people with HF . | Background — The long-term impact of chronic heart failure management programs over the typical life span of affected individuals is unknown . Methods and Results — The effects of a nurse-led , multidisciplinary , home-based intervention ( HBI ) in a typically elderly cohort of patients with chronic heart failure initially r and omized to either HBI ( n=149 ) or usual postdischarge care ( UC ) ( n=148 ) after a short-term hospitalization were studied for up to 10 years of follow-up ( minimum 7.5 years of follow-up ) . Study end points were all-cause mortality , event-free survival ( event was defined as death or unplanned hospitalization ) , recurrent hospital stay , and cost per life-year gained . Median survival in the HBI cohort was almost twice that of UC ( 40 versus 22 months ; P<0.001 ) , with fewer deaths overall ( HBI , 77 % versus 89 % ; adjusted relative risk , 0.74 ; 95 % CI , 0.53 to 0.80 ; P<0.001 ) . HBI was associated with prolonged event-free survival ( median , 7 versus 4 months ; P<0.01 ) . HBI patients had more unplanned readmissions ( 560 versus 550 ) but took 7 years to overtake UC ; the rates of readmission ( 2.04±3.23 versus 3.66±7.62 admissions ; P<0.05 ) and related hospital stay ( 14.8±23.0 versus 28.4±53.4 days per patient per year ; P<0.05 ) were significantly lower in the HBI group . HBI was associated with 120 more life-years per 100 patients treated compared with UC ( 405 versus 285 years ) at a cost of $ 1729 per additional life-year gained when we accounted for healthcare costs including the HBI . Conclusions — In altering the natural history of chronic heart failure relative to UC ( via prolonged survival and reduced frequency of recurrent hospitalization ) , HBI is a remarkably cost- and time-effective strategy over the longer term Systemic arterial compliance ( SAC ) makes an important contribution to cardiac afterload , and thus is a significant determinant of left ventricular work . Previous studies have suggested that arterial compliance may be reduced in patients with congestive heart failure ( CHF ) , and that SAC is increased after a 4-week exercise training programme in healthy , sedentary individuals . The present study aim ed to investigate the effects of an 8-week exercise training programme on arterial mechanical properties , left ventricular performance and quality of life in CHF patients . A total of 21 patients with NYHA class II or III CHF ( mean+/-S.D. age 55+/-13 years ) were r and omly allocated to either an 8-week exercise training group or a " usual lifestyle " control group . SAC , as determined non-invasively using applanation tonometry and Doppler aortic velocimetry , increased from 0.57+/-0.11 to 0.77+/-0.14 arbitrary compliance units ( mean+/-S.E.M. ; P=0.01 ) in the exercise group , while no change occurred in the control group . Left ventricular structure and function was assessed by echocardiography , and these parameters were unchanged over the 8-week study period . Exercise training significantly increased exercise capacity , measured by a 6-min walking test ( 474+/-27 to 547+/-34 m ; P=0.008 ) . Quality of life , as assessed using the Minnesota Living with Heart Failure Evaluation , demonstrated a decrease in heart failure symptoms from 46+/-7 to 24+/-5 units ( P=0.01 ) following the exercise training programme . These data show that exercise training improves SAC in patients with CHF . The accompanying improvement in exercise capacity may be due , in part , to an improvement in arterial function BACKGROUND The time required for oxygen uptake ( O(2 ) ) to return to baseline level ( recovery kinetics ) is prolonged in patients with reduced ventricular function , and the degree to which it is prolonged is related to the severity of heart failure , markers of abnormal ventilation , and prognosis . In the present study , we sought to determine the effect of exercise training on O(2 ) recovery kinetics in patients with reduced ventricular function . METHODS Twenty-four male patients with reduced ventricular function after a myocardial infa rct ion were r and omized to either a 2-month high-intensity residential exercise training program or to a control group . O(2 ) kinetics in recovery from maximal exercise were calculated before and after the study period and expressed as the slope of a single exponential relation between O(2 ) and time during the first 3 min of recovery . RESULTS Peak O(2 ) increased significantly in the exercise group ( 19.4 + /- 3.0 mL/kg/min vs 25.1 + /- 4.7 mL/kg/min , p < 0.05 ) , whereas no change was observed in control subjects . The O(2 ) half-time in recovery was reduced slightly after the study period in both groups ( 108.7 + /- 33.1 to 102.1 + /- 50.5 s in the exercise group and 122.3 + /- 68.7 to 107.5 + /- 36.0 s in the control group ) ; neither the change within or between groups was significant . The degree to which O(2 ) was prolonged in recovery was inversely related to measures of exercise capacity ( peak O(2 ) , watts achieved , and exercise time ; r = - 0.48 to - 0.57 ; p < 0.01 ) and directly related to the peak ventilatory equivalents for oxygen ( r = 0.59 , p < 0.01 ) and carbon dioxide ( r = 0.57 , p < 0.01 ) . CONCLUSION Two months of high-intensity training did not result in a faster recovery of O(2 ) in patients with reduced ventricular function . This suggests that adaptations to exercise training manifest themselves only during , but not in , recovery from exercise AIM To assess changes in quality of life ( QoL ) and oxygen consumption produced by two different patterns of physical training in patients with congestive heart failure ( CHF ) . MATERIAL AND METHODS 42 men ( mean age 55.9+/-8.1 years ) with ischaemic CHF lasting 3.1+/-1.0 years . Patients were r and omised into three groups each consisting of 14 men : group A -- with constant workload , group B-with progressive/increasing workload , each trained up to 6 months and group C -- not trained . QoL was assessed at baseline and at 6 months by means of the Psychological General Well-being Index ( PGWB ) and the Subjective Symptoms Assessment Profile ( SSA-P ) . Cardiopulmonary exercise test and echocardiography were performed twice . RESULTS At 6 months improvement in PGWB total index was observed , both in groups A and B ( p<0.01 ) . Men from groups A and B reported less cardiac symptoms ( p<0.01 ) , emotional distress ( p<0.01 ) , peripheral circulatory symptoms ( p<0.01 ) and dizziness ( p<0.01 ) in SSA-P. Improvement in sexual life was observed only in group B ( p<0.01 ) . Overall improvement of QoL was greater in group B than in group A as well as oxygen uptake ( p<0.01 ) . Higher QoL correlated positively with peak VO2 only in group B ( r=0.56 , p<0.05 ) . CONCLUSIONS Physical training improves QoL in men with CHF , but only progressive/increasing workload seems to markedly improve oxygen uptake . Improvement of QoL is related to psychological well-being and physical complaints associated with CHF BACKGROUND We aim ed to determine the role of skeletal muscle mitochondrial ATP production rate ( MAPR ) in relation to exercise tolerance after resistance training ( RT ) in chronic heart failure ( CHF ) . METHODS AND RESULTS Thirteen CHF patients ( New York Heart Association functional class 2.3 + /- 0.5 ; Left ventricular ejection fraction 26 + /- 8 % ; age 70 + /- 8 years ) underwent testing for peak total body oxygen consumption ( VO(2peak ) ) , and resting vastus lateralis muscle biopsy . Patients were then r and omly allocated to 11 weeks of RT ( n = 7 ) , or continuance of usual care ( C ; n = 6 ) , after which testing was repeated . Muscle sample s were analyzed for MAPR , metabolic enzyme activity , and capillary density . VO(2peak ) and MAPR in the presence of the pyruvate and malate ( P+M ) substrate combination , representing carbohydrate metabolism , increased in RT ( P < .05 ) and decreased in C ( P < .05 ) , with a significant difference between groups ( VO(2peak ) , P = .005 ; MAPR , P = .03 ) . There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption ( VO(2peak ) ) over the study ( r = 0.875 ; P < .0001 ) , the change in MAPR accounting for 70 % of the change in VO(2peak ) . CONCLUSIONS These findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise BACKGROUND Current guidelines broadly recommend comprehensive cardiac rehabilitation ( CR ) , although evidence for this is still limited . It is not known whether evidence from before 1995 is still valid . STUDY DESIGN The DANish Cardiac ReHABilitation ( DANREHAB ) trial was design ed as a central ly r and omized clinical trial to clarify whether hospital-based comprehensive CR is superior to usual care for patients with congestive heart failure , ischemic heart disease , or high risk for ischemic heart disease . A combined primary outcome measure included total mortality , myocardial infa rct ion , or readmissions due to heart disease based on linkage to public registries . The CR was an individually tailored , multidisciplinary program ( 6 weeks of intensive CR and 12 months of follow-up ) including patient education , exercise training , dietary counseling , smoking cessation , psychosocial support , risk factor management , and clinical assessment . STUDY POPULATION Of 5060 discharged patients , 1614 ( 32 % ) were eligible for the trial and 770 patients were r and omized ( 47 % of those eligible ) . Participants were younger ( P < .001 ) and had less comorbidity than non participants ( P < .03 ) . CONCLUSION Our trial shows that a large-scale , central ly r and omized clinical trial on comprehensive CR can be conducted among a broadly defined patient group , but reaching the stipulated number of 1800 patients was difficult . Although the study included relatively many women and older people , elderly patients and patients with high comorbidity were underrepresented , which may influence the external validity BACKGROUND Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure ( HF ) ; this has not been rigorously tested in a large clinical sample . We sought to investigate whether tai chi , as an adjunct to st and ard care , improves functional capacity and quality of life in patients with HF . METHODS A single-blind , multisite , parallel-group , r and omized controlled trial evaluated 100 out patients with systolic HF ( New York Heart Association class I-III , left ventricular ejection fraction ≤40 % ) who were recruited between May 1 , 2005 , and September 30 , 2008 . A group-based 12-week tai chi exercise program ( n = 50 ) or time-matched education ( n = 50 , control group ) was conducted . Outcome measures included exercise capacity ( 6- minute walk test and peak oxygen uptake ) and disease-specific quality of life ( Minnesota Living With Heart Failure Question naire ) . RESULTS Mean ( SD ) age of patients was 67 ( 11 ) years ; baseline values were left ventricular ejection fraction , 29 % ( 8 % ) and peak oxygen uptake , 13.5 mL/kg/min ; the median New York Heart Association class of HF was class II . At completion of the study , there were no significant differences in change in 6-minute walk distance and peak oxygen uptake ( median change [ first quartile , third quartile ] , 35 [ -2 , 51 ] vs 2 [ -7 , 54 ] meters , P = .95 ; and 1.1 [ -1.1 , 1.5 ] vs -0.5 [ -1.2 , 1.8 ] mL/kg/min , P = .81 ) when comparing tai chi and control groups ; however , patients in the tai chi group had greater improvements in quality of life ( Minnesota Living With Heart Failure Question naire , -19 [ -23 , -3 ] vs 1 [ -16 , 3 ] , P = .02 ) . Improvements with tai chi were also seen in exercise self-efficacy ( Cardiac Exercise Self-efficacy Instrument , 0.1 [ 0.1 , 0.6 ] vs -0.3 [ -0.5 , 0.2 ] , P < .001 ) and mood ( Profile of Mood States total mood disturbance , -6 [ -17 , 1 ] vs -1 [ -13 , 10 ] , P = .01 ) . CONCLUSION Tai chi exercise may improve quality of life , mood , and exercise self-efficacy in patients with HF . Trial Registration clinical trials.gov Identifier : NCT00110227 Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies BACKGROUND Heart failure , a condition predominantly affecting the elderly , represents an ever-increasing clinical and financial burden for the NHS . Cardiac rehabilitation , a service that incorporates patient education , exercise training and lifestyle modification , requires further evaluation in heart failure management . AIM The aim of this study was to determine whether a cardiac rehabilitation programme improved on the outcomes of an outpatient heart failure clinic ( st and ard care ) for patients , over 60 years of age , with chronic heart failure . METHODS Two hundred patients ( 60 - 89 years , 66 % male ) with New York Heart Association ( NYHA ) II or III heart failure confirmed by echocardiography were r and omised . Both st and ard care and experimental groups attended clinic with a cardiologist and specialist nurse every 8 weeks . Interventions included exercise prescription , education , dietetics , occupational therapy and psychosocial counselling . The main outcome measures were functional status ( NYHA , 6-min walk ) , health-related quality of life ( MLHF and EuroQol ) and hospital admissions . RESULTS There were significant improvements in MLHF and EuroQol scores , NYHA classification and 6-min walking distance ( meters ) at 24 weeks between the groups ( p<0.001 ) . The experimental group had fewer admissions ( 11 vs. 33 , p<0.01 ) and spent fewer days in hospital ( 41 vs. 187 , p<0.001 ) . CONCLUSIONS Cardiac rehabilitation , already widely established in the UK , offers an effective model of care for older patients with heart failure Benefit from exercise training programmes for patients with chronic heart failure has been demonstrated in relatively young ( mean age 60 years ) and predominantly male subjects . This study was undertaken to assess the effect of an exercise programme for older subjects more representative of the general heart failure population Aim . The aim of this prospect i ve r and omized study was to evaluate the impact of long-term aerobic exercise training on respiratory function , left ventricular systolic function and remodeling in patients with coronary heart disease and ischemic heart failure after successful angioplasty . Design . Patients ( n=185 ) have undergone Doppler echocardiography and ergospirometry . Ninety-five patients practice d 6 month-term aerobic exercise training , less by 10 % to their anaerobic threshold . Ninety patients were studied as controls . They were given only drug treatment without training . Measurements were repeated after 6 and 12 months . Results . Training group patients after 6 months showed significant ( p<0.05 ) improvement in exercise capacity , oxygen consumption and ventilating equivalents . The Doppler echocardiographic findings revealed significant ( p<0.05 ) improvement in ejection fraction , left ventricular and atria morphometric data . Improved ergospirometric and echocardiographic data were established after 12 months , too . Conclusions . Long-term aerobic exercise training is an effective and workable measure improving respiratory efficiency , left ventricular systolic function , attenuating negative remodeling and stopping further progression in patients with coronary heart disease and chronic heart failure after successful angioplasty AIMS Supervised exercise can benefit selected patients with heart failure , however the effectiveness of home-based exercise remains uncertain . We aim ed to assess the effectiveness of a home-based exercise programme in addition to specialist heart failure nurse care . METHODS AND RESULTS This was a r and omized controlled trial of a home-based walking and resistance exercise programme plus specialist nurse care ( n=84 ) compared with specialist nurse care alone ( n=85 ) in a heart failure population in the West Midl and s , UK . PRIMARY OUTCOME Minnesota Living with Heart Failure Question naire ( MLwHFQ ) at 6 and 12 months . SECONDARY OUTCOMES composite of death , hospital admission with heart failure or myocardial infa rct ion ; psychological well-being ; generic quality of life ( EQ-5D ) ; exercise capacity . There was no statistically significant difference between groups in the MLwHFQ at 6 month ( mean , 95 % CI ) ( -2.53 , -7.87 to 2.80 ) and 12 month ( -0.55 , -5.87 to 4.76 ) follow-up or secondary outcomes with the exception of a higher EQ-5D score ( 0.11 , 0.04 to 0.18 ) at 6 months and lower Hospital Anxiety and Depression Scale score ( -1.07 , -2.00 to -0.14 ) at 12 months , in favour of the exercise group . At 6 months , the control group showed deterioration in physical activity , exercise capacity , and generic quality of life . CONCLUSION Home-based exercise training programmes may not be appropriate for community-based heart failure patients CONTEXT Guidelines recommend that exercise training be considered for medically stable out patients with heart failure . Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes . OBJECTIVE To test the efficacy and safety of exercise training among patients with heart failure . DESIGN , SETTING , AND PATIENTS Multicenter , r and omized controlled trial of 2331 medically stable out patients with heart failure and reduced ejection fraction . Participants in Heart Failure : A Controlled Trial Investigating Outcomes of Exercise Training ( HF-ACTION ) were r and omized from April 2003 through February 2007 at 82 centers within the United States , Canada , and France ; median follow-up was 30 months . INTERVENTIONS Usual care plus aerobic exercise training , consisting of 36 supervised sessions followed by home-based training , or usual care alone . MAIN OUTCOME MEASURES Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality , cardiovascular mortality or cardiovascular hospitalization , and cardiovascular mortality or heart failure hospitalization . RESULTS The median age was 59 years , 28 % were women , and 37 % had New York Heart Association class III or IV symptoms . Heart failure etiology was ischemic in 51 % , and median left ventricular ejection fraction was 25 % . Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12 . A total of 759 patients ( 65 % ) in the exercise training group died or were hospitalized compared with 796 patients ( 68 % ) in the usual care group ( hazard ratio [ HR ] , 0.93 [ 95 % confidence interval { CI } , 0.84 - 1.02 ] ; P = .13 ) . There were nonsignificant reductions in the exercise training group for mortality ( 189 patients [ 16 % ] in the exercise training group vs 198 patients [ 17 % ] in the usual care group ; HR , 0.96 [ 95 % CI , 0.79 - 1.17 ] ; P = .70 ) , cardiovascular mortality or cardiovascular hospitalization ( 632 [ 55 % ] in the exercise training group vs 677 [ 58 % ] in the usual care group ; HR , 0.92 [ 95 % CI , 0.83 - 1.03 ] ; P = .14 ) , and cardiovascular mortality or heart failure hospitalization ( 344 [ 30 % ] in the exercise training group vs 393 [ 34 % ] in the usual care group ; HR , 0.87 [ 95 % CI , 0.75 - 1.00 ] ; P = .06 ) . In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics , the HRs were 0.89 ( 95 % CI , 0.81 - 0.99 ; P = .03 ) for all-cause mortality or hospitalization , 0.91 ( 95 % CI , 0.82 - 1.01 ; P = .09 ) for cardiovascular mortality or cardiovascular hospitalization , and 0.85 ( 95 % CI , 0.74 - 0.99 ; P = .03 ) for cardiovascular mortality or heart failure hospitalization . Other adverse events were similar between the groups . CONCLUSIONS In the protocol -specified primary analysis , exercise training result ed in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points . After adjustment for highly prognostic predictors of the primary end point , exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047437 Objective : To determine the short- and long-term effects of an intensive , concentrated rehabilitation programme in patients with chronic heart failure . Design : R and omized controlled trial , with one-month and six-year evaluations . Setting : Residential rehabilitation centre in Switzerl and . Subjects : Fifty patients with chronic heart failure , r and omized to exercise or control groups . Interventions : A rehabilitation programme lasting one month , including educational sessions , a low-fat diet , and 2 hours of individually prescribed exercise daily . Main measures : Exercise test responses , health outcomes and physical activity patterns . Results : Peak Vo2 increased 21.4 % in the exercise group during the rehabilitation programme ( P<0.05 ) , whereas peak Vo2 did not change among controls . After the six-year follow-up period , peak Vo2 was only slightly higher than that at baseline in the trained group ( 7 % , NS ) , while peak Vo2 among controls was unchanged . During long-term follow-up , 9 and 12 patients died in the exercise and control groups , respectively ( P = 0.63 ) . At six years , physical activity patterns tended to be higher in the exercise group ; the mean energy expenditure values over the last year were 2704 ± 1970 and 2085 ± 1522 kcal/week during recreational activities for the exercise and control groups , respectively . However , both groups were more active compared to energy expenditure prior to their cardiac event ( P<0.001 ) . Conclusions : Six years after participation in a residential rehabilitation programme , patients with chronic heart failure had slightly better outcomes than control subjects , maintained exercise capacity and engaged in activities that exceed the minimal amount recommended by guidelines for cardiovascular health BACKGROUND Exercise training is now an accepted therapeutic intervention in patients with reduced ventricular function after a myocardial infa rct ion . However , there are conflicting reports on the effects of training on the remodeling process of the heart , and previous studies have only assessed short-term effects of training . METHODS AND RESULTS Twenty-five patients with reduced ventricular function after myocardial infa rct ion were r and omly assigned to an intensive 2-month exercise training program or to a control group ( control group : n = 13 , aged 55 + /- 7 years , ejection fraction 33.3 % + /- 6 % ; exercise group : n = 12 , aged 56 + /- 5 years , ejection fraction 31.5 % + /- 7 % ) and followed up for 1 year . Measures of left ventricular size , function , and wall thickness in the infa rct and noninfa rct areas were made by magnetic resonance imaging at baseline , after the 2-month training period , and 1 year later . Maximal oxygen uptake increased in the trained group , from 19.7 + /- 3 mL/kg per minute at baseline to 25.1 + /- 5 and 24.2 + /- 5 mL/kg per minute after 2 months and 1 year , respectively ( P < .05 vs baseline for both ) , whereas the control group did not change significantly . Ejection fraction , end-diastolic volumes , and end-systolic volumes did not change at any measurement point throughout the study period in either the trained or control groups . Myocardial wall thickness measurements at end-diastole and end-systole and their differences determined by magnetic resonance imaging yielded no significant interactions between groups . When myocardial wall thickness measurements were classified by infa rct or noninfa rct areas , no differences were observed between groups over the study period . CONCLUSIONS Intensive exercise training in patients with reduced ventricular function result ed in a significant improvement in exercise capacity after 2 months , and this improvement was sustained over 1 year . In contrast to some recent reports , training had no deleterious effects on left ventricular volume , function , or wall thickness regardless of infa rct area Studies on the long-term effects of exercise training programs on functional capacity and the quality of life in patients with chronic heart failure ( CHF ) are sparse . The aim of this study was to evaluate the long-term effects of group-based , high-intensity interval training on functional capacity and the quality of life in 80 patients with stable CHF ( mean age 70.1 + /- 7.9 years ) in New York Heart Association classes II to IIIB . Patients were r and omized to either an exercise group ( n = 40 ) or a control group ( n = 40 ) . The mean ejection fractions at baseline were 31 + /- 8 % in the exercise group and 31 + /- 1 % in the control group . The exercise group exercised twice a week for 4 months in addition to 4 consultations with a CHF nurse . Six-minute walking distance , workload and exercise time on a cycle ergometer test , and the quality of life were measured at baseline and 4 and 12 months after enrollment . After 4 months , functional capacity ( 6-minute walking distance + 58 vs -15 m , p < 0.001 ) and the quality of life ( Minnesota Living With Heart Failure Question naire score + 10 vs -1 point , p < 0.005 ) improved significantly in the exercise group compared with the control group . After 12 months , the improvements were still significant in the exercise group compared with the control group for all parameters ( 6-minute walking distance + 41 vs -20 m , p < 0.001 ; workload + 10 vs -1 W , p = 0.001 ; exercise time + 53 vs -6 seconds , p = 0.003 ; quality of life + 10 vs -6 points , p = 0.003 ) . In conclusion , the results support the implementation of a group-based aerobic interval training program to improve long-term effects on functional capacity and the quality of life in patients with CHF OBJECTIVES We sought to determine whether structured exercise training ( ET ) improves maximal exercise capacity , left ventricular diastolic function , and quality of life ( QoL ) in patients with heart failure with preserved ejection fraction ( HFpEF ) . BACKGROUND Nearly one-half of patients with heart failure experience HFpEF , but effective therapeutic strategies are sparse . METHODS A total of 64 patients ( age 65 ± 7 years , 56 % female ) with HFpEF were prospect ively r and omized ( 2:1 ) to supervised endurance/resistance training in addition to usual care ( ET , n = 44 ) or to usual care alone ( UC ) ( n = 20 ) . The primary endpoint was the change in peak Vo(2 ) after 3 months . Secondary endpoints included effects on cardiac structure , diastolic function , and QoL. RESULTS Peak Vo(2 ) increased ( 16.1 ± 4.9 ml/min/kg to 18.7 ± 5.4 ml/min/kg ; p < 0.001 ) with ET and remained unchanged ( 16.7 ± 4.7 ml/min/kg to 16.0 ± 6.0 ml/min/kg ; p = NS ) with UC . The mean benefit of ET was 3.3 ml/min/kg ( 95 % confidence interval [ CI ] : 1.8 to 4.8 , p < 0.001 ) . E/e ' ( mean difference of changes : -3.2 , 95 % CI : -4.3 to -2.1 , p < 0.001 ) and left atrial volume index ( milliliters per square meter ) decreased with ET and remained unchanged with UC ( -4.0 , 95 % CI : -5.9 to -2.2 , p < 0.001 ) . The physical functioning score ( 36-Item Short-Form Health Survey ) improved with ET and remained unchanged with UC ( 15 , 95 % CI : 7 to 24 , p < 0.001 ) . The ET-induced decrease of E/e ' was associated with 38 % gain in peak Vo(2 ) and 50 % of the improvement in physical functioning score . CONCLUSIONS Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF . This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function . ( Exercise Training in Diastolic Heart Failure-Pilot Study : A Prospect i ve , R and omised , Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [ Ex-DHF-P ] ; IS RCT N42524037 ) Clinical trials design ed to evaluate the effect of drugs and devices on the symptoms and clinical status in chronic heart failure have frequently produced conflicting , inconclusive , or misleading results . These difficulties can be explained by the fact that previous studies have relied on efficacy measures that have inherent limitations and have been analyzed using statistical approaches that ignored episodes of clinical deterioration . Recognition of these pitfalls has led to the development of a new clinical composite score , which combines changes in the New York Heart Association class and the global assessment together with the information provided from the occurrence of major clinical events . Use of this score would have correctly distinguished active therapy from placebo in earlier trials and thus would have avoided some of their misleading conclusions . The new clinical composite score has been prospect ively incorporated into the design of studies evaluating the efficacy of endothelin antagonists , cytokine antagonists , vasopressin antagonists , and cardiac resynchronization in the treatment of chronic heart failure . In the trials that have been completed to date , the clinical composite score has been more sensitive than conventional approaches in discerning the presence or absence of a true treatment effect OBJECTIVES The aim of this study was to assess the effects of regular physical exercise on local inflammatory parameters in the skeletal muscle of patients with chronic heart failure ( CHF ) . BACKGROUND Inflammatory activation with increased serum cytokine levels and expression of inducible nitric oxide synthase ( iNOS ) in the myocardium and peripheral skeletal muscles has been described in CHF . METHODS Twenty male patients with stable CHF ( left ventricular ejection fraction 25 + /- 2 % ; age 54 + /- 2 years ) were r and omized to a training group ( n = 10 ) or a control group ( n = 10 ) . At baseline and after six months , serum sample s and vastus lateralis muscle biopsies were obtained . Serum tumor necrosis factor (TNF)-alpha , interleukin (IL)-6 , and IL-1-beta levels were measured by enzyme-linked immunosorbent assay , local cytokine , and iNOS expression by real-time polymerase chain reaction . RESULTS Exercise training improved peak oxygen uptake by 29 % in the training group ( from 20.3 + /- 1.0 to 26.1 + /- 1.5 ml/kg . min ; p < 0.001 vs. control group ) . While serum levels of TNF-alpha , IL-6 , and IL-1-beta remained unaffected by training , local skeletal muscle TNF-alpha decreased from 1.9 + /- 0.4 to 1.2 + /- 0.3 relative U ( p < 0.05 for change vs. control group ) , IL-6 from 71.3 + /- 16.5 to 41.3 + /- 8.8 relative U ( p < 0.05 vs. begin ) , and IL-1-beta from 2.7 + /- 1.1 to 1.4 + /- 0.6 relative U ( p = 0.02 vs. control group ) . Exercise training also reduced local iNOS expression by 52 % ( from 6.3 + /- 1.2 to 3.0 + /- 1.0 relative U ; p = 0.007 vs. control group ) . CONCLUSIONS Exercise training significantly reduced the local expression of TNF-alpha , IL-1-beta , IL-6 , and iNOS in the skeletal muscle of CHF patients . These local anti-inflammatory effects of exercise may attenuate the catabolic wasting process associated with the progression of CHF Background —Heart failure ( HF ) with preserved left ventricular ejection fraction ( HFPEF ) is the most common form of HF in the older population . Exercise intolerance is the primary chronic symptom in patients with HFPEF and is a strong determinant of their reduced quality of life ( QOL ) . Exercise training ( ET ) improves exercise intolerance and QOL in patients with HF with reduced ejection fraction ( EF ) . However , the effect of ET in HFPEF has not been examined in a r and omized controlled trial . Methods and Results —This 16-week investigation was a r and omized , attention-controlled , single-blind study of medically supervised ET ( 3 days per week ) on exercise intolerance and QOL in 53 elderly patients ( mean age , 70±6 years ; range , 60 to 82 years ; women , 46 ) with isolated HFPEF ( EF ≥50 % and no significant coronary , valvular , or pulmonary disease ) . Attention controls received biweekly follow-up telephone calls . Forty-six patients completed the study ( 24 ET , 22 controls ) . Attendance at exercise sessions in the ET group was excellent ( 88 % ; range , 64 % to 100 % ) . There were no trial-related adverse events . The primary outcome of peak exercise oxygen uptake increased significantly in the ET group compared to the control group ( 13.8±2.5 to 16.1±2.6 mL/kg per minute [ change , 2.3±2.2 mL/kg per minute ] versus 12.8±2.6 to 12.5±3.4 mL/kg per minute [ change , −0.3±2.1 mL/kg per minute ] ; P=0.0002 ) . There were significant improvements in peak power output , exercise time , 6-minute walk distance , and ventilatory anaerobic threshold ( all P<0.002 ) . There was improvement in the physical QOL score ( P=0.03 ) but not in the total score ( P=0.11 ) . Conclusions —ET improves peak and submaximal exercise capacity in older patients with HFPEF . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01113840 This preliminary study tested the effects of a home-based walking intervention on total sleep time ( TST ) , nocturnal awakenings , depressive symptoms , physical function , and quality of life ( QOL ) in older women with diastolic heart failure ( DHF ) . Twenty-three women ( mean age , 68+/-11 years ) with New York Heart Association class II or III DHF were r and omized to either a 12-week home-based walking intervention ( n=13 ) or education-only program ( control , n=10 ) . No between-group differences were found in women in the intervention and control groups on any of the outcome variables . When outcomes were compared within each group at baseline and 12 weeks , intervention-group patients had improvement in TST ( P<.01 ) and heart failure-related QOL ( P<.05 ) and a trend for decreased depressive symptoms ( P<.07 ) . Women r and omized to the control group had no change in any outcomes . These preliminary findings suggest that a progressive walking program may improve TST and QOL in older women with DHF . Findings from this study support the need for larger studies to evaluate the long-term benefits of a walking program on sleep patterns , QOL , and psychologic function in this population Background —Little is known about the optimum way to deliver exercise to older , functionally impaired patients with heart failure . We tested whether an exercise program tailored to the needs of these patients could improve exercise capacity and quality of life or reduce costs to the National Health Service . Methods and Results —The study design was a parallel-group , single-blind , r and omized controlled trial . Patients aged ≥70 years with symptomatic heart failure and left ventricular systolic dysfunction were r and omized to either 24 weeks of exercise training or usual care . Six-minute walk distance was the primary outcome ; markers of physical function , quality of life , health status , and daily activity were measured at baseline and 8 and 24 weeks . Carer strain and healthcare costs were also recorded . A total of 107 participants were r and omized ( mean age , 80 years ; men , 72 [ 67 % ] ) . Six-minute walk distance did not improve compared to that of the control group at 8 weeks ( −16.9 m ; 95 % CI , −41.8 to 7.9 m ; P=0.18 ) or at 24 weeks ( −5.3 m ; 95 % CI , −32.6 to 22.0 m ; P=0.70 ) . For secondary outcomes , only the sit-to-st and test improved significantly at 24 weeks ( −6.4 s ; 95 % CI , −12.2 to 0.6 s ; P=0.03 ) ; there was no difference in change for the Minnesota Living With Heart Failure score ( 0.1 points ; 95 % CI , −0.9 to 1.1 points ; P=0.83 ) at 24 weeks . Carer strain did not decrease at 24 weeks ( difference , −0.5 points ; 95 % CI , −8.3 to 7.3 points ; P=0.80 ) , and there was no difference in overall healthcare costs . Conclusions —This exercise intervention did not improve exercise capacity or quality of life in older patients with heart failure and was not cost saving to the National Health Service . Clinical Trial Registration —URL : http://www.controlled-trials.com . Unique identifier : IS RCT N51615566 BACKGROUND Exercise training in heart failure patients improves exercise capacity , physical function , and quality -of-life . Prior studies indicate a rapid loss of these effects following termination of the training . We wanted to assess any sustained post-training effects on patients global assessment of change in quality -of-life ( PGACQoL ) and physical function . METHODS Fifty-four stable heart failure patients were r and omised to exercise or control . The 4-month exercise programme consisted of bicycle training at 80 % of maximal intensity three times/week , and 49 patients completed the active study period . At 10 months ( 6 months post training ) 37 patients were assessed regarding PGACQoL , habitual physical activity , and dyspnea-fatigue-index . RESULTS Both post-training patients ( n=17 ) and controls ( n=20 ) deteriorated PGACQoL during the 6-month extended follow-up , although insignificantly . However , post-training patients improved PGACQoL slightly but significantly from baseline to 10 months ( P=0.006 ) , differing significantly ( P=0.023 ) from controls who were unchanged . Regarding dyspnea-fatigue-index , post-training patients were largely unchanged and controls deteriorated insignificantly , during the extended follow-up as well as from baseline to 10 months . Both groups decreased physical activity insignificantly during the extended follow-up , and from baseline to 10 months post-training patients tended to decrease whereas controls significantly ( P=0.007 ) decreased physical activity . CONCLUSION There was no important sustained benefit 6 months after termination of an exercise training programme in heart failure patients . A small , probably clinical ly insignificant sustained improvement in PGACQoL was seen in post-training patients . Controls significantly decreased the habitual physical activity over 10 months and post-training patients showed a similar trend . Exercise training obviously has to be continuing to result in sustained benefit BACKGROUND Exercise training is now an accepted component of the therapeutic regimen in patients with heart failure and underlying ischemia , but few data are available on the effects of training in patients with nonischemic dilated cardiomyopathy . METHODS Twenty-four patients ( mean age 55 + /- 9 years , mean ejection fraction 26.6 % + /- 10 % ) were r and omized to an exercise ( n = 12 ) or a control ( n = 12 ) group . Patients in the exercise group underwent 5 45-minute sessions of supervised training per week . Before and after the 2-month study period , exercise testing with respiratory gas exchange and lactate analysis was performed , left ventricular volumes and ejection fraction were measured with magnetic resonance imaging , and left ventricular rotation and relaxation velocities were measured with a novel magnetic resonance imaging tagging technique . RESULTS Training result ed in increases in peak oxygen uptake ( VO2 ) ( 21.7 + /- 4 mL/kg/min to 25.3 + /- 5 mL/kg/min , P < .05 ) and VO2 at the lactate threshold ( 12.8 + /- 4 mL/kg/min to 19.0 + /- 5 mL/kg/min , P < .01 ) . No differences were observed within or between groups in left ventricular end-diastolic volume , end-systolic volume , or ejection fraction . Velocity of left ventricular rotation during systole was unchanged in both groups , and relaxation velocity was higher after training in the exercise group ( 21.2 + /- 5 degrees/s versus 29.7 + /- 12 degrees/s , P < .05 ) . CONCLUSION Training result ed in increases in peak VO2 and VO2 at the lactate threshold . Left ventricular volumes and systolic function ( ie , ejection fraction and rotation velocity ) were unchanged with training , suggesting that training in patients with dilated cardiomyopathy does not lead to further myocardial damage . However , the increase in relaxation velocity after exercise training indicates an improvement in diastolic function . The latter finding suggests an additional potential benefit of exercise training in patients with dilated cardiomyopathy Purpose : The purpose of this study was to compare an Exercise Training Group ( EX ) with an Attention‐Control Group ( AT‐C ) to more specifically assess the impact of exercise training on individuals with heart failure ( HF ) . Methods : Forty‐two individuals with HF were r and omized to AT‐C or EX that met with the same frequency and format of investigator interaction . Baseline , 12‐ and 24‐week measurements of B‐type naturetic peptide ( BNP ) , 6‐minute walk test ( 6‐MWT ) , and the Kansas City Cardiomyopathy Question naire ( KCCQ ) were obtained . Results : BNP tended to increase in the AT‐C while remaining stable in the EX over time . A clinical ly significant increase in 6‐MWT was demonstrated by the EX but not the AT‐C. The EX achieved a clinical ly significant change on the KCCQ at 12 weeks , with further improvement by 24 weeks , while the AT‐C demonstrated a clinical ly significant change at 24 weeks . Conclusions : Attention alone was inadequate to positively impact BNP levels or 6‐MWT distances , but did have a positive impact on quality of life after 24 weeks . Although exercise offers enhanced benefits , individuals with HF unable to participate in an exercise program may still gain quality of life benefits from participation in a peersupport group that discusses topics pertinent to HF Background Exercise training ( ET ) has been shown to improve functional work capacity in patients with stable chronic heart failure ( CHF ) having moderate symptoms ( NYHA class II ) . This analysis was conducted , to evaluate the effects of ET on left ventricular function and haemodynamics in patients with advanced CHF ( NYHA class III ) fulfilling the inclusion criteria of the COPERNICUS trial . Methods Seventy-three patients with moderate and advanced CHF were prospect ively r and omised to a training ( n = 36 ) , or to a control group ( n = 37 ) . At baseline and after six months , patients underwent echocardiography and symptom-limited ergospirometry with measurement of central haemodynamics by thermodilution . Results Nine out of 37 patients in the control group ( C ) and 10 out of 36 patients in the training group ( T ) had symptoms of advanced CHF . Exercise training over a period of six months result ed in an improvement of functional status on average by one NYHA class in patients with advanced CHF . Moreover , oxygen uptake at the ventilatory threshold increased by 49 % ( from 7.7 ± 1.0 to 11.4 ± 0.4 mL/min/kg , P<0.01 versus baseline ) and at peak exercise by 32 % ( from 16.3 ± 1.6 to 21.5 ± 1.2 mL/min/kg , P<0.01 versus baseline ) in training patients . The small , but significant reduction in left ventricular end-diastolic diameter by 7 % ( from 70 ± 2 to 66 ± 2 mm ; P<0.05 versus baseline ) was accompanied by an augmentation in stroke volume at rest by 32 % ( from 45 ± 3 to 60 ± 6 mL , P<0.05 versus baseline ) and at peak exercise by 27 % ( 63 ± 9 to 81 ±9 mL , P<0.05 versus baseline ) as a result of ET in patients with advanced CHF . Conclusion In patients with advanced CHF ( NYHA class III ) , long-term exercise training is associated with an enhanced physical work capacity , an improvement in stroke volume and a reduction in cardiomegaly Acute bouts of exercise have been shown to induce inflammatory cytokine activation and peripheral hypoxia in patients with chronic heart failure ( CHF ) . In this study , we set out to investigate the impact of chronic exercise training on pro‐inflammatory cytokines and markers of endothelial damage To determine the effect of training on insulin sensitivity ( IS ) and how this relates to peak V(.)O(2 ) ( peak oxygen uptake ) in CHF ( chronic heart failure ) , 77 CHF patients ( New York Heart Association class , II/III ; men/women , 59/18 ; age , 60+/-9 years ; body mass index , 26.7+/-3.9 kg/m(2 ) ; left ventricular ejection fraction , 26.9+/-8.1 % ; expressed as means+/-S.D. ) participated in the study . Patients were r and omly assigned to a training or control group ( TrG or CG respectively ) . Sixty-one patients completed the study . Patients participated in training ( combined strength and endurance exercises ) four times per week , two times supervised and two times at home . Before and after intervention , anthropometry , IS ( euglycaemic hyperinsulinaemic clamp ) and peak V(.)O(2 ) ( incremental cycle ergometry ) were assessed . Intervention did not affect IS significantly , even though IS increased by 20 % in TrG and 11 % in CG ( not significant ) . Peak V(.)O(2 ) increased as a result of training ( 6 % increase in TrG ; 2 % decrease in CG ; P < 0.05 ) . In both groups ( TrG and CG ) , the change in IS correlated positively with the change in peak V(.)O(2 ) ( r = 0.30 , P < 0.05 ) . Training result ed in an increase in peak V(.)O(2 ) , but not in IS . Whether physical training actually increases IS in CHF patients remains unclear BACKGROUND There is evidence that exercise training can induce myocardial and coronary adaptations in both animals and humans . However , the significance of these potentially important changes remains to be determined in patients with ischemic heart disease and left ventricular ( LV ) systolic dysfunction . METHODS AND RESULTS To investigate whether exercise training can improve thallium uptake and the contractile response to low-dose dobutamine of dysfunctional myocardium , 46 patients ( 42 men , 4 women ; mean age , 57+/-9 years ) with chronic coronary artery disease and impaired LV systolic function ( ejection fraction < 40 % ) were r and omly assigned to two groups . The exercise group ( n = 26 ) underwent exercise training at 60 % of peak oxygen uptake for 8 weeks . The control group ( n = 20 ) was not exercised . At baseline and after 8 weeks all patients underwent an exercise test with gas exchange analysis and stress echocardiography using low-dose dobutamine ( 5 to 10 microg/kg per minute ) followed by thallium myocardial scintigraphy . Coronary angiography was performed in 23 patients at baseline and after 8 weeks . After 8 weeks , peak oxygen uptake increased significantly only in trained patients ( 24 % ) . Significant improvements in the contractile response to dobutamine and thallium activity were observed in trained patients ( 28 % and 31 % , respectively ; trained versus control : P<.001 for both ) . In a subgroup of trained patients , both improvements were correlated with an increase in the coronary collateral score ( P<.005 and P<.001 , respectively ) . CONCLUSIONS Moderate exercise training improves both thallium activity and the contractile response of dysfunctional myocardium to low doses of dobutamine in patients with ischemic cardiomyopathy . The implication of this study is that even a short-term exercise training may improve quality of life by improvement of LV systolic function during mild-to-moderate physical activity in patients with ischemic cardiomyopathy BACKGROUND We examined the effect of a home-based intervention ( HBI ) on readmission and death among " high-risk " patients with congestive heart failure discharged home from acute hospital care . METHODS Hospitalized patients with congestive heart failure and impaired systolic function , intolerance to exercise , and a history of 1 or more hospital admissions for acute heart failure were r and omized to either usual care ( n=48 ) or HBI at 1 week after discharge ( n=49 ) . Home-based intervention comprised a single home visit ( by a nurse and pharmacist ) to optimize medication management , identify early clinical deterioration , and intensify medical follow-up and caregiver vigilance as appropriate . The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge . Secondary end points included duration of hospital stay and overall mortality . RESULTS During follow-up , patients in the HBI group had fewer unplanned readmissions ( 36 vs 63 ; P=.03 ) and fewer out-of-hospital deaths ( 1 vs 5 ; P=.11 ) : 0.8+/-0.9 vs 1.4+/-1.8 ( mean + /- SD ) events per patient assigned to HBI and usual care , respectively ( P=.03 ) . Patients in the HBI group also had fewer days of hospitalization ( 261 vs 452 ; P=.05 ) and fewer total deaths ( 6 vs 12 ; P=.11 ) . Patients assigned to usual care were more likely to experience 3 or more readmissions for acute heart failure ( P=.02 ) . Predictors of unplanned readmission were ( 1 ) 14 days or more of unplanned readmission during the 6 months before study entry ( odds ratio [ OR ] , 5.2 ; 95 % confidence interval [ CI ] , 1.8 - 16.2 ) , ( 2 ) previous admission for acute myocardial ischemia ( OR , 3.3 ; 95 % CI , 1.2 - 9.1 ) , and ( 3 ) an albumin plasma concentration of 38 g/L or less ( OR , 2.4 ; 95 % CI , 1.2 - 6.0 ) . Home-based intervention was also associated with a trend toward reduced risk of unplanned readmission ( OR , 0.4 ; 95 % CI , 0.2 - 1.1 ) . CONCLUSION Among a cohort of high-risk patients with congestive heart failure , HBI was associated with reduced frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge from the hospital BACKGROUND The effect of home-based exercise training on neurovascular control in heart failure patients is unknown . AIMS To test the hypothesis that home-based training would maintain the reduction in muscle sympathetic nerve activity ( MSNA ) and forearm vascular resistance ( FVR ) acquired after supervised training . METHODS AND RESULTS Twenty-nine patients ( 54+/-1.9 years , EF<40 % ) were r and omised into two groups : untrained control ( n=12 ) and exercise trained ( n=17 ) . Both groups underwent assessment of Quality of Life ( QoL ) , MSNA , and forearm blood flow . The exercise group underwent a 4-month supervised training program followed by 4 months of home-based training . After the initial 4 months of training , patients in the exercise group showed a significant increase in peak VO(2 ) and reduction in MSNA , compared to the untrained group , but this was not maintained during 4 months of home-based training . In contrast , the decrease in FVR ( 56+/-3 vs. 46+/-4 vs. 40+/-2 U , p=0.008 ) and the improvement in QOL that were achieved during supervised training were maintained during home-based training . CONCLUSIONS Home-based training following supervised training is a safe strategy to maintain improvements in QoL and reduction in FVR in chronic heart failure patients , but is an inadequate strategy to maintain fitness as estimated by peak VO(2 ) or reduction in neurohumoral activation Chronic heart failure ( CHF ) is characterized by a skeletal muscle myopathy not optimally addressed by current treatment paradigms or aerobic exercise . Sixteen older women with CHF were compared with 80 age-matched peers without CHF and r and omized to progressive resistance training or control stretching exercises for 10 wk . Women with CHF had significantly lower muscle strength ( P < 0.0001 ) but comparable aerobic capacity to women without CHF . Exercise training was well tolerated and result ed in no changes in resting cardiac indexes in CHF patients . Strength improved by an average of 43.4 + /- 8.8 % in resistance trainers vs. -1.7 + /- 2.8 % in controls ( P = 0.001 ) , muscle endurance by 299 + /- 66 % vs. 1 + /- 3 % ( P = 0.001 ) , and 6-min walk distance by 49 + /- 14 m ( 13 % ) vs. -3 + /- 19 m ( -3 % ) ( P = 0.03 ) . Increases in type I fiber area ( 9.5 + /- 16 % ) and citrate synthase activity ( 35 + /- 21 % ) in skeletal muscle were independently predictive of improved 6-min walk distance ( r2 = 0.78 ; P = 0.0024 ) . High-intensity progressive resistance training improves impaired skeletal muscle characteristics and overall exercise performance in older women with CHF . These gains are largely explained by skeletal muscle and not resting cardiac adaptations Background —The effects of exercise training ( ET ) on left ventricular ( LV ) remodeling in chronic heart failure are not definitively established , and the safety of ET in these patients is still debated . Methods and Results —This multicenter study investigated the long-term effect of moderate ET on LV remodeling , work capacity , and quality of life ( QoL ) in 90 patients with stable chronic heart failure caused by LV systolic dysfunction , r and omized to a 6-month ET program ( T , n=45 ) or a control group ( C , n=45 ) . All patients underwent resting echocardiography , a cardiopulmonary exercise test , 6-minute walking test , and QoL assessment at entry and after 6 months . At entry , end-diastolic ( EDV ) and end-systolic ( ESV ) volume , ejection fraction , work capacity , peak & OV0312;o2 , and walking distance were similar in the 2 groups . After 6 months , LV volumes diminished in T ( EDV , from 142±26 to 135±26 mL/m2 , P < 0.006 ; ESV , from 107±24 to 97±24 mL/m2 , P < 0.05 ) but increased in C ( EDV , from 147±41 to 156±42 mL/m2 , P < 0.01 ; ESV , from 110±34 to 118±34 mL/m2 , P < 0.01 ) . Ejection fraction improved in T ( P < 0.001 ) but was unchanged in C ( P = NS ) . Significant improvement in work capacity ( P < 0.001 ) , peak & OV0312;o2 ( P < 0.006 ) , walking distance ( P < 0.001 ) , and QoL ( P < 0.01 ) was observed in T but not in C ( P = NS ) . T showed a trend toward fewer ( P = 0.05 ) hospital readmissions for worsening dyspnea in the absence of other adverse cardiac events . Conclusions —In stable chronic heart failure , long-term moderate ET has no detrimental effect on LV volumes and function ; rather , it attenuates abnormal remodeling . Furthermore , ET is safe and effective in improving exercise tolerance and PURPOSE To examine the effects of a 12-week tai chi program on quality of life and exercise capacity in patients with heart failure . METHODS Thirty patients with chronic stable heart failure and left ventricular ejection fraction < or = 40 % ( mean [ + /- SD ] age , 64 + /- 13 years ; mean baseline ejection fraction , 23 % + /- 7 % ; median New York Heart Association class , 2 [ range , 1 to 4 ] ) were r and omly assigned to receive usual care ( n = 15 ) , which included pharmacologic therapy and dietary and exercise counseling , or 12 weeks of tai chi training ( n = 15 ) in addition to usual care . Tai chi training consisted of a 1-hour class held twice weekly . Primary outcomes included quality of life and exercise capacity . Secondary outcomes included serum B-type natriuretic peptide and plasma catecholamine levels . For 3 control patients with missing data items at 12 weeks , previous values were carried forward . RESULTS At 12 weeks , patients in the tai chi group showed improved quality -of-life scores ( mean between-group difference in change , -25 points , P = 0.001 ) , increased distance walked in 6 minutes ( 135 meters , P = 0.001 ) , and decreased serum B-type natriuretic peptide levels ( -138 pg/mL , P = 0.03 ) compared with patients in the control group . A trend towards improvement was seen in peak oxygen uptake . No differences were detected in catecholamine levels . CONCLUSION Tai chi may be a beneficial adjunctive treatment that enhances quality of life and functional capacity in patients with chronic heart failure who are already receiving st and ard medical therapy Patients with chronic heart failure ( CHF ) experience progressive deterioration of functional capacity and quality of life ( QoL ) . This prospect i ve , r and omized , controlled trial assesses the effect of exercise training ( ET ) protocol on functional capacity , rehospitalization , and QoL in CHF patients older than 70 years compared with a control group . A total of 343 elderly patients with stable CHF ( age , 76.90±5.67 , men , 195 , 56.9 % ) were r and omized to ET ( TCG , n=170 ) or usual care ( UCG , n=173 ) . The ET protocol involved supervised training sessions for 3 months in the hospital followed by home-telemonitored sessions for 3 months . Assessment s , performed at baseline and at 3 and 6 months , included : ECG , resting echocardiography , NT-proBNP , 6-minute walk test ( 6MWT ) , Minnesota Living with Heart Failure Question naire , and comprehensive geriatric assessment with the InterRAI-HC instrument . As compared to UCG , ET patients at 6 months showed : i ) significantly increased 6MWT distance ( 450±83 vs. 290±97 m , p<0.001 ) ; ii ) increased ADL scores ( 5.00±2.49 vs. 6.94±5.66 , p=0.037 ) ; iii ) 40 % reduced risk of rehospitalisation ( hazard ratio=0.558 , 95%CI , 0.326 - 0.954 , p=0.033 ) ; and iv ) significantly improved perceived QoL ( 28.6±12.3 vs. 44.5±12.3 , p<0.001 ) . In hospital and home-based telemonitored exercise confer significant benefits on the oldest CHF patients , improving functional capacity and subjective QoL and reducing risk of rehospitalisation AIMS Previous studies have shown an abnormal expression of cellular adhesion molecules and cytokines in chronic heart failure , which may be related to endothelial dysfunction characterizing this syndrome . Our study investigates the effects of physical training on serum activity of some peripheral inflammatory markers associated with endothelial dysfunction , such as granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , macrophage chemoattractant protein-1 ( MCP-1 ) , soluble intercellular adhesion molecule-1 ( sICAM-1 ) and soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) in patients with chronic heart failure . METHODS AND RESULTS Serum levels of GM-CSF , MCP-1 , sICAM-1 and sVCAM-1 were determined in 12 patients with stable chronic heart failure ( ischaemic heart failure : 6/12 , dilated cardiomyopathy : 6/12 , New York Heart Association : II-III , ejection fraction : 24+/-2 % ) before and after a 12-week programme of physical training in a r and omized crossover design . In addition , the functional status of chronic heart failure patients was evaluated by using a cardiorespiratory exercise stress test to measure peak oxygen consumption . Physical training produced a significant reduction in serum GM-CSF ( 28+/-2 vs 21+/-2 pg . ml(-1 ) , P<0.001 ) , MCP-1 ( 192+/-5 vs 174+/-6 pg . ml(-1 ) , P<0.001 ) , sICAM-1 ( 367+/-31 vs 314+/-29 ng . ml(-1 ) , P<0.01 ) and sVCAM-1 ( 1247+/-103 vs 1095+/-100 ng . ml(-1 ) , P<0.01 ) as well as a significant increase in peak oxygen consumption ( 14.6+/-0.5 vs 16.5+/-0.5 ml . kg(-1)min(-1 ) , P<0.005 ) . A significant correlation was found between the training-induced improvement in peak oxygen consumption and percentage reduction in soluble adhesion molecules sICAM-1 ( r=-0.72 , P<0.01 ) and sVCAM-1 ( r=-0.67 , P<0.02 ) . CONCLUSION Physical training affects beneficially peripheral inflammatory markers reflecting monocyte/macrophage-endothelial cell interaction . Training-induced improvement in exercise tolerance is correlated with the attenuation of the inflammatory process , indicating that inflammation may contribute significantly to the impaired exercise capacity seen in chronic heart failure OBJECTIVE To estimate the incremental effects on cost and quality of life of cardiac rehabilitation after an acute coronary syndrome . DESIGN Open r and omised controlled trial with 1 year 's follow-up . Analysis was on an intention-to-treat basis . SETTING Two tertiary hospitals in Sydney . INTERVENTION 18 sessions of comprehensive exercise-based outpatient cardiac rehabilitation or conventional care as provided by the treating doctor . PARTICIPANTS 113 patients aged 41 - 75 years who were self-caring and literate in English . Patients with uncompensated heart failure , uncontrolled arrhythmias , severe and symptomatic aortic stenosis or physical impairment were excluded . MAIN OUTCOME MEASURES Costs ( hospitalisations , medication use , outpatient visits , investigations , and personal expenses ) ; and measures of quality of life . Incremental cost per quality -adjusted life year ( QALY ) saved at 1 year ( this estimate combines within- study utility effects with reported 1-year risk of survival and treatment effects of rehabilitation on mortality ) . Sensitivity analyses around a base case estimate included alternative assumptions of no treatment effect on survival , 3 years of treatment effect on survival and variations in utility . RESULTS The estimated incremental cost per QALY saved for rehabilitation relative to st and ard care was 42,535 US dollars when modelling included the reported treatment effect on survival . This increased to 70,580 US dollars per QALY saved if treatment effect on survival was not included . The results were sensitive to variations in utility and ranged from 19,685 US dollars per QALY saved to rehabilitation not being cost-effective . CONCLUSIONS The effects on quality of life tend to reinforce treatment advantages on survival for patients having postdischarge rehabilitation after an acute coronary syndrome . The estimated base case incremental cost per QALY saved is consistent with those historically accepted by decision making authorities such as the Pharmaceutical Benefits Advisory Committee OBJECTIVE The purpose of this study was to investigate the effects of physical exercise on the functional capacity and quality of life in heart failure patients . METHODS Forty-two patients of both sexes with heart failure of NYHA class II and III with different etiologies were r and omly divided into untrained or trained groups . The six-month exercise program consisted of aerobic training , muscle strength training , agility and joint flexibility activities . Physical fitness was evaluated by testing the performance on these trained components . Quality of life was evaluated by scored answers to a st and ardized question naire involving multiple domains . RESULTS Baseline values did not differ between groups . Improvement in the trained group was identified in all components of functional capacity when compared to the untrained group ( p < 0.001 ) . Quality of life improved in the trained patients concerning physical , psychological , social and environmental domains ( p < 0.001 ) , whereas no significant change was found in the untrained patients . CONCLUSIONS Guided and monitored physical exercise is safe and has the potential to improve functional capacity and quality of life in heart failure patients with multiple etiologies Background —Attenuated peripheral perfusion in patients with advanced chronic heart failure ( CHF ) is partially the result of endothelial dysfunction . This has been causally linked to an impaired endogenous regenerative capacity of circulating progenitor cells ( CPC ) . The aim of this study was to eluci date whether exercise training ( ET ) affects exercise intolerance and left ventricular ( LV ) performance in patients with advanced CHF ( New York Heart Association class IIIb ) and whether this is associated with correction of peripheral vasomotion and induction of endogenous regeneration . Methods and Results —Thirty-seven patients with CHF ( LV ejection fraction 24±2 % ) were r and omly assigned to 12 weeks of ET or sedentary lifestyle ( control ) . At the beginning of the study and after 12 weeks , maximal oxygen consumption ( Vo2max ) and LV ejection fraction were determined ; the number of CD34+/KDR+ CPCs was quantified by flow cytometry and CPC functional capacity was determined by migration assay . Flow-mediated dilation was assessed by ultrasound . Capillary density was measured in skeletal muscle tissue sample s. In advanced CHF , ET improved Vo2max by + 2.7±2.2 versus −0.8±3.1 mL/min/kg in control ( P=0.009 ) and LV ejection fraction by + 9.4±6.1 versus −0.8±5.2 % in control ( P<0.001 ) . Flow-mediated dilation improved by + 7.43±2.28 versus + 0.09±2.18 % in control ( P<0.001 ) . ET increased the number of CPC by + 83±60 versus −6±109 cells/mL in control ( P=0.014 ) and their migratory capacity by + 224±263 versus −12±159 CPC/1000 plated CPC in control ( P=0.03 ) . Skeletal muscle capillary density increased by + 0.22±0.10 versus −0.02±0.16 capillaries per fiber in control ( P<0.001 ) . Conclusions —Twelve weeks of ET in patients with advanced CHF is associated with augmented regenerative capacity of CPCs , enhanced flow-mediated dilation suggestive of improvement in endothelial function , skeletal muscle neovascularization , and improved LV function . Clinical Trial Registration —http://www . clinical trials.gov . Unique Identifier : NCT00176384 BACKGROUND Physical training improves exercise capacity in patients with chronic heart failure . It decreases plasma noradrenaline at rest , which may be prognostically favourable . The effect on atrial natriuretic peptide , another prognostic factor , and on catabolic and anabolic hormones remains unknown . Furthermore , to our knowledge , the contribution of exertional hormonal responses to the improved exercise capacity has not been evaluated . METHODS 27 patients with stable chronic heart failure ( New York Heart Association class II-III ) were r and omized to training ( n=12 ) and control ( n=15 ) groups . The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months . The load corresponded to 50 - 60 % of their peak oxygen consumption . For the next 3 months they exercised at home according to personal instructions . The control group did not change its physical activities . The levels of hormones regulating the cardiovascular system and metabolism were determined at rest and after grade d maximal exercise and during exercise with constant submaximal workload . RESULTS Submaximal exercise capacity increased significantly and peak oxygen consumption tended to improve by 12 % in the training group . The plasma noradrenaline at rest tended to decrease by 19 % . The plasma level of N-terminal pro atrial natriuretic peptide did not change . Serum cortisol , a catabolic hormone , was normal at baseline and remained unchanged . The serum levels of anabolic hormones , growth hormone and insulin , as well as dehydroepi and rosteronesulfate and free testosterone were within a normal range at baseline . They were not altered by training . The dehydroepi and rosteronesulfate/cortisol , and the free testosterone/cortisol ratios , reflecting anabolic/catabolic balance , did not change , either . Training result ed in a higher peak noradrenaline response during grade d maximal exercise . The rise in serum cortisol during exercise tended to attenuate . CONCLUSION Physical training , which improves exercise capacity , does not have an unfavourable effect on anabolic/catabolic balance or neurohumoral activation in patients with congestive heart failure . It decreases plasma noradrenaline at rest . Minor changes in hormonal responses during exercise emerged after physical training which unlikely contribute to the improved exercise capacity INTRODUCTION AND OBJECTIVES The objective of this study was to determine whether a home-based intervention can reduce mortality and hospital readmissions and improve quality of life in patients with heart failure . METHODS A r and omized clinical trial was carried out between January 2004 and October 2006 . In total , 283 patients admitted to hospital with a diagnosis of heart failure were r and omly allocated to a home-based intervention ( intervention group ) or usual care ( control group ) . The primary end-point was the combination of all-cause mortality and hospital readmission for worsening heart failure at 1-year follow-up . RESULTS The primary end-point was observed in 41.7 % of patients in the intervention group and in 54.3 % in the control group . The hazard ratio was 0.70 ( 95 % confidence interval [ CI ] 0.55 - 0.99 ) . Taking significant clinical variables into account slightly reduced the hazard ratio to 0.62 ( 95 % CI 0.50 - 0.87 ) . At the end of the study , the quality of life of patients in the intervention group was better than in the control group ( 18.57 vs. 31.11 ; P < .001 ) . CONCLUSIONS A home-based intervention for patients with heart failure reduced the aggregate of mortality and hospital readmissions and improved quality of life In chronic heart failure , oxidative stress is thought to lead to endothelial dysfunction . In this study , we assessed the effect of home‐based exercise training on variables of the NO and purine pathways Background Exercise has been shown to be beneficial for selected patients with heart failure , but questions remain over its effectiveness , cost-effectiveness and uptake in a real world setting . This paper describes the design , rationale and recruitment for a r and omised controlled trial that will explore the effectiveness and uptake of a predominantly home-based exercise rehabilitation programme , as well as its cost-effectiveness and patient acceptability . Methods / design R and omised controlled trial comparing specialist heart failure nurse care plus a nurse-led predominantly home-based exercise intervention against specialist heart failure nurse care alone in a multiethnic city population , served by two NHS Trusts and one primary care setting , in the United Kingdom.169 English speaking patients with stable heart failure , defined as systolic impairment ( ejection fraction ≤ 40 % ) . with one or more hospital admissions with clinical heart failure or New York Heart Association ( NYHA ) II/III within previous 24-months were recruited . Main outcome measures at 1 year : Minnesota Living with Heart Failure Question naire , incremental shuttle walk test , death or admission with heart failure or myocardial infa rct ion , health care utilisation and costs . Interviews with purposive sample s of patients to gain qualitative information about acceptability and adherence to exercise , views about their treatment , self-management of their heart failure and reasons why some patients declined to participate . The records of 1639 patients managed by specialist heart failure services were screened , of which 997 ( 61 % ) were ineligible , due to ejection fraction>40 % , current NYHA IV , no admission or NYHA II or more within the previous 2 years , or serious co-morbidities preventing physical activity . 642 patients were contacted : 289 ( 45 % ) declined to participate , 183 ( 39 % ) had an exclusion criterion and 169 ( 26 % ) agreed to r and omisation . Discussion Due to safety considerations for home-exercise less than half of patients treated by specialist heart failure services were eligible for the study . Many patients had co-morbidities preventing exercise and others had concerns about undertaking an exercise programme OBJECTIVES This study investigated the effect of a very long-term exercise training program is not known in chronic heart failure ( CHF ) patients . BACKGROUND We previously showed that long-term moderate exercise training ( ET ) improves functional capacity and quality of life in New York Heart Association class II and III CHF patients . METHODS We studied 123 patients with CHF whose condition was stable over the previous 3 months . After r and omization , a trained group ( T group , n = 63 ) underwent a supervised ET at 60 % of peak oxygen consumption ( Vo(2 ) ) , 2 times weekly for 10 years , whereas a nontrained group ( NT group , n = 60 ) did not exercise formally . The ET program was supervised and performed mostly at a coronary club with periodic control sessions twice yearly at the hospital 's gym . RESULTS In the T group , peak Vo(2 ) was more than 60 % of age- and gender-predicted maximum Vo(2 ) each year during the 10-year study ( p < 0.05 vs. the NT group ) . In NT patients , peak Vo(2 ) decreased progressively with an average of 52 ± 8 % of maximum Vo(2 ) predicted . Ventilation relative to carbon dioxide output ( VE/Vco(2 ) ) slope was significantly lower ( 35 ± 9 ) in T patients versus NT patients ( 42 ± 11 , p < 0.01 ) . Quality -of-life score was significantly better in the T group versus the NT group ( 43 ± 12 vs. 58 ± 14 , p < 0.05 ) . During the 10-year study , T patients had a significant lower rate of hospital readmission ( hazard ratio : 0.64 , p < 0.001 ) and cardiac mortality ( hazard ratio : 0.68 , p < 0.001 ) than controls . Multivariate analysis selected peak Vo(2 ) and resting heart rate as independent predictors of events . CONCLUSIONS Moderate supervised ET performed twice weekly for 10 years maintains functional capacity of more than 60 % of maximum Vo(2 ) and confers a sustained improvement in quality of life compared with NT patients . These sustained improvements are associated with reduction in major cardiovascular events , including hospitalizations for CHF and cardiac mortality OBJECTIVE To investigate the effect of physical training ( PTr ) on upper leg muscle area , muscle strength and muscle endurance expressed as upper leg muscle function ( ULMF ) in relation to exercise performance in CHF . DESIGN R and omised to a training ( TG ) or control group ( CG ) . SETTING Outpatient cardiac rehabilitation centre of community hospital . PATIENTS 77 CHF patients ( 59 men and 18 women ) , NYHA class II/III , age 59.8+/-9.3 years , LVEF 27+/-8 % . Sixteen patients dropped out during the intervention period , 61 patients ( M/F:46/15 ) completed the study . INTERVENTION PTr ( combined strength and endurance exercises ) four times per week , twice supervised and twice at home , during 26 weeks . MAIN OUTCOME MEASURES LVEF , body composition , daily physical activity , exercise performance , upper leg muscle area and isokinetic leg muscle variables . RESULTS Workload and peak oxygen consumption decreased in the CG ( -4.1 % and -4 % ) but increased in the TG ( + 5 % and + 4 % ) following PTr ( p<0.05 , ANOVA repeated measures ) . Hamstrings area decreased in the CG and did not change in the TG ( p<0.05 , ANOVA repeated measures ) . ULMF improved in the TG , but remained unchanged in the CG ( + 13.0 % and 0.0 , respectively , p<0.05 ; ANOVA repeated measures ) . At baseline and after intervention nearly 60 % of the variance in maximal workload was explained by ULMF and quadriceps muscle area ( multiple regression analysis ) . CONCLUSIONS In CHF patients , home-based training in conjunction with a supervised strength and endurance training program is safe , feasible and effective and does not require complex training equipment . Physical training prevented loss of hamstrings muscle mass and improved exercise performance by enhancing muscle strength and endurance BACKGROUND This study tested the effects of a multicomponent exercise training intervention called " Heart Failure Exercise And Training Camp " ( HEART CAMP ) . The intervention was theoretically derived from B and ura 's social cognitive theory . METHODS An experimental repeated- measures design was used . Participants were r and omized to the HEART CAMP intervention group ( n = 22 ) or the attention control group ( n = 20 ) . Participants were compared on self-efficacy for exercise , symptoms , physical function , and quality of life over 12 weeks . RESULTS The intervention group had a 31 % increase in cardiac exercise self-efficacy and significantly fewer symptoms compared with the attention control group . Quality of life increased significantly in both groups . CONCLUSION A theory-based intervention improved self-efficacy for exercise and symptoms in patients with heart failure BACKGROUND Current guidelines broadly recommend comprehensive cardiac rehabilitation ( CCR ) , although evidence for this is still limited . We investigated the 12-month effect of hospital-based CCR versus usual care ( UC ) for a broadly defined group of cardiac patients within the modern therapeutic era of cardiology . METHODS We conducted a central ly r and omized single-center clinical trial with blinded assessment of the primary outcome : registry-based composite of total mortality , myocardial infa rct ion , or acute first-time readmission due to heart disease . Other outcomes were hospitalization , risk profile , and quality of life . The trial included 770 participants ( 20 - 94 years ) with congestive heart failure ( 12 % ) , ischemic heart disease ( 58 % ) , or high risk of ischemic heart disease ( 30 % ) . Comprehensive cardiac rehabilitation is composed of 6 weeks of intensive intervention and systematic follow-up for 10.5 months . RESULTS We r and omized 380 patients to CCR versus 390 to UC . R and omization was well balanced . The primary outcome occurred in 31 % of both groups ( relative risk 0.96 , 95 % confidence interval 0.78 - 1.26 ) . Compared with the UC group , CCR significantly reduced length of stay by 15 % ( 95 % confidence interval 1.1%-27.1 % , P = .04 ) , mean number of cardiac risk factors above target ( 4.5 vs 4.1 , P = .01 ) , patients with systolic blood pressure below target ( P = .003 ) , physically inactivity ( P = .01 ) , and unhealthy dietary habits ( P = .0003 ) . Short-Form-36 and Hospital Anxiety and Depression Scale did not differ significantly . CONCLUSION At 12 months , the CCR and UC groups did not differ regarding the primary composite outcome . Comprehensive cardiac rehabilitation significantly reduced length of hospital stay and improved cardiac risk factors BACKGROUND Diastolic heart failure ( DHF ) is common in older women . There have been no clinical trials that have identified therapies to improve symptoms in these patients . A total of 32 women with New York Heart Association class II and III DHF ( left ventricular ejection fraction > 45 % and symptoms of dyspnea or fatigue ) were r and omized into a 12-week home-based , low-to-moderate intensity ( 40 % and 60 % , respectively ) exercise and education program ( intervention ) or education only program ( control ) . Methods and results The intervention group improved in the 6-minute walk test from 840 + /- 366 ft to 1043 + /- 317 ft versus 824 + /- 367 ft to 732 + /- 408 ft in the control group ( P = .002 ) . Quality of life also improved in the intervention group compared with the control group as measured by the Living with Heart Failure Question naire ( 41 + /- 26 to 24 + /- 18 vs 27 + /- 18 to 28 + /- 22 at 12 weeks , P = .002 ; 24 + /- 18 to 19 + /- 18 vs 28 + /- 22 to 32 + /- 27 at the 3-month follow-up , P = .014 ) and the Geriatric Depression Scale ( 6 + /- 4 to 4 + /- 4 vs 5 + /- 3 to 7 + /- 5 at 12 weeks , P = .012 ; 4 + /- 4 to 4 + /- 4 vs 7 + /- 5 to 7 + /- 5 at the 3-month follow-up , P = .009 ) . CONCLUSIONS Women with DHF exhibit significant comorbidities and physical limitations . Home-based , low-to-moderate intensity exercise , in addition to education , is an effective strategy for improving the functional capacity and quality of life in women with DHF . Further study is needed to assess the long-term effect of exercise on clinical outcomes Background The impact of exercise programmes for heart failure on those close to the patient is largely unknown . We examined the effect of a hospital and home-based exercise intervention on burden , anxiety and depression of informal caregivers . Design The study was a r and omized , controlled trial . Heart failure patients were r and omized to a seated 12-week hospital-based exercise programme . Caregiver measures were gathered at baseline , 3 months later and 6 months following baseline . Methods Sixty caregivers ( mean age 63.4 years , 65 % female ) of heart failure patients ( n = 82 , mean age 80.5 years , 44 % female ) participating in a trial of an exercise intervention were recruited . Caregiver burden , anxiety and depression were assessed . Results There were no differences in caregiver burden , depression or anxiety between the two groups of caregivers at baseline ( caregiver burden , patient control 33.1 versus patient exercise 34.1 ; anxiety 4.1 versus 5.5 ; depression 2.8 versus 3.8 ) . At 3 months there were no differences between caregivers in the two groups on outcomes . At 6-month follow-up caregivers of heart failure patients in the exercise group had burden scores that were significantly worse than the control group . There were no differences between the carers of exercise and control groups in anxiety and depression . Levels of anxiety and depression in the entire carer sample were marginally higher than reference values in a healthy non- clinical sample . Conclusion The present exercise interventions for frail older patients did not benefit caregivers and was associated with an increase in caregiver burden . We suggest that future exercise interventions for heart failure patients should actively incorporate informal caregivers into research design s. Eur J Cardiovasc Prev Rehabil 13:381–387 © 2006 The European Society of Background Many secondary abnormalities in chronic heart failure ( CHF ) may reflect physical deconditioning . There has been no prospect i ve , controlled study of the effects of physical training on hemodynamics and autonomic function in CHIF . Methods and Results In a controlled crossover trial of 8 weeks of exercise training , 17 men with stable moderate to severe CHF ( age , 61.8±1.5 years ; left ventricular ejection fraction , 19.6±2.3 % ) , increased exercise tolerance ( 13.9±1.0 to 16.5±1.0 minutes , p<0.001 ) , and peak oxygen uptake ( 13.2±0.9 to 15.6±1.0 mI/kg/min , p<0.01 ) significantly compared with controls . Training increased cardiac output at submaximal ( 5.9 - 6.7 1/min , p<0.05 ) and peak exercise ( 6.3 - 7.1 /min , p<0.05 ) , with a significant reduction in systemic vascular resistance . Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production ( −10.5 % , p<0.05 ) . Sympathovagal balance was altered by physical training when assessed by three methods : 1 ) RR variability ( + 19.2 % , p<0.05 ) ; 2 ) autoregressive power spectral analysis of the resting ECG divided into low-frequency ( −21.2 % , p<0.01 ) and high-frequency ( + 51.3 % , p<0.05 ) components ; and 3 ) whole-body radiolabeled norepinephrine spillover ( −16 % , p<0.05 ) . These measurements all showed a significant shift away from sympathetic toward enhanced vagal activity after training . Conclusions Carefully selected patients with moderate to severe CHF can achieve significant , worthwhile improvements with exercise training . Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF , including abnormalities in autonomic balance BACKGROUND The aim of this study was to determine the effects of a home-based exercise program on clinical outcomes . Exercise training improves exercise capacity in patients with heart failure ( HF ) but the long-term effects on clinical outcomes remain unknown . METHODS We r and omized 173 patients with systolic HF to control ( n = 87 ) or home-based exercise ( n = 86 ) . The primary end point was a composite of all-cause hospitalizations , emergency department admissions , urgent transplantation , and death at 12 months . Functional performance ( as assessed by cardiopulmonary exercise testing and the 6-minute walk test ) , quality of life , and psychological states were measured at baseline , 3 months , and 6 months . RESULTS There was no significant difference between experimental and control groups in the combined clinical end point at 12 months and in functional status , quality of life , or psychological states over 6 months . Patients in the exercise group had a lower incidence of multiple ( 2 or more ) hospitalizations compared with the control group : 12.8 % versus 26.6 % , respectively ( P = .018 ) . CONCLUSIONS A home-based walking program that incorporated aerobic and resistance exercise did not result in improved clinical outcomes at 1-year follow-up in this cohort of patients with systolic HF . However , the exercise program result ed in reduced rehospitalization rates BACKGROUND Exercise programs for patients with heart failure have often enrolled and evaluated relatively healthy , young patients . They also have not measured the impact of exercise performance on daily activities and quality of life . METHODS AND RESULTS We investigated the impact of a 6-month supervised and grade d exercise program in 33 elderly patients with moderate to severe heart failure r and omized to usual care or an exercise program . Six of 17 patients did not tolerate the exercise program . Of those who did , peak oxygen consumption increased by 2.4 + /- 2.8 mL/kg/min ( P < .05 ) and 6-minute walk increased by 194 ft ( P < .05 ) . However , outpatient energy expenditure did not increase , as measured by either the doubly labeled water technique or Caltrac accelerometer . Perceived quality of life also did not improve , as measured by the Medical Outcomes Study , Functional Status Assessment , or Minnesota Living With Heart Failure question naires . CONCLUSION Elderly patients with severe heart failure can safely exercise , with an improvement in peak exercise tolerance . However , not all patients will benefit , and daily energy expenditure and quality of life do not improve to the same extent as peak exercise The effect of exercise training on quality of life and exercise capacity was studied in 67 patients with mild to moderate chronic heart failure ( CHF ; age : 65.6+/-8.3 years ; left ventricular ejection fraction : 26.5+/-9.6 % ) . Patients were r and omly allocated to either a training group or to a control group . After intervention a significantly larger decrease in Feelings of Being Disabled ( a subscale of the Heart Patients Psychological Question naire ) and a significantly larger increase in the Self- Assessment of General Well-Being ( SAGWB ) were observed in the training group . Exercise time and anaerobic threshold were increased in the training group only . The increase in exercise time was related to both Feelings of Being Disabled and SAGWB . We conclude that supervised exercise training improves both quality of life and exercise capacity and can be safely performed by chronic heart failure patients BACKGROUND Resistance exercise training was applied to patients with chronic heart failure ( CHF ) on the basis that it may partly reverse deficiencies in skeletal muscle strength and endurance , aerobic power ( VO(2peak ) ) , heart rate variability ( HRV ) , and forearm blood flow ( FBF ) that are all putative factors in the syndrome . METHODS AND RESULTS Thirty-nine CHF patients ( New York Heart Association Functional Class=2.3+/-0.5 ; left ventricular ejection fraction 28%+/-7 % ; age 65+/-11 years ; 33:6 male : female ) underwent 2 identical series of tests , 1 week apart , for strength and endurance of the knee and elbow extensors and flexors , VO(2peak ) , HRV , FBF at rest , and FBF activated by forearm exercise or limb ischemia . Patients were then r and omized to 3 months of resistance training ( EX , n=19 ) , consisting of mainly isokinetic ( hydraulic ) ergometry , interspersed with rest intervals , or continuance with usual care ( CON , n=20 ) , after which they underwent repeat endpoint testing . Combining all 4 movement patterns , strength increased for EX by 21+/-30 % ( mean+/-SD , P<.01 ) after training , whereas endurance improved 21+/-21 % ( P<.01 ) . Corresponding data for CON remained almost unchanged ( strength P<.005 , endurance P<.003 EX versus CON ) . VO(2peak ) improved in EX by 11+/-15 % ( P<.01 ) , whereas it decreased by 10+/-18 % ( P<.05 ) in CON ( P<.001 EX versus CON ) . The ratio of low-frequency to high-frequency spectral power fell after resistance training in EX by 44+/-53 % ( P<.01 ) , but was unchanged in CON ( P<.05 EX versus CON ) . FBF increased at rest by 20+/-32 % ( P<.01 ) , and when stimulated by submaximal exercise ( 24+/-32 % , P<.01 ) or limb ischemia ( 26+/-45 % , P<.01 ) in EX , but not in CON ( P<.01 EX versus CON ) . CONCLUSIONS Moderate-intensity resistance exercise training in CHF patients produced favorable changes to skeletal muscle strength and endurance , VO(2peak ) , FBF , and HRV Exercise is an important behavior for long-term weight control in overweight and obese patients . However , little evidence exists confirming such findings in patients with advanced heart failure ( HF ) . Using a prospect i ve , experimental design , the effects of 24 weeks of a low-level , home-based walking program on weight loss were studied in overweight and obese ( body mass index > or = 27 kg/m(2 ) ) patients with advanced HF who were r and omized to exercise ( n = 48 ) and control ( n = 51 ) groups . Weight changes between the 2 groups at baseline and 6 months were compared using repeated- measures analysis of variance . Patients were on average aged 53.3 + /- 10.1 years and predominantly male ( 75 % ) , Caucasian ( 57 % ) , and married ( 55 % ) . Most patients were in New York Heart Association class III or IV ( 67 % ) , with a mean ejection fraction of 25 % . Patients in the exercise group showed significant weight reduction from baseline to 6 months compared with those in the control group ( -6.37 + /- 11.7 vs -0.33 + /- 9.3 kg , p = 0.002 ) . No significant differences were noted between the 2 groups in 6-minute walk distance or depression , although the changes were in the anticipated direction . Modest weight losses of > 5 % were associated with cardiopulmonary exercise test-documented workload levels at 6 months ( r = 0.331 , p = 0.006 ) , as well as decreased depression ( r = -0.315 , p = 0.01 ) and hostility ( r = -0.355 , p = 0.005 ) . The number of hospital admissions was significantly smaller for patients in the exercise group compared with those in the control group ( 0.63 + /- 0.94 vs 1.07 + /- 0.95 , p < 0.05 ) . In conclusion , the findings demonstrate the beneficial effects of a low-level , home-based walking program on weight loss in overweight and obese patients with advanced HF The purpose of this study is to perform a cost-effectiveness analysis of long-term moderate exercise training ( ET ) in patients with stable chronic heart failure . In particular , the study focuses on the survival analysis and cost savings from the reduction in the hospitalization rate in the exercise group . In the past 10 years , ET has been shown to be beneficial for patients with stable class II and III heart failure in many r and omized clinical trials . However , the cost-effectiveness of a long-term ET program has not been addressed for outcomes related to morbidity/mortality end points or health care utilization . We examined the cost-effectiveness of a 14-month long-term training in patients with stable chronic heart failure . The estimated increment cost for the training group , $ 3,227/patient , was calculated by subtracting the averted hospitalization cost , $ 1,336/patient , from the cost of ET and wage lost due to ET , estimated at $ 4,563/patient . For patients receiving ET , the estimated increment in life expectancy was 1.82 years/person in a time period of 15.5 years , compared with patients in the control group . The cost-effectiveness ratio for long-term ET in patients with stable heart failure was thus determined at $ 1,773/life-year saved , at a 3 % discount rate . Long-term ET in patients with stable chronic heart failure is cost-effective and prolongs survival by an additional 1.82 years at a low cost of $ 1,773 per/life-year saved Background : In heart failure , reduced physical activity level can adversely affect physical and psychosocial functioning . No previous heart failure research has compared effects of home and hospital-based exercise training upon physical activity level , or has objective ly assessed their long-term effects upon physical activity . This study used an activPAL ™ monitor to examine immediate and long-term effects of home and hospital-based aerobic exercise training upon physical activity level . Design : R and omized controlled trial . Methods : Sixty patients with heart failure ( mean age 66 years ; NYHA class II/III ; 51 male/9 female ) were r and omized to home training , hospital training or control . Both programmes consisted of aerobic circuit training , undertaken twice a week for one hour , for eight weeks . All participants wore the activPAL ™ at baseline , and after eight weeks , for one week . Six months after cessation of training , a subgroup of participants from the home and hospital training groups ( n = 10 from each group ) wore the activPAL ™ for a further week . Results : Hospital-based training significantly increased steps taken per day during ‘ extra long ’ ( P = 0.04 ) and ‘ long ’ ( P = 0.01 ) walks . Neither programme had any immediate effect upon physical activity level otherwise . Though daily upright duration for the home group significantly improved six months after cessation of training ( P = 0.02 ) , generally physical activity level was maintained in the long term for both training groups . Conclusions : Hospital-based training enabled participants to walk for longer periods . It is clinical ly important that both training groups maintained physical activity level in the long term , given the potential for heart failure to worsen over this time period BACKGROUND Hospital-based exercise programs using a bicycle ergometer or a combination of exercise modalities have shown positive benefits in heart failure , but may not be readily accessible to many patients . Thus , we sought to evaluate the effects of a 12-week home walking exercise program on functional status and symptoms in patients with heart failure . METHODS A r and omized controlled trial comparing a 12-week progressive home walking exercise program ( n = 42 ) to a " usual activity " control group ( n = 37 ) was conducted in patients with heart failure ( 78 [ 99 % ] male ; mean age 62.6 + /- 10.6 years ; ejection fraction 27 % + /- 8.8 % ; 63 [ 80 % ] New York Heart Association class II ; 15[20 % ] New York Heart Association class III-IV ) from a Veterans Affairs medical center and a university-affiliated medical center . Functional status ( peak oxygen consumption via cardiopulmonary exercise testing , 6-minute walk test , the Heart Failure Functional Status Inventory ) , and symptoms ( Dyspnea-Fatigue Index score with a postglobal rating of symptoms ) were measured at baseline and 12 weeks . RESULTS No adverse events related to exercise training occurred . Overall mean compliance to training was 74 + /- 37 % . Peak oxygen consumption and the Heart Failure Functional Status Inventory were unchanged with training . Compared to the usual activity group , the training group had significantly longer walking distances measured by the 6-minute walk test ( 1264 + /- 255 vs 1337 + /- 272 feet , P = .001 ) , and improved postglobal rating of symptoms ( P = .03 ) . CONCLUSION In patients with heart failure , a progressive home walking exercise program is acceptable , increases walking distance , and decreases global rating of symptoms CONTEXT Exercise training in patients with chronic heart failure improves work capacity by enhancing endothelial function and skeletal muscle aerobic metabolism , but effects on central hemodynamic function are not well established . OBJECTIVE To evaluate the effects of exercise training on left ventricular ( LV ) function and hemodynamic response to exercise in patients with stable chronic heart failure . DESIGN Prospect i ve r and omized trial conducted in 1994 - 1999 . SETTING University department of cardiology/outpatient clinic in Germany . PATIENTS Consecutive sample of 73 men aged 70 years or younger with chronic heart failure ( with LV ejection fraction of approximately 0.27 ) . INTERVENTION Patients were r and omly assigned to 2 weeks of in-hospital ergometer exercise for 10 minutes 4 to 6 times per day , followed by 6 months of home-based ergometer exercise training for 20 minutes per day at 70 % of peak oxygen uptake ( n=36 ) or to no intervention ( control group ; n=37 ) . MAIN OUTCOME MEASURES Ergospirometry with measurement of central hemodynamics by thermodilution at rest and during exercise ; echocardiographic determination of LV diameters and volumes , at baseline and 6-month follow-up , for the exercise training vs control groups . RESULTS After 6 months , patients in the exercise training group had statistically significant improvements compared with controls in New York Heart Association functional class , maximal ventilation , exercise time , and exercise capacity as well as decreased resting heart rate and increased stroke volume at rest . In the exercise training group , an increase from baseline to 6-month follow-up was observed in mean ( SD ) resting LV ejection fraction ( 0.30 [ 0.08 ] vs 0.35 [ 0.09 ] ; P=.003 ) . Mean ( SD ) total peripheral resistance ( TPR ) during peak exercise was reduced by 157 ( 306 ) dyne/s/cm(-5 ) in the exercise training group vs an increase of 43 ( 148 ) dyne/s/cm(-5 ) in the control group ( P=.003 ) , with a concomitant increase in mean ( SD ) stroke volume of 14 ( 22 ) mL vs 1 ( 19 ) mL in the control group ( P=.03 ) . There was a small but significant reduction in mean ( SD ) LV end diastolic diameter of 4 ( 6 ) mm vs an increase of 1 ( 4 ) mm in the control group ( P<.001 ) . Changes from baseline in resting TPR for both groups were correlated with changes in stroke volume ( r=-0.76 ; P<.001 ) and in LV end diastolic diameter ( r=0.45 ; P<.001 ) . CONCLUSIONS In patients with stable chronic heart failure , exercise training is associated with reduction of peripheral resistance and results in small but significant improvements in stroke volume and reduction in cardiomegaly . JAMA . 2000 OBJECTIVES This study determined whether greater volumes of exercise were associated with greater reductions in clinical events . BACKGROUND The HF-ACTION ( Heart Failure : A Controlled Trial Investigating Outcomes of Exercise Training ) trial showed that among patients with heart failure ( HF ) , regular exercise confers a modest reduction in the adjusted risk for all-cause mortality or hospitalization . METHODS Patients r and omized to the exercise training arm of HF-ACTION who were event-free at 3 months after r and omization were included ( n = 959 ) . Median follow-up was 28.2 months . Clinical endpoints were all-cause mortality or hospitalization and cardiovascular mortality or HF hospitalization . RESULTS A reverse J-shaped association was observed between exercise volume and adjusted clinical risk . On the basis of Cox regression , exercise volume was not a significant linear predictor but was a logarithmic predictor ( p = 0.03 ) for all-cause mortality or hospitalization . For cardiovascular mortality or HF hospitalization , exercise volume was a significant ( p = 0.001 ) linear and logarithmic predictor . Moderate exercise volumes of 3 to < 5 metabolic equivalent (MET)-h and 5 to < 7 MET-h per week were associated with reductions in subsequent risk that exceeded 30 % . Exercise volume was positively associated with the change in peak oxygen uptake at 3 months ( r = 0.10 ; p = 0.005 ) . CONCLUSIONS In patients with chronic systolic HF , volume of exercise is associated with the risk for clinical events , with only moderate levels ( 3 to 7 MET-h per week ) of exercise needed to observe a clinical benefit . Although further study is warranted to confirm the relationship between volume of exercise completed and clinical events , our findings support the use of regular exercise in the management of these patients OBJECTIVE To evaluate six-minute walking test ( 6-MWT ) in treatment of CHF and to investigate the effect of exercise training on blood leucocyte and its components and plasma TNF alpha in CHF patients . METHODS 60 cases with NYHA II-III CHF patients underwent 6-MWT within 24 hours after hospitalization . The walking distance , heartbeat , plasma TNF alpha , and blood leucocyte and its components were investigated before and after walking test . These patients were then r and omized into two groups , a training group ( 32 cases ) and a control group ( 28 cases ) . Besides routine medication , 6-MWT was performed in the training group twice a day for 8 weeks . The same parameters were redetermined after 8 weeks of follow-up . 23 cases with NYHA IV CHF patients were investigated with the same parameters in the first day after hospitalization . RESULTS Blood leucocyte count and percentage of granulocytes and mononuclears in cases with NYHA III-IV were significantly higher than those with NYHA II . There were significant reduction of heartbeat and prolongation of walking distance in CHF patients after exercise training . Blood leucocyte count and the percentage of granulocytes and mononuclear and plasma TNFalpha level were reduced more in the training group than the control group after 8 weeks the treatment . CONCLUSIONS There is significantly higher leucocyte count and percentage of granulocytes and mononuclears in CHF with NYHA III-IV than those with NYHA II . 6-MWT , as an exercise training , is simple , safe , and not harmful . It can not only evaluate the severity of CHF but also serve as a therapeutic measure for CHF . Moreover the excessive activation of cytokines as TNFalpha could be reduced by 6-MWT training in CHF patients BACKGROUND The study 's aim was to examine the effect of exercise training on left ventricular diastolic function ( LVDF ) and whether LVDF could predict an improvement in exercise capacity ( EC ) in post-myocardial infa rct ion patients . METHODS Forty-eight males , aged 56.4 + /- 7.2 years , with preserved left ventricular systolic function ( LVSF ) and mild diastolic dysfunction ( the ratio of transmitral early left ventricular filling velocity to early diastolic mitral annulus velocity E/E ' > 8 as the average of the septal and lateral annulus velocities ) , were assigned to either a training group ( TG , n = 32 ) or controls ( n = 16 ) . Before , and at the end of the study , all patients underwent a cardiopulmonary test and echocardiography with tissue Doppler imaging ( TDI ) . RESULTS After a 4.5-month training program , maximal oxygen consumption increased significantly in TG ( 26.66 + /- 3.88 vs. 28.79 + /- 5.00 mL/kg/min , p < 0.0001 ) . TDI-derived E/E ' did not change after the training program . After dividing TG according to septal E/E 's > 10 and < 10 and lateral E/E'l > 8 and < 8 , exercise capacity improved significantly only in patients with E/E 's < 10 and E/E'l < 8 . CONCLUSIONS A 4.5-month training program in post-myocardial infa rct ion patients with preserved LVSF and mild diastolic dysfunction led to improved exercise capacity only in TG . The diastolic function did not change significantly . The improvement in exercise capacity was significantly greater in patients with a better LVDF measured by TDI OBJECTIVES We sought to evaluate the effect of physical training on neurohormonal activation in patients with heart failure ( HF ) . BACKGROUND Patients with HF benefit from physical training . Chronic neurohormonal activation has detrimental effects on ventricular remodeling and prognosis of patients with HF . METHODS A total of 95 patients with HF were assigned r and omly into two groups : 47 patients ( group T ) underwent a nine-month training program at 60 % of the maximal oxygen uptake ( VO2 ) , whereas 48 patients did not ( group C ) . The exercise load was adjusted during follow-up to achieve a progressive training effect . Plasma assay of B-type natriuretic peptide ( BNP ) , amino-terminal pro-brain natriuretic peptide ( NT-proBNP ) , norepinephrine , plasma renin activity , and aldosterone ; quality -of-life question naire ; echocardiogram ; and cardiopulmonary stress test were performed upon enrollment and at the third and ninth month . RESULTS A total of 85 patients completed the protocol ( 44 in group T , left ventricular ejection fraction [ EF ] 35 + /- 2 % , mean + /- SEM ; and 41 in group C , EF 32 + /- 2 % , p = NS ) . At the ninth month , patients who underwent training showed an improvement in workload ( + 14 % , p < 0.001 ) , peak VO2 ( + 13 % , p < 0.001 ) , systolic function ( EF + 9 % , p < 0.01 ) , and quality of life . We noted that BNP , NT-proBNP , and norepinephrine values decreased after training ( -34 % , p < 0.01 ; -32 % , p < 0.05 ; -26 % , p < 0.01 , respectively ) . Increase in peak VO2 with training correlated significantly with the decrease in both BNP/NT-proBNP level ( p < 0.001 and p < 0.01 , respectively ) . Patients who did not undergo training showed no changes . CONCLUSIONS Clinical benefits after physical training in patients with HF are associated with blunting of adrenergic overactivity and of natriuretic peptide overexpression Background : Physiological benefits of exercise training for heart failure ( HF ) patients have been demonstrated , however little is known about the effects of training on the symptoms of fatigue and dyspnea . Aim : The purpose of this study was to examine HF symptoms of fatigue and dyspnea in response to a 24-week exercise training intervention . Methods : This pilot study was a r and omized , two-group repeated measures design . Fifteen subjects in the intervention group completed a combination of aerobic and resistance training three times per week in a st and ard cardiac rehabilitation setting . The control group consisted of 6 subjects who were instructed not to begin any formal exercise program during the 24-week intervention . Results : Subjects ( 19 males and 2 females ) had a mean age of 66.2 ± 10.2 years and mean ejection fraction ( EF ) of 28.4 ± 7.4 % . Non-parametric Friedman Analysis of Variance by Ranks showed the exercise group significantly decreased sensory fatigue ( Piper Fatigue Scale ) over time ( χ 2 = 6.49 , p = .04 ) while the control group did not change ( χ 2 = 0.93 , p = .63 ) . Dyspnea showed a non-significant decrease over time for the exercise group ( χ 2 = 4.16 , p = .13 ) while the control group showed a decrease from baseline to 12 weeks but an increase to above baseline values by week 24 ( χ 2 = 0.18 , p = .91 ) . Conclusion : These results provide support for the beneficial effects of exercise training on symptoms of fatigue and dyspnea in HF patients . Larger studies to evaluate symptom response to exercise are needed BACKGROUND Heart rate recovery ( HRR ) is a marker of vagal tone that is associated with survival , but little is known about the effects of exercise training on HRR in patients with heart failure ( HF ) . METHODS Twenty-four patients with HF were r and omized to a 2-month residential rehabilitation program or to usual care . Symptom-limited exercise testing was performed at baseline and at discharge from the program . Heart rate recovery was expressed as the decline in heart rate from peak exercise through 6 minutes into recovery . In addition , HRR recovery curves were normalized to a range of 1 at peak heart rate and 0 at 6 minutes and adjusted for differences in heart rate reserve , facilitating the comparison of recovery curve shapes between groups . RESULTS Mean peak oxygen uptake and oxygen uptake at the lactate threshold increased 26 % ( P < .05 ) and 39 % ( P < .001 ) , respectively , in the exercise group , whereas neither of these responses changed significantly among controls . Heart rate recovery was significantly more rapid in the exercise group after training ( main effect 12.6 vs 2.6 beat/min in the trained and control groups , respectively , P = .005 ) . The normalized curves showed that the largest improvement in recovery curve shape occurred in the exercise group , but most of the HRR improvement was accounted for by a widening of the difference between peak and resting heart rate . CONCLUSION Exercise training results in a faster HRR in patients with HF . Heart rate recovery , as a simple marker of autonomic function , is an easily acquired response that may be useful for evaluating patient outcomes in cardiac rehabilitation BACKGROUND The purpose of this study was to examine the effects of exercise training on functional capacity in patients with heart failure . METHODS One hundred eighty-one patients in New York Heart Association class I to III , with ejection fraction < 40 % and 6-minute walk distance < 500 meters , were recruited into a r and omized , controlled , single-blind trial comparing 3 months of supervised training , then 9 months of home-based training with usual care . RESULTS There was a significant increase in 6-minute walk distance at 3 and 12 months but no between-group differences . Incremental peak oxygen uptake increased in the exercise group compared with the control group at 3 months ( 0.104 + /- 0.026 L/min vs 0.025 + /- 0.023 L/min ; P = .026 ) and 12 months ( 0.154 + /- 0.074 L/min vs 0.024 + /- 0.027 L/min ; P = .081 ) . Compared with the control group , significant increases were observed in the exercise group for arm and leg strength . No significant changes were observed in cardiac function or quality of life . Adherence to exercise was good during supervised training but reduced during home-based training . CONCLUSIONS Exercise training improves peak oxygen uptake and strength during supervised training . Over the final 9 months of the study , there was little further improvement , suggesting that some supervision is required for these patients . There were no adverse effects on cardiac function or clinical events BACKGROUND Beneficial training outcomes have been reported in patients with chronic heart failure ( CHF ) following leg exercise training . However , data from more comprehensive training programs are limited . The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF . METHODS Twenty-four men and women [ age 63+/-9 years ( mean+/-S.D. ) ] with stable , moderate chronic heart failure ( left ventricular ejection fraction 30+/-10 % ) , were investigated in a r and omized controlled study with a training group of 16 patients and a control group of 8 patients . The training was performed as an aerobic resistance training by activating all the main muscle groups , one at a time . The patients exercised for 1 h , three times per week for 8 weeks . RESULTS Patient groups did not differ at baseline . Peak oxygen uptake ( 8 % , P<0.03 ) , the distance walked in a 6-min walking test ( 11 % , P<0.002 ) , the health-related quality of life ( P<0.001 ) and plasma norepinephrine levels at rest ( 32 % , P<0.003 ) and at submaximal intensities ( P<0.03 ) improved after training . No changes were found in the control group , except for decreased peak oxygen uptake ( P<0.02 ) and quality of life scores ( P<0.03 ) . CONCLUSIONS Since comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels , it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist BACKGROUND Prescription of endurance training and documentation of its efficacy in patients with chronic heart failure ( CHF ) is usually done with reference to maximal ergometric measurements which are subject to form on the day changes and motivational influences . However , the use of submaximal parameters might represent an alternative approach . METHODS This was tested in 54 patients with CHF ( 57 + /- 10 years , NYHA II : n = 40 ; NYHA III : n = 14 ) who were r and omized into training ( T ; n = 26 ) or control group ( CO ; n = 28 ) . Training consisted of 45 minutes cycling at an intensity corresponding to the anaerobic threshold ( AT ) and was conducted for 12 weeks , 4 to 5 times per week . Cardiorespiratory exercise testing was done before and after the experimental phase . Changes in well-being were investigated using a 5-point Likert scale . RESULTS A significant rightward shift in the heart rate curve was demonstrated in T compared with CO ( P = .01 ; T : decrease in resting heart rate by 8 per minute , during exercise by 7 to 11/min ; CO : -1 and -1 to -3 per minute , respectively ) . Anaerobic threshold increased significantly by 11.6 % in T ( + 0.11 + /- 0.11 L min(-1 ) oxygen uptake ) compared with CO ( -0.02 + /- 0.10 L min(-1 ) ) . Positive changes in well-being were significantly larger in T ( P < .01 ) . CONCLUSIONS In patients with CHF , training can be prescribed and its efficacy can be evaluated by the exclusive use of submaximal parameters . Anaerobic threshold represents an appropriate training intensity in this population The present study investigates whether lower-limb dominant exercise training in patients with chronic heart failure ( CHF ) improves endothelial function primarily in the trained lower extremities or equally in the upper and lower extremities . Twenty-eight patients with CHF were r and omized to the exercise or control group . The exercise group underwent cycle ergometer training for 3 months while controls continued an inactive sedentary lifestyle . Exercise capacity ( 6-min walk test ) and flow-mediated vasodilation in the brachial and posterior tibial arteries were evaluated . After 3 months , walking performance increased only in the exercise group ( 488+/-16 to 501+/-14 m [ control ] ; 497+/-23 to 567+/-39 m [ exercise , p<0.05 ] ) . The flow-mediated vasodilation in the brachial arteries did not change in either group ( 4.2+/-0.5 to 4.5+/-0.4 % [ control ] ; 4.3+/-0.5 to 4.6+/-0.4 % [ exercise ] ) , but that in the posterior tibial arteries increased only in the exercise group ( 4.1+/-0.5 to 4.1+/-0.3 % [ control ] ; 3.6+/-0.3 to 6.4+/-0.6 % [ exercise , p<0.01 ] ) . Cycle ergometer training improved flow-mediated vasodilation in the trained lower limbs , but not in the untrained upper limbs . Exercise training appears to correct endothelial dysfunction predominantly by a local effect in the trained extremities PURPOSE The study 's purpose was to analyze the effects of exercise training on exercise tolerance and left ventricular systolic function and structure in heart failure patients with preserved , mild , and moderate to severe reduction of left ventricular ejection fraction ( LVEF ) . METHODS Ninety-eight patients with moderate to severe ( n = 34 ) , mild ( n = 33 ) , and preserved ( n = 31 ) LVEF were r and omly assigned to exercise training plus usual care ( n = 65 ) or usual care alone ( n = 33 ) in a r and omization ratio of 2:1 . Left ventricular function , left ventricular dimensions , and exercise tolerance were assessed before and after each intervention . RESULTS Exercise tolerance and LVEF increased with exercise training in all patient groups , whereas they remained unchanged after usual care alone . Exercise training increased the mean ratio of early to late mitral inflow velocities ( E/A ratio ) and decreased deceleration time ( DT ) of early filling in patients with mild and preserved LVEF . In patients with moderate to severe systolic dysfunction and advanced diastolic dysfunction ( DT < 160 ms ) , exercise training decreased E/A ratio and increased DT , both of which were unchanged after usual care alone . In the remaining patients ( DT > 160 ms ) , exercise training also improved mitral inflow patterns . Exercise training decreased left ventricular dimensions in patients with mild and moderate to severe reduction of LVEF but not in patients with preserved LVEF . CONCLUSIONS These results indicate that exercise training can improve the course of heart failure independent of the degree of baseline left ventricular dysfunction Objective : To study the effect of Tai Chi on exercise tolerance in patients with moderate heart failure . Design : R and omised parallel group study balanced for baseline variables . Setting : Cardiology Department , Royal Hallamshire Hospital . Patients and methods : 52 patients 42 men , mean age 68.9 years , range 4690 years , and 10 women , mean age 70.0 years , range 5882 with chronic heart failure New York Heart Association symptom class IIIII were studied . Patients were r and omised to Tai Chi Chuan twice a week for 16 weeks or to st and ard medical care without exercise rehabilitation . Main outcome measures : The primary outcome measure was the change in the distance walked in the shuttle walk test . Secondary outcome measures were changes in symptom scores and quality of life indices . Results : Objective measures of exercise tolerance did not improve significantly with Tai Chi , but patients having Tai Chi exercise had an improvement in symptom scores of heart failure measured by the Minnesota Living with Heart Failure Question naire comparison of deltas , 2.4 control vs 14.9 ; p0.01 , and depression scores measured by the SCL-90-R question naire 2.9 vs 6.8 ; p0.12 compared with those patients in the control group . Conclusion : In patients with chronic heart failure , 16 weeks of Tai Chi training was safe , with no adverse exercise related problems . It was enjoyed by all taking part and led to significant improvements in symptoms and quality of life Background A follow-up study was carried out on the 5-year status of the surviving patients ( n = 179 at 6 months ) of a 24-week r and omized controlled trial comparing cardiac rehabilitation ( CR ) with heart failure outpatient clinic care ( st and ard care ) . Methods In the original r and omized controlled trial , 200 patients ( 60–89 years , 132 men ) with New York Heart Association II/III heart failure confirmed by echocardiography had been r and omized ( 2000–2001 ) . At the 5-year follow-up , the initial trial measures ( 6-min walk test , Minnesota living with heart failure , EuroQol health-related quality of life , and routine biochemistry ) were repeated if the patient was in a satisfactory condition . Data on deaths and admissions were obtained from the medical records department . Results Over half of the original participants ( n = 119 , 59.5 % ) were alive at 5 years ( mean age 75.2 years ) , and most ( 94 % ) attended the clinic for assessment . A sustained improvement from baseline for both groups in Minnesota living with heart failure , but not in EuroQol was observed , and the majority of the other measures had deteriorated . In contrast to the CR group , the st and ard care group showed a significant deterioration in walking distance ( 5 versus 11 % ; P [ 0.05 ) . More patients in the CR group were taking regular exercise ( 71 versus 51 % ; P [ 0.05 ) . No significant differences between the groups in health care utilization or survival were observed . Conclusion A 24-week CR programme for patients with stable heart failure showed some long-term benefit at 5 years . Differences in the mean values of most of the functional and quality of life measures were evidently to the advantage of the CR group , which also showed a better exercise profile PURPOSE The purpose of this study was to determine whether subjects with chronic heart failure , who completed a 12-week rehabilitation program , would have significantly greater quality of life , better aerobic fitness , less difficulty with symptoms of heart failure , greater self-efficacy for exercise , and higher daily activity levels when compared with subjects in a control group . METHODS Thirty-one males , aged 64 + /- 10 years with left ventricular ejection fraction of 29 + /- 7 % , were r and omized to a moderate intensity supervised aerobic exercise program ( n = 15 ) or a control group ( n = 16 ) . Twenty-seven subjects completed at least 1 follow-up assessment . RESULTS After 12 weeks there were significant differences in the change scores for perceived physical function ( using R AND Corporation 's 36-item short form ) ( P = .025 ) and peak oxygen uptake ( P = .019 ) between the exercise and control groups with the exercise group experiencing improved physical function and fitness . CONCLUSIONS Exercise training in adults with heart failure increases exercise tolerance and perceived physical function . Improved heart failure symptoms , self-efficacy for exercise , or increased physical activity may not be associated with enhancement of exercise tolerance BACKGROUND Patients with chronic heart failure ( CHF ) have sexual dysfunction that impairs quality of life . Recent trials have demonstrated that exercise training ( ET ) improves quality of life ( QOL ) of CHF patients , but it is not established whether this benefit may be associated with an improvement in sexual dysfunction . OBJECTIVE To determine whether ET can improve sexual dysfunction in patients with CHF . METHODS We prospect ively studied 59 male patients ( 57+/-9 years ) with stable CHF in sinus rhythm and without prostatic disease . Patients were r and omized into two groups . A group ( T , n = 30 ) underwent supervised cycle ergometer ET at 60 % of peak VO2 , three times a week , 60 min each session , for 8 weeks . A group ( NT , n = 29 ) was not exercised . Medications were not changed during the study . On study entry and at 8 weeks all patients underwent a symptom-limited cardiopulmonary exercise testing , brachial artery endothelium-dependent ( ED ) and endothelium-independent ( EI ) vasomotor responses , QOL and sexual activity profile assessment ( SAP ) by question naire . RESULTS At 8 weeks , no changes were observed in control patients . In trained patients , however , peak VO2 improved by 18 % ( P < 0.005 ) and was correlated with QOL ( r = 0.80 ; P < 0.001 ) . Flow-mediated dilation improved in trained patients ( from 2.29+/-1.13 % to 5.04+/-1.7 % , P = 0.0001 ) , while EI dilation ( after 0.3 mg sublingual NTG ) did not . In group T , all three domains ( i.e. Domain 1=relationship with the partner ; Domain 2 = quality of penile erection ; Domain 3 = personal wellness ) were significantly improved from baseline ( total score patients : from 3.49+/-3.4 to 6.17+/-3.2 , P < 0.001 ; partners : from 2.47+/-2.7 to 4.87+/-2.5 , P < 0.001 ) . Pre-post training change in SAP total score was correlated with changes in coronary risk profile ( r = -0.49 ; P = 0.01 ) , peak VO2 ( r = 0.67 ; P < 0.001 ) and QOL ( r = 0.73 ; P = 0.01 ) . Multivariate analysis selected the improvement in ED-vasomotor response as the strongest independent predictor of SAP improvement ( r = 0.63 , P < 0.001 ) . CONCLUSIONS In stable CHF , cycle ergometer ET significantly improves brachial artery endothelial dysfunction , suggesting a systemic effect of leg exercise . This benefit was correlated with improvements in sexual activity Patients with heart failure ( HF ) often have profound activity limitations and diminished quality of life ( QOL ) due to symptoms of dyspnea and fatigue . Although recent studies demonstrate positive physiologic and psychological benefits of low to moderate intensity , supervised , aerobic exercise training performed 3 to 5 days/ week for 20 to 40 minutes ' duration , in a monitored setting , the efficacy of a home-based exercise program combining endurance and resistance exercise on symptoms and QOL , are unknown . This r and omized controlled study examined the efficacy , safety , and adherence rates of a 3-month home-based combined walking and resistance exercise program on symptoms and QOL in 40 women and men aged 30 to 76 years with New York Heart Association class II to III HF . Baseline and 3-month evaluations consisted of a chronic HF question naire to assess symptoms and QOL and exercise capacity by symptom-limited treadmill exercise test with respiratory gas analysis . The exercise intervention improved fatigue ( p = 0.02 ) , emotional function ( p = 0.01 ) , and mastery ( p = 0.04 ) . Overall exercise adherence was excellent ( 90 % ) and there were no reported adverse events . A moderate intensity home-based combined walking and resistance program for patients with class II to III HF is safe and effective in reducing symptoms and improving QOL The role of exercise training in the treatment of heart failure remains a paradox , because exercise intolerance is a characteristic finding in patients with this condition . Improved exercise performance after exercise training has been seen in patients with heart failure , but such training is not yet widely incorporated into clinical practice . In addition , the mechanisms by which this improvement occurs are uncertain . Factors that may explain the improvement include an increase in cardiac output [ 1 , 2 ] , an improvement in skeletal muscle metabolism [ 3 - 5 ] , and an increase in peak blood flow to the exercising limb that is caused by a decrease in vascular resistance [ 1 , 2 , 5 ] . Five r and omized trials [ 5 - 9 ] have assessed exercise performance after exercise training in patients with symptomatic heart failure . Two trials that assessed cardiorespiratory fitness as measured by oxygen consumption ( Vo 2 ) showed a 22 % improvement in peak Vo 2 after 4 weeks of exercise training [ 6 ] and a 31 % improvement after 6 months of exercise training [ 5 ] . Two other trials [ 7 , 8 ] showed an increase in exercise duration after 12 weeks of exercise training , and a fifth trial [ 9 ] recently found no significant increase in peak Vo 2 after exercise training . We sought to assess the benefit of exercise training in patients with heart failure caused by left ventricular systolic dysfunction and to further describe the physiologic changes associated with exercise training . Functional capacity and cardiorespiratory fitness were measured before and after exercise training in patients with compensated heart failure who were receiving st and ard medical therapy . Patients were r and omly assigned either to a group that participated in a program of three supervised exercise sessions per week for 24 weeks ( exercise group ) or to a control group that did not exercise . Methods Patients Forty men with compensated heart failure and left ventricular dysfunction were r and omly assigned to the exercise group ( n = 21 ) or the control group ( n = 19 ) . R and omization was done according to a computer-generated r and omization list . Patients were recruited from the outpatient heart failure clinic of a tertiary care hospital or from the office of a cardiologist practicing in the community . Patients meeting the eligibility criteria for the study first received a brief explanation of the study from their cardiologist . Patients willing to participate in the r and omized trial were then referred . The hospital 's institutional review board approved our study , and all patients provided written informed consent . Inclusion criteria were New York Heart Association class II or III , a resting ejection fraction of 35 % or less as measured by echocardiography or gated equilibrium radionuclide angiography , and no change in medical therapy for 30 days before r and omization . Exclusion criteria were atrial fibrillation , acute myocardial infa rct ion within the previous 3 months , angina pectoris at rest or induced by exercise , current enrollment in another clinical trial , and current participation in a regular exercise program ( at least twice weekly ) . Patients were classified as having ischemic cardiomyopathy if they had had a myocardial infa rct ion or had angiographic evidence of coronary artery disease that could explain the extent of ventricular dysfunction . If they did not meet these criteria , they were classified as having idiopathic dilated cardiomyopathy . Study Design Exercise tests were completed before and after a 30-day pre study period . The pre study period was used to document the stability of exercise tolerance , clinical conditions , and prescribed medications . Immediately after completing the second exercise test , patients were r and omly assigned to the exercise group or the control group . Each patient 's assignment was sealed in an envelope until completion of the second exercise test . Exercise testing was repeated at weeks 12 and 24 for patients in both groups . Each patient 's physician was asked not to change a patient 's drug regimen during the study , if possible . Patients in the control group were instructed to maintain their normal daily activity habits and not to begin an exercise regimen . Controls were contacted by telephone every 2 to 3 weeks to assess compliance , cardiac-related symptoms , and continued avoidance of a regular activity program . Exercise Testing Symptom-limited , maximal exercise tests were completed using an upright stationary cycle ergometer ( Monark , Stockholm , Sweden ) , starting at a power output of 25 W and increasing by 25 W every 3 minutes . Tests were discontinued when dyspnea or calf , thigh , or generalized fatigue developed . Patients were monitored by electrocardiography ( Q-3000 , Quinton Instruments , Seattle , Washington ) at rest , during exercise , and during 8 minutes of recovery . Blood pressure , heart rate , rating of perceived exertion ( categorized on the Borg scale ; range , 6 to 20 ) , and a 12-lead electrocardiogram were obtained after 30 minutes of supine rest , within the last 25 seconds of each stage of exercise , and during peak exercise . Air expired during exercise testing was analyzed using a Horizon II Metabolic System ( Sensormedics , Yorba Linda , California ) . Direct measurement and calculations were used to determine peak Vo 2 , carbon dioxide production ( Vco 2 ) , ventilation , oxygen ( O2 ) pulse , and respiratory exchange ratio . Expired air was sample d at a rate of 10 per second and reported as a 15-second average . Exercise tests in the exercise group and the control group represented peak effort , as evidence d by ratings of perceived exertion that were generally 16 or more and respiratory exchange ratios that were greater than 1.1 . Ventilatory derived anaerobic threshold ( V-AT ) was determined using the V-slope method , originally defined by Beaver and colleagues [ 10 ] and later simplified by others [ 11 - 13 ] . This measure , in which Vco 2 is plotted as a function of Vo 2 , can be used to detect the beginning of excess carbon dioxide production caused by the buffering of H+ that arise from lactic acid . Two independent , experienced review ers blinded to the patients ' group assignment and testing periods determined V-AT . For four patients in the exercise group and five patients in the control group , a review er could not determine V-AT in at least one of each patient 's three exercise tests . We also computed the slope of the relation between ventilation and Vco 2 as a marker of the severity of heart failure [ 14 ] . Exercise Training Each exercise training session lasted 43 minutes . During each session , patients completed a 5-minute , slow warm-up phase , a 33-minute aerobic phase ( three different types of exercise equipment were used for 11 minutes each ) , and a 5-minute cool-down phase . Exercise equipment included motor-driven treadmills , stationary cycles , rowing machines , and arm ergometers . Patients attended the exercise training program three times per week . Using the heart rate reserve method [ 15 ] , we set exercise intensity at 60 % for the first 2 weeks and then increased it , as tolerated , to as high as 80 % . A rating of perceived exertion of 12 to 14 was also used to guide exercise intensity . Heart rate and rhythm were monitored during exercise using a single-lead electrocardiography telemetry system . Statistical Analysis Of the 40 patients entered into the study , only those who also completed the exercise tests at weeks 12 and 24 were considered in the data analysis . The 5 patients who dropped out for nonmedical reasons were asked to return for follow-up testing , but they refused . We compared patient characteristics at baseline using an unpaired t-test or the Fisher exact test . We used univariate repeated- measures analysis of variance with the Greenhouse-Geisser [ 16 ] sphericity correction to determine whether a significant ( P < 0.05 ) difference in the change across time occurred between the two groups . For variables for which a significant ( or a tendency toward a significant ) time-group interaction was detected , we used analysis of variance to assess a within-group time effect and used a Student two- sample t-test to assess a group effect . For the latter two analyses , we used the Bonferroni multiple testing adjustment to reduce the level accordingly . Values are expressed as means SE . The SAS software package ( SAS Institute , Cary , North Carolina ) was used for all analyses . Results Compliance , Medical Therapy , and Safety Among patients who completed the study , no differences in demographic characteristics were seen between the two study groups after r and omization ( Table 1 ) . Of the 40 patients r and omly assigned at baseline , 29 completed the study and 11 dropped out ( Table 1 ) . Regardless of the reason for drop out , patients with ischemic cardiomyopathy tended to drop out more frequently ( 7 of 16 patients [ 44 % ] ) than did patients with dilated cardiomyopathy ( 4 of 24 patients [ 17 % ] ) ( P = 0.08 ) . In addition , ejection fraction tended to be lower in patients who dropped out than in those who did not ( 18 % 5 % compared with 23 % 8 % ; P = 0.09 ) , and patients who dropped out tended to be older ( 61 10 years compared with 54 11 years ; P = 0.07 ) . No differences were seen in New York Heart Association class ( II compared with III ) between patients who completed the study and those who dropped out . Table 1 . Baseline Patient Characteristics * Fifteen patients in the exercise group completed the study . Two patients dropped out because of noncardiac medical conditions ( progressive , limiting arthritis in one patient and newly diagnosed cancer in the other ) that developed within 1 month of the start of the exercise program . One patient developed atrial fibrillation between week 12 and week 24 ; 3 other patients stopped exercising for personal reasons before week 12 and refused follow-up testing . Fourteen of the 19 patients in the control group completed the study . Two dropped out for personal reasons and refused follow-up testing , 1 developed atrial fibrillation between week 12 and week 24 , 1 was BACKGROUND Although there are limited clinical data to support the use of exercise training as a means to reduce mortality and morbidity in patients with heart failure , current guidelines state that exercise is beneficial . TRIAL DESIGN The objective of this trial is to determine whether exercise training reduces all-cause mortality or all-cause hospitalization for patients with left ventricular systolic dysfunction and heart failure symptoms . After undergoing baseline assessment s to determine whether they can safely exercise , patients are r and omized to either usual care or exercise training . Patients in the exercise training arm attend 36 supervised facility-based exercise training sessions . Exercise modalities are cycling or walking . After completing 18 sessions , patients initiate home-based exercise and then transition to solely home-based exercise after completing all 36 sessions . Patients return for facility-based training every 3 months to reinforce their exercise training program . Patients are followed for up to 4 years . Physiologic , quality -of-life , and economic end points that characterize the effect of exercise training in this patient population will be measured at baseline and at intervals throughout the trial . Blood sample s will be collected to examine biomarkers such as brain natriuretic peptide , tumor necrosis factor , and C-reactive protein . CONCLUSIONS Because of its relatively low cost , high availability , and ease of use , exercise training is an intervention that could be accessible to most patients with heart failure . The HF-ACTION trial is design ed to definitively assess the effect of exercise training on the clinical ly relevant end points of mortality , hospitalization , and quality of life in patients with heart failure Background Physical training is a well-known complementary treatment for chronic heart failure ( CHF ) ; however , many aspects require further studies . One of them is the impact on remodeling of the left ventricle ( LV ) . The purpose of this study was to evaluate the effect of 6 months of training on LV , exercise capacity and safety issues in patients with ischemic CHF . Methods Fifty patients ( mean age 60.1 ± 9.2 years ) with ischemic CHF , New York Heart Association ( NYHA ) classification class II and III and left ventricular ejection fraction ( LVEF ) ≤ 35 % were r and omized into groups : undergoing 6-month training ( 25 patients ) and not trained ( 25 patients ) . In both groups at baseline and at 6 months a cardiopulmonary exercise test and magnetic resonance imaging ( MRI ) with evaluation of LV were performed . Training was limited by the achievement of 80 % of the predicted heart rate at VO2PEAK achieved at the baseline cardiopulmonary exercise test . Results All patients completed the 6-month observation . No serious adverse events were found in either group . Exercise capacity improved only in the trained group ( VO 2peak increased by 31 % ) . At 6 months in the trained group there was a tendency towards an improvement in some LV parameters : ejection fraction , end-diastolic volume and wall motion score index ( WMSI ) , whereas an opposite trend was seen in the controls ( P < 0.05 , P < 0.05 and P < 0.01 for comparison of LVEFs , end-diastolic volumes and WMSIs , respectively ) . Conclusions Six-month training in ischemic CHF patients is a safe modality . Training improves exercise capacity . There was no negative impact on LV morphology , and a trend towards improvement of functional parameters on MRI may suggest an anti-remodeling effect of training in patients with ischemic CHF . Eur J Cardiovasc Prev Rehabil 14 : 85 - 91 © 2007 The European Society of BACKGROUND Supervised cardiac rehabilitation programs have been offered to patients following myocardial infa rct ( MI ) , coronary artery bypass graft surgery ( CABG ) and percutaneous coronary intervention ( PCI ) for many years . However , limited information is available on the usefulness of rehabilitation programs in chronic heart failure ( CHF ) . The aim of our study was to evaluate the outcome of supervised physical training on CHF patients by measuring both central and peripheral factors . METHODS This was a prospect i ve r and omized study , including 43 patients with CHF , New York Heart Association ( NYHA ) class II or III , mean age 68 years . After initial measurements of VO2 peak , 6 min walk distance , muscle strength , plasma levels of atrial natriuretic peptide ( ANP ) and brain natriuretic peptide ( BNP ) , echocardiogram , measurements of pulmonary function and quality of life question naire , patients were r and omized to either a training group ( n = 21 ) or a control group ( n = 22 ) . The training group had supervised aerobic and resistance training program twice a week for five months . After the training program was completed , all measurements were repeated in both groups . RESULTS No training related adverse events were reported . Significant improvement was found between groups in the six minute walk test ( + 37.1 m vs. + 5.3 m , p = 0.01 ) , work load on the bicycle exercise test ( + 6.1 W vs. + 2.1 W , p = 0.03 ) , time on the bicycle exercise test ( + 41 s vs. + 0 s , p = 0.02 ) and quadriceps muscle strength test ( + 2.8 kg . vs. + 0.2 kg . , p = 0.003 ) . Quality of life factors that reflect exercise tolerance and general health , improved significantly in the training group compared to the control group . No other significant changes were found between the two groups . CONCLUSION Supervised physical training as used in this study appears safe for CHF patients in NYHA class II or III . The improvement in functional capacity observed in the training group seems to be related to peripheral factors rather than in central cardiovascular performance Eighty-two patients aged > or = 70 years with heart failure were r and omized to a gentle , seated exercise program or to usual care . Six-minute walk distance and quality of life did not change between groups , but daily activity as measured by accelerometry increased in the exercise group relative to the control group Objective : To compare the effects of traditional dancing with formal exercise training in terms of functional and cardiovascular benefits and motivation in patients with chronic heart failure . Design : R and omized controlled trial . Setting : Sports Medicine Laboratory . Subjects : Fifty-one Greek male patients aged 67.1±5.5 years with chronic heart failure of New York Heart Association ( NYHA ) class II – III , participated in an eight-month study . Interventions : They were r and omly assigned to either training with Greek traditional dances ( group A , n=18 ) , formal exercise training ( group B , n=16 ) or a sedentary control group ( group C , n=17 ) . Main measures : At entry and the end of the study all patients underwent cardiopulmonary exercise testing , functional ability assessment and quality of life evaluations . The Intrinsic Motivation Inventory was also used to assess participants ’ subjective experience . Results : After training group A showed increased peak oxygen consumption by 33.8 % ( 19.5 vs. 26.1 ml/kg/min , p<0.05 ) and B by 32.3 % ( 19.5 vs. 25.8 ml/kg/min , p<0.05 ) , maximal treadmill tolerance by 48.5 % ( p<0.05 ) and by 46.4 % ( p<0.05 ) , and a decreased Slope of expired minute ventilation for carbon dioxide output ( VE/VCO2 ) slope by 18 % ( p<0.05 ) and 19.5 % ( p<0.05 ) , respectively . Trained patients revealed significant improvement in the quality of life indices . Intrinsic Motivation Inventory was increased only in group A by 26.2 % ( 3.08 vs. 3.87 , p<0.05 ) . Conclusions : Exercise training in chronic heart failure patients with Greek traditional dances led to functional and cardiovascular benefits similar to formal exercise training and to a higher level of motivation BACKGROUND Due to dyspnea and fatigue , patients with chronic heart failure ( CHF ) are often restricted in the performance of everyday activities , which gradually may lead to hypoactivity . AIMS To assess whether aerobic training leads to a more active lifestyle and improved quality of life ( QoL ) in patients with CHF . METHODS Patients with stable CHF ( NYHA II/III ; 59 ( 11 ) years ) were r and omly assigned to a training group ( n=18 ; 3-month aerobic program above st and ard treatment ) or control group ( n=16 ; st and ard treatment without special advice for exercise ) . Measurements were performed on level of everyday physical activity ( PA , novel accelerometry-based activity monitor ) and QoL , and on several related parameters . RESULTS Training did not result in a more active lifestyle or improved QoL , but improved ( P<0.05 ) peak power ( 17 % ) , 6-min walk distance ( 10 % ) , muscle strength ( 13 - 15 % ) and depression ( -1.3 unit ) . Changes in level of everyday PA were related to changes in peak Vo(2 ) ( r=0.58 , P=0.01 ) and knee extension strength ( r=0.48 , P=0.05 ) . CONCLUSIONS At group level training did not result in a more active lifestyle or improved QoL. However , correlations between training-related changes in parameters suggest that aerobic training has the potential to increase levels of everyday PA in CHF OBJECTIVES The present study was design ed to evaluate the effect of an ambulatory training program on ultrastructural morphology and the oxidative capacity of skeletal muscle and its relation to central and peripheral hemodynamic variables in patients with chronic heart failure . BACKGROUND Clinical evidence supports the hypothesis that exercise intolerance in patients with chronic heart failure is not only a consequence of low cardiac output , but is also a result of alterations in oxidative metabolism of skeletal muscle . METHODS Twenty-two patients were prospect ively r and omized either to a training group ( mean [ + /-SD ] ejection fraction 26 + /- 9 % , n = 12 ) participating in an ambulatory training program or to a physically inactive control group ( ejection fraction 27 + /- 10 % , n = 10 ) . At baseline and after 6 months , patients underwent symptom-limited bicycle exercise testing , and central and peripheral hemodynamic variables were measured . Percutaneous needle biopsy sample s of the vastus lateralis muscle were obtained at baseline and after 6 months . The ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry . RESULTS After 6 months , patients in the training group achieved an increase in oxygen uptake at the ventilatory threshold of 23 % ( from 0.86 + /- 0.2 to 1.07 + /- 0.2 liters/min , p < 0.01 vs. control group ) and at peak exercise of 31 % ( from 1.49 + /- 0.4 to 1.95 + /- 0.4 liters/min , p < 0.01 vs. control group ) . There was no significant change in oxygen uptake at the ventilatory threshold and at peak exercise in the control group . The total volume density of mitochondria and volume density of cytochrome c oxidase-positive mitochondria increased significantly by 19 % ( from 4.7 + /- 1.5 to 5.6 + /- 1.5 vol% , p < 0.05 vs. control group ) and by 41 % ( from 2.2 + /- 1.0 to 3.1 + /- 1.0 vol% , p < 0.05 vs. control group ) after 6 months of regular physical exercise . Cardiac output at rest and at submaximal exercise remained unchanged but increased during maximal symptom-limited exercise from 11.9 + /- 4.0 to 14.1 + /- 3.3 liters/min in the training group ( p < 0.05 vs. baseline ; p = NS vs. control group ) . Peak leg oxygen consumption increased significantly by 45 % ( from 510 + /- 172 to 740 + /- 254 ml/min , p < 0.01 vs. control group ) . Changes in cytochrome c oxidase-positive mitochondria were significantly related to changes in oxygen uptake at the ventilatory threshold ( r = 0.82 , p < 0.0001 ) and at peak exercise ( r = 0.87 , p < 0.0001 ) . CONCLUSIONS Regular physical training increases maximal exercise tolerance and delays anaerobic metabolism during submaximal exercise in patients with stable chronic heart failure . Improved functional capacity is closely linked to an exercise-induced increase in the oxidative capacity of skeletal muscle OBJECTIVE To assess the physiological and psychosocial effects of exercise training in chronic heart failure . SUBJECTS/ PATIENTS Twenty-six men with heart failure ( New York Heart Association functional classes II and III ) aged 52.5 ( SD 9.8 ) years , were studied . METHODS The subjects were r and omized either to rehabilitation group ( Group A : 16 patients ) , participating in a 6-month exercise training program , or to control group ( Group B : 10 patients ) . A psychosocial assessment , which included affective ( Beck Depression Inventory and Hospital Anxiety and Depression Scale ) , quality of life ( Quality of Life Index , Minnesota Living with Heart Failure Question naire and the Scale of Life Satisfaction ) and personality ( Eysenck Personality Question naire ) parameters , was performed at the beginning and the end of the study . RESULTS After training VO2 peak increased by 36 % and exercise time by 35 % , p < 0.05 . A significant decrease in anxiety and depression was also observed . Moreover , trained patients demonstrated a significant improvement in quality of life . No significant correlations were found between deltaVO2 peak and all psychosocial parameter gains . However , the more depressed patients showed the largest physiological responses . CONCLUSION An exercise rehabilitation program in patients with chronic heart failure is useful for improving their work capacity and psychosocial status . Improvements in psychological status seem to be independent of the aerobic gains Patterns of medical re source use near the end of life may differ across modes of death . The aim of this study was to characterize patterns of inpatient re source use and direct costs for patients with heart failure ( HF ) who died of sudden cardiac death ( SCD ) , HF , other cardiovascular causes , or noncardiovascular causes during the last year of life . Data were from a r and omized trial of exercise training in patients with HF . Mode of death was adjudicated by an end point committee . Generalized estimating equations were used to compare hospitalizations , inpatient days , and inpatient costs incurred during the final year of life in patients who died of different causes , adjusting for clinical and treatment characteristics . Of 2,331 patients enrolled in the trial , 231 died after ≥1 year of follow-up with an adjudicated mode of death , including 72 of SCD , 80 of HF , 34 of other cardiovascular causes , and 45 of noncardiovascular causes . Patients who died of SCD were younger , had less severe HF , and incurred fewer hospitalizations , fewer inpatient days , and lower inpatient costs than patients who died of other causes . After adjustment for patient characteristics , inpatient re source use varied by 2 to 4 times across modes of death , suggesting that cost-effectiveness analyses of interventions that reduce mortality from SCD compared to other causes should incorporate mode-specific end-of-life costs . In conclusion , re source use and associated medical costs in the last year of life differed markedly in patients with HF who experienced SCD and patients who died of other causes BACKGROUND It is still a matter of debate whether exercise training ( ET ) is a beneficial treatment in chronic heart failure ( CHF ) . METHODS AND RESULTS To determine whether long-term moderate ET improves functional capacity and quality of life in patients with CHF and whether these effects translate into a favorable outcome , 110 patients with stable CHF were initially recruited , and 99 ( 59+/-14 years of age ; 88 men and 11 women ) were r and omized into 2 groups . One group ( group T , n=50 ) underwent ET at 60 % of peak & f1;O2 , initially 3 times a week for 8 weeks , then twice a week for 1 year . Another group ( group NT , n=49 ) did not exercise . At baseline and at months 2 and 14 , all patients underwent a cardiopulmonary exercise test , while 74 patients ( 37 in group T and 37 in group NT ) with ischemic heart disease underwent myocardial scintigraphy . Quality of life was assessed by question naire . Ninety-four patients completed the protocol ( 48 in group T and 46 in group NT ) . Changes were observed only in patients in group T. Both peak & f1;O2 and thallium activity score improved at 2 months ( 18 % and 24 % , respectively ; P<0 . 001 for both ) and did not change further after 1 year . Quality of life also improved and paralleled peak VO2 . Exercise training was associated both with lower mortality ( n=9 versus n=20 for those with training versus those without ; relative risk (RR)=0.37 ; 95 % CI , 0.17 to 0.84 ; P=0.01 ) and hospital readmission for heart failure ( 5 versus 14 ; RR=0.29 ; 95 % CI , 0.11 to 0.88 ; P=0.02 ) . Independent predictors of events were ventilatory threshold at baseline ( beta-coefficient=0.378 ) and posttraining thallium activity score ( beta-coefficient -0.165 ) . CONCLUSIONS Long-term moderate ET determines a sustained improvement in functional capacity and quality of life in patients with CHF . This benefit seems to translate into a favorable outcome CONTEXT Findings from previous studies of the effects of exercise training on patient-reported health status have been inconsistent . OBJECTIVE To test the effects of exercise training on health status among patients with heart failure . DESIGN , SETTING , AND PATIENTS Multicenter , r and omized controlled trial among 2331 medically stable out patients with heart failure with left ventricular ejection fraction of 35 % or less . Patients were r and omized from April 2003 through February 2007 . INTERVENTIONS Usual care plus aerobic exercise training ( n = 1172 ) , consisting of 36 supervised sessions followed by home-based training , vs usual care alone ( n = 1159 ) . R and omization was stratified by heart failure etiology , which was a covariate in all models . MAIN OUTCOME MEASURES Kansas City Cardiomyopathy Question naire ( KCCQ ) overall summary scale and key subscales at baseline , every 3 months for 12 months , and annually thereafter for up to 4 years . The KCCQ is scored from 0 to 100 with higher scores corresponding to better health status . Treatment group effects were estimated using linear mixed models according to the intention-to-treat principle . RESULTS Median follow-up was 2.5 years . At 3 months , usual care plus exercise training led to greater improvement in the KCCQ overall summary score ( mean , 5.21 ; 95 % confidence interval , 4.42 to 6.00 ) compared with usual care alone ( 3.28 ; 95 % confidence interval , 2.48 to 4.09 ) . The additional 1.93-point increase ( 95 % confidence interval , 0.84 to 3.01 ) in the exercise training group was statistically significant ( P < .001 ) . After 3 months , there were no further significant changes in KCCQ score for either group ( P = .85 for the difference between slopes ) , result ing in a sustained , greater improvement overall for the exercise group ( P < .001 ) . Results were similar on the KCCQ subscales , and no subgroup interactions were detected . CONCLUSIONS Exercise training conferred modest but statistically significant improvements in self-reported health status compared with usual care without training . Improvements occurred early and persisted over time . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047437 BACKGROUND Beneficial effects of physical training on exercise tolerance , autonomic and skeletal muscle function and limb blood flow have been demonstrated in chronic heart failure . Because this rehabilitation is expensive , may involve risk , and has unknown effects on prognosis , the possibility of predicting benefit on the basis of individual patient data is intriguing . The most suitable exercise training programme has not yet been established . METHODS AND RESULTS We review ed the progress of 134 stable heart failure patients studied in r and omized controlled trials of physical training . A significant training effect ( + 13 % peak oxygen consumption , + 17 % exercise duration ) was associated with improved autonomic indices ( resting catecholamines and hormones , heart rate variability ) , without significant side-effects . No ventilatory , haemodynamic , autonomic or clinical factor at baseline was a predictor of outcome . Similar beneficial effects were observed in both male and female patients . The improvement in oxygen consumption after 16 weeks training was higher than after 6 weeks ( + 2.6 + /- 3.0 vs + 0.3 + /- 3.1 ml.kg.min-1 , P < 0.05 ) . The combination of cycle ergometer with calisthenic exercises was more beneficial than cycle ergometer alone ( + 2.7 + /- 4.2 vs 1.2 + /- 2.0 ml.kg.min-1 , P < 0.01 ) . The presence of nonsustained ventricular tachycardia did not preclude a training effect . Patients older than 70 years were able to train , although less effectively than the younger ones . No difference in exercise gain was observed whether the patients trained in the hospital or at home . CONCLUSION The positive effects of physical rehabilitation in chronic stable heart failure patients are confirmed . No baseline patient factor was significantly correlated with outcome . A tailored , moderate , home-based , combined cycle ergometer , plus calisthenic exercise training seems safe and beneficial in a large cohort of heart failure patients , with similar benefits in a variety of conditions and different hospital setting Background Decreased exercise capacity is the main factor restricting the daily life of patients with chronic heart failure . N-terminal pro-brain natriuretic peptide ( NT pro-BNP ) is strongly related to the severity of and is an independent predictor of outcome in chronic heart failure . Design The study aim ed to evaluate the effect of exercise training on functional capacity and on changes in NT pro-BNP levels and to assess the effect of exercise training on quality of life . Material s and methods Sixty patients ( 45 men/15 women , mean age 52.7 years ; ±5.3 SD ) , with stable heart failure ( 45 ischaemic/hypertensive and 15 idiopathic patients ) , in New York Heart Association ( NYHA ) functional class II ( n = 35 ) to III ( n = 25 ) , with an ejection fraction less than 40 % , were r and omly assigned to a training ( n = 30 ) and a control group ( n = 30 ) . The training group ( 30 patients ) performed 3 months of supervised physical training programme using a bicycle ergometer for 30 min three times a week at a load corresponding to 60–70 % of their oxygen consumption ( Vo2 ) peak . The control group did not change their previous physical activity . A grade d maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85 % of the peak oxygen load at the baseline and after 3 months were performed , and at the same times NT pro-BNP levels were measured . Results The exercise capacity increased from 15.8 ( ±2.3 SD ) to 29.9 ( ±2.1 SD ) min ( P<0.0001 ) and the peak Vo2 tended to improve from 14.5 ( ±1.4 SD ) to 17.7 ( ±2.6 SD ) ml/kg per min ( P<0.0001 ) during the supervised training period . Vo2 at the anaerobic threshold increased from 12.9 ( ±1.0 SD ) to 15.5 ( ±1.7 SD ) ml/kg per min ( P<0.0001 ) . NT pro-BNP levels decreased from 3376 ( ±3133 SD ) to 1434 ( ±1673 SD ) pg/ml ( P=0.043 ) . The positive training effects were associated with an improvement in the NYHA functional class . Conclusion Physical training of moderate intensity significantly improves the exercise capacity and neurohormonal modulation in patients with chronic heart failure . This is associated with an alleviation of symptoms and improvement in quality of life Background Heart failure is a common and costly condition , particularly in the elderly . A range of models of interventions have shown the capacity to decrease hospitalizations and improve health-related outcomes . Potentially , cardiac rehabilitation models can also improve outcomes . Aim To assess the impact of a nurse-coordinated multidisciplinary , cardiac rehabilitation program to decrease hospitalizations , increase functional capacity , and meet the needs of patients with heart failure . Method In a r and omized control trial , a total of 105 patients were recruited to the study . Patients in the intervention group received an individualized , multidisciplinary 12-week cardiac rehabilitation program , including an individualized exercise component tailored to functional ability and social circumstances . The control group received an information session provided by the cardiac rehabilitation coordinator and then follow-up care by either their cardiologist or general practitioner . This trial was stopped prematurely after the release of state-based guidelines and funding for heart failure programs . Results During the study period , patients in the intervention group were less likely to have been admitted to hospital for any cause ( 44 vs. 69 % , P = 0.01 ) or after a major acute coronary event ( 24 vs. 55 % , P = 0.001 ) . Participants in the intervention group were more likely to be alive at 12 months , ( 93 vs. 79 % ; P = 0.03 ) ( odds ratio = 3.85 ; 95 % confidence interval = 1.0314.42 ; P = 0.0042 ) . Quality of life scores improved at 3 months compared with baseline ( intervention t = 4.37 , P [ 0.0001 ; control t= 3.52 , P [ 0.01 ) . Improvement was also seen in 6-min walk times at 3 months compared with baseline in the intervention group ( t = 3.40 ; P = 0.01 ) . Conclusion This study shows that a multidisciplinary heart failure cardiac rehabilitation program , including an individualized exercise component , coordinated by a specialist heart failure nurse can substantially reduce both all-cause and cardiovascular readmission rates , improve functional status at 3 months and exercise tolerance The purpose of this pilot study was to test the adjunctive effects of a 12-week exercise training intervention vs. st and ard pharmacologic therapy on quality of life , functional status , and mood in heart failure patients . A r and omized , two-group repeated measures design was used to test outcomes at baseline and 12 weeks in 23 subjects ( ejection fraction < or=40 % , st and ard pharmacologic therapy [ diuretics , angiotensin-converting enzyme inhibitors , b blockers , and digoxin ] and no change in medical therapy for 30 days ) . The exercise group had significantly higher adjusted means on the role physical , role emotional , and mental functioning subscales of the Medical Outcomes Study 36-item Short-Form Health Survey compared with the control group . Confusion/bewilderment ( Profile of Mood States subscale ) adjusted mean scores were significantly lower for the exercise group , indicating better mood compared with the control group . Exercise training provided adjunctive benefit in terms of role and mental functioning for these heart failure patients AIMS The Exercise Joins Education : Combined Therapy to Improve Outcomes in Newly-discharged Heart Failure ( EJECTION-HF ) study will evaluate the impact of a supervised exercise training programme ( ETP ) on clinical outcomes in recently hospitalized heart failure patients attending a disease management programme ( DMP ) . Methods This multisite , pragmatic r and omized controlled trial enrols patients discharged from participating hospitals with clinical evidence of heart failure who are willing and able to participate in a DMP and considered clinical ly safe to exercise . Enrolment includes participants with impaired and preserved left ventricular systolic function . Baseline assessment and programme commencement occur within 6 weeks of hospital discharge . The control group DMP includes individualized education and follow-up from a multidisciplinary heart failure team ; a weekly education programme for 12 weeks ; self-management advice ; and medical follow-up . Home exercise is recommended for all participants . In addition , intervention participants are offered 36 supervised , structured gym-based 1 h exercise sessions over 24 weeks . Sessions are tailored to exercise capacity and include aerobic , resistance , and balance exercises . Enrolment target is 350 participants . Primary outcome is 12-month mortality and readmissions . Secondary outcomes include blinded evaluation of depressive symptoms , sleep quality , cognition , and functional status ( activities of daily living , 6 min walk distance , grip strength ) at 3 and 6 months . A cost-utility analysis will be conducted . CONCLUSION This study will enrol a representative group of hospitalized heart failure patients and measure a range of patient and health service outcomes to inform the design of post-hospital DMPs for heart failure . Enrolment will be completed in 2013 . ACTRN12608000263392 |
11,745 | 19,076,911 | RESULTS Due to a lack of consistency among the studies regarding methods and rigor of the studies , the evidence is not entirely clear on the best multicomponent program for addressing overweight in middle adolescents .
The success of an intervention was associated with the dose of the intervention received by the adolescent and parent .
A structured program addressing nutrition , physical activity , and behavioral skills appears to be efficacious in reducing weight and cardiovascular risk factors . | BACKGROUND Being overweight is a global epidemic that occurs in more than 10 % of school-aged children ( age 5 - 17 ) worldwide .
The rate of adolescents being overweight continues to rise despite numerous public health campaigns and programs to increase awareness and modify unhealthy lifestyle patterns .
AIMS The purpose of this systematic review was to determine the most efficacious intervention for treating overweight adolescents .
Evidence from this systematic review could guide clinical practice and future research with this high-risk population in youth .
METHODS In adolescents of 13 - 17 years of age who are above ideal body weight , are multicomponent interventions that integrate nutrition , activity , and behavioral components more efficacious than any type of comparison group in improving weight , body mass index ( BMI ) , percentage body fat , or behaviors of dietary intake or activity level ? | BACKGROUND Little is known about how the intensity of exercise influences cardiovascular fitness and body composition , especially in obese adolescents . OBJECTIVE Our goal was to determine the effects of physical training intensity on the cardiovascular fitness , percentage of body fat ( % BF ) , and visceral adipose tissue ( VAT ) of obese adolescents . DESIGN Obese 13 - 16-y-olds ( n = 80 ) were assigned to 1 ) biweekly lifestyle education ( LSE ) , 2 ) LSE + moderate-intensity physical training , or 3 ) LSE + high-intensity physical training . The intervention lasted 8 mo . Physical training was offered 5 d/wk , and the target energy expenditure for all subjects in physical training groups was 1047 kJ ( 250 kcal)/session . Cardiovascular fitness was measured with a multistage treadmill test , % BF with dual-energy X-ray absorptiometry , and VAT with magnetic resonance imaging . RESULTS The increase in cardiovascular fitness in the high-intensity physical training group , but not in the moderate-intensity group , was significantly greater than that in the LSE alone group ( P = 0.009 ) ; no other comparisons of the 3 groups were significant . Compared with the LSE alone group , a group composed of subjects in both physical training groups combined who attended training sessions > or=2 d/wk showed favorable changes in cardiovascular fitness ( P < 0.001 ) , % BF ( P = 0.001 ) , and VAT ( P = 0.029 ) . We found no evidence that the high-intensity physical training was more effective than the moderate-intensity physical training in enhancing body composition . CONCLUSIONS The cardiovascular fitness of obese adolescents was significantly improved by physical training , especially high-intensity physical training . The physical training also reduced both visceral and total-body adiposity , but there was no clear effect of the intensity of physical training OBJECTIVE A r and omized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for African-American girls over a 2-year period of intervention . RESEARCH METHODS AND PROCEDURES Fifty-seven overweight ( mean BMI percentile , 98.3 ) African-American girls ( mean age , 13.2 years ) were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . Overweight parents were also participants in the study . Forty adolescent-parent dyads ( 70 % ) completed the 2-year trial . Outcome data including BMI , body weight , body composition , and weight loss behaviors were collected at baseline and at 6-month intervals . A computer server tracked use of the web sites . RESULTS An intention-to-treat statistical approach was used , with the last observation carried forward . In comparison with the control condition , adolescents in the behavioral program lost more mean body fat ( BF ) ( -1.12 + /- 0.47 % vs. 0.43 + /- 0.47 % BF , p < 0.05 ) , and parents in the behavioral program lost significantly more mean body weight ( -2.43 + /- 0.66 vs. -0.35 + /- 0.64 kg , p < 0.05 ) during the first 6 months . This weight loss was regained over the next 18 months . After 2 years , differences in fat for adolescents ( -0.08 + /- 0.71 % vs. 0.84 + /- 0.72 % BF ) and weight for parents ( -1.1 + /- 0.91 vs. -0.60 + /- 0.89 kg ) did not differ between the behavioral and control programs . DISCUSSION An internet-based weight management program for African-American adolescent girls and their parents result ed in weight loss during the first 6 months but did not yield long-term loss due to reduced use of the web site over time Objective : Since peers have such an important influence on adolescents , we evaluated the efficacy of adding peer-based ‘ adventure therapy ’ to a st and ard cognitive-behavioral weight control program for overweight adolescents . Methods : Adolescents ( N=76 ) aged 13–16 years and 20 to 80 % overweight ( M=60.56 % , s.d.=15.17 % ) , were r and omly assigned to one of two treatment conditions : cognitive-behavioral group treatment with ‘ adventure therapy ’ similar to Outward Bound ® ( cognitive-behavioral treatment with peer-enhanced adventure therapy ( CBT+PEAT ) ) or cognitive-behavioral group treatment with aerobic exercise ( CBT+EXER ) . Anthropometric and psychosocial measures were obtained at baseline , at the end of the 16-week intervention , and at 10 months following r and omization . Results : Adolescents assigned to both treatment conditions demonstrated significant weight loss over time , F=29.06 , df=2 , 53 , P<0.01 . Average weight loss did not differ significantly between groups ( −5.31 kg for CBT+PEAT and −3.20 kg for CBT+EXER ) at the end of treatment . There was a significant difference in the percentage of participants maintaining a minimum 4.5 kg ( 10 pounds ) weight loss ( 35 % in the CBT+PEAT condition vs 12 % in the CBT+EXER condition , P=0.042 ) 10 months from r and omization . We also observed a significant age by treatment group interaction , such that older adolescents r and omized to CBT+PEAT demonstrated more than four times the weight loss of older adolescents assigned to CBT+EXER ( M=−7.86 kg vs M=−1.72 kg ) at the end of treatment . Conclusions : Peer-based ‘ adventure therapy ’ is a promising adjunct to st and ard cognitive-behavioral weight control intervention for adolescents , and may be most effective for older adolescents OBJECTIVES The primary goals were to underst and the relationship among the inflammatory factors , C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and fibrinogen , and indices of obesity in normoglycemic , insulin-resistant adolescents and to investigate the impact of a lifestyle-only intervention on these nontraditional risk factors for cardiovascular disease ( CVD ) . STUDY DESIGN R and omized controlled lifestyle-only intervention study in adolescents . Of the 21 adolescents studied , 15 obese subjects ( body mass index [ BMI ] = 37.6 + /- 3.3 kg/m 2 ) were r and omized to either a lifestyle intervention program or usual care . The lean controls were studied only at baseline . Analysis of variance ( ANOVA ) for repeated measures was used to study intervention effect and t test , one-way ANOVA , and discriminant function analysis for baseline comparisons . RESULTS The intervention group maintained weight , whereas the control group gained weight ( P = .02 ) . A redistribution of body composition and a decrease in insulin resistance were observed . Elevated circulating concentrations of CRP , fibrinogen , and IL-6 were significantly reduced ( all P < or=.02 ) in response to intervention , but not in controls . CONCLUSIONS Modest lifestyle-only change in previously sedentary obese adolescents redistributes the parameters of body composition in the absence of weight loss and reverses , at least in part , the inflammatory state in association with an improvement of insulin resistance The leisure-time physical activity of 13-year-old Finnish adolescents was assessed in the prospect i ve STRIP study . A self-administered question naire ( N=565 ) was used . The leisure-time physical activity index ( PAI ; MET h/week ) was calculated on the basis of reported exercise intensity , duration and frequency ( N=558 ; 53 % boys ) . The participants were divided into Sedentary , Moderately Active and Active groups by PAI tertiles . A sub population ( N=197 ) also used a heart rate monitor ( 3 days , > /=8 h/day ) to assess the time spent on different activity intensities . The median male PAI was 31.3 ( inter-quartile range ( IQR ) 44.2 ) MET h/week and female 19.5 ( IQR 26.3 ) MET h/week ( P=0.0002 ) . The cutoff points of the PAI tertiles were similar for the Active girls ( 31.3 MET h/week ) and boys ( 32.6 MET h/week ) , but for the Sedentary boys it was 19.5 MET h/week and only 5.0 MET h/week for the Sedentary girls . High self-reported leisure-time physical activity associated poorly with time spent on moderate or vigorous exercise measured by heart rate monitoring . Active mothers had more often Active daughters or sons . In conclusion , the amount of leisure-time physical activity of one-third of 13-year-old girls is extremely low . Sedentary adolescents , especially girls , should therefore be put into focus for active efforts to increase their leisure-time physical activity . Parental models may be important Background : Childhood obesity has become a nutritional problem in China since the 1990s . Aims : A family based behavioural treatment was developed and tested , to see if its use was feasible in China and to evaluate its impact on obese schoolchildren . Methods : In a single school in Beijing , 33 obese children were r and omly assigned to a treatment group and 35 to a control group . The treatment group participated in a family based behavioural treatment programme for two years . Height and weight were measured every six months for all participants . Blood pressure , cholesterol , and triglyceride levels were measured at baseline and after two years of programme implementation . Results : Body mass index ( BMI , kg/m2 ) was significantly reduced in the treatment group ( from 26.6 ( 1.7 ) to 24.0 ( 0.9 ) , 95 % CI 2.06 to 3.18 ) but not in the control group ( from 26.1 ( 1.5 ) to 26.0 ( 1.6 ) ) . Total cholesterol decreased 5.5 % and triglycerides 9.7 % in the treatment group . There was a significant correlation between change in BMI and change in triglycerides . There were no significant changes in plasma lipids in the controls . Blood pressure values also decreased significantly in the treatment , but not the control group . Conclusions : A family based behavioural intervention was feasible to use in treating obesity in schoolchildren in Beijing , China . After two years of implementation , it successfully decreased the degree of obesity , reduced levels of blood pressure , and decreased serum lipids in treatment ; there were no significant changes among control children The purpose s of this article are to present an overview of r and omized clinical trials ( RCTs ) and describe some of the method ological problems inherent in using RCTs in nursing research . Many nursing intervention studies are fraught with problems that defy the stringent control criteria required for RCTs , leading to biased estimates of intervention efficacy . Five threats to validity in RCTs are presented , including problems related to ( a ) differential dropout , ( b ) r and om assignment , ( c ) identifying and maintaining an adequate control condition , ( d ) nonadherence to research protocol s , and ( e ) assessment of clinical ly meaningful change . Three strategies are recommended for addressing some of the problems posed by RCTs and improving inference Recent findings indicate that nearly 50 % of black American women are obese and that adolescence is a critical period for the development of their obesity . This study investigated the efficacy of a behavioral weight control program in 36 black female adolescents with a mean age of 14.0 years , weight of 95.0 kg , and height of 163.2 cm . All subjects participated in the same 16-week program but had different levels of parent participation : ( 1 ) child alone with no parent participation ; ( 2 ) mother and child treated in the same session ; and ( 3 ) mother and child treated in separate but concurrent session . At the end of the 16-week program , children in the three conditions lost 1.6 , 3.7 , and 3.1 kg , respectively . Differences among conditions were not statistically significant ; however , a secondary analysis revealed that the greater the number of sessions attended by mothers , the greater their daughters ' weight losses . Weight reduction was associated with significant improvements in body composition , serum total cholesterol concentrations , and psychological status . Results are discussed in terms of the need to improve the maintenance of weight loss in adolescents and to explore possible differences between black and white females in their preferred body types 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 OBJECTIVE This study evaluates the post-treatment and short-term follow-up efficacy of , as well as participant satisfaction for , a 4-month behavioral weight control program for overweight adolescents initiated in a primary care setting and extended through telephone and mail contact . RESEARCH METHODS AND PROCEDURES 44 overweight adolescents were r and omly assigned to either a multiple component behavioral weight control intervention ( Healthy Habits [ HH ] ; n = 23 ) or a single session of physician weight counseling ( typical care [ TC ] ; n = 21 ) . Weight , height , dietary intake , physical activity , sedentary behavior , and problematic weight-related and eating behaviors and beliefs were assessed before treatment , after the 4-month treatment , and at 3-month follow-up . Participant satisfaction and behavioral skills use were measured . RESULTS HH adolescents evidence d better change in body mass index z scores to post-treatment than TC adolescents . Body mass index z scores changed similarly in the conditions from post-treatment through follow-up . Behavioral skills use was higher among HH than TC adolescents , and higher behavioral skills use was related to better weight outcome . Energy intake , percentage of calories from fat , physical activity , sedentary behavior , and problematic weight-related or eating behaviors/beliefs did not differ by condition or significantly change over time independent of condition . The behavioral intervention evidence d good feasibility and participant satisfaction . DISCUSSION A telephone- and mail-based behavioral intervention initiated in primary care result ed in better weight control efficacy relative to care typically provided to overweight adolescents . Innovative and efficacious weight control intervention delivery approaches could decrease provider and participant burden and improve dissemination to the increasing population of overweight youth Objective : This r and omized controlled trial tested the efficacy of an internetbased lifestyle behavior modification program for weight management in African-American girls . Design : African-American girls were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . The behavioral intervention included internet counseling and was highly interactive . The control intervention was a passive ( non-interactive ) educational program . Parents were also participants in the study . Participants in both treatment groups met in face-to-face sessions on four occasions over the first 12 weeks of a 6-month intervention . Subjects : The study enrolled 57 African-American adolescent girls ( ages 11 to 15 years ) who were overweight or obese and had at least one biological parent who was obese [ body mass index ( BMI ) > 30 kg/m2 ] . Of the 57 participants , 50 ( 88 % ) completed the 6-month trial . Measurements : Outcome data , including BMI , body weight , body composition , dietary intake , and weight loss behaviors were collected at baseline and 6-months later . A computer server tracked utilization of the websites . Participation in the program was measured by number of “ hits ” on the website . Results : Compared to the control condition , adolescents in the behavioral treatment lost more body fat ( group difference = 1.6 % body fat ) and parents lost significantly more body weight ( group difference = 2.1 kg ) . Utilization of the behavioral website by adolescents and parents was associated with positive outcome . Dietary fat intake was lowered for adolescents and parents in the behavioral treatment group . Conclusion : An internet-based behavioral intervention was superior to internet-based health education and yielded decreased body fat for adolescent girls and decreased body weight for parents OBJECTIVE Go Girls was a church-based nutrition and physical activity program design ed for overweight African-American ( AA ) adolescent females . RESEARCH METHODS AND PROCEDURES Ten predominantly middle-socioeconomic churches were r and omized to either a high-intensity ( 20 to 26 sessions ) or moderate-intensity ( six sessions ) culturally tailored behavioral group intervention delivered over 6 months . Each session included an experiential behavioral activity , approximately 30 minutes of physical activity , and preparation and tasting of healthy foods . In the high-intensity group , girls also received four to six telephone counseling calls . From the 10 churches , 123 girls completed baseline and 6-month post-test assessment s. The primary outcome was BMI ; secondary outcomes included waist and hip circumferences , percentage body fat estimated by bioimpedance , serum insulin , glucose , and lipids , and cardiovascular fitness at 6-month follow-up . Selected measures were also collected at 1-year follow-up . RESULTS At 6-month follow-up , the net difference between the high- and moderate-intensity groups was 0.5 BMI units . This difference was not statistically significant ( p = 0.20 ) . There were no significant group differences in secondary outcomes . Girls in the high-intensity condition , however , who attended more than three-quarters of the sessions had significantly lower BMI and percentage body fat relative to girls in the high-intensity group who attended fewer sessions . Findings at 1-year follow-up mirrored those at 6 months . DISCUSSION We concluded that the intervention was not effective in reducing adiposity , although there were some positive findings among high attenders . Despite the null result , the intervention was generally well received by participants . Future interventions may require greater dose and a more structured dietary change program The purpose of the project was to compare the effectiveness of three different types of follow-up of a weight control program in assisting adolescent girls to achieve and maintain ideal body weight . During the initial phase of the weight control program , subjects attended two sessions of approximately one hour each for eight weeks . One session each week included theory and practice of physical exercise . The other session was devoted to behavioral control of eating and diet therapy . After eight weeks , 18 subjects were divided r and omly into three groups for follow-up : Group 1 - -monthly measurements and reinforcement of behavioral , diet , and exercise components of the weight control program ; Group 2 - -monthly measurements ; and Group 3 - -annual measurements . Fifteen subjects completed the 12-month follow-up program . Mean weight loss during follow-up of Group 1 was 3.65 kg , Group 2 was 1.90 kg , while Group 3 had a mean weight gain of 3.44 kg . The results suggest that regular follow-up may be a critical element in successful weight control programs for adolescent girls BACKGROUND Physical activity declines during adolescence , but the underlying reasons remain unknown . METHODS We prospect ively followed 1213 black girls and 1166 white girls enrolled in the National Heart , Lung , and Blood Institute Growth and Health Study from the ages of 9 or 10 to the ages of 18 or 19 years . We used a vali date d question naire to measure leisure-time physical activity on the basis of metabolic equivalents ( MET ) for reported activities and their frequency in MET-times per week ; a higher score indicated greater activity . RESULTS The respective median activity scores for black girls and white girls were 27.3 and 30.8 MET-times per week at base line and declined to 0 and 11.0 by year 10 of the study ( a 100 percent decline for black girls and a 64 percent decline for white girls , P<0.001 ) . By the age of 16 or 17 years , 56 percent of the black girls and 31 percent of the white girls reported no habitual leisure-time activity . Lower levels of parental education were associated with greater decline in activity for white girls at both younger ages ( P<0.001 ) and older ages ( P=0.005 ) ; for black girls , this association was seen only at the older ages ( P=0.04 ) . Pregnancy was associated with decline in activity among black girls ( P<0.001 ) but not among white girls , whereas cigarette smoking was associated with decline in activity among white girls ( P<0.001 ) . A higher body-mass index was associated with greater decline in activity among girls of both races ( P < or = 0.05 ) . CONCLUSIONS Substantial declines in physical activity occur during adolescence in girls and are greater in black girls than in white girls . Some determinants of this decline , such as higher body-mass index , pregnancy , and smoking , may be modifiable BACKGROUND This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls . New Moves was implemented as a multicomponent , girls-only , high-school physical education class . METHODS Six schools were equally r and omized into intervention and control conditions . Data were collected at baseline , postintervention , and 8-month follow-up to assess program impact on physical activity , eating patterns , self-perceptions , and body mass index ( BMI ) among 89 girls in the intervention and 112 girls in the control conditions . Program evaluation also included interviews with school staff , parent surveys , and participant interviews and process evaluation surveys . RESULTS The feasibility of implementing New Moves was high , as indicated by strong satisfaction among participants , parents , and school staff , and by program sustainability . Participants perceived a positive program impact on their physical activity , eating patterns , and self-image . Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up . However , for the majority of outcome variables , differences between intervention and control schools at postintervention and follow-up were not statistically significant . CONCLUSIONS New Moves was well received and fills a needed niche within school physical education programs . An exp and ed intervention and evaluation is needed to enhance and assess long-term program effectiveness Critical appraisal of research studies is the third step in evidence -based practice ( EBP ) , following step one , “ Asking clinical questions in PICO ( i.e. , population , intervention or interest area ; comparison intervention or group , and outcome of interest ) format , ” and step two , “ Search ing for evidence to answer the questions . ” Once research is found to answer a burning PICO clinical question ( e.g. , In teens , is cognitive-behavioral therapy or relaxation techniques more effective in reducing anxiety symptoms ? ) , the clinician must be able to rapidly appraise studies in order to determine their validity and applicability to clinical practice . For years , research courses in many educational curriculums have taught critiquing studies as a very detailed , time consuming process . Unfortunately , this method of teaching the appraisal process has often contributed to lasting negative attitudes about research and misperceptions by clinicians about the length of time that it takes to read and critically appraise a single research report . Many practicing clinicians also believe that critical appraisal is much too difficult or that experts in EBP and research ers are the only individuals who can be competent in the process . Therefore , this paper will present a user-friendly , efficient approach to critically appraising a published r and omized clinical trial ( RCT ) . Implementing this method of critical appraisal should contribute to enhanced confidence in clinicians ’ abilities to swiftly determine whether the findings from a RCT are valid and should be translated to their clinical practice setting |
11,746 | 30,190,481 | Our analyses suggested loss-of-function events to master TF drivers of lineage-fates and their cofactors as being linked to differentiation-failure : genomic data in TCGA and ICGC data bases demonstrated frequent haploinsufficiency of lineage master TFs ( e.g. , GATA4/6 ) in poorly differentiated tumors ; the coactivators that these TFs use to activate genes ( e.g. ARID1A , PBRM1 ) were also frequently inactivated by genetic mutation and /or deletion .
By contrast , corepressor components ( e.g. , DNMT1 , EED , UHRF1 , and BAZ1A/B ) , that oppose coactivators to repress or turn off genes , were frequently amplified instead , and the level of amplification was highest in poorly differentiated lesions .
This selection by neoplastic evolution towards unbalanced activity of transcriptional corepressors suggests these enzymes as c and i date targets for inhibition aim ing to re-engage forward-differentiation . | Chemotherapeutic drugs have a common intent to activate apoptosis in tumor cells .
However , master regulators of apoptosis ( e.g. , p53 , p16/CDKN2A ) are frequently genetically inactivated in cancers , result ing in multidrug resistance .
An alternative , p53-independent method for terminating malignant proliferation is to engage terminal-differentiation .
Normally , the exponential proliferation of lineage-committed progenitors , coordinated by the master transcription factor ( TF ) MYC , is self-limited by forward-differentiation to terminal lineage-fates .
In cancers , however , this exponential proliferation is disengaged from terminal-differentiation .
The mechanisms underlying this decoupling are mostly unknown .
We analyzed key gene alterations in various apoptosis , proliferation and differentiation pathways to determine whether it is possible to predict treatment outcomes and suggest novel therapies . | Patients with malignant endocrine pancreatic tumors ( EPTs ) are responsive to combinations of chemotherapy with streptozotocin and 5‐fluorouracil/doxorubicin , whereas patients with malignant carcinoids are not . For both categories of patients , α‐interferon and /or somatostatin analogs can produce long‐lasting responses . Cisplatin in combination with etoposide has been suggested to be effective in patients with malignant neuroendocrine carcinomas . The authors used this therapy as second‐line or third‐line treatment in patients with poorly differentiated and /or rapidly progressing disease BACKGROUND Mutational inactivation in cancer of key apoptotic pathway components , such as TP53/p53 , undermines cytotoxic therapies that aim to increase apoptosis . Accordingly , TP53 mutations are reproducibly associated with poor treatment outcomes . Moreover , cytotoxic treatments destroy normal stem cells with intact p53 systems , a problem especially for myeloid neoplasms , as these cells reverse the low blood counts that cause morbidity and death . Pre clinical studies suggest that noncytotoxic concentrations of the DNA methyltransferase 1 ( DNMT1 ) inhibitor decitabine produce p53-independent cell-cycle exits by reversing aberrant epigenetic repression of proliferation-terminating ( MYC-antagonizing ) differentiation genes in cancer cells . METHODS In this clinical trial , patients with myelodysplastic syndrome ( n=25 ) received reduced decitabine dosages ( 0.1 - 0.2 mg/kg/day compared with the FDA -approved 20 - 45 mg/m2/day dosage , a 75%-90 % reduction ) to avoid cytotoxicity . These well-tolerated doses were frequently administered 1 - 3 days per week , instead of pulse cycled for 3 to 5 days over a 4- to 6-week period , to increase the probability that cancer S-phase entries would coincide with drug exposure , which is required for S-phase-dependent DNMT1 depletion . RESULTS The median subject age was 73 years ( range , 46 - 85 years ) , 9 subjects had relapsed disease or were refractory to 5-azacytidine and /or lenalidomide , and 3 had received intensive chemoradiation to treat other cancers . Adverse events were related to neutropenia present at baseline : neutropenic fever ( 13 of 25 subjects ) and septic death ( 1 of 25 subjects ) . Blood count improvements meeting the International Working Group criteria for response occurred in 11 of 25 ( 44 % ) subjects and were highly durable . Treatment-induced freedom from transfusion lasted a median of 1,025 days ( range , 186 - 1,152 days ; 3 ongoing ) , and 20 % of subjects were treated for more than 3 years . Mutations and /or deletions of key apoptosis genes were frequent ( present in 55 % of responders and in 36 % of nonresponders ) . Noncytotoxic DNMT1 depletion was confirmed by serial BM γ-H2AX ( DNA repair/damage marker ) and DNMT1 analyses . MYC master oncoprotein levels were markedly decreased . CONCLUSION Decitabine regimens can be re design ed to minimize cytotoxicity and increase exposure time for DNMT1 depletion , to safely and effectively circumvent mutational apoptotic defects . TRIAL REGISTRATION Clinical trials.gov NCT01165996 . FUNDING NIH ( R01CA138858 , CA043703 ) ; Department of Defense ( PR081404 ) ; Clinical and Translational Science Award ( CTSA ) ( UL1RR024989 ) ; and the Leukemia and Lymphoma Society ( Translational Research Program ) BACKGROUND The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( MDS ) are unclear . METHODS We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses . Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles . We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients . An extension cohort included 32 additional patients who received decitabine in different protocol s. RESULTS Of the 116 patients , 53 ( 46 % ) had bone marrow blast clearance ( < 5 % blasts ) . Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile ( 29 of 43 patients [ 67 % ] vs. 24 of 71 patients [ 34 % ] , P<0.001 ) and among patients with TP53 mutations than among patients with wild-type TP53 ( 21 of 21 [ 100 % ] vs. 32 of 78 [ 41 % ] , P<0.001 ) . Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes . However , in this study of 10-day courses of decitabine , neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles . CONCLUSIONS Patients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk , TP53 mutations , or both had favorable clinical responses and robust ( but incomplete ) mutation clearance after receiving serial 10-day courses of decitabine . Although these responses were not durable , they result ed in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT01687400 . ) This report investigated in vivo turnover kinetics of marrow hematopoietic progenitors and precursors using a recently developed stable isotope-mass spectrometric technique ( SIMST ) . Human subjects were administered a 2-day infusion of 6,6-[2H2]-glucose , a nontoxic stable isotope-labeled form of glucose , which becomes incorporated into DNA of all S-phase cells . The percent [2H2]-glucose incorporated into DNA in the form of [2H2]-deoxyadenosine ( % [2H2]-dA enrichment ) was determined by gas chromatography-mass spectrometry . The rate constant of replacement of unlabeled by labeled DNA str and s ( labeling kinetics ) was used to calculate population turnover kinetics of CD34 + cells , CD133 + cells , and CD133-CD34 + cells . The observed mean replacement half-life ( t1/2 ) was 2.6 days for CD34 + cells , 2.5 days for CD133-CD34 + cells , and 6.2 days for CD133 + cells . Results from the estimated rate constant of replacement of labeled by unlabeled DNA ( delabeling kinetics ) also demonstrated slower turnover rates for CD133 + cells than for CD133-CD34 + cells . Although there was a relatively rapid initial decrease in the % [2H2]-dA enrichment , low levels of labeled DNA persisted in CD34 + cells for at least 4 weeks . The results indicate the presence of sub population s of CD34 + cells with relatively rapid turnover rates and sub population s with a slower t1/2 of 28 days . Results also demonstrate that in vivo [2H2]-glucose-SIMST is sensitive enough to detect differences in turnover kinetics between erythroid and megakaryocyte lineage cells . These studies are the first to demonstrate the use of in vivo [2H2]-glucose-SIMST to measure in vivo turnover kinetics of sub population s of CD34 + cells and precursors in healthy human subjects Primary myelofibrosis ( PMF ) and overlap myelodysplastic/myeloproliferative neoplasms ( MDS/MPN ) are clonal hematopoietic disorders that share similar clinical features and molecular abnormalities , such as the Janus kinase 2 ( JAK2 ) valine to phenylalanine mutation at codon 617 ( V617F ) and the tet methylcytosine dioxygenase 2 ( TET2 ) mutation . There are limited therapeutic options available for these diseases , and single agents have only modest efficacy . In this phase 2 study , the authors combined multiple active agents ( thalidomide , arsenic trioxide , dexamethasone , and ascorbic acid [ TADA ] ) to treat patients with these disorders PURPOSE This study was design ed to assess the effectiveness of vinblastine , ifosfamide , and cisplatin ( VeIP ) as second-line therapy in patients with recurrent germ cell tumors with previous treatment with cisplatin plus etoposide , usually in combination with bleomycin . PATIENTS AND METHODS From July 1984 through December 1989 , 135 patients with progressive , disseminated germ cell tumors after cisplatin-etoposide-based combination therapy induction chemotherapy were treated with VeIP . Patients who progressed within 3 weeks of previous cisplatin therapy were not eligible . Progression was documented by biopsy or increasing serum markers . No exclusion was made on the basis of metastatic site or performance status . The dosages were vinblastine 0.11 mg/kg/d ( days 1 and 2 ) , ifosfamide 1.2 gm/m2/d ( days 1 through 5 ) , and cisplatin 20 mg/m2/d ( days 1 through 5 ) , with courses repeated every 21 days for four cycles . RESULTS Sixty-seven ( 49.6 % ) patients achieved a disease-free status after chemotherapy with or without surgical resection of residual carcinoma or teratoma . Overall , 42 ( 32 % ) patients are alive and 32 ( 23.7 % ) are continuously free of disease . None of the 32 patients with nonseminomatous extragonadal tumors are disease-free compared with 30 of 100 patients with gonadal primaries . Two of three extragonadal seminomas are continuously disease-free . CONCLUSION VeIP is capable of producing durable complete remissions in patients with disseminated germ cell cancer who relapse after cisplatin-etoposide-based induction therapy . Long-term disease-free survival is not seen in those patients with extragonadal nonseminomatous germ cell tumors BACKGROUND All-trans retinoic acid ( ATRA ) with chemotherapy is the st and ard of care for acute promyelocytic leukemia ( APL ) , result ing in cure rates exceeding 80 % . Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity . METHODS We conducted a phase 3 , multicenter trial comparing ATRA plus chemotherapy with ATRA plus arsenic trioxide in patients with APL classified as low-to-intermediate risk ( white-cell count , ≤10 × 10(9 ) per liter ) . Patients were r and omly assigned to receive either ATRA plus arsenic trioxide for induction and consolidation therapy or st and ard ATRA-idarubicin induction therapy followed by three cycles of consolidation therapy with ATRA plus chemotherapy and maintenance therapy with low-dose chemotherapy and ATRA . The study was design ed as a noninferiority trial to show that the difference between the rates of event-free survival at 2 years in the two groups was not greater than 5 % . RESULTS Complete remission was achieved in all 77 patients in the ATRA-arsenic trioxide group who could be evaluated ( 100 % ) and in 75 of 79 patients in the ATRA-chemotherapy group ( 95 % ) ( P=0.12 ) . The median follow-up was 34.4 months . Two-year event-free survival rates were 97 % in the ATRA-arsenic trioxide group and 86 % in the ATRA-chemotherapy group ( 95 % confidence interval for the difference , 2 to 22 percentage points ; P<0.001 for noninferiority and P=0.02 for superiority of ATRA-arsenic trioxide ) . Overall survival was also better with ATRA-arsenic trioxide ( P=0.02 ) . As compared with ATRA-chemotherapy , ATRA-arsenic trioxide was associated with less hematologic toxicity and fewer infections but with more hepatic toxicity . CONCLUSIONS ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL . ( Funded by Associazione Italiana contro le Leucemie and others ; Clinical Trials.gov number , NCT00482833 . ) |
11,747 | 30,337,344 | ‘ Very low ’ to ‘ moderate ’ quality evidence from 13 r and omised controlled trials ( RCTs ) showed prenatal exercise did not reduce the odds of suffering from LBP , PGP and LBPP either in pregnancy or the postpartum period .
These findings were supported by ‘ very low ’ quality evidence from other study design s. Conclusion Compared with not exercising , prenatal exercise decreased the severity of LBP , PGP or LBPP during and following pregnancy but did not decrease the odds of any of these conditions at any time point | Objective The purpose of this review was to investigate the relationship between prenatal exercise , and low back ( LBP ) , pelvic girdle ( PGP ) and lumbopelvic ( LBPP ) pain . | Background This pilot r and omized controlled trial evaluated the feasibility of conducting a full scale study and compared the efficacy of exercise , spinal manipulation , and a mind-body therapy called Neuro Emotional Technique for the treatment of pregnancy-related low back pain , a common morbidity of pregnancy . Methods Healthy pregnant women with low back pain of insidious onset were eligible to enroll in the study at any point in their pregnancy . Once enrolled , they remained in the study until they had their babies . Women were r and omly allocated into one of three treatment groups using opaque envelopes . The treatment schedule paralleled the prenatal care schedule and women received individualized intervention . Our null hypothesis was that spinal manipulation and Neuro Emotional Technique would perform no better than exercise in enhancing function and decreasing pain . Our primary outcome measure was the Rol and Morris Disability Question naire and our secondary outcome measure was the Numeric Pain Rating Scale . Intention to treat analysis was conducted . For the primary analysis , regression was conducted to compare groups on the outcome measure scores . In a secondary responder analysis , difference in proportions of participants in attaining 30 % and 50 % improvement were calculated . Feasibility factors for conducting a future larger trial were also evaluated such as recruitment , compliance to study protocol s , cost , and adverse events . Results Fifty-seven participants were r and omized into the exercise ( n = 22 ) , spinal manipulation ( n = 15 ) , and Neuro Emotional Technique ( n = 20 ) treatment arms . At least 50 % of participants in each treatment group experienced clinical ly meaningful improvement in symptoms for the Rol and Morris Disability Question naire . At least 50 % of the exercise and spinal manipulation participants also experienced clinical ly meaningful improvement for the Numeric Pain Rating Scale . There were no clinical ly meaningful or statistically significant differences between groups in any analysis . Conclusions This pilot study demonstrated feasibility for recruitment , compliance , safety , and affordability for conducting a larger study in the future . Spinal manipulation and exercise generally performed slightly better than did Neuro Emotional Technique for improving function and decreasing pain , but the study was not powered to detect the between-group differences as statistically significant . Trial registration Clinical Trials.gov ( Identifier : NCT00937365 ) OBJECTIVE Pregnancy-related lumbopelvic pain is a major problem for the majority of pregnant women . Complementary medicine has been used to alleviate pain , and yoga is one of the most commonly chosen alternative methods . The objective of this study was to assess the effectiveness of Hatha yoga in the reduction of lumbopelvic pain in pregnancy . METHODS A r and omized controlled trial with 60 pregnant women ( age range , 14 - 40 years ) who reported lumbopelvic pain at 12 to 32 weeks of gestation was conducted from June 2009 to June 2011 . Pregnant women who had twin pregnancies , had medical restrictions for exercise , used analgesics , and participated in physical therapy were excluded from the study . Pregnant women were divided into two groups : the yoga group , practicing exercises guided by this method , and the postural orientation group , performing st and ardized posture orientation according to instructions provided in a pamphlet . Treatment in each group lasted 10 weeks . A visual analog scale ( VAS ) was used to measure pain intensity . Lumbar pain and posterior pelvic pain provocation tests were used to confirm the presence of pain . Statistical analysis included the Mann-Whitney test , the McNemar test , a paired Wilcoxon test , and analysis of covariance . RESULTS The median pain score was lower in the yoga group ( p<.0058 ) than the postural orientation group . Lumbar pain provocation tests showed a decreased response in relation to posterior pelvic pain provocation tests and a gradual reduction in pain intensity during 10 yoga sessions ( p<.024 ) . CONCLUSIONS The yoga method was more effective at reducing lumbopelvic pain intensity compared with postural orientation OBJECTIVE To investigate the effect of an exercise program , including specific stabilizing exercises , on pain intensity and functional ability in women with pregnancy-related low back pain . METHODS Fifty women between 16 and 24 weeks of pregnancy were recruited at Tygerberg and Paarl Hospitals , Western Cape , South Africa . Twenty-six women were r and omized to a 10-week exercise program and 24 were r and omized as controls . RESULTS Overall , the most frequent type of back pain experienced was lumbar pain ( 36 [ 72.0 % ] ) . Pain intensity ( P=0.76 ) and functional ability ( P=0.29 ) were comparable between the groups on study entry . In the study group , there was a significant improvement in pain intensity ( P<0.01 ) and an improvement in functional ability ( P=0.06 ) at the end of the study . In the control group , there were no significant changes in pain intensity ( P=0.89 ) or functional ability ( P=0.70 ) at the end of the study . CONCLUSION A specific exercise program decreased back pain intensity and increased functional ability during pregnancy in South African women with lumbar and pelvic girdle pain 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 INTRODUCTION Pelvic girdle pain ( PGP ) is a universally disabling condition affecting three of 10 pregnant women . Qualitative studies on the subject are lacking . OBJECTIVE To describe pregnant women 's experiences of PGP as related to daily life . METHODS In all , 27 women with PGP participating in a r and omised controlled study were interviewed during 2010 - 2011 . Qualitative content analysis was used . RESULTS Five main categories emerged : PGP affects the ability to cope with everyday life ; Coping with motherhood ; Relationships between partners often reached the breaking point ; Question ing one 's identity as defined by profession and work , and Lessons learned from living with PGP . The categories illustrate how women 's everyday lives were interrupted . Their inability to meet their own and others ' expectations put a strain on their lives causing disappointment , sadness and frustration . It made them question and doubt their roles and identities as mothers , partners and professionals , and kept them from looking forward to future pregnancies , in the absence of effective treatment for PGP . Knowledge gained was that women with PGP should seek help immediately , listen to their bodies , and acknowledge their limitations . CONCLUSION PGP severely affects pregnant women 's everyday lives . There appears to be a lack of knowledge and awareness in general , as well as among caregivers and employers of PGP that needs to be highlighted and rectified . There is also a great need to learn how to support those suffering from it . Appropriate support during this important and rare phase in a woman 's life is highly warranted OBJECTIVE To investigate the association of muscle function and subgroups of low back pain ( no low back pain , pelvic girdle pain , lumbar pain and combined pelvic girdle pain and lumbar pain ) in relation to pregnancy . DESIGN Prospect i ve cohort study . SUBJECTS Consecutively enrolled pregnant women seen in gestational weeks 12 - 18 ( n = 301 ) and 3 months postpartum ( n = 262 ) . METHODS Classification into subgroups by means of mechanical assessment of the lumbar spine , pelvic pain provocation tests , st and ard history and a pain drawing . Trunk muscle endurance , hip muscle strength ( dynamometer ) and gait speed were investigated . RESULTS In pregnancy 116 women had no low back pain , 33 % ( n = 99 ) had pelvic girdle pain , 11 % ( n = 32 ) had lumbar pain and 18 % ( n = 54 ) had combined pelvic girdle pain and lumbar pain . The prevalence of pelvic girdle pain/combined pelvic girdle pain and lumbar pain decreased postpartum , whereas the prevalence of lumbar pain remained stable . Women with pelvic girdle pain and /or combined pelvic girdle pain and lumbar pain had lower values for trunk muscle endurance , hip extension and gait speed as compared to women without low back pain in pregnancy and postpartum ( p < 0.001 - 0.04 ) . Women with pelvic girdle pain throughout the study had lower values of back flexor endurance compared with women without low back pain . CONCLUSION Muscle dysfunction was associated with pelvic girdle pain , which should be taken into consideration when developing treatment strategies and preventive measures Objective . To study lumbopelvic pain in women r and omized to a regular exercise program during pregnancy in comparison to women receiving st and ard antenatal care . Design . A two‐armed , two‐center , r and omized controlled trial . Setting . St Olavs Hospital , Trondheim University Hospital and Stavanger University Hospital . Population . A total of 855 pregnant women were r and omized to intervention or control groups . Methods . The intervention was a 12 week exercise program , including aerobic and strengthening exercises , conducted between 20 and 36 weeks of pregnancy . One weekly group session was led by physiotherapists , and home exercises were encouraged twice a week . The control group received st and ard antenatal care . Main outcome measures . Self‐reports of lumbopelvic pain and sick leave due to lumbopelvic pain . The data were analysed according to the “ intention‐to‐treat ” principle . Results . There were no significant differences between groups of women reporting lumbopelvic pain at 36 weeks ( 74 vs. 75 % , p=0.76 ) . The proportion of women on sick leave due to lumbopelvic pain was lower in the intervention group ( 22 % vs 31 % , p=0.01 ) . Conclusions . Exercise during pregnancy does not influence the prevalence of lumbopelvic pain , but women offered a regular exercise course seem to h and le the disorder better Background Antenatal preparation programmes are recommended worldwide to promote a healthy pregnancy and greater autonomy during labor and delivery , prevent physical discomfort and high levels of anxiety . The objective of this study was to evaluate effectiveness and safety of a birth preparation programme to minimize lumbopelvic pain , urinary incontinence , anxiety , and increase physical activity during pregnancy as well as to compare its effects on perinatal outcomes comparing two groups of nulliparous women . Methods A r and omized controlled trial was conducted with 197 low risk nulliparous women aged 16 to 40 years , with gestational age ≥ 18 weeks . Participants were r and omly allocated to participate in a birth preparation programme ( BPP ; n=97 ) or a control group ( CG ; n=100 ) . The intervention was performed on the days of prenatal visits , and consisted of physical exercises , educational activities and instructions on exercises to be performed at home . The control group followed a routine of prenatal care . Primary outcomes were urinary incontinence , lumbopelvic pain , physical activity , and anxiety . Secondary outcomes were perinatal variables . Results The risk of urinary incontinence in BPP participants was significantly lower at 30 weeks of pregnancy ( BPP 42.7 % , CG 62.2 % ; relative risk [ RR ] 0.69 ; 95 % confidence interval [ CI ] 0.51 - 0.93 ) and at 36 weeks of pregnancy ( BPP 41.2 % , CG 68.4 % ; RR 0.60 ; 95%CI 0.45 - 0.81 ) . Participation in the BPP encouraged women to exercise during pregnancy ( p=0.009 ) . No difference was found between the groups regarding to anxiety level , lumbopelvic pain , type or duration of delivery and weight or vitality of the newborn infant . Conclusions The BPP was effective in controlling urinary incontinence and to encourage the women to exercise during pregnancy with no adverse effects to pregnant women or the fetuses . Trial registration Clinical trials.gov , ( NCT01155804 OBJECTIVE To investigate if water-gymnastics during pregnancy may reduce the intensity of back/low back pain and the number of days on sick-leave . METHODS A prospect i ve , r and omized study . One hundred and twenty-nine women were r and omized to participate in water-gymnastics once a week during the second half of pregnancy and 129 were r and omized to a control group . The women in both groups filled in question naires in gestational weeks 18 , 34 and within the first postpartum week . Every day from week 18 to labor they assessed the intensity of back/low back pain . RESULTS Back pain intensity increased during pregnancy . No excess risk for the pregnancy associated with water-gymnastics was observed . The women participating in water-gymnastics recorded a lower intensity of back/low back pain . The total number of days on sick-leave because of back/low back pain was 982 in the water-gymnastics group ( 124 women ) compared with 1484 in the control group ( 120 women ) . After weeks 32 33 , seven women in the water-gymnastics group compared with 17 in the control group were on sickleave because of back/ low back pain ( p=0.031 ) . CONCLUSIONS Intensity of back/low back pain increased with advancing pregnancy . There was no excess risk for urinary or vaginal infections associated with water-gymnastics . Water-gymnastics during the second half of pregnancy significantly reduced the intensity of back/ low back pain . Water-gymnastics decreased the number of women on sick-leave because of back/low back pain . Water-gymnastics during pregnancy can be recommended as a method to relieve back pain and may reduce the need for sick-leave Background Pelvic girdle pain ( PGP ) is a multifactorial condition , which can be mentally and physically compromising both during and after pregnancy . However , long-term pregnancy-related PGP has been poorly investigated . This longitudinal follow-up study uniquely aim ed to describe prevalence and predictors of PGP and its consequences on women ’s health and function up to 11 years after pregnancy . Methods / Design A postal question naire was sent to 530 women who participated in 1 of 3 r and omized controlled studies for PGP in pregnancy . Women who reported experiencing lumbopelvic pain were offered a clinical examination . Main outcome measure was the presence of long term PGP as assessed by an independent examiner . Secondary outcomes were : working hours/week , function ( the Disability Rating Index , and Oswestry Disability Index ) , self-efficacy ( the General Self-Efficacy Scale ) , HRQL ( Euro-Qol 5D and EQ-Visual scale ) , anxiety and depression , ( Hospital anxiety and depression scale , ) and pain-catastrophizing ( Pain Catastrophizing Scale ) , in women with PGP compared to women with no PGP . Results A total of 371/530 ( 70 % ) women responded and 37/ 371 ( 10 % ) were classified with long-term PGP . Pregnancy-related predictors for long-term PGP were number of positive pain provocation tests ( OR = 1.79 ) , history of low back pain ( LBP ) ( OR = 2.28 ) , positive symphysis pressure test ( OR = 2.01 ) , positive Faber ( Patrick ’s ) test ( OR = 2.22 ) , and positive modified Trendelenburg test ( OR = 2.20 ) . Women with PGP had significantly decreased ability to perform daily activities ( p < .001 ) , lower self-efficacy ( p = 0.046 ) , decreased HRQL ( p < .001 ) , higher levels of anxiety and depression ( p < .001 ) , were more prone to pain catastrophizing , and worked significantly fewer hours/week ( p = 0.032 ) compared to women with no PGP . Conclusions This unique long-term follow up of PGP highlights the importance of assessment of pain in the lumbopelvic area early in pregnancy and postpartum in order to identify women with risk of long term pain . One of 10 women with PGP in pregnancy has severe consequences up to 11 years later . They could be identified by number of positive pain provocation tests and experience of previous LBP . Access to evidence based treatments are important for individual and socioeconomic reasons Lower back pain and lordosis are among the most common complications during pregnancy ; their frequency in pregnant women is 4 times that in non-pregnant women [ 1 ] . The present study evaluated the effect of exercise on back pain during pregnancy . Inclusion criteria were maternal age of 20–30 years ; nulliparity ; gestational age of 16 weeks ( according to reliable last menstrual period and ultrasound confirmation in the first trimester ) ; and no regular exercise before entering the study . Exclusion criteria were any kind of systemic disorder or drug use ; any previous trauma , surgery , or damage to the spine or lower limbs ; any complications of pregnancy such as preterm labor , abortion , or pelvic pain ; and absence from the study exercise program on at least 3 occasions . All eligible women completed the Rol and –Morris question naire [ 2 ] , and lordosis was measured using a flexible ruler and the formula Θ=4 × [a rct an(2H/L ) ] ( Fig. 1 ) ; these measurements were repeated after 1 and 2 months . The participants were r and omly assigned to either the study group or the control group . In the study group ( n=15 ) , there was an initial 1-hour training session in which 7 main exercises — together with preparation and relaxation movements — were taught to the participants , who then performed 30 minutes of exercise 3 times per week Table 1 Prevalence of PAI-1 4G/5 G polymorphisms in the different groups of women studied A single center , prospect i ve , r and omized , single blinded , controlled study comparing the effects and safety of " sitting pelvic tilt exercise " in relieving back pain during the third trimester in primigravida was carried out . The sample s were composed of 67 primigravidas who attended the prenatal clinic at King Chulalongkorn Memorial Hospital . All subjects were selected by the r and om sampling technique and allocated into two groups for the experimental group and the control group ; for 32 and 35 pregnants , respectively . The experimental group received the pelvic tilt exercise program for 8 weeks during the third trimester . Pain intensity was measured by visual analogue scale ( VAS ) at day 0 and day 56 in both groups . The result of the study revealed 1 ) The mean VAS of back pain in the experimental group was significantly lower at day 56 than at day 0 and lower than the control group at day 56 ( p < 0.05 ) by unpaired t-test 2 ) There was no incidence of preterm labor , low birth weight or neonatal complication in the experimental group . In conclusion , the " sitting pelvic tilt exercise " during the third trimester in primigravidas could decrease back pain intensity without incidence of preterm labor , low birth weight or neonatal complication Background Many women have low back pain ( LBP ) or pelvic girdle pain ( PGP ) during pregnancy , but there is limited evidence of effective primary and secondary preventive strategies . Objective The purpose of this study was to investigate whether a group-based exercise program can reduce the prevalence and severity of LBP and PGP in pregnant women . Design An observer-blinded r and omized controlled trial with equal assignments to a training group and a control group was conducted . Setting The study was conducted in primary care maternity units in 2 suburban municipalities in the southeastern part of Norway . Patients The participants were 257 pregnant women who were healthy and between 18 and 40 years of age before gestation week 20 . Intervention The training group received supervised exercises in groups once a week , and the control group received st and ard care . Measurements The main outcome measures were self-reported LBP and self-reported PGP . Secondary outcome measures were pain intensity in the morning and evening , disability , and 8-Item Short-Form Health Survey ( SF-8 ) Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) scores . Follow-up measurements were performed at gestation weeks 24 , 28 , 32 , and 36 . Results Overall , there was no effect of the program on the prevalence of PGP ( odds ratio=1.03 , 95 % confidence interval [CI]=0.66 to 1.59 ) or LBP ( odds ratio=0.77 , 95 % CI=0.50 to 1.19 ) . For the secondary outcomes , the estimated mean differences between the groups were −0.4 ( 95 % CI=−0.8 to 0.1 ) for pain intensity in the morning , −0.4 ( 95 % CI=−1.0 to 0.2 ) for pain intensity in the evening , −1.0 ( 95 % CI=−2.2 to 0.0 ) for disability , 1.8 ( 95 % CI=0.0 to 3.7 ) for the SF-8 PCS , and −0.6 ( 95 % CI=−2.2 to 1.4 ) for the SF-8 MCS . Limitations Due to low statistical power , the estimates for the primary outcomes are imprecise . Conclusions Supervised group exercise did not reduce the prevalence of LBP or PGP in pregnancy AIMS ( 1 ) To investigate the course of pregnancy-related low back pain intensity and interference during the third trimester , and ( 2 ) to identify risk factors associated with changes in pain intensity and interference over time . BACKGROUND Pregnancy-related low back pain is common and reaches its peak both in the prevalence and severity in the third trimester . DESIGN A longitudinal design with consecutive sampling . METHODS Three waves of data were collected from pregnant women in an antenatal care centre of a medical centre and a regional hospital in the northern Taiwan from February-June , 2010 . Question naires were administered at gestational ages 28 , 32 and 36 weeks . 214 women were enrolled and 179 participants completed all measures . Generalized estimating equations were used to identify the risk factors associated with changes in pain intensity and pain interference over time . RESULTS Pain interference increased over time during the third trimester . Pain catastrophizing and pain intensity at gestational age 24 weeks and time ( from 28 - 36 weeks ) were associated with increases in pregnancy-related low back pain intensity . These same factors plus depression were associated with an increase in pregnancy-related low back pain interference . CONCLUSIONS This study identified a number of prospect i ve factors related to increases in pain intensity and pain interference during the third trimester . Given that both catastrophizing and depression are modifiable , the findings indicate that research examining the benefits of treatments that address these ( e.g. cognitive-behavioural therapy ) on pain and pain interference is warranted OBJECTIVE Pelvic girdle pain is a common complaint of pregnant women . There are limited data on comparison between the effectiveness of stabilizing exercises and lumbopelvic belt on the treatment of these patients . The objective of this study was to compare the effect of lumbopelvic belt plus information , home based pelvic girdle stabilizing exercises plus information and information alone on pain intensity , functional status and quality of life of pregnant women with pelvic girdle pain . METHODS In this r and omized clinical trial pregnant women with pelvic girdle pain ( n=105 ) were r and omly allocated to three groups ; Control group ( n=35 ) that received general information , exercise group ( n=31 ) that in addition to general information were asked to perform specific pelvic stabilizing exercises at home and belt group ( n=31 ) that received non-rigid lumbopelvic belt and the information . The primary outcome variables were pain intensity and functional status of the participants which were measured using visual analogue scale and Oswestry Disability Index ( ODI ) respectively . Quality of life of participants was measured using WHOQOL-BREF question naire . All measurements were performed at baseline , 3 and 6 weeks after the study conduction . RESULTS The pain intensity of patients in belt group in comparison to other groups was decreased significantly at both 3 and 6 weeks follow-ups . The mean score of ODI of patients in belt group was also improved more than exercise and control groups significantly . CONCLUSIONS On base of our results , it can be found that in short term lumbopelvic belt and information in treatment of pregnant women with pelvic girdle pain is superior to exercise plus information or information alone Background . Prevention of lumbopelvic pain in pregnancy has been sparsely studied . One aim of this study was to assess if a 12‐week training program during pregnancy can prevent and /or treat lumbopelvic pain . A r and omized controlled trial was conducted at Trondheim University Hospital and three outpatient physiotherapy clinics . Three hundred and one healthy nulliparous women were included at 20 weeks of pregnancy and r and omly allocated to a training group ( 148 ) or a control group ( 153 ) . Methods . The outcome measures were self‐reported symptoms of lumbopelvic pain ( once per week or more ) , sick leave , and functional status . Pain drawing was used to document the painful area of the body . The intervention included daily pelvic floor muscle training at home , and weekly group training over 12 weeks including aerobic exercises , pelvic floor muscle and additional exercises , and information related to pregnancy . Results . At 36 weeks of gestation women in the training group were significantly less likely to report lumbopelvic pain : 65/148 ( 44 % ) versus 86/153 ( 56 % ) ( p = 0.03 ) . Three months after delivery the difference was 39/148 ( 26 % ) in the training group versus 56/153 ( 37 % ) in the control group ( p = 0.06 ) . There was no difference in sick leave during pregnancy , but women in the training group had significantly ( p = 0.01 ) higher scores on functional status . Conclusions . A 12‐week specially design ed training program during pregnancy was effective in preventing lumbopelvic pain in pregnancy BACKGROUND most pregnant women experience back pain during pregnancy , a serious issue that negatively impacts life quality during pregnancy . Research into an exercise intervention programme targeting low back pain and daily life interference is lacking . OBJECTIVE this study evaluates how a stability ball exercise programme influences low back pain and daily life interference across the second and third pregnancy trimester . METHODS the study was non-r and omised and controlled , examining a target population of low-risk pregnancy women between 20 and 22 weeks of gestation located in a regional hospital in northern Taiwan . All participants had at least minimal low back pain , no prior history of chronic low back pain before pregnancy , and no indications of preterm labour . In total , 89 individuals participated : 45 in the control group and 44 in the experimental group ( who attended an antenatal stability ball exercise programme ) . This programme lasted 12 weeks , composed of at least three sessions per week . Fitness workouts lasted from 25 to 30 minutes . The women completed their basic personal information , the Brief Pain Inventory-Short Form , and the Family Exercise Support Attitude Question naire . RESULTS after adjusting for demographic data and antenatal exercise status by propensity scores , experimental-group women who participated in the antenatal stability ball exercise programme reported significantly less low back pain and daily life interferences than the control group at 36 weeks of gestation . DISCUSSION the inclusion of stability ball exercises during pregnancy may reduce pregnancy low back pain and boost daily life functions . This stability ball exercise programme provides health-care professionals with an evidence -based intervention 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 BACKGROUND Although many pregnant women experience back pain , it has not considered an important health problem . No study has investigated the effects of a back-pain-reducing program ( BPRP ) during pregnancy for Korean women . OBJECTIVE The purpose of this study was to evaluate the effect of a program design ed to reduce back pain in pregnant women . METHODS A non-equivalent control-group pretest-posttest design was used . Pregnant women who attended an antenatal clinic and experienced back pain during their pregnancy were included in an intervention group ( n=29 ) , and their intensity of back pain , functional limitation and anxiety were compared with women in a control group from another antenatal clinic ( n=27 ) . The data were collected at three time points : prior to intervention , and 6 and 12 weeks after intervention . RESULTS At 12 weeks after intervention , the intensity of back pain experienced by the intervention group was significantly lower than that of the control group . However , there were no statistically significant differences between the groups with respect to functional limitations and anxiety . CONCLUSIONS The findings show that the pain-reducing program developed for this study was effective in reducing the intensity of back pain experienced by pregnant women . Promoting good posture and regular exercise can be recommended as a method to relieve back pain in pregnancy women . Further studies are needed to confirm the effect of the BPRP during pregnancy OBJECTIVE To compare the effect of a l and -based , physical exercise program versus water aerobics on low back or pelvic pain and sick leave during pregnancy . DESIGN R and omized controlled clinical trial . SETTING Three antenatal care centers . PARTICIPANTS 390 healthy pregnant women . INTERVENTIONS A l and -based physical exercise program or water aerobic once a week during pregnancy . MAIN OUTCOME MEASURES Sick leave , pregnancy-related low back pain or pregnancy-related pelvic girdle pain , or both . RESULTS Water aerobics diminished pregnancy-related low back pain ( p=.04 ) and sick leave due to pregnancy-related low back pain ( p=.03 ) more than a l and -based physical exercise program . CONCLUSIONS Water aerobics can be recommended for the treatment of low back pain during pregnancy . The benefits of a l and -based physical exercise program are question able and further evaluation is needed OBJECTIVE To determine whether participation in a group fitness class for pregnant women can prevent and treat pelvic girdle pain and low back pain . DESIGN An observer-blinded r and omized controlled trial . PARTICIPANTS A total of 105 sedentary , nulliparous pregnant women , mean age 30.7 years ( st and ard deviation ( SD ) 4.0 ) , mean pre-pregnancy body mass index ( BMI ) 23.8 ( SD 4.3 ) , were assigned to either control or exercise groups at mean gestation week 17.7 ( SD 4.2 ) . METHODS The exercise intervention followed the guidelines of American College of Obstetricians and Gynecologists and included a 60 min general fitness class , with 40 min of endurance training and 20 min of strength training including stretching , performed at least twice per week for a minimum of 12 weeks . Outcome measures were number of women reporting pelvic girdle pain and low back pain after the intervention ( mean pregnancy week 36.6 ( SD 0.9 ) ) and postpartum ( mean 7.7 ( SD 1.7 ) ) . RESULTS There were no statistically significant differences between the exercisers and controls in numbers reporting the 2 conditions after the intervention ( pelvic girdle pain : odds ratio ( OR ) = 1.34 , CI = 0.56 - 3.20 or low back pain : OR = 1.10 , CI = 0.47 - 2.60 ) or postpartum ( pelvic girdle pain : OR = 0.38 , CI = 0.13 - 1.10 or low back pain : OR = 1.45 , CI = 0.54 - 3.94 ) . A comparison of the women who had attended at least 80 % of the weekly exercise classes with the control participants did not change the results . CONCLUSION Participation in regular group fitness classes during pregnancy did not alter the proportion of women reporting pelvic girdle pain or low back pain during pregnancy or after childbirth Study Design . A r and omized assessor-blinded clinical trial was conducted . Objective . To compare 3 different physical therapy treatments with respect to pain and activity in women with pelvic girdle pain during pregnancy and 3 , 6 , and 12 months postpartum . Summary of Background Data . In spite of the high prevalence of back pain during pregnancy , documented treatment programs are limited . Methods . Based on a clinical examination , 118 women with pelvic girdle pain diagnosed during pregnancy were r and omized into 3 different treatment groups : Information Group , use of a nonelastic sacroiliac belt and oral/written information about pelvic girdle pain ( n = 40 ) ; Home Exercise Group , same as in the Information Group , with the addition of a home exercise program ( n = 41 ) ; and the In Clinic Exercise Group , same as in the Information Group , plus participation in a training program ( n = 37 ) . Pain intensity was rated on a visual analogue scale ( 0–100 mm ) and marked on a pain drawing concerning localization . The activity ability was scored using the Disability Rating Index , covering 12 daily activity items . Outcome measures were obtained at inclusion , on average in gestation week 38 , and 3 , 6 , and 12 months postpartum . Results . There was no significant difference among the 3 groups during pregnancy or at the follow-ups postpartum regarding pain and activity . In all groups , pain decreased and the activity ability increased between gestation week 38 and at 12 months postpartum . Conclusions . Women with pelvic girdle pain seemed to improve with time in all 3 treatment groups . Neitherhome nor in clinic exercises had any additional value above giving a nonelastic sacroiliac belt and information In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted AIM To evaluate the effect of exercise programs on pregnant women with pregnancy-related low back and pelvic pain . BACKGROUND Low back and pelvic pain during pregnancy is a major health problem due to its frequent occurrence and such pain can limit pregnant women in many of their daily activities . DESIGN A r and omized trial with a control group ( n = 48 ) and an intervention group ( n = 48 ) . Trial registration number NCT02189356 . METHODS Department of Obstetrics and Gynecology , between December 2011-May 2012 , an Education and Research Hospital in Turkey . Based on the intention-to-treat principle , all pregnant women were analysed according to the group they were assigned to , regardless of whether they received the intervention or not . Participants in the intervention group received health counselling and exercised regarding low back and pelvic pain for four weeks . The pregnant women in the control group received usual care , comprised of routine clinical practice for pregnancy-related low back and pelvic pain . RESULTS According to Mann-Whitney U test analysis results , there was a statistically significant difference between the control and intervention groups ' Visual Analogue Scale during relaxation scores and Visual Analogue Scale during activity scores at the end of the study . According to Mann-Whitney U test analysis results , the change in the mean Oswestry Disability Index score for the intervention group and the difference in the mean scores between the two groups was statistically significant . CONCLUSIONS A four-week exercise program including individualized health counselling to relieve low back and pelvic pain improved the functional status in pregnant women Eighty-four prenatally depressed women were r and omly assigned to yoga , massage therapy or st and ard prenatal care control groups to determine the relative effects of yoga and massage therapy on prenatal depression and neonatal outcomes . Following 12 weeks of twice weekly yoga or massage therapy sessions ( 20 min each ) both therapy groups versus the control group had a greater decrease on depression , anxiety and back and leg pain scales and a greater increase on a relationship scale . In addition , the yoga and massage therapy groups did not differ on neonatal outcomes including gestational age and birthweight , and those groups , in turn , had greater gestational age and birthweight than the control group |
11,748 | 20,614,443 | The evidence from r and omised controlled trials is currently too limited to draw definitive conclusions about the use of non-surgical interventions for paediatric pes planus .
Only limited interventions commonly used in practice have been studied and there is much debate over the treatment of symptomatic and asymptomatic pes planus | BACKGROUND Paediatric pes planus ( ' flat feet ' ) is a common childhood condition with a reported prevalence of 14 % .
Flat feet can result in pain and altered gait .
No optimal strategy for non-surgical management of paediatric flat feet has been identified .
OBJECTIVES To assess the effectiveness of non-surgical interventions for treatment of paediatric pes planus ( flat feet ) . | A range of patient-oriented and practitioner-oriented outcomes were used to evaluate the efficacy of " gait plate " shoe inlays in controlling symptoms associated with in-toeing in otherwise healthy children . For 18 in-toeing children , parents completed a preintervention question naire . Then , during r and omized trials , foot placement angle was measured both with and without gait plate inlays in the children 's footwear . After the children had worn the gait plates for 1 month , a simple question naire was used to rate parental satisfaction with a range of factors associated with control of symptoms . The use of gait plate inlays result ed in a small but statistically significant reduction in the amount of in-toeing as measured by foot placement angle . Gait plates reduced the reported frequency of tripping in 14 of the 18 cases . The reported parental satisfaction was high or very high in all but one case , suggesting that this intervention warrants further investigation as an alternative to " observational management " for symptomatic in-toeing OBJECTIVE . To compare the clinical efficacy of custom foot orthotics , prefabricated " off-the-shelf " shoe inserts , and supportive athletic shoes worn alone , on reducing pain and improving function for children with juvenile idiopathic arthritis ( JIA ) . METHODS Children with JIA and foot pain ( n = 40 ) were r and omized to one of 3 groups receiving : ( 1 ) custom-made semirigid foot orthotics with shock absorbing posts ( n = 15 ) , ( 2 ) off-the-shelf flat neoprene shoe inserts ( n = 12 ) , or ( 3 ) supportive athletic shoes with a medial longitudinal arch support and shock absorbing soles worn alone ( n = 13 ) . Foot pain and functional limitations were measured using the Pediatric Pain Question naire-visual analog scale ( VAS ) , Timed Walking , Foot Function Index ( FFI ) , and the Physical Functioning Subscale of the Pediatric Quality of Life Inventory ( PedsQL ) . Measures were administered by personnel blinded to group status at baseline ( before wearing the assigned intervention ) and at 3 months ' followup . RESULTS Children in the orthotics group showed significantly greater improvements in overall pain ( p = 0.009 ) , speed of ambulation ( p = 0.013 ) , activity limitations ( p = 0.002 ) , foot pain ( p = 0.019 ) , and level of disability ( p = 0.024 ) when compared with the other 2 groups . Both children and parents in the orthotics group reported clinical ly meaningful improvement in child health-related quality of life , although the group by time interaction did not show statistical significance . Except for a reduction in pain for supportive athletic shoes ( paired t test , p = 0.011 ) , neither the off-the-shelf shoe inserts nor the supportive athletic shoes worn alone showed significant effect on any of the evaluation measures . CONCLUSION In children with JIA , custom-made semirigid foot orthotics with shock-absorbing posts significantly improve pain , speed of ambulation , and self-rated activity and functional ability levels compared with prefabricated off-the-shelf shoe inserts or supportive athletic shoes worn alone Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Background : Orthoses for children with flexible excess pronation are estimated to cost Australian parents millions of dollars per year ; however , there is no high-level evidence that orthoses improve function or reduce pain . Methods : A r and omized parallel , single-blinded , controlled trial of custom-made and ready-made orthoses was conducted in children between the ages of 7 and 11 years with bilateral flexible excess pronation . The diagnosis was based on calcaneal eversion and navicular drop . Outcomes included gross motor proficiency , self-perception , exercise efficiency , and pain . Measurements were taken at baseline , and at 3 and 12 months . Of the 178 children who participated at baseline , 160 continued to the end of the trial . Results : After r and omization , baseline characteristics were similar between the three treatment groups ( custom-made , ready-made , and control ) . Statistical modeling demonstrated that although for most outcome measures there were statistically significant trends over time , none of the group comparisons were statistically significant . A sub-group analysis of those presenting with pain found no significant differences at 3 or 12 months . Conclusions : This study found no evidence to justify the use of in-shoe orthoses in the management of flexible excess foot pronation in children In a survey of 6000 children between 9 and 10 years of age , 122 were found to have unilateral or bilateral hallux valgus . These children were r and omly assigned to no treatment or to the use of a foot orthosis . About three years later 93 again had radiography . The metatarsophalangeal joint angle had increased in both groups but more so in the treated group . During the study , hallux valgus developed in the unaffected feet of children with unilateral deformity , despite the use of the orthosis A Foot Function Index ( FFI ) was developed to measure the impact of foot pathology on function in terms of pain , disability and activity restriction . The FFI is a self-administered index consisting of 23 items divided into 3 sub-scales . Both total and sub-scale scores are produced . The FFI was examined for test-retest reliability , internal consistency , and construct and criterion validity . A total of 87 patients with rheumatoid arthritis were used in the study . Test-retest reliability of the FFI total and sub-scale scores ranged from 0.87 to 0.69 . Internal consistency ranged from 0.96 to 0.73 . With the exception of two items , factor analysis supported the construct validity of the total index and the sub-scales . Strong correlation between the FFI total and sub-scale scores and clinical measures of foot pathology supported the criterion validity of the index . The FFI should prove useful for both clinical and research purpose Pes planovalgus is an extremely common deformity and still not completely understood . Its pathogenesis and the possibilities for treating it with shoe inserts are still under debate . While the controversy between abstentionists and interventionists remains a fact , since a certain number of flat feet persist into adult age and cause disability , a new type of orthosis is proposed . This has been tested on children affected with grade III pes planovalgus and with all the worst clinical , objective and prognostic parameters . The study was carried out with a control group using traditional Lelièvre insoles . The results were extremely good and correction was achieved in a significantly higher number of patients than in the control group OBJECTIVE To assess the method ologic quality of approaches used to allocate participants to comparison groups in r and omized controlled trials from one medical specialty . DESIGN Survey of published , parallel group r and omized controlled trials . DATA SOURCES All 206 reports with allocation described as r and omized from the 1990 and 1991 volumes of four journals of obstetrics and gynecology . MAIN OUTCOME MEASURES Direct and indirect measures of the adequacy of r and omization and baseline comparisons . RESULTS Only 32 % of the reports described an adequate method for generating a sequence of r and om numbers , and only 23 % contained information showing that steps had been taken to conceal assignment until the point of treatment allocation . A mere 9 % described both sequence generation and allocation concealment . In 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 due to chance . In reports of trials in which hypothesis tests had been used to compare baseline characteristics , only 2 % of reported test results were statistically significant , lower than the expected rate of 5 % . CONCLUSIONS Proper r and omization is required to generate unbiased comparison groups in controlled trials , yet the reports in these journals usually provided inadequate or unacceptable information on treatment allocation . Additional analyses suggest that nonr and om manipulation of comparison groups and selective reporting of baseline comparisons may have occurred |
11,749 | 32,096,113 | No significant linear trends in the effects of timing of sodium bicarbonate ingestion or acute increase in blood bicarbonate concentrations on muscular endurance or muscular strength were found .
Overall , sodium bicarbonate supplementation acutely improves muscular endurance of small and large muscle groups , but no significant ergogenic effect on muscular strength was found | The effects of sodium bicarbonate on muscular strength and muscular endurance are commonly acknowledged as unclear due to the contrasting evidence on the topic .
To conduct a systematic review and meta- analysis of studies exploring the acute effects of sodium bicarbonate supplementation on muscular strength and endurance . | CONTEXT Sodium bicarbonate ( NaHCO₃ ) is often ingested at a dose of 0.3 g/kg body mass ( BM ) , but ingestion protocol s are inconsistent in terms of using solution or capsules , ingestion period , combining NaHCO₃ with sodium citrate ( Na₃C₆H₅O₇ ) , and coingested food and fluid . PURPOSE To quantify the effect of ingesting 0.3 g/kg NaHCO₃ on blood pH , [ HCO₃- ] , and gastrointestinal ( GI ) symptoms over the subsequent 3 hr using a range of ingestion protocol s and , thus , to determine an optimal protocol . METHODS In a crossover design , 13 physically active subjects undertook 8 NaHCO₃ experimental ingestion protocol s and 1 placebo protocol . Capillary blood was taken every 30 min and analyzed for pH and [ HCO₃- ] . GI symptoms were quantified every 30 min via question naire . Statistics used were pairwise comparisons between protocol s ; differences were interpreted in relation to smallest worthwhile changes for each variable . A likelihood of > 75 % was a substantial change . RESULTS [ HCO₃- ] and pH were substantially greater than in placebo for all other ingestion protocol s at almost all time points . When NaHCO3 was coingested with food , the greatest [ HCO₃- ] ( 30.9 mmol/kg ) and pH ( 7.49 ) and lowest incidence of GI symptoms were observed . The greatest incidence of GI side effects was observed 90 min after ingestion of 0.3 g/kg NaHCO₃ solution . CONCLUSIONS The changes in pH and [ HCO₃- ] for the 8 NaHCO₃-ingestion protocol s were similar , so an optimal protocol can not be recommended . However , the results suggest that NaHCO₃ coingested with a high-carbohydrate meal should be taken 120 - 150 min before exercise to induce substantial blood alkalosis and reduce GI symptoms ABSTRACT The aim of this study was to investigate the effects of sodium bicarbonate ( NaHCO3 ) on 4 km cycling time trial ( TT ) performance when individualised to a predetermined time to peak blood bicarbonate ( HCO3− ) . Eleven male trained cyclists volunteered for this study ( height 1.82 ± 0.80 m , body mass ( BM ) 86.4 ± 12.9 kg , age 32 ± 9 years , peak power output ( PPO ) 382 ± 22 W ) . Two trials were initially conducted to identify time to peak HCO3− following both 0.2 g.kg−1 BM ( SBC2 ) and 0.3 g.kg−1 BM ( SBC3 ) NaHCO3 . Thereafter , on three separate occasions using a r and omised , double-blind , crossover design , participants completed a 4 km TT following ingestion of either SBC2 , SBC3 , or a taste-matched placebo ( PLA ) containing 0.07 g.kg−1 BM sodium chloride ( NaCl ) at the predetermined individual time to peak HCO3−. Both SBC2 ( −8.3 ± 3.5 s ; p < 0.001 , d = 0.64 ) and SBC3 ( −8.6 ± 5.4 s ; p = 0.003 , d = 0.66 ) reduced the time to complete the 4 km TT , with no difference between SBC conditions ( mean difference = 0.2 ± 0.2 s ; p = 0.87 , d = 0.02 ) . These findings suggest trained cyclists may benefit from individualising NaHCO3 ingestion to time to peak HCO3− to enhance 4 km TT performance The aim of the present study was to examine the effects of sodium bicarbonate ( NaHCO3 ) administration on lower-body , hypertrophy-type resistance exercise ( HRE ) . Using a double-blind r and omized counterbalanced design , 12 resistance-trained male participants ( mean ± SD ; age = 20.3 ± 2 years , mass = 88.3 ± 13.2 kg , height = 1.80 ± 0.07 m ) ingested 0.3 g kg−1 of NaHCO3 or placebo 60 min before initiation of an HRE regimen . The protocol employed multiple exercises : squat , leg press , and knee extension , utilizing four sets each , with 10–12 repetition-maximum loads and short rest periods between sets . Exercise performance was determined by total repetitions generated during each exercise , total accumulated repetitions , and a performance test involving a fifth set of knee extensions to failure . Arterialized capillary blood was collected via fingertip puncture at four time points and analyzed for pH , [ HCO3− ] , base excess ( BE ) , and lactate [ Lac− ] . NaHCO3 supplementation induced a significant alkaline state ( pH : NaHCO3 : 7.49 ± 0.02 , placebo : 7.42 ± 0.02 , P < 0.05 ; [ HCO3− ] : NaHCO3 : 31.50 ± 2.59 , placebo : 25.38 ± 1.78 mEq L−1 , P < 0.05 ; BE : NaHCO3 : 7.92 ± 2.57 , placebo : 1.08 ± 2.11 mEq L−1 , P < 0.05 ) . NaHCO3 administration result ed in significantly more total repetitions than placebo ( NaHCO3 : 139.8 ± 13.2 , placebo : 134.4 ± 13.5 ) , as well as significantly greater blood [ Lac− ] after the exercise protocol ( NaHCO3 : 17.92 ± 2.08 , placebo : 15.55 ± 2.50 mM , P < 0.05 ) . These findings demonstrate ergogenic efficacy for NaHCO3 during HRE and warrant further investigation into chronic training applications Sodium bicarbonate ingestion has been shown to improve performance in single-bout , high intensity events , probably due to an increase in buffering capacity , but its influence on single-bout swimming performance has not been investigated . The effects of sodium bicarbonate supplementation on 200 m freestyle swimming performance were investigated in elite male competitors . Following a r and omised , double blind counterbalanced design , 9 swimmers completed maximal effort swims on 3 separate occasions : a control trial ( C ) ; after ingestion of sodium bicarbonate ( SB : NaHCO3 300 mg . kg ( -1 ) body mass ) ; and after ingestion of a placebo ( P : CaCO3 200 mg . kg ( -1 ) body mass ) . The SB and P agents were packed in gelatine capsules and ingested 90 - 60 min prior to each 200 m swim . Mean 200 m performance times were significantly faster for SB than C or P ( 1 : 52.2 + /- 4.7 ; 1 : 53.7 + /- 3.8 ; 1 : 54.0 + /- 3.6 min : ss ; p < 0.05 ) . Base excess , pH and blood bicarbonate were all elevated pre-exercise in the SB compared to C and P trials ( p < 0.05 ) . Post-200 m blood lactate concentrations were significantly higher following the SB trial compared with P and C ( p < 0.05 ) . It was concluded that SB supplementation can improve 200 m freestyle performance time in elite male competitors , most likely by increasing buffering capacity We tested the hypothesis that reducing hydrogen ion accumulation during training would result in greater improvements in muscle oxidative capacity and time to exhaustion ( TTE ) . Male Wistar rats were r and omly assigned to one of three groups ( CON , PLA , and BIC ) . CON served as a sedentary control , whereas PLA ingested water and BIC ingested sodium bicarbonate 30 min prior to every training session . Training consisted of seven to twelve 2-min intervals performed five times/wk for 5 wk . Following training , TTE was significantly greater in BIC ( 81.2 + /- 24.7 min ) compared with PLA ( 53.5 + /- 30.4 min ) , and TTE for both groups was greater than CON ( 6.5 + /- 2.5 min ) . Fiber respiration was determined in the soleus ( SOL ) and extensor digitorum longus ( EDL ) , with either pyruvate ( Pyr ) or palmitoyl carnitine ( PC ) as substrates . Compared with CON ( 14.3 + /- 2.6 nmol O(2).min(-1).mg dry wt(-1 ) ) , there was a significantly greater SOL-Pyr state 3 respiration in both PLA ( 19.6 + /- 3.0 nmol O(2).min(-1).mg dry wt(-1 ) ) and BIC ( 24.4 + /- 2.8 nmol O(2).min(-1).mg dry wt(-1 ) ) , with a significantly greater value in BIC . However , state 3 respiration was significantly lower in the EDL from both trained groups compared with CON . These differences remained significant in the SOL , but not the EDL , when respiration was corrected for citrate synthase activity ( an indicator of mitochondrial mass ) . These novel findings suggest that reducing muscle hydrogen ion accumulation during running training is associated with greater improvements in both mitochondrial mass and mitochondrial respiration in the soleus PURPOSE Fifteen males were studied before , during , and in recovery from exhaustive resistance exercise 105 min after ingesting 0.3 g.kg-1 of either a placebo ( white flour ) or sodium bicarbonate ( NaHCO3 ) . METHODS The exercise consisted of five maximal sets on a leg press machine , The load was adjusted to maintain the number of repetitions per set for each subject at approximately 12 repetitions . A significant ( P < 0.05 ) increase in pH ( 7.40 to 7.47 ) , oxygenated base excess ( OxyBE ) ( -1.3 to 4.0 mEq . L-1 ) , and bicarbonate concentration ( [ HCO3- ] ) ( 22.8 to 27.4 mM ) was achieved before exercise with the ingestion of NaHCO3 . RESULTS The exercise protocol produced significant changes in acid base status consistent with metabolic acidosis for both trials ( pH sets 1 - 5 : placebo , 7.4 to 7.26 ; NaHCO3 , 7.47 to 7.33 ) , ( OxyBE sets 1 - 5 : placebo , -1.3 to -12.3 mEq . L-1 ; NaHCO3 , 4.0 to -6.9 mEq . L-1 ) and ( [ HCO3- ] sets 1 - 5 : placebo , 22.9 to 14.0 mM ; NaHCO3 , 27.4 to 17.6 mM ) . After every set ; pH , OxyBE , and [ HCO3- ] were significantly higher in the NaHCO3 trial . Blood lactate concentration ( [ La- ] ) significantly increased throughout exercise for both trials ( [ La- ] sets 1 - 5 : placebo , 4.6 to 11.3 mM ; NaHCO3 , 4.8 to 13.4 mM ) . After sets 4 and 5 , blood [ La- ] was significantly higher in the NaHCO3 trial . Bicarbonate ingestion did not improve performance ( total repetitions : NaHCO3 = 59 + /- 3 ; placebo = 60 + /- 2 ) . CONCLUSIONS This may be a result of a lower dem and on the whole body metabolic system in comparison with that for other modes of exercise in which ergogenic effects have been found Alkalosis enhances human exercise performance , and reduces K+ loss in contracting rat muscle . We investigated alkalosis effects on K+ regulation , ionic regulation and fatigue during intense exercise in nine untrained volunteers . Concentric finger flexions were conducted at 75 % peak work rate ( 3 W ) until fatigue , under alkalosis ( Alk , NaHCO3 , 0.3 g kg(-1 ) ) and control ( Con , CaCO3 ) conditions , 1 month apart in a r and omised , double-blind , crossover design . Deep antecubital venous ( v ) and radial arterial ( a ) blood was drawn at rest , during exercise and recovery , to determine arterio-venous differences for electrolytes , fluid shifts , acid-base and gas exchange . Finger flexion exercise barely perturbed arterial plasma ions and acid-base status , but induced marked arterio-venous changes . Alk elevated [ HCO3- ] and PCO2 , and lowered [ H+ ] ( P < 0.05 ) . Time to fatigue increased substantially during Alk ( 25 + /- 8 % , P < 0.05 ) , whilst both [K+]a and [K+]v were reduced ( P < 0.01 ) and [K+]a-v during exercise tended to be greater ( P= 0.056 , n= 8) . Muscle K+ efflux at fatigue was greater in Alk ( 21.2+/- 7.6 micromol min(-1 ) , 32 + /- 7 % , P < 0.05 , n= 6 ) , but peak K+ uptake rate was elevated during recovery ( 15 + /- 7 % , P < 0.05 ) suggesting increased muscle Na+,K+-ATPase activity . Alk induced greater [Na+]a , [Cl-]v , muscle Cl- influx and muscle lactate concentration ( [ Lac- ] ) efflux during exercise and recovery ( P < 0.05 ) . The lower circulating [ K+ ] and greater muscle K+ uptake , Na+ delivery and Cl- uptake with Alk , are all consistent with preservation of membrane excitability during exercise . This suggests that lesser exercise-induced membrane depolarization may be an important mechanism underlying enhanced exercise performance with Alk . Thus Alk was associated with improved regulation of K+ , Na+ , Cl- and Lac- Six weight trained males were studied prior to , during , and in recovery from exhaustive resistance exercise , 105 min after ingesting 300 mg.kg-1 of either a placebo or NaHCO3 . The exercise test consisted of four sets of 12 repetitions with a fifth set to volitional fatigue on a Universal leg press machine at a resistance equaling approximately 70 % of the subjects 1-repetition maximum . Arterialized venous blood was analyzed for lactate concentration , blood gas , and acid-base parameters . The ingestion of NaHCO3 produced a significant increase in resting pH ( 7.39 to 7.46 ) , HCO3- ( 22.9 to 28.3 mEq.l-1 ) , and oxygenated base excess ( -1.3 to 4.4 mEq.l-1 ) . With the completion of each exercise set , a progressive decline in the acid-base status of both groups was observed ( pH set 1 - 5 : NaHCO3 , 7.40 to 7.31 ; placebo , 7.34 to 7.25 ; HCO3- set 1 - 5 : NaHCO3 , 25.3 to 17.9 ; placebo , 21.7 to 15.3 mEq.l-1 ; base excess set 1 - 5 : NaHCO3 , 3.7 to -7.1 ; placebo , -1.4 to -10.7 mEq.l-1 ) ; however , the NaHCO3 condition was significantly more alkaline than the placebo condition . Blood lactate concentration [ La ] progressively increased with the completion of each exercise set ( [ La ] set 1 - 5 : NaHCO3 , 1.37 to 11.15 ; placebo , 1.31 to 9.81 mM ) ; but were not significantly different between treatments . Repetitions performed in the final exercise set were not significantly different between groups ( NaHCO3 : 19.6 + /- 1.6 , placebo : 18.2 + /- 1.1 repetitions ) . ( ABSTRACT TRUNCATED AT 250 WORDS 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 . To defend against hydrogen cation accumulation and muscle fatigue during exercise , sodium bicarbonate ( NaHCO3 ) ingestion is commonplace . The individualized dose-response relationship between NaHCO3 ingestion and blood biochemistry is unclear . The present study investigated the bicarbonate , pH , base excess and sodium responses to NaHCO3 ingestion . Sixteen healthy males ( 23 ± 2 years ; 78.6 ± 15.1 kg ) attended three r and omized order-balanced , nonblinded sessions , ingesting a single dose of either 0.1 , 0.2 or 0.3 g·kg-1BM of NaHCO3 ( Intralabs , UK ) . Fingertip capillary blood was obtained at baseline and every 10 min for 1 hr , then every 15 min for a further 2 hr . There was a significant main effect of both time and condition for all assessed blood analytes ( p ≤ .001 ) . Blood analyte responses were significantly lower following 0.1 g·kg-1BM compared with 0.2 g·kg-1BM ; bicarbonate concentrations and base excess were highest following ingestion of 0.3 g·kg-1BM ( p ≤ .01 ) . Bicarbonate concentrations and pH significantly increased from baseline following all doses ; the higher the dose the greater the increase . Large interindividual variability was shown in the magnitude of the increase in bicarbonate concentrations following each dose ( + 2.0 - 5 ; + 5.1 - 8.1 ; and + 6.0 - 12.3 mmol·L-1 for 0.1 , 0.2 and 0.3 g·kg-1BM ) and in the range of time to peak concentrations ( 30 - 150 ; 40 - 165 ; and 75 - 180 min for 0.1 , 0.2 and 0.3 g·kg-1BM ) . The variability in bicarbonate responses was not affected by normalization to body mass . These results challenge current practice s relating to NaHCO3 supplementation and clearly show the need for athletes to individualize their ingestion protocol and trial varying dosages before competition Abstract Duncan , MJ , Weldon , A , and Price , MJ . The effect of sodium bicarbonate ingestion on back squat and bench press exercise to failure . J Strength Cond Res 28(5 ) : 1358–1366 , 2014—This study examined the acute effects of NaHCO3 ingestion on repetitions to failure and rating of perceived exertion in the back squat and bench press in trained men . Eight resistance-trained men took part in this double-blind , r and omized crossover experimental study whereby they ingested NaHCO3 ( 0.3 g·kg−1 body mass ) or placebo ( sodium chloride NaCl : 0.045 g·kg−1 body mass ) solution 60 minutes before completing a bout of resistance exercise ( 3 sets of bench press and back squat exercise to failure at an intensity of 80 % 1 repetition maximum ) . Experimental conditions were separated by at least 48 hours . Participants completed more repetitions to failure in the back squat after NaHCO3 ingestion ( p = 0.04 ) but not for bench press ( p = 0.679 ) . Mean ± SD of total repetitions was 31.3 ± 15.3 and 24.6 ± 16.2 for back squat and 28.7 ± 12.2 and 26.7 ± 10.2 for bench press in NaHCO3 and placebo conditions , respectively . Repetitions to failure decreased as set increased for the back squat and bench press ( p = 0.001 , both ) . Rating of perceived exertion significantly increased with set for the back squat and bench press ( p = 0.002 , both ) . There was no significant change in blood lactate across time or between conditions . There were however treatment × time interactions for blood pH ( p = 0.014 ) and blood HCO3 concentration ( p = 0.001 ) . After ingestion , blood pH and HCO3 ( p = 0.008 ) concentrations were greater for the NaHCO3 condition compared with the placebo condition ( p < 0.001 ) . The results of this study suggest that sodium bicarbonate ingestion can enhance resistance exercise performance using a repetition to failure protocol in the first exercise in a resistance exercise session Four groups of male subjects participated in anaerobic testing on a Repco EX10 cycle ergometer to determine the effectiveness of sodium bicarbonate ( 0.3 g kg-1 body mass ) as an ergogenic aid during exercise of 10 , 30 , 120 and 240 s duration . Blood was collected 90 min prior to ingestion of sodium bicarbonate ( NaHCO3 ) , after ingestion of NaHCO3 and immediately post-exercise from a heated ( 43 - 46 degrees C ) fingertip and analysed immediately post- collection for pH , base excess , bicarbonate and lactate . The total work undertaken ( kJ ) and peak power achieved during the tests were also obtained via a Repco Work Monitor Unit . Blood bicarbonate levels were again increased above the control and placebo conditions ( P < 0.001 ) and blood lactate levels were also increased following the bicarbonate trials . The pH levels fell significantly ( P < 0.05 ) below the control and placebo conditions in all trials . The results indicate that NaHCO3 at this dosage has no ergogenic benefit for work of either 10 or 30 s duration , even though blood bicarbonate levels were significantly increased ( P < 0.05 ) following ingestion of NaHCO3 . For work periods of 120 and 240 s , performance was significantly increased ( P < 0.05 ) above the control and placebo conditions following NaHCO3 ingestion Background Sodium bicarbonate ( NaHCO3 ) is a well-established nutritional ergogenic aid , though gastrointestinal ( GI ) distress is a common side-effect . Delayed-release NaHCO3 may alleviate GI symptoms and enhance bicarbonate bioavailability following oral ingestion , although this has yet to be confirmed . Methods In a r and omised crossover design , pharmacokinetic responses and acid-base status were compared following two forms of NaHCO3 , as were GI symptoms . Twelve trained healthy males ( mean ± SD age 25.8 ± 4.5 years , maximal oxygen uptake ( V̇O2max$$ \dot{\mathrm{V}}{\mathrm{O}}_{2\max } $ $ ) 58.9 ± 10.9 mL kg min−1 , height 1.8 ± 0.1 m , body mass 82.3 ± 11.1 kg , fat-free mass 72.3 ± 10.0 kg ) underwent a control ( CON ) condition and two experimental conditions : 300 mg kg−1 body mass NaHCO3 ingested as an aqueous solution ( SOL ) and encased in delayed-release capsules ( CAP ) . Blood bicarbonate concentration , pH and base excess ( BE ) were measured in all conditions over 180 min , as were subjective GI symptom scores . Results Incidences of GI symptoms and overall severity were significantly lower ( mean difference = 45.1 % , P < 0.0005 and 47.5 % , P < 0.0005 for incidences and severity , respectively ) with the CAP than with the SOL . Symptoms displayed increases at 40 to 80 min post-ingestion with the SOL that were negated with CAP ( P < 0.05 ) . Time to reach peak bicarbonate concentration , pH and BE were significantly longer with CAP than with the SOL . Conclusions In summary , CAP can mitigate GI symptoms induced with SOL and should be ingested earlier to induce similar acid-base changes . Furthermore , CAP may be more ergogenic in those who experience severe GI distress with SOL , although this warrants further investigation Abstract The aim of this study was to determine if inducing metabolic alkalosis would alter neuromuscular control after 50 min of st and ardized submaximal cycling . Eight trained male cyclists ( mean age 32 years , s = 7 ; [Vdot]O2max 62 ml · kg−1 · min−1 , s = 8) ingested capsules containing either CaCO3 ( placebo ) or NaHCO3 ( 0.3 g · kg−1 body mass ) in eight doses over 2 h on two separate occasions , commencing 3 h before exercise . Participants performed three maximal isometric voluntary contractions ( MVC ) of the knee extensors while determining the central activation ratio by superimposing electrical stimulation both pre-ingestion and post-exercise , followed by a 50-s sustained maximal contraction in which force , EMG amplitude , and muscle fibre conduction velocity were assessed . Plasma pH , blood base excess , and plasma HCO3 were higher ( P < 0.01 ) during the NaHCO3 trial . After cycling , muscle fibre conduction velocity was higher ( P < 0.05 ) during the 50-s sustained maximal contraction with NaHCO3 than with placebo ( 5.1 m · s−1 , s = 0.4 vs. 4.2 m · s−1 , s = 0.4 ) while the EMG amplitude remained the same . Force decline rate was less ( P < 0.05 ) during alkalosis-sustained maximal contraction and no differences were shown in central activation ratio . These data indicate that induced metabolic alkalosis can increase muscle fibre conduction velocity following prolonged submaximal cycling |
11,750 | 29,282,846 | Analysis for adequate stimulation parameters was not significantly different , and there was no effect on disability . | null | null |
11,751 | 16,856,093 | The six included studies suggested that counseling approaches might have beneficial effects for the treatment of cannabis dependence .
Group and individual sessions of cognitive behavioral therapy ( CBT ) had both efficacy for the treatment of cannabis dependence and associated problems , CBT produced better outcomes than a brief intervention when CBT was delivered in individual sessions .
Abstinence rates were relatively small overall but favored the individual CBT 9-session ( or more ) condition .
All included trials reported a statistically significant reductions in frequency of cannabis use and dependence symptoms .
But other measures of problems related to cannabis use were not consistently different .
The studies comparing different therapeutic modalities raise important questions about the duration , intensity and type of treatment .
However , the low abstinence rate indicated that cannabis dependence is not easily treated by psychotherapies in outpatient setting | BACKGROUND Cannabis use disorder is the most common illicit substance use disorder in general population .
Despite that , only a minority seek assistance from a health professional , but the dem and for treatment is now increasing internationally .
Trials of treatment have been published but to our knowledge , there is no published systematic review .
OBJECTIVES To evaluate the efficacy of psychosocial interventions for cannabis abuse or dependence . | An interactive CD-ROM program design ed to reduce adolescent substance use was developed and evaluated . The program uses video vignettes to teach refusal skills and socially acceptable responses to substance use situations , specifically offers of marijuana . In a r and omized pretest-to-posttest experiment with 74 public school students from six classes in three high schools , significant changes were observed at posttest on ( 1 ) the adolescent 's personal efficacy to refuse the offer of marijuana , ( 2 ) the adolescent 's intention to refuse marijuana if offered , and ( 3 ) the adolescent 's perceptions of the social norms associated with substance use and the importance of respecting another 's decision to refuse a drug offer . In addition , adolescents in the treatment condition were able to recall approximately 50 % of the portrayed refusal strategies . Findings are discussed with regard to the potential benefits of an interactive multimedia approach for conducting substance use interventions We sought to characterize attrition-related characteristics of three subgroups of adults ( i.e. early dropouts , late dropouts , treatment completers ) who had participated in a marijuana-dependence treatment outcome study involving two alternative forms of outpatient group counseling . Early dropouts were younger , earned less income , were more likely to rent rather than own their domiciles , were less able to pay bills , and had a higher level of psychological distress than was the case with treatment completers . Late dropouts and completers were quite similar on a number of measures ( e.g. , age , income , home ownership , ability to pay bills , psychological stress level , confidence in being abstinent in the future ) , yet the lower rates of abstinence in the late dropouts largely resembled the treatment outcomes of early dropouts . The findings suggest that attrition prevention in the early phase of counseling ought to focus on motivational ambivalence as well as assisting the client in dealing with schedule conflicts or financial impediments to continued involvement . In the later stage of counseling , attrition reduction is more likely to be accomplished through efforts to better underst and and address the client 's dissatisfaction with treatment components delivered at that stage AIMS Our objective was to identify client characteristics and other factors associated with pre-treatment drop-out by people with marijuana dependence . DESIGN AND PARTICIPANTS Data from the Marijuana Treatment Project 's screening assessment were used to examine correlates of pre-treatment drop-out . Information from all eligible study participants ( n = 813 ) ( i.e. those who were interested in receiving treatment for their marijuana dependence and were determined to be eligible for the r and omized treatment efficacy trial ) was used to examine differences between the 450 participants who initiated treatment ( by enrolling in the trial ) and the 363 individuals who declined enrollment . SETTING The study was conducted at three community-based outpatient treatment facilities in Farmington , CT , Seattle , WA and Miami , FL . MEASUREMENTS The information gathered in the screening interview included demographic characteristics , residential stability variables , employment and education history and referral source . Substance use variables included the number of days and the number of times per day marijuana was used , self-perceived dependence on marijuana , alcohol or other drugs , other drug use history and current treatment ( i.e. substance abuse , medical , psychiatric ) situation . FINDINGS Stepwise logistic regression was conducted to confirm variables associated with treatment initiation in bivariate analyses . Pre-treatment drop-out was associated with being younger , unmarried , unemployed , less educated and Asian American or Native American . It was also associated with self-perceived dependence on marijuana and use of other drugs . CONCLUSIONS By recognizing demographic and substance use factors that may serve as barriers for individuals accessing treatment for marijuana dependence , clinicians may target clients with these characteristics proactively to encourage treatment initiation and subsequent attendance The effects of fasting on the intake and subjective effects of marijuana were studied in five marijuana smokers . A within-subjects design was used in which subjects smoked either active ( 0.8 and 3.6 % THC ) or placebo ( 0.0 % THC ) marijuana after eating normally or after fasting for 24 hr . Six experimental sessions were conducted in a r and omized order . Each 3-hr . session consisted of two periods : a sampling period in which subjects took 4 controlled puffs from a cigarette of a given potency , followed about one hour later by a 30-min . self-administration period , in which subjects could smoke as much or as little of the sample d marijuana as desired . Subjective and physiological measures ( i.e. , carbon monoxide level and heart rate ) were assessed before and 5 , 20 , and 60 min . after the four puffs during the sampling period . During the self-administration period , the number of puffs taken was recorded . Dose-dependent effects of marijuana , such as elevated heart rate and “ high ” ratings , were observed during the sampling period , but these effects of marijuana were not affected by the feeding manipulation . Subjects varied widely in their marijuana self-administration , but self-administration was not systematic ally affected by fasting . We conclude that an acute period of food deprivation does not affect the mood-altering effects of different potencies of marijuana . We could not adequately demonstrate whether fasting increases the reinforcing efficacy of marijuana , since self-administration rate of active marijuana did not exceed that of placebo marijuana self-administration One hundred and fifty five drug-dependent women in an urban hospital emergency room in Detroit , Michigan , were the subjects for this 3-year exploratory field study . Subjects were women who told the emergency room staff that while they wanted assistance with their presenting health problems , they wanted no assistance with their drug addiction . The women were r and omly assigned to either the experimental or control study group . Both groups received a pretest in the emergency room , a posttest between 8 and 12 weeks after their emergency room visit , and a follow-up test 6 months after the posttest . In addition , the experimental women were seen by project nurses , primarily in their homes , for a maximum of eight visits on a once-a-week basis . The experimental women were treated using " Personalized Nursing , " a nursing intervention model , which focused on providing assistance for client-identified concerns . It was hypothesized that interaction with the Personalized Nursing Intervention Model would be associated with : a decrease in daily drug cost and a decrease in perceived stress . Results show that while there were no differences between the study groups at the pretest interview , the experimental group reported a lower daily drug cost ( F(1 , 95 ) = 2.90 ; p = 0.09 ) , a lower daily heroin cost ( U = 165 ; p = .01 ) , less perceived stress ( F(1 , 84 ) = 3.00 ; p = .09 ) and emotional distress ( F(1 , 83 ) = 3.70 ; p = .06 ) than control subjects at the 8-week posttest . The experimental subjects also reported less perceived stress ( t(65 ) = -2.35 ; p = .02 ) at 6-month follow-up than control subjects . It was found that results could be improved if members of the experimental clients ' social networks were treated simultaneously and if project nurses were correctly utilizing the model . Implication s for substance abuse treatment programs are discussed . The encouraging results of this exploratory study warrant follow-up and replication This study investigated the efficacy of brief strategic family therapy ( BSFT ) with Hispanic behavior problem and drug using youth , an underrepresented population in the family therapy research literature . One hundred twenty-six Hispanic families with a behavior problem adolescent were r and omly assigned to 1 of 2 conditions : BSFT or group treatment control ( GC ) . Results showed that , compared to GC cases , BSFT cases showed significantly greater pre- to post-intervention improvement in parent reports of adolescent conduct problems and delinquency , adolescent reports of marijuana use , and observer ratings and self reports of family functioning . These results extend prior findings on the efficacy of family interventions to a difficult to treat Hispanic adolescent sample BACKGROUND The present study addresses diffusion of a psychosocial-based substance abuse prevention program , including : ( a ) teacher adoption , implementation , and maintenance ; ( b ) teacher characteristics associated with implementation ; ( c ) the relationship between integrity of program delivery and program outcomes ; and ( d ) the effectiveness of teacher training and school principal involvement in increasing implementation . METHODS Participants were teachers ( n = 60 ) , school principals ( n = 25 ) , and fifth- grade students ( n = 1147 ) from four Los Angeles area school districts . Districts were r and omly assigned to an intensive or brief teacher training condition . Schools were r and omly assigned to a principal-intervention or a no-principal-intervention condition . Assessment s included teacher and principal self-reports , classroom observations of program delivery , and evaluation of immediate program outcomes . RESULTS During the first year , 78 % of trained teachers implemented one or more program lessons . During the second year , only 25 % maintained implementation of the program . Implementors reported fewer years of teaching experience and stronger self-efficacy , enthusiasm , preparedness , teaching methods compatibility , and principal encouragement than did nonimplementors . The principal intervention increased rates of implementation , but the intensive teacher training did not . Integrity of program delivery was positively associated with immediate program outcomes . CONCLUSIONS Program implementation was highly variable , suggesting that widespread teacher use of psychosocial-based programs can not be taken for granted . Strategies for increasing implementation and maintenance need to be developed R and om assignment was made of 182 clinical ly referred marijuana- and alcohol-abusing adolescents to one of three treatments : multidimensional family therapy ( MDFT ) , adolescent group therapy ( AGT ) , and multifamily educational intervention ( MEI ) . Each treatment represented a different theory base and treatment format . All treatments were based on a manual and were delivered on a once-a-week outpatient basis . The therapists were experienced community clinicians trained to model-specific competence prior to the study and then supervised throughout the clinical trial . A theory-based multimodal assessment strategy measured symptom changes and prosocial functioning at intake , termination , and 6 and 12 months following termination . Results indicate improvement among youths in all three treatments , with MDFT showing superior improvement overall . MDFT participants also demonstrated change at the 1-year follow-up period in the important prosocial factors of school/academic performance and family functioning as measured by behavioral ratings . Results support the efficacy of MDFT , a relatively short-term , multicomponent , multitarget , family-based intervention in significantly reducing adolescent drug abuse and facilitating adaptive and protective developmental processes The increasing dem and for cannabis dependence treatment has led to the identification of significant gaps in the knowledge of effective interventions . A r and omized controlled trial of brief cognitive-behavioral interventions ( CBT ) for cannabis dependence was undertaken to address this issue . A total of 229 participants were assessed and allocated to either a 6-session CBT program , a single-session brief intervention , or a delayed-treatment control group . This paper demonstrates that individuals with cannabis use disorder will present for a brief intervention program . While they report similar patterns of cannabis use to nontreatment sample s , they report a range of serious health and psychosocial consequences . While they appear relatively socially stable , they typically demonstrated severe cannabis dependence and significantly elevated levels of psychological distress , with the most commonly cited reason for cannabis use being stress relief . There were clinical ly relevant gender differences among the sample . This study provides more evidence of the dem and for , and nature of issues relevant to , interventions for cannabis use disorders , and supports the need for further research into how best to assist individuals with these disorders We have examined whether practitioner ratings ( immediately post-intervention ) or other recorded characteristics of a single-session 1-hour motivational intervention were predictive of 3-month cannabis use outcome . In the context of a cluster r and omized trial involving 200 non help-seeking illegal drug users ( age range 16 - 20 ) , 105 were r and omized to the intervention , of whom 97 ( 92 % ) were interviewed for followup at 3 months , 96 of whom were current cannabis users at study entry . Six intervention characteristics and seven practitioner ratings as well as patterns of self-motivational statements were investigated in relation to substantial change in use , ( which was defined as cessation or reduction by more than 50 % ) . Both practitioner ratings post-session , and also the subject 's own elicited self-motivational statements , were found to be predictive of outcome 3 months later . The strongest predictor of substantial change , however , was simply whether change had been discussed during the session . On the basis of the above findings , it does indeed appear possible for outcome to be predicted by the motivational interviewing practitioner immediately following delivery of the intervention , on the basis of simple observations and ratings . This area warrants more specific study This study presents one-year follow-up data from an evaluation study testing the effectiveness of a cognitive-behavioral substance abuse prevention approach which emphasizes the teaching of social resistance skills within the larger context of an intervention design ed to enhance general social and personal competence . The follow-up study involved 998 eighth grade rs from 10 suburban New York junior high schools . Two schools were assigned to each of the following conditions ( a ) peer-led intervention , ( b ) peer-led intervention with booster sessions , ( c ) teacher-led intervention , ( d ) teacher-led intervention with booster sessions , and ( e ) control . The original intervention was implemented in the seventh grade ; the booster intervention was implemented during the eighth grade . Results indicate that this type of prevention strategy , when implemented by peer leaders in the seventh grade and when additional booster sessions are provided during the eighth grade , can reduce tobacco , alcohol , and marijuana use . Similar effects are evident for females when the prevention program is implemented with fidelity by classroom teachers . Moreover , the prevention program is also capable of producing a significant impact on several hypothesized mediating variables OBJECTIVE To evaluate the long-term efficacy of a school-based approach to drug abuse prevention . DESIGN R and omized trial involving 56 public schools that received the prevention program with annual provider training workshops and ongoing consultation , the prevention program with videotaped training and no consultation , or " treatment as usual " ( ie , controls ) . Follow-up data were collected 6 years after baseline using school , telephone , and mailed surveys . PARTICIPANTS A total of 3597 predominantly white , 12th- grade students who represented 60.41 % of the initial seventh- grade sample . INTERVENTION Consisted of 15 classes in seventh grade , 10 booster sessions in eighth grade , and five booster sessions in ninth grade , and taught general " life skills " and skills for resisting social influences to use drugs . MEASURES Six tobacco , alcohol , and marijuana use self-report scales were recorded to create nine dichotomous drug use outcome variables and eight polydrug use variables . RESULTS Significant reductions in both drug and polydrug use were found for the two groups that received the prevention program relative to controls . The strongest effects were produced for individuals who received a reasonably complete version of the intervention -- there were up to 44 % fewer drug users and 66 % fewer polydrug ( tobacco , alcohol , and marijuana ) users . CONCLUSIONS Drug abuse prevention programs conducted during junior high school can produce meaningful and durable reductions in tobacco , alcohol , and marijuana use if they ( 1 ) teach a combination of social resistance skills and general life skills , ( 2 ) are properly implemented , and ( 3 ) include at least 2 years of booster sessions AIMS This paper provides a description of the rationale , study design , treatments and assessment procedures used in the Cannabis Youth Treatment ( CYT ) experiment . DESIGN CYT was design ed to ( a ) test the relative effectiveness , cost and benefit-cost of five promising treatment interventions under field conditions and ( b ) provide evidence based manual-guided models of these interventions to the treatment field . SETTING The study involved two community-based treatment programs and two major medical centers . PARTICIPANTS Participants were 600 adolescents recruited from the regular intake who were between the ages of 12 and 18 , had used marijuana in the past 90 days , and met one or more criteria of dependence or abuse . INTERVENTIONS Participants were r and omly assigned to one of five interventions : Motivational Enhancement Therapy ( MET ) , Cognitive Behavioral Therapy ( CBT ) , Family Support Network ( FSN ) , Adolescent Community Reinforcement Approach ( ACRA ) , or Multidimensional Family Therapy ( MDFT ) . MEASUREMENTS Self-report data were collected at intake , 3 , 6 , 9 and 12 months post discharge using the Global Appraisal of Individual Needs ( GAIN ) , as well as several supplemental self-reports , collateral reports , urine testing , and service logs . FINDINGS This paper reports on the study 's implementation including the psychometric properties of the measures ( alphas over 0.8 ) , validity of self-report ( kappa over 0.6 ) , high rates of treatment completion ( 81 % completed two or more months ) , and high rates of follow-up ( over 94 % per wave ) . CONCLUSIONS The feasibility of implementing the CYT manual-guided treatment and quality assurance model in community-based adolescent treatment programs is discussed AIMS Risk factors among adolescent substance abusers have been shown to correlate with substance use severity . Characteristics related to severity , such as demographic and family factors , peer influences , psychiatric co-morbidity and HIV risk behaviors , are examined for a sample of adolescent cannabis users entering treatment . DESIGN These data are from a clinical trial study utilizing blocked r and om assignment of clients to one of five treatment conditions . The study targeted adolescents entering outpatient treatment for primarily cannabis abuse or dependence . SETTING Treatment and research facilities in four metropolitan areas of the US were used to recruit study participants . Treatment was delivered in outpatient drug-free setting s. PARTICIPANTS Participants were 600 clients , ages 12 - 18 , admitted to outpatient substance abuse treatment programs for cannabis problems , 96 % with DSM-IV diagnoses of substance abuse or dependence , with the remaining 4 % having at least one symptom of dependence plus significant problems indicating need for treatment . MEASUREMENTS The Global Appraisal of Individual Needs ( GAIN ) was used to collect the information presented in this paper . The GAIN incorporates DSM-IV criteria for substance use disorders , conduct disorder and attention deficit hyperactivity disorder , as well as dimensional ( scale ) measures for physical and mental health . FINDINGS All participants reported at least one symptom of substance use disorders , and 46 % met the DSM-IV criteria for substance dependence , while 50 % met criteria for a diagnosis of abuse . Only 20 % of the participants perceived any need for help with problems associated with their drug or alcohol use . Clients participating in the study typically presented multiple problems at treatment entry , most often including conduct disorder , attention deficit hyperactivity disorder ( ADHD ) , internal ( mental ) distress , and physical health distress . The co-occurrence of conduct disorder and ADHD was found in 30 % of the sample . Clients meeting criteria for substance dependence tended to have more co-occurring problems and significantly less denial at admission . CONCLUSIONS The characteristics of this sample exemplify the complex nature of adolescent substance use and abuse among adolescents entering outpatient treatment programs . Patterns of co-occurring problems are at rates comparable to those found in other clinical studies . Those with more severe substance use disorders tend to manifest more problems of social functioning , more mental health problems , and physical health problems . Implication s of these findings are discussed in terms of treatment needs , challenges , and prognostic implication Young marijuana abusers rarely seek treatment themselves and are difficult to engage in treatment when referred by social agencies . To evaluate treatment engagement strategies in this population , 65 young probation-referred marijuana abusers were r and omly assigned to either three-session motivational enhancement therapy ( MET alone ) or three-session MET plus contingency management ( MET/CM ) , with vouchers for treatment attendance . A significantly higher number of participants in the MET/CM condition completed the three-session intervention as compared with MET alone . Participants in both conditions reported significant reductions in marijuana use and improvement in legal problems . These findings suggest that young marijuana abusers benefit from scientifically vali date d treatments AIMS To evaluate the agreement between adolescent self-reported cannabis use , " on-site " qualitative urine screening , and quantitative laboratory testing . DESIGN A cross-sectional study of intake and follow-up data from 248 adolescents entering substance abuse treatment for cannabis use disorders ( abuse or dependence ) . This is part of the multi-site cooperative agreement Cannabis Youth Treatment study . SETTING Data collected from adolescents r and omly assigned to one of five outpatient treatments at four sites : Operation PAR , Inc. , Florida ; Chestnut Health Systems , Illinois ; University of Connecticut Health Center , Connecticut ; and Children 's Hospital of Philadelphia , Pennsylvania . PARTICIPANTS The data represent 248 unique individuals from a sample of 297 adolescents ranging in age from 12 to 18 years . MEASUREMENTS Prevalence , agreement , kappa , sensitivity , specificity , positive and negative predictive value . FINDINGS The self-report rates were higher at intake than either urine test ( 82.4 % vs. 77.0 % vs. 52.7 % ) , but both lower and higher at the 3-month follow-up ( 55.5 % vs. 70.0 % vs. 47.3 % ) and 6-month follow-up ( 60.2 % vs. 73.5 % vs. 55.8 % ) . The disagreements went in both directions and the kappa coefficients were only in the moderate range ( 0.4 ) . Over two-thirds of these frequent cannabis users tested positive when they said they had not used in 1 week and one-third tested positive even though they said it had been more than 4 weeks since last use . CONCLUSIONS The findings suggest both the advantages of multiple sources of information and the need for further work on the latency of cannabis metabolites in clinical population This study evaluated the efficacy of 2 brief interventions for cannabis-dependent adults . A multisite r and omized controlled trial compared cannabis use outcomes across 3 study conditions : ( a ) 2 sessions of motivational enhancement therapy ( MET ) ; ( b ) 9 sessions of multicomponent therapy that included MET , cognitive-behavioral therapy , and case management ; and ( c ) a delayed treatment control ( DTC ) condition . Participants were 450 adult marijuana smokers with a Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; American Psychiatric Association , 1994 ) diagnosis of cannabis dependence . Assessment s were conducted at baseline , and at 4 , 9 , and 15 months postr and omization . The 9-session treatment reduced marijuana smoking and associated consequences significantly more than the 2-session treatment , which also reduced marijuana use relative to the DTC condition . Most differences between treatments were maintained over the follow-up period . Discussion focuses on the relative efficacy of these brief treatments and the clinical significance of the observed changes in marijuana use AIMS Recent findings regarding the prevalence of marijuana dependence and associated consequences indicate the need for empirically vali date d treatments for this population . The Marijuana Treatment Project ( MTP ) was a multi-site study of two treatments for adults with marijuana dependence . DESIGN Participants ( N= 450 ) were r and omly assigned to one of three conditions at each of three sites : 1 ) a 9-session cognitive behavioral treatment ( CBT ) with motivational enhancement therapy ( MET ) and case management ( CM ) components ; 2 ) a 2-session MET intervention ; or 3 ) a delayed treatment control ( DTC ) . SETTING The study was conducted in outpatient drug treatment clinics in three U.S. cities . PARTICIPANTS Participants were individuals aged 18 or over who met diagnostic criteria for cannabis dependence and who voluntarily presented for treatment . MEASUREMENT Study variables included DSM-IV dependence criteria , timeline follow-back assessment of drug use , Addiction Severity Index composite scores , and problems related to marijuana use . FINDINGS Participants were daily users , who smoked marijuana multiple times per day , and had been doing so for more than 15 years . They reported multiple dependence symptoms and negative consequences related to marijuana use . Approximately 32 % of the sample was female , and 30 % of the sample was either Hispanic ( 17 % ) , African American ( 12 % ) , or of mixed racial background s ( 1 % ) . CONCLUSIONS The multi-site nature of the MTP allowed for the recruitment of a more ethnically and gender diverse sample than had been studied previously but there were few differences in the clinical characteristics of participants at the geographically and sociodemographically diverse study sites OBJECTIVE The study examined the association between fidelity of programs to the assertive community treatment model and client outcomes in dual disorders programs . METHODS Assertive community treatment programs in the New Hampshire dual disorders study were classified as low-fidelity programs ( three programs ) or high-fidelity programs ( four programs ) based on extensive longitudinal process data . The study included 87 clients with a dual diagnosis of severe mental illness and a comorbid substance use disorder . Sixty-one clients were in the high-fidelity programs , and 26 were in the low-fidelity programs . Client outcomes were examined in the domains of substance abuse , housing , psychiatric symptoms , functional status , and quality of life , based on interviews conducted every six months for three years . RESULTS Clients in the high-fidelity assertive community treatment programs showed greater reductions in alcohol and drug use and attained higher rates of remission from substance use disorders than clients in the low-fidelity programs . Clients in high-fidelity programs had higher rates of retention in treatment and fewer hospital admissions than those in low-fidelity programs . No differences between groups were found in length of hospital stays and other residential measures , psychiatric symptoms , family and social relations , satisfaction with services , and overall life satisfaction . CONCLUSIONS Faithful implementation of , and adherence to , the assertive community treatment model for persons with dual disorders was associated with superior outcomes in the substance use domain . The findings underscore the value of measures of model fidelity , and they suggest that local modifications of the assertive community treatment model or failure to comply with it may jeopardize program success The effectiveness of a 20 session cognitive-behavioral approach to substance abuse prevention was tested on seventh grade students ( n = 1,311 ) from 10 suburban New York junior high schools . The prevention strategy attempted to reduce intrapersonal pressure to smoke , drink excessively , or use marijuana by fostering the development of general life skills as well as teaching students tactics for resisting direct interpersonal pressure to use these substances . Additionally , this study was design ed to compare the relative effectiveness of this type of prevention program when implemented by either older peer leaders or regular classroom teachers . Results indicated that the prevention program had a significant impact on cigarette smoking , excessive drinking , and marijuana use when implemented by peer leaders . Furthermore , significant changes were also evident with respect to selected cognitive , attitudinal , and personality predisposing variables in a direction consistent with non-substance use . These results provide further support for the efficacy of a broad-spectrum smoking prevention strategy and tentative support for its applicability to the prevention of other forms of substance abuse This study examined the long-term substance use outcomes of 2 brief interventions design ed for general population families of young adolescents . Thirty-three public schools were r and omly assigned to 3 conditions : the 5-session Preparing for the Drug Free Years Program , the 7-session Iowa Strengthening Families Program , and a minimal contact control condition . The pretest involved 667 6th grade rs and their families . Assessment s included multiple measures of initiation and current use of alcohol , tobacco , and marijuana . Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade . Significant intervention-control differences in initiation and current use were found for both interventions . It is concluded that brief family skills-training interventions design ed for general population s have the potential to reduce adolescent substance use and thus have important public health implication The increasing dem and for treatment for cannabis dependence in Australia and internationally has led to the identification of significant gaps in knowledge of effective interventions . A r and omized controlled trial of brief cognitive-behavioral interventions ( CBT ) for cannabis dependence was undertaken to address this issue . A total of 229 participants were assessed and r and omly assigned to either a six-session CBT program ( 6CBT ) , a single-session CBT intervention ( 1CBT ) , or a delayed-treatment control ( DTC ) group . Participants were assisted in acquiring skills to promote cannabis cessation and maintenance of abstinence . Participants were followed-up a median of 237 days after last attendance . Participants in the treatment groups reported better treatment outcomes than the DTC group . They were more likely to report abstinence , were significantly less concerned about their control over cannabis use , and reported significantly fewer cannabis-related problems than those in the DTC group . Those in the 6CBT group also reported more significantly reduced levels of cannabis consumption than the DTC group . While the therapist variable had no effect on any outcome , a secondary analysis of the 6CBT and 1CBT groups showed that treatment compliance was significantly associated with decreased dependence and cannabis-related problems . This study supports the attractiveness and effectiveness of individual CBT interventions for cannabis use disorders and the need for multisite replication trials Students ( N = 4,466 ) attending 56 schools in New York State were involved in a 3-year study testing the effectiveness of a cognitive-behavioral approach to substance abuse prevention . In a r and omized block design , schools were assigned to receive ( a ) the prevention program with formal provider training and implementation feedback , ( b ) the prevention program with videotaped provider training and no feedback , or ( c ) no treatment . After pretest equivalence and comparability of conditions with respect to attrition were established , students who received at least 60 % of the prevention program ( N = 3,684 ) were included in analyses of program effectiveness . Significant prevention effects were found for cigarette smoking , marijuana use , and immoderate alcohol use . Prevention effects were also found for normative expectations and knowledge concerning substance use , interpersonal skills , and communication skills AIMS To evaluate the construct and predictive validity of six different subtyping classifications selected on the basis of their empirical support in the literature on adolescent substance abuse . METHODS Typological data were collected from a heterogeneous sample of 600 adolescents presenting for marijuana treatment . The classification schemes were gender , onset age , family history , externalizing disorders , internalizing disorders and temperament . Subgroups were compared in terms of substance use frequency , substance abuse problems , social support for substance use , family conflict , school problems and negative peer associations . RESULTS Each of the categorical classification schemes differentiated subtypes significantly on some or all of the construct validation measures after controlling for demographic factors , thereby indicating that each has valuable explanatory power from a theoretical perspective . Externalizing disorders , onset age , difficult temperament and internalizing disorders continued to add unique variance to discrimination after the effects of the other subtypes had been removed . At 12-month follow-up there were no differences between subtypes on substance use frequency , but adolescents with higher levels of externalizing disorders and internalizing disorders continued to experience more substance use problems . CONCLUSION Categorical subtypes may have particular relevance to the development of treatment interventions as well as prevention measures This study tested the ability of sets of demographic , socioeconomic , marijuana use/abuse , psychological distress , and self-efficacy variables to predict posttreatment indices of marijuana intake and problems related to use . Subjects were 167 adults who participated in one of two outpatient treatments for marijuana dependence and completed the 3- , 6- , and 12-month posttreatment follow-ups . Only pretreatment marijuana quantity-frequency of intake and self-efficacy variables made significant and consistent contributions to the regression equations predicting posttreatment frequency of use . In contrast , socioeconomic and severity of abuse indicators predicted posttreatment marijuana-related problems . Contrary to social cognitive theory ( B and ura , 1986 ) , there was no evidence that self-efficacy mediated the effects of other predictors . Results are discussed in terms of the specificity of predictor- outcome relationships and the need for improvements in self-efficacy measurement There is a noticeable lack of targeted treatment options for marijuana dependence , in particular pharmacologic approaches . This is the first study evaluating a targeted pharmacologic approach for marijuana dependence . The goals of the study were to determine if such patients would seek pharmacologic treatment , whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients , and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence . We found that marijuana-dependent patients will seek treatment , and such patients can be adequately maintained in a pharmacologic trial . Regardless of treatment group , patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability . Given the lack of proven effective treatments for marijuana dependence , pharmacotherapies should be sought . The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group The five manual-guided treatment models tested in the Cannabis Youth Treatment study funded by the Center for Substance Abuse Treatment are described . The five models include ( a ) a 6-week intervention consisting of two sessions of individual motivational enhancement therapy plus three sessions of group cognitive behavioral therapy ( MET/CBT5 ) ; ( b ) a 12-week intervention consisting of two sessions of motivational enhancement therapy plus 10 sessions of group cognitive behavioral therapy treatment ( MET/CBT12 ) ; ( c ) a 12-week intervention consisting of MET/CBT12 plus the family support network ( FSN ) , a multi-component intervention that includes parent education , family therapy and case management ; ( d ) a 12-week intervention based on the adolescent community reinforcement approach ( ACRA ) , an individual behavioral treatment approach design ed to help adolescents and their parents reshape their environment and learn new skills ; and ( e ) multi-dimensional family therapy ( MDFT ) , a multi-faceted , developmentally and context ually oriented family-based model targeting individual , family and social systems . For each model , we describe the treatment background and /or its empirical support , its theoretical underpinnings , its goals and proposed treatment mechanism and the structure and content of each treatment . Procedures used for maintaining treatment fidelity and monitoring quality assurance are also described . These interventions represent the first readily available , manual-guided interventions to be evaluated in a large r and omized field study for this population . Consequently , these manuals have the potential to advance treatment and research for adolescents with substance use disorders |
11,752 | 24,308,029 | Interactive KT education for health care providers has a positive effect on patients ' function , but its benefits for other health provider- and patient-related outcomes are inconsistent .
Interactive education for patients leads to improvements in knowledge and function .
Little research evidence supports the effectiveness of structural changes in health systems and quality improvement processes or coordination of care .
CONCLUSIONS KT interventions incorporating interactive education in chronic noncancer pain led to positive effects on patients ' function and knowledge about pain . | BACKGROUND Reliable evidence detailing effective treatments and management practice s for chronic noncancer pain exists .
However , little is known about which knowledge translation ( KT ) interventions lead to the uptake of this evidence in practice .
OBJECTIVES To conduct a systematic review of the effectiveness of KT interventions for chronic noncancer pain management . | Background There has been considerable interest recently in developing and evaluating interventions to increase research use by clinicians . However , most work has focused on medical practice s ; and nursing is not well represented in existing systematic review s. The purpose of this article is to report findings from a systematic review of interventions aim ed at increasing research use in nursing . Objective To assess the evidence on interventions aim ed at increasing research use in nursing . Methods A systematic review of research use in nursing was conducted using data bases ( Medline , CINAHL , Healthstar , ERIC , Cochrane Central Register of Controlled Trials , and Psychinfo ) , grey literature , ancestry search ing ( Cochrane Data base of Systematic Review s ) , key informants , and manual search ing of journals . R and omized controlled trials and controlled before- and after- studies were included if they included nurses , if the intervention was explicitly aim ed at increasing research use or evidence -based practice , and if there was an explicit outcome to research use . Method ological quality was assessed using pre-existing tools . Data on interventions and outcomes were extracted and categorized using a pre-established taxonomy . Results Over 8,000 titles were screened . Three r and omized controlled trials and one controlled before- and after- study met the inclusion criteria . The method ological quality of included studies was generally low . Three investigators evaluated single interventions . The most common intervention was education . Investigators measured research use using a combination of surveys ( three studies ) and compliance with guidelines ( one study ) . Research er-led educational meetings were ineffective in two studies . Educational meetings led by a local opinion leader ( one study ) and the formation of multidisciplinary committees ( one study ) were both effective at increasing research use . Conclusion Little is known about how to increase research use in nursing , and the evidence to support or refute specific interventions is inconclusive . To advance the field , we recommend that investigators : ( 1 ) use theoretically informed interventions to increase research use , ( 2 ) measure research use longitudinally using theoretically informed and psychometrically sound measures of research use , as well as , measuring patient outcomes relevant to the intervention , and ( 3 ) use more robust and method ologically sound study design s to evaluate interventions . If investigators aim to establish a link between using research and improved patient outcomes they must first identify those interventions that are effective at increasing research use BACKGROUND AND PURPOSE An active strategy was developed for the implementation of the clinical guidelines on physical therapy for patients with low back pain . The effect of this strategy on patients ' physical functioning , coping strategy , and beliefs regarding their low back pain was studied . SUBJECTS One hundred thirteen primary care physical therapists treated a total of 500 patients . METHODS The physical therapists were r and omly assigned to 1 of 2 groups . The control group received the guidelines by mail ( st and ard passive method of dissemination ) . The intervention group , in contrast , received an additional active training strategy consisting of 2 sessions with education , group discussion , role playing , feedback , and reminders . Patients with low back pain , treated by the participating therapists , completed question naires on physical functioning , pain , sick leave , coping , and beliefs . RESULTS Physical functioning and pain in the 2 groups improved substantially in the first 12 weeks . Multilevel longitudinal analysis showed no differences between the 2 groups on any outcome measure during follow-up . DISCUSSION AND CONCLUSION The authors found no additional benefit to applying an active strategy to implement the physical therapy guidelines for patients with low back pain . Active implementation strategies are not recommended if patient outcomes are to be improved & NA ; This paper presents the results of a detailed study of the pain epidemiology and health related quality of life ( HRQL ) in 150 chronic non‐malignant pain patients consecutively referred to a Danish multidisciplinary pain center . Mean pain severity was 71.6 ( SD=18.5 ) on the VAS scale . Forty‐two percent reported poor quality of sleep . HRQL was evaluated with the Medical Outcome Study ‐Short Form ( SF‐36 ) , the Hospital Anxiety and Depression scale ( HAD ) and the Psychological General Well‐Being Scale ( PGWB ) . Compared with the normal population ( NP ) both SF‐36 scores and PGWB scores were significantly reduced ( P<0.001 ) indicating that physical , psychological and social well‐being were severely reduced . On the HAD scale 58 % were found to have a depressive or anxiety disorder . Statistically significant but modest correlations were found between pain severity and HRQL . Psychological and social well‐being was closely correlated . Sixty‐three percent of the referred patients had neurogenic pain conditions . Of these , only 25 % were treated with antidepressants or anticonvulsants at referral . Seventy‐three percent were treated with opioids at referral . Mean opioid consumption was 64 mg of morphine per day ( range 1–280 mg ) . Compared with the NP the chronic pain patients had used the health care system five times more often in the years prior to referral ( P<0.001 ) . The study confirms the severe multidimensional impact of chronic pain and demonstrates that HRQL of chronic non‐malignant pain patients is among the lowest observed for any medical condition Purpose The Canadian STOP-PAIN Project was design ed to document the human and economic burden of chronic pain in individuals on waitlists of Multidisciplinary Pain Treatment Facilities ( MPTF ) . This paper describes the societal costs of their pain . Methods A subgroup of 370 patients was selected r and omly from The Canadian STOP-PAIN Project . Participants completed a self-administered costing tool ( the Ambulatory and Home Care Record ) on a daily basis for three months . They provided information about publicly financed re sources , such as health care professional consultations and diagnostic tests as well as privately financed costs , including out-of-pocket expenditures and time devoted to seeking , receiving , and providing care . To determine the cost of care , re sources were valued using various costing methods , and multivariate linear regression was used to predict total cost . Results Overall , the median monthly cost of care was $ 1,462 ( CDN ) per study participant . Ninety-five percent of the total expenditures were privately financed . The final regression model consisted of the following determinants : educational level , employment status , province , pain duration , depression , and health-related quality of life . This model accounted for 35 % of the variance in total expenditure ( P < 0.001 ) . Conclusion The economic burden of chronic pain is substantial in patients on waitlists of MPTFs . Consequently , it is essential to consider this burden when making decisions regarding re source allocation and waitlist assignment for a MPTF . Re source allocation decision-making should include the economic implication s of having patients wait for an assessment and for care . RésuméObjectifLe projet canadien STOP-PAIN a été élaboré afin de documenter le fardeau humain et économique que représentait la douleur chronique pour les personnes se trouvant sur les listes d’attente des établissements pluridisciplinaires de traitement de la douleur ( MPTF – Multidisciplinary Pain Treatment Facilities ) . Cet article décrit les coûts sociétaux de leur douleur . MéthodeUn sous-groupe de 370 patients a été aléatoirement choisi parmi les participants au projet canadien STOP-PAIN . Les participants ont rempli quotidiennement un outil auto-administré de calcul des coûts ( le fichier de soins ambulatoires et à domicile - Ambulatory and Home Care Record ) pendant trois mois . Ils ont fourni des renseignements concernant les res sources financées par le secteur public , comme par exemple les consultations auprès de professionnels de la santé et les tests diagnostiques , ainsi que les coûts privés , notamment les sorties effectives d’argent et le temps consacré à chercher , recevoir et fournir des soins . Afin de déterminer le coût des soins , les res sources ont été estimées à l’aide de plusieurs méthodes de calcul des coûts , et une analyse par régression linéaire multivariée a été appliquée afin d’estimer le coût total . RésultatsGlobalement , le coût mensuel moyen des soins était de 1462 $ ( CDN ) par participant à l’étude . Quatre-vingt-quinze pour cent des dépenses totales étaient prises en charge de façon privée . Le modèle de régression final était composé des déterminantes suivantes : niveau d’éducation , situation d’emploi , province , durée de la douleur , dépression , et qualité de vie par rapport à la santé . Ce modèle a justifié 35 % de la variance des dépenses totales ( P < 0,001 ) . Conclusion Le fardeau économique que représente la douleur chronique est substantiel pour les patients sur les listes d’attente des MPTF . Pour cette raison , il est nécessaire de tenir compte de ce fardeau lors de la prise de décision concernant l’attribution des res sources et l’affectation à la liste d’attente d’un MPTF . La prise de décision concernant l’attribution des res sources devrait inclure les implication s économiques liées à l’attente des patients pour une évaluation de leur état et pour les soins Study Design . A r and omized clinical trial . Objectives . To evaluate long-term clinical and economical effects of a light mobilization program on the duration of sick leave for patients with subacute low back pain . Summary of Background Data . Twelve-month follow-up results from a previous study showed that early intervention with examination at a spine clinic , giving the patients information , reassurance , and encouragement to engage in physical activity as normal as possible had significant effect in reducing sick leave . At 12-month follow-up , 68.4 % in the intervention group were off sick leave , as compared with 56.4 % in the control group . Patients in this study were followed-up for a period of 3 years to investigate possible long-term effects . Material s and Methods . Four hundred fifty-seven patients placed on a sick list for 8 to 12 weeks for low back pain were r and omized into two groups : an intervention group ( n = 237 ) and a control group ( n = 220 ) . The intervention group was examined at a spine clinic and given information and advice to stay active . The control group was not examined at the clinic but was treated within the primary health care . Results . Over the 3 years of observation , the intervention group had significantly fewer days of sickness compensation ( average 125.7 d/person ) than the control group ( 169.6 d/person ) . This difference is mainly caused by a more rapid return to work during the first year . There was no significant difference for the second or third year . In particular , there is no increased risk for reoccurrence of illness from early return to work . At 6-month follow-up , patients in the intervention group were less likely to use bed rest and more likely to use stretching and walking to cope with their back pain compared with the control group . This effect diminished . At 12-month follow-up , the only significant difference between the groups was in the use of stretching . Economic returns of the intervention were calculated in terms of increases in the net present value of production for the society because of the reduction in number of days on sick leave . Net benefits accumulated over 3 years of treating the 237 patients in the intervention group amount to approximately $ 2,822 per person . Conclusions . For patients with subacute low back pain , a brief and simple early intervention with examination , information , reassurance , and encouragement to engage in physical activity as normal as possible had economic gains for the society . The effect occurred during the first year after intervention . There were no significant long-term effects of the intervention . The initial gain obtained during the first year does not lead to any increased costs or increased risks for reoccurrence of illness over the next 2 years OBJECTIVE To assess the prevalence , treatment and impact of chronic pain in Canada . METHODS A stratified r and om sample of 2012 adult Canadians ( weighted by sex , age and region according to 1996 census data ) was surveyed by telephone in 2001 to determine the prevalence of chronic pain , defined as continuous or intermittent pain for at least six months . A second sample of 340 chronic pain sufferers who were taking prescription medication for their pain was studied in detail to determine current therapeutic approaches and to assess the social and economic impact of chronic pain . RESULTS Chronic noncancer pain was reported by 29 % of the respondents , with increased frequency in women and older age groups . The average duration of pain was 10.7 years and the average intensity was 6.3 ( on a scale from 1 to 10 ) , with 80 % reporting moderate or severe pain . Anti-inflammatory agents were prescribed for 49 % of respondents and opioid analgesics were prescribed for 22 % ( two-thirds of these were codeine ) . Almost 70 % were worried about addiction potential , and one-third felt that strong analgesics should be reserved for terminal illnesses . Almost one-half were unable to attend social and family events , and the mean number of days absent from work in the past year due to chronic pain was 9.3 . INTERPRETATION Chronic noncancer pain is common in Canadian adults and has a major social and economic impact . Despite growing evidence supporting the efficacy and safety of major opioid analgesics for chronic noncancer pain , less than 10 % of chronic pain patients taking prescription medication were treated with a major opioid . Chronic pain is undertreated in Canada , and major opioid analgesics are probably underutilized in the management of moderate to severe pain as part of a multidisciplinary treatment program BACKGROUND Similar to other countries worldwide , Scotl and lacked a national view of whether the quality of the physiotherapy management of low back pain was compliant with national guidelines . Anecdotal evidence suggested that st and ards of care varied considerably despite the wide availability of clinical guidelines to clinicians . AIM To develop a framework that supports National Health Service ( NHS ) Scotl and in providing consistently applied high- quality physiotherapy assessment and management of low back pain in line with guideline recommendations . DESIGN Prospect i ve , multicentred national study , data collection and improvement phase . SETTING All NHS boards in Scotl and ( n=14 ) plus two private provider sites . PARTICIPANTS One hundred and eighty-six individual NHS sites and two private providers of services to patients with low back pain . METHOD A national data set was developed from evidence - and consensus-based guideline sources . All sites collected data ( two 5-week periods ) over 1 year ( 2008 - 2009 ) using a web-based data base . This was interspersed by an improvement phase during which required improvements were considered and implemented . Issues were shared through a national network and national meeting . RESULTS Data from 2147 patients showed improvements in the documented physiotherapy management of low back pain over the two cycles . All participants developed and implemented remedial action plans based on the results of the first cycle . CONCLUSION It is possible to implement a framework , which is led nationally but driven and owned locally , supporting physiotherapists in an active programme of locally determined improvement . However , although process and outcome are linked , the direct impact of this initiative on patient outcome is not known Background There are increasing numbers of r and omised trials and systematic review s examining the efficacy of interventions design ed to bring about a change in clinical practice . The findings of this research are being used to guide strategies to increase the uptake of evidence into clinical practice . Knowledge of the outcomes measured by these trials is vital not only for the interpretation and application of the work done to date , but also to inform future research in this exp and ing area of endeavour and to assist in collation of results in systematic review s and meta-analyses . Methods The objective of this review was to identify methods used to measure change in the clinical practice s of health professionals following an intervention aim ed at increasing the uptake of evidence into practice . All published trials included in a recent , comprehensive Health Technology Assessment of interventions to implement clinical practice guidelines and change clinical practice ( n = 228 ) formed the sample for this study . Using a st and ardised data extraction form , one review er ( SH ) , extracted the relevant information from the methods and /or results sections of the trials . Results Measures of a change of health practitioner behaviour were the most common , with 88.8 % of trials using these as outcome measures . Measures that assessed change at a patient level , either actual measures of change or surrogate measures of change , were used in 28.8 % and 36.7 % of studies ( respectively ) . Health practitioners ' knowledge and attitudes were assessed in 22.8 % of the studies and changes at an organisational level were assessed in 17.6 % . Conclusion Most trials of interventions aim ed at changing clinical practice measured the effect of the intervention at the level of the practitioner , i.e. did the practitioner change what they do , or has their knowledge of and /or attitude toward that practice changed ? Less than one-third of the trials measured , whether or not any change in practice , result ed in a change in the ultimate end-point of patient health status Objective : Estimate the impact of diabetes and neuropathic pain on the US workforce . Methods : Data on lost productive time ( LPT ) was collected by telephone interview in a r and om sample of the US population ( N = 36,634 ) . Of 19,075 occupation-eligible working adults included in the analysis , 1003 reported a physician diagnosis of diabetes ; 38 % of these reported numbness or tingling in feet or h and s due to diabetes ( symptom group ) . We compared diabetes respondents with and without symptoms to other respondents for LPT and related cost . Results : Health-related LPT was 18 % higher in the symptom ( P < 0.05 ) and 5 % higher in the non-symptom ( P < 0.05 ) groups versus for those without diabetes . The symptom group lost 1.4 hours of work per week more than the non-symptom group ( P < 0.05 ) . Conclusions : Workers who have diabetes with neuropathic symptoms lose the equivalent of $ 3.65 billion/yr in health-related LPT Learning Objectives Recall the overall magnitude of lsot productive time ( LPT ) and its dollar cost as found in the American Productivity Audit , and the respective contributions of absenteeism and decreased producitivity at work . Be aware of how LPT varies with a number of demographic and workrelated factors . Compare the factors predisposing to LPT for personal and family-related reasons . The American Productivity Audit ( APA ) is a telephone survey of a r and om sample of 28,902 U.S. workers design ed to quantify the impact of health conditions on work . Lost productive time ( LPT ) was measured for personal and family health reasons and expressed in hours and dollars . Health-related LPT cost employers $ 225.8 billion/year ( $ 1685/employee per year ) ; 71 % is explained by reduced performance at work . Personal health LPT was 30 % higher in females and twice as high in smokers ( ≥1 pack/day ) versus nonsmokers . Workers in high-dem and , low-control jobs had the lowest average LPT/week versus the highest LPT for those in low-dem and , high-control jobs . Family health-related work absence accounted for 6 % of all health-related LPT . Health-related LPT costs are substantial but largely invisible to employers . Costs vary significantly by worker characteristics , suggesting that intervention needs vary by specific subgroups Cost estimates of the impact of chronic pain on work have largely focussed on absenteeism , excluding the hidden contribution of reduced work effectiveness to lost productivity . This paper aims to estimate the cost of lost productivity due to chronic pain in Australia , not only in terms of absenteeism but also reduced work effectiveness . Data on chronic pain in Australia and its impact on work were obtained from the 1997 New South Wales Health Survey ( n=17,543 ) and the Northern Sydney Area Pain Study ( n=2,092 ) , both of which were population -based and used r and om-digit dialing sampling methods . This was combined with relevant Australian population and labour force data obtained from the Australian Bureau of Statistics . From this we estimated annual lost productivity costs arising from both chronic pain-related days absent and ' reduced-effectiveness workdays ' . There were estimated to be 9.9 million workdays absent due to chronic pain annually in Australia , equating to a cost of AUD 1.4 billion per annum . Under the assumption that reduced-effectiveness workdays affect productivity costs in the same way as lost work days , the total number of lost workday equivalents was 36.5 million , with the total annual cost of lost productivity due to chronic pain estimated as AUD 5.1 billion per annum . In conclusion , while the impact of reduced work effectiveness on days worked with pain on productivity is uncertain , it has the potential to account for the majority of lost productivity costs associated with chronic pain . Interventions which target working despite pain have the potential to significantly reduce lost productivity costs due to chronic pain Objectives A back school is a m and atory part of the multimodal rehabilitation program for patients with chronic low back pain in Germany . However , no st and ardized and evaluated back school program has been available for routine use . In this study , we report the evaluation of a new back school that was developed based on theories of health behavior , treatment evidence , practice guidelines , and quality criteria for patient education . Methods R and omized controlled trial of patients with low back pain ( n=360 ) in inpatient orthopedic rehabilitation clinic in Germany . Intervention patients received the new back school , whereas control patients a traditional back school ( usual care ) . Illness knowledge ( primary outcome ) and secondary behavioral and health outcomes were assessed at admission , discharge , and 6 and 12 months follow-up . Results Results showed a significant medium between-group treatment effect in patients ' knowledge about back pain at discharge ( & eegr;2=0.081 ) , after 6 ( & eegr;2=0.056 ) , and 12 months ( & eegr;2=0.026 ) . Furthermore , small-to-medium effects were observed among the secondary self-management behaviors , such as physical activity , back exercises , back posture habits , and coping with pain , after 6 and 12 months . Discussion The superior effectiveness of the back school based on a biopsychosocial approach was demonstrated with regard to illness knowledge and self-management behaviors up to 1 year . Thus , the program may be recommended for dissemination within medical rehabilitation OBJECTIVE We performed a prevalence estimate of chronic pain with neuropathic pain ( NeP ) symptoms to determine its frequency and associations with morbidity . DESIGN We conducted a telephone-based survey based upon a r and om sampling of both urban and rural households of the general population in one Canadian province to determine NeP prevalence and its impact upon financial well-being and quality of life . OUTCOME MEASURES Telephonic use of the DN4 question naire ( DN4Q ) , used to identify NeP symptoms in those patients with chronic pain , was vali date d within selected clinical population s of chronic pain . Epidemiological data was obtained for all subjects . EuroQoL (EQ)-5D data estimating quality of life was measured . RESULTS Chronic pain was present in 35.0 % of the surveyed population of 1,207 subjects , with NeP symptoms present in 17.9 % . The NeP group had significantly more pain , was female predominant , had a greater belief of being economically disadvantaged , suffered from more restrictions in mobility and in usual activities , and had overall lower EQ-5D utility scores compared with subjects with non-NeP. DN4Q validation demonstrated that pain entities not normally defined as NeP are recorded as such using the DN4Q , and that a spectrum of NeP features may occur across a host of painful conditions . CONCLUSION Despite limitations of the DN4Q , symptoms of NeP may be more prevalent in the general population than expected and has a greater impact upon patients ' lives than non-NeP. Limitations of the DN4Q may relate to the concept of a spectrum of NeP existent amongst heterogenous NeP and non-NeP syndromes PURPOSE We examined whether a continuing medical education intervention increased general practitioners ' ability to select the proper pharmacological treatment for patients with osteoarthritis . SUBJECTS AND METHODS Eight towns in Quebec , Canada were r and omly allocated to one of four intervention options , workshop and decision tree , workshop , decision tree , or no intervention . All general practitioners practicing in each town were eligible to participate . We evaluated all dispensed prescriptions for either a cyclooxygenase (COX)-2 inhibitor , nonselective nonsteroidal anti-inflammatory drug or acetaminophen written by eligible general practitioners between May 2000 and June 2001 to elderly patients suffering from osteoarthritis . We used a multi-level Bayesian hierarchical model to assess the impact of the interventions on prescription adequacy . RESULTS We analyzed 5318 dispensed prescriptions written by 249 general practitioners in the five-month preintervention period and 4610 dispensed prescriptions written by the same physicians in the five-month postintervention period . A score of zero or one was given to every prescription , with one indicating prescription adequacy according to guidelines provided during the interventions . Bayesian hierarchical models showed some improvement in scores in the post- versus preintervention periods in all four groups . The probability of an improvement in the towns allocated the workshop and decision tree over the control was 94 % , compared with 74 % in the workshop group and 55 % in the decision tree group . CONCLUSION An interactive approach offered by peers and complemented by easy to use guidelines may enhance the general practitioner 's ability to manage osteoarthritis patients RATIONALE The concept of evidence -based medicine is important in providing efficient health care . The process uses research findings as the basis for clinical decision making . Evidence -based practice helps optimize current health care and enables the practitioners to be suitably accountable for the interventions they provide . Little work has been undertaken to examine how allied health professionals change their clinical practice in light of the latest evidence . The use of opinion leaders to disseminate new evidence around the management of low back pain into practice has been proposed . AIMS The aim of this study was to investigate if physiotherapists ' clinical management of patients with low back pain would change following an evidence -based education package , which utilized local opinion leaders and delivered the best evidence . METHOD Thirty musculoskeletal physiotherapists from a Community Trust in North Staffordshire were cluster r and omized by location of work , to two groups . The intervention group received an evidence -based programme on the management of low back pain , including advice regarding increasing activity levels and return to normal activity and challenging patients ' fears and beliefs about their pain . The control group received a st and ard in-service training package on the management of common knee pathologies . The physiotherapists ' clinical management of patients with low back pain was measured prior to training and 6 months post training . Outcome measures were based on physiotherapists completing ' discharge summary ' question naires , which included information relating to the use and importance of therapies for treating their low back pain patients . RESULTS There were few significant differences in treatment options between the intervention and control groups post training . Whilst there was some indication that physiotherapists were already utilizing aspects of psychosocial management for patients with low back pain , there was little change in what physiotherapists perceived to be important to patient recovery and actual clinical practice following the intervention . CONCLUSIONS Psychosocial factors have been identified as an important factor in the recovery of patients with low back pain . This project incorporated the latest evidence on the management of low back pain and utilized the theory of opinion leaders to disseminate this evidence into clinical practice . Whilst there were some limitations in the overall size of the study , the results help to give an insight into the challenges faced by the health care system and research ers alike to ensure quality evidence is actually utilized by practitioners for the benefits of patient care Study Design . Quasi-experimental , nonr and omized , nonequivalent , parallel group-controlled study involving before and after telephone surveys of the general population . Objective . To measure the magnitude of any sustained change in population beliefs about back pain 3 years after cessation of a population -based intervention design ed to alter beliefs about back pain . Summary of Background Data . A media campaign , which ran between September 1997 and December 1999 in Victoria , Australia , provided simple evidence -based advice about back pain . Following the campaign , there were significant improvements in both community and physicians ' beliefs about back pain , as well as a decline in number of workers ' compensation back cl aims . Methods . The campaign 's impact on population beliefs about back pain and fear-avoidance beliefs was measured using telephone surveys . Demographically identical population groups in Victoria and the adjacent control state , New South Wales , were surveyed at 4 times : before , during , immediately after , and 3 years after the media campaign in Victoria ( surveys 1−4 , respectively ) . Back beliefs were measured using the Back Beliefs Question naire ( BBQ ) ( possible score 9–45 , for which a higher score indicates a more positive belief about low back trouble ) . Fear-avoidance beliefs were measured using the Fear-Avoidance Beliefs Question naire consisting of 2 subscales for physical activity and work activity ( possible scores 0–24 and 0–36 , respectively ) , for which a lower score indicates fewer fear-avoidance beliefs . Results . A total of 6230 individuals in the general population completed the surveys . Large statistically significant improvements in population beliefs about back pain were still observed in Victoria 3 years after cessation of the campaign ( mean scores on the BBQ were 26.5 , 28.4 , 29.7 , and 28.8 for surveys 1–4 , respectively ) . No changes were observed in New South Wales ( mean scores on the BBQ were 26.3 , 26.2 , 26.3 , and 26.1 for surveys 1–4 , respectively ) . Of those individuals who reported back pain during the previous year , fear-avoidance beliefs aboutphysical activity in Victoria were also significantly better than at baseline ( mean scores on the Fear-Avoidance Beliefs Question naire for physical activity were 14.0 , 12.5 , 11.6 , and 12.3 for surveys 1–4 , respectively ) . Conclusions . Significant sustained improvements in population beliefs about back pain were observed 3 years after cessation of a media campaign of provision of positive messages about back pain . This result provides further evidence that a primary preventive strategy of altering population beliefs about back pain may be a highly effective way for reducing back-related disability Study Design . Cluster r and omized controlled trial . Objective . To improve quality of care for patients with low back pain ( LBP ) a multifaceted general practitioner education alone and in combination with motivational counseling by practice nurses has been implemented in German general practice s. We studied effects on functional capacity ( main outcome ) , days in pain , physical activity , quality of life , or days of sick leave ( secondary outcomes ) compared with no intervention . Summary of Background Data . International research has lead to the development of the German LBP guideline for general practitioners . However , there is still doubt about the most effective implementation strategy . Although effects on process of care have been observed frequently , changes in patient outcomes are rarely seen . Methods . We recruited 1378 patients with LBP in 118 general practice s , which were r and omized to 1 of 3 study arms : a multifaceted guideline implementation ( GI ) , GI plus training of practice nurses in motivational counseling ( MC ) , and the postal dissemination of the guideline ( controls , C ) . Data were collected ( question naires and patient interviews ) at baseline and after 6 and 12 months . Multilevel mixed effects modeling was used to adjust for clustering of data and potential confounders . Results . After 6 months , functional capacity was higher in the intervention groups with a cluster adjusted mean difference of 3.650 between the MC group and controls ( 95 % CI = 0.320–6.979 , P = 0.032 ) and 2.652 between the GI group and controls ( 95 % CI = −0.704 to 6.007 , P = 0.120 ) . Intervention effects were more pronounced regarding days in pain per year with an average reduction of 16 ( GI ) to 17 days ( MC ) after 6 months ( 12 and 9 days after 12 months ) compared with controls . Conclusion . Active implementation of the German LBP guideline results in slightly better outcomes during 6 months follow-up than its postal dissemination . Results are more distinct when practice nurses are trained in motivational counseling OBJECTIVE Determine whether lectures by national experts and a publicly available online program with similar educational objectives can improve knowledge , attitudes , and beliefs ( KAB ) important to chronic pain management . DESIGN A pretest-posttest r and omized design with two active educational interventions in two different physician groups and a third physician group that received live education on a different topic to control for outside influences , including retesting effects , on our evaluation . PARTICIPANTS A total of 136 community-based primary care physicians met eligibility criteria . All physicians attended the educational program to which they were assigned . Ninety-five physicians ( 70 % ) provided complete data for evaluation . MEASUREMENTS Physician responses to a st and ardized 50-item pain management KAB survey before , immediately after , and 3 months following the interventions . RESULTS The study groups and the 41 physicians not providing outcomes information were similar with respect to age , sex , race , percent engaged in primary care , and number of patients seen per week . Physician survey scores improved immediately following both pain education programs ( live : 138.0 - ->150.6 , P < 0.001 ; online : 143.6 - ->150.4 , P = 0.007 ) , but did not change appreciably in the control group ( 139.2 - ->142.5 , P > 0.05 ) . Findings persisted at 3 months . Satisfaction measures were high ( 4.00 - 4.72 on 1 - 5 scale ) and not significantly different ( P = 0.072 - 0.893 ) between groups . CONCLUSIONS When used under similar conditions , national speakers and a publicly available online CME program were associated with improved pain management KAB in physicians . The benefits lasted for 3 months . These findings support the continued use of these pain education strategies Low back pain has long been described as a challenge for both primary care physicians and specialists . Management of low back pain has also been criticized as frequently arbitrary , inappropriate , or ineffective . Contributing factors have been an inadequate evidence base and a need for more rigorous appraisal s of the available literature . Evidence -based medicine , an approach to clinical problem solving , is predicated on the premise that high- quality health care will result from practice s consistent with the best evidence . In contrast to the traditional medical paradigm that placed a heavy reliance on expert opinion , authority , and un systematic clinical observations , evidence -based medicine emphasizes the need for rigorous critical appraisal s of the scientific literature to inform medical decision making . Evidence -based medicine places strong weight on the requirement for valid studies , particularly r and omized controlled trials , to appropriately evaluate the effectiveness of health care interventions . Because of the rapidly increasing volume of medical literature , however , most clinicians are unable to keep up-to- date with all the new data . Two types of preprocessed evidence that can aid busy clinicians in medical decision making are systematic review s and evidence -based clinical practice guidelines . Like primary studies , systematic review s and clinical practice guidelines must adhere to high method ologic st and ards to reduce error and bias . As in other areas of medicine , the approach to the management of low back pain has been positively affected by the availability of more clinical trials and better use of critical appraisal techniques to evaluate and apply research findings . In addition to more rigorous primary studies , an increasing number of high- quality systematic review s and evidence -based clinical practice guidelines for low back pain are also available . Although some research gaps and method ologic shortcomings persist , the richer evidence base has greatly improved our underst and ing of what does and does not work for low back pain . Despite these advances , the best available evidence often does not inform everyday clinical decisions for low back pain . Nonetheless , there is widespread agreement that adherence to evidence -based practice will help improve low back pain patient outcomes and reduce arbitrary variations in care . This article review s basic principles of evidence -based medicine , discusses evidence -based medicine in the context of low back pain management , and summarizes some useful evidence -based medicine re sources 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 OBJECTIVE The aim was to examine the effect of using a Web-based computer program that provides personalized feedback to migraine patients , on the interactions of patients and providers . Background .-Despite the widespread availability of evidence -based migraine treatment guidelines , patients often do not receive optimal treatment to reduce migraine pain and disability . METHODS To address these quality gaps in migraine care , we developed a Web-based computer program , to be used by migraine patients before doctor visits . The feedback is design ed to prompt patients to ask questions that lead to higher quality of care . This study was conducted to examine the effect of using the program on migraine-specific doctor-patient communications . Patients were r and omized to use the Website before ( intervention ) or after ( control ) a visit with their provider . The outcome measures were the migraine-specific topics discussed during the visit , measured by an exit survey after the visit . RESULTS Fifty of 53 subjects r and omized completed the postvisit measures ( 94 % ) . Overall , the mean age was 42.0 years , most patients were female ( 86.5 % ) , all were white , and 58.5 % saw a headache specialist during their visit . Most ( 75.0 % ) reported having headaches at least once per week and 48.1 % rated their headaches as " severe . " Intervention patients were significantly more likely to " discuss whether you had migraine headaches or some other type of headache ? " ( 89.3 % vs 54.5 % ; P < .01 ) and to " discuss whether or not there may be a more serious cause of your headaches ? " ( 50.0 % vs 13.6 % ; P < .01 ) . Intervention patients were more likely to report discussing 8 of 12 migraine-related topics more frequently and a greater overall number of topics ( 5.5 vs 4.3 ) than control patients . This difference was not statistically significant . CONCLUSIONS These results suggest that the Website may have a positive impact on migraine-specific doctor-patient communications . A larger study , including important quality of life and utilization outcomes , is warranted Objectives .The objective of the study was to evaluate the effectiveness of 2 educational strategies aim ed at improving prescribing st and ards in primary care . Methods .A pragmatic controlled trial was design ed ; the study population included general and family practitioners in Galicia ( northwestern Spain ) divided into 3 study groups : a one-to-one education group ( n = 98 ) , a by-group education group ( n = 92 ) , and a control group ( n = 405 ) . The educational intervention included explicit recommendations for selecting nonsteroidal anti-inflammatory drugs ( NSAIDs ) for inflammation signs . Some of the subjects were given reminders . Mixed-effect linear models were applied to data analysis . Analyses were done by intention-to-treat . The dependent variable is a rate with a numerator that is the number of prescribed units of the NSAIDs recommended during intervention ; the denominator is the total number of prescribed units of the NSAID total . Results .One-to-one education obtained an average prescribing behavior improvement of 6.5 % ( P < 0.001 ) in the 9 months after intervention . In the education group , the average improvement was 2.4 % ( P < 0.05 ) for the same period . Statistically significant differences were observed between the group intervention and one-to-one groups . The reminder increased significantly the effectiveness of the one-to-one intervention . Conclusions .A single , short educational session to primary care doctors can improve their prescribing st and ards during long periods of ≥9 months . Of the 2 strategies followed in the trial , one-to-one education has shown to be the most effective . Results also show that the effectiveness of these interventions increases when presented together with written material & NA ; The overall population impact of chronic pain on work performance has been underestimated as it has often been described in terms of work‐related absence , excluding more subtle effects that chronic pain may have on the ability to work effectively . Additionally , most studies have focussed on occupational and /or patient cohorts and treatment seeking , rather than sampling from the general population . We undertook a population ‐based r and om digit dialling computer‐assisted telephone survey with participants r and omly selected within households in order to measure the impact of chronic pain on work performance . In addition , we measured the association between pain‐related disability and litigation . The study took place in Northern Sydney Health Area , a geographically defined urban area of New South Wales , Australia , and included 484 adults aged 18 or over with chronic pain . The response rate was 73.4 % . Working with pain was more common ( on an average 83.8 days in 6 months ) than lost work days due to pain ( 4.5 days ) among chronic pain participants in full‐time or part‐time employment . When both lost work days and reduced‐effectiveness work days were summed , an average of 16.4 lost work day equivalents occurred in a 6‐month period , approximately three times the average number of lost work days . In multiple logistic regression modelling with pain‐related disability as the dependent variable , past or present pain‐related litigation had the strongest association ( odds ratio (OR)=3.59 , P=0.001 ) . In conclusion , chronic pain had a larger impact on work performance than has previously been recognised , related to reduced performance while working with pain . A significant proportion were able to work effectively with pain , suggesting that complete relief of pain may not be an essential therapeutic target . Litigation ( principally work‐related ) for chronic pain was strongly associated with higher levels of pain‐related disability , even after taking into account other factors associated with poor functional outcomes Study Design . A r and omized controlled trial comparing usual care with a program for the coordination of primary health care ( CORE ) for the treatment of subacute low-back pain patients . Objectives . To measure the effectiveness of the CORE program as a mean for implementing clinical practice guidelines for low-back pain in an urban community . Summary of Background Data . Clinical practice guidelines have been developed for primary care physicians and patients on the clinical management of low-back pain . The implementation of the guidelines in a large community is difficult with the multiplicity of medical and nonmedical back care providers and products . The CORE program was design ed to make the guidelines fit in this complex environment . Methods . One hundred ten workers compensated for low-back pain for 4 to 8 weeks in metropolitan Montreal were r and omized in two groups : usual care ( N=56 ) and the CORE program ( N=54 ) . Coordination of primary health care was performed by two primary care physicians and a nurse in liaison with the treating physicians , and included a complete examination , recommendations for the clinical management , and support to carry out the recommendations . All workers were followed for 6 months . Back pain and functional status were assessed at baseline , 3 months , and 6 months . Results . In the 6-month follow-up , the CORE group returned to work 6.6 days ( st and ard error = 8.9 ) quicker than the control group , a difference that was not statistically significant . However , the CORE group showed a sustained improvement in pain and functional status with two-fold differences at the end of the 6 months of follow-up . This represented nine points on the Oswestry scale ( P = 0.02 ) and 12 points on the Quebec Back Pain Disability Scale ( P = 0.01 ) . The CORE group also used three times less specialized imaging tests of the spine at 3 months ( P < 0.01 ) and exercised twice as much at 6 months ( P < 0.05 ) than the controls . Conclusions . The therapeutic results for workers with low-back pain could be improved by implementing the clinical practice guidelines with primary care physicians in a large community , without delaying the return to work . The CORE intervention for back pain patients ishighly relevant to primary care practice . It is simple in its application , flexible to accommo date physicians ’ and patients ’ preferences in health care , and it is effective on patients ’ clinical outcome |
11,753 | 22,242,793 | Patient involvement is important for long-term success | This article systematic ally review s the literature on the impact of collaboration between pharmacists and general practitioners and describes its effect on patients ' health . | BACKGROUND Collaboration between physicians and pharmacists is one approach to address drug-related morbidity and achieve therapeutic goals . A collaborative practice of pharmaceutical care has been used in the Fairview Clinics System of Minneapolis-St Paul since 1999 . METHODS The quality of therapeutic determinations made by pharmacists within this collaborative practice of pharmaceutical care was studied by a 12-member panel of physicians and pharmacists who used r and omly selected patient records . This was a quality improvement and care process validation component of a study evaluating the effects of drug therapy management in patients receiving prepaid medical assistance . An implicit review process was used to evaluate the clinical credibility of therapeutic determinations made by pharmaceutical care practitioners . RESULTS A total of 5780 drug therapy problems were resolved for 2524 patients receiving pharmaceutical care . The rate of therapeutic goals achieved increased from 74 % at the time of patients ' initial pharmaceutical care encounters to 89 % at patients ' latest encounters . In this quality assessment analysis panel members performed a total of 4779 evaluations of clinical decisions . Panelists indicated agreement with the evaluations in 94.2 % of cases , expressed a neutral opinion in 3.6 % of cases , and disagreed in 2.2 % of cases . Intraclass correlation coefficients ranged from 0.73 to 0.85 . CONCLUSIONS The decisions made by pharmaceutical care practitioners working in collaboration with physicians to provide drug therapy management services are clinical ly credible based on the evaluations and comments of a peer review panel . This study provides information on the quality of care provided by pharmacists when collaborating with physicians to provide drug therapy management services OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes The effect of clinical pharmacy services on prescribing patterns and drug costs for nonsteroidal anti-inflammatory drugs ( NSAIDs ) and salicylates in a primary -care clinic operated by a health-maintenance organization ( HMO ) was studied . Two pharmacists provided clinical services to a r and omly selected cluster of family practice physicians in the HMO for six months . A second family practice cluster served as a control group . The pharmacists alerted prescribers to the availability of low-cost alternatives ( such as ibuprofen and salicylates ) and review ed the medication profiles of patients receiving high-cost NSAIDs . Data were collected for both physician clusters for nine months before and six months after the pharmacists ' intervention . Changes in the mean numbers of prescriptions for ibuprofen and piroxicam per 1000 enrollees per physician in the baseline and evaluation periods were not significantly different between the two groups . Significantly more prescriptions for salicylates were written by physicians in the intervention group than in the control group during the evaluation period . Annualized mean drug ingredient costs per enrollee and per prescription for NSAIDS and salicylates decreased during the evaluation period in both groups , but these differences were not significant . In relatively unstructured interactions with physicians and nurses , clinical pharmacists were not able to reduce the costs associated with NSAIDs but did have a modest effect on altering salicylate prescribing patterns . This clinical pharmacy program was not economically self-sustaining during the first six months of operation , since operating costs exceeded anticipated savings Purpose To examine the impact of systematic medication reconciliations upon hospital admission and of a medication review while in hospital on the number of inappropriate medications and unscheduled drug-related hospital revisits in elderly patients . Methods This was a prospect i ve , controlled study in 210 patients , aged 65 years or older , who were admitted to one of three internal medicine wards at a University Hospital in Sweden . Intervention patients received the complete Lund Integrated Medicines Management model ( medication reconciliation upon admission and discharge , and medication review and monitoring ) provided by a multi-professional team , including a clinical pharmacist . Control patients received st and ard care and medication reconciliation upon discharge . Blinded review ers evaluated the appropriateness of the prescribing ( using the Medication Appropriateness Index ) on admission and discharge , and assessed the probability that a drug-related problem was the reason for any patient readmitted to hospital or visiting the emergency department within 3 months of discharge ( using World Health Organisation causality criteria ) . Results There was a greater decrease in the number of inappropriate drugs in the intervention group than in the control group for both the intention-to-treat population { 51 % [ 95 % confidence interval ( CI ) 43–58 % ] vs. 39 % ( 95 % CI 30–48 % ) ; p = 0.0446 } and the per- protocol population [ 60 % ( 95 % CI 51–67 % ) vs. 44 % ( 95 % CI 34–52 % ) ; p = 0.0106 ) ] . There were six revisits to hospital in the intervention group which were judged as ‘ possibly , probably or certainly drug-related ’ , compared with 12 in the control group ( p = 0.0469 ) . Conclusions In this study , medication reconciliation and review provided by a clinical pharmacist in a multi-professional team significantly reduced the number of inappropriate drugs and unscheduled drug-related hospital revisits among elderly patients BACKGROUND The pharmaceutical care approach serves as a model for medication review , involving collaboration between GPs , pharmacists , patients , and carers . Its use is advocated with older patients who are typically prescribed several drugs . However , it has yet to be thoroughly evaluated . AIM To estimate the effectiveness of pharmaceutical care for older people , shared between GPs and community pharmacists in the UK , relative to usual care . DESIGN OF STUDY Multiple interrupted time-series design in five primary care trusts which implemented pharmaceutical care at 2-month intervals in r and om order . Patients acted as their own controls , and were followed over 3 years including their 12 months ' participation in pharmaceutical care . SETTING In 2002 , 760 patients , aged > or = 75 years , were recruited from 24 general practice s in East and North Yorkshire . Sixty-two community pharmacies also took part . A total of 551 participants completed the study . METHOD Pharmaceutical care was undertaken by community pharmacists who interviewed patients , developed and implemented pharmaceutical care plans together with patients ' GPs , and thereafter undertook monthly medication review s. Pharmacists and GPs attended training before the intervention . Outcome measures were the UK Medication Appropriateness Index , the Short Form-36 Health Survey ( SF-36 ) , and serious adverse events . RESULTS The intervention did not lead to any statistically significant change in the appropriateness of prescribing or health outcomes . Although the mental component of the SF-36 decreased as study participants become older , this trend was not affected by pharmaceutical care . CONCLUSION The RESPECT model of pharmaceutical care ( R and omised Evaluation of Shared Prescribing for Elderly people in the Community over Time ) shared between community pharmacists and GPs did not significantly change the appropriateness of prescribing or quality of life in older patients BACKGROUND Studies have demonstrated that blood pressure ( BP ) control can be improved when clinical pharmacists assist with patient management . The objective of this study was to evaluate if a physician and pharmacist collaborative model in community-based medical offices could improve BP control . METHODS This was a prospect i ve , cluster r and omized , controlled clinical trial with clinics r and omized to a control group ( n = 3 ) or to an intervention group ( n = 3 ) . The study enrolled 402 patients ( mean age , 58.3 years ) with uncontrolled hypertension . Clinical pharmacists made drug therapy recommendations to physicians based on national guidelines . Research nurses performed BP measurements and 24-hour BP monitoring . RESULTS The mean ( SD ) guideline adherence scores increased from 49.4 ( 19.3 ) at baseline to 53.4 ( 18.1 ) at 6 months ( 8.1 % increase ) in the control group and from 40.4 ( 22.6 ) at baseline to 62.8 ( 13.5 ) at 6 months ( 55.4 % increase ) in the intervention group ( P = .09 for adjusted between-group comparison ) . The mean BP decreased 6.8/4.5 mm Hg in the control group and 20.7/9.7 mm Hg in the intervention group ( P < .05 for between-group systolic BP comparison ) . The adjusted difference in systolic BP was -12.0 ( 95 % confidence interval [ CI ] , -24.0 to 0.0 ) mm Hg , while the adjusted difference in diastolic BP was -1.8 ( 95 % CI , -11.9 to 8.3 ) mm Hg . The 24-hour BP levels showed similar effect sizes . Blood pressure was controlled in 29.9 % of patients in the control group and in 63.9 % of patients in the intervention group ( adjusted odds ratio , 3.2 ; 95 % CI , 2.0 - 5.1 ; P < .001 ) . CONCLUSIONS A physician and pharmacist collaborative intervention achieved significantly better mean BP and overall BP control rates compared with a control group . Additional research should be conducted to evaluate efficient strategies to implement team-based chronic disease management . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00201019 Abstract Objective : To determine whether a pharmacist can effectively review repeat prescriptions through consultations with elderly patients in general practice . Design : R and omised controlled trial of clinical medication review by a pharmacist against normal general practice review . Setting : Four general practice s. Participants : 1188 patients aged 65 or over who were receiving at least one repeat prescription and living in the community . Intervention : Patients were invited to a consultation at which the pharmacist review ed their medical conditions and current treatment . Main outcome measures : Number of changes to repeat prescriptions over one year , drug costs , and use of healthcare services . Results : 590 ( 97 % ) patients in the intervention group were review ed compared with 233 ( 44 % ) in the control group . Patients seen by the pharmacist were more likely to have changes made to their repeat prescriptions ( mean number of changes per patient 2.2 v 1.9 ; difference=0.31 , 95 % confidence interval 0.06 to 0.57 ; P=0.02 ) . Monthly drug costs rose in both groups over the year , but the rise was less in the intervention group ( mean difference £ 4.72 per 28 days , −£7.04 to -£2.41 ) ; equivalent to £ 61 per patient a year . Intervention patients had a smaller rise in the number of drugs prescribed ( 0.2 v 0.4 ; mean difference −0.2 , −0.4 to −0.1 ) . There was no evidence that review of treatment by the pharmacist affected practice consultation rates , outpatient consultations , hospital admissions , or death rate . Conclusions : A clinical pharmacist can conduct effective consultations with elderly patients in general practice to review their drugs . Such review results in significant changes in patients ' drugs and saves more than the cost of the intervention without affecting the workload of general practitioners . What is already known on this topic Review of patients on long term drug treatment is important but is done inadequately Evidence from the United States shows that pharmacists can improve patient care by review ing drug treatment What this study adds Consultations with a clinical pharmacist are an effective method of review ing the drug treatment of older patients Review by a pharmacist results in more drug changes and lower prescribing costs than normal care plus a much higher review rate Use of healthcare services by patients is not Background —R and omized controlled trials have demonstrated that collaborative medication review s can improve outcomes for patients with heart failure . We aim ed to determine whether these results translated into Australian practice , where collaborative review s are nationally funded . Methods and Results —This retrospective cohort study using administrative cl aims data included veterans 65 years and older receiving bisoprolol , carvedilol , or metoprolol succinate for which prescribing physicians indicated treatment was for heart failure . We compared those exposed to a general practitioner – pharmacist collaborative home medication review with those who did not receive the service . The service includes physician referral , a home visit by an accredited pharmacist to identify medication-related problems , and a pharmacist report with follow-up undertaken by the physician . Kaplan-Meier analyses and Cox proportional hazards models were used to compare time until next hospitalization for heart failure between the exposed and unexposed groups . There were 273 veterans exposed to a home medicines review and 5444 unexposed patients . Average age in both groups was 81.6 years ( no significant difference ) . The median number of comorbidities was 8 in the exposed group and 7 in the unexposed ( P<0.0001 ) . Unadjusted results showed a 37 % reduction in rate of hospitalization for heart failure at any time ( hazard ratio , 0.63 ; 95 % CI , 0.44 to 0.89 ) . Adjusted results showed a 45 % reduction ( hazard ratio , 0.55 ; 95 % CI , 0.39 to 0.77 ) among those who had received a home medicines review compared with the unexposed patients . Conclusion —Medicines review in the practice setting is effective in delaying time to next hospitalization for heart failure in those treated with heart failure medicines BACKGROUND Patients 80 years or older are underrepresented in scientific studies . The objective of this study was to investigate the effectiveness of interventions performed by ward-based pharmacists in reducing morbidity and use of hospital care among older patients . METHODS A r and omized controlled study of patients 80 years or older was conducted at the University Hospital of Uppsala , Uppsala , Sweden . Four hundred patients were recruited consecutively between October 1 , 2005 , and June 30 , 2006 , and were r and omized to control ( n = 201 ) and intervention ( n = 199 ) groups . The interventions were performed by ward-based pharmacists . The control group received st and ard care without direct involvement of pharmacists at the ward level . The primary outcome measure was the frequency of hospital visits ( emergency department and readmissions [ total and drug-related ] ) during the 12-month follow-up period . RESULTS Three hundred sixty-eight patients ( 182 in the intervention group and 186 in the control group ) were analyzed . For the intervention group , there was a 16 % reduction in all visits to the hospital ( quotient , 1.88 vs 2.24 ; estimate , 0.84 ; 95 % confidence interval [ CI ] , 0.72 - 0.99 ) and a 47 % reduction in visits to the emergency department ( quotient , 0.35 vs 0.66 ; estimate , 0.53 ; 95 % CI , 0.37 - 0.75 ) . Drug-related readmissions were reduced by 80 % ( quotient , 0.06 vs 0.32 ; estimate , 0.20 ; 95 % CI , 0.10 - 0.41 ) . After inclusion of the intervention costs , the total cost per patient in the intervention group was $ 230 lower than that in the control group . CONCLUSION If implemented on a population basis , the addition of pharmacists to health care teams would lead to major reductions in morbidity and health care costs BACKGROUND regular medication review has been recommended for those over 75 and those on multiple drug therapy . Pharmacists are a potential source of assistance in review ing medication . Evidence of the benefits of this process is needed . OBJECTIVE to study the effect of medication review led by a pharmacist on resolution of pharmaceutical care issues , medicine costs , use of health and social services and health-related quality of life . DESIGN r and omized , controlled trial . SETTING general medical practice s in the Grampian region of Scotl and . SUBJECTS patients aged at least 65 years , with at least two chronic disease states who were taking at least four prescribed medicines regularly . METHODS pharmacists review ed the drug therapy of 332 patients , using information obtained from the practice computer , medical records and patient interviews . In 168 patients , a pharmaceutical care plan was then drawn up and implemented . The 164 control patients continued to receive normal care . All outcome measures were assessed at baseline and after 3 months . RESULTS all patients had at least two pharmaceutical care issues at baseline . Half of these were identified from the prescription record , the rest from notes and patient interview . Of all the issues , 21 % were resolved by information found in notes and 8.5 % by patient interview . General practitioners agreed with 96 % of all care issues documented on the care plans in the intervention group . At the time of follow-up , 70 % of the remaining care issues had been resolved in the intervention group , while only 14 % had been resolved in the control group . There were no changes in medicine costs or health-related quality of life in either group . There were small increases in contacts with health-care professionals and slightly fewer hospital admissions among the intervention group than the control group . CONCLUSIONS pharmacist-led medication review has the capacity to identify and resolve pharmaceutical care issues and may have some impact on the use of other health services Objective The objective of the Cardiovascular Health Awareness Program ( CHAP ) is to improve the processes of care related to the cardiovascular health of older adults . Participants Two Ontario communities including family physicians ( FP ) , pharmacists , public health units and nurses , volunteer peer health educators , older adult patients and community organizations . Setting Community pharmacies and family physician offices . InterventionCHAP is design ed to close a process of care loop around cardiovascular health awareness that originates from , and returns to , the FP . Older patients are invited by their FP to attend pharmacy CHAP sessions . At these sessions , trained volunteer peer health educators ( PHEs ) assist patients both in recording their blood pressure using a calibrated automated device and in completing a cardiovascular risk profile . This information is relayed to their respective FP via an automated computerized data base . Pharmacists and patients receive copies of the results . Based on these cumulative risk profiles , patients are advised to follow-up with their FP . Outcomes Of the FPs and pharmacists asked , 47 % and 79 % , respectively , agreed to participate in the project . 39 % of older adult patients invited by their FPs attended the CHAP community pharmacy sessions . Of these , 100 % agreed to having their risk profile , including their blood pressure readings , forwarded to their FP . Positive feedback about CHAP was expressed by the volunteer PHEs , the FPs and the pharmacists . Conclusion The community-based pharmacy CHAP sessions are a feasible way of improving patient , physician , and pharmacist access to reliable blood pressure measurements and to cardiovascular health information . A r and omized trial is in progress that will assess the impact of CHAP on monitoring of blood pressure . RésuméObjectifL’objectif du programme communautaire de sensibilisation à l’hypertension CHAP ( Cardiovascular Health Awareness Program ) est d’améliorer les soins apportés aux personnes âgées en matière de santé cardiovasculaire . Participants Deux localités de l’Ontario , des médecins de famille , des pharmaciens , des infirmières de santé publique , des bénévoles-éducateurs en santé des pairs , des personnes âgées , des bureaux de santé publique et des organismes communautaires . MilieuPharmacies communautaires et cabinets de médecins de famille . InterventionCHAP est un programme conçu pour boucler la boucle des soins en matière de sensibilisation à la santé cardiovasculaire qui débute et se termine avec le médecin de famille . Des personnes âgées reçoivent une invitation de leur médecin de famille de participer au programme CHAP . Au cours de ces séances , des éducateurs-bénévoles en santé des pairs ayant reçu une formation aident les patients à mesurer leur tension artérielle à l’aide d’un appareil calibré et automatisé , ainsi qu’à remplir un profil de risques cardiovasculaires . Ces renseignements sont ensuite transmis à leurs médecins de famille à l’aide d’une banque de données informatisée ; les pharmaciens et patients reçoivent aussi des copies des résultats . Selon leur profil cumulé de risques , on conseille aux patients de consulter leur médecin . RésultatsParmi les médecins et pharmaciens approchés , 47 % et 79 % respectivement ont accepté de participer au projet . Chez les aînés , 39 % des personnes ayant reçu une invitation de leur médecin de famille ont participé aux séances d’évaluation de la tension artérielle . De ce groupe , 100 % ont consenti à ce que leur profil de risques et leurs chiffres tensionnels soient transmis au médecin de famille . Les bénévoles-éducateurs , médecins de famille et pharmaciens ont exprimé des commentaires positifs au sujet du CHAP . Conclusion Ces séances en pharmacies communautaires sont une façon viable d’améliorer l’accès des patients , des médecins et des pharmaciens à des mesures précises de la tension artérielle et à des renseignements sur la santé cardiovasculaire Objective To assess the impact of an intervention initiated by community pharmacists , involving the provision of educational material and general practitioner ( GP ) referral , on asthma knowledge and self-reported asthma control and asthma-related quality of life ( QOL ) in patients who may have suboptimal management of their asthma , as evidence d by pharmacy dispensing records . Setting Community pharmacies throughout Tasmania , Australia . Methods Forty-two pharmacies installed a software application that data mined dispensing records and generated a list of patients with suboptimal asthma management , as indicated by having three or more canisters of inhaled short-acting beta-2-agonists dispensed in the preceding 6 months . Identified patients were r and omised to an intervention or control group . At baseline , intervention patients were mailed intervention packs consisting of a letter encouraging them to see their GP for a review , educational material , asthma knowledge , asthma control and asthma-related QOL question naires , and a letter with a dispensing history to give to their GP . Pharmacists were blinded to the control patients ’ identities for 6 months , after which time intervention patients were sent repeat question naires , and control patients were sent intervention packs . Main outcome measures Asthma knowledge , asthma control and asthma-related QOL scores . Results Thirty-five pharmacies completed the study , providing 706 intervention and 427 control patients who were eligible to receive intervention packs . Intervention patients ’ asthma control and asthma-related QOL scores at 6 months were significantly higher compared to the control patients ( P < 0.01 and P < 0.05 , respectively ) and to the intervention patients ’ baseline scores ( P < 0.001 and P < 0.05 , respectively ) . Symptom-related QOL was significantly higher compared to the control patients ( P < 0.01 ) and activities-related QOL significantly improved compared to baseline ( P < 0.05 ) . No significant change was observed in asthma knowledge . Conclusion The results suggest that community pharmacists are ideally placed to identify patients with suboptimal asthma management and refer such patients for a review by their GP . This type of collaborative intervention can significantly improve self-reported asthma control and asthma-related QOL in patients identified as having suboptimal management of their asthma . A larger trial is needed to confirm the effects are real and sustained BACKGROUND Pharmacists can improve patient outcomes in institutional and pharmacy setting s , but little is known about their effectiveness as consultants to primary care physicians . We examined whether an intervention by a specially trained pharmacist could reduce the number of daily medication units taken by elderly patients , as well as costs and health care use . METHODS We conducted a r and omized controlled trial in family practice s in 24 sites in Ontario . We r and omly allocated 48 r and omly selected family physicians ( 69.6 % participation rate ) to the intervention or the control arm , along with 889 ( 69.5 % participation rate ) of their r and omly selected community-dwelling , elderly patients who were taking 5 or more medications daily . In the intervention group , pharmacists conducted face-to-face medication review s with the patients and then gave written recommendations to the physicians to resolve any drug-related problems . Process outcomes included the number of drug-related problems identified among the senior citizens in the intervention arm and the proportion of recommendations implemented by the physicians . RESULTS After 5 months , seniors in the intervention and control groups were taking a mean of 12.4 and 12.2 medication units per day respectively ( p = 0.50 ) . There were no statistically significant differences in health care use or costs between groups . A mean of 2.5 drug-related problems per senior was identified in the intervention arm . Physicians implemented or attempted to implement 72.3 % ( 790/1093 ) of the recommendations . INTERPRETATION The intervention did not have a significant effect on patient outcomes . However , physicians were receptive to the recommendations to resolve drug-related problems , suggesting that collaboration between physicians and pharmacists is feasible OBJECTIVES To test the effect of an adapted U.S. model of pharmaceutical care on prescribing of inappropriate psychoactive ( anxiolytic , hypnotic , and antipsychotic ) medications and falls in nursing homes for older people in Northern Irel and ( NI ) . DESIGN Cluster r and omized controlled trial . SETTING Nursing homes r and omized to intervention ( receipt of the adapted model of care ; n=11 ) or control ( usual care continued ; n=11 ) . PARTICIPANTS Residents aged 65 and older who provided informed consent ( N=334 ; 173 intervention , 161 control ) . INTERVENTION Specially trained pharmacists visited intervention homes monthly for 12 months and review ed residents ' clinical and prescribing information , applied an algorithm that guided them in assessing the appropriateness of psychoactive medication , and worked with prescribers ( general practitioners ) to improve the prescribing of these drugs . The control homes received usual care . MEASUREMENTS The primary end point was the proportion of residents prescribed one or more inappropriate psychoactive medicine according to st and ardized protocol s ; falls were evaluated using routinely collected falls data m and ated by the regulatory body for nursing homes in NI . RESULTS The proportion of residents taking inappropriate psychoactive medications at 12 months in the intervention homes ( 25/128 , 19.5 % ) was much lower than in the control homes ( 62/124 , 50.0 % ) ( odds ratio=0.26 , 95 % confidence interval=0.14 - 0.49 ) after adjustment for clustering within homes . No differences were observed at 12 months in the falls rate between the intervention and control groups . CONCLUSION Marked reductions in inappropriate psychoactive medication prescribing in residents result ed from pharmacist review of targeted medications , but there was no effect on falls Background : Warfarin remains a high-risk drug for adverse events , especially following discharge from the hospital . New approaches are needed to minimize the potential for adverse outcomes during this period . Objective : To evaluate the clinical outcomes of a collaborative , home-based postdischarge warfarin management service adapted from the Australian Home Medicines Review ( HMR ) program . Methods : In a prospect i ve , nonr and omized controlled cohort study , patients discharged from the hospital and newly initiated on or continuing warfarin therapy received either usual care ( UC ) or a postdischarge service ( PDS ) of 2 or 3 home visits by a trained , HMR-accredited pharmacist in their first 8 to 10 days postdischarge . The PDS involved point-of-care international normalized ratio ( INR ) monitoring , warfarin education , and an HMR , in collaboration with the patient 's general practitioner and community pharmacist . The primary outcome measure was the combined incidence of major and minor hemorrhagic events in the 90 days postdischarge . Secondary outcome measures included the incidences of thrombotic events , combined hemorrhagic and thombotic events , unplanned and warfarin-related hospital readmissions , death , INR control , and persistence with therapy al 8 and 90 days postdischarge . Results : The PDS ( n = 129 ) was associated with statistically significantly decreased rates of combined major and minor hemorrhagic events to day 90 ( 5.3 % vs 14.7 % ; p = 0.03 ) and day 8 ( 0.9 % vs 7.2 % ; p = 0.01 ) compared with UC ( n = 139 ) . The rate of combined hemorrhagic and thrombotic events to day 90 also decreased ( 6.4 % vs 19.0 % ; p = 0.008 ) and persistence with warfarin therapy improved ( 95.4 % vs 83.6 % ; p = 0.004 ) . No significant differences in readmission and death rates or INR control were demonstrated . Conclusions : This study demonstrated the ability of appropriately trained accredited pharmacists working within the Australian HMR framework to reduce adverse events and improve persistence In patients taking warfarin following hospital discharge . Widespread implementation of such a service has the potential to enhance medication safety along the continuum of care . KEY WORDS : adverse drug events , community pharmacy services , international normalized ratio , patient discharge , warfarin OBJECTIVE to measure the impact of pharmacist-conducted clinical medication review with elderly care home residents . DESIGN r and omised controlled trial of clinical medication review by a pharmacist against usual care . SETTING sixty-five care homes for the elderly in Leeds , UK . PARTICIPANTS a total of 661 residents aged 65 + years on one or more medicines . INTERVENTION clinical medication review by a pharmacist with patient and clinical records . Recommendations to general practitioner for approval and implementation . Control patients received usual general practitioner care . MAIN OUTCOME MEASURES primary : number of changes in medication per participant . Secondary : number and cost of repeat medicines per participant ; medication review rate ; mortality , falls , hospital admissions , general practitioner consultations , Barthel index , St and ardised Mini-Mental State Examination ( SMMSE ) . RESULTS the pharmacist review ed 315/331 ( 95.2 % ) patients in 6 months . A total of 62/330 ( 18.8 % ) control patients were review ed by their general practitioner . The mean number of drug changes per patient were 3.1 for intervention and 2.4 for control group ( P < 0.0001 ) . There were respectively 0.8 and 1.3 falls per patient ( P < 0.0001 ) . There was no significant difference for GP consultations per patient ( means 2.9 and 2.8 in 6 months , P = 0.5 ) , hospitalisations ( means 0.2 and 0.3 , P = 0.11 ) , deaths ( 51/331 and 48/330 , P = 0.81 ) , Barthel score ( 9.8 and 9.3 , P = 0.06 ) , SMMSE score ( 13.9 and 13.8 , P = 0.62 ) , number and cost of drugs per patient ( 6.7 and 6.9 , P = 0.5 ) ( pounds sterling 42.24 and pounds sterling 42.94 per 28 days ) . A total of 75.6 % ( 565/747 ) of pharmacist recommendations were accepted by the general practitioner ; and 76.6 % ( 433/565 ) of accepted recommendations were implemented . CONCLUSIONS general practitioners do not review most care home patients ' medication . A clinical pharmacist can review them and make recommendations that are usually accepted . This leads to substantial change in patients ' medication regimens without change in drug costs . There is a reduction in the number of falls . There is no significant change in consultations , hospitalisation , mortality , SMMSE or Barthel scores Objective To characterise the nature of the drug-related problems with warfarin therapy identified in pharmacist-conducted medication review s during a collaborative post-discharge warfarin management service , with a focus on potentially serious drug interactions . Setting Australian community pharmacy practice . Method Medication review reports su bmi tted by pharmacists to patients ’ general practitioners as part of the service were review ed and the type and clinical significance of the warfarin-associated drug-related problems , and the pharmacists ’ recommendations were classified . The prevalence of prescribing of ‘ potentially hazardous ’ warfarin drug interactions was investigated and compared with the frequency of documentation of these interactions in the medication review reports . Main outcome measure The number and nature of warfarin-associated drug-related problems identified and the rate of documentation of ‘ potentially hazardous ’ warfarin drug interactions in the reports from pharmacist-conducted medication review s. Results A total of 157 warfarin-associated drug-related problems were documented in 109 medication review reports ( mean 1.4 per patient , 95 % CI 1.3–1.6 , range 0–5 ) . Drug selection and Education or information were the most commonly identified warfarin-associated drug-related problems ; most drug-related problems were of moderate clinical significance . Eight of 23 potentially serious warfarin drug interactions ( 34.8 % ) were identified in the medication review reports . Conclusion Pharmacists addressing drug selection and warfarin education drug-related problems during medication review s may have contributed to the positive outcomes of the post-discharge service . Warfarin drug interactions were frequently identified ; however , well-recognised potentially hazardous interactions were under-reported . Improved communication along the continuum of care would permit improved targeting of drug-related problem reporting , especially in relation to preventable drug interactions BACKGROUND One important task for physicians is to optimize their patients ' medication regimen . Involvement of clinical pharmacists who have specific training in drug regimen design has been associated with improved patient outcomes for specific medical conditions , eg , hypertension and anticoagulation . This prospect i ve , r and omized trial investigated whether a single consultation by a clinical pharmacist with high-risk patients and their primary physicians would result in improved prescribing outcomes . METHODS Patients at risk for medication-related problems were identified and r and omized to receive a pharmacotherapy consultation ( consult group ) or usual medical care ( control group ) . Outcomes , including the number of drugs , number of doses per day , cost of medications , and patient reports of adverse effects , were recorded at baseline and at 6 months following the intervention . RESULTS Fifty-six subjects were evaluable : 29 in the control group , and 27 in the consult group . Six months after the consultation , the number of drugs , the number of doses , and the 6-month drug costs all decreased in the consult group and increased in the control group ; the net difference was 1.1 drugs ( P = .004 ) , 2.15 doses per day ( P = .007 ) , $ 586 per year ( P = .008 ) . The side effects score improved by 1.8 points more in the consult group compared with the control group ( P = NS ) . Similarly , the prescribing convenience score in the consult group improved by 1.4 points more than that of the control group ( P = NS ) . CONCLUSIONS This study demonstrates several important benefits of integration of a clinical pharmacist into a primary care setting , including improvement in cost and simplification of the medication regimen with no reduction in quality of care Aim of study : This study sought to determine whether multidisciplinary case conference review s improved outcomes for nursing home residents , and the effects of this team approach to resident care on carers , including the h and s-on carers employed by the nursing home , and health professionals . Method : 245 residents of three Canberra nursing homes were enrolled in this non-r and omised controlled trial . The intervention consisted of sessions of three case conference review s held between 10/4sol;96 and 4sol;12sol;96 . These sessions were attended by the General Practitioners ( GPs ) of the residents discussed , the GP project officer from the ACT Division of General Practice , a clinical pharmacist , senior nursing staff , other health professionals eg physiotherapist , and occasionally the resident concerned or their representative . At each review , a case presentation by the resident 's GP was followed by a multidisciplinary discussion of all aspects , medical and non-medical , of the resident 's care . The review concluded with a management plan for the resident . In total 75 residents were review ed . Main outcome measures : Medication use and cost , and mortality . Results : One month after the review s were completed comparisons between those who were review ed and those who were not showed non-significant reductions in medication orders , medication cost , and mortality in the review ed group . Many of the 92 recommendations in the management plans that were carried out benefited the residents ( n=37 ) and /or carers ( n=24 ) . The responses of the GPs and the Directors of Nursing to the review s were overwhelmingly positive . Conclusion : Recommendations arising from multidisciplinary case conferences were carried out to the benefit of patients and carers . Given the support shown by key stakeholders , multidisciplinary conferences should be used more Aim : The objective of this prospect i ve study was to conduct medication management review s ( MMR ) in people from a non-English speaking background ( NESB ) ( Bosnian/Serbian/ Croatian , from former Yugoslavia , currently residing in Australia ) in their native language in order to identify medication-related problems ( needs analysis ) and implement appropriate therapeutic interventions , in collaboration with their general practitioners ( GPs ) . Methods : Twenty-five participants entered the study . Each was interviewed and medication-related issues were identified by the health care team . Results : Various interventions ( over 150 for the whole group , an average of 6 per participant ) , based on actual and potential medication-related problems , were design ed to improve the use of medicines . The MMRs introduced effective changes into the participants ’ health care . Psychological ( e.g. , feeling depressed ) and sociological factors ( e.g. , costs of medicines , not underst and ing labels written in English ) were identified as having significant impacts on medication management . Conclusions : These data confirmed there are avoidable medication-related problems in people from a NESB . GPs and pharmacists working in health care teams with a trained interpreter could greatly improve medication use through regular review and a team approach to problem identification and solving PURPOSE The impact of pharmacist interventions on the care and outcomes of patients with depression in a primary care setting was evaluated . METHODS Patients diagnosed with a new episode of depression and started on anti-depressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) for one year . EC consisted of a pharmacist collaborating with primary care providers to facilitate patient education , the initiation and adjustment of antidepressant dosages , the monitoring of patient adherence to the regimen , the management of adverse reactions , and the prevention of relapse . The patients in the UC group served as controls . Outcomes were measured by the Hopkins Symptom Checklist , Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for major depression , health-related quality of life , medication adherence , patient satisfaction , and use of depression-related health care services . An intent-to-treat analysis was used . RESULTS Seventy-four patients were r and omized to EC or UC . At baseline , the EC group included more patients diagnosed with major depression than did the UC group ( p = 0.04 ) . All analyses were adjusted for this difference . In both groups , mean scores significantly improved from baseline for symptoms of depression and quality of life at three months and were maintained for one year . There were no statistically significant differences between treatment groups in depression symptoms , quality of life , medication adherence , provider visits , or patient satisfaction . CONCLUSION Frequent telephone contacts and interventions by pharmacists and UC in a primary care setting result ed in similar rates of adherence to antidepressant regimens and improvements in the outcomes of depression at one year OBJECTIVE : To develop a pharmacist intervention to improve depression care and outcomes within a primary care setting . METHODS : Pragmatic , r and omized trial of a clinical pharmacist collaborative care intervention versus usual care in a busy , academic family practice clinic . RESULTS : Seventy-four patients diagnosed with a new episode of major depression and started on antidepressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) groups . EC consists of a clinical pharmacist collaborating with primary care providers ( PCPs ) to facilitate education , initiation , and titration of acute-phase antidepressant treatment to monitor treatment adherence and to prevent relapse . Control patients receive UC by their PCP . The main end point is reduction of depression symptoms over time as measured by the Hopkins Symptom Checklist ( SCL-20 ) . Other outcomes include the Diagnostic and Statistical Manual of Mental Disorders , ( DSM-IV ) criteria for major depression , health-related quality of life measured by the Medical Outcomes Study Short Form 12 ( SF-12 ) , medication adherence , patient satisfaction , and healthcare utilization . The main end point and the cost of treating major depression will be used to estimate the cost-effectiveness of the collaborative care model . CONCLUSIONS : The study is a unique , ongoing trial that may have important implication s for the treatment of depression in primary care setting s as well as new roles for clinical pharmacists BACKGROUND Older people are prone to problems related to use of medicines . As they tend to use many different medicines , monitoring pharmacotherapy for older people in primary care is important . AIM To determine which procedure for treatment review s ( case conferences versus written feedback ) results in more medication changes , measured at different moments in time . To determine the costs and savings related to such an intervention . DESIGN OF STUDY R and omised , controlled trial , r and omisation at the level of the community pharmacy . SETTING Primary care ; treatment review s were performed by 28 pharmacists and 77 GPs concerning 738 older people ( > or = 75 years ) on polypharmacy ( > five medicines ) . METHOD In one group , pharmacists and GPs performed case conferences on prescription-related problems ; in the other group , pharmacists provided results of a treatment review to GPs as written feedback . Number of medication changes was counted following clinical ly-relevant recommendations . Costs and savings associated with the intervention at various times were calculated . RESULTS In the case-conference group significantly more medication changes were initiated ( 42 versus 22 , P = 0.02 ) . This difference was also present 6 months after treatment review s ( 36 versus 19 , P = 0.02 ) . Nine months after treatment review s , the difference was no longer significant ( 33 versus 19 , P = 0.07 ) . Additional costs in the case-conference group seem to be covered by the slightly greater savings in this group . CONCLUSION Performing treatment review s with case conferences leads to greater uptake of clinical ly-relevant recommendations . Extra costs seem to be covered by related savings . The effect of the intervention declines over time , so performing treatment review s for older people should be integrated in the routine collaboration between GPs and pharmacists Abstract Objective : To evaluate the feasibility and impact of a structured approach for community pharmacist input as a member of the multidisciplinary team caring for patients with type-2 diabetes and health professional providing advice on medication . Methods : Prospect i ve pretest-posttest single group study . Sixty-two patients on oral hypoglycaemic therapy , identified as regular customers of four Scottish ( UK ) community pharmacies , were recruited . Each patient underwent an initial assessment : review of medical general practice notes/community pharmacy PMR ( Patient medication record ) system and structured interview . St and ardised documentation was completed , a pharmaceutical care plan ( PCP ) prepared , peer- review ed and then discussed face-to-face with patients ' GPs ( general practitioners ) . A second ( final ) assessment was conducted 24 to 28 weeks from the initial interview . Main outcome measures : Pharmaceutical care issues ( PCIs ) throughout study period ; change in parameters from initial to final assessment : patient knowledge of oral hypoglycaemic and anti-hypertensive therapy ; HbA1c ; blood pressure ; total cholesterol ; medication compliance . Results : A total of 178 PCIs were identified ( mean [ range ] 2.9 [ 1–5 ] per patient ) and categorised : drug therapy problems ( n=76 ) ; monitoring ( n=21 ) ; and patient knowledge ( n=81 ) . Drug therapy problems discussed with the GPs were agreed for 74 ( 97 % ) and resolved for 55 ( 72 % ) at final assessment . Biological outcome measures were assessed for 59 patients ( 3 drop-outs ) . A reduction ( P < 0.05 ) in HbA1c , blood pressure and total cholesterol was observed over the study period . Patients knowledge was poor for oral hypoglycaemic therapy but improved ( initial-51 % , final-72 % , P < 0.05 ) . Conclusion : This study demonstrated a feasible pharmaceutical care model for diabetes patients in an European country . The results have shown the pharmacist to be effective and well accepted by GPs and patients Objective The objective of this study was to assess implementation of a pharmaceutical care model for the multidisciplinary care of elderly patients in nursing homes . Setting Prospect i ve study , medication review , from January 2007 to December 2009 in ten nursing homes affiliated to the Pharmacie interjurassienne ( PIJ ) , Switzerl and . Method Medication use data were collected and review ed by a pharmacist , focusing on drug indication , dosing , side effects , renal/hepatic elimination and interactions . Drug-related problems ( DRPs ) were discussed face-to-face with the responsible physician and a nurse . The pharmaceutical care issues were formulated and medication interventions proposed during this meeting . DRPs and interventions were documented using the Pharmaceutical Care Network Europe scheme version 5.00 ( PCNE V5.00 ) . The economic impact of the service was estimated through a retrospective evaluation of annual drug costs . A satisfaction evaluation was conducted among practitioners and nurses . Main outcome measures DRPs , interventions , treatment changes implemented . Results Drug therapy of 329 patients was review ed . The number of medicines per patient ranged from 2 to 27 ( mean 12.8 ) . A total of 1,225 DRPs were detected and discussed with the physician and the nurse . Medication review led to 343 medical evaluations secondary to drug-drug interactions and 803 treatment adaptations : 373 drugs were stopped , 197 dosages changed , 95 instructions for use amended , 86 drug choices were altered , 35 drug formulations changed and 17 new drugs started . According to the Anatomical Classification System , the main classes involved in interventions were related to Alimentary tract and metabolism ( n = 285 ) , Nervous system ( n = 189 ) and Cardiovascular system ( n = 115 ) . Since the outset of the PIJ , the annual drug costs decreased in nursing homes with medication review including a pharmacist , whereas it was stable in the other nursing homes . The satisfaction evaluation showed a very positive appreciation by practitioners and nurses . Conclusion The study showed an efficient pharmaceutical care model , well accepted by physicians and nurses . It also indicated that for elderly patients , continuous drug review contributed to improved drug therapy , reduced unnecessary polypharmacy and reduced pharmaceutical costs OBJECTIVE To evaluate the effects of pharmacist-conducted medication therapy review ( MTR ) and intervention on the quality of care of patients in a family medicine clinic . DESIGN Prospect i ve , observational , cohort study . SETTING Family medicine clinic in Minnesota during 2000 - 2001 . PATIENTS Patients were enrolled in a statewide nonprofit managed care organization ; selected patients were seen by a clinical pharmacist . INTERVENTION Following MTR , medication-related problems ( MRPs ) were identified and resolved . MAIN OUTCOME MEASURES MRPs identified and resolved , improvement in clinical status , achievement of therapeutic goals , important medication use , and reduction in number of medications . RESULTS 92 patients were included in the study , with a total of 203 patient encounters . MRPs were identified in 90 % of patients , with a total of 250 identified . Overall status of medical conditions improved in 45 % of patients , 46 % stayed the same , and 9 % declined ( P < 0.001 ) . Significant improvement in status was found for hypertension ( P = 0.007 ) , dyslipidemia ( P = 0.002 ) , and asthma ( P = 0.011 ) . Significant improvement was seen for aspirin use for myocardial infa rct ion prevention ( 50 % vs. 93 % , P = 0.031 ) and inhaled steroids for asthma ( 36 % vs. 64 % , P = 0.031 ) . The number of medications was reduced from an average of 3.92 to 3.04 ( P < 0.001 ) per patient . CONCLUSION MTR and intervention by a pharmacist positively affected quality of care in this family medicine clinic OBJECTIVE To assess whether home-based medication review by a pharmacist for at-risk older patients in a primary care setting can reduce hospital admissions . DESIGN R and omised controlled trial comparing home-based medication review with st and ard care . SETTING Home-based medication review of 136 patients registered with one general practice . METHOD Study participants were over 80 years of age , living at home , taking four or more medicines , and had at least one additional medicines-related risk factor . The intervention comprised two home visits by a community pharmacist who educated the patient/carer about their medicines , noted any pharmaceutical care issues , assessed need for an adherence aid , and subsequently met with the lead GP to agree on actions . MAIN OUTCOME MEASURE Total non-elective hospital admissions within 6 months . Secondary outcomes included number of deaths , care home admissions and quality of life ( EQ-5d ) . Impact on number of medicines prescribed was also assessed . RESULTS At 6 months , no difference in hospital admissions ( 21 intervention versus 20 control P = 0.80 ) , and no difference in care home admissions or deaths were detected between groups . There was a small ( non-significant ) decrease in quality of life in the intervention group . There was a statistically significant reduction in the mean number of medicines prescribed ( -0.87 items in favour of the intervention group , 95 % confidence interval -1.66 to -0.08 , P = 0.03 ) . CONCLUSIONS No positive impact on clinical outcomes or quality of life was demonstrated , however , this intervention did appear to reduce prescribing . This is in line with other evidence and suggests that this form of intervention may not have a clear health gain , but may lead to modest savings in terms of reduced prescribing . Future research should focus on whether such a prescribing effect would make this type of intervention cost effective Background : Medical in patients are at risk for suboptimal health outcomes from adverse drug events and under-use of evidence -based therapies . We sought to determine whether collaborative care including a team-based clinical pharmacist improves the quality of prescribed drug therapy and reduces hospital readmission . Methods : Multicenter , quasi-r and omized , controlled clinical trial . Consecutive patients admitted to 2 internal and 2 family medicine teams in 3 teaching hospitals between January 30 , 2006 and February 2 , 2007 were included . Team care patients received proactive clinical pharmacist services ( medication history , patient-care round participation , resolution of drug-related issues , and discharge counseling ) . Usual care patients received traditional reactive clinical pharmacist services . The primary outcome was the overall quality score measured retrospectively by a blinded chart review er using 20 indicators targeting 5 conditions . Secondary outcomes included 3- and 6-month readmission . Results : A total of 452 patients ( 220 team care , 231 usual care , mean age : 74 years , 46 % male ) met eligibility criteria . Team care patients were more likely than usual care patients to receive care specified by the indicators overall ( 56.4 % vs. 45.3 % ; adjusted mean difference : 10.4 % ; 95 % confidence interval [ CI ] : 4.9 % , 15.7 % ) and for each targeted disease state except for heart failure . Team care patients experienced fewer readmissions at 3 months ( 36.2 % vs. 45.5 % ; adjusted OR : 0.63 ; 95 % CI : 0.42 , 0.94 ) but not at 6 months ( 50.7 % vs. 56.3 % ; adjusted OR ; 0.78 ; 95 % CI : 0.53 , 1.15 ) . Conclusions : In patients admitted to internal and family medicine teams , team-based care including a clinical pharmacist , improved the overall quality of medication use and reduced rates of readmission INTRODUCTION Australia has a rapidly ageing population , especially in rural areas , and strategies to address medicines and the elderly are particularly relevant . The aims of this 18 month study , therefore , were to : ( 1 ) determine the influence of a medication review on the quality of life of elderly ambulatory patients managed by a general practitioner ; and ( 2 ) assess the impact of the medication review process on health outcomes such as medication-related hospital admissions in ambulant elderly patients actively managed by their GP . METHODS The study was conducted within the area serviced by the rural Riverina Division of General Practice , New South Wales , Australia . Patients were identified by clinical audit , and recruited to the study if they met the inclusion criteria of being : older than 65 years , ambulant , living independently and on five or more medications . The study sample consisted of 402 participants ( 156 men , 38.8 % ; 246 women , 61.2 % ) . Fifty-eight participants withdrew from the study for a variety of reasons . A two-group ( intervention , control ) pre- and post-intervention r and omized study design was utilized . Quality of life was assessed using SF-36 . The medication history and clinical details of the 202 study participants were review ed by the project pharmacist and their GP . Medication changes were suggested to patients by their GP and follow-up SF36 and review of hospitalisation episodes were conducted after 6 months . RESULTS 3382 medications were identified as being taken , an average of 8.4 medications per patient . After the initial medication review , the study pharmacist suggested an alteration in dose , form or frequency for 687 medications in the intervention group . The GPs recommended an alteration in 243 of patient medications . Of the entire study population ( n = 402 ) , only two participants ' admission to hospital was specifically attributed to medication-related issues . There were no significant differences between the quality of life assessment s for the combined groups ; however , the intervention group recorded significantly higher scores in two of the nine dimensions measured : vitality ( p 0.009 ) and mental health ( p 0.0001 ) , at the post-intervention assessment . CONCLUSION While the intervention did not reduce hospitalisation episodes and only led to a modest improvement in quality of life , the development of a mutually acceptable form of face-to-face pharmacist/GP medication review , identification of potentially serious adverse drug reactions , identification of previously unreported complementary medicine use , and enhanced GP awareness of the risks of polypharmacy were positive outcomes of the study AIMS To examine the effectiveness of a multidisciplinary service model delivering medication review to patients at risk of medication misadventure in the community . METHODS The study was carried out in three Australian states ; Queensl and , New South Wales and Western Australia , and conducted as a r and omized , controlled effectiveness trial with the general practitioner ( GP ) as the unit of r and omization . In total , 92 GPs , 53 pharmacists and 400 patients enrolled in the study . The multidisciplinary service model consisted of GP education , patient home visits , pharmacist medication review s , primary healthcare team conferences , GP implementation of action plans in consultation with patients , and follow-up surgery visits for monitoring . Effectiveness was assessed using the four clinical value compass domains of ( i ) functional status , ( ii ) clinical outcomes , ( iii ) satisfaction and ( iv ) costs . The domains of functional status ( assessed by the health-related quality of life measure SF-36 subscales ) and clinical outcomes ( as assessed by adverse drug events ( ADEs ) , number of GP visits , hospital services and severity of illness ) were measured at baseline and endpoint . Satisfaction was measured by success in implementation and by participant satisfaction at endpoint , and costs ( as assessed using medication and healthcare service costs , less intervention costs ) were measured preintervention and during the trial . In addition , process evaluation was conducted for intervention patients , in which problems and recommendations from the medication review s were described . RESULTS The model was successfully implemented with 92 % of intervention GPs suggesting that the model had improved the care of participating patients , a view shared by 94 % of pharmacists . In addition , positive trends in clinical outcomes ( ADEs and severity of illness ) and costs ( an ongoing trend towards reduction in healthcare service costs ) were evident , although the trial was limited to a 6-month intervention time . No differences between intervention and control groups were identified for the health-related quality of life domain . The cost-effectiveness ratio for the intervention based on cost savings , reduced adverse events and improved health outcomes was small . The most common problems identified in the medication review s were potential adverse drug reactions , suboptimal monitoring and adherence/lack of concordance issues . In total , 54.4 % of recommendations were enacted , and 23.9 % were implemented precisely as recommended in the medication review . Follow-up evaluation showed that 70.9 % of actions had a positive outcome , 15.7 % no effect and 3.7 % had a negative outcome . CONCLUSIONS Most studies emphasize efficacy and the best achievable clinical outcomes rather than whether an intervention will be effective in practice . The current trial showed that three of the four domains in the clinical value compass showed trends of improvement or were indeed improved in the relatively short follow-up period of the trial , suggesting that a service based on this model could achieve similar benefits in practice . A domiciliary medication review programme similar to this model has now been implemented into national Australian practice , where GPs and pharmacists are reimbursed by the Australian government for the provision of these services Background Hospital admissions are a risk factor for the occurrence of unintended medication discrepancies between drugs used before admission and after discharge . To diminish such discrepancies and improve quality of care , medication reconciliation has been developed . The exact contribution of patient counseling to the medication reconciliation process is unknown , especially not when compared with community pharmacy medication records , which are considered reliable in the Netherl and s. Objective To examine the effect of medication reconciliation with and without patient counseling among patients at the time of hospital discharge on the number and type of interventions aim ed at preventing drug-related problems . Methods A prospect i ve observational study in a general teaching hospital was performed . Patients discharged from the pulmonology department were included . A pharmacy team assessed the interventions with and without patient counseling on discharge medications for each patient . Results Two hundred sixty-two patients were included . Medication reconciliation without patient counseling was responsible for at least one intervention in 87 % of patients ( mean 2.7 interventions /patient ) . After patient counseling , at least one intervention ( mean 5.3 interventions /patient ) was performed in 97 % of patients . After patient counseling , discharge prescriptions were frequently adjusted due to discrepancies in use or need of drug therapy . Most interventions led to the start of medication due to omission and dose changes due to incorrect dosages being prescribed . Patients also addressed their problems/concerns with use of the drug , which were discussed before discharge . Conclusions Significantly more interventions were identified after patient counseling . Therefore , patient information is essential in medication reconciliation As asthma is associated with an enormous social , psychological , and economic burden , various patient education programs have been developed to improve outcomes , including quality of life . The authors evaluated the effectiveness of community pharmacy-based interventions on lung function , health-related quality of life , and self-management in asthma patients in a 12-month controlled intervention study in 26 intervention and 22 control pharmacies . Pharmacies opted whether to take part as intervention or control pharmacies . According to this , patients ( ages 18 - 65 ) with mild to severe asthma attending the pharmacies were allocated to the intervention ( n = 161 ) or control group ( n = 81 ) , respectively . Intervention patients were educated on their disease , pharmacotherapy , and self-management ; inhalation technique was assessed and , if necessary , corrected . Pharmaceutical care led to significantly improved inhalation technique . Asthma-specific quality of life and the mental health summary score of the SF-36 improved significantly in the intervention group . At 12 months , the intervention group showed significant improvements with regard to evening peak flow , self-efficacy , and knowledge BACKGROUND Drug-related problems ( DRPs ) in Australian aged care homes have been studied previously . However , little is known about the acceptance and implementation of pharmacists ' recommendations by general practitioners ( GPs ) to resolve DRPs . OBJECTIVES The primary objective of this study was to investigate the number and nature of DRPs identified by accredited clinical pharmacists . The secondary objective was to study the GP acceptance and implementation of pharmacist recommendations to resolve DRPs . METHODS This was a retrospective study of 500 r and omly selected , de-identified medication review s performed by 10 accredited clinical pharmacists over 6 months across 62 aged care homes . The DRPs identified by pharmacists were subsequently classified by the drugs involved , types of problem ( indication , effectiveness and safety ) and medical diagnoses of the patient . GP written feedback on the medication review reports determined implementation of pharmacists ' recommendations to resolve the DRPs . RESULTS A total of 1433 DRPs were identified in 480 of the 500 residents . Potential DRPs were frequently classified as risk of adverse drug reactions , need for additional monitoring and inappropriate choice of a drug . Alimentary , cardiovascular , central nervous system and respiratory drugs were most frequently implicated , accounting for more than 75 % of the DRPs . GPs ' acceptance and implementation of pharmacists recommendations were 72.5 % ( 95 % CI ; 70.2 , 74.8 ) and 58.1 % ( 95 % CI ; 55.5 , 60.6 ) , respectively . CONCLUSIONS Over 96 % of the residents had potential DRPs identified by pharmacists . GP acceptance of pharmacists ' recommendations was independent of the drug category , but not independent of the disease category AIMS To determine whether a medicine review and education programme influences the compliance and knowledge of older people in general practice . METHODS Older people taking at least three medicines were r and omly allocated to a control or intervention group . Both groups received three visits from a clinical pharmacist : Visit 1 : Assessment and patients ' medicines rationalized in intervention group . Visit 2 : Intervention group given medicines education . Visit 3 : Knowledge and compliance in both groups assessed by structured question naire RESULTS Compliance in the intervention group was 91.3 % , compared with 79.5 % in the control group ( P < 0.0001 ) . The number of intervention group patients correctly underst and ing the purpose of their medicines increased from 58 % to 88 % on the second visit , compared with 67 % to 70 % in the control group ( P < 0.0005 ) . CONCLUSIONS A general practice based medication review and education programme improved medicine compliance and knowledge of older people in the short term The effects of pharmaceutical care on medication cost and quality of care in a university-based family- practice clinic were studied . Prognostic indicators were used to target patients who should receive pharmaceutical care . Those patients who received care . Those patients who received pharmaceutical care over a 14-month period during 1988 - 89 were included in the study . A pharmacist interviewed each targeted patient , obtained the patient 's medication history , made therapeutic recommendations to the patient 's physician , and counseled the patient on his or her therapy . The pharmacist 's recommendations were noted , and the outcome of each recommendation was documented on subsequent patient visits . For each recommendation , drug cost avoidance was calculated and patient outcome was analyzed . For quality assessment , a panel of three health-care professionals review ed the pharmacist 's recommendations for 25 % of the study patients ( r and omly selected ) and noted their agreement or disagreement with the pharmacist 's actions . Over the study period , 184 targeted patients received pharmaceutical care . Clinic physicians accepted 297 ( 82.5 % ) of 360 pharmacist recommendations . Annual extrapolated cost avoidance associated with the pharmacist 's recommendations was $ 19,076 . For 213 ( 80.4 % ) of the 265 accepted recommendations for which outcome data were available , improvement or resolution of the patient 's disease state occurred . For 8 ( 16 % ) of 50 unaccepted recommendations , the patient 's status declined . The peer review panel agreed with 86 % of the pharmacist 's recommendations . The provision of comprehensive pharmaceutical care in an ambulatory-care clinic can both reduce medication costs and improve quality of care BACKGROUND Medication review by pharmacists is increasingly being implemented in the primary care setting and has been incorporated into the new pharmacy contract in the UK . This study aims to determine the cost effectiveness of home-based medication review in older people . METHODS This economic evaluation was based on a r and omised controlled trial ( the HOMER [ HOME-based medication Review ] trial ) . Patients aged > 80 years ( n = 872 ) were recruited if admitted as an emergency to an acute or community hospital in Norfolk or Suffolk ( any cause ) , returning to their own home or warden-controlled accommodation , and taking two or more drugs daily on discharge . Patients r and omised to the intervention group received two home visits by a pharmacist within 2 and 8 weeks of discharge to educate patients and carers about their drugs , remove out-of- date drugs , inform GPs of drug reactions or interactions and inform the local pharmacist if an adherence aid was needed . The control arm received usual care . Economic evaluation was performed from the UK NHS perspective , with follow-up for 6 months and cost data from 2000 . Re source use data were collected from hospital episode statistics and from a sample of GP records of trial participants . Intervention , hospital , ambulance and general practice costs were considered to determine average costs and incremental cost-effectiveness ratios . Use of the EQ-5D question naire permitted outcomes to be expressed as QALYs . Probabilistic sensitivity analysis was employed to calculate cost-effectiveness acceptability curves . RESULTS Mortality and admission data were available for 829 of 855 patients included in the study ( 415 intervention and 414 control patients ) . Of those patients r and omised to the intervention group , 358 had a medication review at a total intervention cost of 51,622 pound ( or 124 pound per r and omised patient ) . The intervention did not reduce hospital admissions . The average cost per intervention group patient was 1695 pound compared with 1424 pound for control patients . The incremental cost per life year gained through the intervention was 33,541 pound . The incremental cost per QALY gained in the intervention was 54,454 pound . Sensitivity analysis suggested a 25 % probability that home-based medication review is cost effective using a threshold of 30,000 pound per QALY . CONCLUSION The current policy imperative for implementing medicines review needs to be reconsidered in the light of the findings of this study : a small , non significant gain in quality of life , no reduction in hospital admissions and a low probability of cost effectiveness BACKGROUND There have been recent moves to extend the role of the community pharmacist to include medicine management . METHODS A r and omized controlled trial was conducted in nine sites in Engl and . Patients with coronary heart disease were identified from general practice computer systems , recruited and r and omized ( 2:1 ) to intervention or control . The 12-month intervention comprised an initial consultation with a community pharmacist to review appropriateness of therapy , compliance , lifestyle , social and support issues . Control patients received st and ard care . The primary outcome measures were appropriate treatment [ derived from the National Service Framework ( NSF ) ] , health status ( SF-36 , EQ-5D ) and an economic evaluation . Secondary outcome measures were patient risk of cardiovascular death and satisfaction . RESULTS The study involved 1493 patients ( 980 intervention and 513 control ) , 62 pharmacists and 164 GPs . No statistically significant differences between intervention and control groups were shown at follow-up for any of the primary outcome measures such as numbers on aspirin or lifestyle measures . There were few differences in quality of life ( SF-36 ) between the intervention and control groups at baseline or follow-up or with overall EQ-5D score over time . The total National Health Service cost increased between baseline and at 12 months in both groups but to a greater extent in the intervention group . Significant improvements were found in the satisfaction score for patients ' most recent pharmacy visit for prescription medicines among the intervention group , compared with control group . Self-reported compliance was good for both groups at baseline and no significant differences were shown at follow-up . CONCLUSION There was no change in the proportion of patients receiving appropriate medication as defined by the NSF . The pharmacist-led service was more expensive than st and ard care OBJECTIVES To evaluate the cost-effectiveness of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in Northern Irel and ( Fleetwood NI Study ) . DESIGN Economic evaluation alongside a cluster r and omized controlled trial . SETTING Nursing homes in NI r and omized to intervention ( receipt of the adapted model of care ; n=11 ) or control ( usual care continued ; n=11 ) . PARTICIPANTS Residents aged 65 and older who provided informed consent ( N=253 ; 128 intervention , 125 control ) and who had full re source use data at 12 months . INTERVENTION Trained pharmacists review ed intervention home residents ' clinical and prescribing information for 12 months , applied an algorithm that guided them in assessing the appropriateness of psychoactive medication , and worked with prescribers ( general practitioners ) to make changes . The control homes received usual care in which there was no pharmacist intervention . MEASUREMENTS The proportion of residents prescribed one or more inappropriate psychoactive medications ( according to st and ardized protocol s ) , costs , and a cost-effectiveness acceptability curve . The latter two outcomes are the focus for this article . RESULTS The proportions of residents receiving inappropriate psychoactive medication at 12 months in the intervention and control group were 19.5 % and 50.4 % , respectively . The mean cost of healthcare re sources used per resident per year was $ 4,923 ( 95 % confidence interval (CI)=$4,206 - 5,640 ) for the intervention group and $ 5,053 ( 95 % CI=$4,328 - 5,779 ) for the control group . The probability of the intervention being cost-effective was high , even at low levels of willingness to pay to avoid a resident receiving inappropriately prescribed psychoactive medication . CONCLUSION The Fleetwood NI model of care was more cost-effective than usual care OBJECTIVE To evaluate the impact of regular multidisciplinary team interventions on the quantity and quality of psychotropic drug prescribing in Swedish nursing homes . DESIGN A r and omized controlled trial . SETTING A sample of 33 nursing homes : 15 experimental homes and 18 control homes representing 5 % of all Swedish nursing homes . PARTICIPANTS The sample consisted of 1854 long-term care residents with an average age of 83 years . Seventy percent of the residents were women , and 42 % had a documented diagnosis of dementia . An additional 5 % had a psychotic disorder , and 7 % had a diagnosis of depression . INTERVENTION Experimental homes participated in an outreach program that was design ed to influence drug use through improved teamwork among physicians , pharmacists , nurses , and nurses ' assistants . Multidisciplinary team meetings were held on a regular basis throughout the 12-month study period . MEASUREMENTS Lists of each resident 's prescriptions were collected 1 month before and 1 month after the 12-month intervention . Measures included the proportion of residents with any psychotropic drug , polymedicine , and therapeutic duplication and proportion of residents with nonrecommended and acceptable drugs in each psychotropic drug class , as defined by current Swedish guidelines . RESULTS Baseline results show extensive psychotropic drug prescribing , with the most commonly prescribed drugs being hypnotics ( 40 % ) , anxiolytics ( 40 % ) , and antipsychotics ( 38 % ) . After 12 months of team meetings in the experimental homes , there was a significant decrease in the prescribing of psychotics ( -19 % ) , benzodiazepine hypnotics ( -37 % ) , and antidepressants ( -59 % ) . Orders for more acceptable antidepressants also increased in the experimental homes . In the control homes there was increased use of acceptable antidepressants , but there were no significant reductions in other drug classes . CONCLUSIONS There is excessive prescription of psychotropic drugs in Swedish nursing homes . Improved teamwork among caregivers can improve prescribing as defined by clinical guidelines BACKGROUND efficient strategies are needed to provide specialist advice in nursing homes to ensure quality medical care . We describe a case conference intervention involving a multidisciplinary team of health professionals . OBJECTIVES to evaluate the impact of multidisciplinary case conferences on the appropriateness of medications and on patient behaviours in high-level residential aged care facilities . DESIGN cluster-r and omised controlled trial . SETTING ten high-level aged care facilities . PARTICIPANTS 154 residents with medication problems and /or challenging behaviours were selected for case conference by residential care staff . INTERVENTION two multidisciplinary case conferences involving the resident 's general practitioner , a geriatrician , a pharmacist and residential care staff were held at the nursing home for each resident . MEASUREMENTS outcomes were assessed at baseline and 3 months . The primary outcome was the Medication Appropriateness Index ( MAI ) . The behaviour of each resident was assessed via the Nursing Home Behaviour Problem Scale . RESULTS 45 residents died before follow-up . Medication appropriateness improved in the intervention group [ MAI mean change 4.1 , 95 % confidence interval ( CI ) 2.1 - 6.1 ] compared with the control group ( MAI mean change 0.4 , 95 % CI -0.4 - 1.2 ; P < 0.001 ) . There was a significant reduction in the MAI for benzodiazepines ( mean change control -0.38 , 95 % CI -1.02 - 0.27 versus intervention 0.73 , 95 % CI 0.16 - 1.30 ; P = 0.017 ) . Resident behaviours were unchanged after the intervention and the improved medication appropriateness did not extend to other residents in the facility . CONCLUSION multidisciplinary case conferences in nursing homes can improve care . Outreach specialist services can be delivered without direct patient contact and achieve improvements in prescribing OBJECTIVES There are conflicting results in studies of pharmacists undertaking medication review s for older people . With increasing promotion and funding for ' medication review s ' there is a need for them to be st and ardised , and to determine their effectiveness and the feasibility of providing them from a community pharmacy . The objective was to determine whether involvement of community pharmacists undertaking clinical medication review s , working with general practitioners , improved medicine-related therapeutic outcomes for patients . METHODS A r and omised controlled trial was carried out in people 65 years and older on five or more prescribed medicines . Community pharmacists undertook a clinical medication review ( Comprehensive Pharmaceutical Care ) and met with the patient 's general practitioner to discuss recommendations about possible medicine changes . The patients were followed-up 3-monthly . The control group received usual care . The main outcome measures were Quality of Life ( SF-36 ) and Medication Appropriateness Index . KEY FINDINGS A total of 498 patients were enrolled in the study . The quality -of-life domains of emotional role and social functioning were significantly reduced in the intervention group compared to the control group . The Medication Appropriateness Index was significantly improved in the intervention group . Only 39 % of the 44 pharmacists who agreed to participate in the study provided adequate data , which was a limitation of the study and indicated potential barriers to the generalisability of the study . CONCLUSION Clinical medication review s in collaboration with general practitioners can have a positive effect on the Medication Appropriateness Index . However , pharmacist withdrawal from the study suggests that community pharmacy may not be an appropriate environment from which to exp and clinical medication review s in primary care Background The Drug Burden Index ( DBI ) is an evidence -based tool that associates medication exposure with functional outcomes in older people . Accredited clinical pharmacists performing medication review s could consider including the DBI in their medication review s to optimize prescribing in older people . Objective To examine the impact of residential medication management review s ( RMMRs ) performed by accredited clinical pharmacists on DBI in older people living in aged-care homes . Methods A retrospective analysis was performed of a r and om sample of 500 de-identified RMMR reports from residents aged ( mean±SD ) 84±9.0 years who had medication review s conducted by ten accredited clinical pharmacists from 1 January 2008 through 30 June 2008 . The data on medication use were collected over 8 months across 62 aged-care homes . DBI scores were calculated at baseline , after the recommendations had been made by the pharmacist and after uptake of pharmacist recommendations by the general practitioner ( GP ) . Results A statistically significant decrease ( p<0.001 ) in median DBI score was observed as a result of uptake of pharmacist recommendations by the GP . GPs were more likely to take up recommendations made by pharmacists that result ed in a decrease in DBI score than recommendations that result ed in an increase in DBI score ( 60.7 % vs 34.6 % , respectively ) . The mean decrease in DBI as a result of pharmacist recommendations was 0.12 ( 95 % CI 0.09 , 0.14 ) representing a 20 % decrease in mean baseline DBI for residents . When GPs implemented pharmacists ’ recommendations , DBI decreased by a mean of 12 % from baseline ( mean decrease 0.07 ; 95 % CI 0.05 , 0.08 ) . Most of the recommendations proposed by the pharmacists involved withdrawing benzodiazepines or reducing antipsychotic drug dosage . Conclusions This is the first study in which DBI has been used as a tool to evaluate the impact of RMMRs conducted by accredited clinical pharmacists . The study demonstrates that pharmacist-conducted medication review s can reduce prescribing of sedative and anticholinergic drugs in older people , result ing in a significant decrease in the DBI score Background : There are concerns that automated drug dispensing may increase inappropriate drug use . Automated dispensing could lead to perpetual repeating of drug therapies without the necessary re-evaluation . Objectives : The aim of this study was to examine the effect of a pharmacist-led medication review on drug-related problems ( DRPs ) in older patients receiving their drugs via automated dispensing . Methods : This was a pragmatic r and omized controlled study conducted in primary care . Patients were recruited from six Dutch community pharmacies . They were eligible if they lived at home , were aged ≥65 years , and used five or more different drugs , of which at least one had to be dispensed via an automated system . Patients were r and omly allocated to receive a medication review at the start of the study ( intervention group ) or after 6 months ( waiting-list group ) . Each patient was independently review ed by two pharmacist review ers . The results of these medication review s were sent to the community pharmacist to be discussed with the patient ’s general practitioner ( GP ) . The primary outcome measure was the number of DRPs leading to a recommendation for drug change . Secondary outcomes were the total number of drug changes and the number of drug changes related to a recommendation . In order to analyse drug changes , medication records were collected 6 months after the medication review or index date in the waiting-list group . Potential DRPs were classified using the DOCUMENT classification . Results : There were no baseline differences between the 63 patients in the intervention group and the 55 patients in the waiting-list group with respect to age , sex , number of drugs per patient and type of drug prescribed . The mean number of DRPs per patient at baseline in the intervention group and waiting list combined was 8.5 , with no difference between the groups . At baseline , the mean number of DRPs leading to a recommendation for drug change was 4.5 per patient and did not differ between the two groups . After 6 months , the number of DRPs leading to a recommendation for drug change decreased by 29 % in the intervention group versus 5 % in the waiting-list group ( p < 0.01 ) . Recommendations for cessation of a drug were more frequently accepted than recommendations to add a new drug ( 82 % vs 44 % , p = 0.01 ) . Conclusions : This study shows that patients using automated drug dispensing have a high number of DRPs . Medication review decreases the number of DRPs among these patients . We recommend that all patients with automatic drug dispensing should have a thorough medication review by pharmacists and prescribers Background : Few studies have reported the efficacy of collaborative care involving family physicians and community pharmacists for patients with dyslipidemia . Methods : We r and omly assigned clusters consisting of at least two physicians and at least four pharmacists to provide collaborative care or usual care . Under the collaborative care model , pharmacists counselled patients about their medications , requested laboratory tests , monitored the effectiveness and safety of medications and patients ’ adherence to therapy , and adjusted medication dosages . After 12 months of follow-up , we assessed changes in low-density lipoprotein ( LDL ) cholesterol ( the primary outcome ) , the proportion of patients reaching their target lipid levels and changes in other risk factors . Results : Fifteen clusters representing a total of 77 physicians and 108 pharmacists were initially recruited , and a total of 51 physicians and 49 pharmacists were included in the final analyses . The collaborative care teams followed a total of 108 patients , and the usual care teams followed a total of 117 patients . At baseline , mean LDL cholesterol level was higher in the collaborative care group ( 3.5 v. 3.2 mmol/L , p = 0.05 ) . During the study , patients in the collaborative care group were less likely to receive high-potency statins ( 11 % v. 40 % ) , had more visits with health care professionals and more laboratory tests , were more likely to have their lipid-lowering treatment changed and were more likely to report lifestyle changes . At 12 months , the crude incremental mean reduction in LDL cholesterol in the collaborative care group was −0.2 mmol/L ( 95 % confidence interval [ CI ] −0.3 to −0.1 ) , and the adjusted reduction was −0.05 ( 95 % CI −0.3 to 0.2 ) . The crude relative risk of achieving lipid targets for patients in the collaborative care group was 1.10 ( 95 % CI 0.95 to 1.26 ) , and the adjusted relative risk was 1.16 ( 95 % CI 1.01 to 1.34 ) . Interpretation : Collaborative care involving physicians and pharmacists had no significant clinical impact on lipid control in patients with dyslipidemia . International St and ard R and omized Controlled Trial register no. IS RCT N66345533 |
11,754 | 28,170,080 | Based on the short-term results , glue may reduce postoperative chronic pain and not simultaneously increase the recurrence rate , compared with sutures for mesh fixation in Lichtenstein hernia repair .
Glue may therefore be a sensible alternative to suture for mesh fixation in Lichtenstein repair . | BACKGROUND Chronic pain following mesh-based inguinal hernia repair is frequently reported , and has a significant impact on quality of life .
Whether mesh fixation with glue can reduce chronic pain without increasing the recurrence rate is still controversial .
OBJECTIVES To determine whether tissue adhesives can reduce postoperative complications , especially chronic pain , with no increase in recurrence rate , compared with sutures for mesh fixation in Lichtenstein hernia repair . | Introduction With an average incidence rate of 11 % , chronic pain is considered the most serious complication of inguinal hernioplasty after surgical site infection . One of the proposed solutions to this problem is to use tissue adhesive for mesh fixation , which helps prevent nerve and tissue damage . Aim The goal of this study was to compare mesh fixation with the use of sutures vs. adhesive in Lichtenstein 's inguinal hernia repair in a r and omized , double-blind one-center study . Material and methods The study group consisted of 41 males with primary inguinal hernia undergoing Lichtenstein 's repair ( 20 – adhesive ; 21 – suture ) and remaining in follow-up from July 2008 to November 2010 . R and omization took place during the operation . The follow-up was performed by one surgeon ( blinded ) according to a pre-agreed schedule ; the end-of- study unblinding was performed during the last follow-up visit , usually 16 months postoperatively . Results In 1 patient from the “ adhesive ” group , a recurrence was observed one year after the initial repair . The early postoperative pain was less intense in this group . In later postoperative periods the method of mesh fixation had no influence on the pain experienced by the patient . Other complications were not correlated with the method of mesh fixation . Conclusions In this r and omized , one-center double-blind clinical study of males with primary inguinal hernia it has been show during follow-up that the use of Glubran 2 cyanoacrylate adhesive for mesh implant fixation yields similar recurrence and chronic pain rates as the classical suture technique . In the early postoperative period , the pain reported by these patients was relatively weaker ; patients undergoing adhesive mesh fixation experienced a quicker return to daily household activities BACKGROUND We compared the effectiveness of n-butyl-2-cyanoacrylate ( NBCA ) and traditional suture for patch fixation in Lichtenstein tension-free herniorrhaphy for inguinal hernias . METHODS A total of 110 patients with primary unilateral inguinal hernia were assigned r and omly to either experimental or control groups . In the experimental group , NBCA adhesive was used during Lichtenstein herniorrhaphy ; traditional suture was used in the control group . We evaluated operation time , postoperative duration of stay , visual analogue scale ( VAS ) pain score , incidence of chronic pain and hematoma formation , and hernia recurrence . RESULTS There was no hernia recurrence or wound infection in either group . In the experimental group , 2 local hematomas occurred while no patients experienced chronic postoperative pain ; in the control group , 10 hematomas occurred , and 6 patients experienced chronic pain . There was no difference in postoperative duration of stay between the groups ( P > .05 ) , but the experimental group had a lesser operation time and postoperative VAS score ( P < .05 ) . CONCLUSION The use of NBCA medical adhesive in tension-free inguinal herniorrhaphy is effective and safe The Lichtenstein hernioplasty has become a popular method in inguinal hernia repair . This study compared two methods of mesh fixation and wound closure . Forty-six men with unilateral inguinal hernia were r and omized into two groups . In the control group polypropylene mesh was anchored with 3/0 Dexon sutures , fascia and skin were closed with sutures 3/0 Dexon and 3/0 Monosof . In the study group , the mesh was secured with butyl-2-cyanoacrylate adhesive and the fascia and skin were also glued with the adhesive . The costs of material s , duration of the operation , amount of postoperative analgesic doses , pain score after the first and the 7th postoperative day and return to daily activity were recorded . No recurrences during the mean follow-up of 4.7 months were observed and the cosmetic effect was very good . In the study group with tissue adhesive the patients had significantly lower pain score after the first postoperative day and had a tendency to require less analgetic doses and to return earlier to their daily activity . Duration of the operation was similar in both groups . The cost of sutures and tissue adhesive used in both procedures was comparable . The use of tissue adhesive in mesh fixation and wound closure seems to be a promising technique in Lichtenstein hernia repair Introduction : This was a prospect i ve , r and omised study undertaken from January 2001 to July 2003 firstly to assess the possibility of using glues to fix meshes , secondly to verify whether or not this leads to a higher hernia recurrence rate , and thirdly to assess post-operative pain . Methods : This study covered a total of 55 patients with bilateral hernias who presented similar characteristics on both sides and on whom fixation of the mesh was undertaken differently , depending on the side . On the right side polypropylene sutures were used ( prolene 2/0 ) , while on the left , attachment was done using glue ( Tissucol ) . Results and conclusions : Results were similar in both inguinal regions , although there was less post-operative pain and less inflammatory reaction on the left side . There was no hernia recurrence in the follow-up at the end of 1 Purpose The aim of the present r and omised study was to find out whether usage of lightweight mesh in inguinal hernia repair , compared with heavyweight mesh , results in decreased incidence of chronic groin pain and foreign body feeling , as well as to evaluate the risk factors for chronic pain development and hernia recurrences . Methods The patients were r and omised into the heavyweight mesh ( HW ) group and lightweight mesh ( LW ) group . A tension-free mesh repair using the Lichtenstein technique was performed on all patients . Pain scores during different activities were measured on visual analogue scale . All patients underwent a clinical examination for any evidence of hernia recurrence . Results Of the patients , 17.2 % in the HW group and 29.3 % in the LW group reported that they experienced pain at 3-year follow-up ( P = 0.1323 ) . Pain was most often reported during physical activity . The median VAS score of all studied activities was 30.5 in the HW group and 30.0 in the LW group . There were more patients in the HW group than in the LW group who stated that they could feel the mesh in the groin ( 27.6 vs. 20.7 % , P = 0.3967 ) . Among all patients , 42.9 % who had severe pain preoperatively also reported pain during different activities and 19.6 % of the patients who did not have severe pain preoperatively reported pain during different activities ( P = 0.0481 ) . At 3-year follow-up , there was 1 hernia recurrence in the HW group and 1 hernia recurrence in the LW group . Conclusions Our study shows that compared with HW mesh , LW mesh has no advantage in reducing chronic groin pain and foreign body feeling at the operation site after inguinal hernioplasty at 3-year follow-up . Severe preoperative pain was correlated with the development of chronic pain . There was no difference between the two study groups in the recurrence rates A pre-trial was conducted to investigate the reliability of using the surgical adhesive , BioGlue ™ ( CryoLife ® , Inc. , Kennesaw , Georgia , USA ) for mesh fixation in Lichtenstein repair of inguinal hernia . From February to August 2008 , 60 patients with unilateral inguinal hernia underwent a Lichtenstein repair . In 30 of the patients , BioGlue ™ was used for mesh fixation and in the other 30 cases a conventional suture was used . The patients were sorted into two groups ( BioGlue ™ -group and suture-group ) . No differences were noted in demographic characteristics . The main criteria for dropout were incarceration , relapse , operation , and /or scrotal hernia . Twenty-four hours postoperative , pain intensity was measured with a numeric analogous scale ( NAS ) that reached from 0 ( no pain ) to 10 ( heavy pain ) . The pain intensity in the BioGlue ™ -group was 2.4 points and 4.3 points in the suture-group . The cut-suture time was 30 minutes in the BioGlue ™ -group and 56 minutes in the suture-group . In the first nine months , no relapses , no mesh infections , nor serom-formations were reported ; however , one superficial wound infection did occur in the BioGlue ™ -group . Lichtenstein-repair using BioGlue ™ for mesh-fixation is a safe , new method without early recurrences and less pain-intensity in relation to suture-supported Lichtenstein repair OBJECTIVE Three different mesh fixation techniques were compared to find out how to perform a safe and cost-effective open inguinal hernioplasty in day-case setting with the best outcomes with regard to chronic pain . SUMMARY BACKGROUND DATA Mesh fixation method may influence on the incidence of chronic pain after Lichtenstein hernioplasty . METHODS Lichtenstein hernioplasty was performed under local anesthesia in 625 patients as day-case surgery in 8 Finnish hospitals . The patients were r and omized to receive either a cyanoacrylate glue ( Histoacryl , n = 216 ) , self-gripping mesh ( Parietex ProGrip , n = 202 ) , or conventional nonabsorbable sutures ( Prolene 2 - 0 , n = 207 ) for mesh fixation . The incidence of wound complications , pain , recurrences , and patients discomfort was recorded on days 1 , 7 , 30 , and 1 year after surgery . The primary endpoint was the sensation of pain measured by pain scores and the need of analgesics after 1 year of surgery . RESULTS The type and size of inguinal hernias were similar in the 3 study groups . The duration of operation was 34 ± 13 , 32 ± 9 , and 38 ± 9 minutes in the glue , self-gripping , and suture groups , respectively ( P < 0.001 ) . There were no significant differences postoperatively in pain response or need for analgesics between the study groups . Two superficial infections ( 0.3 % ) , 31 wound seromas ( 5.0 % ) , and 4 recurrent hernias ( 0.6 % ) were recorded during a 1-year follow-up . Some 25 patients ( 4.2 % ) needed occasionally analgesics for chronic groin pain . A feeling of a foreign object and quality of life were similar in all study groups . CONCLUSIONS This r and omized trial failed to prove that mesh fixation without sutures causes less inguinodynia than suture fixation in Lichtenstein hernioplasty . Mesh fixation without sutures is feasible without compromising postoperative outcome Background Complications associated with sutured mesh fixation following open groin hernia repair have prompted surgeons to evaluate methods of atraumatic fixation such as the use of human fibrin glue . Small trials with Tissucol/Tisseel fibrin glue ( Baxter Healthcare , Deerfield , IL , USA ) have shown promising results that warrant further investigation . Methods TIMELI ( Tissucol/Tisseel for MEsh fixation in LIchtenstein hernia repair ) is an international , controlled , r and omized , patient- and evaluator-blinded study that is comparing mesh fixation with Tissucol or sutures in patients with inguinal hernia . The primary endpoint evaluates the incidence of disabling complications ( chronic pain and /or numbness and /or groin discomfort ) at 12 months post-surgery . Results Patient enrolment started in February 2006 and ended on 19 April 2007 , with a total of 325 patients recruited . Initial results are expected in early 2008 . Conclusions TIMELI is a major international trial that will provide important information on the efficacy and safety of Tissucol , compared with sutures , for mesh fixation in patients undergoing Lichtenstein technique for primary inguinal hernia repair Background Early post-operative pain after inguinal hernia repair delays management in ambulatory setting . The type of mesh used for repair appears to influence their incidence . Aims The aim of this r and omized , prospect i ve study using the alternation principle was to compare post-operative early pain and the quality of life of patients operated on for inguinal hernia depending on the type of mesh used and their impact on management in ambulatory setting . Patients and methods Fifty successive patients were included prospect ively . Hernia repair was performed using the Lichtenstein procedure with two types of mesh , namely st and ard polypropylene 100 g/m2 ( Prolène ® ) or light polypropylene ( 55 g/m2 ) with a natural beta-d-glucan coating ( Glucamesh ® ) . The main assessment criterion was post-operative pain evaluated twice daily by the patient for 7 days , using the visual analogue scale ( VAS ) and their use of analgesics . The secondary assessment criteria were the rate of unscheduled admissions the evening of the intervention and the hospital length of stay and the quality of life evaluated by the SF12 question naire at pre-operative stage and on days 7 and 30 . Results The two groups were comparable . The operative duration s were identical ( 38.8 ± 10.2 vs 48 ± 15.4 min ) . On the evening of the intervention before discharge , the pain was less intense in the Glucamesh ® group ( mean VAS score 21.6 ± 2.4 vs 31.7 ± 6.2 , p = 0.02 ) . On day 4 , 20 % of patients from the Glucamesh ® group and none of the patients from the Prolène ® group had a VAS score of 0 ( p = 0.02 ) . There were no unscheduled admissions in either group , but the hospital stay was significantly shorter in the Glucamesh ® group compared with the Prolène ® group ( 288 ± 35 vs 360 ± 48 min , p = 0.02 ) . The post-operative quality of life evaluated by the SF12 question naire from day 7 to day 30 was the same in both groups ( 38 ± 4.8 vs 37 ± 5.2 ) and altered as at pre-operative stage compared with a control population ( normal = 50 ) . Conclusions This r and omized , prospect i ve study showed that the use of a self-adhesive , light mesh , reducing the fixation sutures and coated with factors favouring tissue integration , such as the Glucamesh ® prosthesis , significantly reduced early post-operative pain compared with conventional prostheses and could increase the percentage of patients likely to undergo an ambulatory hernia repair Introduction Secure fixation of the mesh in groin hernia repair is essential to avoid mesh dislocation . The fixation , however , is also thought to be a source of chronic postoperative pain . We tested the new self-fixating mesh Parietene progrip © vs. traditional suture fixating Lichtenstein repair in a double-blinded r and omized study evaluating postoperative pain and the use of analgesics . Methods Fifty patients were r and omized into two groups : Patients of group A ( 24 patients ) were operated with the new self-fixating Parietene progrip © mesh without fixation sutures and patients of group B ( 26 patients ) were operated with the traditional Lichtenstein repair . Postoperative course including pain and the use of analgesics were monitored . Patients were reinvestigated after 6 months regarding pain score and the amount of analgesics used during this interval . Primary end point was pain on the first operative day . Results The visual analog scale pain score showed at the first postoperative day a significantly lower level in group A than in group B ( mean 17.9 vs. 32.3 mm , p = 0.03 ) . Additionally , the cumulative dose of postoperatively required analgesics was lower in group A than in group B. The operative time in group A was significantly shorter than in group B. Six months after the operation , a trend toward a lower pain score was observed in group A , but this did not reach statistical significance . Conclusions This is the first r and omized study to show a beneficial effect of the new self-fixating mesh on pain score . According to our investigations , operative time is reduced , which is a considerable fact with regard to economic aspects as well as the beneficial aspects for the patients . A study with a larger cohort of patients should be conducted to confirm the promising results of this exploratory study Abstract . Chronic inguinal pain occurs in 20–30 % of patients after hernia surgery . A prospect i ve r and omized study of 162 patients was undertaken to determine whether absorbable sutures cause less pain than continuous polypropylene fixation of the mesh in the Lichtenstein operation . All patients were operated on under local anesthesia by the same senior surgeon . One-half of the meshes were fixed with continuous 2 - 0 Dexon II sutures and one-half with continuous 2 - 0 Prolene sutures . The incidence of pain and recurrence was investigated after a mean follow-up of 2 years . Patient characteristics and operative outcome were similar in the two groups and statistically nonsignificant in both . The rate of significant wound hematomas ( n=3 ) , infections ( n=1 ) , and recurrences ( n=2 ) were low and not related to the type of sutures . In both study groups 24–26 % of the patients felt some pain in follow-up , but over 90 % were very satisfied with the operation . The absorbable suture material does not appear to cause less neuropathic pain after Lichtenstein operation than nonabsorbable sutures Inguinal hernia repair , according to Lichtenstein , is very popular due to its minimal invasiveness ( local anaesthesia ) , easy and reproducible technique , low recurrence rate , and low morbidity . However , recent publications demonstrate an elevated rate of chronic irritations and pain , probably due to tension or nerve compression by the fixing sutures . We , therefore , established a concept to avoid these sutures by attaching the prosthesis with glue . After a pilot study , a r and omised prospect i ve trial was started . The aim of our study was to compare the results of the classical Lichtenstein repair ( group 1 ) vs the " Sutureless Lichtenstein " ( group 2 ) in terms of postoperative complications and recurrences . Operative access and management of the hernial sac was equal to Lichtenstein for both groups . In group 1 , we sutured the mesh with PDS 2/0 ; in group 2 , the mesh was glued with n-butyl-cyanoacrylate . In both groups , the operation was then completed according to Lichtenstein , and unrestricted activity was allowed after 2 weeks . A total of 46 patients have been operated on . The follow-up results at 3 weeks and { 3 months}were : group 1 ( n=24 ) vs group 2 ( n=22 ) : recurrences 0 { 0 } vs 0 { 0 } , minor pain 8 { 4 } vs 4 { 1 } , local numbness 14 { 10 } vs 10 {6}. No adhesive-related complications were seen . Patients will be followed for 2 years . The results in group 2 were excellent , and there was no difference vs group 1 . Furthermore , there was a tendency for better results in group 2 . These results are very promising and justify a continuation of the study Introduction In inguinal hernia repair , many complications are due to mesh fixation technique . Therefore , new types of atraumatic methods of fixation have been proposed . In this article , we present the results of a prospect i ve multicentric parallel r and omized controlled trial aim ing to compare two mesh fixation techniques : fibrin sealant ( QUIXIL ® , Omrix Biopharmaceuticals S.A. , Belgium ) and Lichtenstein technique . Method Adult patients with primary uncomplicated inguinal hernia were r and omized in two groups : fibrin sealant group ( FSG ) and Lichtenstein group ( LTG ) . The two groups underwent a follow-up of 15 months . Operative time is the primary outcome . Intraoperative and postoperative outcomes were analyzed . Moreover , a differential cost analysis was performed . Patients and evaluators ( with exception of the surgeon who treated the patient ) were blinded . Results A total of 102 patients , 50 in FSG and 52 in LTG , were enrolled from January 2009 to June 2010 , and two patients were lost to follow-up at the twelfth month . No significant differences in baseline and clinical characteristics were observed in the two groups . Operative time was longer in LTG ( median/ interquartile range : 35 min/30–42.5 min vs. 31 min/28–35 min ; effect size : 0.65/95 % CI 0.50–0.91 ; p < 0.05 ) . No differences in intraoperative complications were observed . No significant differences were observed in early complication rate ( RR = 0.62 ; p > 0.05 ) . Numbness rate was lower in the FSG at 1 week ( RR = 0.43 ; p < 0.01 ) and at 1 month ( RR = 0.17 ; p < 0.05 ) . No significant differences were observed after 6 months . Postoperative pain was lower in the FSG at 1 week ( 0/0–1 vs. 1/0–2 ; p < 0.05 ) and at 1 month ( 0/0–0 vs. 0/0–1 ; p < 0.05 ) . Pain disappeared in all patients after 6 months . Analgesic assumption rate was lower in the FSG ( RR = 0.42 ; p < 0.05 ) . Twenty per cent of FSG and 9.62 % of LTG patients were discharged within 12 h ; 78 % of FSG and 90.38 % of LTG patients were discharged within 24 h. The only one recurrence we observed was in FSG group . About costs , although fibrin sealant needed for one mesh fixation is about 10 times more costly than the needed sutures , the total costs of the two procedures did not change significantly . This was mainly due to reduction in operative time . Conclusions The use of fibrin sealant determined a significant reduction in short-term numbness rate and postoperative pain . There was no relevant difference in total costs per patient between the two procedures BACKGROUND We sought to determine the efficacy of sutures , human fibrin glue and N-butyl-2-cyanoacrylate for mesh fixation in patients undergoing the plug and mesh procedure for groin hernia . METHODS A total of 156 patients with 167 inguinal hernias ( 11 bilateral ) underwent a plug and mesh procedure and were r and omly assigned to received either sutures ( n = 59 hernias ) , human fibrin glue ( n = 52 ) or N-butyl-2-cyanoacrylate ( n = 56 ) for mesh fixation . RESULTS The overall morbidity rate was 38.98 % in the suture group , 9.62 % in the fibrin glue group and 10.71 % in the N-butyl-2-cyanoacrylate group ( suture v. fibrin glue , p < 0.001 ; suture v. N-butyl-2-cyanoacrylate , p < 0.001 ) . There was no significant difference in morbidity between the fibrin glue and N-butyl-2-cyanoacrylate groups . Overall , short-term morbidity was significantly higher in the suture group ( 27.12 % ) than in the fibrin glue ( 9.62 % , p = 0.01 ) or N-butyl-2-cyanoacrylate ( 8.93 % , p = 0.004 ) groups , but there was no significant difference between the fibrin glue and N-butyl-2-cyanoacrylate groups . There was no significant difference between the groups in terms of mean postoperative stay ( 32.6 h in the suture group v. 30.8 h in the fibrin glue group v. 32.0 h in the N-butyl-2-cyanoacrylate group ) or mean time to return to work ( 20.4 d in the suture group v. 20.3 d in the fibrin glue group v. 19.8 d in the N-butyl-2-cyanoacrylate group ) . Overall , long-term morbidity was significantly higher in the suture group ( 11.86 % ) than in the fibrin glue ( 0 % , p = 0.001 ) or N-butyl-2-cyanoacrylate ( 1.78 % , p = 0.03 ) groups . There was no recurrence in any of the groups . Two cases ( 3.39 % ) of chronic groin pain were reported in patients in the suture group . A sensation of extraneous body was reported in 5 ( 8.47 % ) patients who received sutures and in 1 ( 1.78 % ) patient in the N-butyl-2-cyanoacrylate group ; there were no reported cases in the fibrin glue group ( suture v. fibrin glue , p = 0.01 ; suture v. N-butyl-2-cyanoacrylate , p = 0.03 ; fibrin glue v. N-butyl-2-cyanoacrylate , p = 0.30 ) . CONCLUSION The use of human fibrin glue or N-butyl-2-cyanoacrylate is better tolerated than sutures in tension-free inguinal open repair using the plug and mesh technique in terms of overall immediate results , and there is a better trend in the long-term data INTRODUCTION The use of synthetic glues has become normal practice in several surgical fields . The objective of this study is to compare the short and medium term results of glue and conventional suture in the fixation of the prosthesis in open inguinal hernia repair with a plug and patch technique . MATERIAL S AND METHODS A comparative prospect i ve study was conducted on 198 patients with a diagnosis of a non-recurrent inguinal hernia subjected to open surgery and r and omly assigned to mesh fixation with cyanoacrylate glue ( n=101 ) or with suture ( n=98 ) . The demographic characteristics , short-term complications , hospital stay , time off work , hernia recurrence , and chronic inguinal neuralgia , were analysed . RESULTS The overall morbidity was 13.9 % in the glue group , and 30.9 % in the suture group . No undue inflammatory reactions or mesh migration were observed in the group . The post-operative stay was 14.7h for the glue group , and 19.1h in the suture group ( P<.0001 ) . No differences were found regarding days off work . The short-term morbidity was higher in the suture group ( 19.6 % vs. 10.9 % ) . After one year , there was one recurrence in the suture group ( 1 % ) , and none in the glue group . However , the incidence of moderate/severe intensity chronic neuralgia was 2.9 % in the glue group , and 10.3 % in the suture group ( P=.03 ) . CONCLUSION The use of cyanoacrylate is safe and effective in open inguinal hernia repair , with good results in the short and medium term The aim of the present r and omized trial was to compare the Shouldice procedure and the Lichtenstein hernia repair with respect to recurrence rate , technical difficulty , convalescence and chronic pain . A further aim was to determine to what extent general surgeons in routine surgical practice were able to reproduce the excellent results reported from specialist hernia centres Background . The morbidity linked to the use of sutures in inguinal hernioplasty is well known . Tissue adhesives may be an alternative , so as to be able to improve levels of postoperative comfort , but clinical experience using them is limited . The aim of this study is to evaluate the efficiency of cyanoacrylate as a substitute for sutures in the treatment of inguinal hernias . Patients . R and omized clinical trial in abdominal wall unit . A total of 208 patients were operated upon for inguinal hernias of which 102 were unilateral hernias via open surgery using the Lichtenstein technique , r and omized to receive prolene sutures ( n = 52 ) or n-hexyl-α-cyanoacrylate glue ( n = 50 ) and 106 were patients with bilateral inguinal hernias operated upon via totally extraperitoneal laparoscopy and r and omized to receive either tackers ( n = 54 ) or glue ( n = 52 ) . Main Outcome Measures . The primary endpoints were pain and recurrence . Secondary endpoints were operating time , postoperative morbidity , pain , and analgesic consumption . Results . No morbidity associated with the use of the glue existed . The use of glue significantly reduced the mean of surgical time ( 12 minutes in open surgery , 13 minutes in laparoscopic surgery ) , pain , and analgesics consumption , both via the open and laparoscopic approaches ( P < .001 ) . After 1 year the adhesive did not change the recurrence rate in either of the approaches . The economic analysis shows potential yearly savings of 123 916.3 Euros . Conclusions . Substituting sutures with glue ( n-hexyl-α-cyanoacrylate ) in open or laparoscopic inguinal hernioplasty is safe with less postoperative pain and the same possibilities of recurrence PURPOSE The aim of this study is to evaluate pain and further disabling complications in patients undergoing Lichtenstein technique for primary inguinal hernia repair by fixing the mesh with fibrin sealant versus sutures . METHODS This study was carried out on 116 patients between January 2009 and July 2009 . All patients were male , between the ages of 20 and 75 years . Lichtenstein , using a polypropylene mesh as prosthetic material . A total of 116 hernias were operated on . Group I : 54 operations were done using the conventional repair procedure with polypropylene sutures ( prolene 2/0 ) for mesh fixation . Group II : 62 operations were done using fibrin glue for fixation of the mesh . All patients were operated as day cases , with a maximum hospital stay of 12 hours ; none required readmission . RESULTS No complications were observed in follow-up at 1 week , 1 month , 6 months and 12 months . At 12 months , none of the patients had developed a recurrence . The mean time for complete healing of wound after herniorrhaphy plus fibrin sealant was 8.13±7.88 days ( range 6 - 28 days ) . This was markedly increased in group 1 patients ( mean 12.08±8.59days , and range 8 - 32 ) ( p < 0.001).12 months after surgery , The median VAS pain score was significantly lower in group 2 patients ( P < 0·001 ) . The mean ( SD ) duration of incapacity for work was 5 ( 2 - 12 ) days in group 2(p < 0.001 ) . CONCLUSIONS This study confirms the effectiveness of fibrin glue in securing prosthetic meshes and reducing chronic inguinal pain . KEY WORDS Chronic pain , Fibrin glue , Inguinal hernia repair BACKGROUND Patients who underwent primary inguinal hernia repair still report a high rate of postoperative pain after operation due to the effect of mesh fixation by suture . An alternative is the use of human fibrin glue . We compared the two techniques . METHODS 468 patients r and omly underwent primary inguinal hernia Lichtenstein repair fixing the mesh by suture or by human fibrin glue ( HFG ) ; in both cases the mesh was fixed to the posterior wall of the inguinal canal and to the inguinal ligament . RESULTS No significant differences were recorded between the two groups in terms of complications , while the sutureless technique reduces the operative time and the postoperative pain . CONCLUSIONS A widespread technique for the treatment of inguinal hernia is the application of a mesh using Lichtenstein procedure . The prosthesis can be fixed by traditional suture or using a new method of sutureless fixation with adhesive material s that shows an excellent local tolerability and lack of adverse effects and contraindications Objective To evaluate the efficacy of mesh fixation with fibrin sealant ( FS ) in laparoscopic preperitoneal inguinal hernia repair and to compare it with stapled fixation . Summary Background Data Laparoscopic hernia repair involves the fixation of the prosthetic mesh in the preperitoneal space with staples to avoid displacement leading to recurrence . The use of staples is associated with a small but significant number of complications , mainly nerve injury and hematomas . FS ( Tisseel ) is a biodegradable adhesive obtained by a combination of human-derived fibrinogen and thrombin , duplicating the last step of the coagulation cascade . It can be used as an alternative method of fixation . Methods A prosthetic mesh was placed laparoscopically into the preperitoneal space in both groins in 25 female pigs and fixed with either FS or staples or left without fixation . The method of fixation was chosen by r and omization . The pigs were killed after 12 days to assess early graft incorporation . The following outcome measures were evaluated : macroscopic findings , including graft alignment and motion , tensile strength between the grafts and surrounding tissues , and histologic findings ( fibrous reaction and inflammatory response ) . Results The procedures were completed laparoscopically in 49 sites . Eighteen grafts were fixed with FS and 16 with staples ; 15 were not fixed . There was no significant difference in graft motion between the FS and stapled groups , but the nonfixed mesh had significantly more graft motion than in either of the fixed groups . There was no significant difference in median tensile strength between the FS and stapled groups . The tensile strength in the nonfixed group was significantly lower than the other two groups . FS triggered a significantly stronger fibrous reaction and inflammatory response than in the stapled and control groups . No infection related to method of fixation was observed in any group . Conclusion An adequate mesh fixation in the extraperitoneal inguinal area can be accomplished using FS . This method is mechanically equivalent to the fixation achieved by staples and superior to nonfixed grafts . Biologic soft fixation with FS will prevent early graft migration and will avoid the complications associated with staple use Purpose Groin hernia is one of the most common disease requiring surgical intervention ( 8–10 % of the male population ) . Nowadays , the application of prosthetic material s ( mesh ) is the technique most widely used in hernia repair . Although they are simple and rapid to perform , and lower the risk of recurrence , these techniques may lead to complications . The aim of the present study is to assess the incidence and degree of chronic pain , as well as the impairment in daily life , in two procedures : ( 1 ) the “ Lichtenstein technique ” with polypropylene mesh fixed with non-absorbable suture , and ( 2 ) the “ sutureless ” technique carried out by using a partially absorbable mesh ( light-weight mesh ) fastened with fibrin glue . Methods This was a study conducted over a period of 3 years from July 2006 to July 2009 . A total of 148 consecutive male patients suffering from groin hernia were divided r and omly into two groups : ( 1 ) Group A : patients operated with “ sutureless ” technique with partially absorbable mesh and plug fastened with 1 ml haemostatic sealant ; ( 2 ) Group B : patients operated with Lichtenstein technique using non-absorbable mesh and plug anchored with polypropylene suture . Follow-up took place after 7 days , and 1 , 6 and 12 months and consisted of examining and question ing patients about chronic pain as well as the amount of time required to return to their normal daily activities . Results No major complications or mortality were observed in either group . In group A there was a faster return to work and daily life activities . Six patients ( 7.8 % ) in group B suffered from chronic pain , whereas no patient in group A demonstrated this feature . Conclusions Our experience shows that the combined use of light-weight mesh and fibrin glue gives significantly better results in terms of postoperative pain and return to daily life Background Following Lichtenstein hernia repair , up to 25 % of patients experience prolonged postoperative and chronic pain as well as discomfort in the groin . One of the underlying causes of these complaints are the compression or irritation of nerves by the sutures used to fixate the mesh . We compared the level and rate of chronic pain in patients operated with the classical Lichtenstein technique fixated by sutures to patients with sutureless mesh fixation technique . Methods A two-armed r and omized trial with 264 male patients was performed . After consent , patients were r and omized preoperatively . For the fixation of the mesh we used either sutures with slow-absorbing material ( PDS 2.0 ) ( group I , n = 133 ) or tissue glue ( Histoacryl ) ( group II , n = 131 ) . Follow-up examinations were performed after 3 , 12 months and after 5 years . Results Patient characteristics in the two groups were similar . No cross-over between groups was observed . After 5 years , long-term follow-up could be completed for 59 % of subjects . After 5 years , 10/85 ( 11.7 % ) patients in group I and 3/70 ( 4.2 % ) in group II suffered from chronic pain in the groin region ( P = 0.108 ) . The operation time was significantly shorter in group II ( 79 min vs 73 min , P = 0.01 ) . One early recurrence occurred in group II ( 3 months ) . The recurrence rate was 0 and 0 % after 12 months and 5.9 % ( 5/85 ) and 10 % ( 7/70 ) after 5 years in group I and group II , respectively ( P = 0.379 ) . Conclusion After 5 years , the two techniques of mesh fixation result ed in similar rates of chronic pain . Whereas recurrence rates were comparable , fixation of the mesh with tissue glue decreased operating room time significantly . Hence , suture less mesh fixation with Histoacryl is a sensible alternative to suture fixation and should be especially considered for patients prone to pain Objective : Test the hypothesis that fibrin sealant mesh fixation can reduce the incidence of postoperative pain/numbness/groin discomfort by up to 50 % compared with sutures for repair of inguinal hernias using the Lichtenstein technique . Background : Inguinal hernia repair is the most common procedure in general surgery , thus improvements in surgical techniques , which reduce the burden of undesirable postoperative outcomes , are of clinical importance . Methods : A r and omized , controlled , patient- and evaluator-blinded study ( Tissucol/Tisseel for MEsh fixation in LIchtenstein hernia repair [ TIMELI ] ; trial NCT00306839 ) was conducted among patients eligible for Lichtenstein repair of uncomplicated unilateral primary inguinal small – medium sized hernia . Patients were subject to mesh fixation with either fibrin sealant or sutures . Main outcome measures were visual analogue scale ( VAS ) assessment s for “ pain , ” “ numbness , ” and “ groin discomfort ” on a scale of 0 = best and 100 = worst outcome . The primary endpoint was a composite that evaluated the prevalence of chronic disabling complications ( VAS score > 30 for pain/numbness/groin discomfort ) at 12 months after surgery . Results : In total , 319 patients were r and omized between January 2006 and April 2007 ( 159 fibrin sealant , 160 sutures ) . At 12 months , the prevalence of 1 or more disabling complication was significantly lower in the fibrin sealant group than in the sutures group ( 8.1 % vs 14.8 % ; P = 0.0344 ) . Less pain was reported in the fibrin sealant group than in the sutures group at 1 and 6 months ( P = 0.0132 ; P = 0.0052 ) , as reflected by a lower proportion of patients using analgesics in the fibrin group over the study duration ( 65.2 % vs 79.7 % ; P = 0.0009 ) . Only 3 of 316 patients ( 0.9 % ) experienced recurrence . The incidences of wound-healing complications and other adverse events were comparable between groups . Conclusions : Fibrin sealant for mesh fixation in Lichtenstein repair of small – medium sized inguinal hernias is well tolerated and reduces the rate of pain/numbness/groin discomfort by 45 % relative to sutures without increasing hernia recurrence ( NCT00306839 ) Purpose Various methods for the fixing of prosthetic mesh in open inguinal hernia repair are in vogue . We describe a novel way of fixing the mesh in Lichtenstein ’s method of hernia repair using tissue glue [ gelatin – resorcin – formalin ( GRF ) glue ] and compare it with the traditional method of fixing the mesh using non-absorbable sutures . Methods Eighty patients with uncomplicated inguinal hernia were alternately assigned to one of two groups of 40 patients each , i.e. , control group ( conventional Lichtenstein repair ) and study group ( repair using GRF glue ) . The primary end point was post-operative pain measured by the visual analog score and post-operative analgesic requirement . Results The post-operative pain was found to be significantly less in the study group as compared to the control group . Conclusions Using tissue ( GRF ) glue to fix the prosthetic mesh in Lichtenstein ’s method of hernia repair is a feasible and better alternative to non-absorbable sutures |
11,755 | 30,229,998 | Many nurses experienced napping during their night-shift although no clear policy emerged .
Napping is beneficial to the well-being of nurses and could improve their psychomotor vigilance and performance .
The evidence on reducing sleepiness and fatigue was also insufficient and napping in nursing still faces challenges .
Although research on this topic has just started , napping during night-shift is beneficial to nurses ' health and performance . | AIMS To synthesize research on the influence of night-shift napping on nurses .
BACKGROUND Shift work is common for hospital nurses .
Various studies corroborate that shift work causes adverse health consequences for nurses .
Night-shift napping is a countermeasure to address the adverse outcomes of shift work . | This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer In 2007 , the International Agency for Research on Cancer declared shift work that involved circadian disruption to be a " probable " carcinogen ( group 2A ) , noting that human evidence was limited . Using data from 2 prospect i ve cohort studies , the Nurses ' Health Study ( 1988 - 2012 ; n = 78,516 ) and Nurses ' Health Study II ( 1989 - 2013 ; n = 114,559 ) , we examined associations between rotating night-shift work and breast cancer risk . In the 2 cohorts , there were a total of 9,541 incident invasive breast malignancies and 24 years of follow-up . In the Nurses ' Health Study , women with 30 years or more of shift work did not have a higher risk of breast cancer ( hazard ratio ( HR ) = 0.95 , 95 % confidence interval ( 95 % CI ) : 0.77 , 1.17 ; P for trend = 0.63 ) compared with those who never did shift work , although follow-up occurred primarily after retirement from shift work . Among participants in the Nurses ' Health Study II , who were younger than participants in the other cohort , the risk of breast cancer was significantly higher in women with 20 years or more of shift work at baseline , reflecting young-adult exposure ( HR = 2.15 , 95 % CI : 1.23 , 3.73 ; P for trend = 0.23 ) , and was marginally significantly higher for women with 20 years or more of cumulative shift work when we used up date d exposure information ( HR = 1.40 , 95 % CI : 1.00 , 1.97 ; P for trend = 0.74 ) . In conclusion , long-term rotating night-shift work was associated with a higher risk of breast cancer , particularly among women who performed shift work during young adulthood . Further studies should explore the role of shift work timing on breast cancer risk CONTEXT Neuroendocrine and immune stresses imposed by chronic sleep restriction are known to be involved in the harmful cardiovascular effects associated with poor sleep . OBJECTIVES Despite a well-known beneficial effect of napping on alertness , its effects on neuroendocrine stress and immune responses after sleep restriction are largely unknown . DESIGN This study was a strictly controlled ( sleep-wake status , light environment , caloric intake ) , crossover , r and omized design in continuously polysomnography-monitored subjects . SETTING The study was conducted in a laboratory-based study . PARTICIPANTS The subjects were 11 healthy young men . INTERVENTION We investigated the effects on neuroendocrine and immune biomarkers of a night of sleep restricted to 2 h followed by a day without naps or with 30 minute morning and afternoon naps , both conditions followed by an ad libitum recovery night starting at 20:00 . MAIN OUTCOME MEASURES Salivary interleukin-6 and urinary catecholamines were assessed throughout the daytime study periods . RESULTS The increase in norepinephrine values seen at the end of the afternoon after the sleep-restricted night was not present when the subjects had the opportunity to take naps . Interleukin-6 changes observed after sleep deprivation were also normalized after napping . During the recovery day in the no-nap condition , there were increased levels of afternoon epinephrine and dopamine , which was not the case in the nap condition . A recovery night after napping was associated with a reduced amount of slow-wave sleep compared to after the no-nap condition . CONCLUSIONS Our data suggest that napping has stress-releasing and immune effects . Napping could be easily applied in real setting s as a countermeasure to the detrimental health consequences of sleep debt 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 Shift work has been hypothesized as a risk factor for obesity . In this study , we investigated the association between current shift work and body mass index ( BMI ) among female nurses in Korea . The relationship between duration of shift work and BMI of the participants was also evaluated . Methods This cross-sectional survey evaluated participants in the Korean Nurses ’ Survey , conducted from October to December 2011 , using web-based self-administered question naires . A total of 9,989 nurses were included among 10,000 who registered on the survey web site ( 5,287 shift workers and 4,702 non-shift workers ) . Current shift workers were divided into tertiles of shift work duration ( 0.08–3.00 years , n = 1,732 ; 3.08–6.75 years , n = 1,731 ; and 6.83–38.00 years , n = 1,686 ) . The BMI thresholds of overweight and obesity were ≥23 kg/m2 and ≥25 kg/m2 , respectively . Data were analyzed using SPSS software . Results Mean participant age was 33.2 ± 8.6 years and the mean BMI was 20.9 ± 2.5 kg/m2 . There were statistically significant differences in current smoking status , regular drinking habit , dietary habits , regular exercise , sleep problems and self-perceived health status according to duration of shift work . The overall prevalence of overweight/obesity ( 18.6 % ) and obesity ( 7.4 % ) increased significantly as shift work duration increased from the lowest to highest tertile ( P for trend < 0.001 ) . Multivariate logistic regression analysis revealed no association between current shift work and BMI . However , after adjusting for potential confounders , the participants with the longest duration of shift work were 1.63 ( 95 % CI , 1.22–2.17 ) times more likely to be overweight or obese than those with the shortest duration . There was a significant positive association between obesity and shift work duration in the unadjusted analysis ; however , it was attenuated and no longer significant in the multivariate model . Conclusions The duration of shift work was positively associated with prevalence of overweight/obesity in nurses in Korea . Although these findings need to be confirmed in prospect i ve studies , they suggest that special attention should be paid to female nurses with a long duration of shift work STUDY OBJECTIVES To assess sleep inertia following 10-min and 30-min naps during a simulated night shift . METHODS Thirty-one healthy adults ( aged 21 - 35 y ; 18 females ) participated in a 3-day laboratory study that included one baseline ( BL ) sleep ( 22:00 - 07:00 ) and one experimental night involving r and omization to either : total sleep deprivation ( NO-NAP ) , a 10-min nap ( 10-NAP ) or a 30-min nap ( 30-NAP ) . Nap opportunities ended at 04:00 . A 3-min psychomotor vigilance task ( PVT-B ) , digit-symbol substitution task ( DSST ) , fatigue scale , sleepiness scale , and self-rated performance scale were undertaken pre-nap ( 03:00 ) and at 2 , 17 , 32 , and 47 min post-nap . RESULTS The 30-NAP ( 14.7 ± 5.7 min ) had more slow wave sleep than the 10-NAP ( 0.8 ± 1.5 min ; P < 0.001 ) condition . In the NO-NAP condition , PVT-B performance was worse than pre-nap ( 4.6 ± 0.3 1/sec ) at 47 min post-nap ( 4.1 ± 0.4 1/sec ; P < 0.001 ) . There was no change across time in the 10-NAP condition . In the 30-NAP condition , performance immediately deteriorated from pre-nap ( 4.3 ± 0.3 1/sec ) and was still worse at 47 min post-nap ( 4.0 ± 0.5 1/sec ; P < 0.015 ) . DSST performance deteriorated in the NO-NAP ( worse than pre-nap from 17 to 47 min ; P < 0.008 ) , did not change in the 10-NAP , and was impaired 2 min post-nap in the 30-NAP condition ( P = 0.028 ) . All conditions self-rated performance as better than pre-nap for all post-nap test points ( P < 0.001 ) . CONCLUSIONS This study is the first to show that a 10-min ( but not a 30-min ) nighttime nap had minimal sleep inertia and helped to mitigate short-term performance impairment during a simulated night shift . Self-rated performance did not reflect objective performance following a nap OBJECTIVES To evaluate the effectiveness of a broad , literature -based night shiftwork intervention for enhancement of emergency physicians ' ( EPs ' ) adaptation to night rotations . METHODS A prospect i ve , double-blind , active placebo-controlled study was conducted on 6 attending physicians in a university hospital ED . Three data sets were collected under the following conditions : baseline , after active placebo intervention , and after experimental intervention . In each condition , data were collected when the physicians worked both night and day shifts . Measurements included ambulatory polysomnographic recordings of the main sleep periods , objective performance tests administered several times during the subjects ' shifts , and daily subjective ratings of the subjects ' sleep , moods , and intervention use . RESULTS The subjects slept an average of 5 hr 42 min across all conditions . After night shifts , the subjects slept significantly less than they did after day shifts ( 5 hr 13 min vs 6 hr 20 min ; p < 0.05 ) . The physicians ' vigilance reaction times and times for intubation of a mannequin were significantly slower during night shifts than they were during day shifts ( p = 0.007 and p < 0.04 , respectively ) , but performances on ECG analysis did not significantly differ between night and day shifts . Mood ratings were significantly more negative during night shifts than they were during day shifts ( more sluggish p < 0.04 , less motivated p < 0.03 , and less clear thinking p < 0.04 ) . The strategies in the experimental intervention were used 85 % of the time according to logbook entries . The experimental and active placebo interventions did not significantly improve the physician 's performance , or mood on the night shift , although the subjects slept more after both interventions . CONCLUSIONS Although the experimental intervention was successfully implemented , it failed to significantly improve attending physicians ' sleep , performance , or mood on night shifts . A decrease in speed of intubation , vigilance reaction times , and subjective alertness was evident each time the physicians rotated through the night shift . These findings plus the limited sleep across all conditions and shifts suggest that circadian-mediated disruptions of waking neurobehavioral functions and sleep deprivation are problems in EPs IMPORTANCE Prospect i ve studies linking shift work to coronary heart disease ( CHD ) have been inconsistent and limited by short follow-up . OBJECTIVE To determine whether rotating night shift work is associated with CHD risk . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 189,158 initially healthy women followed up over 24 years in the Nurses ' Health Studies ( NHS [ 1988 - 2012 ] : N = 73,623 and NHS2 [ 1989 - 2013 ] : N = 115,535 ) . EXPOSURES Lifetime history of rotating night shift work ( ≥3 night shifts per month in addition to day and evening shifts ) at baseline ( up date d every 2 to 4 years in the NHS2 ) . MAIN OUTCOMES AND MEASURES Incident CHD ; ie , nonfatal myocardial infa rct ion , CHD death , angiogram-confirmed angina pectoris , coronary artery bypass graft surgery , stents , and angioplasty . RESULTS During follow-up , 7303 incident CHD cases occurred in the NHS ( mean age at baseline , 54.5 years ) and 3519 in the NHS2 ( mean age , 34.8 years ) . In multivariable-adjusted Cox proportional hazards models , increasing years of baseline rotating night shift work was associated with significantly higher CHD risk in both cohorts . In the NHS , the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half ( P=.02 for interaction ) , suggesting waning risk after cessation of shift work . Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 ( P<.001 for trend ) . [ table : see text ] CONCLUSIONS AND RELEVANCE Among women who worked as registered nurses , longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk . Further research is needed to explore whether the association is related to specific work hours and individual characteristics |
11,756 | 31,304,974 | WIDER IMPLICATION S There is emerging evidence from RCT that PA may improve pregnancy rates in women with reproductive health problems .
Comparative studies indicate that PA intervention may be as effective as other commonly used clinical intervention strategies for improving reproductive health outcomes .
While the type , intensity , frequency , and duration of optimal PA intervention , and the role of PA independent of weight loss , remain unclear , these preliminary findings suggest that PA may be an affordable and feasible alternative or complementary therapy to fertility treatments | BACKGROUND In the context of increasing rates of overweight and obesity in young adult women , and the increasing numbers of women seeking help for fertility problems , it is important to underst and whether physical activity ( PA ) could help with management of reproductive health problems , with or without weight loss .
OBJECTIVE AND RATIONALE The primary aim of this systematic review and meta- analysis was to assess the effects of PA on selected reproductive health outcomes in young adult women , in order to inform best practice advice for women in terms of promoting fertility and reproductive health in young adulthood . | Obesity worsens and modest weight loss improves female fertility . Overweight women were r and omised to lifestyle or st and ard treatment pre‐in vitro fertilisation with treatment cessation at embryo transfer . There was a greater reduction in weight ( P < 0.001 ) for lifestyle treatment ( −3.8 ± 3.0 kg , P < 0.001 ) compared with no changes for st and ard treatment ( −0.5 ± 1.2 kg , P = 0.092 ) . Both the intervention ( −5.3 ± 4.6 cm ) and control ( −3.5 ± 3.5 cm ) group had reductions in waist circumference ( P < 0.001 ) with no differences between the two groups ( P = 0.215 ) . The overall pregnancy rate was 53 % ( 20/38 ) for the intervention and control group combined INTRODUCTION The aims of this prospect i ve cohort study were to examine 16-year trajectories of weight and BMI in young adult women who had a healthy BMI in 1996 and determinants of remaining in the healthy BMI category . METHODS A total of 4,881 women with healthy BMI at baseline and either healthy , overweight , or obese BMI at 16-year follow-up reported their weight , height , health , and health behaviors in six surveys of the Australian Longitudinal Study on Women 's Health between 1996 ( aged 18 - 23 years ) and 2012 ( aged 34 - 39 years ) . Determinants of BMI maintenance were estimated using binary logistic regression and generalized estimating equations in 2015 . RESULTS Almost 60 % remained in the healthy BMI category from 1996 to 2012 , ( mean weight gain , 0.19 kg/year ) , 29 % transitioned to overweight BMI ( 0.83 kg/year ) , and 11.6 % transitioned to obese ( 1.73 kg/year ) . The mean rates of annual weight gain in each group were consistent over time . Only three factors ( low alcohol , moderate/high physical activity , having a university degree ) were positively associated with maintaining a healthy BMI . Additional behavioral factors ( smoking , high sitting time , energy intake , dieting , takeaway food , and use of oral contraceptives ) , as well as blue collar occupation , separation/divorce/widowhood , and major illness were negatively associated with BMI maintenance . CONCLUSIONS To prevent the transition from healthy to overweight/obese BMI , weight gain must be limited to < 0.5 kg/year . Women with healthy BMI , but with higher rates of weight gain in their early 20s , could be identified by health professionals for assistance with prevention of becoming overweight/obese Introduction : Several established tools are available to assess study quality and reporting of r and omized controlled trials ; however , these tools were design ed with clinical intervention trials in mind . In exercise training intervention trials some of the traditional study quality criteria , such as participant or research er blinding , are extremely difficult to implement . Methods : We developed the Tool for the assEssment of Study qualiTy and reporting in EXercise ( TESTEX ) – a study quality and reporting assessment tool , design ed specifically for use in exercise training studies . Our tool is a 15-point scale ( 5 points for study quality and 10 points for reporting ) and addresses previously unmentioned quality assessment criteria specific to exercise training studies . Results : There were no systematic differences between the summated TESTEX scores of each observer [ H(2 ) = 0.392 , P = 0.822 ] . There was a significant association between the summated TESTEX scores of the three observers , with almost perfect agreement between observers 1 and 2 [ intra-class correlation coefficient ( ICC ) = 0.93 , 95 % confidence interval ( CI ) 0.82–0.97 , P < 0.001 ] , observers 1 and 3 ( ICC = 0.96 , 95 % CI 0.89–0.98 , P < 0.001 ) and observers 2 and 3 ( ICC = 0.91 , 95 % CI 0.75–0.96 , P < 0.001 ) . Conclusions : The TESTEX scale is a new , reliable tool , specific to exercise scientists , that facilitates a comprehensive review of exercise training trials OBJECTIVE To investigate whether r and omized diet and /or physical exercise influence serum levels of antimüllerian hormone ( AMH ) in obese women with polycystic ovary syndrome ( PCOS ) . DESIGN R and omized , 4-month trial with three interventions . SETTING Women 's health clinical research unit at a university hospital . PATIENT(S ) Fifty-seven overweight/obese women with PCOS . INTERVENTION(S ) Diet , physical exercise , or both , using programs individually adapted and supervised by a dietician and /or a physiotherapist . MAIN OUTCOME MEASURE(S ) Serum AMH levels before and after the interventions and correlations to reproductive function , body composition , and endocrine and metabolic variables . RESULT ( S ) After intervention , serum levels of AMH were significantly decreased only in the diet group , and the levels were significantly lower than in the exercise group . The strongest predictor of decreased AMH was a decrease in free T , whereas weight loss had no significant influence . Normalized levels of AMH were associated with improvements in menstrual cyclicity and hyper and rogenism but not in metabolic variables . CONCLUSION ( S ) This r and omized study supports that diet reduces serum AMH in association with decreased and rogen levels in obese women with PCOS . Increased serum AMH may be used as a marker of ovulatory dysfunction and hyper and rogenism but not as a marker of insulin resistance . CLINICAL TRIAL REGISTRY NUMBER IS RCT N48342048 This pilot study assessed the effects of exercise and nutritional counseling on hormonal , menstrual , and reproductive function in women with polycystic ovary syndrome ( PCOS ) . Twelve females with a clinical , biochemical , and ultrasonographic diagnosis of PCOS were r and omly assigned to endurance and resistance exercise plus nutritional counseling ( EN ) or nutritional counseling only ( N ) for a period of 12 weeks . Anthropometry , resting metabolic rate ( RMR ) , selected hormones , and ovarian follicle population were measured pre and post-intervention . Following the 12 week intervention , greater decreases in sum of 2 skinfolds ( p = 0.002 ) and a greater increase in estimated VO2 max ( p = 0.017 ) occurred in the exercise group . Significant decreases in waist girth ( p = 0.001 ) and insulin levels ( p = 0.03 ) occurred in both groups . Hormonal changes were not statistically significant ; however , a trend towards an improved hormonal profile , specifically sex-hormone binding globulin ( EN , 39 % increase ; N , 8 % increase ) and lutenizing hormone : follicle-stimulating hormone ( LH : FSH ) ( EN , 9 % decrease ; N , 27 % decrease ) occurred in the absence of weight loss . These findings suggest exercise and nutritional counseling may benefit the metabolic and reproductive abnormalities associated with PCOS Aim of this study was to compare the effects of metformin and a body weight reduction regimen using sibutramine on insulinemia , insulin sensitivity , and ovarian function in women with anovulatory cycles or infertility . 30 women with anovulatory cycles and hyperinsulinemia were treated with metformin and 15 anovulating women with obesity were treated with sibutramine in combination with a caloric restriction diet and physical exercise . In the metformin group there was a mild decrease of the body mass index ( BMI ) , a decrease of fasting and stimulated insulinemia ( I0 , p < 0.05 , I120 , p < 0.01 ) , a significant reduction of insulin resistance calculated as index FIRI ( p < 0.05 ) , serum LH ( p < 0.05 ) and testosterone levels ( p < 0.05 ) . There was an improvement of menstrual cycles in 21 ( 70 % ) of women , and 6 of them became pregnant . In the sibutramine group we found a significant decrease of BMI ( p < 0.01 ) , waist circumference ( p < 0.01 ) , fasting and stimulated insulinemia ( p < 0.05 , p < 0.01 ) and a significant improvement of insulin sensitivity ( FIRI , p < 0.01 ) . However , the levels of FSH , LH , and testosterone were not significantly changed . There was a significantly greater reduction of insulin levels and FIRI after sibutramine treatment compared with metformin treatment , while the changes of LH were not signifcantly different . Testosterone was changed more after metformin therapy . We conclude that although the body weight reduction using sibutramine has a more pronounced effect on insulinemia and insulin sensitivity , metformin may be more effective in the prompt restoration of ovarian function . ( Tab . 3 , Ref . 24 . ) CONTEXT Polycystic ovary syndrome ( PCOS ) is an insulin-resistant ( IR ) state . Visceral fat ( VF ) is independently associated with IR . OBJECTIVES The objectives of the study were to explore mechanisms underpinning IR by assessing the effect of exercise training on IR and body composition in overweight PCOS and non-PCOS women . DESIGN This was a prospect i ve exercise intervention study . SETTING AND PARTICIPANTS The study was conducted at an academic medical center . Participants included 20 overweight PCOS and 14 overweight non-PCOS women . INTERVENTION The intervention included 12 wk of intensified aerobic exercise ( 3 h/wk ) . MAIN OUTCOME MEASURES IR on euglycemic hyperinsulinemic clamp , body composition including abdominal visceral and sc fat distribution by computer tomography and lipids was measured . RESULTS PCOS subjects were more IR ( P = 0.02 ) and had more VF ( P = 0.04 age adjusted ) than non-PCOS women . In PCOS women , IR correlated with VF ( r = -0.78 , P < 0.01 ) . With exercise training , both groups maintained weight but within PCOS , VF ( -12.0 cm(2 ) , P = 0.03 ) and within non-PCOS abdominal sc fat ( -40.2 cm(2 ) , P = 0.02 ) decreased . Despite exercise-induced improvement in IR within PCOS ( + 27.9 mg · m(-2 ) · min(-1 ) , P = 0.03 ) , no relationship with decreased VF ( r = -0.08 , P = 0.84 ) and no differential changes in IR and VF between groups were noted . Triglycerides decreased within PCOS ( -0.27 mmol/liter , P = 0.02 ) and decreased differentially between groups ( P < 0.01 ) . CONCLUSIONS Higher IR was related to increased VF in PCOS , suggesting an etiological role for VF in intrinsic IR in PCOS ; however , changes with exercise intervention did not support a causal relationship . Triglycerides were modulated more by exercise training in PCOS than non-PCOS women . Within-group exercise-induced reductions in cardiometabolic risk factors including IR , triglycerides , and VF in PCOS were observed without significant weight loss and if confirmed in future controlled trials , suggest weight loss should not be the sole focus of exercise programs CONTEXT Lifestyle modification is recommended in women with polycystic ovary syndrome ( PCOS ) prior to conception but there are few r and omized trials to support its implementation or benefit . OBJECTIVE This study aim ed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS . DESIGN , SETTING , AND PARTICIPANTS This was a r and omized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS , age 18 - 40 y and body mass index 27 - 42 kg/m(2 ) . INTERVENTION Women were r and omly assigned to receive either 16 weeks of 1 ) continuous oral contraceptive pills ( OCPs ) ( ethinyl estradiol 20 mcg/1 mg norethindrone acetate ) ( " OCP " ) ; 2 ) lifestyle modification consisting of caloric restriction with meal replacements , weight loss medication ( either sibutramine , or orlistat ) , and increased physical activity to promote a 7 % weight loss ( " Lifestyle " ) ; or 3 ) combined treatment with both OCP and lifestyle modification ( " Combined " ) . After preconception intervention , women underwent st and ardized ovulation induction with clomiphene citrate and timed intercourse for four cycles . Pregnancies were followed with trimester visits until delivery . MAIN OUTCOME MEASURES Weight , ovulation , and live birth were measured . RESULTS We consented 216 and r and omly assigned 149 women ( Lifestyle : n = 50 ; OCP : n = 49 ; Combined : n = 50 ) . We achieved significant weight loss with both Lifestyle ( mean weight loss , -6.2 % ; 95 % confidence interval ( CI ) , -7.4 - -5.0 ; and Combined ( mean weight loss , -6.4 % ; 95 % CI , -7.6 - -5.2 ) compared with baseline and OCP ( both P < .001 ) . There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP ( odds ratio [ OR , 2.47 ; 95 % CI , 1.42 - 4.27 ) whereas no change in metabolic syndrome was detected in the Lifestyle ( OR , 1.18 ; 95 % CI , 0.63 - 2.19 ) or Combined ( OR , 0.72 ; 95 % CI , 0.44 - 1.17 ) groups . Cumulative ovulation rates were superior after weight loss : OCP , 46 % ; Lifestyle , 60 % ; and Combined , 67 % ( P < .05 ) . Live birth rates were OCP , 12 % ; Lifestyle , 26 % ; and Combined , 24 % ( P = .13 ) . CONCLUSIONS A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and , compared with oral contraceptive pretreatment , leads to higher ovulation rates We assessed the impact of energy deficiency on menstrual function using controlled feeding and supervised exercise over four menstrual cycles ( 1 baseline and 3 intervention cycles ) in untrained , eumenorrheic women aged 18 - 30 yr . Subjects were r and omized to either an exercising control ( EXCON ) or one of three exercising energy deficit ( ED ) groups , i.e. , mild ( ED1 ; -8 ± 2 % ) , moderate ( ED2 ; -22 ± 3 % ) , or severe ( ED3 ; -42 ± 3 % ) . Menstrual cycle length and changes in urinary concentrations of estrone-1-glucuronide , pregnanediol glucuronide , and midcycle luteinizing hormone were assessed . Thirty-four subjects completed the study . Weight loss occurred in ED1 ( -3.8 ± 0.2 kg ) , ED2 ( -2.8 ± 0.6 kg ) , and ED3 ( -2.6 ± 1.1 kg ) but was minimal in EXCON ( -0.9 ± 0.7 kg ) . The overall sum of disturbances ( luteal phase defects , anovulation , and oligomenorrhea ) was greater in ED2 compared with EXCON and greater in ED3 compared with EXCON AND ED1 . The average percent energy deficit was the main predictor of the frequency of menstrual disturbances ( f = 10.1 , β = -0.48 , r(2 ) = 0.23 , P = 0.003 ) even when weight loss was included in the model . The estimates of the magnitude of energy deficiency associated with menstrual disturbances ranged from -22 ( ED2 ) to -42 % ( ED3 ) , reflecting an energy deficit of -470 to -810 kcal/day , respectively . This is the first study to demonstrate a dose-response relationship between the magnitude of energy deficiency and the frequency of exercise-related menstrual disturbances ; however , the severity of menstrual disturbances was not dependent on the magnitude of energy deficiency Polycystic ovary syndrome ( PCOS ) is a common condition in women associated with menstrual irregularity and anovulation . While obesity worsens and weight loss or exercise improves reproduction function in PCOS , the mechanism for this is unclear . The aim of this study was to examine the effect of exercise on ovarian hormones [ anti-Müllerian hormone ( AMH ) ] and menstrual and ovulatory function in women with and without PCOS . Overweight women with ( n=7 ) and without ( n=8 ) PCOS of comparable age , weight and BMI undertook a 12-week intensified endurance exercise training program ( 1 h 3 times/week ) with no structured energy restriction . Primary outcomes were AMH , ovulation ( weekly urinary pregnanediol ) and menstrual regularity . Secondary outcomes were insulin resistance ( euglycemic hyperinsulinemic clamp ) and body composition ( computed tomography and dual X-ray absorptiometry ) . Exercise decreased BMI , total and and roid fat mass and improved insulin sensitivity for all women . AMH was significantly higher in women with PCOS compared to controls before ( p<0.001 ) and after exercise ( p=0.001 ) . There was a significant interaction between AMH changes with exercise and PCOS status ( p=0.007 ) such that women without PCOS had no change in AMH ( + 1.4±5.2 pmol/l , p=0.48 ) while women with PCOS had a decrease in AMH ( - 13.2±11.7 pmol/l , p=0.025 ) . Exercise is associated with improvements in ovarian hormones in women with abnormal ovarian function . This suggests that mechanisms associated with ovarian dysfunction can be improved by exercise in PCOS For women attempting pregnancy , obesity reduces fertility and is an independent risk factor for obstetric and neonatal complications . The aim of this evaluator‐blinded , r and omized controlled trial was to evaluate a weight loss intervention on pregnancy rates in obese women undertaking fertility treatment . Forty‐nine obese women , aged ≤37 years , presenting for fertility treatment were r and omized to either a 12‐week intervention ( n = 27 ) consisting of a very‐low‐energy diet for the initial 6 weeks followed by a hypocaloric diet , combined with a weekly group multidisciplinary programme ; or a control group ( n = 22 ) who received recommendations for weight loss and the same printed material as the intervention . Anthropometric and reproductive parameters were measured at baseline and at 12 weeks . The 22 women who completed the intervention had greater anthropometric changes ( –6.6 ± 4.6 kg and −8.7 ± 5.6 cm vs. −1.6 ± 3.6 kg and −0.6 ± 6.3 cm ) compared with the control group ( n = 17 ; P < 0.001 ) . The intervention group achieved a pregnancy rate of 48 % compared with 14 % ( P = 0.007 ) , took a mean two fertility treatment cycles to achieve each pregnancy compared with four in the control group ( P = 0.002 ) , and had a marked increase in the number of live births ( 44 % vs. 14 % ; P = 0.02 ) . A group weight loss programme , incorporating dietary , exercise and behavioural components , is associated with a significant improvement in pregnancy rates and live births in a group of obese women undergoing fertility treatment Recent estimates suggest that 35.3 % of adult Australians are overweight and a further 27.5 % are obese . The Australian Longitudinal Study on Women ’s Health ( ALSWH ) is a prospect i ve study of women ’s health that commenced in Australia in 1996 . The study recruited approximately 40,000 women in three birth cohorts , 1973–1978 , 1946–1951 and 1921–1926 , who have since been followed up approximately every three years using self-report surveys . Six surveys have been completed to date . This review aims to describe the changes in weight and weight status over time in the three ALSWH cohorts , and to review and summarise the published findings to date relating to the determinants and health consequences of weight gain , overweight and obesity . Future plans for the ALSWH include on-going surveys for all cohorts , with a seventh survey in 2013–2015 , and establishment of a new cohort of women born in 1990–1995 , which is currently being recruited CONTEXT Polycystic ovary syndrome ( PCOS ) is an endocrine disease closely related to several risk factors for cardiovascular disease . An impaired cardiopulmonary functional capacity was previously demonstrated in PCOS women . No data regarding the effects of a structured exercise training ( ET ) program on cardiopulmonary functional capacity in PCOS women are available . OBJECTIVE Our objective was to evaluate the effects of a 3-month ET program on cardiopulmonary functional capacity in young PCOS women . DESIGN AND SETTING A prospect i ve baseline-r and omized clinical study was conducted at the University " Federico II " of Naples , School of Medicine ( Italy ) . PATIENTS Ninety young overweight PCOS women were enrolled . MEAN OUTCOME MEASURES Ninety young PCOS women were r and omly subdivided into two groups , each composed of 45 subjects . The PCOS-T ( trained ) group underwent a 3-month structured ET program , whereas the PCOS-UnT ( untrained ) group did not . Hormonal and metabolic profiles and cardiopulmonary and exercise parameters were evaluated . RESULTS After 3-month ET , PCOS-T showed a significant improvement in peak oxygen consumption ( + 35.4 % ; P<0.001 ) and in maximal workload ( + 37.2 % ; P<0.001 ) . In PCOS-T we also observed a significant reduction in body mass index ( -4.5 % ; P<0.001 ) and in C-reactive protein ( -10 % ; P<0.001 ) , and a significant ( P<0.001 ) improvement in insulin sensitivity indexes . After 3 months , no changes were observed in PCOS-UnT. CONCLUSIONS A 3-month structured ET program improves cardiopulmonary functional capacity in young PCOS women BACKGROUND Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome ( PCOS ) . The aims of the current pilot study were ( i ) to compare the efficacy on reproductive functions of a structured exercise training ( SET ) programme with a diet programme in obese PCOS patients and ( ii ) to study their clinical , hormonal and metabolic effects to eluci date potentially different mechanisms of action . METHODS Forty obese PCOS patients with anovulatory infertility underwent a SET programme ( SET group , n = 20 ) and a hypocaloric hyperproteic diet ( diet group , n = 20 ) . Clinical , hormonal and metabolic data were assessed at baseline , and at 12- and 24-week follow-ups . Primary endpoint was cumulative pregnancy rate . RESULTS The two groups had similar demographic , anthropometric and biochemical parameters . After intervention , a significant improvement in menstrual cycles and fertility was noted in both groups , with no differences between groups . The frequency of menses and the ovulation rate were significantly ( P < 0.05 ) higher in the SET group than in diet group but the increased cumulative pregnancy rate was not significant . Body weight , body mass index , waist circumference , insulin resistance indexes and serum levels of sex hormone-binding globulin , and rostenedione and dehydroepi and rosterone sulphate changed significantly ( P < 0.05 ) from baseline and were significantly different ( P < 0.05 ) between the two groups . CONCLUSIONS Both SET and diet interventions improve fertility in obese PCOS patients with anovulatory infertility . We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms OBJECTIVE To compare the effect of clomiphene citrate , metformin , and lifestyle modification on treatment of patients with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve r and omized double-blind study . SETTING University-based infertility clinic and research center . PATIENT(S ) Three hundred forty-three overweight infertile women with PCOS . INTERVENTION(S ) The participating women were assigned to four groups : clomiphene ( n = 90 ) , metformin ( n = 90 ) , clomiphene + metformin ( n = 88 ) , and lifestyle modification ( n = 75 ) . The patients in each group received st and ardized dietary and exercise advice from a dietitian . MAIN OUTCOME MEASURE(S ) The primary outcome variables were change in menstrual cycle , waist circumference measurements , endocrine parameters , and lipid profile . The main secondary outcome variable was clinical pregnancy rate . RESULT ( S ) The clinical pregnancy rate was 12.2 % in clomiphene group , 14.4 % in metformin group , 14.8 % in clomiphene + metformin group , and 20 % in lifestyle modification group . Lifestyle modification group achieved a significant reduction in waist circumference , total and rogen , and lipid profile . CONCLUSION ( S ) Lifestyle modification improves the lipid profile in PCOS patients . Therefore , lifestyle modification may be used as the first line of ovulation induction in PCOS patients |
11,757 | 22,161,362 | No studies reported on rare but potentially serious adverse effects of epidural analgesia .
Epidural analgesia appears to be effective in reducing pain during labour .
However , women who use this form of pain relief are at increased risk of having an instrumental delivery .
Epidural analgesia had no statistically significant impact on the risk of caesarean section , maternal satisfaction with pain relief and long-term backache and did not appear to have an immediate effect on neonatal status as determined by Apgar scores . | BACKGROUND Epidural analgesia is a central nerve block technique achieved by injection of a local anaesthetic close to the nerves that transmit pain and is widely used as a form of pain relief in labour .
However , there are concerns regarding unintended adverse effects on the mother and infant .
OBJECTIVES To assess the effects of all modalities of epidural analgesia ( including combined-spinal-epidural ) on the mother and the baby , when compared with non-epidural or no pain relief during labour . | Background The minimum local analgesic concentration ( MLAC ) has been defined as the median effective local analgesic concentration ( EC50 ) in a 20-ml volume for epidural analgesia in the first stage of labor . The aim of this study was to determine the relative local anesthetic sparing efficacies of intravenous and epidural fentanyl by comparison of their effects on the MLAC of bupivacaine . Methods In this double-blind , r and omized , prospect i ve study , 84 parturients at ≤ 7-cm cervical dilation who requested epidural analgesia were allocated to one of two groups . After lumbar epidural catheter placement , 20 ml bupivacaine ( n = 44 ) or bupivacaine with 3 & mgr;g/ml ( 60 & mgr;g ) fentanyl ( n = 40 ) was administered . The plain bupivacaine group then received 60 & mgr;g intravenous fentanyl . The bupivacaine – fentanyl group received intravenous saline . The concentration of bupivacaine was determined by the response of the previous patient in that group to a higher or lower concentration using up – down sequential allocation . Analgesic efficacy was assessed using 100-mm visual analog pain scores , with ≤ 10 mm within 30 min defined as effective . Results The MLAC of bupivacaine – intravenous fentanyl was 0.064 % wt/vol ( 95 % confidence interval , 0.049–0.080 ) , and the MLAC of bupivacaine – epidural fentanyl was 0.034 % wt/vol ( 95 % confidence interval , 0.017–0.050 ) . Epidural fentanyl significantly increased the analgesic potency of bupivacaine by a factor of 1.88 ( 95 % confidence interval , 1.09–3.67 ) compared with intravenous fentanyl . The epidural fentanyl group demonstrated significantly higher dermatomal spread ( P = 0.0064 ) and increased pruritus ( P = 0.01 ) . Conclusions Epidural fentanyl significantly reduced the MLAC of bupivacaine when compared with intravenous fentanyl for the parturients in this study . The significantly enhanced local anesthetic sparing , dermatomal level , and pruritus with epidural fentanyl suggest a primarily spinal site of action OBJECTIVE To evaluate the effects of epidural analgesia using 0.2 % Ropivacaine on the mother , newborn and during labor . METHODS This study was conducted at the Zeynep Kamil Obstetric , Gynecology , and Pediatric Research and Training Hospital in Istanbul , Turkey , between July 2003 and April 2004 . Eighty pregnant women of 37 - 41 weeks ' gestation were enrolled in the study . Forty cases received epidural analgesia ( group 1 ) and the control group composed 40 cases ( group 2 ) . Duration of labor , systolic and diastolic blood pressures at initial , 15th , 30th , 45th and 60th minutes , and number of breathing per minute , pulse rates , fetal heart rates and presence of motor block were recorded . Blood gas assessment s from the umbilical cord , 1st and 5th minute Apgar scores were noted following the delivery . Way of delivery , adverse effects and complications of the epidural analgesia were recorded . RESULTS Mean age of the cases was 24.79 + /- 4.72 years . Duration between full cervical dilation and delivery ( phase 2 ) was significantly longer in group 1 ( p<0.01 ) . Sixty minutes systolic arterial pressure was significantly lower in group 1 ( p<0.05 ) . In group 1 , diastolic arterial pressures at 15th , 45th , 60th minutes ( p<0.01 ) and 30th minute ( p<0.05 ) were significantly lower when compared to the initial values . No significant differences were recorded in terms of breathing rates , umbilical cord CO2 , O2 , pH levels and Apgar scores between the 2 groups . The most common adverse effect of epidural analgesia was sedation ( 59 % ) . The second dose of Ropivacaine was needed in 24 ( 61.5 % ) cases in group 1 . In group 1 , 29 ( 74.4 % ) patients expressed their pleasure as very good regarding the epidural analgesia . CONCLUSION Epidural analgesia , if administered by a specialist to a properly selected patient at proper time , leads to a comfortable delivery by relieving the pain . It can be performed safely after taking an informed consent Purpose Epidural analgesia is associated with hyperthermia during labor and presumably causes it , although no convincing mechanism has been postulated . It seems likely that fever associated with pyrogenic factors related to labor is suppressed by opioids , whereas it is expressed normally in patients given epidural analgesia . We examined this hypothesis and the possible etiology of temperature elevation in labor . Methods In this prospect i ve , r and omized , controlled study , we assessed 201 parturients during spontaneous labor . Analgesia was r and omly provided with one of four treatment groups : ( 1 ) epidural ropivacaine alone , ( 2 ) IV remifentanil alone , ( 3 ) epidural ropivacaine plus IV remifentanil , and ( 4 ) epidural ropivacaine plus IV acetaminophen . At r and omization , patients were normothermic . Intrapartum hyperthermia ( ≥38 ° C ) was correlated to the analgesic technique . Results The maximum increase in oral temperature was greatest in the ropivacaine group ( 0.7 ± 0.6 ° C ) and least in the remifentanil group ( 0.3 ± 0.4 ° C ; P = 0.013 ) . The percentage of patients who became hyperthermic ( ≥38 ° C ) during the first 6 h of labor was greatest in the ropivacaine group ( 14 % ) and least in the remifentanil-alone group ( 2 % ) , but the difference was not statistically significant . The maximum forearm-finger gradients were lower ( less vasoconstriction ) in the remifentanil group when compared to the gradients in patients with epidural analgesia ( 1.4 ± 1.8 vs 3.0 ± 1.7 , respectively ; P < 0.001 ) . Conclusion Our results are consistent with the theory that low-dose opioids inhibit fever in patients not given epidural analgesia . However , in view of the negative results , the hypothesis of epidural-induced hyperthermia may be question able Background Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries . However , only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery . The authors ' primary purpose in this r and omized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative : patient-controlled intravenous analgesia . Methods Seven hundred fifteen women of mixed parity in spontaneous labor at full term were r and omly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia . Epidural analgesia was maintained with a continuous epidural infusion of 0.125 % bupivacaine with 2 micro gram/ml fentanyl . Patient-controlled analgesia was maintained with 10 - 15 mg meperidine given every 10 min as needed using a patient-controlled pump . Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman r and omized in the study . Results A total of 358 women were r and omized to receive epidural analgesia , and 243 ( 68 % ) of these women complied with the epidural analgesia protocol . Similarly , 357 women were r and omized to receive patient-controlled intravenous meperidine analgesia , and 259 ( 73 % ) of these women complied with the patient-controlled intravenous analgesia protocol . Only five women who were r and omized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief . There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original r and omization ( epidural analgesia , 4 % [ 95 % CI : 1.9 - 6.2 % ] compared with patient-controlled intravenous analgesia , 5 % [ 95 % CI : 2.6 - 7.2 % ] ) . Similar results were observed for the analysis of the protocol -compliant groups ( epidural analgesia , 5 % [ 95 % CI : 2.6 - 8.5 % ] compared with patient-controlled intravenous analgesia , 6 % [ 95 % CI : 3 - 8.9 % ] ) . Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia . Conclusions Epidural analgesia was not associated with increased numbers of cesarean delivery when compared with a suitable alternative method of analgesia OBJECTIVE To estimate the effect of epidural analgesia on the Friedman labor curve . METHODS This study was a secondary analysis of a previously reported r and omized trial of the effects of patient‐controlled epidural analgesia during labor compared with patient‐controlled meperidine on cesarean delivery rate . All subjects had a singleton , cephalic , nonanomalous fetus at or beyond 37 weeks ' gestation . This secondary analysis was limited to women who had cervical dilatation commencing of at least 3 cm ( ie , active phase of labor ) . RESULTS A total of 459 women were r and omized . Twenty‐five women were excluded for a cervix less than 3 cm dilated , leaving 220 women allocated to patient‐controlled epidural analgesia and 214 to patient‐controlled intravenous meperidine available for analysis . There were no significant demographic differences between the two groups , including age , race , gestational age , and cervix on admission . The active phase of labor was 1 hour longer in the epidural‐treated group ( 6.0 ± 3.2 hours versus 5.0 ± 3.2 hours , P < .001 ) . The rate of cervical dilation was significantly less with epidural analgesia ( 1.4 cm/h versus 1.6 cm/h , P < .002 ) . The duration of the second stage tended to be longer in the epidural group ( 1.1 ± 1.5 hours versus 0.9 ± 1.0 hours , P = .079 ) . CONCLUSION Epidural analgesia prolonged the active phase of labor by 1 hour compared with Friedman 's original criteria Background Whether epidural analgesia for labor prolongs the active-first and second labor stages and increases the risk of vacuum-assisted delivery is a controversial topic . Our study was conducted to answer the question : does lumbar epidural analgesia with lidocaine affect the progress of labor in our obstetric population ? Method 395 healthy , nulliparous women , at term , presented in spontaneous labor with a singleton vertex presentation . These patients were r and omized to receive analgesia either , epidural with bolus doses of 1 % lidocaine or intravenous , with meperidine 25 to 50 mg when their cervix was dilated to 4 centimeters . The duration of the active-first and second stages of labor and the neonatal apgar scores were recorded , in each patient . The total number of vacuum-assisted and cesarean deliveries were also measured . Results 197 women were r and omized to the epidural group . 198 women were r and omized to the single-dose intravenous meperidine group . There was no statistical difference in rates of vacuum-assisted delivery rate . Cesarean deliveries , as a consequence of fetal bradycardia or dystocia , did not differ significantly between the groups . Differences in the duration of the active-first and the second stages of labor were not statistically significant . The number of newborns with 1-min and 5-min Apgar scores less than 7 , did not differ significantly between both analgesia groups . Conclusion Epidural analgesia with 1 % lidocaine does not prolong the active-first and second stages of labor and does not increase vacuum-assisted or cesarean delivery rate BACKGROUND Epidural analgesia initiated early in labor ( when the cervix is less than 4.0 cm dilated ) has been associated with an increased risk of cesarean delivery . It is unclear , however , whether this increase in risk is due to the analgesia or is attributable to other factors . METHODS We conducted a r and omized trial of 750 nulliparous women at term who were in spontaneous labor or had spontaneous rupture of the membranes and who had a cervical dilatation of less than 4.0 cm . Women were r and omly assigned to receive intrathecal fentanyl or systemic hydromorphone at the first request for analgesia . Epidural analgesia was initiated in the intrathecal group at the second request for analgesia and in the systemic group at a cervical dilatation of 4.0 cm or greater or at the third request for analgesia . The primary outcome was the rate of cesarean delivery . RESULTS The rate of cesarean delivery was not significantly different between the groups ( 17.8 percent after intrathecal analgesia vs. 20.7 percent after systemic analgesia ; 95 percent confidence interval for the difference , -9.0 to 3.0 percentage points ; P=0.31 ) . The median time from the initiation of analgesia to complete dilatation was significantly shorter after intrathecal analgesia than after systemic analgesia ( 295 minutes vs. 385 minutes , P<0.001 ) , as was the time to vaginal delivery ( 398 minutes vs. 479 minutes , P<0.001 ) . Pain scores after the first intervention were significantly lower after intrathecal analgesia than after systemic analgesia ( 2 vs. 6 on a 0-to-10 scale , P<0.001 ) . The incidence of one-minute Apgar scores below 7 was significantly higher after systemic analgesia ( 24.0 percent vs. 16.7 percent , P=0.01 ) . CONCLUSIONS Neuraxial analgesia in early labor did not increase the rate of cesarean delivery , and it provided better analgesia and result ed in a shorter duration of labor than systemic analgesia A prospect i ve trial compared 100 normal labouring women who had epidural analgesia with 102 similar women given conventional analgesia . Fetal welfare was assessed by five parameters . Statistical analysis of these parameters in the two groups shows that babies born to mothers who had epidural analgesia were in better condition To establish the spontaneous miscarriage rate and compare it with the procedure related miscarriage rate for amniocentesis and chorionic villus sampling ( CVS ) by experienced operators Some authors have suggested that the intensity of labor pain may be related to labor dystocia . We performed a secondary analysis of a previously published r and omized investigation of the effects of epidural analgesia during labor compared with patient-controlled IV meperidine on cesarean delivery . Two-hundred-fifty-nine women who received patient-controlled IV meperidine were identified for analysis . All women were in spontaneous labor with a singleton , term gestation . Women requiring 50 mg or more of meperidine per hour during labor were compared with those who required < 50 mg/h . In addition , their pain scores ( visual analog scale ) were compared before and after analgesia administration . Pain scores were significantly higher in women requiring 50 mg/h of meperidine ( 8.7 vs 8.0 , P = 0.05 ) , and their labors tended to be longer ( 9 vs 5 h , P = 0.09 ) . More cesarean deliveries for obstructed labor were performed in women requiring > 50 mg/h of meperidine ( 14 % vs 1.4 % , P = 0.001 ) . Neonatal outcomes were similar in the two groups The incidence of shivering in women during epidural analgesia in labour is up to 33 % , and may be highly distressing . Its mechanism is unclear , but the most widely held theory is that it is thermogenic . Pharmacological suppression may adversely effect the foetus or induce maternal hypothermia , and although physical remedies such as direct heat application are effective , they are also expensive and cumbersome . We recently found that the space blanket , a simple aluminised metallic foil , used pre‐emptively , reduces shivering after general anaesthesia . We investigated the effect of the space blanket on the incidence and intensity of shivering , axilliary skin temperature , and subjective perception of cold during epidural analgesia for labour in 50 women over a four‐hour time frame . Patients were r and omised into group 1 , who were wrapped in a space blanket immediately after commencement of epidural analgesia with bupivacaine , and group 2 ( matched controls ) . Shivering was defined as visible tremor of the head , neck , trunk or limbs as observed by the attending midwives . Twenty‐nine percent of group 1 and 35 % of group 2 shivered ( not significant ) , but a reduction in shivering intensity was observed in group 1 ( P<0.05 ) . There was no significant difference in skin temperatures in either group , and no significant temperature change within the groups . Both groups had similar thermal comfort scores throughout the study , which correlated poorly with the presence of shivering . We conclude that there is no benefit in application of the space blanket to reduce epidural‐analgesia related shivering in labour , which may indicate a non‐thermogenic mechanism for this phenomenon We compared the incidence of Caesarean delivery in nulliparous women r and omized to receive epidural analgesia with those r and omized to intramuscular ( i.m . ) pethidine . On admission to the delivery suite in established labour , 802 nulliparae had already agreed to be r and omized with respect to their first analgesia . One hundred and eighty-eight women required either no analgesia or 50 % nitrous oxide in oxygen ( Entonox ) only . Of the remaining 614 women , 310 were r and omly allocated to receive i.m . pethidine up to 300 mg and 304 to receive epidural bupivacaine . Labour management was st and ardized according to the criteria for active management of labour . The intention-to-treat analysis showed similar Caesarean section rates in those r and omized to epidural ( 12 % ) or pethidine analgesia ( 13 % ) . The difference in Caesarean rate was -1.1 % with 95 % confidence intervals from -6.3 % to + 4.1 % . The normal vaginal delivery rates were similar ( epidural , 59 % ; pethidine , 61 % ) OBJECTIVES To prospect ively study the intervention rate , duration of labour , malpositions , fetal outcome , maternal satisfaction , voiding complications and adverse events in healthy primigravidae in spontaneous labour at term following epidural analgesia . METHODS A prospect i ve r and omized study involving 55 patients in the epidural group and 68 in the control pethidine -- inhalational entonox group . RESULTS There were significantly more obstetric interventions ( instrumental deliveries ) in the epidural group ( p < 0.01 ) . The total duration of labour and the duration of the second stage was prolonged in the epidural group ( p < 0.01 ) . There were more malpositions at the second stage of labour in the epidural group ( p < 0.02 ) . There were no differences in fetal outcome ( Apgar scores and Special Care Nursery admissions ) . Patients in the epidural group were consistently happier with their method of pain relief ( p < 0.01 ) . Two patients required blood patches while another 2 patients had persistent backache post epidural analgesia . CONCLUSION Epidural analgesia in primigravidae in spontaneous labour at term led to an increased instrumental delivery rate , prolonged duration of labour , greater rate of malpositions in the second stage , increased oxytocin requirements but with no difference in fetal outcomes but with happier mothers as compared to the control group In a r and omised controlled trial epidural analgesia with bupivacaine 0·5 % ( mean dose 112·8 mg ) was compared with pethidine ( mean dose 200 mg ) and inhalational analgesia in primipara ( 28 and 30 mothers ) and multipara ( 17 and 18 mothers ) . Mothers who had an uneventful pregnancy and labour and agreed to have either treatment were studied during labour and followed‐up at interviews for 5 months after delivery . Epidural block was rated significantly superior in respect of pain relief and comfort , there were no differences between the groups in reports of perineal discomfort . Twice as many primipara required forceps delivery after epidural block . Very few mothers , in each group , reported something missing in their experience of childbirth . Two thirds of each group would use the same method again . Epidural block can therefore be recommended to uncommitted mothers as a satisfying and effective method of pain relief for labour OBJECTIVE Our purpose was to examine the effect of epidural analgesia on dystocia-related cesarean delivery in actively laboring nulliparous women . STUDY DESIGN Active labor was confirmed in nulliparous women by uterine contractions , cervical dilatation of 4 cm , effacement of 80 % , and fetopelvic engagement . Patients were r and omized to one of two groups : epidural analgesia or narcotics . A strict protocol for labor management was in place . Patients recorded the level of pain at r and omization and at hourly intervals on a visual analog scale . Elective outlet operative vaginal delivery was permitted . RESULTS One hundred women were r and omized . No difference in the rate of cesarean delivery for dystocia was noted between the groups ( epidural 8 % , narcotic 6 % ; p = 0.71 ) . No significant differences were noted in the lengths of the first ( p = 0.54 ) or second ( p = 0.55 ) stages of labor or in any other time variable . Women with epidural analgesia underwent operative vaginal delivery more frequently ( p = 0.004 ) . Pain scores were equivalent at r and omization , but large differences existed at each hour thereafter . The number of patients r and omized did not achieve pre study estimates . A planned interim analysis of the results demonstrated that we were unlikely to find a statistically significant difference in cesarean delivery rates in a trial of reasonable duration . CONCLUSIONS With strict criteria for the diagnosis of labor and with use of a rigid protocol for labor management , there was no increase in dystocia-related cesarean delivery with epidural analgesia OBJECTIVE The effects of epidural analgesia on the progress of labor are controversial . The objective of this study was to determine the effect of epidural analgesia on cesarean delivery rates in a population of patients r and omly assigned to receive either epidural analgesia or intravenous opioids for intrapartum pain relief . STUDY DESIGN From January 1995 to May 1996 , 318 spontaneously laboring , term , nulliparous patients were r and omly assigned to receive either intravenous opioids or epidural analgesia for pain relief . Labor was managed according to the principles of active management of labor . Cesarean delivery was performed for obstetric indications . Data analysis was conducted on an intent-to-treat basis . A sub analysis was subsequently performed on patients who were compliant with the allocated form of treatment . RESULTS One hundred sixty-two patients were r and omly assigned to receive intravenous meperidine and 156 were r and omly assigned to receive epidural analgesia . Maternal age , gravidity , race , gestational age , and cervical dilatation at admission and at first analgesic dose did not differ between the groups . Intent-to-treat data analysis revealed no significant difference in the cesarean delivery rate between the 2 groups , being 13.6 % in the opioid group and 9.6 % in the epidural group ( relative risk 0.70 , 95 % confidence interval 0.38 - 1.31 , P > .05 ) . Cesarean delivery rates for the indication of dystocia also did not differ , being 10.5 % in the opioid group and 5.8 % in the epidural group ( relative risk 0.56 , 95 % confidence interval 0.26 - 1.21 , P > .05 ) . Sub analysis of the data from patients who were compliant with the allocated form of treatment revealed that patients in the epidural group ( n = 147 ) were 3 times more likely to have an active phase duration > /=8 hours and were 10 times more likely to require > /=2 hours in the second stage of labor than were those in the opioid group ( n = 78 ) . There were no significant differences in cesarean delivery rates in this sub analysis , being 7.7 % in the opioid group and 8.8 % in the epidural group ( relative risk 1.15 , 95 % confidence interval 0.45 - 2.91 , P > . 05 ) . The cesarean delivery rates for dystocia were also similar in the sub analysis , being 3.8 % in the opioid group and 5.5 % in the epidural group ( relative risk 1.42 , 95 % confidence interval 0.39 - 5 . 22 , P > .05 ) . CONCLUSION Epidural analgesia provides safe and effective intrapartum pain control and may be administered without undesirable effects on labor outcome Objective To evaluate the relief of pain in labour with subcutaneous and intracutaneous injections of sterile water , compared with placebo Abstract Objective : To determine whether epidural analgesia during labour is associated with long term backache . Design : Follow up after r and omised controlled trial . Analysis by intention to treat Setting : Department of obstetrics and gynaecology at one NHS trust Participants : 369 women : 184 r and omised to epidural group ( treatment as allocated received by 123 ) and 185 r and omised to non-epidural group ( treatment as allocated received by 133 ) . In the follow up study 151 women were from the epidural group and 155 from the non-epidural group Main outcome measures : Self reported low back pain , disability , and limitation of movement assessed through one to one interviews with physiotherapist , question naire on back pain and disability , physical measurements of spinal mobility Results : There were no significant differences between groups in demographic details or other key characteristics . The mean time interval from delivery to interview was 26 months . There were no significant differences in the onset or duration of low back pain , with nearly a third of women in each group reporting pain in the week before interview . There were no differences in self reported measures of disability in activities of daily living and no significant differences in measurements of spinal mobility Conclusions : After childbirth there are no differences in the incidence of long term low back pain , disability , or movement restriction between women who receive epidural pain relief and women who receive other forms of pain OBJECTIVE The purpose of this study was to compare the peripartum and perinatal effects of epidural with intravenous labor analgesia in women with pregnancy-induced hypertension . STUDY DESIGN Women with pregnancy-induced hypertension who had consented to participate were r and omized to receive either epidural or intravenous analgesia for labor pain . Both methods were given according to st and ardized protocol s. All women received magnesium sulfate seizure prophylaxis . Obstetric and neonatal outcomes were compared according to intent-to-treat allocation . RESULTS Seven hundred thirty-eight women were r and omized : 372 women were given epidural analgesia , and 366 women were given intravenous analgesia . Maternal characteristics were similar , including the severity of hypertension . Epidural analgesia was associated with a significantly prolonged second-stage labor , an increase in forceps deliveries , and an increase in chorioamnionitis . Cesarean delivery rates and neonatal outcomes were similar . Pain relief was superior with the epidural method . Hypotension required treatment in 11 % of women in the epidural group . CONCLUSION Epidural labor analgesia provides superior pain relief but no additional therapeutic benefit to women with pregnancy-induced hypertension OBJECTIVE : To determine whether early initiation of neuraxial analgesia ( anesthetic[s ] placed around the nerves of the central nervous system ) compared with systemic opioid analgesia , followed later in labor by epidural analgesia , increases the rate of cesarean delivery in nulliparas undergoing induction of labor . METHODS : Nulliparas undergoing induction of labor who requested analgesia when cervical dilation was less than 4 cm participated in the study . Patients were r and omized to neuraxial ( early ) or systemic opioid ( late ) analgesia at the first analgesia request . Patient-controlled epidural analgesia was initiated in the early group at the second analgesia request and in the late group at cervical dilation of 4 cm or greater or at the third analgesia request . The primary outcome was the rate of cesarean delivery . RESULTS : The rate of cesarean delivery was not different between groups ( neuraxial [ early ] 32.7 % compared with systemic [ late ] 31.5 % , 95 % confidence interval of the difference -3 % to 6 % , P=.65 ) . A sample size of 30,500 would be required to detect a difference at the observed rate . There were no differences in the mode of vaginal delivery or Apgar scores . Pain scores were significantly lower ( median 1 compared with 5 on a 0–10 scale , P<.001 ) and labor duration shorter ( median 528 minutes compared with 569 minutes , P=.047 ) in the early group . The incidence of reassuring fetal heart rate tracings after analgesia was not different between groups . CONCLUSION : Early-labor neuraxial analgesia does not increase the cesarean delivery rate compared with late epidural analgesia in nulliparas undergoing induction of labor . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00380978 LEVEL OF EVIDENCE : The maternal plasma HGH , insulin , glucose and FFA levels were determined during the course of induced labours in 28 healthy mothers . Every second patient was given segmental epidural analgesia for pain relief during the first stage of labour ( epidural ) group ) . The others acted as a control group . HGH did not change significantly during the labour in either group . Insulin decreased during the first stage of labour in both groups . This decrease was more pronounced and statistically almost significant in the control group . Thereafter the insulin increased in both groups . Glucose levels did not change during the first stage , but at the moment of delivery they were significantly higher than the initial levels in both groups . FFA levels became raised in both groups during labour , reaching a peak at the moment of delivery . The results are discussed in relation to stress and effectiveness of pain relief during the first stage of labour Background Combined spinal‐epidural ( CSE ) analgesia produces rapid‐onset pain relief and allows ambulation in early labor . Epidural local anesthetics may contribute to an increase in operative deliveries by decreasing perineal sensation and causing motor weakness . Operative delivery rates might be reduced with CSE , by avoiding or delaying administration of local anesthetics . This study compares the operative delivery rates associated with a CSE technique and those associated with intravenous meperidine for labor analgesia . Methods Healthy parturients at full term were assigned r and omly to receive CSE or intravenous meperidine analgesia . The CSE group received 10 [ micro sign]g intrathecal sufentanil , followed by epidural bupivacaine and fentanyl at their next request for analgesia . Parturients receiving intravenous meperidine had 50 mg on dem and ( maximum , 200 mg in 4 h ) . Labor and delivery outcomes in both groups were recorded and compared . Results An intent‐to‐treat analysis of 1,223 women indicated that CSE does not increase the rate of cesarean delivery for dystocia in nulliparous and parous women ( CSE , 3.5 % vs. intravenous meperidine , 4 ; P = not significant ) or in nulliparous women alone ( CSE , 7 % vs. intravenous meperidine , 8 % ; P = not significant ) . Profound fetal bradycardia that necessitated emergency cesarean delivery within 1 h of the time the mother received sufentanil occurred in 8 of 400 parturients ( compared with 0 of 352 who received meperidine ; P < 0.01 ) . However , the method of fetal monitoring differed between the two groups . Despite this , neonatal outcomes were similar overall . Conclusions Combined spinal‐epidural analgesia during labor does not increase the cesarean delivery rate for dystocia in healthy parturient patients at full term , regardless of parity . However , an unexpected increase in the number of cesarean deliveries for profound fetal bradycardia after intrathecal sufentanil was observed . Further investigation is warranted Purpose To evaluate the usefulness of intravenous patient-controlled analgesia ( PCA ) fentanyl for labour analgesia , its effectiveness for maternal pain and safety for the fetus and newborn . Methods Twenty primigravidas were r and omised to receive intravenous PCA fentanyl or epidural analgesia for labour pain . Maternal pain , heart rate and arterial oxyhaemoglobin saturation ( SpO2 ) were monitored . Fetal and neonatal monitoring included cardiotocogram ( CTG ) , APGAR , neurological scoring and static-charge-sensitive bed ( SCSB ) recording for 12 hr postnatally with ECG and SpO2 . Fentanyl concentrations and pH of umbilical artery and vein were analysed . Results Initially , epidural analgesia was more effective ( P = 0.01 ) , and three patients in the fentanyl group were given epidural due to unsatisfactory pain relief . Overall satisfaction for analgesia did not differ between the groups . Maternal side-effects were more frequent in the fentanyl group ( dizziness and tiredness most often , P = 0.0001 ) . Severe side-effects were not reported . In CTG there were no differences between groups . All the newborns were healthy , APGAR and pH were normal . Naloxone was not used . Neurological scoring was similar in both groups . In 12 hr monitoring heart rate , breathing frequency and movement time were similar in both groups , but SpO2 was lower in the fentanyl group ( P < 0.001 ) . Umbilical cord fentanyl concentrations were low or beyond the detection limit . Conclusion Intravenous fentanyl can be used for labour analgesia with the doses reported here as an alternative to epidural analgesia . However , the fetus and neonate must be appropriately monitored . Naloxone and oxygen should be available if neonatal distress occurs . RésuméObjectifÉvaluer l ’ importance de l’analgésie intraveineuse auto-contrôlée ( PCA ) au fentanyl en analgésie obstétncale en tenant compte de son efficacité et de la sécurité foeto-maternelle . MéthodesVingt pnmipares ont été assignées aléatoirement à recevoir soit du fentanyl intraveineux en PCA soit une analgésie épidurale dans le but de soulager la douleur de l’accouchement . La douleur maternelle , la fréquence cardiaque et la saturation arténelle ( SpO2 ) ont été notées . Le monitorage foetal et néonatal incluait la cardiotocographie ( CTG ) , le score d’APGAR , l’évaluation neurologique et l’enregistrement au lit sensible à la statique ( SCSB ) pendant 12 h après la naissance avec l’ÉCG ET la SpO2 . La concentration de fentanyl et le pH de l’artère et de la veine ombilicales étaient mesurés . RésultatsInitialement , l’analgésie épidurale s’est avérée plus efficace ( P = 0,01 ) et trois patientes du groupe fentanyl ont dû accepter une analgésie épidurale à cause du manque de soulagement . La satisfaction globale en rapport avec l’analgésie n’a pas différé entre les groupes . Des effets maternels secondaires sans gravité sont survenus plus souvent dans le groupe fentanyl ( surtout des étourdissements et de la fatigue , P = 0,0001 ) . Le CTG n’a pas révélé de différences intergroupes . Tous les enfants sont nés en bon état avec des scores d’APGAR et des pH normaux . On n’a pas administré de naloxone . Lévaluation neurologique était identique dans les deux groupes . Après 12 h de monitorage de la fréquence cardiaque , la fréquence respiratoire et le temps de mouvement étaient identiques dans les deux groupes mais la SpO2 était plus basse dans le groupe fentanyl ( P < 0,001 ) . Les concentrations ombilicales de fentanyl étaient faibles ou impossible à déceler . Conclusion Pour l’analgésie de l’accouchement , on peut substituer le fentanyl intraveineux selon les doses utilisées à l’analgésie épidurale . Cependant , le foetus et le nouveau-né doivent être surveillés de près . Il faut avoir du naloxone ou de l’oxygène à portée de main pour traiter la détresse néonatale potentielle A number of recent studies have suggested that the analgesic effects of highly lipid-soluble opioids are similar when these agents are administered either epidurally or intravenously . We sought to test whether the lipid-soluble opioid sufentanil was more effective when administered intrathecally than when administered epidurally or intravenously . Twenty-four women during active labor received sufentanil 10 micrograms either intrathecally ( n = 9 ) , epidurally ( n = 8) , or intravenously ( n = 7 ) , using a combined spinal-epidural technique . The sufentanil was administered alone , without concomitant local anesthetics . Analgesia was assessed using the visual analogue score as well as the time elapsed from the administration of study drug to the patient 's request for additional analgesia via the epidural catheter ( bupivacaine 0.25 % ) . The median duration of analgesia ( median , interquartile range ) was 84 ( 70 - 92 ) min in the intrathecal group , 30 ( 23 - 32 ) min in the epidural group , and 34 ( 17 - 30 ) min in the intravenous group ( P < 0.001 ) . The intrathecal group showed rapid and significant decrease in visual analogue scale scores , whereas visual analogue scale scores in the other two groups did not decrease and remained significantly elevated compared to those of the intrathecal group at all observation points . Side effects were limited to pruritus in 3 patients ( 2 moderate and 1 severe ) in the intrathecal group . No patient developed post-dural puncture headache . We conclude that sufentanil 10 micrograms intrathecally provides rapid and effective analgesia of 1 - 2-h duration during labor . Epidural and intravenous use of this dose of sufentanil did not provide evidence of satisfactory analgesia . ( ABSTRACT TRUNCATED AT 250 WORDS This prospect i ve study evaluated the extent to which the analgesic procedures available result ed in efficient pain relief in 833 Finnish parturients . Their pain ratings were recorded according to their own assessment of pain intensity during labour before and after pain management and according to their total pain experience recalled on the third day after delivery . Only regional blocks significantly diminished pain scores during labour and a striking decrease in pain level ( P < 0.0001 ) was maintained until the second stage by epidural analgesia ( EDA ) alone . The EDA-group consisted mainly of the primiparous ( 71 % ) with induced ( 17 % ) and most painful deliveries . After delivery 60 % of parturients in this group recalled labour pain as being very severe or intolerable . This was partly due to delays in receiving epidural blockade and partly due to the parturient 's reticence in requesting analgesia . Pain relief was rated as excellent or good by 94 % of the EDA group but by only 50 % of the remaining patients In a prospect i ve r and omized study we evaluated the opinion of 97 parturients on either epidural analgesia or parenteral pethidine with respect to analgesic efficacy , general feelings and symptoms during labour and delivery . The analgesic effect of the epidural block was significantly superior to pethidine with regard to the pain score ( visual analogue scale (VAS)0 during the first stage of labour ( mean VAS 11 contrasting 65 ) . Moreover , 30 ( 59 % ) women in the epidural group compared to 9 ( 20 % ) in the pethidine group had a painless labour and delivery . Significantly more parturients ( 37 ( 73 % ) ) in the epidural group would request an epidural blockade rather than pethidine treatment ( 14 ( 30 % ) ) in a subsequent labour . Fewer side effects were registered in the epidural group compared to the pethidine group , however only significantly concerning sleepiness . It is concluded that in this study low-dose epidural analgesia during the first stage of labour was superior to parenteral pethidine regarding pain relief and side effects OBJECTIVES To compare analgesic efficacy of intramuscular opioids : meperidine and tramadol with epidural analgesia . METHODS One hundred and twenty-eight term nulliparous women with singleton pregnancy and vertex presentation were r and omized to receive either epidural ( n=43 ) , meperidine ( n=39 ) or tramadol ( n=44 ) . A visual analog scale ( VAS ) was used to assess the severity of pain . The parameters analyzed were analgesic efficacy , effect on labor , other maternal side effects , perinatal outcome and maternal satisfaction . RESULTS Median VAS scores following first dose were 0 ( 0 - 5 ) , 5 ( 3 - 8 ) and 5 ( 3 - 8 ) in epidural , meperidine and tramadol groups , respectively . Ninety percent of women rated analgesia as good to excellent in the epidural group as compared with 72 % of women in the meperidine group and 65 % in tramadol group . However , epidural caused a significant prolongation of first ( P<0.05 ) and second ( P<0.01 ) stage of labor with an increased number of operative deliveries ( 27 % in the epidural , 7.6 % in the meperidine , and 11.4 % in the tramadol groups , P<0.05 ) . In the epidural group 40 % women had urinary retention and 16 % had motor weakness , whereas sedation was the only side effect seen in the meperidine ( 41 % ) and tramadol groups ( 9 % ) . Respiratory depression was noted among three neonates in the meperidine group , two in the tramadol group and none in the epidural group . CONCLUSIONS The analgesic efficacy and maternal satisfaction is better with epidural analgesia than with opioids . Analgesia provided by meperidine and tramadol is comparable and approximately 50 % of women rated the analgesia as good . Meperidine is better in the second stage than tramadol . Hence in developing nations where availability of facilities is the main limiting factor , intramuscular opioids can be considered suitable alternatives Continuous lumbar epidural analgesia ( L.E.A. ) is considered to be the most effective technique for providing pain relief during labour and delivery . A prospect i ve r and omized study of 52 patients with pre-eclamptic toxemia in labour was carried out to investigate various aspects of the use of L.E.A. in view of the considerable disagreement concerning its effect . The results were compared to a control group ( n = 52 ) receiving i.v . infusion of Hydralazine ( Apresoline ) and MgSO4 according to Zuspan recommendations . The results were evaluated statistically . The incidence of neonatal jaundice was higher in the control group ( P less than 0.005 ) . Maternal postpartum complications were similar in both groups . There were fewer forceps deliveries in the control group ( P less than 0.05 ) . The decrease in systolic BP after L.E.A. is well documented up to 120 min after the first injection of Marcaine ( P less than 0.001 - 0.025 ) , while after 120 min , by which time the Marcaine effect has finished , the systolic BP rises again ( time for topping up ) . The decrease in the average diastolic BP as compared to the control group is statistically significant ( P less than 0.001 - 0.01 ) until 180 min after initiation of the L.E.A. After that , the average diastolic BP rises again , unless Marcaine is topped up . Our results favour L.E.A. as the obstetric analgesic method of choice in cases of severe pre-eclampsia BACKGROUND Although epidural anaesthesia has become a st and ard method for labour analgesia all over the world , it is far from being ideal because of side effects and contraindications . Many alternative techniques have therefore been proposed , including the continuous infusion of remifentanil . Encouraged by positive reports , we compared the efficacy of patient-controlled remifentanil infusion ( PCA ) with patient-controlled continuous epidural analgesia ( PCEA ) . METHODS Fifty-two ASA I and II parturients were arbitrarily allocated , without r and omisation , to two groups to receive PCEA with 0.125 % bupivacaine and 0.2 microg kg(-1 ) fentanyl ( basic infusion 1 mL h(-1 ) , bolus 4 mL , lock-out time 15 min ) or remifentanil PCA ( 0.2 microg kg(-1 ) bolus doses , without basic infusion , lock-out time 2 min ) . The intensity of pain was assessed using the VAS scale every 15 min in the PCEA group and every 10 min in the PCA group . RESULTS During the first two hours of labour , the VAS score was significantly lower in the PCEA group . Later there was no difference between the groups . The clinical status of the newborns was similar . CONCLUSION The results are difficult to interpret since there was no r and omisation and parturients participated in decisions about allocation to one of the study groups . Analgesia provided by remifentanil was assessed as highly acceptable by the patients and the drug can be regarded as a safe alternative to epidural analgesia during labour OBJECTIVE To estimate whether the cesarean delivery rate differs between women with severe preeclampsia who receive intrapartum epidural analgesia versus patient‐controlled intravenous opioid analgesia . METHODS Women with severe preeclampsia at at least 24 weeks ' gestation were r and omly assigned to receive either intrapartum epidural ( n = 56 ) versus patient‐controlled intravenous opioid analgesia ( n = 60 ) , and each was administered by a st and ardized protocol . The sample size was selected to have 80 % power to detect at least a 50 % difference in the predicted intergroup cesarean delivery rates . Data were analyzed by intent to treat . RESULTS Selected maternal characteristics and neonatal outcomes were similar in the two groups . The cesarean delivery rates in the epidural group ( 18 % ) and the patient‐controlled analgesia group ( 12 % ) were similar ( P = .35 ) . Women who received epidural analgesia were more likely to require ephedrine for the treatment of hypotension ( 9 % versus 0 % , P = .02 ) , but their infants were less likely to require naloxone at delivery ( 9 % versus 54 % , P < .001 ) . Epidural analgesia provided significantly better pain relief as determined by a visual analogue intrapartum pain score ( P < .001 ) and a postpartum pain management survey ( P = .002 ) . CONCLUSION Compared with patient‐controlled intravenous opioid analgesia , intrapartum epidural analgesia did not significantly increase the cesarean delivery rate in women with severe preeclampsia at our level III center , and it provided superior pain relief OBJECTIVE To estimate the effects of initiation of epidural analgesia on fetal heart rate ( FHR ) patterns compared with intravenous meperidine analgesia . METHODS Fetal heart rate patterns in 200 nulliparous women with term pregnancies r and omized to epidural analgesia with 0.25 % bupivacaine were compared with those of 156 similar women given intravenous meperidine . Fetal heart rate patterns occurring within 40 minutes of initiation of labor analgesia were retrospectively read by three maternal – fetal medicine specialists who were blind to clinical events , including type of labor analgesia . RESULTS Meperidine , compared with epidural analgesia , was associated with statistically significantly less beat-to-beat variability ( absent or less than 5 beats per minute ) of the FHR ( 30 % versus 7 % of fetuses , P < .001 ) in the first 40 minutes after initiation of analgesia , as well as with fewer FHR accelerations ( 88 % versus 62 % of fetuses , P < .001 ) . Neither the incidence of FHR decelerations nor the type of deceleration were significantly different between methods of labor analgesia . Specifically , 41 % of women given meperidine exhibited FHR decelerations within 40 minutes , compared with 34 % given epidural analgesia ( P = .353 ) . CONCLUSION Epidural analgesia does not have deleterious effects on FHR BACKGROUND Concern has been expressed that epidural analgesia for labour may be associated with a higher incidence of backache . METHODS A prospect i ve r and omized trial investigating the effect of epidural analgesia on the outcome of labour in nulliparae , mothers were r and omized to receive either epidural analgesia or meperidine . A question naire on postnatal symptoms was sent to them 6 months after delivery . RESULTS In all , 611 mothers were studied ; 310 were r and omly allocated to receive i.m . meperidine up to 300 mg and 301 to receive epidural bupivacaine . The response rate to our question naire was 83 % . Intention-to-treat analysis showed similar prevalence rates of postpartum backache in the epidural ( 48 % ) and meperidine groups ( 50 % ) , with an observed difference ( epidural-meperidine ) of -2 % ( 95 % CI , -11 to + 6 % ) . After excluding mothers with backache before delivery , there were also similar incidence rates of postpartum backache in the epidural ( 29 % ) and meperidine groups ( 28 % ) , observed difference 1 % ( 95 % CI , -8 to + 10 % ) . CONCLUSIONS Epidural analgesia in labour was not associated with an increase in the prevalence or incidence of backache A prospect i ve r and omized study was performed to evaluate the influence of epidural analgesia compared to parenteral pethidine in parturients with pain in the first stage of labour on the progress of labour and the frequency of instrumental deliveries . There was no significant difference in the two groups in the duration of either the first or second stage of labour . The overall instrumental delivery rate was 25 % , with no difference between the groups . The analgesic efficacy of the epidural blockade was significantly better than that of parenteral pethidine . We conclude that epidural bupivacaine with our technique and obstetric practice did neither prolong labour nor increase the frequency of instrumental delivery Objectives To investigate possible short and long term side effects of epidural analgesia , compared with non‐epidural analgesia for pain relief in labour Background Controversy concerning increased cesarean births as a result of epidural analgesia for relief of labor pain has been attributed , in large part , to difficulties interpreting published studies because of design flaws . In this study , the authors compared epidural analgesia to intravenous meperidine analgesia using patient-controlled devices during labor to evaluate the effects of labor epidural analgesia , primarily on the rate of cesarean deliveries while minimizing limitations attributable to study design . Methods Four hundred fifty-nine nulliparous women in spontaneous labor at term were r and omly assigned to receive either epidural analgesia or intravenous meperidine analgesia . Epidural analgesia was initiated with 0.25 % bupivacaine and was maintained with 0.0625 % bupivacaine and fentanyl 2 & mgr;g/ml at 6 ml/h with 5-ml bolus doses every 15 min as needed using a patient-controlled pump . Women in the intravenous analgesia group received 50 mg meperidine with 25 mg promethazine hydrochloride as an initial bolus , followed by 15 mg meperidine every 10 min as needed , using a patient-controlled pump . A written procedural manual that prescribed the intrapartum obstetric management was followed for each woman r and omized in the study . Results A total of 226 women were r and omized to receive epidural analgesia , and 233 women were r and omized to receive intravenous meperidine analgesia . Protocol violations occurred in 8 % ( 38 of 459 ) of women . There was no difference in the rate of cesarean deliveries between the two analgesia groups ( epidural analgesia , 7 % [ 16 of 226 ; 95 % confidence interval , 4–11%]vs . intravenous meperidine analgesia , 9 % [ 20 of 233 ; 95 % confidence interval , 5–13%];P = 0.61 ) . Significantly more women r and omized to epidural analgesia had forceps deliveries compared with those r and omized to meperidine analgesia ( 12 % [ 26 of 226]vs . 3 % [ 7 of 233];P < 0.001 ) . Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received intravenous meperidine analgesia . Conclusions Epidural analgesia compared with intravenous meperidine analgesia during labor does not increase cesarean deliveries in nulliparous women OBJECTIVE Our purpose was to determine the effect of epidural analgesia on nulliparous labor and delivery . STUDY DESIGN Normal term nulliparous women in early spontaneous labor were r and omized to receive either narcotic or epidural analgesia . RESULTS When compared with the group receiving narcotic analgesia ( n = 45 ) , the group receiving epidural analgesia ( n = 48 ) had a significant prolongation in the first and second stages of labor , an increased requirement for oxytocin augmentation , and a significant slowing in the rate of cervical dilatation . Epidural analgesia was associated with a significant increase in malposition ( 4.4 % vs 18.8 % , p < 0.05 ) . Cesarean delivery occurred more frequently in the epidural group ( 2.2 % vs 25 % , p < 0.05 ) , primarily related to an increase in cesarean section for dystocia ( 2.2 % vs 16.7 % , p < 0.05 ) . CONCLUSIONS In a r and omized , controlled , prospect i ve trial epidural analgesia result ed in a significant prolongation in the first and second stages of labor and a significant increase in the frequency of cesarean delivery , primarily related to dystocia Objective To compare the effects of epidural analgesia with intravenous ( IV ) analgesia on the outcome of labor . Methods Thirteen hundred thirty women with uncomplicated term pregnancies and in spontaneous labor were r and omized to be offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor . Results Comparison of the allocation groups by intent to treat revealed a significant association between epidural allocation and operative delivery for dystocia . However , only 65 % of each r and omization group accepted the allocated treatment . Four hundred thirty-seven women accepted and received meperidine as allocated , and they were compared with 432 women accepting epidural allocation . Significant associations result ed between epidural administration and prolongation of labor , increased rate of oxytocin administration , chorioamnionitis , low forceps , and cesarean delivery . Because of the high rate of noncompliance with treatment allocation , a multifactorial regression analysis was performed on the entire cohort , and a twofold relative risk of cesarean delivery persisted in association with epidural treatment . The impact of epidural treatment on cesarean delivery was significant for both nulliparous and parous women ( risk ratios 2.55 and 3.81 , respectively ) . Epidural analgesia provided significantly better pain relief in labor than did parenteral meperidine . Conclusion Although labor epidural analgesia is superior to meperidine for pain relief , labor is prolonged , uterine infection is increased , and the number of operative deliveries are increased . A two- to fourfold increased risk of cesarean delivery is associated with epidural treatment in both nulliparous and parous women In a r and omised double blind trial , 36 patients in the first stage of labour received either epidural or intramuscular fentanyl at the same time as the epidural test dose of bupivacaine . Analgesia was more rapid in onset and more complete in the epidural fentanyl group . Supplementary doses of bupivacaine were required within the first hour in 62 % of the intramuscular fentanyl group compared with only 16 % in the epidural group . Plasma fentanyl concentrations showed wide interindividual variation , but after epidural fentanyl the peak occurred earlier . There was no correlation between analgesia and plasma fentanyl concentration , and epidural fentanyl produced superior analgesia but a systemic contribution to this effect can not be ruled out We have previously demonstrated that continuous epidural infusions of fentanyl without local anesthetics elicit analgesia by a systemic mechanism . In this study , we examined the hypothesis that , in the presence of epidural bupivacaine , continuous infusions of epidural fentanyl elicit analgesia by a spinal mechanism . Forty-eight nulliparous women in active labor participated in this prospect i ve , r and omized , double-blinded study . Women received lumbar epidural analgesia with 20–30 mL bupivacaine 0.125 % until pain free . Subjects were then r and omized to either IV or epidural ( EPI ) fentanyl infusion groups . Each infusion delivered fentanyl 30 & mgr;g/h . All women received an epidural infusion of bupivacaine at a rate of 20 mL/h , the concentration of which was determined by the response of the previous woman in the same group to the analgesic regimen used . Unlike previous studies that assessed the minimum local analgesic concentration ( MLAC ) for bolus administration at the initiation of analgesia , this study assessed MLACinfusion for the maintenance of analgesia throughout the first stage of labor . MLACinfusion was determined using the up-down sequential analysis described by Dixon and Massey . The MLACinfusion of epidural bupivacaine was 0.063 % ( 95 % confidence interval , 0.058–0.068 ) and 0.019 % ( 95 % confidence interval , 0.000–0.038 ) in the IV and EPI groups respectively . A continuous infusion of fentanyl was more than three times as potent when administered by the epidural than by the IV route . This marked increase in potency for the epidural route is highly suggestive for a predominantly spinal mechanism of action for infused epidural fentanyl under the conditions of this study OBJECTIVE To evaluate the safety and analgesic efficacy of patient controlled intravenous analgesia ( PCIA ) with tramadol , and to compare its benefits and risks with combined spinal-epidural analgesia (CSEA)+ patient controlled epidural analgesia ( PCEA ) . METHODS Eighty American Society of Anesthesiologist ( ASA ) I-II at term parturients in active labor were r and omly divided into 3 groups : the control group ( n = 30 ) received no analgesia ; group A ( n = 30 ) received spinal administration with ropivacaine 2.5 mg and fentanyl 5 microg , then with PCEA ; group B ( n = 20 ) received 1 mg/kg tramadol loading dose i.v . PCIA with 0.75 % tramadol and it included : PCA dose 2 ml , lockout time 10 minutes , background infusion 2 ml/h , total dose no more than 400 mg . The intensity of pain was evaluated using Visual Analogue Scale ( VAS ) . RESULTS Both group A and B showed good pain relief . VAS pain scores were significantly decreased in group A and B compared with those in the control group ( P < 0.01 ) . In comparison with group B , the VAS pain scores decreased in group A ( P < 0.05 ) . The onset times of analgesia in group A were shorter than those in group B ( P < 0.05 ) . Apgar scores in group B were lower than those in group A ( P < 0.05 ) . The periods of second stage of labor in group A were longer than those in the control group and group B ( P < 0.05 ) . The cesarean delivery rate was significantly higher in the control group ( 16.7 % ) than in group A ( 3.3 % ) and group B ( 5.0 % ) , but it did not differ between group A and B. There were no significant differences in vital signs , fetal heart rate , degree of motor block , and uterine contractions among the 3 groups . CONCLUSIONS PCIA with tramadol is now a useful alternative when patients are not c and i date s for CSEA for labor , or do not want to have a neuraxial block anesthesia . However , sometimes it may not provide satisfactory analgesic effect Objective : To assess maternal satisfaction with childbirth and intrapartum pain relief in nulliparous women labouring at term In this multicenter , r and omized , controlled trial , we sought to determine whether patient-controlled epidural analgesia ( PCEA ) for labor affected the incidence of cesarean delivery when compared with patient-controlled IV opioid analgesia ( PCIA ) . Healthy , term nulliparous patients in 4 Canadian institutions were r and omly assigned to receive PCIA with fentanyl ( n = 118 ) or PCEA with 0.08 % bupivacaine and fentanyl 1.6 & mgr;g/mL ( n = 124 ) . There was no difference in the incidence of cesarean delivery—10.2 % ( 12 of 118 ) versus 9.7 % ( 12 of 124)—or instrumental vaginal delivery—21.2 % ( 25 of 118 ) versus 29 % ( 36 of 124)—between groups . The duration of the second stage of labor was increased in the PCEA group by a median of 23 min ( P = 0.02 ) . Fifty-one patients ( 43 % ) in the PCIA group received epidural analgesia : 39 ( 33 % ) because of inadequate pain relief and 12 ( 10 % ) to facilitate operative delivery . Patients in the PCIA group required more antiemetic therapy ( 17 % versus 6.4 % ; P = 0.01 ) and had more sedation ( 39 % versus 5 % ; P < 0.001 ) . Maternal mean pain and satisfaction with analgesia scores were better in the PCEA group ( P < 0.001 and P = 0.02 , respectively ) . More neonates in the PCIA group required active resuscitation ( 52 % versus 31 % ; P = 0.001 ) and naloxone ( 17 % versus 3 % ; P < 0.001 ) . These observations support the hypothesis that PCEA does not result in an increased incidence of obstetrical intervention compared with PCIA . PCEA provides superior analgesia and less maternal and neonatal sedation compared with PCIA AIMS To investigate the effects of massage on pain reaction and anxiety during labour . BACKGROUND Labour pain is a challenging issue for nurses design ing intervention protocol s. Massage is an ancient technique that has been widely employed during labour , however , relatively little study has been undertaken examining the effects of massage on women in labour . METHODS A r and omized controlled study was conducted between September 1999 and January 2000 . Sixty primiparous women expected to have a normal childbirth at a regional hospital in southern Taiwan were r and omly assigned to either the experimental ( n=30 ) or the control ( n=30 ) group . The experimental group received massage intervention whereas the control group did not . The nurse-rated present behavioural intensity ( PBI ) was used as a measure of labour pain . Anxiety was measured with the visual analogue scale for anxiety ( VASA ) . The intensity of pain and anxiety between the two groups was compared in the latent phase ( cervix dilated 3 - 4 cm ) , active phase ( 5 - 7 cm ) and transitional phase ( 8 - 10 cm ) . RESULTS In both groups , there was a relatively steady increase in pain intensity and anxiety level as labour progressed . A t-test demonstrated that the experimental group had significantly lower pain reactions in the latent , active and transitional phases . Anxiety levels were only significantly different between the two groups in the latent phase . Twenty-six of the 30 ( 87 % ) experimental group subjects reported that massage was helpful , providing pain relief and psychological support during labour . CONCLUSIONS Findings suggest that massage is a cost-effective nursing intervention that can decrease pain and anxiety during labour , and partners ' participation in massage can positively influence the quality of women 's birth experiences Background : Although the labour and delivery outcomes of epidural analgesia have been investigated extensively , the effects on breast‐feeding success are not clearly identified |
11,758 | 26,642,915 | Testing was performed on average 3 - 5 min after stretching , and most studies did not include poststretching dynamic activities ; when these activities were included , no clear performance effect was observed .
DS produced small-to-moderate performance improvements when completed within minutes of physical activity .
SS and PNF stretching had no clear effect on all-cause or overuse injuries ; no data are available for DS .
All forms of training induced ROM improvements , typically lasting < 30 min .
Changes may result from acute reductions in muscle and tendon stiffness or from neural adaptations causing an improved stretch tolerance .
Considering the small-to-moderate changes immediately after stretching and the study limitations , stretching within a warm-up that includes additional poststretching dynamic activity is recommended for reducing muscle injuries and increasing joint ROM with inconsequential effects on subsequent athletic performance | Recently , there has been a shift from static stretching ( SS ) or proprioceptive neuromuscular facilitation ( PNF ) stretching within a warm-up to a greater emphasis on dynamic stretching ( DS ) .
The objective of this review was to compare the effects of SS , DS , and PNF on performance , range of motion ( ROM ) , and injury prevention . | Contractile force is transmitted to the skeleton through tendons and aponeuroses , and , although it is appreciated that the mechanocharacteristics of these tissues play an important role for movement performance with respect to energy storage , the association between tendon mechanical properties and the contractile muscle output during high-force movement tasks remains elusive . The purpose of the study was to investigate the relation between the mechanical properties of the connective tissue and muscle performance in maximal isometric and dynamic muscle actions . Sixteen trained men participated in the study . The mechanical properties of the vastus lateralis tendon-aponeurosis complex were assessed by ultrasonography . Maximal isometric knee extensor force and rate of torque development ( RTD ) were determined . Dynamic performance was assessed by maximal squat jumps and countermovement jumps on a force plate . From the vertical ground reaction force , maximal jump height , jump power , and force-/velocity-related determinants of jump performance were obtained . RTD was positively related to the stiffness of the tendinous structures ( r = 0.55 , P < 0.05 ) , indicating that tendon mechanical properties may account for up to 30 % of the variance in RTD . A correlation was observed between stiffness and maximal jump height in squat jumps and countermovement jumps ( r = 0.64 , P < 0.05 and r = 0.55 , P < 0.05 ) . Power , force , and velocity parameters obtained during the jumps were significantly correlated to tendon stiffness . These data indicate that muscle output in high-force isometric and dynamic muscle actions is positively related to the stiffness of the tendinous structures , possibly by means of a more effective force transmission from the contractile elements to the bone The aim of this study was to measure if passive stretching would influence delayed onset muscle soreness ( DOMS ) , dynamic muscle strength , plasma creatine kinase concentration ( CK ) and the ratio of phosphocreatine to inorganic phosphate ( PCr/P(i ) ) following eccentric exercise . Seven healthy untrained women , 28 - 46 years old , performed eccentric exercise with the right m. quadriceps in an isokinetic dynamometer ( Biodex , angle velocity : 60 degrees.s-1 ) until exhaustion , in two different experiments , with an interval of 13 - 23 months . In both experiments the PCr/P(i ) ratio , dynamic muscle strength , CK and muscle pain were measured before the eccentric exercise ( day 0 ) and the following 7 d. In the second experiment daily passive stretching ( 3 times of 30 s duration , with a pause of 30 s in between ) of m. quadriceps was included in the protocol . The stretching was performed before and immediately after the eccentric exercise at day 0 , and before measurements of the dependent variables daily for the following 7 d. The eccentric exercise alone led to significant decreases in PCr/P(i ) ratio ( P < 0.001 ) and muscle strength ( P < 0.001 ) , and an increase in CK concentration ( P < 0.01 ) . All subjects reported pain in the right m. quadriceps with a peak 48 h after exercise . There was no difference in the reported variables between experiments one and two . It is concluded that passive stretching did not have any significant influence on increased plasma-CK , muscle pain , muscle strength and the PCr/P(i ) ratio , indicating that passive stretching after eccentric exercise can not prevent secondary pathological alterations To study the efficacy of an injury prevention program in a r and omized trial , 12 teams ( 180 players ) in a male senior soccer division were followed up for 6 months . The 12 teams were allocated at r and om to two groups of six teams , one being given a prophylactic program and the other serving as control . The program was based on previous studies of injury mechanisms . It comprised ( 1 ) correction of training , ( 2 ) provision of optimum equipment ; ( 3 ) prophylactic ankle taping ; ( 4 ) controlled rehabilitation ; ( 5 ) exclusion of players with grave knee instability ; ( 6 ) information about the impor tance of disciplined play and the increased risk of injury at training camps ; and ( 7 ) correction and supervision by doctor(s ) and physiotherapist(s ) . The injuries in the test teams were 75 % fewer than in the controls . The most common types of soccer injuries , sprains and strains to ankles and knees , were all significantly reduced . It is concluded that the pro posed prophylactic program , including close supervi sion and correction by doctors and physiotherapists , significantly reduces soccer injuries PURPOSE To analyze the effectiveness in reducing the number of sport injuries after application of different strategies of preventive physiotherapy during competition periods in an America 's Cup yachting crew . METHODS A prospect i ve physiotherapy intervention study during competition periods for three seasons was conducted on an America 's Cup yachting race crew of 30 professional sailors . In the first two acts ( 2004 ) , athletes did not receive any preventive physiotherapy . In the two acts celebrated in 2005 , preventive intervention ( phase 1 ) consisted of stretching exercises before the yacht race and preventative taping . During the four acts corresponding to the 2006 season , the physiotherapy program was implemented adding articular mobilization before competition , ice baths after competition , and kinesiotaping ( phase 2 ) . In the last act and the Louis Vuitton Cup ( 2007 ) , a recovery program with " core stability " exercises , postcompetition stretching exercises , and 12 h of compressive clothing were added ( phase 3 ) . RESULTS In the preintervention phase ( 2004 ) , the rate of injured sailors/competition day was 1.66 , decreasing to 0.60 in 2007 ( phase 3 ) . The number of athletes with more than one injury was significantly reduced from 53 % ( 8 of 15 ) to 6.5 % ( 2 of 12 ) . In the preintervention period , mastmen , grinders , and bowmen showed a rate of 2.88 injuries per competition day . After phase 3 , this group only suffered 0.35 injuries per competition day . CONCLUSIONS The implementation of a program of preventive physiotherapy decreased the risk of injuries suffered during competition by an America 's Cup yacht crew CONTEXT Some research ers have suggested that an alteration of stretch perception could be responsible for the success of the contract-relax ( CR ) stretch , a stretch technique derived from proprioceptive neuromuscular facilitation ( PNF ) . OBJECTIVE This study was conducted to determine if the alteration of the stretch perception is a possible explanation for the range of motion ( ROM ) gains of the CR stretch . PARTICIPANTS Eighteen subjects performed two stretches in r and omized order : the slow stretch and the CR stretch . MAIN OUTCOME MEASURE The stretch intensity was controlled . The stretch force was measured and compared between the slow stretch and CR stretch . RESULTS There was a significant difference between the stretch force that could be applied in the PNF stretch ( 126.0 N ) and the slow stretch ( 108.4 N ) ; P = 0.00086 . The average stretch tolerance progressively increased with successive trials from 120.6 N in the first trial to 132.4 N in the fourth trial . CONCLUSION The alteration of stretch perception plays a role in the success of the CR form of PNF stretching . At least four repetitions of the CR stretch are recommended to get the greatest ROM gain The purpose of this study was to determine the effect of different static and dynamic stretch protocol s on 20-m sprint performance . The 97 male rugby union players were assigned r and omly to 4 groups : passive static stretch ( PSS ; n = 28 ) , active dynamic stretch ( ADS ; n = 22 ) , active static stretch ( ASST ; n = 24 ) , and static dynamic stretch ( SDS ; n = 23 ) . All groups performed a st and ard 10-minute jog warm-up , followed by two 20-m sprints . The 20-m sprints were then repeated after subjects had performed different stretch protocol s. The PSS and ASST groups had a significant increase in sprint time ( p ≤ 0.05 ) , while the ADS group had a significant decrease in sprint time ( p ≤ 0.05 ) . The decrease in sprint time , observed in the SDS group , was found to be nonsignificant ( p ≥ 0.05 ) . The decrease in performance for the 2 static stretch groups was attributed to an increase in the musculotendinous unit ( MTU ) compliance , leading to a decrease in the MTU ability to store elastic energy in its eccentric phase . The reason why the ADS group improved performance is less clear , but could be linked to the rehearsal of specific movement patterns , which may help increase coordination of subsequent movement . It was concluded that static stretching as part of a warm-up may decrease short sprint performance , whereas active dynamic stretching seems to increase 20-m sprint performance Abstract Maddigan , ME , Peach , AA , and Behm , DG . A comparison of assisted and unassisted proprioceptive neuromuscular facilitation techniques and static stretching . J Strength Cond Res 26(5 ) : 1238–1244 , 2012—Proprioceptive neuromuscular facilitation ( PNF ) stretching often requires a partner . Straps are available allowing an individual to perform PNF stretching alone . It is not known if a strap provides similar improvements in the range of motion ( ROM ) as partner-assisted PNF or static stretching . The purpose of this study was to compare assisted and unassisted ( with a strap ) PNF stretching and static stretching . Hip joint ROM , reaction time ( RT ) , and movement time ( MT ) were measured prestretching and poststretching . Thirteen recreationally active adults participated in this study . The participants were subjected to 5 different stretch interventions in a r and om order on separate days . Stretch conditions included unassisted PNF stretching using ( a ) isometric , ( b ) concentric , and ( c ) eccentric contractions with a stretch strap , ( d ) partner-assisted isometric PNF , and ( e ) static stretching . The RT , MT , dynamic , active , passive hip flexion angle , and angular velocity with dynamic hip flexion were measured before and after the intervention . The ROM improved ( p < 0.05 ) 2.6 , 2.7 , and 5.4 % , respectively , with dynamic , active static , and passive static ROM , but there was no significant difference between the stretching protocol s. There was a main effect for time ( p < 0.05 ) with all stretching conditions negatively impacting dynamic angular velocity ( 9.2 % ) . Although there was no significant effect on RT , MT showed a negative main effect for time ( p < 0.05 ) slowing 3.4 % . In conclusion , it was found that all 3 forms of active stretching provided similar improvements in the ROM and poststretching performance decrements in MT and angular velocity . Thus , individuals can implement PNF stretching techniques with a partner or alone with a strap to improve ROM , but athletes should not use these techniques before important competitions or training because of the impairment of limb velocity and MT Curry , BS , Chengkalath , D , Crouch , GJ , Romance , M , and Manns , PJ . Acute effects of dynamic stretching , static stretching and light aerobic activity on muscular performance in women . J Strength Cond Res 23(6 ) : 1811 - 1819 , 2009-The purpose of this study was to compare three warm-up protocol s-static stretching , dynamic stretching , and light aerobic activity-on selected measures of range of motion and power in untrained females and to investigate the sustained effects at 5 and 30 minutes after warm-up . A total of 24 healthy females ( ages 23 - 29 years ) attended one familiarization session and three test sessions on nonconsecutive days within 2 weeks . A within-subject design protocol with the testing investigators blinded to the subjects ' warm-up was followed . Each session started with 5 minutes of light aerobic cycling followed by pretest baseline measures . Another 5 minutes of light aerobic cycling was completed and followed by one of the three r and omly selected warm-up interventions ( static stretching , dynamic stretching , or light aerobic activity ) . The following posttest outcome measures were collected 5 and 30 minutes following the intervention : modified Thomas test , countermovement jump , and isometric time to peak force knee extension measured by dynamometer . Analysis of the data revealed significant time effects on range of motion and countermovement jump changes . No significant differences ( p > 0.05 ) were found between the warm-up conditions on any of the variables . The variation in responses to warm-up conditions emphasizes the unique nature of individual reactions to different warm-ups ; however , there was a tendency for warm-ups with an active component to have beneficial effects . The data suggests dynamic stretching has greater applicability to enhance performance on power outcomes compared to static stretching AIM The interaction between running , stretching and practice jumps during warm-up for jumping tests has not been investigated . The purpose of the present study was to compare the effects of running , static stretching of the leg extensors and practice jumps on explosive force production and jumping performance . METHODS Sixteen volunteers ( 13 male and 3 female ) participated in five different warm-ups in a r and omised order prior to the performance of two jumping tests . The warm-ups were control , 4 min run , static stretch , run + stretch , and run + stretch + practice jumps . After a 2 min rest , a concentric jump and a drop jump were performed , which yielded 6 variables expressing fast force production and jumping performance of the leg extensor muscles ( concentric jump height , peak force , rate of force developed , drop jump height , contact time and height/time ) . RESULTS Generally the stretching warm-up produced the lowest values and the run or run + stretch + jumps warm-ups produced the highest values of explosive force production . There were no significant differences ( p<0.05 ) between the control and run + stretch warm-ups , whereas the run yielded significantly better scores than the run + stretch warm-up for drop jump height ( 3.2 % ) , concentric jump height ( 3.4 % ) and peak concentric force ( 2.7 % ) and rate of force developed ( 15.4 % ) . CONCLUSION The results indicated that submaximum running and practice jumps had a positive effect whereas static stretching had a negative influence on explosive force and jumping performance . It was suggested that an alternative for static stretching should be considered in warm-ups prior to power activities Warm-up prior to physical activity is a well accepted practice believed to reduce the risk of injury and enhance performance ( McArdle , Katch , & Katch , 1991 ; Safran , Seaber , & Garrett , 1989 ) . Various stretching techniques are commonly included in a warm-up to reduce muscle stiffness and increase the range of motion ( ROM ) at joints . Stanley and McNair ( 1996 ) compared the effects of running , static stretching , and combined running and stretching on muscle stiffness and ROM . While the combination of running and stretching were most effective for increasing ankle ROM , stretching added nothing to running to decrease musculotendinous ( MTEN ) stiffness . Although stretching is generally effective for inducing acute and chronic changes in ROM ( Alter : 1996 ; Wienmann & Hahn 1997;Wiktorsson-Moller , Oberg , Ekstr and , & Gillquist , 1983 ) , its effects on MTEN stiffness and the optimum stiffness for physicalperformance are not so clear ( WIlson,1991 ) . Eight weeks ofstatic stretching training of the pectoral muscle group has been shown to result in a 7.2 % decrease in MTEN stiffness , as measured by an oscillation technique ( Wilson , Elliott , & Wood , 1992 ) . This was accompanied by a significant increase in bench press performance when this exercise was performed using The purpose of this study was to compare the acute effects of different modes of stretching on vertical jump performance . Eighteen male university students ( age , 24.3 ± 3.2 years ; height , 181.5 ± 11.4 cm ; body mass , 78.1 ± 6.4 kg ; mean ± SD ) completed 4 different conditions in a r and omized order , on different days , interspersed by a minimum of 72 hours of rest . Each session consisted of a st and ard 5-minute cycle warm-up , accompanied by one of the subsequent conditions : ( a ) control , ( b ) 10-minute static stretching , ( c ) 10-minute ballistic stretching , or ( d ) 10-minute proprioceptive neuromuscular facilitation ( PNF ) stretching . The subjects performed 3 trials of static and countermovement jumps prior to stretching and poststretching at 5 , 15 , 30 , 45 , and 60 minutes . Vertical jump height decreased after static and PNF stretching ( 4.0 % and 5.1 % , p < 0.05 ) and there was a smaller decrease after ballistic stretching ( 2.7 % , p > 0.05 ) . However , jumping performance had fully recovered 15 minutes after all stretching conditions . In conclusion , vertical jump performance is diminished for 15 minutes if performed after static or PNF stretching , whereas ballistic stretching has little effect on jumping performance . Consequently , PNF or static stretching should not be performed immediately prior to an explosive athletic movement Forty-seven male subjects were r and omly assigned to 4 different groups . Three groups of 10 subjects trained three times a week with a modified contract-relax ( CR ) method for improving muscle flexibility . Seventeen sub jects trained during the same time with a traditional ballistic stretch ( BS ) method . After 30 days ( 14 training sessions ) the latter group switched over to the CR method . The results showed that the CR method was significantly better than the BS method for improving muscle flexibility in the four different , bilateral muscle groups studied . After the initial 30 days the three groups of 10 subjects trained one , three , and five times a week , respectively , for another 30 days . The results showed that once a week was enough to maintain improved flexibility , while three and five times a week increased it further . The former BS group improved muscle flexibility between the 30th and 60th day , as expected from the results of the initial 30 days with the three CR groups , when training with the CR method three times a week Eccentric activities are an important component of physical conditioning and everyday activities . Delayed onset muscle soreness ( DOMS ) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise . An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living . The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS . In the selection of treatment methods , emphasis was directed toward treatments that could be rendered independently by an individual , therefore making the treatment valuable to an athletic trainer in team setting . DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer . All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced . Data were collected on 15 dependent variables : active and passive wrist flexion and extension , forearm girth , limb volume , visual analogue pain scale , muscle soreness index , isometric strength , concentric and eccentric wrist total work , concentric and eccentric angle of peak torque . Data were collected on six occasions : pre- and post-induced DOMS , 20 minutes after treatment , and 24 , 48 , and 72 hours after treatment . Subjects were r and omly assigned to 1 of 7 groups ( 6 treatment and 1 control ) . Treatments included a nonsteroidal anti-inflammatory drug , high velocity concentric muscle contractions on an upper extremity ergometer , ice massage , 10-minute static stretching , topical Amica montana ointment , and sublingual A. montana pellets . A 7 x 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables . Significant main effects ( p < .05 ) were found for all of the dependent variables on time only . There were no significant differences between treatments . Therefore , we conclude that none of the treatments were effective in abating the signs and symptoms of DOMS . In fact , the NSAID and A. montana treatments appeared to impede recovery of muscle function Hough , PA , Ross , EZ , and Howatson , G. Effects of dynamic and static stretching on vertical jump performance and electromyographic activity . J Strength Cond Res 23(2 ) : 507 - 512 , 2009-The results of previous research have demonstrated that static stretching ( SS ) can reduce muscular performance and that dynamic stretching ( DS ) can enhance muscular performance . The purpose of this study was to assess the effects of SS and DS on vertical jump ( VJ ) performance and electromyographic ( EMG ) activity of the m. vastus medialis . Eleven healthy men ( age 21 ± 2 years ) took part in 3 conditions ( no stretching [ NS ] , SS , and DS ) , on separate occasions in a r and omized , crossover design . During each condition , measurements of VJ height and EMG activity during the VJ were recorded . A repeated- measures analysis of variance and post hoc analysis indicated that VJ height was significantly less ( 4.19 ± 4.47 % ) after SS than NS ( p < 0.05 ) and significantly greater ( 9.44 ± 4.25 % ) in DS than SS ( p < 0.05 ) . There was significantly greater EMG amplitude in the DS compared with the SS ( p < 0.05 ) . The results demonstrated that SS has a negative influence on VJ performance , whereas DS has a positive impact . Increased VJ performance after DS may be attributed to postactivation potentiation , whereas the reduction in VJ performance after SS may be attributable to neurological impairment and a possible alteration in the viscoelastic properties of the muscular tendon unit ( MTU ) . This investigation provides some physiological basis for the inclusion of DS and exclusion of SS in preparation for activities requiring jumping performance Stretching in the warm-up was been shown to decrease several muscular performance variables , but the dose-response of this effect is unknown . This study documented the change in isometric grip strength over ten trials in a convenience sample of young adults r and omly assigned to control ( n=22 ) or repeated bouts of 10-s static stretches of the wrist flexors ( n=35 ) . There was a significant ( P<0.05 ) difference in the change in mean normalized grip strength between the control and stretching groups that was not significantly different across gender . Grip strengths in the control group were consistent with a linear trend , while the grip strengths in the stretching group declined in a logarithmic fashion to 88.8 % with 100 s of stretching . Statistically significant ( P<0.05 ) differences in normalized grip strength between the two groups appeared after 40 s of stretching . Meaningful decreases in isometric grip strength following static stretching are likely to appear in young adults following 20–40 s of static stretching Hamstring muscle strain is the most prevalent injury in Australian Rules Football , accounting for 16 % of play ing time missed as a result of injury . Thirty-seven pro fessional footballers from an Australian Football League team had preseason measurements of ham string and quadriceps muscle concentric peak torque at 60 , 180 , and 300 deg/sec measured on a Cybex 340 dynamometer . Players were studied prospect ively throughout the 1995 season . During that time , six play ers sustained clinical ly diagnosed hamstring muscle injuries that caused them to miss match-playing time . The injured hamstring muscles were all weaker than in the opposite leg in absolute values and hamstring-to- quadriceps muscle ratios . According to our t-test re sults , hamstring muscle injury was significantly asso ciated with a low hamstring-to-quadriceps muscle peak torque ratio at 60 deg/sec on the injured side and a low hamstring muscle side-to-side peak torque ratio at 60 deg/sec . Flexibility ( as measured by the sit- and -reach test ) did not correlate with injury . Discriminant-function analysis using the two significant ratio variables re sulted in a canonical correlation with injury of 0.4594 and correctly classified legs into injury groups with 77.4 % success . These results indicate that preseason isokinetic testing of professional Australian Rules foot ballers can identify players at risk of developing ham string muscle strains Many activities necessitate a high degree of static joint range of motion ( ROM ) for an extended duration . The objective of this study was to examine whether ROM could be improved with a short duration and volume of static stretching within a warm-up , without negatively impacting performance . Ten male recreationally active participants completed 2 separate protocol s to examine changes in ROM and performance , respectively , with different warm-ups . The warm-up conditions for the ROM protocol were static stretching ( SS ) , consisting of 6 repetitions of 6 s stretches ; 10 min of running prior to the SS ( AS ) ; and 5 min of running before and after the SS ( ASA ) . The performance protocol included a control condition of 10 min of running . Measures for the ROM protocol included hip flexion ROM , passive leg extensor tension , and hamstring electromyographic ( EMG ) activity at pre-warm-up , and at 1 , 10 , 20 , and 30 min post-warm-up . Performance measures included countermovement jump ( CMJ ) height , reaction time ( RT ) , movement time ( MT ) , and balance at pre-warm-up and at 1 and 10 min post-warm-up . The ASA produced greater ROM overall than the SS and AS conditions ( p < 0.0001 ) , persisting for 30 min . There were no significant alterations in passive muscle tension or EMG . For the performance protocol , there were no main effects for condition , but there was a main effect for time , with CMJ height being greater at 1 and 10 min post-warm-up ( p = 0.0004 ) . Balance ratios and MT improved at 10 min post-warm-up ( p < 0.0001 ) . Results indicate that the ASA method can provide ROM improvements for 30 min with either facilitation or no impairment in performance . This may be especially important for athletes who substitute later into a game with minimal time for a full warm-up The purpose of the present research was to identify the contribution of central vs. peripheral factors to the force loss after passive muscle stretching . Thirteen men r and omly performed both a 5-min constant-torque stretch of the plantar flexors on an isokinetic dynamometer and a resting condition on 2 separate days . The triceps surae electromyogram ( EMG ) was recorded simultaneously with plantar flexor isometric torque . Measures of central drive , including the EMG amplitude normalized to the muscle compound action potential amplitude ( EMG/M ) , percent voluntary activation and first volitional wave amplitude , and measures of peripheral function , including the twitch peak torque , 20-to-80-Hz tetanic torque ratio and torque during 20-Hz stimulation preceded by a doublet , were taken before and immediately and 15 min after each condition . Peak torque ( -15.7 % ) , EMG/M ( -8.2 % ) , and both twitch ( -9.4 % ) and 20-Hz peak torques ( -11.5 % ) were reduced immediately after stretch but recovered by 15 min . There were strong correlations between the torque loss and the reductions in central drive parameters ( r = 0.65 - 0.93 ) . Torque recovery was also strongly correlated with the recovery in EMG/M and percent voluntary activation ( r = 0.77 - 0.81 ) . The moderate decreases in measures of peripheral function were not related to the torque loss or recovery . These results suggest that 1 ) central factors were strongly related to the torque reduction immediately after stretch and during torque recovery ; and 2 ) the muscle 's contractile capacity was moderately reduced , although these changes were not associated with the torque reduction , and changes in excitation-contraction coupling efficiency were not observed Abstract Paradisis , GP , Pappas , PT , Theodorou , AS , Zacharogiannis , EG , Skordilis , EK , and Smirniotou , AS . Effects of static and dynamic stretching on sprint and jump performance in boys and girls . J Strength Cond Res 28(1 ) : 154–160 , 2014—The aim of this study was to investigate the acute effects of static ( SS ) and dynamic stretching ( DS ) on explosive power , flexibility , and sprinting ability of adolescent boys and girls and to report possible gender interactions . Forty-seven active adolescent boys and girls were r and omly tested after SS and DS of 40 seconds on quadriceps , hamstrings , hip extensors , and plantar flexors ; no stretching was performed at the control condition . Pretreatment and posttreatment tests examined the effects of stretching on 20-m sprint run ( 20 m ) , countermovement jump ( CMJ ) height , and sit and reach flexibility test . In terms of performance , SS hindered 20 m and CMJ in boys and girls by 2.5 and 6.3 % , respectively . Dynamic stretching had no effect on 20 m in boys and girls but impaired CMJ by 2.2 % . In terms of flexibility , both SS and DS improved performance with SS being more beneficial ( 12.1 % ) compared with DS ( 6.5 % ) . No gender interaction was found . It can therefore be concluded that SS significantly negates sprinting performance and explosive power in adolescent boys and girls , whereas DS deteriorates explosive power and has no effect on sprinting performance . This diversity of effects denotes that the mode of stretching used in adolescent boys and girls should be task specific Dalrymple , KJ , Davis , SE , Dwyer GB , and Moir , GL . Effect of static and dynamic stretching on vertical jump performance in collegiate women volleyball players . J Strength Cond Res 24(1 ) : 149 - 155 , 2010-The purpose of this study was to determine the effect of stretching on peak jump height during a series of vertical jumps , specifically focusing on a ) static stretching ( SS ) , b ) dynamic stretching ( DS ) and c ) no stretching ( NS ) performed immediately before a series of countermovement vertical jumps ( CMJ ) . Twelve female collegiate volleyball players ( mean ± SD ; age 19.5 ± 1.1 yr ; height 1.71 ± 0.06 m ; mass 71.3 ± 8.54 kg ) volunteered for this study . Data collection lasted a total of 3 weeks , and each subject performed all 3 stretching protocol s , 1 session per week , with 1 week between sessions . The order of the stretching protocol s was r and omized for each subject . During each testing session , all subjects performed a 5-minute light jog as a warm-up , followed by 8 minutes of 1 of the stretching protocol s. One minute after the completion of each protocol , 5 maximal CMJ were performed on a force platform , with each jump separated by 1 minute of passive recovery . Jump heights were calculated by integrating the vertical force trace . There were no significant differences between the SS , DS , and NS conditions for any of the jumps ( p > 0.05 ) . Despite the lack of significant effects for the group , there were notable individual responses to each of the warm-up conditions . Practitioners should be aware of the individual responses of their athletes to different types of warm-up protocol s before athletic performance and the possible impact of prescribing or eliminating certain exercises Needham , RA , Morse , CI , and Degens , H. The acute effect of different warm-up protocol s on anaerobic performance in elite youth soccer players . J Strength Cond Res 23(9 ) : 2614 - 2620 , 2009-The purpose of the study was to investigate the acute effect of different warm-up protocol s on anaerobic performance in elite youth soccer players . Twenty elite youth soccer players ( mean age 17.2 ± 1.2 years ) performed 3 different warm-up protocol s in a r and om order on nonconsecutive days . Each warm-up protocol consisted of a 5-minute low-intensity jog followed by 10 minutes of static stretching ( SS ) , dynamic stretching ( DS ) , or dynamic stretching followed by 8 front squats + 20 % body mass ( DSR ) . Subjects performed a countermovement jump followed by a 10- and 20-m sprint test immediately and at 3 and 6 minutes after each warm-up protocol . Vertical jump performance following DSR was better at 3 and 6 minutes than after DS , which in turn was better than after SS at 0 , 3 , and 6 minutes ( p < 0.05 ) . Jump performance was better at 3 minutes than immediately after , and this improvement was maintained at 6 minutes after DSR ( p < 0.05 ) . A better sprint performance was observed after DSR and DS compared with SS immediately and at 3 and 6 minutes following each warm-up protocol ( p < 0.05 ) . The results of the study suggest that a dynamic warm-up with the inclusion of resistance enhances jumping ability more than dynamic exercise alone . In addition , a dynamic warm-up produces a superior sprint and jump performance compared to a warm-up consisting of static stretching Christensen , BK , and Nordstrom , BJ . The Effects of Proprioceptive Neuromuscular Facilitation and Dynamic Stretching Techniques on Vertical Jump Performance . J Strength Cond Res 22(6 ) : 1826 - 1831 , 2008-The purpose of this study was to investigate the effects of 3 different warm-ups on vertical jump performance . The warm-ups included a 600-m jog , a 600-m jog followed by a dynamic stretching routine , and a 600-m jog followed by a proprioceptive neuromuscular facilitation ( PNF ) routine . A second purpose was to determine whether the effects of the warm-ups on vertical jump performance varied by gender . Sixty-eight men and women NCAA Division I athletes from North Dakota State University performed 3 vertical jumps on a Just Jump pad after each of the 3 warm-up routines . The subjects were split into 6 groups and rotated between 3 warm-up routines , completing 1 routine each day in a r and om order . The results of the 1-way repeated measures analysis of variance showed no significant differences in the combined ( p = 0.927 ) , men 's ( p = 0.798 ) , or women 's ( p = 0.978 ) results . The results of this study showed that 3 different warm-ups did not have a significant affect on vertical jumping . The results also showed there were no gender differences between the 3 different warm-ups The purpose of this study was to examine the effectiveness of a stretching exercise program ( SEP ) on low back pain ( LBP ) and exercise self-efficacy among nurses in Taiwan . A total of 127 nurses , who had been experiencing LBP for longer than 6 months and had LBP with pain scores greater than 4 on the Visual Analogue Scale for Pain ( VASP ) , were r and omly assigned to an experimental group and a control group . The experimental group ( n = 64 ) followed an SEP , whereas the control group ( n = 63 ) was directed to perform usual activities for 50 minutes per time , three times a week . Data were collected at four time points : at baseline , and 2 , 4 , and 6 months after the intervention . During the 6-month follow-up , the experimental group had significantly lower VASP scores than did the control group at the second , fourth , and sixth months . In addition , the experimental group showed significantly higher exercise self-efficacy than did the control group at the fourth and sixth months . A total of 81 % of the participants in the experimental group reported a moderate to high level of LBP relief . The findings can be used to enhance self-care capabilities with SEP for nurses that experience LBP or are vulnerable to such work-related pain . SEP is an effective and safe nonpharmacological intervention for the management of LBP Abstract The main purpose s of this study were to ( a ) investigate acute effects of static and dynamic lower limb stretching routines on total response time , pre-motor time and motor time of the medial and lateral hamstrings during maximal eccentric isokinetic knee flexion ; and ( b ) determine whether static and dynamic routines elicit similar responses . A total of 38 active adults completed the following intervention protocol s in a r and omised order on separate days : ( a ) non-stretching ( control condition ) , ( b ) static stretching and ( c ) dynamic stretching . After the stretching or control intervention , total response time , pre-motor time and motor time of the medial and lateral hamstrings were assessed during eccentric knee flexion movements with participants prone . Measures were compared via a mixed- design factorial ANOVA . There were no main effects for total response time , pre-motor time and motor time . The results suggest that dynamic and static stretching has no influence on hamstrings response times ( total response time , pre-motor time and motor time ) and hence neither form of stretching reduces this primary risk factor for anterior cruciate ligament injury The aim of this study was to explore the effects of static and dynamic stretching of the leg flexors and extensors on concentric and eccentric peak torque ( PT ) and electromyography ( EMG ) amplitude of the leg extensors and flexors in women athletes . Ten elite women athletes completed the following intervention protocol in a r and omized order on separate days : ( a ) non-stretching ( control ) , ( b ) static stretching , and ( c ) dynamic stretching . Stretched muscles were the quadriceps and hamstring muscles . Before and after the stretching or control intervention , concentric and eccentric isokinetic PT and EMG activity of the leg extensors and flexors were measured at 60 and 180 degrees/s . Concentric and eccentric quadriceps and hamstring muscle strength at both test speeds displayed a significant decrease following static stretching ( P<0.01 - 0.001 ) . In contrast , a significant increase was observed after dynamic stretching for these strength parameters ( P<0.05 - 0.001 ) . Parallel to this , normalized EMG amplitude parameters exhibited significant decreases following static ( P<0.05 - 0.001 ) and significant increases following dynamic stretching ( P<0.05 - 0.001 ) during quadriceps and hamstring muscle actions at both concentric and eccentric testing modes . Our findings suggest that dynamic stretching , as opposed to static or no stretching , may be an effective technique for enhancing muscle performance during the pre-competition warm-up routine in elite women athletes Abstract The purpose of this study was to examine the effects of dynamic stretching on the passive biomechanical properties and isometric muscle strength of the knee flexors . Fourteen healthy men ( mean ± s : age = 24 ± 3 years ) performed passive range of motion assessment s and isometric maximal voluntary contractions of the knee flexors at knee joint angles of 35 ° , 50 ° , 65 ° , 80 ° , and 95 ° below full knee extension before and after dynamic stretching . In addition , electromyographic amplitude was recorded from the biceps femoris during the maximal voluntary contractions . Passive stiffness and passive resistive torque were measured during pre- and post-dynamic stretching . The dynamic stretching included the participant extending their right leg outwards to the end range motion and pulling their leg back towards the body while seated in the isokinetic dynamometer for four 30-s bouts with 20-s rest between bouts . Passive range of motion increased while passive stiffness and passive resistive torque decreased following dynamic stretching . Peak torque decreased at knee joint angles of 65 ° and 80 ° below full extension , while electromyographic amplitude decreased following dynamic stretching . Dynamic stretching result ed in changes to passive stiffness and passive resistive torque that are typically reported following static stretching , however , there were decreases in peak torque at two of the knee joint angles This prospect i ve study was design ed to evaluate whether static stretching can prevent training-related injuries in Japan Ground Self-Defense Force military recruits . A total of 901 recruits between 1996 and 1998 were divided into two groups . Of which , 518 recruits were assigned to the stretching group and practice d static stretching before and after each physical training session . The control subjects ( 383 recruits in the nonstretching group ) did not stretch statically prior to exercise . The static stretching consisted of 18 exercises . We collected injury data from medical records and assessed the incidence and the location of injury . The total injury rate was almost the same between two groups ; however , the incidences of muscle/tendon injury and low back pain were significantly lower in the stretching group ( p < 0.05 ) . Static stretching decreased the incidence of muscle-related injuries but did not prevent bone or joint injuries OBJECTIVE To examine electromyography ( EMG ) activity , passive torque , and stretch perception during static stretch and contract-relax stretch . DESIGN Two separate r and omized crossover protocol s : ( 1 ) a constant angle protocol on the right side , and ( 2 ) a variable angle protocol on the left side . SUBJECTS 10 male volunteers . INTERVENTION Stretch-induced mechanical response in the hamstring muscles during passive knee extension was measured as knee flexion torque ( Nm ) while hamstring surface EMG was measured . Final position was determined by extending the knee to an angle that provoked a sensation similar to a stretch maneuver . Constant angle stretch : The knee was extended to 10 degree below final position , held 10sec , then extended to the final position and held for 80 sec. Variable angle stretch : The knee was extended from the starting position to 10 degrees below the final position , held 10sec , then extended to the onset of pain . Subjects produced a 6-sec isometric contraction with the hamstring muscles 10 degrees below the final position in the contract-relax stretch , but not in the static stretch . MAIN OUTCOME MEASURES Passive torque , joint range of motion , velocity , and hamstring EMG were continuously recorded . RESULTS Constant angle contract-relax and static stretch did not differ in passive torque or EMG response . In the final position , passive torque declined 18 % to 21 % in both contract-relax and static stretch ( p<.001 ) , while EMG activity was unchanged . In the variable angle protocol , maximal joint angle and corresponding passive torque were significantly greater in contract-relax compared with static stretch(p<.01 ) , while EMG did not differ . CONCLUSION At a constant angle the viscoelastic and EMG response was unaffected by the isometric contraction . The variable angle protocol demonstrated that PNF stretching altered stretch perception The purpose of this study was to compare a 5-minute treadmill activity at 70 % maximum heart rate ( MHR ) and 5 to 6 minutes of ballistic stretching to a 5-minute treadmill activity at 60 % of MHR and 5 to 6 minutes of static stretching . Thirty healthy college students , 7 men and 23 women , volunteered . Most volunteers were moderately active . All participants signed an informed consent . Participants received the aforementioned warm-ups in r and om order with 48 to 72 hours between warm-ups . The stretching exercises were a back stretch , a quad- riceps stretch , and a hamstring stretch . Three trials for 30 seconds each were given . After each warm-up the participants performed the modified – modified Schober test for low back flexibility , active knee extension test for hamstring flexibility , and plantar flexion for ankle flexibility . There were no significant differences on any of the 3 range of motion ( ROM ) tests although the ankle ROM test was almost significantly greater ( 68.8 ° ) after the warm-up with static stretching compared with 65.9 ° after the warm-up with ballistic stretching . A more intense cardiovascular activity and ballistic stretching were similar to a less intense cardiovascular activity and static stretching on flexibility . If athletes perform a warm-up and static or ballistic stretching before their workouts , then they should continue to perform the warm-up and the stretching routine with which they are most familiar and comfortable The purpose of this study was to evaluate the effect of a health education intervention on running injuries . The intervention consisted of information on , and the sub sequent performance of , st and ardized warm-up , cool- down , and stretching exercises . Four hundred twenty- one male recreational runners were matched for age , weekly running distance , and general knowledge of preventing sports injuries . They were r and omly split into an intervention and a control group : 167 control and 159 intervention subjects participated throughout the study . During the 16-week study , both groups kept a daily diary on their running distance and time , and reported all injuries . In addition , the intervention group was asked to note compliance with the st and ardized program . At the end of the study period , knowledge and attitude were again measured . There were 23 injuries in the control group and 26 in the intervention group . Injury incidence for control and intervention sub jects was 4.9 and 5.5 running injuries per 1000 hours , respectively . The intervention was not effective in re ducing the number of running injuries ; it proved signifi cantly effective ( P < 0.05 ) in improving specific knowl edge of warm-up and cool-down techniques in the intervention group . This positive change can perhaps be regarded as a first step on the way to a change of behavior , which may eventually lead to a reduction of running injuries This study compared the effects of repeated contractions and repeated passive stretches on the viscoelastic properties of muscle . The tibialis anterior ( TA ) muscles of eight anesthetized male New Zeal and white rabbits were studied . In each rabbit , one hindlimb was r and omly assigned to the repeated muscular contraction group ( CON ) and the contralateral hindlimb to the repeated passive stretch group ( STRETCH ) . The passive tension at neutral length was measured in all muscles before and after both repeated muscular contractions or repeated passive stretches . In the CON hindlimb , the peroneal nerve was stimulated with a nerve stimulator for 1 s , and the result ing contractile force was measured . Stimulations were repeated every 10 s for a total of 10 contractions . In the STRETCH hindlimb , the TA was stretched from its shortest in vivo length to its maximum in vivo length 10 times at 20 cm x min-1 . The maximum force generated during the first contraction in the CON group averaged 21.74 + /- 1.41 N , with a subsequent reduction with each muscle contraction to 13.66 + /- 0.81 N by the tenth contraction . The average peak tensile force in the STRETCH group was 17.39 + /- 2.61 N for the first passive stretch , decreasing to 13.57 + /- 1.84 by the tenth stretch . After repeated muscular contractions in the CON hindlimbs , the passive tension at neutral length decreased from 0.88 + /- 0.22 N to 0.42 + /- 0.08 N. After repeated passive stretches in the STRETCH hindlimbs , the passive tension at neutral length decreased from 1.16 + /- 0.17 N to 0.67 + /- 0.09 N. The percentage decreases in passive tension between the CON and STRETCH groups were not statistically significant ( P = 0.24 ) . The results show that stretching and contracting both result in tissue relaxation of the muscle-tendon unit . This finding may be a result of changes in the viscous elements of the connective tissue secondary to the forces generated by either stretches or contractions . This study suggests that well controlled isometric muscular contractions may result in decreased passive tension in a muscle at neutral length , a finding that one normally associates with passive stretching In the December 1998 issue of Research Quarterly for Exercise and Sport , we presented data showing that acute static stretching of the hip , thigh , and calf muscles before the performance of a one-repetition maximum lift ( lRM ) result ed in a decreased IRM for both knee flexion and knee extension ( Kokkonen , Nelson , & Cornwell , 1998 ) . Since then , we have had the opportunity to engage in dialogue with many individuals who were interested in discussing the implication s and mechanisms that accompanied our finding . The foremost question has dealt with the type of stretching activity used in the study . Because static stretching was used , many people asked if the negative impact of stretching was present following ballistic stretching . Unfortunately , we could not answer this question with any precision . In the Kokkonen et al. ( 1998 ) study , the issue of ballistic stretching had been avoided , because most exercise physiology textbooks recommend against doing ballistic stretching ( see deVries & Housh , 1994 ; Foss & Keteyian , 1998 ; Plowman & Smith , 1997 ; Powers & Howley , 2001 ; Robergs & Roberts , 1997 ) . The basis behind these recommendations is that ballistic stretching increases the chance of muscle injury , because the athlete is trying to lengthen the muscle while the myotatic reflex is The present study sought to investigate the effects of preexercise stretching on delayed onset muscle soreness ( DOMS ) , i.e. soreness , tenderness and loss of muscle force , that usually occurs after strenuous or unaccustomed eccentric exercise . Ten female volunteers performed 10 sets of 10 maximal isokinetic eccentric contractions for knee flexion with both legs after a 5-min ergometer cycling warm-up . Prior to the exercise for one leg , r and omly chosen , 4 x 20 s of static stretching for the hamstring muscle group was implemented . Rated soreness , tenderness on algometer pressure and loss of maximal eccentric contractile force was evaluated preexercise and 24 , 48 and 96 h postexercise . The exercise bout produced severe DOMS , with parameters peaking and troughing at 48 h postexercise . However , no significant differences were found , regarding any of the parameters , when comparing stretched and nonstretched legs . The present study thus suggests that preexercise static stretching has no preventive effect on the muscular soreness , tenderness and force loss that follows heavy eccentric exercise lthough stretching exercises that enhance flexibility A are regularly included in the training programs and pre-event warm-up activities of most athletes , research suggests that preexercise stretching could negatively impact the performance of skills for which success is related to maximal force output . Wilson , Murphy , and Pryor ( 1994 ) suggested that a stifFmusculotendinous system allows for an improved force production by the contractile component and provided evidence to support this suggestion by demonstrating that concentric performance in the bench press was significantly related to musculotendinous stiffness . The findings of Wilson et al. ( 1994 ) , coupled with the results of several studies ( Magnusson , Simonsen , Aagaard , & Kjaer , 1996 ; Rosenbaum & Hennig , 1995 ; Taylor , Dalton , Seaber , & Garrett , 1990 ) , indicating that the musculotendinous unit becomes less stiff as a result of acute stretching , lead Kokkonen , Nelson , & Cornwell ( 1998 ) to investigate the effect of acute stretching on knee extension and knee flexion onerepetition maximum ( IRM ) lifts . Kokkonen et al. ( 1998 ) reported that a regimen of acute stretching inhibited the one-repetition maximum lift ( IRM ) of both knee extension and knee flexion . Kokkonen et al. ( 1998 ) , however , could only speculate about the mechanisms responsible for this phenomenon . One speculated mechanism was derived from a Wilson et al. ( 1994 ) supposition that the lesser force Although several studies have investigated the acute effect of static stretching exercises , the duration of exercises that negatively affects performance has not been ascertained . This study was conducted to determine the acute effect of different static stretching duration s on quadriceps isometric and isokinetic peak torque production . The 50 participants were r and omly allocated into five equivalent sized groups and were asked to perform a stretching exercise of different duration ( no stretch , 10-second stretch , 20-second stretch , 30-second stretch , and 60-second stretch ) . The knee flexion range of motion and the isometric and concentric isokinetic peak torques of the quadriceps were measured before and after a static stretching exercise in the four experimental groups . The same parameters were examined in the control group ( no stretch ) without stretching , before and after a 5-minute passive rest . There were no significant differences among groups before the experimentation regarding their physical characteristics and performances ( P > 0.05 ) . These results reflect the different groups ' homogeneity . Significant knee joint flexibility increases ( P < 0.001 ) and significant isometric and isokinetic peak torque reductions ( P < 0.05 - 0.001 ) have been shown to occur only after 30 and 60 seconds of quadriceps static stretching . Stretching reduced isometric peak torque by 8.5 % and 16.0 % , respectively . Concerning isokinetic peak torque after 30 and 60 seconds of stretching , it was reduced by 5.5 % vs. 11.6 % at 60 ° /s and by 5.8 % vs. 10.0 % at 180 ° /s . We suggest that torque decrements are related to changes of muscle neuromechanical properties . It is recommended that static stretching exercises of a muscle group for more than 30 seconds of duration be avoided before performances requiring maximal strength Stretching with proprioceptive neuromuscular facilitation ( PNF ) is frequently used before exercise . The prophylactic effect of PNF on symptoms of muscle damage induced by eccentric exercise of the wrist extensors was examined in this study . Twenty-eight healthy males were r and omly divided into the PNF group ( n = 14 ) and the control group ( n = 14 ) . PNF was used before eccentric exercise induction in the wrist extensors . All subjects were tested to examine muscle damage characteristics including sensory-motor functions at baseline , immediately , and from 1st to 8th days after the exercise-induced muscle damage ( EIMD ) . The results demonstrated that the PNF group showed a lesser deficit in some sensory-motor functions ( p < 0.05 ) than the control group . The prior PNF stretching application could be useful for attenuating the signs and symptoms of muscle damage after eccentric exercise Chaouachi A , Castagna C , Chtara M , Brughelli M , Turki O , Galy O , Chamari K , and Behm DG . Effect of warm-ups involving static or dynamic stretching on agility , sprinting , and jumping performance in trained individuals . J Strength Cond Res 24(8 ) : 2001 - 2011 , 2010-The objective of the present study was to investigate the effects of static and dynamic stretching alone and in combination on subsequent agility , sprinting , and jump performance . Eight different stretching protocol s : ( a ) static stretch ( SS ) to point of discomfort ( POD ) ; ( b ) SS less than POD ( SS < POD ) ; ( c ) dynamic stretching ( DS ) ; ( d ) SS POD combined with DS ( SS POD + DS ) ; ( v ) SS < POD combined with DS ( SS < POD + DS ) ; ( vi ) DS combined with SS POD ( DS + SS POD ) ; ( vii ) DS combined with SS < POD ( DS + SS < POD ) ; and ( viii ) a control warm-up condition without stretching were implemented with a prior aerobic warm-up and followed by dynamic activities . Dependent variables included a 30-m sprint , agility run , and jump tests . The control condition ( 4.2 ± 0.15 seconds ) showed significant differences ( p = 0.05 ) for faster times than the DS + SS < POD ( 4.28s ± 0.17 ) condition in the 30-m ( 1.9 % ) sprint . There were no other significant differences . The lack of stretch-induced impairments may be attributed to the trained state of the participants or the amount of time used after stretching before the performance . Participants were either professional or national level elite athletes who trained 6 - 8 times a week with each session lasting ∼90 minutes . Based on these findings and the literature , trained individuals who wish to implement static stretching should include an adequate warm-up and dynamic sport-specific activities with at least 5 or more minutes of recovery before their sport activity O'Hora , J , Cartwright , A , Wade , CD , Hough , AD , and Shum , GLK . Efficacy of static stretching and proprioceptive neuromuscular facilitation stretch on hamstrings length after a single session . J Strength Cond Res 25(6 ) : 1586 - 1591 , 2011—A number of studies have investigated the efficacy of several repetitions of proprioceptive neuromuscular facilitation stretching ( PNF ) and static stretching ( SS ) . However , there is limited research comparing the effects of a single bout of these stretching maneuvers . The aim of this study was to compare the effectiveness of a single bout of a therapist-applied 30-second SS vs. a single bout of therapist-applied 6-second hamstring ( agonist ) contract PNF . Forty-five healthy subjects between the ages of 21 and 35 were r and omly allocated to 1 of the 2 stretching groups or a control group , in which no stretching was received . The flexibility of the hamstring was determined by a range of passive knee extension , measured using a universal goniometer , with the subject in the supine position and the hip at 90 ° flexion , before and after intervention . A significant increase in knee extension was found for both intervention groups after a single stretch ( SS group = 7.53 ° , p < 0.01 and PNF group = 11.80 ° , p < 0.01 ) . Both interventions result ed in a significantly greater increase in knee extension when compared to the control group ( p < 0.01 ) . The PNF group demonstrated significantly greater gains in knee extension compared to the SS group ( mean difference 4.27 ° , p < 0.01 ) . It can be concluded that a therapist applied SS or PNF results in a significant increase in hamstring flexibility . A hamstring ( agonist ) contract PNF is more effective than an SS in a single stretching session . These findings are important to physiotherapists or trainers working in clinical and sporting environments . Where in the past therapists may have spent time conducting multiple repetitions of a PNF and an SS , a single bout of either technique may be considered just as effective . A key component of the study methodology was the exclusion of a warm-up period before stretching . Therefore , the findings of efficacy of a single PNF are of particular relevance in sporting environments and busy clinical setting s where time may be limited The purpose of this study was to investigate the effect of manipulating the static and dynamic stretch components associated with a traditional track- and -field warm-up . Eighteen experienced sprinters were r and omly assigned in a repeated- measures , within-subject design study with 3 interventions : active dynamic stretch ( ADS ) , static passive stretch combined with ADS ( SADS ) , and static dynamic stretch combined with ADS ( DADS ) . A st and ardized 800-m jogged warm-up was performed before each different stretch intervention , followed by two 50-m sprints . Results indicated that the SADS intervention yielded significantly ( p ≤ 0.05 ) slower 50-m sprint times then either the ADS or DADS intervention . The decrease in sprint time observed after the ADS intervention compared to the DADS intervention was found to be nonsignificant ( p > 0.05 ) . The decrease in performance post – SADS intervention was attributed to a decrease in the musculotendinous unit ( MTU ) stiffness , possibly due to a reduction in muscle activation prior to ground contact , leading to a decrease in the MTU 's ability to store and transfer elastic energy after the use of passive static stretch techniques . The improved 50-m sprint performance associated with the ADS and DADS interventions was linked to the rehearsal of specific movement patterns , helping proprioception and preactivation , allowing a more optimum switch from eccentric to concentric muscle contraction . It was concluded that passive static stretching in a warm-up decreases sprint performance , despite being combined with dynamic stretches , when compared to a solely dynamic stretch approach This study investigated effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on relative risk of selected injuries in 1093 male Army recruits undertaking 12 weeks of intensive training . Prior to training , ankle dorsiflexion range was measured and recruits were allocated to stretch and control groups using a quasi-r and om procedure . The stretch group stretched calf muscles under supervision prior to all intense exercise . The control group stretched upper limb muscles instead . Forty-eight injuries were recorded . Survival analysis indicated that ankle dorsiflexion range was a strong predictor of injury ( p = 0.03 ) . Definitive evidence of an effect of stretching on injury risk was not found ( p = 0.76 ) , but the sample size may have been insufficient to detect such an effect It has been suggested in the lay literature that static stretching and /or warm-up will prevent the occurrence of Delayed-Onset Muscle Soreness ( DOMS ) . The primary purpose of this study was to determine the effects of static stretching and /or warm-up on the level of pain associated with DOMS . Sixty-two healthy male and female volunteers were r and omly assigned to four groups : ( a ) subjects who statically stretched the quadriceps muscle group before a step , ( b ) subjects who only performed a stepping warm-up , ( c ) subjects who both stretched and performed a stepping warm-up prior to a step test , and ( d ) subjects who only performed a step test . The step test ( Asmussen , 1956 ) required subjects to do concentric work with their right leg and eccentric work with their left leg to voluntary exhaustion . Subjects rated their muscle soreness on a ratio scale from zero to six at 24-hour intervals for 5 days following the step test . A 4x2x2 ANOVA with repeated measures on legs and Duncan 's New Multiple Range post-hoc test found no difference in peak muscle soreness among the groups doing the step test or for gender ( p greater than .05 ) . There was the expected significant difference in peak muscle soreness between eccentrically and concentrically worked legs , with the eccentrically worked leg experiencing greater muscle soreness . We concluded that static stretching and /or warm-up does not prevent DOMS result ing from exhaustive exercise AIM This study investigated the effects of warm-up involving static stretching on leg power . It was expected that the inclusion of static stretching in the warm-up would decrease leg power . METHODS Twenty-seven healthy volunteers ( 16 male , 11 female ) participated in the study . A prospect i ve , repeated measures design was implemented where volunteers underwent 2 testing sessions at least 24 hours apart . One testing session involved a control warm-up ( 5 min submaximal cycling ) followed by 4 10-s leg power tests at 5 , 20 , 40 and 60 min postwarm-up . For the other testing session , the subjects performed 5 min of submaximal cycling followed by 15 min of lower body static stretching and then the four leg power tests . Relative peak power , time to peak power and relative total work were measured for each leg power test . RESULTS Peak power and total work were significantly greater after the static stretching warm-up compared to the control warm-up on all power tests . Peak power was achieved more quickly for the static stretching warm-up compared to the control warm-up on the 5 min test only . CONCLUSIONS A warm up that includes static stretching has beneficial effects on anaerobic power events in comparison to submaximal cycling alone AIM There is an emerging body of knowledge indicating static stretching ( SS ) acutely and adversely affects muscle performance . The practical value of this research is limited considering the lengthy stretch duration s under investigation . It is unclear if stretch duration s typical of those used pre-exercise similarly affect muscle performance . The purpose of this study was to determine if SS using more representative stretch duration s affects muscle performance and to establish if changes in muscle performance were influenced by the duration of stretch . METHODS Following 2 familiarization sessions , 16 recreationally trained males and females participated in 2 r and omly ordered experimental sessions . In each session maximal effort hamstring performance was assessed prior to and immediately after 1 of 2 stretching protocol s. During one of the protocol s participants were required to hold each stretch for 15 s while stretch duration in the second protocol was 30 s. Both protocol s consisted of 3 repetitions of 2 stretching exercises . A Kincom isokinetic dynamometer was used to assess hamstring performance during isometric , concentric , and eccentric actions . RESULTS For each of the three muscle actions a repeated measures ANOVA revealed a significant main effect of time ( pre- vs poststretch , P<0.05 ) but no interaction effect ( time x SS protocol ) . Furthermore , the stretch-induced deficits in muscle performance were consistent across muscle action type . CONCLUSIONS SS incorporating stretch duration s typical of those employed pre-exercise were sufficient to impair muscle performance and the duration of stretch did not influence the degree of force loss . Inclusion of SS , even with short stretch duration s , in preparation for strength activities is not appropriate PURPOSE This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury . METHODS 1538 male army recruits were r and omly allocated to stretch or control groups . During the ensuing 12 wk of training , both groups performed active warm-up exercises before physical training sessions . In addition , the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up . The control group did not stretch . RESULTS 333 lower-limb injuries were recorded during the training period , including 214 soft-tissue injuries . There were 158 injuries in the stretch group and 175 in the control group . There was no significant effect of preexercise stretching on all-injuries risk ( hazard ratio [ HR ] = 0.95 , 95 % CI 0.77 - 1.18 ) , soft-tissue injury risk ( HR = 0.83 , 95 % CI 0.63 - 1.09 ) , or bone injury risk ( HR = 1.22 , 95 % CI 0.86 - 1.76 ) . Fitness ( 20-m progressive shuttle run test score ) , age , and enlistment date all significantly predicted injury risk ( P < 0.01 for each ) , but height , weight , and body mass index did not . CONCLUSION A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinical ly meaningful reductions in risk of exercise-related injury in army recruits . Fitness may be an important , modifiable risk factor INTRODUCTION Loading characteristics of stretching techniques likely influence the specific mechanisms responsible for acute increases in range of motion ( ROM ) . Therefore , the effects of a version of contract-relax ( CR ) proprioceptive neuromuscular facilitation stretching , static stretching ( SS ) , and maximal isometric contraction ( Iso ) interventions were studied in 17 healthy human volunteers . METHODS Passive ankle moment was recorded on an isokinetic dynamometer , with EMG recording from the triceps surae , simultaneous real-time motion analysis , and ultrasound-imaging-recorded gastrocnemius medialis muscle and Achilles tendon elongation . Subjects then performed each intervention r and omly on separate days before re assessment . RESULTS Significant increases in dorsiflexion ROM ( 2.5 ° -5.3 ° ; P < 0.01 ) and reductions in whole muscle-tendon stiffness ( 10.1%-21.0 % ; P < 0.01 ) occurred under all conditions , with significantly greater changes detected following CR stretching ( P < 0.05 ) . Significant reductions in tendon stiffness were observed after CR stretching and Iso ( 17.7%-22.1 % ; P < 0.01 ) but not after SS ( P > 0.05 ) , whereas significant reductions in muscle stiffness occurred after CR stretching and SS ( 16.0%-20.5 % ; P < 0.01 ) but not after Iso ( P > 0.05 ) . Increases in peak passive moment ( stretch tolerance ) occurred after Iso ( 6.8 % ; P < 0.05 ) , CR stretching ( 10.6 % ; P = 0.08 ) , and SS ( 5.2 % ; P = 0.08 ) ; no difference in changes between conditions was found ( P > 0.05 ) . Significant correlations ( rs = 0.69 - 0.82 ; P < 0.01 ) were observed between changes in peak passive moment and maximal ROM under all conditions . CONCLUSIONS Although similar ROM increases occur after Iso and SS , changes in muscle and tendon stiffness are distinct . Concomitant reductions in muscle and tendon stiffness after CR stretching suggest a broader adaptive response that likely explains its superior efficacy in acutely increasing ROM . Although mechanical changes appear tissue-specific between interventions , similar increases in stretch tolerance after all interventions are strongly correlated with changes in ROM Beedle , B , Rytter , SJ , Healy , RC , and Ward , TR . Pretesting static and dynamic stretching does not affect maximal strength . J Strength Cond Res 22(6 ) : 1838 - 1843 , 2008-The purpose of this study was to determine whether there was a significant difference in static stretching ( SS ) , dynamic stretching ( DS ) , and no stretching ( NS ) on maximal strength ( one-repetition maximum [ 1RM ] ) in the bench and leg presses using free weights on 19 college-aged men and 32 women . Most of the participants were moderately to very active and had previous experience with weight training . The design was repeated measures , with each treatment being r and omly assigned . Each testing session was separated by 72 hours . Moderate-intensity stretching was defined as stretching as far as possible without any assistance , and subjects were encouraged to do their best . For the SS routine , the chest , shoulder , triceps , quadriceps , and hamstrings were stretched . Three repetitions were performed for 15 seconds , each separated by a 10-second rest . For DS , the upper-body stretch was swinging each arm , one at a time , as far forward and then as far backward as possible in a diagonal plane . For the legs , the same movement was done for each leg , except performed in a sagittal plane . Each forward and backward movement took about 2 seconds . Three 30-second sets were administered , and a 10-second rest was allowed between sets . Next , 1RM was determined for the bench and leg presses in r and om order . Two warm-up sets were given , followed by several 1RM attempts . The last successful lift was recorded as the 1RM . Data were reported using means ± SD . A one-way ANOVA with repeated measures was used with alpha set at 0.05 . There was no significant difference among the treatments . Moderate-intensity stretching does not seem to adversely affect 1RM in the bench and leg presses |
11,759 | 31,789,296 | This systematic review and meta-analyses showed a significant effect of WBV on total fat mass ( kg ) , however clinical ly insignificant effects of 6 - 24 weeks of WBV therapy on % body fat . | Whole Body Vibration ( WBV ) is a popular and a purported alternative to physical activity to reduce body fat , but reports of efficacy are inconsistent .
We aim ed to describe the efficacy of WBV therapy for reducing fat mass in the adult general population . | The purpose of this pilot study was to evaluate the effectiveness of whole body vibration ( WBV ) training as a modality for inducing changes in body composition , cardiovascular condition , and muscular strength in sedentary postmenopausal women . WBV training was compared with other training regimens , ie , aerobic training and circuit resistance training , commonly used to promote weight loss , cardiovascular conditioning , and muscular strength . Postmenopausal women ( aged 48–60 years ) were r and omly assigned to WBV training , circuit resistance training , or aerobic training . Participants trained three times per week for 8 weeks . The training regimens were progressive in nature , with increases in training intensity and duration occurring throughout the 8-week period . Body composition was assessed using dual-energy X-ray absorptiometry analyses . A modified Bruce treadmill protocol was used to assess aerobic capacity ( VO2peak ) and time to peak exhaustion . Upper and lower body strengths were determined by one repetition maximum ( 1-RM ) chest and leg presses , respectively . Variables were analyzed using separate 3 ( exercise mode ) × 2 ( time ) repeated- measures analysis of variance with effect sizes due to the small sample size . No significant main effects or interactions were seen for any body composition variable ; however , moderate to large effect sizes ( η2=0.243 and η2=0.257 ) were detected regarding interactions for percent body fat and lean body mass favoring aerobic training and circuit resistance training . For VO2peak , no significant main effects or interactions were detected ( time , η2=0.150 ; P=0.11 ; time × group , η2=0.139 ; P=0.30 ) ; but a significant time effect was observed for time to peak exhaustion ( η2=0.307 ; P=0.017 ) . A significant interaction for upper body strength ( η2=0.464 ; P=0.007 ) , and main effect for time in lower body strength ( η2=0.663 ; P=0.0001 ) was detected . Post hoc analysis indicated a significant increase in upper body strength for circuit resistance training ( P=0.023 ) and a decrease for WBV training ( P=0.015 ) . Our results indicate that WBV may not be an effective alternative to traditional training with regard to body composition or aerobic capacity , but could have a positive impact on lower body strength Abstract The aim of the study was to compare the effect of an unsupervised whole body vibration ( WBV ) training and two different supervised multi- purpose exercise programmes , with and without WBV , on body composition , functional fitness and self-reported well-being in middle-aged adults . Fifty-four healthy participants ( age 48.6 ± 6.7 years ) were r and omly assigned to a vibration group ( VG ) , a multi- purpose exercise group ( MG ) and a multi- purpose exercise with vibration group ( VMG ) and trained 3 days a week for 4 months . VG performed a st and ardised unsupervised WBV protocol , MG a supervised multi- purpose exercise and VMG a multi- purpose exercise including vibration . After training , drop out was significantly higher in VG group ( P = 0.016 ) when compared to VMG group . In both MG and VMG , body composition , sit-up , push-up , sit and reach , agility test , hopping test and self-reported general health significantly improved ( P < 0.05 ) . No additive effects were generated by the vibration stimulus . Percentage of body fat and agility test in VG had a significant opposite trend compared to VMG group ( P < 0.05 ) . In summary , an unsupervised WBV training should not be chosen for training protocol . However , positive effects on physical fitness and the best results in adherence could be achieved integrating WBV practice into a multi- purpose exercise training Lamont , HS , Cramer , JT , Bemben , DA , Shehab , RL , And erson , MA , and Bemben , MG . Effects of 6 weeks periodized squat training with or without whole-body vibration upon short-term adaptations in squat strength and body composition . J Strength Cond Res 25(7 ) : 1839 - 1848 , 2011—The purpose of this study was to examine the effects of a 6-week , periodized squat training program , with or without whole-body low-frequency vibration ( WBLFV ) , applied before and between sets to 1RM squat strength and body composition . Thirty men aged between 20 and 30 years with at least 6 months of recreational weight training experience completed the study . Subjects were r and omly assigned to either 1 of 2 training groups or to an active control group ( CON ) . Group 1 ( CON ; n = 6 ) did not participate in the training protocol but participated only in testing sessions . Group 2 ( SQTV , n = 13 ) performed 6 weeks of squat training while receiving WBLFV ( 50 Hz ) , before , and in-between sets . The third group ( SQT , n = 11 ) performed 6 weeks of squat training only . Subjects completed 12 workouts with variable loads ( 55 - 90 % one repetition maximum [ 1RM ] ) and sets ( 3 - 5 ) , performing squats twice weekly separated by 72 hours . The RM measures were recorded on weeks ( W ) 1 , 3 , and 7 . During the second workout of a week , the load was reduced by 10 - 15 % , with “ speed squats ” performed during the final 3 weeks . Rest periods in between sets were set at 240 seconds . The WBLFV was applied while subjects stood on a WBLFV platform holding an isometric quarter squat position ( knee angle 135 ± 5 ° ) . Initially , WBLFV was applied at 50 Hz for 30 seconds at low amplitude ( peak-peak 2 - 4 mm ) . A rest period of 180 seconds followed WBLFV exposure before the first set of squats . The WBLFV was then applied intermittently ( 3 × 10 seconds ) at 50 Hz , high amplitude ( peak-peak , 4 - 6 mm ) at time points , 60 , 120 , and 180 seconds into the 240-second rest period . Total body dual x-ray absorptiometry scans were performed at W0 ( week before training ) and W7 ( week after training ) . Measures recorded included total body mass ( kg ) , total body lean mass ( TLBM , kg ) , trunk lean mass ( kg ) , leg lean mass ( kg ) , total body fat percentage , trunk fat percentage , and leg fat percentage ( LF% ) . Repeated- measures analysis of variance and analysis of covariance revealed 1RM increased significantly between W1-W3 , W3-W7 , and W1-W7 for both experimental groups but not for control ( p = 0.001 , effect size [ ES ] = 0.237 , 1 − β = 0.947 ) . No significant differences were seen for % Δ ( p > 0.05 ) . Significant group by trial and group effects were seen for TLBM , SQTV > CON at W7 ( p = 0.044 ) . A significant main effect for time was seen for LF% , W0 vs. W7 ( p = 0.047 ) . No other significant differences were seen ( p > 0.05 ) . “ Practical trends ” were seen favoring “ short-term ” neuromuscular adaptations for the SQTV group during the first 3 weeks ( p = 0.10 , ES = 0.157 , 1 − β = 0.443 , mean diff ; SQTV week 3 4.72 kg > CON and 2.53 kg > SQT ) . Differences in motor unit activation patterns , hypertrophic responses , and dietary intake during the training period could account for the trends seen Aim : To determine the effect of whole body vibration ( WBV ) , combined with caloric restriction , on weight , body composition and metabolic risk factors in overweight and obese adults . Methods : A r and omized , controlled study with a 6-month intervention period and a 6-month ‘ no intervention ’ follow-up . 61 of the 79 participants completed the study . Data were collected at baseline and at 3 , 6 and 12 months in the control group ( CONTROL ) , the diet only group ( DIET ) , the diet plus fitness group ( FITNESS ) and the diet plus WBV group ( VIBRATION ) . Results : Weight decreased significantly in all three intervention groups . Only FITNESS and VIBRATION managed to maintain a weight loss of 5 % or more in the long term . Visceral adipose tissue ( VAT ) changed most in VIBRATION : –47.8 ± 41.2 and –47.7 ± 45.7 cm2 after 6 and 12 months respectively compared to CONTROL ( –3.6 ± 20.5 or + 26.3 ± 30.6 cm2 ) , DIET ( –24.3 ± 29.8 or –7.5 ± 28.3 cm2 ) and FITNESS ( –17.6 ± 36.6 or –1.6 ± 33.3 cm2 ) ( p < 0.001 ) . Conclusions : Combining aerobic exercise or WBV training with caloric restriction can help to achieve a sustained long-term weight loss of 5–10 % . These preliminary data show that WBV training may have the potential to reduce VAT more than aerobic exercise in obese adults , possibly making it a meaningful addition to future weight loss programs Whole-body vibration ( WBV ) is being promoted as an efficient complement to resistance training . The aim of this study was to investigate the effects of an 8-week program of WBV in combination with resistance training on knee extensors muscular performance . A group of 29 young adults ( 25 men , 4 women ; age 21.8 ± 1.5 ) performed a WBV plus resistance training program ( WBV + RES ) or an identical exercise program in absence of vibration ( placebo plus resistance training , PL + RES ) . Participants were evaluated for anthropometry , muscle strength ( half-squat three repetition maximum , 3RM ) , knee extensors isokinetic dynamometry ( 180 ° and 60 ° s−1 ) and counter-movement jump ( CMJ ) . After the intervention , percent body fat significantly decreased 2.1 % only in WBV + RES ( P < 0.001 ) , while muscle mass significantly increased in both groups ( P < 0.01 ) : 2.2 and 2.8 kg in PL + RES and WBV + RES , respectively . No significant differences were observed in isokinetic strength or CMJ , and 3RM significantly increased in both groups ( P < 0.001 ) : 64.2 kg ( 52 % of baseline ) in PL + RES , and 46.9 kg ( 43 % ) in WBV + RES . The addition of WBV to resistance training during 8 weeks , in recreationally active young adults , did not result in a larger muscular performance improvement compared to an identical exercise program in absence of vibration . Muscle mass also seemed to be equally affected with or without vibration , yet body fat could be exclusively decreased by WBV . Further research is required to clarify whether WBV , as a complement to resistance training , produces additional specific benefits Objective ( i ) to determine the outcomes of whole-body vibration training ( WBVT ) on obese individuals , and the intervention setting s producing such effects ; ( ii ) identify potential improper or harmful use of WBVT . Design Systematic review . Data sources Medline , Scopus , Web of Science , PEDro and Scielo until July 2018 . Eligibility criteria Full papers evaluating the effect of WBVT on body composition , cardiovascular status and functional performance in obese adults . Papers with PEDro score<4 were excluded . Study appraisal and synthesis Risk of bias and quality of WBVT reporting were assessed with PEDro scale ( r and omized controlled trials ) or TREND checklist ( non-r and omized studies ) and a 14-items checklist , respectively . Weighted acceleration , daily exposure and Hedges ’ adjusted g were computed . Results We included 18 papers published 2010–2017 . Typical interventions consisted in three sessions/week of exercises ( squats , calf-raises ) performed on platforms vibrating at 25–40 Hz ( amplitude : 1–2 mm ) ; according to ISO 2631–1:1997 , daily exposure was “ unsafe ” in 7/18 studies . Interventions lasting ≥6 weeks improved cardiac autonomic function and reduced central /peripheral arterial stiffness in obese women ; 10 weeks of WBVT produced significant weight/fat mass reduction , leg strength improvements as resistance training , and enhanced glucose regulation when added to hypocaloric diet . No paper evidence d losses of lean mass . Isolated cases of adverse effects were reported . Summary To date , WBVT is a promising adjuvant intervention therapy for obese women ; long-term studies involving larger cohorts and male participants are required to demonstrate the associated safety and health benefits . The therapeutic use of WBVT in the management of obese patients is still not st and ardised and should be supported by an extensive knowledge on the causality between vibration parameters and outcomes The applied use of new technologies to enhance performance and improve health has been increasing . Initially , whole body vibration training ( WBVT ) was used as system to improve elite athlete performance . However , this is also used to improve body composition , especially there is a great attention on the effectiveness of WBVT to reduce fat and body weight , with a potential increase in muscle tissue . The aim of this study was to investigate the effects of a 6-week vibration-training program on total and segmental body composition in a group of physically healthy participants . The final study sample included 64 healthy young adults . Subjects were r and omly allocated into the control group ( CG : n = 26 ; 16 males and 10 females ) and the experimental group ( EGWBVT : n = 38 ; 19 males and 19 females ) . The program lasted six weeks with a frequency of three sessions per week and each session varied in intensity . There were not found statistically significant differences in any of the body composition variables analysed . This study suggests that a six-week vibration-training program with an increasing intensity ( 7.2 g-32.6 g ) in healthy young adults that are not overweight did not alter total and segmental body composition |
11,760 | 31,848,792 | By contrast , dispensing β-blockers at discharge was associated with 35 % lower risk of all-cause deaths in HFrEF and has a weak association with borderline statistical significance on improving overall survival in HFpEF . | null | null |
11,761 | 32,319,026 | Model-based cost-effectiveness analyses of systemic mCRC treatments have adopted varied modelling methods and structures , result ing in substantially different outcomes .
As models generally focus on first-line treatment without consideration of downstream treatments , there is a profound source of structural uncertainty implying that the cost-effectiveness of treatments across the mCRC pathway remains uncertain | The aim of this systematic review was to provide a comprehensive and detailed review of structural and method ological assumptions in model-based cost-effectiveness analyses of systemic metastatic colorectal cancer ( mCRC ) treatments , and discuss their potential impact on health economic outcome estimates . | Abstract Background : Systematic evaluation and validation of new prognostic and predictive markers , technologies and interventions for colorectal cancer ( CRC ) is crucial for optimizing patients ’ outcomes . With only 5–15 % of patients participating in clinical trials , generalizability of results is poor . Moreover , current trials often lack the capacity for post-hoc subgroup analyses . For this purpose , a large observational cohort study , serving as a multiple trial and biobanking facility , was set up by the Dutch Colorectal Cancer Group ( DCCG ) . Methods / design : The Prospect i ve Dutch ColoRectal Cancer cohort is a prospect i ve multidisciplinary nationwide observational cohort study in the Netherl and s ( yearly CRC incidence of 15 500 ) . All CRC patients ( stage I – IV ) are eligible for inclusion , and longitudinal clinical data are registered . Patients give separate consent for the collection of blood and tumor tissue , filling out question naires , and broad r and omization for studies according to the innovative cohort multiple r and omized controlled trial design ( cm RCT ) , serving as an alternative study design for the classic RCT . Objectives of the study include : 1 ) systematic ally collected long-term clinical data , patient-reported outcomes and bio material s from daily CRC practice ; and 2 ) to facilitate future basic , translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods , even for studies with stringent inclusion criteria . Results : Seven months after initiation 650 patients have been enrolled , eight centers participate , 15 centers await IRB approval and nine embedded cohort- or cm RCT - design ed studies are currently recruiting patients . Conclusion : This cohort provides a unique multidisciplinary data , biobank , and patient-reported outcomes collection initiative , serving as an infrastructure for various kinds of research aim ing to improve treatment outcomes in CRC patients . This comprehensive design may serve as an example for other tumor types PURPOSE Fluoropyrimidines are frequently prescribed anticancer drugs . A polymorphism in the fluoropyrimidine metabolizing enzyme dihydropyrimidine dehydrogenase ( DPD ; ie , DPYD*2A ) is strongly associated with fluoropyrimidine-induced severe and life-threatening toxicity . This study determined the feasibility , safety , and cost of DPYD*2A genotype-guided dosing . PATIENTS AND METHODS Patients intended to be treated with fluoropyrimidine-based chemotherapy were prospect ively genotyped for DPYD*2A before start of therapy . Variant allele carriers received an initial dose reduction of ≥ 50 % followed by dose titration based on tolerance . Toxicity was the primary end point and was compared with historical controls ( ie , DPYD*2A variant allele carriers receiving st and ard dose described in literature ) and with DPYD*2A wild-type patients treated with the st and ard dose in this study . Secondary end points included a model-based cost analysis , as well as pharmacokinetic and DPD enzyme activity analyses . RESULTS A total of 2,038 patients were prospect ively screened for DPYD*2A , of whom 22 ( 1.1 % ) were heterozygous polymorphic . DPYD*2A variant allele carriers were treated with a median dose-intensity of 48 % ( range , 17 % to 91 % ) . The risk of grade ≥ 3 toxicity was thereby significantly reduced from 73 % ( 95 % CI , 58 % to 85 % ) in historical controls ( n = 48 ) to 28 % ( 95 % CI , 10 % to 53 % ) by genotype-guided dosing ( P < .001 ) ; drug-induced death was reduced from 10 % to 0 % . Adequate treatment of genotype-guided dosing was further demonstrated by a similar incidence of grade ≥ 3 toxicity compared with wild-type patients receiving the st and ard dose ( 23 % ; P = .64 ) and by similar systemic fluorouracil ( active drug ) exposure . Furthermore , average total treatment cost per patient was lower for screening ( € 2,772 [ $ 3,767 ] ) than for nonscreening ( € 2,817 [ $ 3,828 ] ) , outweighing screening costs . CONCLUSION DPYD*2A is strongly associated with fluoropyrimidine-induced severe and life-threatening toxicity . DPYD*2A genotype-guided dosing results in adequate systemic drug exposure and significantly improves safety of fluoropyrimidine therapy for the individual patient . On a population level , upfront genotyping seemed cost saving UNLABELLED In February 2010 , the Medical Advisory Secretariat ( MAS ) began work on evidence -based review s of the literature surrounding three pharmacogenomic tests . This project came about when Cancer Care Ontario ( CCO ) asked MAS to provide evidence -based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario . Evidence -based analyses have been prepared for each of these technologies . These have been completed in conjunction with internal and external stakeholders , including a Provincial Expert Panel on Pharmacogenomics ( PEPP ) . Within the PEPP , subgroup committees were developed for each disease area . For each technology , an economic analysis was also completed by the Toronto Health Economics and Technology Assessment Collaborative ( THETA ) and is summarized within the reports . THE FOLLOWING REPORTS CAN BE PUBLICLY ACCESSED AT THE MAS WEBSITE AT : www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlGENE EXPRESSION PROFILING FOR GUIDING ADJUVANT CHEMOTHERAPY DECISIONS IN WOMEN WITH EARLY BREAST CANCER : An Evidence -Based and Economic Analysis Epidermal Growth Factor Receptor Mutation ( EGFR ) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor ( TKI ) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer : an Evidence -Based and Economic Analysis K-RAS testing in Treatment Decisions for Advanced Colorectal Cancer : an Evidence -Based and Economic Analysis . OBJECTIVE The objective of this systematic review is to determine the predictive value of KRAS testing in the treatment of metastatic colorectal cancer ( mCRC ) with two anti-EGFR agents , cetuximab and panitumumab . Economic analyses are also being conducted to evaluate the cost-effectiveness of KRAS testing . CLINICAL NEED CONDITION AND TARGET POPULATION Metastatic colorectal cancer ( mCRC ) is usually defined as stage IV disease according to the American Joint Committee on Cancer tumour node metastasis ( TNM ) system or stage D in the Duke 's classification system . Patients with advanced colorectal cancer ( mCRC ) either present with metastatic disease or develop it through disease progression . KRAS ( Kristen-RAS , a member of the rat sarcoma virus ( ras ) gene family of oncogenes ) is frequently mutated in epithelial cancers such as colorectal cancer , with mutations occurring in mutational hotspots ( codons 12 and 13 ) of the KRAS protein . Involved in EGFR-mediated signalling of cellular processes such as cell proliferation , resistance to apoptosis , enhanced cell motility and neoangiogenesis , a mutation in the KRAS gene is believed to be involved in cancer pathogenesis . Such a mutation is also hypothesized to be involved in resistance to targeted anti-EGFR ( epidermal growth factor receptor with tyrosine kinase activity ) treatments such as cetuximab and panitumumab , hence , the important in evaluating the evidence on the predictive value of KRAS testing in this context . KRAS MUTATION TESTING IN ADVANCED COLORECTAL CANCER : Both cetuximab and panitumumab are indicated by Health Canada in the treatment of patients with metastatic colorectal cancer whose tumours are WT for the KRAS gene . Cetuximab may be offered as monotherapy in patients intolerant to irinotecan-based chemotherapy or in patients who have failed both irinotecan and oxaliplatin-based regimens and who received a fluoropyrimidine . It can also be administered in combination with irinotecan in patients refractory to other irinotecan-based chemotherapy regimens . Panitumumab is only indicated as a single agent after failure of fluoropyrimidine- , oxaliplatin- , and irinotecan-containing chemotherapy regimens . In Ontario , patients with advanced colorectal cancer who are refractory to chemotherapy may be offered the targeted anti-EGFR treatments cetuximab or panitumumab . Eligibility for these treatments is based on the KRAS status of their tumour , derived from tissue collected from surgical or biopsy specimens . It is believed that KRAS status is not affected by treatments , therefore , for patients for whom surgical tissue is available for KRAS testing , additional biopsies prior to treatment with these targeted agents is not necessary . For patients that have not undergone surgery or for whom surgical tissue is not available , a biopsy of either the primary or metastatic site is required to determine their KRAS status . This is possible as status at the metastatic and primary tumour sites is considered to be similar . RESEARCH QUESTION To determine if there is predictive value of KRAS testing in guiding treatment decisions with anti-EGFR targeted therapies in advanced colorectal cancer patients refractory to chemotherapy . RESEARCH METHODS LITERATURE SEARCH The Medical Advisory Secretariat followed its st and ard procedures and on May 18 , 2010 , search ed the following electronic data bases : Ovid MEDLINE , EMBASE , Ovid MEDLINE In-Process & Other Non-Indexed Citations , Cochrane Central Register of Controlled Trials , Cochrane Data base of Systematic Review s and The International Network of Agencies for Health Technology Assessment data base . The subject headings and keywords search ed included colorectal cancer , cetuximab , panitumumab , and KRAS testing . The search was further restricted to English- language articles published between January 1 , 2009 and May 18 , 2010 result ing in 1335 articles for review . Excluded were case reports , comments , editorials , non systematic review s , and letters . Studies published from January 1 , 2005 to December 31 , 2008 were identified in a health technology assessment conducted by the Agency for Healthcare Research and Quality ( AHRQ ) , published in 2010 . In total , 14 observational studies were identified for inclusion in this EBA : 4 for cetuximab monotherapy , 7 for the cetuximab-irinotecan combination therapy , and 3 to be included in the review for panitumumab monotherapy INCLUSION CRITERIA English- language articles , and English or French- language HTAs published from January 2005 to May 2010 , inclusive . R and omized controlled trials ( RCTs ) or observational studies , including single arm treatment studies that include KRAS testing . Studies with data on main outcomes of interest , overall and progression-free survival . Studies of third line treatment with cetuximab or panitumumab in patients with advanced colorectal cancer refractory to chemotherapy . For the cetuximab-irinotecan evaluation , studies in which at least 70 % of patients in the study received this combination therapy . EXCLUSION CRITERIA Studies whose entire sample was included in subsequent publications which have been included in this EBA . Studies in pediatric population s . Case reports , comments , editorials , or letters . OUTCOMES OF INTEREST Overall survival ( OS ) , medianProgression-free-survival ( PFS ) , median . Response rates . Adverse event rates . Quality of life ( QOL ) . SUMMARY OF FINDINGS OF SYSTEMATIC REVIEW : CETUXIMAB OR PANITUMUMAB MONOTHERAPY : Based on moderate GRADE observational evidence , there is improvement in PFS and OS favouring patients without the KRAS mutation ( KRAS wildtype , or KRAS WT ) compared to those with the mutation . CETUXIMAB-IRINOTECAN COMBINATION THERAPY : There is low GRADE evidence that testing for KRAS may optimize survival benefits in patients without the KRAS mutation ( KRAS wildtype , or KRAS WT ) compared to those with the mutation . However , cetuximab-irinotecan combination treatments based on KRAS status discount any effect of cetuximab in possibly reversing resistance to irinotecan in patients with the mutation , as observed effects were lower than for patients without the mutation . Clinical experts have raised concerns about the biological plausibility of this observation and this conclusion would , therefore , be regarded as hypothesis generating . ECONOMIC ANALYSIS Cost-effectiveness and budget impact analyses were conducted incorporating estimates of effectiveness from this systematic review . Evaluation of relative cost-effectiveness , based on a decision-analytic cost-utility analysis , assessed testing for KRAS genetic mutations versus no testing in the context of treatment with cetuximab monotherapy , panitumumab monotherapy , cetuximab in combination with irinotecan , and best supportive care . Of importance to note is that the cost-effectiveness analysis focused on the impact of testing for KRAS mutations compared to no testing in the context of different treatment options , and does not assess the cost-effectiveness of the drug treatments alone . CONCLUSIONS KRAS status is predictive of outcomes in cetuximab and panitumumab monotherapy , and in cetuximab-irinotecan combination therapy . While KRAS testing is cost-effective for all strategies considered , it is not equally cost-effective for all treatment options Trust and confidence are critical to the success of health care models . There are two main methods for achieving this : transparency ( people can see how the model is built ) and validation ( how well the model reproduces reality ) . This report describes recommendations for achieving transparency and validation developed by a taskforce appointed by the International Society for Pharmacoeconomics and Outcomes Research and the Society for Medical Decision Making . Recommendations were developed iteratively by the authors . A nontechnical description -- including model type , intended applications , funding sources , structure , intended uses , inputs , outputs , other components that determine function , and their relationships , data sources , validation methods , results , and limitations --should be made available to anyone . Technical documentation , written in sufficient detail to enable a reader with necessary expertise to evaluate the model and potentially reproduce it , should be made available openly or under agreements that protect intellectual property , at the discretion of the modelers . Validation involves face validity ( wherein experts evaluate model structure , data sources , assumptions , and results ) , verification or internal validity ( check accuracy of coding ) , cross validity ( comparison of results with other models analyzing the same problem ) , external validity ( comparing model results with real-world results ) , and predictive validity ( comparing model results with prospect ively observed events ) . The last two are the strongest form of validation . Each section of this article contains a number of recommendations that were iterated among the authors , as well as among the wider modeling taskforce , jointly set up by the International Society for Pharmacoeconomics and Outcomes Research and the Society for Medical Decision Making PURPOSE In a previous study of treatment for advanced colorectal cancer , the LV5FU2 regimen , comprising leucovorin ( LV ) plus bolus and infusional fluorouracil ( 5FU ) every 2 weeks , was superior to the st and ard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen . This phase III study investigated the effect of combining oxaliplatin with LV5FU2 , with progression-free survival as the primary end point . PATIENTS AND METHODS Four hundred twenty previously untreated patients with measurable disease were r and omized to receive a 2-hour infusion of LV ( 200 mg/m(2)/d ) followed by a 5FU bolus ( 400 mg/m(2)/d ) and 22-hour infusion ( 600 mg/m(2)/d ) for 2 consecutive days every 2 weeks , either alone or together with oxaliplatin 85 mg/m(2 ) as a 2-hour infusion on day 1 . RESULTS Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival ( median , 9.0 v 6.2 months ; P = .0003 ) and better response rate ( 50.7 % v 22.3 % ; P = .0001 ) when compared with the control arm . The improvement in overall survival did not reach significance ( median , 16.2 v 14.7 months ; P = . 12 ) . LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia ( 41 . 7 % v 5.3 % of patients ) , grade 3/4 diarrhea ( 11.9 % v 5.3 % ) , and grade 3 neurosensory toxicity ( 18.2 % v 0 % ) , but this did not result in impairment of quality of life ( QoL ) . Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment ( P = .004 ) . CONCLUSION The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer , demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of BACKGROUND Fluoropyrimidine treatment can result in severe toxicity in up to 30 % of patients and is often the result of reduced activity of the key metabolic enzyme dihydropyrimidine dehydrogenase ( DPD ) , mostly caused by genetic variants in the gene encoding DPD ( DPYD ) . We assessed the effect of prospect i ve screening for the four most relevant DPYD variants ( DPYD*2A [ rs3918290 , c.1905 + 1G > A , IVS14 + 1G > A ] , c.2846A > T [ rs67376798 , D949V ] , c.1679T > G [ rs55886062 , DPYD*13 , I560S ] , and c.1236G > A [ rs56038477 , E412E , in haplotype B3 ] ) on patient safety and subsequent DPYD genotype-guided dose individualisation in daily clinical care . METHODS In this prospect i ve , multicentre , safety analysis in 17 hospitals in the Netherl and s , the study population consisted of adult patients ( ≥18 years ) with cancer who were intended to start on a fluoropyrimidine-based anticancer therapy ( capecitabine or fluorouracil as single agent or in combination with other chemotherapeutic agents or radiotherapy ) . Patients with all tumour types for which fluoropyrimidine-based therapy was considered in their best interest were eligible . We did prospect i ve genotyping for DPYD*2A , c.2846A > T , c.1679T > G , and c.1236G > A. Heterozygous DPYD variant allele carriers received an initial dose reduction of 25 % ( c.2846A > T and c.1236G > A ) or 50 % ( DPYD*2A and c.1679T > G ) , and DPYD wild-type patients were treated according to the current st and ard of care . The primary endpoint of the study was the frequency of severe ( National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 grade ≥3 ) overall fluoropyrimidine-related toxicity across the entire treatment duration . We compared toxicity incidence between DPYD variant allele carriers and DPYD wild-type patients on an intention-to-treat basis , and relative risks ( RRs ) for severe toxicity were compared between the current study and a historical cohort of DPYD variant allele carriers treated with full dose fluoropyrimidine-based therapy ( derived from a previously published meta- analysis ) . This trial is registered with Clinical Trials.gov , number NCT02324452 , and is complete . FINDINGS Between April 30 , 2015 , and Dec 21 , 2017 , we enrolled 1181 patients . 78 patients were considered non-evaluable , because they were retrospectively identified as not meeting inclusion criteria , did not start fluoropyrimidine-based treatment , or were homozygous or compound heterozygous DPYD variant allele carriers . Of 1103 evaluable patients , 85 ( 8 % ) were heterozygous DPYD variant allele carriers , and 1018 ( 92 % ) were DPYD wild-type patients . Overall , fluoropyrimidine-related severe toxicity was higher in DPYD variant carriers ( 33 [ 39 % ] of 85 patients ) than in wild-type patients ( 231 [ 23 % ] of 1018 patients ; p=0·0013 ) . The RR for severe fluoropyrimidine-related toxicity was 1·31 ( 95 % CI 0·63 - 2·73 ) for genotype-guided dosing compared with 2·87 ( 2·14 - 3·86 ) in the historical cohort for DPYD*2A carriers , no toxicity compared with 4·30 ( 2·10 - 8·80 ) in c.1679T > G carriers , 2·00 ( 1·19 - 3·34 ) compared with 3·11 ( 2·25 - 4·28 ) for c.2846A > T carriers , and 1·69 ( 1·18 - 2·42 ) compared with 1·72 ( 1·22 - 2·42 ) for c.1236G > A carriers . INTERPRETATION Prospect i ve DPYD genotyping was feasible in routine clinical practice , and DPYD genotype-based dose reductions improved patient safety of fluoropyrimidine treatment . For DPYD*2A and c.1679T > G carriers , a 50 % initial dose reduction was adequate . For c.1236G > A and c.2846A > T carriers , a larger dose reduction of 50 % ( instead of 25 % ) requires investigation . Since fluoropyrimidines are among the most commonly used anticancer agents , these findings suggest that implementation of DPYD genotype-guided individualised dosing should be a new st and ard of care . FUNDING Dutch Cancer Society BACKGROUND Fluoropyrimidine therapy including capecitabine or 5-fluorouracil can result in severe treatment-related toxicity in up to 30 % of patients . Toxicity is often related to reduced activity of dihydropyrimidine dehydrogenase , the main metabolic fluoropyrimidine enzyme , primarily caused by genetic DPYD polymorphisms . In a large prospect i ve study , it was concluded that upfront DPYD-guided dose individualisation is able to improve safety of fluoropyrimidine-based therapy . In our current analysis , we evaluated whether this strategy is cost saving . METHODS A cost-minimisation analysis from a health-care payer perspective was performed as part of the prospect i ve clinical trial ( NCT02324452 ) in which patients prior to start of fluoropyrimidine-based therapy were screened for the DPYD variants DPYD*2A , c.2846A > T , c.1679T > G and c.1236G > A and received an initial dose reduction of 25 % ( c.2846A > T , c.1236G > A ) or 50 % ( DPYD*2A , c.1679T > G ) . Data on treatment , toxicity , hospitalisation and other toxicity-related interventions were collected . The model compared prospect i ve screening for these DPYD variants with no DPYD screening . One-way and probabilistic sensitivity analyses were also performed . RESULTS Expected total costs of the screening strategy were € 2599 per patient compared with € 2650 for non-screening , result ing in a net cost saving of € 51 per patient . Results of the probabilistic sensitivity and one-way sensitivity analysis demonstrated that the screening strategy was very likely to be cost saving or worst case cost-neutral . CONCLUSIONS Upfront DPYD-guided dose individualisation , improving patient safety , is cost saving or cost-neutral but is not expected to yield additional costs . These results endorse implementing DPYD screening before start of fluoropyrimidine treatment as st and ard of care Background Fusions involving one of three tropomyosin receptor kinases ( TRK ) occur in diverse cancers in children and adults . We evaluated the efficacy and safety of larotrectinib , a highly selective TRK inhibitor , in adults and children who had tumors with these fusions . Methods We enrolled patients with consecutively and prospect ively identified TRK fusion – positive cancers , detected by molecular profiling as routinely performed at each site , into one of three protocol s : a phase 1 study involving adults , a phase 1–2 study involving children , or a phase 2 study involving adolescents and adults . The primary end point for the combined analysis was the overall response rate according to independent review . Secondary end points included duration of response , progression‐free survival , and safety . Results A total of 55 patients , ranging in age from 4 months to 76 years , were enrolled and treated . Patients had 17 unique TRK fusion – positive tumor types . The overall response rate was 75 % ( 95 % confidence interval [ CI ] , 61 to 85 ) according to independent review and 80 % ( 95 % CI , 67 to 90 ) according to investigator assessment . At 1 year , 71 % of the responses were ongoing and 55 % of the patients remained progression‐free . The median duration of response and progression‐free survival had not been reached . At a median follow‐up of 9.4 months , 86 % of the patients with a response ( 38 of 44 patients ) were continuing treatment or had undergone surgery that was intended to be curative . Adverse events were predominantly of grade 1 , and no adverse event of grade 3 or 4 that was considered by the investigators to be related to larotrectinib occurred in more than 5 % of patients . No patient discontinued larotrectinib owing to drug‐related adverse events . Conclusions Larotrectinib had marked and durable antitumor activity in patients with TRK fusion – positive cancer , regardless of the age of the patient or of the tumor type . ( Funded by Loxo Oncology and others ; Clinical Trials.gov numbers , NCT02122913 , NCT02637687 , and NCT02576431 . |
11,762 | 28,726,172 | OS and PFS did not significantly differ between combination therapy and WBRT alone .
No advantages of concurrent WBRT and TMZ were observed in breast cancer patients with brain metastases .
Combination therapy was associated with improved ORR in NSCLC patients , especially in Chinese patients .
As a “ surrogate endpoint ” for OS , ORR may allow a conclusion to be made about the management of NSCLC with brain metastases with the combination of WBRT and TMZ . | Brain metastasis is the leading cause of death among advanced non-small cell lung cancer ( NSCLC ) and breast cancer patients .
The st and ard treatment for brain metastases is radiotherapy .
The combination of radiotherapy and chemotherapy has been tested .
However , the management of brain metastases has yet to be successful .
Here , we aim ed to determine the efficacy and safety of whole brain radiotherapy ( WBRT ) alone or in combination with temozolomide ( TMZ ) in NSCLC and breast cancer patients with brain metastases . | Purpose : This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer ( SCLC ) . Experimental Design : Patients with disease progression after one or two prior chemotherapy regimens received temozolomide at 75 mg/m2/d for 21 days of a 28-day cycle . The primary endpoint was the overall response rate [ ORR ; complete response ( CR ) plus partial response ( PR ) ] , which was evaluated separately in sensitive and refractory cohorts . In the available tissue , we assessed O6-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation status by PCR and MGMT expression by immunohistochemistry . Results : Sixty-four patients were accrued : 48 patients in the sensitive cohort and 16 in the refractory group . One CR and 10 PRs were noted in sensitive patients [ ORR , 23 % ; 95 % confidence interval ( CI ) , 12%–37 % ] . Two PRs were seen in the refractory cohort ( ORR , 13 % ; 95 % CI , 2%–38 % ) . As second- and third-line treatment , the ORR was 22 % ( 95 % CI , 9%–40 % ) and 19 % ( 95 % CI , 7%–36 % ) , respectively . Among patients with target brain lesions , 38 % had a CR or PR ( 95 % CI , 14%–68 % ) . Grade ≥3 thrombocytopenia and neutropenia were observed in nine patients ( 14 % ) . A greater number of cases with methylated MGMT had a response compared to those with unmethylated MGMT ( 38 % vs. 7 % ; P = 0.08 ) . Conclusion : Temozolomide has activity in relapsed SCLC , particularly for brain metastases . Response to temozolomide may correlate with MGMT methylation in SCLC . Clin Cancer Res ; 18(4 ) ; 1138–45 . © 2012 AACR BACKGROUND AND METHODS Cisplatin ( cis-diamminedichloroplatinum ) has been reported to enhance the cell-killing effect of radiation , an effect whose intensity varies with the schedule of administration . We r and omly assigned 331 patients with nonmetastatic inoperable non-small-cell lung cancer to one of three treatments : radiotherapy for two weeks ( 3 Gy given 10 times , in five fractions a week ) , followed by a three-week rest period and then radiotherapy for two more weeks ( 2.5 Gy given 10 times , five fractions a week ) ; radiotherapy on the same schedule , combined with 30 mg of cisplatin per square meter of body-surface area , given on the first day of each treatment week ; or radiotherapy on the same schedule , combined with 6 mg of cisplatin per square meter , given daily before radiotherapy . RESULTS Survival was significantly improved in the radiotherapy-daily-cisplatin group as compared with the radiotherapy group ( P = 0.009 ) : survival in the radiotherapy-daily-cisplatin group was 54 percent at one year , 26 percent at two years , and 16 percent at three years , as compared with 46 percent , 13 percent , and 2 percent , respectively , in the radiotherapy group . Survival in the radiotherapy-weekly-cisplatin group was intermediate ( 44 percent , 19 percent , and 13 percent ) and not significantly different from survival in either of the other two groups . The survival benefit of daily combined treatment was due to improved control of local disease ( P = 0.003 ) . Survival without local recurrence was 59 percent at one year and 31 percent at two years in the radiotherapy-daily-cisplatin group ; 42 percent and 30 percent , respectively , in the radiotherapy-weekly-cisplatin group ; and 41 percent and 19 percent , respectively , in the radiotherapy group . Cisplatin induced nausea and vomiting in 86 percent of the patients given it weekly and in 78 percent of those given it daily ; these effects were severe in 26 percent and 28 percent , respectively . CONCLUSIONS Cisplatin , given daily in combination with the radiotherapy described here to patients with nonmetastatic but inoperable non-small-cell lung cancer , improved rates of survival and control of local disease at the price of substantial side effects |
11,763 | 16,777,466 | Evidence , however , indicated that not only the passive , but also the active and control subsystems of the shoulder may need to be considered when determining the direction of the translational gliding of the HOH . | Kaltenborn 's convex-concave rule is a familiar concept in joint treatment techniques and arthrokinematics .
Recent investigations on the glenohumeral joint appear to question this rule and thus accepted practice guidelines .
An evidence -based systematic review was conducted to summarize and interpret the evidence on the direction of the accessory gliding movement of the head of the humerus ( HOH ) on the glenoid during physiological shoulder movement . | Background No quantitative data on glenohumeral translation exist allowing one to distinguish insufficiency of the active or passive stabilizers in different forms of shoulder instability . Hypothesis To determine whether 1 ) in traumatic or atraumatic shoulder instability an increase of glenohumeral translation can be observed in specific relevant arm positions , 2 ) muscle activity leads to recentering of the humeral head , and 3 ) there exist differences between traumatic and atraumatic instability . Study Design Prospect i ve clinical trial . Methods In 12 patients with traumatic and 10 patients with atraumatic instability , both shoulders were examined in different arm positions — with and without muscle activity — by using open magnetic resonance imaging and a three-dimensional postprocessing technique . Results At 90 ° of abduction and external rotation , translation ( anterior-inferior ) was significantly higher in patients with traumatic unstable shoulders compared with their contralateral side ( 3.6 ± 1.5 versus 0.7 ± 1.6 mm ) . In patients with atraumatic instability , significantly increased translation ( 4.7 ± 2.0 mm ) was observed , with the direction being nonuniform . Muscle activity led to significant recentering in traumatic but not in atraumatic instability . Conclusions In traumatic instability , increased translation was observed only in functionally important arm positions , whereas intact active stabilizers demonstrate sufficient recentering . In atraumatic instability , a de central ized head position was recorded also during muscle activity , suggesting alterations of the active stabilizers . Clinical Relevance Clinical Relevance : These data are relevant for optimizing diagnostics and therapeutic strategies Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists 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 . Descriptive studies have shown that shoulder complaints can be persistent and recurrent , requiring long term evaluation of treatment.1 Unfortunately , in most r and omised studies comparing treatments for shoulder complaints the study period varies from a few weeks ( trials of non-steroidal anti-inflammatory drugs ) to 3 - 6 months ( injection therapy and physiotherapy trials).2–4 ) In a trial in 1994 - 5 of treatment of shoulder complaints in general practice we showed that in a study period of 11 weeks , injection therapy with a corticosteroid was superior to physiotherapy and manipulative therapy in the patients whose complaints originated from the structures of the glenohumeral joint , the subacromial space , or the acromioclavicular joint ( synovial group).5 In the patients whose complaints related to functional disorders of the cervical spine , the upper thoracic spine , or the adjoining ribs ( shoulder girdle group ) , manipulation was superior to physiotherapy . To assess the various treatments in A method for directly measuring the position of the humeral head on the face of the glenoid in different positions of abduction of the arm was developed . We studied three subject groups : 12 patients with normal shoulders ( group 1 ) , 15 patients with stage II impingement syndrome ( group 2 ) , and 20 patients with rotator cuff tears or stage III impingement ( group 3 ) . The study consisted of a series of anteroposterior roentgenograms in the plane of the scapula with the arm in neutral rotation . Roentgenograms were obtained at 20 degrees intervals as the arm was elevated in the plane of the scapula from 0 degree to 120 degrees . Patients held a weight equal to 2 1/2 % of body weight in the h and . The parameters measured were excursion of the humeral head on the glenoid face , expressed as the distance that the center of the head lies above or below the center of the glenoid , arm angle , scapulothoracic angle , and glenohumeral angle . For patients with normal shoulders ( group 1 ) , there was no significant change in position of the humeral head with arm elevation . In contrast , those with stage II impingement ( group 2 ) had significant ( p < 0.05 ) superior displacement of the center of the humeral head with arm elevation . Patients with rotator cuff tears ( group 3 ) demonstrated a significant rise ( p < 0.05 ) during the first 40 degrees of abduction . The average position of the humeral head in the two pathologic patient groups was superior ( p < 0.05 ) to the average head position in the normal patient group . There was no significant difference in head position between patients with stage II impingement and patients with rotator cuff tear . The ratio of the glenohumeral angle to the scapulothoracic angle during abduction was calculated for our patient groups . In both patient groups , arm abduction had a larger scapulothoracic component than for normal shoulders . The superior migration of the humeral head is a probable result of cuff failure , either partial or complete |
11,764 | 11,686,983 | Studies of general surgery contain considerable numbers of colorectal patients . | BACKGROUND Colorectal surgery implies higher risk of postoperative thromboembolic complications as deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) than general surgery .
The best prophylaxis in general surgery is heparin and grade d compression stockings .
No systematic review on combination prophylaxis or on thrombosis prophylaxis in colorectal surgery has been published .
OBJECTIVES To compare the incidence of postoperative thromboembolism after colorectal surgery using prophylactic methods focussing on heparins and mechanical methods alone and in combinations . | PURPOSE : Routine deep venous thrombosis prophylaxis is controversial in Asian patients , because deep venous thrombosis incidence was considered negligible . Because of recent reports of significantly higher incidences , a r and omized , controlled trial was conducted to assess the effectiveness and complications of enoxaparin prophylaxis ( low molecular weight heparins ) in major colorectal surgery . METHODS : Three hundred twenty consecutive patients were r and omly assigned to control or low molecular weight heparins groups . Patients in the low molecular weight heparins group were given perioperative enoxaparin starting 12 hours before surgery . The surgeon ( blinded ) assessed for difficulties related to possible enoxaparin administration . Independent blinded observers performed daily clinical assessment s and Doppler studies ( at the 3rd and 5th postoperative day ) . Deep venous thrombosis was confirmed by duplex ultrasound , and pulmonary embolism was confirmed by lung scans or postmortem examinations . RESULTS : Deep venous thrombosis developed in 5 of 169 ( 3 percent ) controls and 0 of 134 low molecular weight heparins patients ( P=0.045 ) . Three of the deep venous thrombosis patients had pulmonary embolism , which was fatal in one patient . The surgeons were unable to perceive any increased surgical difficulties in the low molecular weight heparins group . The bleeding-related complications were significantly higher in the low molecular weight heparins patients ( controls , n=3 ( 1.8 percent ) ; low molecular weight heparins , n=9 ( 6.7 percent ) ) . However , apart from one subdural hematoma and two abdominal hemorrhages needing re-exploration , which also occurred in one of the controls , these complications were minor bruises at the wounds , drains , or injection sites . CONCLUSION : Deep venous thrombosis prophylaxis is needed in Asian patients undergoing major colorectal surgery In a r and omized , prospect i ve , double‐blind multicentre trial , the effect of conventional low‐dose heparin 5000 units twice daily , was compared with that of a low molecular weight heparin fragment ( 4000–5000 ) 5000 anti‐factor Xa units once daily . Four hundred and thirty‐two patients fulfilled the inclusion criteria and were analysed for development of deep vein thrombosis ( 125I‐labelled fibrinogen test ) and haemorrhagic complications . Thrombosis occurred in a 4.3 per cent of patients in the low‐dose heparin group and in 6.4 per cent of patients in the heparin fragment group , a difference which is not significant . There was a significant delay in the onset of thrombosis in the heparin fragment group . Mortality did not differ between the groups , nor did peroperative blood loss or transfusion requirements or infectious complications . Haemorrhagic complications occurred significantly more often in the fragment group ( 11.6 per cent ) than in the conventional heparin group ( 4.6 per cent ) . Patients in the heparin fragment group experienced local pain following the subcutaneous injection significantly less often Abstract Heparin ( 1 IU kg -1 h -1 ) given intravenously for 3 - 5 days during and after operation in a double-blind r and omised study , significantly reduced the frequency of deep-vein thrombosis detected by 125 I-fibrinogen uptake , and pulmonary embolism . 22 % ( 11/50 ) control patients and 4 % ( 2/45 ) patients receiving heparin had deep-vein thrombosis or pulmonary embolism . Heparin administration was not associated with any increase in preoperative or postoperative bleeding In a prospect i ve , r and omized multicentre trial the efficacy and safety of the low molecular weight heparin ( LMWH ) fraction Fraxiparin ® and unfractionated calcium heparin ( Calciparin ® ) were compared for the prevention of postoperative deep vein thrombosis . Of 1909 patients included in the trial 1896 underwent abdominal surgery and received either one daily subcutaneous injection of 7500 anti‐X a units Fraxiparin or 5000 units calcium heparin three times a day subcutaneously . Elastic compression stockings were worn by both groups of patients in the postoperative period . Before r and omization the patients were stratified in two subgroups with or without malignant disease . To assess the rate of deep vein thrombosis ( DVT ) , 125I‐labelled fibrinogen leg scanning was performed daily for 7 postoperative days . Positive results were confirmed by phlebography whenever possible . Venous thrombosis occurred in 27 of 960 patients ( 2.8 per cent ) given Fraxiparin and in 42 of 936 patients ( 4.5 per cent ) given calcium heparin ( P = 0.034 ) . The rates of proximal vein thrombosis were 0.4 per cent ( 4 patients ) and 1.4 per cent ( 13 patients ) respectively ( P<0.05 ) . Pulmonary embolism occurred in 2 of 960 patients ( 0.2 per cent ) treated with Fraxiparin and in 5 of 936 patients ( 0.5 per cent ) treated with calcium heparin . The two treatments were equally well tolerated . Intra‐ and postoperative blood loss , the number of wound haematomas as well as frequency and volume of transfusions were similar in both groups . The present trial demonstrates that a single daily subcutaneous injection of Fraxiparin is more effective than the established low dose subcutaneous heparin prophylaxis with 5000 units three times per day in preventing postoperative DVT after abdominal surgery in patients wearing compression stockings In a prospect i ve , double-blind , r and omized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery . Six hundred and seventy-three patients were r and omly allocated to the two prophylaxis groups ; 20 of these , however , did not undergo surgery and did not receive any prophylaxis . Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day . Treatment was initiated 2 h preoperatively and continued for 7 to 10 days . The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography . Venous thrombosis was diagnosed in 24 of 323 patients ( 7.4 % ) treated with low molecular weight heparin and in 26 of 330 patients ( 7.9 % ) treated with low-dose heparin . DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group . During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin . No pulmonary embolism was found in patients treated with low molecular weight heparin . Both prophylactic schemes were well tolerated . Intra- and postoperative blood loss , incidence of wound hematoma , frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group . ( ABSTRACT TRUNCATED AT 250 WORDS The effect of low-dose heparin prophylaxis on venous thrombosis and bleeding after major elective surgery was studied in a prospect i ve controlled study of 820 patients . The total incidence of venous thrombosis detected with leg-scanning using fibrinogen labeled with radioactive iodine ( 125I ) was reduced from 16.0 % in the control group to 4.2 % in treated patients . More important , the incidence of popliteal or femoral vein thrombosis was reduced from 2.9 % to 1.0 % . Prophylaxis result ed in a slight increase in bleeding-minor wound hematoma , mean volume of blood transfused , and a post-operative hematocrit fall in treated patients . However , increased bleeding was clinical ly minor , and prophylaxis was well tolerated Fourty patients who underwent general surgery have been enrolled in a double-blind controlled trial which evaluated the efficacy and safety of Fragmin , a new low molecular weight heparin , chosen to be the 1st OMS International St and ard for LMWH . Fragmin 2500 UI anti-Xa once daily and unfractionated heparin 5000 UI twice daily were administered to prevent postoperative deep venous thrombosis . Prophylaxis began two hours before surgery and continued for the next 5 postoperative days . The incidence of isotopic venous thrombosis , thromboembolic disorders and bleeding complications have been evaluated . Results have shown a similar efficacy and safety profile of the two drugs , although Fragmin doses are markedly inferior to unfractionated heparin 's . Moreover , Fragmin has the advantage of a single daily administration , with a better patients ' compliance and an easier and less expensive nursing care The potential antithrombotic effect of a new low molecular weight heparinoid , Org 10172 , was examined in a r and omized , double-blind , placebo-controlled , dose-ranging pilot study of the prevention of deep venous thrombosis ( DVT ) in 45 high-risk patients having major thoracic or abdominal surgery for cancer . Org 10172 was given in doses of 500 , 750 or 1000 U bd subcutaneously . DVT occurred in 9 of 14 patients given placebo and in 4 of 11 patients given 500 U bd but in none of the 20 patients given 750 or 1000 U bd . Operative blood loss and post-operative bleeding were not significantly different between the groups but one patient given 1000 U bd had major post-operative bleeding . Average mid-interval and trough plasma anti-Xa levels reached 0.26 and 0.20 U/ml respectively following the highest dose . It is concluded that Org 10172 is a potentially useful antithrombotic agent and that the effective and safe dose appears to be between 500 and 1000 U bd for prevention of DVT in high-risk patients The prophylactic effect of a semisynthetic heparin analogue ( SSHA ) on deep vein thrombosis was investigated in a prospect i ve double‐blind multicentre trial . 440 major general surgical and gynaecological patients were r and omized to one of three treatment groups : 50 mg SSHA , 37.5 mg SSHA and 5000 units sodium heparin subcutaneously 12‐hourly . Deep venous thrombosis ( DVT ) was diagnosed with the fibrinogen uptake test and verified with phlebography . Bleeding complications and other side‐effects were carefully monitored . There were no significant differences between the three treatment groups of patients in age , sex , type of operation or risk factors . A DVT was diagnosed in 16 patients ( 12 per cent ) in the SSHA 50 mg group , in 21 patients ( 15 per cent ) in the SSHA 37.5 mg group and 21 patients ( 14 per cent ) in the heparin‐treated group . No significant differences were found in the number of patients who bled unexpectedly in the postoperative period , required transfusion or developed wound haematomas . Blood loss at operation was similar in all three groups . Three pulmonary emboli were diagnosed by pulmonary scintigraphy , one in each group Objective To compare the effectiveness and safety of low-dose unfractionated heparin and a low-molecular-weight heparin as prophylaxis against venous thromboembolism after colorectal surgery . Methods In a multicenter , double-blind trial , patients undergoing resection of part or all of the colon or rectum were r and omized to receive , by subcutaneous injection , either calcium heparin 5,000 units every 8 hours or enoxaparin 40 mg once daily ( plus two additional saline injections ) . Deep vein thrombosis was assessed by routine bilateral contrast venography performed between postoperative day 5 and 9 , or earlier if clinical ly suspected . Results Nine hundred thirty-six r and omized patients completed the protocol and had an adequate outcome assessment . The venous thromboembolism rates were the same in both groups . There were no deaths from pulmonary embolism or bleeding complications . Although the proportion of all bleeding events in the enoxaparin group was significantly greater than in the low-dose heparin group , the rates of major bleeding and reoperation for bleeding were not significantly different . Conclusions Both heparin 5,000 units subcutaneously every 8 hours and enoxaparin 40 mg subcutaneously once daily provide highly effective and safe prophylaxis for patients undergoing colorectal surgery . However , given the current differences in cost , prophylaxis with low-dose heparin remains the preferred method at present Deep vein thrombosis and its sequel , pulmonary embolus , are possibly the greatest threats to recovery after surgical operation . In a r and omized , controlled clinical trial in which the 125I-fibrinogen uptake test , Doppler ultrasound , and phlebography were used for diagnosis , it was found that low doses of calcium heparinate administered subcutaneously and sodium pentosan polysulfate intramuscularly were effective in preventing deep vein thrombosis ( DVT ) , postoperatively . The incidence of DVT was as follows : 9 % in the group treated with heparinate ; 15 % in the group treated with sodium pentosan polysulfate ; nad 51 % in the untreated control group BACKGROUND Various studies have been performed in general surgery patients comparing low molecular weight heparin ( LMWH ) with st and ard heparin ( SH ) for the prevention of postoperative deep vein thrombosis ( DVT ) , revealing contradicting results . Therefore , we have compared the efficacy and safety of a LMWH for the prevention of DVT after major general surgery . PATIENTS AND METHODS Patients received either 20 mg LMWH ( enoxaparin ) once daily , or 5,000 IU SH TID , starting preoperatively in a prospect i ve , r and omized , double-blind international multicenter trial . DVT was diagnosed using fibrinogen I 125 leg scanning . Major and minor bleeding were assessed clinical ly . RESULTS A total of 718 patients were r and omized to LMWH , and 709 patients to SH . DVT was detected in 58 LMWH-treated patients ( 8.1 % , 95 % confidence interval [ CI ] 6.2 % to 10.3 % ) and in 45 patients allocated to SH ( 6.3 % , 95 % CI 4.7 % to 8.4 % , P > 0.05 ) . Major bleeding complications occurred in 11 LMWH-treated patients ( 1.5 % , 95 % CI 0.8 % to 2.7 % ) and in 18 patients to whom st and ard heparin was administered ( 2.5 % , 95 % CI 1.5 % to 3.9 % , P > 0.05 ) . Four LMWH-treated patients ( 0.6 % ) required reoperation for bleeding as compared to 13 patients in the SH group ( 1.8 % , P = 0.03 ) . CONCLUSION This LMWH appeared as effective and safe as SH . In view of its more convenient way of administration , this LMWH might be preferred for thromboprophylaxis We have used the 125I-fibrinogen test to asses the value of an improved method of peroperative intermittent calf compression as a prophylactic measure against postoperative thrombosis . In a group of 99 patients over the age of 40 undergoing operations lasting more than 30 minutes the technique reduced the incidence of postoperative thrombosis by over 75 % . In patients suffering from malignant disease , who are generally considered to be in the very high risk category , the reduction achieved was almost 90 % One hundred ninety-four patients undergoing elective general abdominal surgery were r and omized in a single-blind study to receive one daily subcutaneous injection of a low-molecular-weight heparin , dalteparin sodium ( 2500 IU , n = 97 ) or nadroparin calcium ( 3075 IU , n = 97 ) , two regimens that are approved in Europe to prevent deep venous thrombosis . On the eight postoperative day , bilateral ascending leg phlebography ( n = 185 ) showed the presence of deep venous thrombosis in 45 cases ( 24.3 % ; 95 % confidence interval , 18 % to 31 % ) , with a significantly higher rate ( on intention-to-treat ) among the patients who received the lower dosage ( 30 vs 15 deep venous thromboses ) . We conclude that the two regimens of low-molecular-weight heparin that were used in this study failed to prevent postoperative phlebographically proved deep venous thrombosis in one of four patients A prospect i ve , r and omized , controlled clinical trial was performed comparing the antithrombotic efficacy of the low molecular weight heparin LMWH 21–23 , ( Braun ) with an unfractionated heparin in elective general surgical patients over an observation period of 7 postoperative days . A total of 230 patients were admitted : 103 ( group I ) received low molecular weight heparin and 100 ( group II ) low-dose unfractionated heparin treatment given subcutaneously . In group I 41 patients ( 46 % ) were operated on for malignant disease and in group II 54 patients ( 54 % ) . Due to the large amount of great abdominal procedures the intra- and perioperative application of hydroxyethyl starch was allowed for volume substitution . None of the patients died due to fatal pulmonary embolism . In group I four patients revealed positive 125I-labeled fibrinogen uptake ( 3.9 % ) ; two patients belonged to the hydroxyethyl starch subgroup . In group II five patients displayed a positive fibrinogen uptake ( 5 % ) ; two belonged to the hydroxyethyl starch subgroup . The results of the hemostaseological investigations ( e.g. , prothrombin time , activated partial thromboplastin time , thrombin clotting time , fibrinogen , antithrombin III , protein C , plasminogen , α2-antiplasmin , tissue-type plasminogen activator , plasminogen activator inhibitor ) revealed no statistically significant differences between groups I and II or their subgroups , although a tendency to prolonged clotting times was observed . The antifactor Xa activity values , however , displayed a statistically significant difference between the two groups ( P < 0.05 ) . The antifactor Xa activity measured up to 0.16 U/ml for the low molecular weight heparin ( group I ) and 0.05 U/ml for the unfractionated heparin ( group II ) in the postoperative period . Major bleeding complications were not encountered in this study . Fundamental for the low incidence of thrombosis , the additive administration of hydroxyethyl starch appeared in almost one-third of the patients in both study groups The etiology of postoperative deep venous thrombosis ( DVT ) is thought to be due to a combination of factors including stasis , a hypercoagulable state and venous endothelial damage . Methods of prophylaxis are directed toward correcting one or more of these pathologic events . Methods counteracting more than one of these factors can be expected to be even more effective . The combination of dihydroergotamine ( DHE ) and heparin was anticipated to minimize stasis and the hypercoagulable state respectively . Based upon current experimental evidence and current theory , an additional benefit might include minimizing venous endothelial injury by controlling venomotor tone . A prospect i ve , r and omized , double-blind , multicenter trial was design ed and performed in the United States evaluating the prophylactic efficacy of DHE 0.5 mg plus heparin 5000 U , DHE 0.5 mg plus heparin 2500 U , heparin 5000 U , and DHE 0.5 mg versus placebo . General surgical patients including those undergoing noncardiac thoracic and pelvic operations who were identified at moderate to high risk for postop DVT were included . Study medications were injected subcutaneously two hours preoperatively and every 12 hours postoperatively for 5 - 7 days or until the 125I-fibrinogen-uptake test ( RFUT ) became positive . Eight hundred and eighty eight patients were entered into this trial and 744 ( 85 % ) completed the study . Results showed a statistically significant benefit from DHE/Hep 5000 compared to placebo ( p less than 0.01 ) and compared to other active agents ( p less than 0.05 ) . None of the other active agents showed a statistically significant prophylactic benefit . ( ABSTRACT TRUNCATED AT 250 WORDS Purpose : to evaluate the accuracy of triplex ultrasound ( TUS ) compared with venography as a screening test for deep venous thrombosis ( DVT ) , and to evaluate interobserver variation in the interpretation of the venographic studies . Material and Methods : A total of 133 postoperative hip fracture patients , asymptomatic of DVT , were prospect ively examined with TUS and venography . All venograms were review ed blindly and in case of disagreement a consensus was arrived at . Results : the incidence of DVT was 20 % , with isolated calf vein thrombi in 63 % of the cases . There were 7 false-negative and one false-positive result /s at TUS , with a sensitivity of 74 % , specificity of 99 % and accuracy of 97 % . the kappa values ranged from 0.58 to 0.82 . the false-negative results were all caused by missed calf vein thrombi in technically inadequate examinations . at sonography 2 % of vein segments were noninterpretable , compared to 29 % at venography . Conclusion : Venous US is less sensitive as a test for DVT in this study of asymptomatic patients than in earlier studies on symptomatic patients . Still , sonographic screening of high-risk patients would be both effective and cost effective . Fresh thrombi may cause a false-negative compression test In this prospect i ve r and omized double-blind study the thromboprophylactic effect of postoperative low molecular weight heparin ( tinzaparin ) was compared with placebo in 80 patients undergoing emergency abdominal surgery . The fibrinogen uptake test was used but because of withdrawal of the labelled fibrinogen from the market the calculated number of patients was not reached . However , this is one of the few studies in emergency abdominal surgery we thought it important to report . The frequency of deep vein thrombosis was reduced with prophylaxis from 22 % ( 95 % conf . intervall 11 - 38 % ) to 8 % ( 2 - 21 % ) , a risk reduction of 65 % , which is however not significant . Together with data from the few previously published studies it can be concluded that patients undergoing emergency abdominal surgery seem to benefit from prophylaxis , which should be instituted either before operation or at latest 24 hours after . The exact prophylactic relation between pre- and post-operative start would , however , require a separate , r and omized study This study was design ed to prospect ively evaluate a previously published prognostic index for predicting deep venous thrombosis ( DVT ) in general surgical patients with conventional prophylaxis . Patients undergoing procedures of at least 1 hr duration ( abdominal , thoracic , head and neck , inguinal ) requiring general or spinal anesthetic were prospect ively r and omized into the following groups : Group 1 , sequential pneumatic compression devices during surgery and 2 days postoperatively ; Group 2 , subcutaneous heparin ( 5000 U q 12 hr ) starting 1 hr before surgery and for 7 days postop ; Group 3 , control group . All patients underwent duplex evaluation of bilateral lower extremity deep venous systems preoperatively and on postoperative Days 1 , 3 , and 30 . In addition , a previously developed predictive DVT incidence indicator , the prognostic index ( PI ) , was calculated for each patient . A total of 137 patients were entered into the study with 29 removed for patient/staff reasons . There were no differences in PI among the three groups at the 0.05 level ( ANOVA ) . The distribution of risk factors for DVT including increased age , body size , hemoglobin ( Hb ) , and colorectal procedures were distributed evenly among the groups . Additional factors such as diabetes , COPD , PVD , immobilization , and cancer were also evenly distributed among the groups . The PI predicted a 20 % incidence of DVT . For Groups 1 ( n = 25 ) , 2 ( n = 38 ) , and 3 ( n = 45 ) no DVTs were detected over the 30 days of study . During the study period , 8 DVTs were detected by duplex evaluation in general surgical patients not in the study ( 1.5 % ) . In conclusion , in a prospect i ve r and omized study using sequential pneumatic compression devices , subcutaneous heparin or no prophylaxis in matched general surgical patients at moderate to high risk for thromboembolism , no DVTs occurred for up to 30 days . Furthermore , neither a PI nor other factors associated with DVT accurately predicted the incidence of DVT in this patient population The efficacy of dextran-40 infusions or low-dose heparin or xantinol-nicotinate administration in preventing postoperative thromboembolic complications has been investigated in a prospect i ve , controlled , r and omised trial as part of an international multicentre trial . 382 patients over the age of forty years undergoing elective major general surgery were investigated ; 100 had a complete protocol in the control , 94 in the heparin , 92 in the dextran , and 32 in the xantinol-nicotinate group . 31 patients died : 13 in the control group , 10 in the heparin group , 6 in the dextran group , and 2 in the xantinol-nicotinate group . In 4 controls , 6 in the heparin group , and 1 in the dextran group the cause of death was acute pulmonary embolism . 4 further controls , 1 in the heparin group , and 2 in the dextran group had emboli found at necropsy , which either contributed to the deaths or were incidental findings . The distribution of pulmonary emboli in this study did not show the difference between the control and the heparin group reported in the multicentre trial . The 125I-fibrinogen test was done in all patients . The frequency of isotopic deep-vein thrombosis was 36 - 0 % in the controls , 12 - 8 % in the heparin group , 21 - 7 % in the dextran group , and 40 - 6 % in the xantinol-nicotinate group . The difference between the controls and the heparin groups was highly significant and between the control and the dextran group , probably significant . There were significantly more side-effects in the heparin group than in the dextran group The frequency of deep venous thrombosis ( DVT ) was studied in 98 patients undergoing major abdominal surgery . All the patients received low dose heparin prophylaxis 5000 i.u . every 12 h for 5–7 days . In each patient , a graduated compression stocking was also worn and r and omly allocated to one of the legs and the other leg served as a control . DVT was diagnosed by the 125I‐fibrinogen method . Four patients developed bilateral DVT and 8 patients unilateral DVT , all of whom developed it in the control leg . The difference in unilateral DVT between stockinged and control legs was significant ( P < 0·004 ) . It is concluded that a combination of low dose heparin and graduated compression stockings is more effective than low dose heparin alone in reducing the frequency of postoperative DVT . It is suggested that this combination of prophylaxis might be of value in high risk patients The efficacy and safety of a low‐molecular‐weight ( LMW ) heparin fraction in preventing postoperative venous thrombo‐embolism , was assessed in a double blind , r and omly allocated trial , and in an ‘ open ’ study . of 395 patients included in the double blind trial , 199 received unfractionated ( UF ) calcium heparin , and 196 the LMW heparin fraction . The data were analysed on an ‘ intention to treat ’ basis . The two groups were well matched for risk factors which could predispose to the development of venous thrombosis . Fifteen ( 7.5 per cent ) of one hundred and ninety‐nine patients receiving UF heparin , and five ( 2.5 per cent ) of one hundred and ninety‐six patients in the LMW heparin group developed DVT ( P<0.05 ) . There was no significant difference between the two groups in terms of excessive incisional or total blood loss during surgery , postoperative drainage or wound haematoma formation . Of 910 patients included in the ‘ open ’ study who received a single injection of LMW heparin every day , 30 ( 3.2 per cent ) died during the postoperative period ; in none of the autopsied patients were pulmonary emboli detected . Thirty‐one ( 3.4 per cent ) patients developed isotopic DVT ; twentyseven ( 2.9 per cent ) were receiving prophylaxis at the time the DVT was diagnosed . Thirty‐six ( 3.9 per cent ) patients developed wound haematoma ; twenty‐five ( 12.4 per cent ) of those were in the two hundred and one undergoing surgery for gynaecological conditions , and eleven ( 1.5 per cent ) in the seven hundred and nine patients having general abdominal surgery . This difference is statistically significant ( P<0.001 ) . The results of a double blind trial indicate that a single daily injection of 1850 APTT units ( 7500 antifactor X a units ) of a LMW heparin is more effective than 10000 APTT units of commercially available UF heparin in preventing postoperative DVT . The findings of the ‘ open ’ study suggest that this regimen also provides an effective prophylaxis against postoperative major pulmonary embolism Abstract In a double-blind investigation thromboembolic prophylaxis with subcutaneous low-dose heparin was studied in 112 patients admitted for elective major surgery . Pulmonary embolism was diagnosed by photoscanning on the third or fourth day after operation , and plain chest X-rays were taken simultaneously . Deep vein thrombosis ( D.V.T. ) was detected by the 125 I-fibrinogen leg scanning technique . 58 patients were treated with heparin , each receiving 5000 units every 12 hours for 5 days , starting 2 - 5 hours before operation . In this group 11 patients ( 19 % ) had pulmonary embolism and /or D.V.T. Of the 54 patients in the control group 30 ( 56 % ) had pulmonary embolism and /or D.V.T. Thus low doses of heparin reduce the incidence of tromboembolism after major surgery Eighty patients undergoing pelvic or abdominal surgery for cancer were r and omized in two groups for prevention of postoperative thromboembolism : 40 patients received a 15,000 IU day-1 Calciparine prophylaxis and 40 patients a 5000 anti-Xa U/d Fragmin prophylaxis for 10 days . In the Calciparine group , two patients ( 5 % ) developed postoperative pulmonary embolism but none developed it in the Fragmin group . Two patients in the Fragmin group ( 5 % ) developed isotopic DVT , which was not confirmed by phlebography . There was no deep vein thrombosis of the lower limbs in the two groups . Important postoperative bleeding ( one patient in the Calciparine group and two patients in the Fragmin group ) was similar in both groups . Moderate and minor bleeding were significantly lower in the Fragmin group . Haemoglobin and haematocrit changes , total blood loss and transfusion requirements were not different in both groups . It is concluded that , over a 10-day period , one daily 5000 U Fragmin prophylaxis was as effective and safe as three daily 5000 IU Calciparine injections A total of 1290 patients were enrolled in a r and omized multicentre double blind study in order to investigate the use of two doses of a new low molecular weight heparin , Logiparin ® , in the prevention of deep vein thrombosis ( DVT ) in general surgery . Patients who were included had no contraindication to heparin therapy and had at least one of the recognized risk factors for DVT . Patients were r and omized to receive unfractionated heparin ( UH ) 5000 units b.d . , Logiparin 2500 units daily or Logiparin 3500 units daily . Each treatment was given subcutaneously 2h before surgery and continued for 7–10 days . Daily 125I‐labelled fibrinogen uptake tests ( FUTs ) were performed from day 2 to day 7 to detect DVT , and phleboangiography was used to confirm the diagnosis . The wound was examined on a daily basis to check for haematoma formation , and all patients were followed up for 1 month after operation . All three treatment arms were well matched for age , sex , weight , diagnosis and type of operation performed . The three major inclusion criteria in the trial were malignancy , age over 60 years and a history of varicose veins . Positive FUTs ( UH=4·2 per cent , Logiparin 2500 units daily = 7·9 per cent , Logiparin 3500 units daily = 3·7 per cent ) and positive angiograms ( UH=3·0 per cent , Logiparin 2500 units daily = 5·6 per cent , Logiparin 3500 units daily = 2·3 per cent ) were significantly more common in the Logiparin 2500 units daily group than in the UH and Logiparin 3500 units daily groups . The rates of major complications ( severe haemorrhage , death , pulmonary embolism , reintervention ) were similar in the three groups The effectiveness of low-molecular weight heparin CY 216 in the prophylaxis of fatal pulmonary embolism in patients undergoing general surgery was assessed in a multicentre , double-blind , r and omized , clinical trial against placebo . A total of 4,498 patients aged over 40 undergoing general surgery were enrolled in the 18 centres which took part in the trial . Patients received a single daily subcutaneous injection of 7,500 anti-Xa units I.C. of CY 216 or placebo two hours before surgery , 12 hours after the initial injection and then daily for at least seven days . A post-mortem examination had to be carried out in every patient who died . The two groups of patients were well-matched for age , sex , type of disease , site and duration of operation as well as for incidence of risk factors which could predispose to the development of thromboembolism . Twenty-six deaths were recorded and vali date d : eight ( 0.36 % ) in the CY 216 group and 18 ( 0.80 % ) in the placebo group ( p less than 0.05 ) . At the post-mortem examination , carried out in 23 patients ( 88.5 % ) , two deaths were found to be directly due to pulmonary embolism ( 0.09 % ) in the CY 216 group and four ( 0.18 % ) in the placebo group . Pulmonary embolism contributed to death in four other placebo-treated patients . Pulmonary or extrapulmonary thromboembolism was a significantly less frequent direct cause of death ( p less than 0.05 ) in the CY 216 group ( two pulmonary embolisms ) than in the placebo group ( four pulmonary embolisms , one acute myocardial infa rct ion , one disseminated intravascular coagulation , two ischemic cerebral strokes ) . ( ABSTRACT TRUNCATED AT 250 WORDS This double-blind , r and omised , multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis ( VT ) prophylaxis using 750 anti-factor Xa units of Orgaran ( a mixture of low molecular weight heparinoids ) given subcutaneously ( sc ) twice-daily with that of twice-daily injections of 5,000 units st and ard heparin . The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning , and the onset of clinical ly significant venous thromboembolism or bleeding . " Intent to treat " analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis ( 10.4 % ) than after heparin ( 14.9 % ) and there was no difference in bleeding complications between the two study groups . Results remained similar if only patients who completed the intended course of therapy ( " compliant patients ") were analysed . Other trials have shown that Orgaran prevents VT after hip surgery and stroke . We now show it is also safe and effective in patients having major surgery for cancer In a double blind r and omized trial on 250 patients undergoing elective abdominal surgery the effect of Fragmin was compared with heparin . Patients over 40 years of age except appendectomy and herniotomy were included . The dose of heparin was 5,000 IU b.i.d . whilst Fragmin was given in a dose of 2,500 U once per day and the second injection was a placebo . Prophylaxis started 2 h preoperatively and was maintained for 7 days . The fibrinogen uptake test was used as a screening method for thrombosis which was confirmed by phlebography . 124 patients were in the heparin group and 126 in the Fragmin group . Comparability between groups was found in : age , sex , Broca index , amount and type of risk factors , type of surgery . Thromboembolism was found in 10 cases in each group . Blood transfusions on the postoperative days 1 to 6 were required in 2 Fragmin and in 12 heparin patients . The total amount of blood given during that time was 6 units in the Fragmin and 37 units in the heparin group . These differences were significant BACKGROUND During surgery , the balance between thrombosis and fibrinolysis is altered . Methods reported to increase fibrinolysis , such as compression devices , may reduce venous thrombosis . However , there are no prospect i ve studies comparing methods and the effect on fibrinolysis . MATERIAL S AND METHODS In a prospect i ve study , general surgical patients were r and omized to either sequential compression devices ( Group 1 ) or subcutaneous heparin ( Group 2 ) , and fibrinolysis factors were measured in order to determine the effect on the fibrinolysis system . Blood sample s were drawn at a similar time of the day with the tourniquet off . Specifically , t-PA antigen , plasminogen activator inhibitor-1 ( PAI-1 ) , and D-dimer were measured preoperatively ( preop ) and on Postoperative Days ( POD ) 1 and 7 by the ELISA method . Fibrinolysis factors were reported as the mean + /- SD and as percentage change from preoperative values . Noninvasive vascular studies were performed preop , and on POD 1 , 7 , and 30 , by an examination of the infrainguinal venous system and external iliac veins in bilateral lower extremities . Nonambulatory patients were excluded from the study and DVT prophylaxis methods were initiated at surgery and used through POD 2 . RESULTS For the 136 patients in the study , there were no differences in clinical characteristics such as age , surgical time ( all > 60 min ) , anesthesia type ( general or spinal ) , type of surgical procedure , or other risk factors for DVT . Two DVTs occurred at POD 1 and 30 ( both Group 2 ) , and one pulmonary embolism in each group ( POD 7 for Group 1 ; POD 1 for Group 2 ) . For subjects without thrombosis , D-dimer changes were parallel for both groups , increasing through POD 7 . Similarly , t-PA antigen levels rose from baseline on POD 1 in both groups , with a return toward baseline by POD 7 . The PAI-1 levels increased on POD 1 in both groups , but severalfold more in Group 1 ( compression devices ) . The elevation in PAI-1 decreased by 50 % in Group 1 by POD 7 , while values returned to normal in Group 2 . These changes were not significant using the Mann-Whitney test . Only three patients had thrombotic episodes so that data on changes in fibrinolysis factors are difficult to compare with the larger group . CONCLUSIONS This is the first report of a prospect i ve , r and omized comparison of fibrinolysis factors using sequential compression devices in comparison to low dose unfractionated heparin in general surgical patients , and comparing postoperative values to preop . Both groups showed an enhanced fibrinolysis by elevation in t-PA antigen and D-dimer on POD 1 , as expected when fibrinolysis occurs . While PAI-1 and t-PA work in parallel , the marked elevation of PAI-1 on POD 1 ( although only slightly above reference values ) and continuing into POD 7 for subjects using compression devices requires further inquiry . The elevation of PAI-1 in the face of elevated t-PA and D-dimer has been reported , but the comparison between patients using sequential compression devices and mini-dose heparin has not been reported . The reason for the elevation requires additional study into other influences on the synthesis , secretion , and /or function of PAI-1 that do not affect t-PA In an open controlled study , 248 consecutive patients ( age more than 40 yrs ) admitted for major abdominal surgery were r and omized to one of three prophylactic antithrombotic treatments . Eighty-five patients received subcutaneous heparin , 74 patients had graduated compression stockings to the knee ( TED stockings ) , and 89 patients had both subcutaneous heparin and stockings . Treatment began on the evening before operation and continued to complete mobilization , or for not less than five days postoperatively . On the fourth or fifth postoperative day , the patients underwent a 99mTc-plasmin test of the lower limbs as a test for deep vein thrombosis . There were 29.7 % positive tests in the stocking group , 29.4 % in the group with heparin prophylaxis , and 25.8 % in the combined group . Differences between treatments were not statistically significant A prospect i ve r and omized trial is described in 119 patients undergoing major abdominal general surgical procedures . Half of the patients were treated prophylactically with intermittent pneumatic calf compression , begun after the induction of anesthesia and continued until the patient was walking ; the other half acted as controls . Deep venous thrombosis was detected by iodine-125 fibrinogen scanning and confirmed by venography , and did not differ significantly in the control and treated groups . One fatal pulmonary embolism occurred in each group . The presence of malignancy of the gastrointestinal tract did not influence the results . The findings suggest that pneumatic compression delayed the development of deep venous thrombosis postoperatively and that perhaps it should be continued until discharge from hospital One hundred fifty patients over the age of 30 who had undergone major abdominal operations were stratified according to the risk of deep venous thrombosis and r and omized into three groups to receive different prophylactic regimens : group A , electrical calf stimulation ; group B , low-dose subcutaneous heparin ; group C , intermittent sequential compression and thromboembolism-deterrent ( TED ) stockings . All the patients were scanned with the 125I-fibrinogen test for the whole stay in hospital . The incidence of 125I-fibrinogen detected deep venous thrombi was 18 % in group A , 9 % in group B , and 4 % in group C. The results indicate that the regimen of intermittent sequential compression and TED stockings is as effective as low-dose subcutaneous heparin . Electrical calf stimulation is less effective In a r and omized , controlled clinical trial of two methods of preventing postoperative leg vein thrombosis patients undergoing major surgery were divided into three groups . One received intermittent electrical calf muscle stimulation during surgery , the second subcutaneous heparin calcium 5000 IU every eight hours for six days , and the third no specific prophylaxis . Leg vein thrombosis was detected by the 125-I-fibrinogen uptake test . Neither method was effective in patients undergoing open bladder or prostatic surgery . Stimulation did not reduce the incidence of leg vein thrombosis in patients with malignant disease undergoing laparotomy , but heparin calcium was highly successful in this group ( P smaller than 0 - 001 ) . When the laparotomy was for a benign condition , however , both heparin calcium ( P smaller than 0 - 001 ) and stimulation ( P smaller than 0 - 01 ) were effective 2136 patients in general surgery , gynaecology and urology were investigated by the 125I-fibrinogen-uptake-test for detection of postoperative deep vein thrombosis ( DVT ) . They received at r and om one of low-dose heparin , dihydroergotamine , the fixed combination of both drugs ( Heparin-Dihydergot ) , low molecular weight dextran and acetylsalicylic-acid ( ASS ) . When DVT was detected repeated lung perfusion scintigraphies were carried out for diagnosis of embolic pulmonary perfusion defects . Results demonstrate the outst and ing effect of Heparin-Dihydergot , which is not only 2 - 3 times better than the anti-thrombotic st and ard low-dose heparin but also eliminates almost completely the risk of postoperative embolism . The preventive efficacy of ASS and dextran must be considered to be poor and not comparable to that obtained when using heparin , dihydroergotamine or the combination . Now Heparin-Dihydergot is the new st and ard with which all prophylactic procedures should be compared Three consecutive r and omized open studies have been carried out to determine the optimal dosage of low molecular weight heparin ( LMWH ) in the prevention of postoperative thrombosis in general surgery ( 892 patients ) . All patients undergoing abdominal , gynaecological , thoracic or urological surgery were over 40 years old and presented at least one of the following risk factors for thrombosis : previous thromboembolism , obesity , varicose veins , malignancy ( 30 per cent ) , pre‐operative hospitalization over 5 days , oestrogen therapy , chronic cardiac disease or bronchitis . Isotopic venous thrombosis and bleeding complications were assessed after subcutaneous administration of a LMWH fragment ( LMWH , Enoxaparine ) or unfractionated heparin ( UH ) . The three studies compared 3 × 5000 units UH daily with 1 × 60 mg , 1 × 40 mg , 1 × 20 mg LMWH daily . Thromboembolic events rates were not significantly different from group to group ( UH : 3.8 per cent , 2.7 per cent , 7.6 per cent respectively compared with LMWH : 2.9 per cent , 2.8 per cent , 3.8 per cent ) . Bleeding episodes including wound haematoma formation , perioperative blood losses and systemic haemorrhage were not significantly different in patients receiving LMWH or UH . Significant decreases in haematocrit and haemoglobin were only observed in patients receiving 60 mg Enoxaparine ( as compared to UH ) . An analysis using the ‘ intention to treat ’ approach gave results consistent with those of an analysis of good compliers . An overview of isotopic thromboses in the three studies gave no evidence of differences amongst the effects of the three doses of LMWH ( P = 0.20 ) , and pooling the results of the three studies using the Mantel‐Haenszel procedure gave no evidence of a global difference between Enoxaparine and UH ( P = 0.54 ) . These results suggest that an optimal dosage of 20 mg/day of Enoxaparine is safe and effective in the prevention of postoperative thrombosis in this population The effect of sequential pneumatic leg compression on venous flow velocity was studied in 25 patients . At the usual pressures of 35 to 55 mm Hg , venous flow velocity was only 175 percent of the control value , but 366 percent when pressures were between 90 and 100 mm Hg . The incidence of post-operative thrombosis was studied in three groups of patients . In 24 patients receiving sequential compression prophylaxis of 90 to 100 mm Hg , there was one case of thrombosis , whereas there were three cases among the 25 patients with compression of 35 mm Hg and three cases among the 25 patients receiving 5,000 units of heparin three times per day . Sequential intermittent compression with high pressures , 10 compression cycles three times daily , is recommended for all patients unable to undertake physically active prophylactic measures . An absolute indication exists in those patients who can not be mobilized and those in whom there are additional contraindications to the use of anticoagulants . Sequential compression is no alternative to antithrombosis stockings which must be worn from the day of hospitalization until discharge and also during the period of pneumatic compression One hundred five patients over age 40 undergoing various major operations were r and omly divided into control and treated groups ; all were treated by subcutaneous injection containing either 5,000 international units aqueous heparin sodium or a placebo one hour prior to operation and every 12 hours thereafter for eight days . Deep vein thrombosis ( DVT ) was detected by daily -125I-fibrinogen injection and leg scanning , and confirmed by ascending phlebography . Both groups were comparably distributed by age , sex , variety of operation , incidence of previous thromboembolism , and myocardial and cerebrovascular disease . Blood loss was not increased in the treated group . Incidence of DVT was 8.6 percent for the total group , 7.5 percent in the heparin-tested group ( four of 53 ) , and 9.6 percent in the control group ( five of 52 ) , including one control patient with a normal scan ( who later had a pulmonary embolus 1 . The effectiveness of 3 X 5000 IU s. c. heparin daily ( starting preoperatively ) for the prevention of postoperative deep vein thrombosis was evaluated in a prospect i ve , controlled , r and omized study including general surgical and urological patients . 125I-fibrinogen test was performed daily in all patients . 2 . 178 patients fulfilled the conditions of the protocol . 35.8 % of the 95 patients in the control group developed deep vein thrombosis , but only 13.3 % of 83 subjects in the heparin group did so . The difference is statistically highly significant ( p less than 0.001 ) . 3 . The vast majority of all thrombi in both groups appeared before the 3rd postoperative day . 4 . With 1 exception , all deep vein thrombi in the heparin group started in the mid-calf region . In the control group 5 deep thrombi originated in the popliteal vein . 5 . Heparin displays a better effect in males ( n = 34 ; p less than 0.01 ) than in females ( n = 49 ; p less than 0.025 ) . 6 . In patients undergoing surgery for malignant disease heparin does not reduce the incidence of deep vein thrombosis . 7 . Heparin is far more effective in patients under 60 years of age than in those over 60 ( p less than 0.005 ) . 8 . Heparin is more effective in obese patients than in those of normal body build . 9 . Heparin prophylaxis also reduces the incidence of deep vein thrombosis in patients who exhibit predisposing factors . In patients of the control group with preexisting disease of the venous system , there were significantly more deep vein thrombi ( p less than 0.01 ) than in those without predisposing factors . 10 . In the heparin group 29 % of all thrombin time determinations show a definite prolongation of more than 26 sec ( normal value 15 sec ) . 11 . In 14 patients ( = 16.9 % ) of the heparin group , 21 side effects or complications were seen . Bleeding complications were the main problem , comprising 5 wound hematomas and hematomas at the injection site , 4 postoperative bleeding episodes and 2 reoperations . There were no complications in the control group . 12 . According to the results of 10 well controlled studies , there is no doubt that in general surgery small doses of subcutaneous heparin , commencing preoperatively , do reduce the incidence of postoperative deep vein thrombosis to a significant degree . However , whether this form of prophylaxis is also effective in patients with fractures of the hip and in elective hip surgery can not , on the evidence available , be decided . In the fields of gynecological surgery and urology as well , more data are needed before this form of heparin prophylaxis can be recommended Sixty-one consecutive patients were enrolled in a r and omized , controlled trial of thromboprophylaxis with a low molecular weight heparin ( Seleparina , CY 216 ) in major abdominal oncological surgery . Thirty patients received 2 x 3,825 anti-Xa international units of CY 216 subcutaneously on the day of surgery followed by a single daily 3,825 anti-Xa international units injection for 7 days ; thirty-one patients did not receive any form of prophylaxis . The occurrence of deep vein thrombosis ( DVT ) was detected by 125I-labelled fibrinogen leg scan . Postoperative DVT developed in 2 patients in the CY 216 group and in 11 patients in the control group ( 6.8 % vs 35.4 % , p < 0.01 ) . Although there was a higher postoperative transfusional requirement in the group receiving CY216 ( p < 0.05 ) , the total number of patients transfused was similar in the two groups ( 14 vs 13 ) . On day 1 after surgery , the two patients who later developed DVT in the CY216 group had plasma anti-Xa activity significantly lower ( p < 0.01 ) than the remaining patients . As a good relationship was found between plasma anti-Xa activity and body weight , adoption of a personalized dosage schedule might improve efficacy of CY 216 prophylaxis In a r and omized double-blind study of 660 patients with predominantly abdominal-surgical procedures the thrombosis-preventing effect of the following was compared : heparin 5000 ( low-dose heparin ) , heparin 2500 , a combination of heparin 2500 and 0.5 mg dihydroergotamine ( HDHE 2500 ) , 0.5 mg dihydroergotamine ( DHE ) , and placebo . All preparations were administered three times daily . Radiofibrinogen test gave the following thrombosis incidence : heparin 5000 - 15.4 % ; heparin 2500 - 24 % ; HDHE 2500 - 13.2 % ; DHE-24.6 % ; placebo-28.9 % . Bleeding complications , included postoperative blood loss ( more than 500 ml ) , unusually marked bleeding from drains , seroma , wound haematoma , and re-operation . The rate of these complications was 18.5 % with heparin 5000 , 7.8 % with placebo , 5.6 % with DHE , 4 % with heparin 2500 and 3.1 % with HDHE 2500 . The non-specific tolerance to the various preparations was good , especially in that there was no increased risk of coronary complications with HDHE or DHE , and there was no pointer to peripheral vasospasms . This study confirms the synergistic thrombosis-preventing effect of combined heparin-dihydroergotamine DVT is a very frequent complication of general surgery . Heparin and , more recently , LMWHs can successfully prevent post surgical thromboembolism . One thous and one hundred and twenty-two patients ( 533 males and 589 females ; mean age 62.2 + /- 11.4 yrs ) were enrolled in a multicentre controlled study , to evaluate the efficacy and safety of enoxaparin in comparison to calcium heparin in the prevention of deep venous thrombosis ( DVT ) following general surgery . Patients assigned to the enoxaparin and the calcium heparin groups received 1 daily dose of 20 mg ( 2000 I.U. ) and 2 daily doses of 0.2 ml ( 5000 I.U. ) , respectively starting 2 hours before the operation . Both drugs were given by subcutaneous route . A Doppler or Duplex Scan diagnosis of DVT was made in 3 ( 0.5 % ) patients in the enoxaparin group ( 2 cases during treatment and 1 patient at the end of treatment ) and in 6 ( 1.1 % ) patients in the calcium heparin group ( 5 cases during treatment and 1 , bilateral , after the end of treatment ) . Pulmonary embolism ( PE ) was ascertained by angiography in 1 patient ( 0.18 % ) in the enoxaparin group and in 2 patients ( 0.36 % ) in the calcium heparin one . Hemorrhagic complications occurred in 29 patients ( 5.2 % ) in the enoxaparin group and in 34 ( 6.1 % ) in the calcium heparin group . Haematomas located in the injection site were reported in 16.1 % and 25.3 % in the enoxaparin and calcium heparin groups respectively ( p = 0.0001 ) . Local pain in the injection site at the 5th day of treatment was reported in 8.4 % and 16.6 % in the enoxaparin and calcium heparin groups respectively ( p = 0.0001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS The safety and efficacy of a low molecular weight heparin fragment Kabi 2165 , given in the dose 2,500 anti-Xa units once daily , in preventing postoperative venous thromboembolism , was assessed against calcium heparin in the dose 5,000 IU twice daily , in a multicenter double blind r and omized study . On an intention to treat basis 385 patients scheduled for major surgery were included in this study . Six patients ( 3.1 % ) out of 195 developed isotopic DVT in the Kabi 2165 group . Corresponding figures for calcium heparin was 7 patients ( 3.7 % ) . There was no statistically significant difference between the two groups with respect to the bleeding variables ; blood loss during operation , postoperative drainage , blood transfusion , haemoglobin and haematocrit levels ; wound haematoma and haematoma at the injection sites . No patient had to undergo evacuation of wound haematoma or reoperation due to bleeding . It is concluded that one single daily injection of Kabi 2165 provides a convenient safe and effective prophylaxis against thromboembolism in general surgery A double-blind , placebo-controlled study was carried out in 100 patients undergoing major surgery to investigate the efficacy of a new low molecular weight heparin ( LMWH ) preparation in the prevention of deep venous thrombosis . Patients were allocated at r and om to receive either placebo or LMWH ( 7500 AXaU ) each day by subcutaneous injection ( abdominal fold method ) , starting 2 hours before the operation and continuing for the following 7 days . Clinical and laboratory tests revealed deep venous thrombosis in 3 ( 6 % ) patients in the placebo group whereas no thrombotic episodes were observed in any of the patients treated with LMWH . Blood loss during the peri-operative and post-operative period and the number of blood units transfused were not significantly different in the two groups . Moreover , no side-effects were revealed in the LMWH group that could be attributed to the drug Abstract The comparative effects of a combination of dipyridamole and aspirin ( D-ASA ) and of low doses of heparin ( H ) on the prophylaxis of deep venous thrombosis ( D.V.T. ) in abdominal surgery were studied . One hundred and forty six patients were r and omized into three groups : controls ( n = 66 ) , D-ASA ( n = 38 ) , H ( n = 42 ) . Dipyridamole ( 30 mg ) and ASA ( 300 mg ) were administered intra-venously two hours before surgery and then three times a day for the first 2–3 days . These drugs were then taken orally three times a day in tablets containing dipyridamole ( 50 mg ) and ASA ( 330 mg ) . Heparin ( 5000 IU ) was given subcutaneously twice a day . Treatment was begun two hours pre-operatively . D.V.T. was detected by the 125 I fibrinogen method . The treated groups , studied together , present a lower incidence of D.V.T. ( 8 % ) than the control group ( 21 % ) ( The prophylaxis of thromboembolism with Heparin-Dihydroergotamin was performed on 300 patients . The fundamentals of clinical studies were discussed The safety and efficacy of the low molecular weight heparin fragment ( Fragmin ) administered as a single daily injection of 2,500 anti Xa units has been evaluated in 183 patients undergoing major elective general surgery . The study was double-blinded and placebo controlled . The active agent , or placebo , was given subcutaneously with the preoperative medication and continued postoperatively for 5 - 9 days . Ninety five patients received Fragmin and 88 were r and omized to receive the placebo . The clinical characteristics of the two treatment groups were similar . Fragmin significantly reduced the incidence of deep venous thrombosis , as detected by a positive 125I fibrinogen leg scan , relative to the placebo treated patients ( 4/95 , 4.2 % v. 14/88 , 15.9 % ; p = 0.008 ) . The thrombotic events occurred predominantly ( 73 % ) amongst patients with malignancy . Haemorrhagic endpoints necessitating discontinuation of the trial treatment were 4 % in each group . No severe adverse reactions or drug related deaths occurred . These results indicate that 2,500 anti Xa units of Fragmin given only once daily is effective thromboprophylaxis for patients undergoing major elective abdominal surgery Abstract Objective : To determine the efficacy of antiplatelet therapy as prophylaxis against deep venous thrombosis or pulmonary embolism in surgical and high risk medical patients . Design : Overviews of all r and omised trials of antiplatelet therapy that could have been available by March 1990 and in which deep venous thrombosis was assessed systematic ally . Setting : 53 trials ( total 8400 patients ) of an average of two weeks of antiplatelet therapy versus control in general or orthopaedic surgery ; nine trials ( 600 patients ) of antiplatelet therapy versus control in other types of immobility ; 18 trials ( 1000 patients ) of one antiplatelet regimen versus another . Results : Overall , a few weeks of antiplatelet therapy produced a highly significant ( 2P < 0.00001 ) reduction in deep venous thrombosis . 25 % of patients allocated antiplatelet therapy versus 34 % of appropriately adjusted controls had deep venous thrombosis detected by systematic fibrinogen scanning or venography , representing prevention in about 90 patients per 1000 allocated antiplatelet therapy . There was an even greater proportional reduction in pulmonary embolism : such emboli were detected among 47 ( 1.0 % ) antiplatelet allocated patients versus an adjusted control total of 129 ( 2.7 % ) , representing prevention among about 17 patients per 1000 treated ( 2P < 0.00001 ) . In analyses confined to surgical trials , the proportional reductions were similar and separately significant for nonfatal pulmonary embolism ( 0.7 % antiplatelet therapy upsilion 1.8 % control ; 2P < 0.00001 ) and for deaths attributed to pulmonary embolism ( 0.2 % upsilion 0.9 % ; 2P = 0.0001 ) . There was a slight but non - significant excess of deaths from other causes ( 1.0 % upsilion 0.7 % ) , which made the difference in total mortality non-significant , though still favourable ( 1.2 % upsilion 1.5 % ) . Information on adding antiplatelet therapy to heparin was limited but , at least for pulmonary embolism , suggested more protection from the combination than from heparin alone . Conclusion : It had previously been supposed that antiplatelet therapy did not influence venous thromboembolism , and many surgeons and physicians do not use it routinely for thromboprophylaxis , even for patients who are at substantial risk of deep venous thrombosis or pulmonary embolism . These results indicate that antiplatelet therapy - either alone or , for greater effect , in addition to other proved forms of thromboprophylaxis ( such as subcutaneous heparin ) - should be considered |
11,765 | 24,142,059 | Results Continent women undergoing anterior compartment prolapse surgery have a lower rate of de novo stress urinary incontinence ( SUI ) after anterior repair than armed mesh procedures ( grade A ) .
Data are conflicting on whether colposuspension should be performed prophylactically in continent women undergoing sacral colpopexy ( grade C ) .
No clear conclusion can be made regarding the management of continent women undergoing prolapse surgery without occult SUI .
In continent women undergoing POP surgery with occult SUI the addition of continence surgery reduces the rate of postoperative SUI ( grade A ) .
In women with prolapse and SUI symptoms prolapse procedures alone ( transobturator mesh and anterior repair ) are associated with low success rates for SUI .
Concomitant continence procedures reduce the risk of postoperative SUI ( grade B ) . | Introduction and hypothesisThe aim was to determine the impact of pelvic organ prolapse surgery on bladder function . | OBJECTIVE This study was undertaken to compare outcomes after anterior colporrhaphy with and without a solvent dehydrated cadaveric fascia lata graft . STUDY DESIGN A total of 162 women were enrolled in a prospect i ve , r and omized trial that evaluated the impact of a solvent dehydrated cadaveric fascia lata patch on recurrent anterior vaginal prolapse . Subjects were r and omly assigned to st and ard colporrhaphy with or without a patch . Before and after surgery , subjects were evaluated by both the Baden-Walker and pelvic organ prolapse quantification systems . " Failure " was defined as stage II anterior wall prolapse or worse . RESULTS Of 154 women r and omly assigned ( 76 patch : 78 no patch ) , all underwent surgery and 153 ( 99 % ) returned for follow-up . Sixteen women ( 21 % ) in the patch group and 23 ( 29 % ) in the control group experienced recurrent anterior vaginal wall prolapse ( P = .229 ) . Only 26 % of all recurrences were symptomatic . Concomitant transvaginal Cooper 's ligament sling procedures were associated with a dramatic decrease in recurrent prolapse ( odds ratio [ OR ] 0.105 , P < .0001 ) . CONCLUSION Solvent dehydrated fascia lata as a barrier does not decrease recurrent prolapse after anterior colporrhaphy . Transvaginal bladder neck slings were associated with a significant reduction in the risk of recurrent anterior wall prolapse Introduction and hypothesisThe objective of this study was to assess the effect of the tension-free vaginal mesh ( Prolift ™ ) procedure on the non-treated and initially unaffected vaginal compartments . Methods This prospect i ve observational cohort study involved 150 patients who underwent a Prolift ™ procedure . Pelvic organ prolapse ( POP ) quantification and evaluation of prolapse symptoms with vali date d question naires was performed pre-operatively and 6 and 12 months postoperatively . Primary outcome was the rate of POP stage ≥II in the non-treated vaginal compartments . Results Twenty-three percent of all patients developed a de novo POP stage ≥II in the untreated compartment . This occurred in 46 % and 25 % of patients after an isolated anterior and isolated posterior Prolift ™ , respectively . Conclusion Tension-free vaginal mesh treatment of one vaginal compartment seems to provoke the development of vaginal prolapse in initially unaffected vaginal compartments , particularly after an isolated anterior Prolift ™ procedure OBJECTIVES This prospect i ve , r and omised study investigated whether a prophylactic procedure , performed during colposacropexy for prolapse repair , prevents ex novo postoperative incontinence . Sixty-six consecutive continent patients with advanced prolapse were r and omised into two groups : group A underwent sacropexy combined with a Burch colposuspension ; no anti-incontinence procedure was performed in group B patients . METHODS Work-up included clinical assessment ( Halfway System and International Continence Society [ ICS ] classification for prolapse and Ingelman Sunderberg scale for incontinence ) , the Urogenital Distress Inventory and Impact Incontinence Quality of Life question naires , urogynaecologic ultrasound scans , and complete urodynamic testing that included the urethral pressure profile and Valsalva leak point pressure with reduced prolapse . Check-ups were done at 3 , 6 , 12 mo postoperatively and then yearly . Mean follow-up time was 39.5 mo . RESULTS The mean age ( + /- st and ard deviation ) was 62+/-9 yr . All patients presented with grade ( G ) 3 - 4 prolapse . Postoperative incontinence was present in 12 of the 34 patients in group A : 7 G1 ; 4 G2 , and 1 G3 . Postoperative incontinence was present in 3 of the 32 patients in group B : 2 G1 , 1 G3 . The frequency of postoperative incontinence was significantly greater in patients who had undergone colposuspension ( p<0.05 ) . CONCLUSIONS These preliminary data cast doubt on whether colposuspension should be performed during sacropexy for severe urogenital prolapse as prophylaxis for postoperative incontinence because it seems to emerge as overtreatment . Incontinence developed ex novo in 35 % of continent patients treated with colposuspension combined with sacropexy Introduction and hypothesisThe surgical management of multi-compartment prolapse is challenging and often requires a combination of techniques . This study evaluates anterior vaginal mesh repair , sacrospinous hysteropexy and posterior fascial plication in women with anterior compartment dominated uterovaginal prolapse . Methods Consecutive women who underwent the aforementioned surgery were prospect ively evaluated . Main outcome measures included objective ( pelvic organ prolapse quantification stage < 2 ) and subjective success rates , patient satisfaction , functional outcomes and complications . Results One hundred and seventeen women were eligible , and 100 agreed to participate . At 12 months , objective success rate at the anterior compartment was 87 % and at all compartments , 75 % . Subjective success was 84 % , and mean patient satisfaction was 8.5/10 . There were no stage 3 or 4 recurrences at any site . Conclusions The combination of anterior vaginal mesh , sacrospinous hysteropexy and posterior fascial plication is reasonably effective in restoring the anatomy and achieving favourable bladder , bowel and sexual function OBJECTIVE To compare changes in urinary symptoms before and after pelvic organ prolapse ( POP ) surgery , using either laparoscopic sacrocolpopexy ( LSC ) or transvaginal porcine dermis hammock placement with sacrospinous ligament suspension ( VS ) . MATERIAL S AND METHODS Data were prospect ively collected from all women undergoing POP surgery between May 2001 and October 2009 . Pre- and postoperative urinary symptoms , Urinary Distress Inventory ( UDI ) , and Urinary Impact Question naires ( UIQ ) scores were compared within and between groups . A generalized linear model was used for multivariate analysis . RESULTS Out of the 151 patients included , 87 patients underwent LSC , and 64 VS . Overall , after a median follow-up of 32.4 months , POP surgery improved urinary frequency ( P = 0.006 ) , voiding difficulty ( P = 0.001 ) , stress urinary incontinence ( SUI ) ( P = 0.001 ) , but not urgency ( P = 0.29 ) . VS was more effective in treating SUI ( P < 0.001 vs. 0.52 ) while LSC more effective on voiding difficulty ( P = 0.01 vs. 0.08 ) . Postoperative de novo symptoms were observed in 35.8 % of patients with no difference between the groups ( P = 0.06 ) . UDI ( P = 0.04 ) and UIQ ( P = 0.01 ) scores were significantly lower after surgery . However , LSC significantly improved UDI ( P = 0.03 ) with no effect on UIQ ( P = 0.29 ) scores while VS significantly improved both scores ( P = 0.02 and 0.001 , respectively ) . Upon multivariate analysis , only the improvement in the impact of urinary symptoms on daily living was independently associated to VS ( OR = 5.45 [ 95 % confidence interval 2.20 - 13.44 ] , P = 0.01 ) . CONCLUSION Most preoperative urinary symptoms decreased after POP surgery with equivalent proportion of de novo symptoms after vaginal and laparoscopic approaches OBJECTIVE The purpose of this study was to compare 2 anti-incontinence procedures in women who had severe genital prolapse and potential stress incontinence . STUDY DESIGN In addition to vaginal reconstructive surgery , 50 patients with stage II or higher anterior defect and a positive stress test result with prolapse reduction received either tension-free vaginal tape or plication of the endopelvic fascia . Preoperative evaluation included history , physical examination , stress test , and urodynamic assessment . Data were analyzed with the Student t test , the Fisher 's exact test , and the Wilcoxon signed-rank test . RESULTS The median follow-up time was similar for both groups , 26 and 24 months . Subjective ( 96 % vs 64 % ; P=.01 ) and objective ( 92 % vs 56 % ; P<.01 ) continence rates were higher after the tension-free vaginal tape procedure . Time for the resumption of spontaneous voiding , rates of urinary retention , or de novo urge incontinence were similar in the 2 groups . CONCLUSION Tension-free vaginal tape can be recommended for patients with prolapse and occult stress incontinence OBJECTIVE Polypropylene mesh in the treatment of genital prolapse in women was introduced at the turn of the millennium with the rationale of decreasing surgical invasiveness , reinforcing weak tissues and to possibly complement insufficient surgical techniques . Prospect i ve r and omized studies comparing traditional and modern operations are lacking . SUBJECT Prospect i ve multicentre r and omized study . SETTING Department of Obstetrics and Gynaecology , The First Faculty of Medicine , Charles University in Prague . SUBJECT AND METHOD A prospect i ve multicentre trial was approved by the Ministry of Health of the Czech Republic and registered with the FDA planning to recruit 500 patients with vaginal prolapse , 18 years of age and over , undergoing surgery at 5 major urogynaecologic centres . The patients were divided into three groups according to prolapse predominance . The surgical techniques used were : anterior and posterior prolift , and r and omly allocated total prolift or sacrospinous fixation . The examination setup included lower urinary tract ultrasound , MRI , POP-Q assessment and QoL question naires before surgery and six and 24 month after the surgery . CONCLUSION Preliminary analysis of partial data of 225 women showed an acceptable rate of complications and a better success rate in the mesh groups , whereas operation time and blood loss was lower in the classical operation group . Quality of life question naires documented that all the methods used have comparably good results . The surgical techniques used are acceptable methods for pelvic organ prolapse repair with low complication rates and excellent impact on the subjective perception of the patient 's quality of life Introduction and hypothesisEndoFast Reliant ™ system is a novel technology for pelvic organ prolapse ( POP ) repair that attaches mesh directly with metal fasteners . Methods This was a prospect i ve multicenter study in 20 women who underwent vaginal POP repair to evaluate safety and efficacy . The patients were followed for 12 months , using POP-Q measures , question naires on symptoms ( PFDI ) , and sexual function ( FSFI ) . Results No intraoperative complications occurred . Prolapse has been anatomically resolved ( < stage 2 ) in 85 % at 1-year follow-up ( 17/20 patients ) . Pelvic Floor Distress Inventory ( PFDI ) scores showed significant improvement for 1 year in symptoms related to prolapse ( 4.1–0.7 , p < 0.001 ) and bladder ( 1.4–0.7 , p = 0.06 ) but not to rectum . Female Sexual Function Index ( FSFI ) scores did not change significantly . One case of mesh exposure was found ( 5 % ) and treated conservatively . No migration of fasteners was observed on X-ray . Conclusions The EndoFast Reliant ™ system was found safe and efficacious . Future studies are needed to evaluate its advantages over techniques using trocars Introduction and hypothesisThe optimal duration of urethral catheterization during and after pelvic reconstructive surgery is not established . This study investigated the optimal duration of urinary catheterization in patients undergoing anterior vaginal repair with or without other vaginal surgeries . Methods A total of 90 patients were included from April 2007 to March 2008 . They were r and omly divided into 2 , 3 , and 4 days urinary catheterization groups based on the color of the question naire papers they blindly chose . After catheter removal , the amount of post-void residual urine was used to measure the efficacy of bladder emptying . Differences between groups were determined using Chi-square test , Fisher 's exact test , or Kruskal – Wallis test , as appropriate . Results No significant differences were found in the amount of post-void residual urine between the three catheterization groups . Conclusions Our findings suggest that the duration of urethral catheterization after anterior colporrhaphy need not exceed 2 days Introduction and hypothesisVaginal mesh kits are increasingly used in the management of pelvic organ prolapse . This study aim ed to determine similarity of outcomes of the Anterior Prolift ® with Perigee ® systems for anterior compartment prolapse . Methods Consecutive women undergoing Perigee ® or Anterior Prolift ® for symptomatic stage 2 or greater anterior vaginal prolapse were prospect ively evaluated . Main outcome measures included objective and subjective success rates , perioperative outcomes , patient satisfaction , and complications . Results One hundred and six women ( Prolift , 52 ; Perigee , 54 ) completed question naires , and 91 ( Prolift , 46 ; Perigee , 45 ) were examined postoperatively . At follow-up ( Prolift : median , 11.0 ; range , 5–23 months ; Perigee : median , 11.5 ; range , 6–23 months ) , objective success rates ( Prolift , 89 % ; Perigee , 80 % ; p = 0.23 ) , subjective success rates ( Prolift , 94 % ; Perigee , 96 % ; p = 0.62 ) , mean ± SD patient satisfaction ( Prolift , 8.2 ± 2.0 ; Perigee , 8.2 ± 1.8 ; p = 0.91 ) , and complication rates did not differ significantly between the two groups . Conclusions The Anterior Prolift ® was found to not differ significantly from Perigee ® at 11 months The aim of this study was to compare the efficiency of polypropylene mesh surgery with the site-specific repair surgeries in the treatment of cystocoeles . We r and omized 90 patients into two groups according to a computer-based program . After a 12-month ( mean ) follow up , we noticed that the polypropylene mesh surgery yielded good anatomical results . Acceptable anatomical cure rates were 91 and 72 % in the mesh surgery group and site-specific surgery group , respectively . There were three cases ( 6.9 % ) of mesh erosion . One case of urinary retention and two cases of de novo dyspareunia were seen in the mesh surgery group . De novo stress urinary incontinence developed in three patients in the site-specific surgery group . We concluded that surgery with light polypropylene mesh ( Sofradim ® , Parietene ) is superior to the site-specific surgery in the treatment of cystocoeles We compared safety and efficacy of Gynemesh PS ® and Pelvicol ® for recurrent cystocele repair . One hundred ninety patients were r and omly divided into Gynemesh PS ® and Pelvicol ® groups and underwent tension-free cystocele repair . The Chi-square test was used to compare categorical variables , the paired t test for continuous parametric variables , and the Mann – Whitney test for continuous nonparametric variables . Ninety-six Gynemesh PS ® patients and 94 Pelvicol ® patients were studied . Mesh erosions occurred in 6.3 % of Gynemesh PS ® patients . No erosions were observed in Pelvicol ® patients ( p = 0.02 ) . Objective cure was 71.9 % for Gynemesh PS ® and 56.4 % for Pelvicol ® ( p = 0.06 ) . Subjective cure was the same in both groups except for better sexuality in the Pelvicol ® group . At 24 months follow-up , only Gynemesh PS ® patients had mesh erosions . Anatomical outcome was similar in the two groups . Pelvicol ® gave a better impact on voiding and sexuality Objective . To locate preoperatively continent women with pelvic organ prolapse at risk of developing incontinence after surgery by means of reducing the prolapse preoperatively with a speculum and a pessary . Design . Prospect i ve observational cohort study . Setting . Departments of Obstetrics and Gynecology at Northern Alvborgs County Hospital , Varbergs Hospital , and Sahlgrenska University Hospital , Sweden , between 2000 and 2004 . Population . Patients scheduled for anterior wall repair with no history of incontinence . Methods . Data were collected using a question naire , a voiding diary , a gynecological examination including staging of prolapse with the Pelvic Organ Quantification System and clinical testing preoperatively and one year after vaginal repair . The first test included a cough test while the prolapse was reduced with a speculum . The second test was performed with the patient undergoing a st and ardized quantification test and a 48‐hour pad test after reducing the prolapse with a pessary . Postoperatively , clinical testing was repeated one year after surgery without any device in place . Main Outcome Measures . Reported symptoms of leakage during movement or coughing . Results . Seventy‐four patients were included . Before surgery , six ( 8.1 % ) women tested positive during the speculum test and seven ( 9.5 % ) during the pessary test . Eight women ( 10.8 % ) were found to have subjective urinary stress incontinence after 1 year . This was only confirmed in four women during stress testing . The positive predictive values for subjective stress incontinence of the speculum and the pessary tests were 42.9 % ( 95%CI 12.0–76.9 ) and 33.3 % ( 95%CI −4.4 to + 71.5 ) , respectively . The negative predictive values of the tests were 92.5 % ( 95%CI 90.3–1.00 ) and 91.1 % ( 95%CI 88.5–99.7 ) . Conclusions . The tested preoperative methods predicting de novo subjective stress incontinence after anterior wall repair did not show sufficient positive predictive values to be clinical ly useful OBJECTIVE To describe the perioperative course and medium-term anatomic and functional outcomes of the transobturator-infracoccygeal hammock for posthysterectomy vaginal vault prolapse repair . METHODS A prospect i ve consecutive series of 52 women with a stage 2 vaginal vault prolapse or higher that occurred after total hysterectomy who underwent surgery between 2003 and 2007 . Principal outcome measures were anatomic cure ( stage 1 or lower ) and impact on quality of life measured using the pelvic floor distress inventory ( PFDI ) and pelvic floor impact self-reported question naire ( PFIQ ) . Anatomical results were analyzed using chi(2 ) and Fisher exact tests , and PFDI and PFIQ scores were analyzed using the Wilcoxon test . RESULTS With a median follow-up of 36months , the anatomic cure rate was 96 % . Significant improvements were noted in POPQ-S scores after surgery ( P<0.05 ) . Stress urinary incontinence was cured in 73 % of patients and improved in 15 % of patients . The PFDI and PFIQ scores were improved ( P<0.05 ) . One mesh extrusion was observed . The rates of mesh contraction and new cases of dyspareunia were 31 % and 13 % , respectively . CONCLUSION The transvaginal mesh hammock represents a useful treatment for recurrent and major vaginal vault prolapse , and has few complications Introduction and hypothesisThe effect of a Pelvicol ® graft compared with a conventional anterior vaginal repair was evaluated in this r and omised controlled study . Methods Only patients with a stage II or higher ( Ba ≥ −1 ) defect were included . Results Thirty-one patients were allocated to a conventional anterior repair ; 30 to Pelvicol ® graft . At 12 months follow-up , four patients among controls ( 15 % ) and two in the graft group ( 7 % ) had objective recurrence . Among controls , the difference at 3 months follow-up in Ba was 6.0 cm when compared with the position of Ba prior to surgery . In the graft group , the difference was 7.0 cm ( P < 0.05 ) . This difference was still present at 12 months follow-up ( 6.0 vs. 7.0 cm ; P < 0.05 ) . Conclusions The implantation of a Pelvicol ® graft does not improve the POP-Q stage The purpose of this study was to evaluate the effectiveness of the anterior colporrhaphy procedure reinforced with four-corner anchored polypropylene mesh in patients with severe ( stage III or IV ) anterior vaginal prolapse . Thirty-eight consecutive women were enlisted for this prospect i ve study . The procedure consisted of an extensive vaginal dissection to join the vesicovaginal and retropubic space and an anchoring of a polypropylene mesh patch between the two Arcus Tendineus Fasciae Pelvis in a tension-free manner . The mean age of the study group was 63 ( 33–80 ) years . The success rate was 87 % ( 33/38 ) at a mean follow-up interval of 21 ( 12–29 ) months . A total of eight ( 100 % ) patients were also cured of concomitant stress incontinence ( five overt and three occult type ) with an additional tension-free vaginal tape ( TVT ) operation . During follow-up , there were five de-novo stress incontinence cases ( 16.7 % ) and four vaginal erosions of mesh ( 10.5 % ) . Four clinical variables — diabetes mellitus , recurrent anterior vaginal prolapse , chronic cough and vaginal erosions of mesh — were found to have a significant correlation with an unsatisfactory surgical result with large values of hazard ratios found by survival analysis . We concluded that the anterior colporrhaphy procedure reinforced with four-corner anchored polypropylene mesh was effective for most , but failed in some patients who had specific risk factors within short convalescence periods . Concomitant stress incontinence can be successfully treated by a TVT operation in combination with the anterior colporrhaphy procedure reinforced with four-corner anchored polypropylene mesh . However , the anterior colporrhaphy procedure may itself have adverse effects on urethral sphincter function Introduction and hypothesisThe aim of this study was to compare the number of temporary catheter replacements and urinary tract infections after indwelling catheterization for 2 versus 5 days following an anterior colporrhaphy . Methods Two hundred forty-six patients were r and omly assigned to 2 or 5 days of indwelling catheterization . Outcome measures were temporary catheter replacements because of post-voiding residual > 200 mL after removal of the indwelling catheter , urinary tract infections , and hospital stay . All patients were analyzed according to the intention to treat principle . Results Compared to the 5-day protocol group , in the 2-day protocol group more patients needed temporary catheter replacement ( 9 % versus 28 % , odds ratio ( OR ) 4.0 , confidence interval ( CI ) 1.9–8.3 , p < 0.01 ) , whereas less patients had a urinary tract infection ( 37 % versus 22 % , OR 0.5 , CI 0.3–0.9 , p = 0.02 ) and median hospital stay was lower . Conclusions Removal of an indwelling catheter after 2 versus 5 days following anterior colporrhaphy is associated with more temporary catheter replacements , but less urinary tract infections and a shorter hospital stay AIMS To assess the effects of trocar guided transvaginal mesh on lower urinary tract symptoms after anterior vaginal wall prolapse repair . METHODS One hundred twenty-one patients undergoing anterior transvaginal mesh surgery was prospect ively evaluated at baseline and 1 year after surgery using the urogenital distress inventory ( UDI ) . RESULTS Overall UDI scores declined from 91 before surgery to 31 one year after surgery ( P < 0.001 ) . UDI subscales for obstructive and irritative symptoms improved 1 year after surgery ( P < 0.001 for both ) while stress symptoms did not ( P = 0.11 ) . CONCLUSION Trocar guided transvaginal mesh surgery for anterior vaginal wall prolapse was associated with an overall resolution of most symptoms associated with overactive bladder syndrome and bladder outlet obstruction . These beneficial effects should be weighed against an increased risk for stress urinary incontinence related to the procedure Introduction and hypothesis Assessment of the 2-year outcome of anterior Prolift ™ for women with recurrent anterior vaginal wall prolapse . This is a prospect i ve study which was conducted in a tertiary unit in the North West of Engl and and comprised 36 consecutive women with recurrent anterior vaginal wall prolapse . Methods Women were assessed preoperatively and postoperatively at 6 months and 2 years . Women completed the Prolapse Quality of Life Question naire ( P-QOL ) , Prolapse and Incontinence Sexual Function Question naire-Short Form ( PISQ-12 ) , and postoperatively , the Global Impression of Improvement Question naire . Women were examined using the Pelvic Organ Prolapse Quantification System ( POP-Q ) . Anatomical success was defined as stage ≤1 prolapse in the anterior compartment . Main outcome measures Postoperative POP-Q stage , quality of life domains and mesh exposure rate . Results Preoperatively all but two women had stage 2 or greater anterior vaginal wall prolapse . At a mean follow-up of 24.6 months , 19 women ( 53 % ) had stage ≤1 anterior wall prolapse . Fifteen women had stage 2 anterior wall prolapse and two women had stage 3 prolapse . Twenty-nine women felt improvement in their prolapse symptoms . 16 women were sexually active preoperatively , of whom seven reported worsening dyspareunia . There was poor correlation between anatomical and functional outcomes . Seven women had mesh exposure . Five needed revision in theatre . Conclusions Anterior Prolift ™ for recurrent anterior vaginal wall prolapse has 53 % anatomical success rate in the medium term , with mesh exposure rate of 19 % . Majority of patients felt overall improvement in their symptoms , but this did not correlate with the anatomical outcome PURPOSE To test the hypothesis that advanced stages of pelvic organ prolapse can result in a functional obstruction of the urethra , we studied the effects of manual prolapse reduction on urodynamic and urethral electromyographic parameters in women with stage III and IV pelvic organ prolapse . MATERIAL S AND METHODS Women with advanced pelvic organ prolapse undergoing clinical multichannel urodynamics with concentric needle electromyography of the urethra were invited to participate in this institutional review board approved study . Women underwent filling cystometry and electromyography with prolapse everted and with prolapse reduced . Women were r and omized to cystometry order ( reduced vs everted ) . All subjects underwent a third study with prolapse reduction . Maximum urethral closure pressure and quantitative electromyography of the striated urethral sphincter were determined at maximum cystometric capacity . During the pressure flow study voiding parameters , including urethral electromyography quieting , were determined . The nonparametric paired sign test was used to evaluate differences in urodynamic parameters and quantitative electromyography with pelvic organ prolapse reduced and unreduced . Results were considered significant at the 5 % level . RESULTS The 31 participants had mean age of 60 years ( range 36 to 78 ) and 83 % were white . There were no clinical ly significant differences in maximum cystometric capacity , voided volume , maximal flow and detrusor pressure at maximal flow or time to maximal flow between the reduced and everted prolapse states . Prolapse reduction result ed in a clinical ly and statistically significant decrease in maximum urethral closure pressure ( -31 % ) but it had no impact on quantitative urethral electromyography . CONCLUSIONS These findings demonstrate that , although prolapse reduction significantly decreases maximum urethral closure pressure , it does not alter intrinsic neuromuscular activity of the striated urethral sphincter . Prolapse reduction does not alter any other filling or pressure flow parameter BACKGROUND The use of st and ardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years , but it is unclear whether this approach results in better outcomes than traditional colporrhaphy . METHODS In this multicenter , parallel-group , r and omized , controlled trial , we compared the use of a trocar-guided , transvaginal polypropylene-mesh repair kit with traditional colporrhaphy in women with prolapse of the anterior vaginal wall ( cystocele ) . The primary outcome was a composite of the objective anatomical design ation of stage 0 ( no prolapse ) or 1 ( position of the anterior vaginal wall more than 1 cm above the hymen ) , according to the Pelvic Organ Prolapse Quantification system , and the subjective absence of symptoms of vaginal bulging 12 months after the surgery . RESULTS Of 389 women who were r and omly assigned to a study treatment , 200 underwent prolapse repair with the transvaginal mesh kit and 189 underwent traditional colporrhaphy . At 1 year , the primary outcome was significantly more common in the women treated with transvaginal mesh repair ( 60.8 % ) than in those who underwent colporrhaphy ( 34.5 % ) ( absolute difference , 26.3 percentage points ; 95 % confidence interval , 15.6 to 37.0 ) . The surgery lasted longer and the rates of intraoperative hemorrhage were higher in the mesh-repair group than in the colporrhaphy group ( P<0.001 for both comparisons ) . Rates of bladder perforation were 3.5 % in the mesh-repair group and 0.5 % in the colporrhaphy group ( P=0.07 ) , and the respective rates of new stress urinary incontinence after surgery were 12.3 % and 6.3 % ( P=0.05 ) . Surgical reintervention to correct mesh exposure during follow-up occurred in 3.2 % of 186 patients in the mesh-repair group . CONCLUSIONS As compared with anterior colporrhaphy , use of a st and ardized , trocar-guided mesh kit for cystocele repair result ed in higher short-term rates of successful treatment but also in higher rates of surgical complications and postoperative adverse events . ( Funded by the Karolinska Institutet and Ethicon ; Clinical Trials.gov number , NCT00566917 . ) OBJECTIVE Our purpose was to compare two antiincontinence procedures in patients with severe genitourinary prolapse and coexisting clinical or potential stress incontinence . STUDY DESIGN In addition to cystopexy , 109 patients with a urethrocystocele of grade 2 or more and a positive stress test result with prolapse reduction received posterior pubourethral ligament plication or Pereyra suspension . RESULTS Of 55 patients undergoing posterior pubourethral ligament plication , 15 were clinical ly and 40 potentially incontinent ; the same figures were 21 and 33 , respectively , among 54 patients undergoing the Pereyra procedure . Follow-up was for 3 to 9 years . Subjective ( 60 % vs 71 % , p = 0.72 ) and objective ( 27 % vs 57 % , p = 0.14 ) cure rates were not statistically different among patients who were clinical ly incontinent ( posterior pubourethral ligament plication vs Pereyra suspension ) . Among potentially incontinent patients , subjective ( 85 % vs 100 % , p = 0.03 ) and objective ( 50 % vs 76 % , p = 0.04 ) continence rates were higher after the Pereyra procedure . Overall , the cotton swab test had negative results ( maximum straining angle < or = 30 degrees ) after successful surgery in 79 % and 96 % , respectively , of patients ( p = 0.03 ) . Four subjects ( 7 % ) underwent removal of one Pereyra suture because of urinary retention or suprapubic wound infection . CONCLUSION Cystopexy with Pereyra suspension is recommended , particularly for patients with prolapse and potential stress incontinence OBJECTIVES To present a surgical technique in which cadaveric fascia lata is used for cystocele repair . METHODS Twenty-one consecutive women ( mean age 67 + /- 10 years ) with severe cystocele were prospect ively enrolled . All patients underwent meticulous clinical and urodynamic preoperative evaluations . Solvent-dehydrated , Tutoplast-processed , cadaveric fascia lata was used for cystocele repair . The fascia was anchored transversally between the bilateral arcus tendineus and the cardinal and uterosacral ligaments . St and ard endopelvic plication was performed thereafter as a second layer . Patients with overt or occult sphincteric incontinence underwent concomitant pubovaginal sling ( PVS ) surgery as well , using the same material . The main outcome measures included recurrent urogenital prolapse , persistent or de novo urinary incontinence ( stress or urge ) , and dyspareunia . RESULTS Of the 21 patients , 19 underwent concomitant PVS , 3 concomitant vaginal hysterectomy , and 8 posterior colporrhaphy in addition to their cystocele repair . The mean follow-up was 20.1 + /- 6.7 months ( range 12 to 30 ) . No postoperative complications related to the material or technique occurred . None of the patients developed a recurrent cystocele . Two patients ( 9 % ) , one of whom underwent concomitant posterior colporrhaphy , developed mild recto-enterocele at 4 to 6 months postoperatively . Six patients underwent concomitant PVS for occult sphincteric incontinence . None developed postoperative stress incontinence . Thirteen other patients underwent concomitant PVS for overt sphincteric incontinence . All but two were stress-continent postoperatively . One half of the patients with preoperative urge or mixed incontinence had persistent urge incontinence postoperatively . None of the patients developed postoperative de novo urge incontinence or dyspareunia . CONCLUSIONS The use of solvent-dehydrated cadaveric fascia lata for cystocele repair , as well as PVS , is associated with encouraging short and medium-term results . Long-term follow-up is needed to evaluate whether these results are durable PURPOSE We evaluated the efficacy of the Pelvicol porcine collagen implant for preventing recurrent anterior vaginal wall prolapse in women undergoing primary surgery for pelvic organ prolapse . MATERIAL S AND METHODS This was a prospect i ve , r and omized , multicenter trial in 206 women with stage II or greater anterior vaginal wall prolapse ( point Ba -1 or greater ) according to the pelvic organ prolapse quantification system . The patients were r and omly assigned to undergo anterior vaginal repair or the same procedure with Pelvicol implant reinforcement . SPSS software was used for data analysis . RESULTS A total of 201 women were available for surgical outcome analysis , including 98 and 103 in the implant and no implant groups , respectively . All completed the 1-year followup visit . Most women were satisfied with the postoperative condition with a significant decrease in the visual analog scale score in each group ( p < 0.001 ) . Anatomical anterior recurrence ( point Ba greater than -1 ) was observed in 7 women ( 7 % ) in the implant group and in 20 ( 19 % ) in the other groups ( OR 3.13 , 95 % CI 1.26 - 7.78 , p = 0.019 ) . Additionally , there were 11 women ( 3 and 8 , respectively , or 5 % ) with posterior recurrence and 6 ( 3 per group or 3 % ) with unsatisfactory results at the upper vaginal segment . One patient who received a porcine implant had vaginal extrusion of the mesh 1 month after surgery . CONCLUSIONS Our data show that the Pelvicol implant can be easily and readily used to augment and reinforce anterior colporrhaphy . The prolapse recurrence rate was considerably lower in the implant group compared with outcomes in patients treated with simple anterior repair PURPOSE We reevaluated and brought up to date the 8-year followup of a previous published , r and omized , controlled trial of the impact of Burch colposuspension as a prophylactic anti-incontinence procedure in patients without urinary incontinence who underwent abdominal pelvic organ prolapse repair . MATERIAL S AND METHODS A total of 66 continent women with pelvic organ prolapse were r and omly assigned to abdominal pelvic organ prolapse repair and concomitant Burch colposuspension in 34 ( group 1 ) or pelvic organ prolapse repair alone without an anti-incontinence procedure in 32 ( group 2 ) . Primary study end points were the anatomical outcome and changes in incontinence status . Secondary end points were changes in subjective symptoms and quality of life . RESULTS Median followup was 97 months ( range 72 to 134 ) . Three group 1 and 1 group 2 patients were lost to followup . Three group 1 patients had a stage I rectocele and 1 had a stage I cystocele . Four group 2 patients had a stage I rectocele and 3 had a stage I cystocele . Nine of 31 group 1 patients ( 29 % ) were incontinent compared with 5 of 31 ( 16 % ) in group 2 ( p = 0.553 ) . In group 1 all except 1 patient were successfully treated for voiding dysfunction . Storage symptoms had disappeared in 1 patient and de novo storage symptoms had developed in 2 since the previous followup . De novo incontinence developed in 2 group 2 patients after midterm outcomes were reported . Median Urogenital Distress Inventory-6 and Incontinence Impact on Quality of Life-7 scores were improved in all groups at last followup ( p 0.0001 ) . CONCLUSIONS Long-term results cast doubt on whether Burch colposuspension should be done during pelvic organ prolapse repair in continent women OBJECTIVE To prospect ively assess the anatomic and functional outcome of high- grade genital prolapse repair using a nonabsorbable hammock placement with anterior trans-obturator and posterior infracoccygeal extensions after hysterectomy . METHODS Forty-four women with stage III or IV prolapse underwent surgery between January 2002 and June 2005 . Patients had physical examination for prolapse assessment according to the International Continence Society pelvic organ prolapse staging system and were evaluated for subjective prolapse symptoms preoperatively and postoperatively . Follow-up was done at 6 wk and 6 mo and then once a year . RESULTS Median follow-up was 29.3 mo ( range : 9 - 47 mo ) . Thirty-six ( 81.8 % ) women had optimal anatomic results and seven ( 15.9 % ) had persistent asymptomatic stage I prolapse . One patient ( 2.7 % ) had symptomatic recurrence of a posterior vaginal wall stage III prolapse . The subjective cure rate was 97.7 % ( 43 of 44 ) . All subjective symptoms of prolapse decreased after surgery . The only intraoperative complication was an uneventful rectal injury . The rates of vaginal erosions and mesh infections were 13.6 % and 4.5 % , respectively . CONCLUSIONS These results suggest that nonabsorbable hammock placement using anterior trans-obturator and posterior infracoccygeal extensions could be a safe and effective treatment for high- grade genital prolapse . Further studies are warranted to determine long-term outcome and to compare this approach with previously accepted surgical procedures The aim of this study is to describe results of reduction testing in stress-continent women undergoing sacrocolpopexy and to estimate whether stress leakage during urodynamic testing with prolapse reduction predicts postoperative stress incontinence . Three hundred twenty-two stress-continent women with stages II – IV prolapse underwent st and ardized urodynamics . Five prolapse reduction methods were tested : two at each site and both performed for each subject . Clinicians were masked to urodynamic results . At sacrocolpopexy , participants were r and omized to Burch colposuspension or no Burch ( control ) . P-values were computed by two-tailed Fisher ’s exact test or t-test . Preoperatively , only 12 of 313 ( 3.7 % ) subjects demonstrated urodynamic stress incontinence ( USI ) without prolapse reduction . More women leaked after the second method than after the first ( 22 % vs. 16 % ; p = 0.012 ) . Preoperative detection of USI with prolapse reduction at 300ml was pessary , 6 % ( 5 of 88 ) ; manual , 16 % ( 19 of 122 ) ; forceps , 21 % ( 21 of 98 ) ; swab , 20 % ( 32 of 158 ) ; and speculum , 30 % ( 35 of 118 ) . Women who demonstrated preoperative USI during prolapse reduction were more likely to report postoperative stress incontinence , regardless of concomitant colposuspension ( controls 58 % vs. 38 % ( p = 0.04 ) and Burch 32 % vs. 21 % ( p = 0.19 ) ) . In stress-continent women undergoing sacrocolpopexy , few women demonstrated USI without prolapse reduction . Detection rates of USI with prolapse reduction varied significantly by reduction method . Preoperative USI leakage during reduction testing is associated with a higher risk for postoperative stress incontinence at 3 months . Future research is warranted in this patient population to evaluate other treatment options to refine predictions and further reduce the risk of postoperative stress incontinence Objective To compare cystopexy alone versus cystopexy with posterior pubourethral ligaments plication for the occurrence of postoperative stress incontinence after prolapse surgery , and to compare the two surgical series in terms of complications and urodynamic effects . Methods One hundred two continent patients r and omly underwent cystopexy alone ( N = 52 ) or cystopexy with posterior pubourethral ligaments plication ( N = 50 ) . All had a urethrocystocele grade 2 or greater and a negative stress test with the prolapse repositioned . A full urodynamic investigation was repeated 6 months after surgery . Results Twelve ( 23 % ) and 14 ( 28 % ) patients ( P = .73 ) required intermittent self-catheterization for 11.1 ± 5.1 and 16.5 ± 11.1 days , respectively ( cystopexy alone versus cystopexy with posterior pubourethral ligaments plication , P = .002 ) . Long-lasting difficulties in voiding were present in zero and five ( 10 % ) patients ( P = .02 ) . One subject receiving posterior pubourethral ligaments plication underwent urethral dilation for complete urinary retention . At 1 year follow-up , four patients ( 8 % ) in each series developed postoperative stress incontinence ( P = .62 ) . Symptomatic detrusor instability complicated the postoperative course in one patient ( 2 % ) of each group . Conclusion Cystopexy alone implied lower morbidity in terms of resumption of spontaneous voiding and long-lasting difficulties in voiding . The procedure could be recommended as an effective and safe treatment for continent patients with severe urethrocystocele . Additional plication of the posterior pubourethral ligaments did not seem superior to cystopexy alone in preventing the postoperative occurrence of stress incontinence Aim : To compare the effect of suprapubic and transurethral catheterization on postvoid residual volumes ( PRVs ) after cystocele repair . Methods : 126 women who underwent pelvic organ prolapse surgery including cystocele repair were r and omized to suprapubic or transurethral catheterization . At the third postoperative day , PRVs were measured . The number of women with PRV > 150 ml , need for prolonged catheterization , recatheterization , length of hospital stay , frequency of urinary tract infections and complications were determined . Results : PRVs exceeded 150 ml in 13 out of 64 ( 20 % ) and 14 out of 62 ( 23 % ) women in the suprapubic and transurethral group , respectively ( p = 0.76 ) . In the suprapubic group a higher rate of urine leakage was noted ( 27 vs. 7 % , p = 0.003 ) . 10 women ( 16 % ) allocated to the suprapubic group switched to transurethral catheterization , because of problems with the suprapubic catheter . No protocol deviations were reported in the transurethral group . Of the women in both groups , 9 % developed urinary tract infections ( p = 0.93 ) . Conclusions : Suprapubic catheterization was comparable to transurethral catheterization in the prevention of postoperative voiding dysfunction after vaginal prolapse surgery , but it was associated with a higher rate of complications Objective To compare the Burch colposuspension and the anterior colporrhaphy in women with both stress urinary incontinence and advanced anterior vaginal wall prolapse ( cystocele ) OBJECTIVE To prospect ively evaluate the efficacy of a tension-free vaginal mesh ( TVM ) procedure for pelvic organ prolapse ( POP ) . METHODS Between December 2005 and April 2008 , 310 female patients ( mean age 67.2 years , range 42 - 84 ) with POP underwent TVM procedures at our institute . Fifty-six individuals were qualified as stage 2 according to the POP quantification system and 162 and 92 were stage 3 and 4 , respectively . One hundred ninety-one patients underwent anterior TVM , and seven underwent posterior TVM . One hundred twelve cases underwent both anterior and posterior TVM procedures . Each patient was systematic ally assessed at 1 , 3 , 6 and 12 months after surgery . Quality of life ( QOL ) was also assessed by using the Short Form-36 and the prolapse-QOL question naires . RESULTS Perioperative complications were the following : five bladder injuries ( 1.6 % ) , no rectal injuries and three hemorrhages greater than 400 mL ( 1.0 % ) . The anatomical cure rate ( % stage 0 cases ) at 3 , 6 and 12 months after surgery were 94.1 % , 93.5 % , and 92.3 % , respectively . Short Form-36 and prolapse-QOL parameters were significantly improved , and maintained during the follow-up period . Postoperative complications were the following : five pelvic hematomas ( 1.6 % ) , one wound infection ( 0.3 % ) , 10 vaginal mesh extrusions ( 3.2 % ) , and three cases of pelvic pain ( 1.0 % ) . Complications concerning lower urinary tract function were : eight cases of postoperative stress urinary incontinence ( 2.6 % ) , three cases of transient urinary retention ( 1.0 % ) , and two cases of de novo overactive bladder ( 0.6 % ) . CONCLUSIONS The TVM procedure provides a good outcome at 1 year with a low incidence of surgical complications and recurrence . Further evaluation with a longer follow up is needed PURPOSE We determined whether genital prolapse causes obstruction that may be relieved by a vaginal pessary as well as the degree to which voiding difficulty , urethral hypermobility , bladder outlet obstruction , occult stress incontinence , detrusor instability and impaired detrusor contractility are associated with prolapse . MATERIAL S AND METHODS We prospect ively evaluated 60 women with a mean age of 52 years who had genital prolapse , including 35 ( 58 % ) with grade 1 or 2 and 25 ( 42 % ) with grade 3 or 4 cystocele , using pressure-flow video urodynamics and cotton swab testing . Leak point pressure and uroflowmetry were repeated in patients with severe prolapse after insertion of a ring pessary . RESULTS Urethral hypermobility ( p<0.05 ) and symptoms of voiding difficulty ( p<0.01 ) were more common in women with grade 3 or 4 cystocele . Urodynamics revealed bladder outlet obstruction in 2 patients ( 4 % ) with grade 1 or 2 cystocele and 18 ( 58 % ) with grade 3 or 4 cystocele ( p<0.001 ) . After vaginal pessary placement bladder outlet obstruction reverted to normal free flow in 17 women ( 94 % ) with grade 3 or 4 cystocele . Seven women ( 20 % ) with grade 1 or 2 cystocele versus 13 ( 52 % ) with grade 3 or 4 cystocele had detrusor instability ( p<0.05 ) . Impaired detrusor contractility was noted in each group ( p>0.05 ) . In patients with stress incontinence intrinsic sphincter deficiency did not correlate with the degree of prolapse and urethral hypermobility did not correlate with leak point pressure . CONCLUSIONS Lower urinary tract symptoms are common in women with genital prolapse . Voiding difficulty , bladder outlet obstruction and occult stress incontinence may coexist and they are associated with prolapse . Detrusor instability and urethral hypermobility also correlate with the degree of prolapse but impaired detrusor contractility and intrinsic sphincter deficiency do not . In women with severe prolapse ring pessary reduction of prolapse during urodynamics is useful to determine symptomatic and occult conditions OBJECTIVE : To compare efficacy and safety of trocar-guided tension-free vaginal mesh insertion with conventional vaginal prolapse repair in patients with recurrent pelvic organ prolapse . METHODS : Patients with recurrent pelvic organ prolapse stage II or higher were r and omly assigned to either conventional vaginal prolapse surgery or polypropylene mesh insertion . Primary outcome was anatomic failure ( pelvic organ prolapse stage II or higher ) in the treated vaginal compartments . Secondary outcomes were subjective improvement , effects on bother , quality of life , and adverse events . Question naires such as the Incontinence Impact Question naire and Urogenital Distress Inventory were administered at baseline , 6 months , and 12 months . Anatomic outcomes were assessed by an unblinded surgeon . Power calculation with & agr;=0.05 and & bgr;=0.80 indicated that 194 patients were needed . RESULTS : Ninety-seven women underwent conventional repair and 93 mesh repair . The follow-up rate after 12 months was 186 of 190 patients ( 98 % ) . Twelve months postsurgery , anatomic failure in the treated compartment was observed in 38 of 84 patients ( 45.2 % ) in the conventional group and in eight of 83 patients ( 9.6 % ) in the mesh group ( P<.001 ; odds ratio , 7.7 ; 95 % confidence interval , 3.3–18 ) . Patients in either group reported less bulge and overactive bladder symptoms . Subjective improvement was reported by 64 of 80 patients ( 80 % ) in the conventional group compared with 63 of 78 patients ( 81 % ) in the mesh group . Mesh exposure was detected in 14 of 83 patients ( 16.9 % ) . CONCLUSION : At 12 months , the number of anatomic failures observed after tension-free vaginal mesh insertion was less than after conventional vaginal prolapse repair . Symptom decrease and improvement of quality of life were equal in both groups . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00372190 . LEVEL OF EVIDENCE : OBJECTIVE The objective of this study was to evaluate the impact of transvaginal prolapse surgery on overactive bladder symptoms in elderly women . STUDY DESIGN Women ( > or = 65 years old ) with stage III or IV prolapse who enrolled in a prospect i ve study that compared vaginal reconstructive surgery ( n = 39 ) to obliterative surgery ( n = 26 ) and who underwent preoperative urodynamics are the subjects of this study . The women completed the Pelvic Floor Distress Inventory at baseline and again 6 months and 12 months after surgery . Postoperative changes in symptoms of urinary urgency , frequency , and urge urinary incontinence were assessed . The association between a baseline urodynamic diagnosis of detrusor overactivity and pre- and postoperative overactive bladder symptoms was also determined . RESULTS Data were analyzed from 65 subjects with a mean age of 75.3 years ( range , 65.5 - 87.0 years ) . Detrusor overactivity was documented in 25 % of subjects . There was no difference in the proportion of baseline urge incontinence ( P = .38 ) , urinary frequency ( P = .53 ) , or urgency ( P = .76 ) in comparing women with and without detrusor overactivity . Surgery result ed in a significant reduction of urgency and frequency symptoms 6 months after surgery and a similar significant reduction in urgency and urge incontinence at 1 year after surgery . Overall , a clinical ly and statistically significant improvement in the irritative subscale of the Pelvic Floor Distress Inventory was noted at 6 months ( 18.3 % ; P < .0001 ) and 12 months ( 17.6 % ; P < .0001 ) after surgery . In our cohort , performance of a mid urethral sling , a bladder neck sling , or a Kelly plication was not associated with a reduction in postoperative symptoms of urgency , frequency , or urge incontinence ( P = .48 ) . Likewise , there was no difference in postoperative symptom reduction ( urgency , frequency , or urge incontinence ) between women who received reconstructive surgery vs women who had obliterative surgery ( P = .84 ) . CONCLUSION Vaginal surgery for stage III or IV pelvic organ prolapse significantly reduces overactive bladder symptoms in elderly women . In our cohort , symptom reduction was unrelated to the type of vaginal surgery ( obliterative vs reconstructive ) or the inclusion of a procedure to treat stress incontinence . Furthermore , preoperative urodynamic findings did not correlate with the presence or absence of overactive bladder symptoms PURPOSE We evaluated the impact of Burch colposuspension as an anti-incontinence measure in patients with urinary incontinence undergoing abdominal surgery for pelvic organ prolapse repair . MATERIAL S AND METHODS A total of 47 women with pelvic organ prolapse and urinary incontinence were r and omly assigned to abdominal pelvic organ prolapse repair and concomitant Burch colposuspension ( 24 patients , group A ) or pelvic organ prolapse repair alone without an anti-incontinence procedure ( 23 patients , group B ) . They were followed up at 3 , 6 and 9 months after surgery , and then annually . The primary outcome measures were anatomical outcome and changes in incontinence status as indicated by a bladder diary , the number of daily pads and the stress test . Secondary end points were changes in subjective symptoms and quality of life as measured by the Urogenital Distress Inventory and the Incontinence Impact Question naire . RESULTS In group A 13 of 24 patients ( 54.2 % ) were still incontinent after surgery compared with 9 of 23 ( 39.1 % ) in group B. The intragroup difference was significant ( group A p = 0.003 , group B p = 0.0001 ) , but there was no significant intergroup difference ( p = 0.459 for A vs B ) . No significant intergroup difference emerged in anatomical outcome . Urogenital Distress Inventory and Incontinence Impact Question naire scores improved in both groups ( p = 0.0001 ) but the intergroup difference was not significant in either question naire ( p = 0.769 and p = 0.327 , respectively ) . CONCLUSIONS Burch colposuspension does not provide any additional benefit in pelvic organ prolapse repair in patients with urinary incontinence Introduction and hypothesisThis study aims to compare the result of an incontinence procedure performed at the time of prolapse repair or 3 months later in women with pelvic organ prolapse ( POP ) and stress urinary incontinence ( SUI ) . Methods In a multicenter prospect i ve r and omized trial , women with POP and SUI were r and omized to have a tension-free vaginal tape ( TVT ) at the time of prolapse repair ( n = 87 ; group I ) or 3 months later ( n = 94 ; group II ) . Women in group II were evaluated for SUI 3 months after the prolapse repair . Those with confirmed SUI had a TVT performed ( n = 53 ) . The main evaluation of all women was 1 year after the last surgery . Results On-treatment analysis result ed in 95 % cure of SUI in group I and 89 % in group II ( p = 0.12 ) . Twenty-seven percent were cured after prolapse surgery alone . Conclusions No differences were found between the two treatment strategies , but almost one third of women were cured of SUI by prolapse surgery alone AIMS To investigate the urodynamic effects of anterior vaginal wall prolapse surgery using either trocar guided transvaginal mesh or colporraphy . METHODS A prospect i ve , r and omized multicenter trial enrolling 50 patients : 27 underwent anterior colporrhaphy and 23 anterior trocar guided transvaginal mesh . Urodynamic assessment was performed pre- and two months postoperatively . RESULTS De novo stress urinary incontinence was significantly more common after trocar guided transvaginal mesh surgery compared to colporraphy . In comparison to baseline urodynamics , transvaginal mesh surgery result ed in a significant decrease in maximal urethral closing pressures ( MUCP ) whereas conventional anterior colporraphy had no significant effect on urodynamic parameters . CONCLUSION Trocar guided transvaginal mesh of anterior vaginal wall prolapse results in a lowering of MUCPs and increases the risk for de novo stress urinary incontinence compared to colporraphy OBJECTIVE To compare infracoccygeal sacropexy ( IS ) and sacrospinous suspension ( SS ) for the treatment of uterine or vault prolapse . METHODS A r and omized trial of 49 women assigned to either the IS group using IVS tape ( n=24 ) or SS group ( n=25 ) . Concomitant hysterectomy and repairs were performed as appropriate . Evaluations included prolapse staging using the POP-Q system and vali date d question naires for symptoms ( PFDI ) , quality of life ( PFIQ ) , and sexuality ( PISQ-12 ) . The primary outcome measure was postoperative pain . RESULTS Patients ' characteristics were similar in both groups . IS was quicker , easier , and less painful than SS ( P<0.01 ) . Hemorrhage or hematoma rates were similar . Neither rectal injury nor vaginal erosion occurred . Mean follow-up was 16.8 months . Prolapse cure rates , symptom scores , and quality of life were similar . Postoperative cystocele occurred in 4.8 % of women after IS and 25 % after SS ( P>0.05 ) . CONCLUSION Infracoccygeal sacropexy is equivalent to sacrospinous suspension , with a decreased rate of postoperative pain and cystocele recurrence OBJECTIVES To study the prevalence of occult stress urinary incontinence ( SUI ) among Indian women with genitourinary prolapse , and determine the risk of developing SUI after vaginal hysterectomy and pelvic floor repair in Indian women with occult SUI . METHODS A prospect i ve cohort study of 78 women with significant genitourinary prolapse without symptoms of SUI was conducted at Christian Medical College , Vellore , India . Before the surgical intervention , the prolapse was repositioned using a pessary and a Pyridium ( Parke Davis , Morris Plains , NJ , USA ) pad test was performed to detect occult SUI . The primary outcome studied was the risk of developing postoperative urinary incontinence . RESULTS Preoperatively , 67.9 % of women were found to have occult SUI . The prevalence of SUI was 43.6 % postoperatively , and 64.2 % of the women with a positive result to the preoperative Pyridium pad test after pessary insertion were found to have urinary incontinence postoperatively . Postmenopausal women had twice the risk of developing occult SUI . CONCLUSION Preoperative testing is useful to identify women with genitourinary prolapse who have occult SUI . Women with a positive result may need a systematic clinical evaluation and urodynamic studies to characterize the incontinence . They can be then counseled preoperatively regarding concomitant anti-incontinence procedures BACKGROUND We design ed this trial to assess whether the addition of st and ardized Burch colposuspension to abdominal sacrocolpopexy for the treatment of pelvic-organ prolapse decreases postoperative stress urinary incontinence in women without preoperative symptoms of stress incontinence . METHODS Women who did not report symptoms of stress incontinence and who chose to undergo sacrocolpopexy to treat prolapse were r and omly assigned to concomitant Burch colposuspension or to no Burch colposuspension ( control ) and were evaluated in a blinded fashion three months after the surgery . The primary outcomes included measures of stress incontinence ( symptoms , stress testing , or treatment ) and measures of urge symptoms . Enrollment was stopped after the first interim analysis because of a significantly lower frequency of stress incontinence in the group that underwent the Burch colposuspension . RESULTS Of 322 women who underwent r and omization , 157 were assigned to Burch colposuspension and 165 to the control group . Three months after surgery , 33.6 percent of the women in the Burch group and 57.4 percent of the controls met one or more of the criteria for stress incontinence ( P<0.001 ) [ Corrected ] . There was no significant difference between the Burch group and the control group in the frequency of urge incontinence ( 32.7 percent vs. 38.4 percent , P=0.48 ) . After surgery , women in the control group were more likely to report bothersome symptoms of stress incontinence than those in the Burch group who had stress incontinence ( 24.5 percent vs. 6.1 percent , P<0.001 ) . CONCLUSIONS In women without stress incontinence who are undergoing abdominal sacrocolpopexy for prolapse , Burch colposuspension significantly reduced postoperative symptoms of stress incontinence without increasing other lower urinary tract symptoms OBJECTIVE Severe prolapse may mask potential genuine stress urinary incontinence in women . Some have suggested that a suspending urethropexy be performed in women who have potential genuine stress incontinence demonstrated by barrier reduction of the prolapse preoperatively . Our aim was to compare outcomes after prolapse surgery that included a formal bladder neck suspension with those operations that did not . STUDY DESIGN This prospect i ve r and omized clinical trial assigned 32 women with bladder neck hypermobility and stage III or IV pelvic organ prolapse to receive either a needle colposuspension or bladder neck endopelvic fascia plication as part of the vaginal reconstructive surgery . Twenty-nine subjects underwent detailed clinical , anatomic , urodynamic , and quality -of-life evaluations before and 6 weeks and 6 months after surgery ; 23 completed urinary diary and quality -of-life evaluations after a mean of 2.9 years . RESULTS Needle colposuspension increased short-term complications without providing additional protection from de novo stress incontinence . Barrier testing before surgery predicted urethral sphincteric resistance after surgery ; however , such testing neither predicted a patient 's function after surgery nor indicated the need for a suspending urethropexy . The combination of a needle colposuspension with a sacrospinous ligament suspension predisposed to the early development of support defects of the upper anterior vaginal segment and to failure of bladder neck support . CONCLUSIONS Preoperative barrier testing in women with severe prolapse is not useful in identifying individuals who require a suspending urethropexy . Needle colposuspension increases short-term complications , lacks durability , and may predispose to early and severe recurrent anterior prolapse when performed with a sacrospinous ligament vault suspension OBJECTIVE The purpose of this study was to show 12-month outcomes of a r and omized trial that compared vaginal prolapse repair with and without mesh . STUDY DESIGN Women with stage ≥2 prolapse were assigned r and omly to vaginal repair with or without mesh . The primary outcome was prolapse stage ≤1 at 12 months . Secondary outcomes included quality of life and complications . RESULTS All 65 evaluable participants were followed for 12 months after trial stoppage for mesh exposures . Thirty-two women had mesh repair ; 33 women had traditional repair . At 12 months , both groups had improvement of pelvic organ prolapse-quantification test points to similar recurrence rates . The quality of life improved and did not differ between groups : 96.2 % mesh vs 90.9 % no-mesh subjects reported a cure of bulge symptoms ; 15.6 % had mesh exposures , and reoperation rates were higher with mesh . CONCLUSION Objective and subjective improvement is seen after vaginal prolapse repair with or without mesh . However , mesh result ed in a higher reoperation rate and did not improve 1-year cure OBJECTIVES : To report anatomic and functional outcomes 2 years after sacrocolpopexy in stress-continent women with or without prophylactic Burch colposuspension . METHODS : In the Colpopexy and Urinary Reduction Efforts ( CARE ) trial , stress-continent women undergoing sacrocolpopexy were r and omized to receive or not receive a Burch colposuspension . Outcomes included urinary symptoms , other pelvic symptoms , and pelvic support . St and ardized pelvic organ prolapse quantification examinations and vali date d outcome measures including the Pelvic Floor Distress Inventory and the Pelvic Floor Impact Question naire were completed before surgery and at several postoperative intervals , including at 2 years . RESULTS : This analysis is based on 302 of 322 r and omized participants . Most were Caucasian ( 94 % ) , with a mean age of 62±10 years ( mean±st and ard deviation ) . Two years after surgery , 32.0 % and 45.2 % of women in the Burch and control groups , respectively , met the stress incontinence endpoint ( presence of symptoms or positive cough stress test or interval treatment for stress incontinence , P=.026 ) . The apex was well supported ( point C within 2 cm of total vaginal length ) in 95 % of women , and this was not affected by concomitant Burch ( P=.18 ) . There was a trend toward fewer urgency symptoms in the Burch group ( 32.0 % versus 44.5 % no Burch , P=.085 ) . Twenty participants experienced mesh or suture erosions . CONCLUSION : The early advantage of prophylactic Burch colposuspension for stress incontinence that was seen at 3 months remains at 2 years . Apical anatomic success rates are high and not affected by concomitant Burch . CLINICAL TRIAL REGISTRATION : www . clinical trials.gov , Clinical Trials.gov , NCT00065845 LEVEL OF EVIDENCE : |
11,766 | 24,556,770 | The majority of the articles , however , reported that TBL provided a positive learning experience for students . | PURPOSE Team-based learning ( TBL ) , a structured form of small-group learning , has gained popularity in medical education in recent years .
A growing number of medical schools have adopted TBL in a variety of combinations and permutations across a diversity of setting s , learners , and content areas .
The authors conducted this systematic review to establish the extent , design , and practice of TBL programs within medical schools to inform curriculum planners and education design ers . | PURPOSE Team-based learning ( TBL ) has been successfully used in non-medical curricula , but its effectiveness in medical education has not been studied extensively . We evaluated the impact of TBL on the academic performance of Year 2 medical students at Wright State University by comparing this active learning strategy against a traditional method of case-based group discussion ( CBGD ) . METHODS A prospect i ve crossover design assigned 83 Year 2 medical students to either CBGD or TBL for 8 pathology modules in the systems-based curriculum . The effectiveness of both learning methods was assessed by performance on pathology-based examination questions contained in end-of-course examinations . The highest and lowest academic quartiles of students were evaluated separately . Students ' opinions of both methods were surveyed . RESULTS No significant differences in whole group performance on pathology-based examination questions were observed as a consequence of experiencing TBL versus CBGD . However , students in the lowest academic quartile showed better examination performance after experiencing TBL than CBGD in 4 of 8 modules ( P = 0.035 ) . Students perceived that the contributions of peers to learning were more helpful during TBL than CBGD ( P = 0.003 ) . CONCLUSION This study demonstrates that TBL and CBGD are equally effective active learning strategies when employed in a systems-based pre- clinical pathology curriculum , but students with lower academic performance may benefit more from TBL than CBGD |
11,767 | 12,819,163 | Although there was evidence that naloxone increased alveolar ventilation , no data were found on the specified primary outcomes of this review : the need for assisted ventilation or admission to a neonatal unit .
CONCLUSIONS There is a need for a r and omised controlled trial to determine if naloxone confers any clinical ly important benefits on newborn infants with respiratory depression that may be due to transplacentally acquired narcotic | BACKGROUND Naloxone , a specific opiate antagonist , is available for the treatment of newborn infants with respiratory depression that may be due to transplacentally acquired opiates .
AIMS To determine if this treatment has any clinical ly important benefits , and whether there are any harmful effects . | Nalorphine and naloxone were compared as to their effectiveness as pethidine antagonists . 85 infants were divided into a control group containing 19 newborn babies whose mothers did not receive pethidine and the babies received no antagonist , and three groups in which the mothers all received pethidine and the babies had either no antagonist ( 24 ) , nalorphine IV ( 16 ) , or naloxone IV ( 26 ) . All the babies were assessed by measuring their neurobehavioural states and respiratory functions . A further 12 newborn babies had naloxone plasma levels measured by radioimmunoassay . Although st and ard doses of nalorphine effectively antagonised the depressive effect on respiration induced by pethidine , there was a pronounced and undesirable excitatory agonist action . Naloxone was not observed to have any agonist activity , but the recommended IV dose ( 0.01 mg/kg ) had only a slight and delayed antagonist action as measured by respiratory function tests . A more rapid and improved antagonism was noted after this dose was doubled ( 0.02 mg/kg ) . The plasma elimination-phase half-life of naloxone after intravenous cord injection was about 3 To investigate the presence of subtle narcotic depression following maternal narcotic analgesia , we have evaluated the effects of naloxone versus placebo in a double-blind parallel group study in 43 normal term newborn infants whose mothers had received routine narcotic analgesia within six hours prior to delivery . Infants were given either an intramuscular injection of 20 microgram/kg naloxone or 0.20 ml/kg placebo after determination of the one-minute Apgar score , and the following measurements were compared : Apgar scores at one and five minutes , capillary blood gas values at one , 60 , 120 , and 240 minutes , and neurobehavioral assessment s at one , 4 , and 24 hours . No adverse effects from naloxone were observed . Neither Apgar scores nor capillary blood gas determinations differed significantly between the two groups . Response to sound was significantly higher in the naloxone group at 24 hours . The alertness score was significantly higher for the naloxone group at one and four hours ; the general assessment score for the naloxone group was significantly higher at four and 24 hours . Average scores of naloxone and placebo groups were also different at four and 24 hours of age . These data demonstrate that maternal narcotic analgesia may produce subtle changes in alertness and general behavior not reflected by Apgar scores or respiratory status , potentially reversible by administration of naloxone shortly following delivery Abstract . Infants born to mothers receiving 100 mg of pethidine during labor , were r and omly given either 100 μg of naloxone ( n = 14 ) or 0.25 ml 0.9 % NaCl ( n = 13 ) one hour post partum . Infant behavior was assessed with the Brazelton Neonatal Behavioral Assessment Scale ( BNBAS ) and the Broussard Neonatal Perception Inventory ( NPI ) . No differences in cluster scores on the BNBAS were found between the two groups . Both groups improved scores over time in 4 out of 7 clusters . On the NPI , mothers assessed naloxone infants as having less optimal behavior than did the control mothers . The results of this study on the effects of naloxone on infant behavior and maternal perception of newborn behavior do not warrant administration of naloxone after maternal analgesia with pethidine in the absence of clinical evidence of respiratory depression in the newborn The effects on mature newborn have been compared at 0.5 , 4 , 8 12 24 and 48 hr after birth , of maternally administered epidural bupivacaine ( 11 babies ) or pethidine ( 18 babies ) or pethidine reversed by naloxone administered intramuscularly to the newborn ( 15 babies ) . Bupivacaine ( mean dose 130 mg ) had less effect that pethidine ( mean dose 183.3 mg ) on alveolar carbon dioxide tension ( PACO2 ) at 0.5 hr after birth , but had a similar effect to pethidine on feeding , elicited reflexes and produced more depression of muscle tone up to 48 hr . Bupivacaine had more effect on PACO2 feeding measures , elicited reflexes and muscle tone at almost all examination periods than pethidine ( mean dose 157.0 mg ) reversed by naloxone ( 200 micrograms intramuscularly ) . Except at delivery , the effects of bupivacaine or pethidine on respiration and feeding up to 48 hr after birth were similar . There were more signs of depression with both drugs than when pethidine had been reversed by naloxone Twenty neonates whose mothers had received meperidine ( 1.0 to 1.5 mg/kg ) intravenously within three hours of delivery were studied to determine the effectiveness of naloxone in reversing neonatal respiratory depression . The following measurements were carried out within 20 to 30 minutes after delivery : minute ventilation , end tidal CO2 , and ventilatory response to CO2 . These determinations were repeated after administration of either placebo or naloxone , 0.01 mg/kg intramuscularly . Minute ventilation and PAco were within a normal range before medication in both groups , but the slope of the CO2 response curve was decreased , indicating mild-to-moderate respiratory depression . After administration of placebo the test results did not change significantly . After administration of naloxone , VE increased significantly ( P less than 0.05 ) and the slope of the CO2 response curve doubled ( P less than 0.001 ) . Naloxone effectively reverses narcotic depression of the respiratory center in the newborn infant |
11,768 | 20,186,025 | These results are not significantly affected by the type of induction therapy or the timing of restaging .
The ability to identify patients who have achieved mediastinal downstaging other than by a careful primary mediastinoscopy is poor | BACKGROUND Many clinicians use restaging after induction therapy as a way to select patients for surgery . | Surgical therapy for stage III non-small cell lung cancer ( NSCLC ) has not result ed in substantial long-term survival . Neoadjuvant treatment programs that could down-stage the tumor and achieve increased long-term survival would be of obvious benefit . We have used preoperative simultaneous chemotherapy and irradiation in 85 patients with clinical stage III non-small cell lung cancer considered c and i date s for surgical resection . One group of 56 patients was treated with cisplatin , 5-fluorouracil , and simultaneous irradiation for five days every other week for a total of four cycles . After treatment , 39 patients underwent resection , and the operative mortality was 2 ( 5 % ) of 39 . A second trial was undertaken in which etoposide ( VP-16 ) was added because of its synergism with cisplatin . In this group , 29 patients were considered to have potentially resectable disease , and 23 underwent thoracotomy with 1 operative death ( 4 % ) . Of the total of 62 patients having thoracotomy , 60 underwent resection ( 97 % ) . Complications were major , and there were four bronchopleural fistulas . For the 85 patients eligible for surgical intervention in these two groups of patients , the Kaplan-Meier median survival estimate is 40 % at 3 years . The median survival of the 62 patients having thoracotomy is 36.6 months . Combination preoperative chemotherapy and irradiation is feasible with acceptable toxicity and operative mortality in patients with clinical stage III non-small cell lung cancer . Prospect i ve r and omized studies are suggested for further evaluation of this treatment program OBJECTIVES Surgical resection after preoperative chemotherapy in patients with non-small cell lung cancer might only be best for patients who are responders . We compared positron emission tomographic scanning with 2-fluoro-2-deoxy-d-glucose ( FDP-PET scanning ) with computed tomographic scanning to evaluate their ability to predict this response for the primary tumor , N1 and N2 lymph nodes . METHODS All patients with non-small cell lung cancer who had an initial FDP-PET scan staging with tissue biopsy , neoadjuvant chemotherapy , repeat FDP-PET scanning , and repeat biopsies were prospect ively studied . RESULTS There were 34 patients ( 24 men ; median age , 64 years ) . Eleven patients had N2 disease , and 7 had N1 disease . Twenty-seven patients received chemotherapy , and 7 patients received chemotherapy and radiation . All but 9 patients underwent resection . Statistical analysis showed FDP-PET scanning to be more specific ( P < .0001 ) , to have a higher positive predictive value ( P = .0018 ) , and to have a higher negative predictive value ( P < .0001 ) than computed tomographic scanning for predicting residual tumor at the primary site . FDP-PET scanning was more sensitive ( P < .0001 ) and more accurate ( P < .0001 ) , had a higher positive predictive value ( P < .0001 ) , and had a higher negative predictive value ( P = .0002 ) than computed tomographic scanning for paratracheal nodes ( number 2 and 4 lymph nodes ) . FDP-PET scanning had a higher positive predictive value ( P < .0001 ) than computed tomographic scanning for the other N2 ( numbers 5 , 6 , 7 , 8 , and 9 ) lymph nodes . CONCLUSIONS Repeat FDP-PET scanning is more specific and has a higher positive predictive value and negative predictive value than computed tomographic scanning for detecting residual tumor in the lung in patients with non-small cell lung cancer who have received preoperative chemotherapy . It is more sensitive and accurate for paratracheal N2 nodes as well . However , there is no significant difference in its detection of N1 lymph nodes PURPOSE A number of studies have demonstrated that 18F-fluorodeoxyglucose positron emission tomography ( FDG-PET ) is effective for staging of lung cancer . However , the efficacy of FDG-PET for staging lung cancer after neoadjuvant treatment is still controversial . This study compared FDG-PET and computed tomography ( CT ) for lung cancer staging , and evaluated the ability of the two methods to predict the pathologic response of the primary tumor to neoadjuvant treatment . PATIENTS AND METHODS Twenty-two patients who underwent neoadjuvant treatment followed by surgery were investigated . Eighteen patients received chemoradiotherapy and four patients received chemotherapy only . One hundred and three lymph node stations in the 22 patients were evaluated by FDG-PET and CT . The pathologic responses of the tumors were compared by FDG-uptake and tumor size on CT for the 15 patients who underwent FDG-PET and CT both before and after neoadjuvant treatment . RESULTS There was no significant difference in the ability of FDG-PET or CT to predict residual viable tumor . Although positive predictive value by FDG-PET ( 0.29 ) was lower than that by CT ( 0.64 ) ( p=0.04 ) in the mediastinal lymph nodes , there were no statistically significant differences in the other results of lymph nodes by FDG-PET and CT . Both decrease in FDG-uptake and decrease in tumor size by CT after neoadjuvant treatment correlated significantly with pathologic response in the 15 patients ( p=0.003 and 0.009 , respectively ) . CONCLUSION FDG-PET did not appear to offer any advantages over CT for lymph node staging or for predicting the pathologic response after neoadjuvant treatment of non-small cell lung cancer PURPOSE This phase II trial was design ed to evaluate the feasibility , toxicity , response rates , and survival for neoadjuvant chemotherapy and radiotherapy ( RT ) followed by surgical resection in newly diagnosed patients with surgically staged IIIA non-small-cell lung carcinoma ( NSCLC ) . PATIENTS AND METHODS Previously untreated patients with NSCLC underwent bronchoscopy , chest and abdominal computed tomography ( CT ) , bone scan , and surgical staging of the mediastinum . Neoadjuvant treatment consisted of concurrent chemotherapy and RT . Patients then underwent surgical resection , which was followed in turn by additional chemotherapy and RT . Chemotherapy included cisplatin 100 mg/m2 on days 1 and 29 , vinblastine 3 mg/m2 on days 1 and 3 and 29 and 31 , and fluorouracil ( 5-FU ) 30 mg/kg/d by infusion on days 1 to 3 and 29 to 31 ( FVP ) . RT began on day 1 and included 3,000 cGy in 15 fractions . Surgery took place on day 55 , and one more cycle of chemotherapy and an additional 3,000 cGy of RT began on day 85 . RESULTS Forty-one eligible patients ( median follow-up , 53 months ) were studied . N2 disease was present in 80 % , whereas 20 % had T3N0 or T3N1 lesions . Response to neoadjuvant chemotherapy and RT included no complete responses ( CR ) , 21 ( 51 % ) partial responses ( PR ) or regressions , 19 ( 46 % ) stable disease ( SD ) , and one ( 2 % ) progressive disease ( PD ) . Thirty-one patients underwent surgery , and 25 were resected . In four of the 25 resection specimens , no viable tumor was present , whereas in three of the six unresectable patients , extensive biopsy results demonstrated only necrotic tumor . The maximum response achieved using all protocol treatment was 27 ( 66 % ) CRs , seven ( 17 % ) PRs or regression , six ( 15 % ) SDs , and one ( 2 % ) PD . Toxicity was substantial and primarily hematologic . There were six ( 15 % ) treatment-related deaths , which included three perioperative deaths and three chemotherapy-related toxicity deaths . The Kaplan-Meier curve indicated a 1-year survival of 58 % and a median survival of 15.5 months . Nine patients ( 22 % ) remain disease-free . CONCLUSIONS There was a reasonably high rate of PR associated with concurrent neoadjuvant chemotherapy and RT , and a high percentage of patients who ultimately were rendered completely disease-free . However , treatment-related morbidity and mortality was common . Median survival seemed to be only modestly improved beyond that achieved with less intensive means of treatment . However , a group has emerged of patients who enjoy prolonged disease-free survival and possible cure To evaluate the usefulness of transbronchial needle aspiration biopsy ( TBNA ) for the diagnosis of mediastinal involvement , we have prospect ively examined 316 patients with morphologically verified bronchogenic carcinoma . The percentage of positive aspirations ( 149 of 316 ) from the three basic lymph node groups in the mediastinum was not significantly different . Tumor cells were aspirated from the mediastinum in 75 of 112 patients with radiologically positive findings and in patients with 74 of 204 radiologically negative findings . Mediastinal involvement was verified even in 61 of 196 patients with a normal endoscopic picture . Metastases were proved in 14 of 39 patients with peripheral versus 135 of 277 patients with central carcinoma . Tumor cells were aspirated in 47 of 76 patients with undifferentiated small cell carcinoma , 92 of 227 patients with squamous cell carcinoma , and 10 of 13 patients with adenocarcinoma . Our results suggest that TBNA being a highly diagnostic and less invasive method , will prove its clinical importance BACKGROUND Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases ( N2 ) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival . We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with st and ard concurrent chemotherapy and definitive radiotherapy without resection . METHODS Patients with stage T1 - 3pN2M0 non-small-cell lung cancer were r and omly assigned in a 1:1 ratio to concurrent induction chemotherapy ( two cycles of cisplatin [ 50 mg/m(2 ) on days 1 , 8 , 29 , and 36 ] and etoposide [ 50 mg/m(2 ) on days 1 - 5 and 29 - 33 ] ) plus radiotherapy ( 45 Gy ) in multiple academic and community hospitals . If no progression , patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy . Two additional cycles of cisplatin and etoposide were given in both groups . The primary endpoint was overall survival ( OS ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00002550 . FINDINGS 202 patients ( median age 59 years , range 31 - 77 ) were assigned to group 1 and 194 ( 61 years , 32 - 78 ) to group 2 . Median OS was 23.6 months ( IQR 9.0-not reached ) in group 1 versus 22.2 months ( 9.4 - 52.7 ) in group 2 ( hazard ratio [ HR ] 0.87 [ 0.70 - 1.10 ] ; p=0.24 ) . Number of patients alive at 5 years was 37 ( point estimate 27 % ) in group 1 and 24 ( point estimate 20 % ) in group 2 ( odds ratio 0.63 [ 0.36 - 1.10 ] ; p=0.10 ) . With N0 status at thoracotomy , the median OS was 34.4 months ( IQR 15.7-not reached ; 19 [ point estimate 41 % ] patients alive at 5 years ) . Progression-free survival ( PFS ) was better in group 1 than in group 2 , median 12.8 months ( 5.3 - 42.2 ) vs 10.5 months ( 4.8 - 20.6 ) , HR 0.77 [ 0.62 - 0.96 ] ; p=0.017 ) ; the number of patients without disease progression at 5 years was 32 ( point estimate 22 % ) versus 13 ( point estimate 11 % ) , respectively . Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 ( 77 [ 38 % ] and 20 [ 10 % ] , respectively ) and group 2 ( 80 [ 41 % ] and 44 [ 23 % ] , respectively ) . In group 1 , 16 ( 8 % ) deaths were treatment related versus four ( 2 % ) in group 2 . In an exploratory analysis , OS was improved for patients who underwent lobectomy , but not pneumonectomy , versus chemotherapy plus radiotherapy . INTERPRETATION Chemotherapy plus radiotherapy with or without resection ( preferably lobectomy ) are options for patients with stage IIIA(N2 ) non-small-cell lung cancer . FUNDING National Cancer Institute , Canadian Cancer Society , and National Cancer Institute of Canada Thirty-three patients with T3,N2,M0 or T4,N2,M0 , non-small-cell lung cancer ( NSCLC ) took part in a phase 2 study in an attempt to evaluate the feasability of neoadjuvant chemotherapy followed by surgery and thoracic radiotherapy . Chemotherapy consisted of daily administration of the following treatment : etoposide , 100 mg/m2 ; cisplatin , 25 mg/m2 ; ifosfamide , 1.5 g/m2 ; and mesna , 1.8 g/m2 for 4 days . Three cycles were planned starting every 21 days . Responding patients underwent a thoracotomy in order to attempt a resection and then received a 45 Gy of thoracic radiotherapy . The results of response and resection rates have been published and the present final report deals with the long-term results . Chemotherapy induced a 55 percent partial response rate and a 15 percent complete response rate allowing a complete resection in 55 percent of the patients . Complete remission was histologically confirmed for the five complete responders . Although the median survival was short ( 10 months ) , six patients were long-term survivors ( 3-year survival rate : 19 percent ) . Survival was significantly influenced by the type of resection : patients for whom a complete resection was possible survived the longest with a median survival three times that of the other patients . Modalities of relapses differed according to the results of surgery : 8 of the 15 patients who did not undergo a complete surgical resection experienced a local relapse during the first 18 months of follow-up whereas in the complete resection group , central nervous system metastasis was the main site of relapse . We conclude that the neoadjuvants ifosfamide , cisplatin , and etoposide in patients with locally advanced NSCLC are feasible to use and allow a 19 percent 3-year survival rate . These results are the rationale of an ongoing r and omized study comparing neoadjuvant chemotherapy followed by surgery and surgery alone . This study is design ed to test whether neoadjuvant chemotherapy improves survival of patients with locally advanced NSCLC In the scope of a prospect i ve multi-centre study after neoadjuvant combined chemotherapy ( carboplatin , ifosfamide , etoposide , vindesine ) and radiotherapy ( 45 Gy ) 40 resection specimens of locally advanced non-small-cell lung cancer were analysed in order to establish reproducible pathological/anatomical results of tumour regression . Resection specimens of 28 squamous cell carcinomas and 12 adenocarcinomas were investigated using serial sections of the primary lesion . The mean age of the patients was 57 years . The results were compared to spontaneous regressive changes in a control group of 50 untreated non-small-cell lung cancers . Marked scarry fibrosis in the region of the former primary tumour , concentric foci of fresh tumour necroses and surrounding foam cell clusters with transition into vascular granulation tissue could be established as characteristic features of therapy-induced tumour regression , whereas untreated carcinomas revealed necroses with adjoining vital tumour tissue . Using a threestep regression system , 3 tumours could be classified as grade I ( no or only slight tumour regression ) , 10 tumours as grade IIA ( marked but incomplete tumour regression , more than 10 % vital tumour tissue ) , 20 tumours as grade IIB ( less than 10 % vital tumour tissue ) and 7 tumours as grade III ( complete tumour regression without vital tumour tissue ) . After a median follow-up period of 32.3 months in patients with grade IIB or III tumour regression ( “ responders ” ) the median survival time of 27.9 months was found to be significantly longer than in patients with grade I or IIA tumour regression ( “ non-responders ” ) with a median survival period of 13.7 months ( log-rank test , P=0.020 ) . The resection specimens analysed , which were obtained 7 weeks ( on average ) after the end of radiochemotherapy , did not show specific changes due to preoperative therapy , but quite characteristic histological alterations in the former tumour area were registered , which had been induced by combined neoadjuvant radiation and chemotherapy . The grade of therapy-induced tumour regression could be shown to be a significant prognostic factor in non-small-cell lung cancer CONTEXT Up to 40 % of thoracotomies performed for non-small cell lung cancer are unnecessary , predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion ( T4 ) . Mediastinoscopy and the novel , minimally invasive technique of transesophageal ultrasound-guided fine-needle aspiration ( EUS-FNA ) target different mediastinal lymph node stations . In addition , EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus . OBJECTIVE To investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non-small cell lung cancer . DESIGN , SETTING , AND PATIENTS Prospect i ve , nonr and omized multicenter trial performed in 1 referral and 5 general hospitals in the Netherl and s. During a 3-year period ( 2000 - 2003 ) , 107 consecutive patients with potential resectable non-small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy . Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative . Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed . INTERVENTION The EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients . MAIN OUTCOME MEASURE Detection of mediastinal tumor invasion ( T4 ) and lymph node metastases ( N2/N3 ) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone . RESULTS The combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases ( 36 % ; 95 % confidence interval [ CI ] , 27%-46 % ) compared with either mediastinoscopy alone ( 20 % ; 95 % CI , 13%-29 % ) or EUS-FNA ( 28 % ; 95 % CI , 19%-38 % ) alone . This indicated that 16 % of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy . However , 2 % of the EUS-FNA findings were false-positive . CONCLUSION These preliminary findings suggest that EUS-FNA , when added to mediastinoscopy , improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion BACKGROUND Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer ( NSCLC ) . We hypothesized that , following a response to induction chemotherapy , surgical resection would be superior to thoracic radiotherapy as locoregional therapy . METHODS Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy . Responding patients were subsequently r and omly assigned to surgical resection or radiotherapy . Survival curves were estimated using Kaplan-Meier analyses from time of r and omization . RESULTS Induction chemotherapy result ed in a response rate of 61 % ( 95 % confidence interval [ CI ] = 57 % to 65 % ) among the 579 eligible patients . A total of 167 patients were allocated to resection and 165 to radiotherapy . Of the 154 ( 92 % ) patients who underwent surgery , 14 % had an exploratory thoracotomy , 50 % a radical resection , 42 % a pathologic downstaging , and 5 % a pathologic complete response ; 4 % died after surgery . Postoperative radiotherapy was administered to 62 ( 40 % ) of patients in the surgery arm . Among the 154 ( 93 % ) irradiated patients , overall compliance to the radiotherapy prescription was 55 % , and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4 % and 7 % ; one patient died of radiation pneumonitis . Median and 5-year overall survival for patients r and omly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7 % versus 14 % , respectively ( hazard ratio = 1.06 , 95 % CI = 0.84 to 1.35 ) . Rates of progression-free survival were also similar in both groups . CONCLUSION In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy , surgical resection did not improve overall or progression-free survival compared with radiotherapy . In view of its low morbidity and mortality , radiotherapy should be considered the preferred locoregional treatment for these patients Purpose : This prospect i ve study evaluated the prognostic significance of 18F-fluorodeoxyglucose ( 18F-FDG ) uptake in primary non-small cell lung cancer ( NSCLC ) at positron emission tomography , in a carefully staged population , while correcting for partial volume effects . Experimental Design : Two hundred eight potentially resectable NSCLC patients were referred for FDG positron emission tomography staging after thoracic computed tomography . Each tumor stage was confirmed surgically , or for some stage IV tumors by additional imaging . The tumor maximum pixel-st and ardized uptake value ( maxSUV ) and the maxSUV partial volume corrected for lesion size ( PVCmaxSUV ) were compared with overall survival and disease-free survival using Cox proportional hazards regression . Results : Stage distribution : stage I , 36 % ; stage II , 15 % ; stage III , 30 % ; stage IV , 19 % . Patients were followed for a median of 33.6 months , with 90 deaths from NSCLC ( median survival for all stages , 43.3 months ) . With respect to overall survival , the most significant cutoff value for both maxSUV and PVCmaxSUV was 7 . MaxSUV ≥7 was significantly associated with an increased risk of death from NSCLC in univariable analysis , whereas PVCmaxSUV ≥7 was only marginally associated . However , in multivariable analyses , neither maxSUV ≥7 nor PVCmaxSUV ≥7 provided significant additional prognostic information over stage , tumor size , and age . In the 103 patients who underwent surgical resection only , surgical stage , but not maxSUV or PVCmaxSUV , was univariably associated with survival or recurrence . SUV definitions based on lean body mass , body surface area , and plasma glucose correction yielded identical results . Conclusions : As expected , tumor stage is prognostic in NSCLC . However , tumor FDG uptake does not provide additional prognostic information . This prospect i ve study contradicts prior reports Background : Accurate prediction of pathologic response to chemoradiation ( CHEMO-XRT ) has a significant impact on the treatment of patients with non-small cell lung cancer ( NSCLC ) and mediastinal lymph node ( LN ) metastasis ( N2 disease ) . Objective : This pilot study evaluates the ability of EUS-FNA to predict pathologic response in LN following CHEMO-XRT in NSCLC patients with N2 disease . Patients and Methods : Retrospective analysis of prospect ively collected data on patients with NSCLC and biopsy-proven N2 disease who underwent restaging by EUS following CHEMO-XRT . At restaging , FNA was performed on the same LN , if present , or any other visible LN in the posterior mediastinum . Response to therapy ( N0 disease ) was defined by either absence of mediastinal LN or residual disease on FNA . Those staged N0 by EUS underwent tumor resection with complete LN dissection . Results : Fourteen patients met the criteria for evaluation . Restaging by EUS suggested disease response in 7 patients and residual disease in 6 ; tissue yield was unsatisfactory in 1 patient . Eleven of 14 patients in whom mediastinal LN were seen at restaging by EUS underwent FNA : the aspirate was benign in 4 , residual disease was found in 6 , and an inadequate sample was obtained in 1 patient . In 3 patients no mediastinal LN were evident at EUS . Final diagnosis on the 7 patients in whom EUS suggested N0 disease was established at surgery : EUS was true negative in 6 and false negative in 1 . Of the 6 patients with residual disease , 5 underwent palliative CHEMO-XRT and 1 underwent extended tumor resection . The patient in whom tissue sampling was inadequate was found to have residual disease at surgery . The diagnostic accuracy of EUS-FNA for predicting mediastinal response to preoperative CHEMO-XRT was 86 % . Conclusions : EUS-FNA appears to qualify as an accurate , safe and minimally invasive diagnostic technique for restaging of mediastinal LN after CHEMO-XRT in NSCLC patients . Given this promising preliminary data , a prospect i ve evaluation is justified This study was performed to investigate the utility of FDG-PET for : ( 1 ) initial staging , and ( 2 ) restaging of the primary and mediastinal nodal lesions 2 weeks after the completion of preoperative chemoradiotherapy in patients with stage III non-small cell lung cancer ( NSCLC ) . Twenty-six patients with histologically confirmed stage III NSCLC were accrued to this study from April 1993 to July 1998 . They included 21 with stage IIIA ( N2 ) NSCLC who were enrolled into an institutional phase II study , and 5 patients with a highly selected subset of stage IIIB disease characterized by the presence of microscopic metastatic disease in contralateral mediastinal lymph nodes who were also treated with preoperative chemoradiotherapy ; N3 lesions ( n=3 ) and minimal T4 lesions . Demographic characteristics included median age 62 years ( a range from 47 to 73 ) and gender ratio of male 15 to female 11 . Histologic types of tumor consisted of squamous cell carcinoma 6 , adenocarcinoma 11 , large cell carcinoma 5 , and non-small cell carcinoma 4 . All patients had FDG-PET imaging of the chest before the initiation and 2 weeks after completion of preoperative therapy . The FDG-PET images were evaluated qualitatively for uptake at the primary tumor sites and mediastinal lymph nodes . St and ard uptake values ( SUVs ) were also calculated for the primary tumors and all PET findings were correlated with surgical histopathologic data . Preoperative chemoradiotherapy result ed in complete pathologic response in 8 of 26 primary lesions . By qualitative analysis , 96 % of these tumors showed level 3 or 4 uptake before preoperative chemoradiotherapy . After chemoradiotherapy , 57 % ( 15/26 ) of patients showed at least a one level decrease in uptake , and the sensitivity and specificity of FDG-PET for differentiating residual tumor from pathologic complete response were 67 % ( 12/18 ) and 63 % ( 5/8 ) . Mean SUV was 14.87+/-7.11 at baseline and decreased to 5.72+/-3.35 after chemoradiotherapy ( n=21 , P<0.00001 ) . When a value of 3.0 was used as the SUV cut-off , sensitivity and specificity were 88 and 67 % , respectively . The mean values of visual intensity were 3.87+/-0.35 and 3.8+/-0.51 for patients who achieved pathologic complete response ( n=8 ) and for those who showed residual cancer after the preoperative therapy ( n=18 ) , respectively . The mean SUVs were 16.97+/-8.52 and 14.03+/-6.61 for patients who achieved pathologic complete response ( n=6 ) and for those who showed residual cancer ( n=15 ) after the preoperative therapy , respectively . Therefore , the degree of FDG uptake before preoperative chemoradiotherapy did not provide predictive value for subsequent tumor response . For mediastinal initial staging , the sensitivity and specificity of FDG-PET were 75 and 90.5 % . The sensitivity and specificity of FDG-PET for mediastinal restaging were 58.0 and 93.0 % . These results indicate that FDG-PET is useful for monitoring the therapeutic effect of neoadjuvant chemoradiotherapy in patients with stage III NSCLC . For the primary lesions , SUV based analysis has high sensitivity but limited specificity for detecting residual tumor . In contrast , for restaging of mediastinal lymph nodes , FDG-PET is highly specific , but has limited sensitivity BACKGROUND The ability to accurately predict pathologic response to preoperative chemotherapy may have a significant impact on the treatment strategy for non-small cell lung cancer ( NSCLC ) . The purpose of this study was to examine the accuracy of positron emission tomography ( PET ) scanning in predicting the pathologic response to preoperative chemotherapy in the primary tumor and draining lymph nodes . METHODS A total of 25 patients were enrolled in two separate phase II trials investigating induction chemotherapy for NSCLC . All patients underwent pre-treatment and post-treatment PET scans followed by surgical resection . A significant PET scan response was defined as a reduction in the st and ard uptake value by 50 % or more . We defined a major pathologic response as either no disease or microscopic disease only in the primary tumor . The percentage change in st and ard uptake value was then calculated and correlated with pathologic response in the primary tumor . In addition , the presence or absence of nodal metastases as determined by the postchemotherapy PET scan was compared with final pathologic nodal stage . RESULTS The positive and negative predictive values for PET detection of major pathologic response in the primary tumor were 43 % and 100 % , respectively . Positron emission tomography did not accurately predict nodal status in 52 % of patients . The positive and negative predictive values of PET to detect node-positive disease were 73 % and 64 % , respectively . For N2 disease the positive predictive value of PET scans was less than 20 % . CONCLUSIONS Positron emission tomography scanning does not reliably predict pathologic response to preoperative chemotherapy in NSCLC in either the primary tumor or the draining lymph nodes Purpose The aim of this study was to evaluate FDG-PET for assessment of therapy response and for prediction of patient outcome after neo-adjuvant radio-chemotherapy ( NA RCT ) of advanced non-small cell lung cancer ( NSCLC ) . Methods Seventy patients with histologically proven stage III NSCLC underwent FDG-PET investigations before and after NA RCT . Changes in FDG uptake and PET findings after completion of NA RCT were compared with ( 1 ) the histology of tumour sample s obtained at surgery or repeat mediastinoscopy , and ( 2 ) treatment results in terms of achieved operability and long-term survival . Results The mean average FDG uptake of the primary tumours in the patient group decreased significantly during NA RCT ( p = 0.004 ) . Sensitivity , specificity and overall accuracy of FDG-PET were 94.5 % , 80 % and 91 % , respectively , for the detection of residual viable primary tumour , and 77 % , 68 % and 73 % , respectively , for the presence of lymph node metastases . A negative PET scan or a reduction in the st and ardised uptake value ( SUV ) of more than 80 % was the best predictive factor for a favourable outcome of further treatment . Progressive disease according to PET ( new tumour manifestations or increasing SUV ) was significantly correlated with an unfavourable outcome ( p = 0.005 ) . In this subgroup , survival of patients who underwent surgery was not significantly different from survival among those who did not undergo surgery , whereas for the whole patient group , complete tumour resection had a significant influence on outcome . Conclusion FDG-PET is suitable to assess response to NA RCT in patients with stage III NSCLC accurately . It was highly predictive for treatment outcome and patient survival . PET may be helpful in improving restaging after NA RCT by allowing reliable assessment of residual tumour viability BACKGROUND The efficacy of surgery for patients with non-small-cell lung cancer is limited , although recent studies suggest that preoperative chemotherapy may improve survival . We conducted a r and omized trial to examine the possible benefit of preoperative chemotherapy and surgery for the treatment of patients with non-small-cell lung cancer . METHODS We studied 60 patients ( 59 men and 1 woman ) with stage IIIA non-small-cell lung cancer . The patients were r and omly assigned to receive either surgery alone or three courses of chemotherapy ( 6 mg of mitomycin per square meter of body-surface area , 3 g of ifosfamide per square meter , and 50 mg of cisplatin per square meter ) given intravenously at three-week intervals and followed by surgery . All patients received mediastinal radiation after surgery . The resected tumors were evaluated by means of K-ras oncogene analysis and flow cytometry . RESULTS The median period of survival was 26 months in the patients treated with chemotherapy plus surgery , as compared with 8 months in the patients treated with surgery alone ( P < 0.001 ) ; the median period of disease-free survival was 20 months in the former group , as compared with 5 months in the latter ( P < 0.001 ) . The rate of recurrence was 56 percent in the group treated with chemotherapy plus surgery and 74 percent in the group treated with surgery alone . The prevalence of mutated K-ras oncogenes was 15 percent among the patients receiving preoperative chemotherapy and 42 percent among those treated with surgery alone ( P = 0.05 ) . Most of the patients treated with chemotherapy plus surgery had tumors that consisted of diploid cells , whereas the patients treated with surgery alone had tumors with aneuploid cells . CONCLUSIONS Preoperative chemotherapy increases the median survival in patients with non-small-cell lung cancer To assess the effect of neoadjuvant platinum-based chemotherapy on resectability , stage of disease at resection , and patterns of recurrence and survival in patients with IIIA , N2 non-small-cell lung cancer , we examined the first 60 patients treated with neoadjuvant chemotherapy followed by attempted resection in our institution . Of 67 patients identified , 7 patients were ineligible because of comorbidities , 3 patients refused chemotherapy , and 1 consented but died before treatment . Fifty-six received neoadjuvant chemotherapy . Complications of chemotherapy were minor , with no deaths . Fifty-four patients had thoracotomy ; 75 % ( n = 42 ) had complete resection and 25 % ( n = 14 ) had unresectable lesions . One postoperative death occurred ( 2 % ) . Pathologic review of specimens and nodal groups revealed that 41 % ( n = 23 ) were downstaged , 39 % ( n = 22 ) remained stage IIIA , and 19 % ( n = 11 ) progressed . Squamous histologic type was predictive of resectability , 18 of 20 patients having resectable squamous cell tumors ( p < 0.05 ) . Actuarial survivals at 1 and 2 years were 74 % and 52 % , respectively . In patients with resectable tumors survivals at 1 and 2 years were 85 % and 67 % , respectively . For those with unresectable lesions , survivals were 43 % and 14 % . Relapse-free survivals at 1 and 2 years for patients with resectable lesions were 70 % and 42 % , respectively . Relapses were local in 25 % ( n = 4 ) , at a distant site only in 50 % ( n = 8) , combined local and distant in 25 % ( n = 4 ) . Distant relapse occurred in the central nervous system only in 7 of 8 patients ( 88 % ) . Complete resectability was highly predictive of improved survival ( p < 0.0002 ) . Weight loss did not affect resectability but was associated with decreased survival ( p < 0.003 ) . Neoadjuvant chemotherapy appears to improve resectability and to pathologically downstage N2 non-small-cell lung cancer from stage IIIA . Multiinstitutional r and omized trials are needed to further demonstrate the efficacy of this approach BACKGROUND After induction treatment restaging of mediastinal disease in patients with stage III non-small cell lung cancer ( NSCLC ) may lead to selection of c and i date s for further surgical treatment . Nodal down-staging is the best predictive characteristic for proceeding with surgery . We report our experience in restaging with endoscopic ultrasound-guided fine needle aspirations ( EUS-FNA ) and with repeated integrated positron emission tomography and computed tomography ( PET-CT ) . METHODS Twenty-eight patients with stage III NSCLC were staged with integrated PET-CT , cerebral magnetic resonance imaging ( MRI ) and pathologically proven nodal disease . Restaging was performed with PET-CT and EUS-FNA on the same nodes that showed initially metastatic disease provided these nodal sites determined the tumor stage . Cerebral MRI was not repeated . When restaging EUS-FNA revealed no malignant cells anymore , patients were operated . The postoperative pathologic results were compared with the preoperative restaging EUS-FNA results . Also , patterns of decreased fluoro-2-deoxyglucose ( FDG ) uptake were compared with the postoperative pathologic results . RESULTS Restaging EUS-FNA was well tolerated in all patients even in those with clinical signs of radiation esophagitis . Of the 28 patients 15 were down-staged based on cytologic findings with restaging EUS-FNA and in one patient the cytology was not conclusive . Of these 15 patients , down-staging was histologically confirmed after mediastinal exploration in 11 patients and 1 patient had persistent nodal disease at resection . In 3 patients no mediastinal tissue verification was performed . Two subjects were not fit for operation , and in the other patient intraoperative nodal staging was omitted . The negative predictive value for restaging EUS-FNA was 91.6 % . The accuracy of EUS-FNA was 92.3 % . Concordance between findings of restaging EUS-FNA and metabolic response of lymph node metastases occurred in 17 out of 27 patients . CONCLUSION Restaging with EUS-FNA after induction chemo(-radiotherapy ) is well tolerated and predicts the absence of nodal metastasis reliably . Although changes in mediastinal FDG-PET uptake show a high concordance with EUS-FNA , pathological confirmation is still superior and therefore necessary . EUS-FNA is the procedure of first choice for mediastinal restaging OBJECTIVES The aim of the present study was to evaluate the feasibility and diagnostic value of repeat mediastinoscopy as part of the response-evaluation protocol of 2 phase II multimodality studies for either stage IIIA/B non-small cell lung cancer or small cell lung cancer . METHODS From January 1991 through December 1998 , 104 patients ( 79 men and 25 women ) with stage IIIA/B non-small cell lung cancer ( 84 patients ) or small cell lung cancer ( 17 patients ) were enrolled in 2 different multimodality trials and underwent remediastinoscopy after induction chemoradiotherapy . The median age was 56 years ( range , 34 - 72 years ) . Sensitivity , specificity , accuracy , and predictive values of remediastinoscopy were calculated by using st and ard definitions . RESULTS Remediastinoscopy was feasible in 98 % of cases . Mortality was nil , and morbidity very low ( 1.9 % ) . Lymph node downstaging ( N0 ) was observed in 84 patients , persisting N2 disease was observed in 15 patients , and N3 disease was observed in 5 patients . Sensitivity was 61 % , specificity was 100 % , and accuracy was 88 % . Positive predictive and negative predictive values reached 100 % and 85 % , respectively . According to the results of remediastinoscopy , 81 patients underwent surgical intervention , 3 refused the operation , and an unnecessary thoracotomy could be avoided in the remaining 20 . CONCLUSIONS Remediastinoscopy provides a histologic proof of mediastinal downstaging with high diagnostic accuracy , is technically feasible with low morbidity , and still remains a valuable tool , even in an era of highly sophisticated imaging and endoscopic procedures . Persisting nodal disease at repeat mediastinoscopy carries a poor survival in the majority of cases because of occult metastases , so that indication for surgical intervention in such an unfavorable group of patients should be evaluated very carefully A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical research ers to find a new treatment modality to improve the curative potential of surgery . Many Phas II trials have been carried out with induction chemo- or chemo-radiotherapy prior to surgery . From June 1988 to July 1991 , 46 patients with non-small cell lung cancer ( NSCLC ) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial . Patients received 2 - 3 cycles of high-dose cisplatin and etoposide . Forty-five were evaluable for response ; the response rate was 82 % ( 37/45 : 3 CR , 34 PR ) . Toxicity was primarily hematologic . Surgical resection was performed in 35 patients ; radical resection was possible in 28 patients ( 62 % ) ; three patients were incompletely resected and two patients were only explored . Three deaths were surgery-related . Median survival was 24.5 months with a 2-year survival of 53 % . Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate . The median survival seems to be prolonged and therefore , r and omized trials are needed to compare this approach with other treatment modalities PURPOSE Mediastinal restaging after induction therapy for non-small-cell lung cancer remains a difficult and controversial issue . The goal of this prospect i ve study was to compare the performance of integrated positron emission tomography (PET)--computed tomography ( CT ) and remediastinoscopy in the evaluation of mediastinal lymph node metastasis after induction chemotherapy . PATIENTS AND METHODS Thirty consecutive stage IIIA-N2 non-small-cell lung cancer patients surgically treated at our institution were entered onto this prospect i ve study . N2 disease was proven by cervical mediastinoscopy , at which a mean number of 3.8 lymph node levels were biopsied . After completion of induction chemotherapy , the mediastinum was reassessed by integrated PET-CT and remediastinoscopy . All patients underwent thoracotomy with attempted complete resection and systematic nodal dissection . RESULTS PET-CT showed no evidence of nodal disease ( N0 ) in 13 patients , Hilar nodal disease ( N1 ) disease in three patients , and residual mediastinal disease ( N2 ) in 14 patients . Remediastinoscopy was positive in only five patients . The preinduction involved lymph node level could be accurately re-evaluated in 18 patients . This was not the case in the other 12 because of extensive fibrosis and adhesions . In 17 patients , persistent N2 disease was found at thoracotomy . The sensitivity , specificity , and accuracy of PET-CT were 77 % , 92 % , and 83 % , respectively . These parameters for remediastinoscopy were 29 % , 100 % , and 60 % , respectively . Sensitivity ( P < .0001 ) and accuracy ( P = .012 ) were significantly better for PET-CT . CONCLUSION After a thorough staging mediastinoscopy , postinduction remediastinoscopy had a disappointing sensitivity because of adhesions and fibrosis . Integrated PET-CT yielded a better result than that obtained in previous studies with side-by-side PET and CT images OBJECTIVE This phase II trial assessed the feasibility , as measured by response rate , toxicity , resectability rate , and surgical morbidity and mortality rates , of perioperative paclitaxel and carboplatin chemotherapy in patients with early-stage non-small cell lung carcinoma . METHODS All patients required negative mediastinoscopy results and adequate medical parameters to undergo induction chemotherapy and an operation . Superior sulcus patients were excluded . Chemotherapy consisted of paclitaxel 225 mg/m(2 ) over 3 hours and carboplatin ( area under the curve = 6 ) every 21 days for 2 cycles preoperatively . Three postoperative cycles of chemotherapy were planned for patients undergoing complete resection . RESULTS Between June 1996 and July 1998 , 94 patients were entered into the study . Sixty-five ( 69 % ) were men , and the median age was 64 years ( range , 34 - 79 years ) . After induction chemotherapy , 53 of 94 ( 56 % ; 95 % confidence interval , 46%-67 % ) had a major objective response , 88 ( 94 % ) underwent surgical exploration , and 81 ( 86 % ; 95 % confidence interval , 78%-92 % ) underwent complete resection . Reasons for not undergoing an operation included disease progression ( n = 3 ) , clinical ly unresectable status ( n = 1 ) , death ( n = 1 ) , and patient lost to follow-up ( n = 1 ) . Two postoperative deaths occurred . Six ( 6 % ; 95 % confidence interval , 0%-13 % ) pathologic complete responses were observed . Ninety ( 96 % ) patients received the planned preoperative chemotherapy versus 45 % receiving postoperative chemotherapy . No unexpected chemotherapy or surgical morbidity occurred . The 1-year survival is currently estimated at 85 % , and the median survival has not yet been reached . CONCLUSIONS Induction chemotherapy with paclitaxel and carboplatin is feasible and produces a high response rate with acceptable morbidity and mortality rates in early-stage non-small cell lung carcinoma . A prospect i ve r and omized trial comparing 3 cycles of induction chemotherapy and surgery with surgery alone in early-stage non-small cell lung carcinoma is planned BACKGROUND Repeat positron emission tomography ( PET ) with 18F-fluorodeoxyglucose ( FDG ) and chest computed tomography ( CT ) are used to assess the effectiveness of chemoradiotherapy in patients with non-small cell lung cancer ( NSCLC ) ; however , the change in the st and ardized uptake values ( SUV ) has not been correlated with the pathologic change of the primary tumor . METHODS This is a retrospective cohort study of a prospect i ve data base of 56 patients who had NSCLC , FDG-PET , and chest CT scans both before and after neoadjuvant therapy , followed by complete resection of their cancer . Maximum SUVs ( maxSUV ) and tumor size were measured , and the percentage of change was compared with the percentage of nonviable tumor cells . The primary objective was to measure the degree of correlation between these values . RESULTS The change in the maxSUV has a near linear relationship to the percent of nonviable tumor cells in the resected tumors . FDG-PET 's maxSUV is better correlated to pathology than the change in size on CT scan ( r2 = 0.75 , r2 = 0.03 , p < 0.001 ) . When the maxSUV decreased by 80 % or more , a complete pathologic response could be predicted with a sensitivity of 90 % , specificity of 100 % , and accuracy of 96 % . CONCLUSIONS The change in maxSUV on FDG-PET scan after neoadjuvant therapy holds a near linear relationship with pathologic response . It is a more accurate predictor than the change of size on CT scan . When the maxSUV decreases by 80 % or more it is likely that the patient is a complete responder irrespective of cell type , neoadjuvant treatment , or the final absolute maxSUV . These findings may help guide treatment strategies PURPOSE To evaluate the feasibility and efficacy of an intensive multimodality approach with combination chemotherapy , hyperfractionated accelerated chemoradiotherapy , and definitive surgery in prognostically unfavorable subgroups of locally advanced non-small-cell lung cancer stages IIIA and IIIB ( LAD-NSCLC ) . PATIENTS AND METHODS Following staging , including mediastinoscopy , 94 patients with inoperable LAD-NSCLC were treated preoperatively with chemotherapy ( three courses of split-dose cisplatin and etoposide [ PE ] ) followed by concurrent chemoradiotherapy ( one course of PE combined with 45 Gy hyperfractionated accelerated radiotherapy ) . After repeat mediastinoscopy , patients underwent surgery 4 weeks postradiation . RESULTS Of 94 consecutive patients ( 52 stage IIIA [ > or = two lymph node levels involved ] and 42 stage IIIB [ no pleural effusion , no supraclavicular nodes ] ) , 62 ( 66 % ) completed induction and underwent surgery . Complete resection ( R0 ) was achieved in 50 ( 53 % of all patients ) and pathologic complete response ( PCR ) in 24 ( 26 % ) . After a median follow-up of 43 months , the median survival time was 20 months for IIIA , 18 months for IIIB , and 42 months for R0 patients . Calculated survival rates at 4 years were 31 % , 26 % , and 46 % . Two patients died of sepsis preoperatively and four died postoperatively of pleural empyema ( n = 1 ) , stump insufficiency ( n = 2 ) , and cardiac failure ( n = 1 ) . Other toxicities were acceptable-mainly hematologic during chemotherapy or chemoradiotherapy and esophagitis during chemoradiotherapy . CONCLUSION This intensive multimodality treatment is feasible and demonstrates high efficacy in prognostically unfavorable LAD-NSCLC subgroups with high R0 rates and improved long-term survival compared with historical BACKGROUND The accuracy of restaging in patients with stage IIIa non-small cell lung cancer after neoadjuvant chemoradiotherapy is unknown . METHODS A prospect i ve trial of patients with biopsy-proven N2 disease who underwent initial clinical staging with mediastinoscopy , integrated positron emission tomography/computed tomography ( PET/CT ) , and CT . Patients then were clinical ly restaged by the same imaging techniques 4 to 12 weeks after their induction chemoradiation therapy and then underwent definitive pathologic staging . RESULTS Ninety-three patients had their lymph nodes pathologically restaged . Repeat PET/CT after neoadjuvant therapy missed residual N2 disease in 13/65 ( 20 % ) patients and falsely suggested it in 7 of 28 ( 25 % ) . It was more accurate than repeat CT for restaging at all pathologic stages ( stage 0 , 92 % vs 39 % , P = .03 ; and stage I 89 % vs 36 % , P = .04 ) . When the maximum st and ardized uptake value of the primary tumor is decreased by 75 % or more , it is highly likely ( likelihood ratio , + LR , 6.1 ) the patient is a complete responder ; when it decreased by 55 % or more , it is highly likely ( + LR , 9.1 ) the patient is a partial responder . When the maximum st and ardized uptake value of the N2 node initially involved with metastatic cancer is decreased by more than 50 % , it is highly likely ( + LR , 7.9 ) the node is now benign . CONCLUSION Repeat integrated PET/CT is superior to repeat CT for the restaging of patients with stage IIIa non-small cell lung cancer . The percent decrease in the maximum st and ardized uptake value of the primary and of the involved lymph node is predictive of pathology ; however , nodal biopsies are required since a persistently high maximum st and ardized uptake value does not equate to residual cancer PURPOSE To evaluate whether preoperative chemotherapy ( PCT ) could improve survival in resectable stage I ( except T1N0 ) , II , and IIIA non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A r and omized trial compared PCT to primary surgery ( PRS ) . PCT consisted of two cycles of mitomycin ( 6 mg/m(2 ) , day 1 ) , ifosfamide ( 1.5 g/m(2 ) , days 1 to 3 ) and cisplatin ( 30 mg/m(2 ) , days 1 to 3 ) , and two additional postoperative cycles for responding patients . In both arms , patients with pT3 or pN2 disease received thoracic radiotherapy . RESULTS Three hundred fifty-five eligible patients were r and omized . Overall response to PCT was 64 % . There were two preoperative toxic deaths . Postoperative mortality was 6.7 % in the PCT arm and 4.5 % in the PRS arm ( P = .38 ) . Median survival was 37 months ( 95 % confidence interval [ CI ] , 26.7 to 48.3 ) for PCT and 26.0 months ( 95 % CI , 19.8 to 33.6 ) for PRS ( P = .15 ) . Survival differences between both arms increased from 3.8 % ( 95 % CI , 1.3 % to 25.1 % ) at 1 year to 8.6 % ( 95 % CI , 2.64 % to 24.4 % ) at 4 years . A quantitative interaction between N status and treatment was observed , with benefit confined to N0 to N1 disease ( relative risk [ RR ] , 0.68 ; 95 % CI , 0.49 to 0.96 ; P = .027 ) . After a nonsignificant excess of deaths during treatment , the effect of PCT was significantly favorable on survival ( RR , 0.74 ; 95 % CI , 0.56 to 0.99 ; P = .044 ) . Disease-free survival time was significantly longer in the PCT arm ( P = .033 ) . CONCLUSION Although impressive differences in median , 3-year , and 4-year survival were observed , they were not statistically significant , except for stage I and II disease PURPOSE The 5-year survival rates with surgical resection for preoperatively identified stage IIIA N2 non-small-cell lung cancer ( NSCLC ) are less than 10 % . A pilot study of mitomycin , vindesine , and cisplatin ( MVP ) induction chemotherapy was undertaken in an attempt to improve the curative potential of surgery in this group of patients . PATIENTS AND METHODS Thirty-nine patients with mediastinoscopy stage IIIA N2 NSCLC received two cycles of MVP . Responding patients underwent thoracotomy for resection and two further courses of MVP . RESULTS The overall response rate was 64 % ( 25 of 39 ) with three complete and 22 partial responses . Twenty-two patients were resected , which included a radical mediastinal node dissection . Eighteen resections were complete and four were incomplete . Pathologically , three patients ( 7.7 % ) had no tumor remaining . Toxicity included two postoperative deaths secondary to a bronchopleural ( BP ) fistula , mitomycin pulmonary toxicity in two patients , and septic deaths in four patients . Twenty-eight patients have died ; 20 have recurrent or progressive disease . Eight of the 18 patients completely resected have recurred , with a median time to recurrence of 20.6 months . Sites of recurrence include two locoregional , five distant ( two in brain ) , and one in both . Median survival of all 39 patients is 18.6 months , with a 3-year survival of 26 % . The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40 % . CONCLUSIONS We conclude ( 1 ) that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC ; ( 2 ) the median survival seems to be prolonged ; and ( 3 ) the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a phase III r and omized trial to compare it with other treatment modalities From October 1989 to February 1992 , 74 patients with mediastinoscopically staged IIIA ( N2 ) non-small-cell lung cancer from 30 CALGB-affiliated hospitals received two cycles of preresectional cisplatin and vinblastine chemotherapy . Patients with responsive or stable disease underwent st and ardized surgical resection and radical lymphadenectomy . Patients who underwent resection received sequential adjuvant therapy with two cycles of cisplatin and vinblastine , followed by thoracic irradiation ( 54 Gy after complete resection and 59.4 Gy after incomplete resection or no resection at 1.8 Gy per fraction ) . There were no radiographic complete responses to the neoadjuvant chemotherapy , although 65 ( 88 % ) patients had either a response or no disease progression . During induction chemotherapy , disease progressed in seven patients ( 9 % ) . Sixty-three patients ( 86 % ) had exploratory thoracotomy , and 46 of those ( 75 % ) had resectable lesions . A complete surgical resection was accomplished in 23 patients , and 23 patients had an incomplete resection with either a diseased margin or diseased highest node resected . Operative mortality was 3.2 % ( 2/63 ) . In 10 patients ( 22 % of the 46 having resection ) the disease was pathologically downstaged . There was no correlation between radiographic response to the induction chemotherapy and downstaging at surgical resection . The full protocol was completed by 33 patients ( 45 % of original cohort ) . Overall survival at 3 years was 23 % . Patients undergoing resection had significantly improved survival at 3 years compared with patients not having resection : 46 % for complete resection ( median 20.9 months ) , 25 % for incomplete resection ( median 17.8 months ) , and 0 % for no resection ( median 8.5 months ) . Five deaths occurred during the treatment period . A total of 18 of the 46 ( 39 % ) patients who underwent resection are either alive and disease-free or have died without recurrence 53 patients with stage IIIA non-small cell carcinoma of the lung ( NSCCL ) were treated with multimodality therapy consisting of induction radiotherapy ( 55.8 Gy ) and two cycles of concurrent chemotherapy with cisplatin , 25 mg/m2 for 4 days by continuous infusion and bolus etoposide , 100 mg/m2 on days 2 and 4 of each cycle followed by surgery and adjuvant chemotherapy . Of 53 evaluable patients , 47 achieved clinical responses ( 9 complete response , 38 partial response ) after induction therapy for a response rate of 89 % . 47 patients were resectable after induction therapy , but 8 patients refused surgery and 6 patients were not eligible for surgery based on poor pulmonary function ( medical contraindications ) . 33 patients underwent thoracotomy and in 6 patients , resection was technically unfeasible . Thus complete surgical resection was accomplished in 27 patients . After all therapy , 28 patients achieved a complete response ( 53 % ) and 19 patients a partial response ( 36 % ) . Toxicities were mild . At a maximum of 75 months ( median , 28 months ) of follow-up , the median survival of the entire group is 24 months . The median survival of resected patients has not been reached ; their 6-year survival rate is 55 % . Unresected patients survived for a median of 11 months . This multimodality regimen is well-tolerated , induces a high response and resectability rate and prolongs survival in resected patients PURPOSE The objective of this study was to determine the accuracy of ( early ) response measurements using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography ( 18FDG PET ) with respect to survival of patients with stage IIIA-N2 non-small-cell lung cancer ( NSCLC ) undergoing induction chemotherapy ( IC ) , with a comparative analysis of PET methods . PATIENTS AND METHODS In a prospect i ve multicenter study , PET was performed in patients before IC and after one and three cycles . Computed tomography ( CT ) was performed before and after IC . Glucose consumption ( metabolic rate of glucose [ MRglu ] ) was measured using Patlak graphical analysis and correlated with simplified methods . Mediastinal lymph node ( MLN ) status was assessed visually . Cox proportional hazards analysis was used to determine the prognostic relevance of CT and PET measures of response with respect to survival . RESULTS Complete PET data sets were available in 47 patients . Median survival was 21 months . MLN status after IC by PET predicted survival ( hazard ratio [ HR ] , 2.33 ; 95 % CI , 1.04 to 5.22 ; P = .04 ) in contrast with CT ( HR , 1.87 ; 95 % CI , 0.81 to 4.30 ; P = .14 ) . Residual MRglu after IC proved to be the best prognostic factor ( HR , 1.95 ; 95 % CI , 1.28 to 2.97 ; P = .002 ) . Multivariate stepwise analysis showed that PET identified prognostically different strata in patients considered responsive according to CT . Residual MRglu after one cycle selected patients with different outcomes ( HR , 2.04 ; 95 % CI , 1.18 to 3.52 ; P = .01 ) . Simplified quantitative 18FDG PET methods were correlated with Patlak graphical analysis during and after therapy ( r > or = 0.90 ) . CONCLUSION 18FDG PET has additional value over CT in monitoring response to IC in patients with stage IIIA-N2 NSCLC , and it seems feasible to predict survival early during IC . Simple semiquantitative and complex PET methods perform equally well PURPOSE A multicenter , phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer ( NSCLC ) and examined prognostic factors for patients not benefiting from surgery . PATIENTS AND METHODS Ninety patients with previously untreated , potentially operable stage IIIA ( mediastinoscopically pN2 ) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2 , with subsequent surgical resection . RESULTS Administered dose-intensities were docetaxel 85 mg/m2/3 weeks ( range , 53 to 96 ) and cisplatin 95 mg/m2/3 weeks ( range , 0 to 104 ) . The 265 cycles were well tolerated , and the overall response rate was 66 % ( 95 % confidence interval [ CI ] , 55 % to 75 % ) . Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16 % and 35 % of patients , respectively ( perioperative mortality , 3 % ; morbidity , 17 % ) . Pathologic complete response occurred in 19 % of patients with tumor resection . In patients with tumor resection , downstaging to N0 - 1 at surgery was prognostic and significantly prolonged event-free survival ( EFS ) and overall survival ( OS ; P = .0001 ) . At median follow-up of 32 months , the median EFS and OS were 14.8 months ( range , 2.4 to 53.4 ) and 33 months ( range , 2.4 to 53.4 ) , respectively . Local relapse occurred in 27 % of patients with tumor resection , with distant metastases in 37 % . Multivariate analyses identified mediastinal clearance ( hazard ratio , 0.22 ; P = .0003 ) and complete resection ( hazard ratio , 0.26 ; P = .0006 ) as strongly prognostic for increased survival . CONCLUSION Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC . Resection is recommended only for patients with mediastinal downstaging after chemotherapy Background : Surgical resection alone remains suboptimal for patients with early-stage ( I or II ) non-small cell lung cancer . Two similar r and omized phase II trials were conducted to define an active preoperative regimen in this disease state . Methods : In the first study , patients were r and omized to receive gemcitabine 1000 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1 ( GC ) or gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin area under the curve 5.5 on day 1 ( GCb ) . In the second trial , patients received the same regimen of GCb or gemcitabine 1000 mg/m2 on days 1 and 8 plus paclitaxel 200 mg/m2 on day 1 ( GP ) . Cycles were repeated every 21 days for three cycles . The primary end point was pathologic complete response ( pCR ) rate . Results : Eighty-seven eligible patients were r and omized ( GC n = 12 , GP n = 35 , and GCb n = 40 ) , and 71 ( 82 % ) underwent surgery after chemotherapy . The confirmed pCR rate was 2.3 % ( 2 of 87 , 95 % confidence interval 0.3–8.1 ) . Clinical response rate was 28.7 % , complete resection rate was 91.5 % ( 65 of 71 patients ) , and perioperative mortality rate was 2.8 % . As of October 2006 , median survival for all patients was 45 months ( 65.5 % censored ) , with 87.2 % alive at 1 year and 69.8 % alive at 2 years . Discussion : Neoadjuvant chemotherapy with gemcitabine was feasible and well tolerated , and outcomes were similar to other reports of this treatment strategy . However , no regimen achieved the predefined pCR rate that would be sufficient to warrant further evaluation in the phase III setting . This trial design provides an efficient way of providing a rationale for choosing or rejecting regimens of potential value |
11,769 | 17,636,693 | Photodynamic therapy in people with choroidal neovascularisation due to AMD is probably effective in preventing visual loss though there is doubt about the size of the effect . | BACKGROUND In neovascular age-related macular degeneration ( AMD ) new vessels grow under the retina distorting vision and leading to scarring .
This is exacerbated if the blood vessels leak .
Photodynamic therapy ( PDT ) has been investigated as a way to treat the neovascular membranes without affecting the retina .
OBJECTIVES The aim of this review was to examine the effects of PDT in the treatment of neovascular AMD . | OBJECTIVE To describe fluorescein angiographic guidelines for the use of verteporfin therapy in patients with subfoveal choroidal neovascularization ( CNV ) secondary to age-related macular degeneration ( AMD ) or other conditions based on 2-year vision outcomes from the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy ( TAP ) Investigation and Verteporfin in Photodynamic Therapy ( VIP ) Trial . METHODS Three multicenter , double-masked , placebo-controlled r and omized clinical trials at 28 ophthalmology clinical centers in Europe and North America involving prospect ively identified patients with best-corrected visual acuity ( Snellen equivalent ) of approximately 20/20 to 20/200 , subfoveal CNV secondary to AMD or pathologic myopia with evidence of CNV , and a lesion greatest linear dimension of 5400 micro m or less . Fluorescein angiography was to be performed on all patients at enrollment and at regular 3-month follow-up visits through 2 years . The initial treatment laser spot size and all subsequent treatment decisions were based on the investigator 's interpretation of these fluorescein angiograms . Photographic material s forwarded to the Wilmer Photograph Reading Center were review ed by masked grade rs . MAIN OUTCOME MEASURES Baseline angiographic features , including lesion composition and size , morphologic response to treatment during follow-up ( eg , absence of leakage ) , and reliability ( kappa values ) of grading selected characteristics based on a 10 % regrading of baseline visits . RESULTS Terms and examples of different lesions and lesion components are provided to assist recognition of fluorescein angiographic characteristics of choroidal neovascular lesions that were important in determining when and where to apply verteporfin therapy . The kappa statistics for agreement of identification of lesion characteristics by the Wilmer Photograph Reading Center for these trials ranged from 0.70 to 0.85 . CONCLUSIONS Ophthalmologists should consider interpreting fluorescein angiographic images of subfoveal lesions with terms provided to follow recommendations regarding which patients are most likely to benefit from verteporfin therapy based on results from the TAP Investigation and VIP Trial PURPOSE To determine if photodynamic therapy with verteporfin ( Visudyne ; Novartis AG , Bülach , Switzerl and ) , termed verteporfin therapy , can safely reduce the risk of vision loss compared with a placebo ( with sham treatment ) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization , or with presumed early onset classic choroidal neovascularization with good visual acuity letter score . METHODS This was a double-masked , placebo-controlled ( sham treatment ) , r and omized , multicenter clinical trial involving 28 ophthalmology practice s in Europe and North America . The study population was patients with age-related macular degeneration , with subfoveal choroidal neovascularization lesions measuring no greater than 5400 microm in greatest linear dimension with either 1 ) occult with no classic choroidal neovascularization , best-corrected visual acuity score of at least 50 ( Snellen equivalent approximately 20/100 ) , and evidence of hemorrhage or recent disease progression ; or 2 ) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 ( better than a Snellen equivalent of approximately 20/40 ) ; assigned r and omly ( 2:1 ) to verteporfin therapy or placebo therapy . Verteporfin ( 6 mg per square meter of body surface area ) or placebo ( 5 % dextrose in water ) was administered by means of intravenous infusion of 30 ml over 10 minutes . Fifteen minutes after the start of the infusion , a laser light at 689 nm delivered 50 J/cm(2 ) by application of an intensity of 600 mW/cm(2 ) over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina . At follow-up examinations every 3 months , retreatment with the same regimen was applied if angiography showed fluorescein leakage . The main outcome measure was at least moderate vision loss , that is , a loss of at least 15 letters ( approximately 3 lines ) , adhering to an intent-to-treat analysis with the last observation carried forward to impute for missing data . RESULTS Two hundred ten ( 93 % ) and 193 ( 86 % ) of the 225 patients in the verteporfin group compared with 104 ( 91 % ) and 99 ( 87 % ) of the 114 patients in the placebo group completed the month 12 and 24 examinations , respectively . On average , verteporfin-treated patients received five treatments over the 24 months of follow-up . The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination , although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group . Between the month 12 and 24 examinations , the treatment benefit grew so that by the month 24 examination , the verteporfin-treated eyes were less likely to have moderate or severe vision loss . Of the 225 verteporfin-treated patients , 121 ( 54 % ) compared with 76 ( 67 % ) of 114 placebo-treated patients lost at least 15 letters ( P = .023 ) . Likewise , 67 of the verteporfin-treated patients ( 30 % ) compared with 54 of the placebo-treated patients ( 47 % ) lost at least 30 letters ( P = .001 ) . Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization . This subgroup included 166 of the 225 verteporfin-treated patients ( 74 % ) and 92 of the 114 placebo-treated patients ( 81 % ) . In these patients , 91 of the verteporfin-treated group ( 55 % ) compared with 63 of the placebo-treated group ( 68 % ) lost at least 15 letters ( P = .032 ) , whereas 48 of the verteporfin-treated group ( 29 % ) and 43 of the placebo-treated group ( 47 % ) lost at least 30 letters ( P = .004 ) . Other secondary outcomes , including visual acuity letter score worse than 34 ( approximate Snellen equivalent of 20/200 or worse ) , mean change in visual acuity letter score , development of classic choroidal neovascularization , progression of classic choroidal neovascularization and size of lesion , favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline . Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions ( 4 disc areas or less ) or lower levels of visual acuity ( letter score less than 65 , an approximate Snellen equivalent of 20/50(-1 ) or worse ) at baseline . Prospect ively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit . ( ABSTRACT TRUNCATED Aims : ( 1 ) A prospect i ve study to assess visual function measures and quality of life ( QoL ) in patients with wet age related macular degeneration ( AMD ) treated with photodynamic therapy ( PDT ) . ( 2 ) To assess if PDT prevents severe visual loss ( loss of six or more lines of distance visual acuity ) in the treated eye . Methods : 48 of 51 recruited patients with predominantly classic subfoveal choroidal neovascularisation ( CNV ) secondary AMD who were treated with PDT were followed up for 1 year . Assessment included distance and near visual acuity , contrast sensitivity , vision related quality of life and fluorescein angiography . Photodynamic therapy using Visudyne was carried out according to st and ard protocol . Patients were followed up every 3 months and treatment repeated if there was significant leakage from CNV . Results : At the 12 month follow up , 71 % ( n = 34 ) of the patients lost less than three lines of best corrected distance visual acuity . Although there were significant decreases in some of the QoL items tested , patients were significantly less anxious and more independent outdoors at the 12 month follow up . Conclusion : This study is in keeping with published literature with PDT preventing severe visual loss in two thirds of treated patients with predominantly classic CNV Purpose : To provide broad clinical experience and to gather safety data on photodynamic therapy with verteporfin ( Visudyne , Novartis AG , Basel , Switzerl and ) , also termed verteporfin therapy , in patients with predominantly classic subfoveal choroidal neovascularization ( CNV ) secondary to age-related macular degeneration ( AMD ) . The Verteporfin in Age-related Macular Degeneration ( VAM ) Study was design ed to provide exp and ed access to verteporfin therapy after beneficial results for these cases were reported but before regulatory approval in North America . Methods : This open-label multicenter study from September 1999 through June 2000 enrolled among 222 centers patients 50 years or older in the United States , or 40 years or older in Canada , with age-related macular degeneration and subfoveal CNV with a lesion composition that was predominantly classic CNV on fluorescein angiography . Corrected visual acuity with habitual eyewear in the office setting was 20/40 to 20/200 , inclusive . All patients received verteporfin therapy and returned for follow-up every 3 months . At those follow-up examinations , additional courses of treatment were recommended if any fluorescein leakage from CNV was identified . Safety information was collected from patient self-reporting , question ing ( in person and by telephone ) , and physician evaluation . Safety was assessed by evaluating the effect of treatment on corrected distance visual acuity and by evaluating adverse events . Results : A total of 4,435 patients were enrolled of whom 4,051 ( 91 % ) completed the study after receiving 6,701 treatments . Most patients received only one treatment in VAM before regulatory approval of verteporfin in the United States and Canada . Three hundred patients ( 6.8 % ) experienced an adverse event considered by the treating ophthalmologist to be associated with treatment , including 115 ( 2.6 % ) with abnormal or decreased vision , of whom 25 ( 0.6 % ) experienced acute severe visual acuity decrease , and 14 ( 0.3 % ) with transient infusion-related back pain . Patients were advised to avoid exposure to direct sunlight for 24 hours ; however , after verteporfin administration only 2 ( 0.05 % ) reported a photosensitivity reaction . An additional course of verteporfin therapy was administered to 1,739 of 2,314 patients ( 75.2 % ) who had a month 3 examination that was not their close-out visit and 177 of 266 ( 66.5 % ) who had a month 6 examination that was not their close-out visit . Conclusions : Verteporfin therapy exhibited no additional or new safety concerns . The therapy associated with a low incidence of adverse events when exp and ed access was provided in a large , open-label , multicenter study , including a low incidence ( 0.05 % ) of reported photosensitivity reactions despite a short photosensitivity protection period ( 24 hours ) following verteporfin administration PURPOSE To evaluate vascular changes documented by confocal indocyanine green angiography ( ICGA ) through 2 years after photodynamic therapy ( PDT ) with verteporfin of neovascular age-related macular degeneration ( AMD ) . DESIGN Single-center , 2-year , r and omized , double-masked , interventional , placebo-controlled trial ( subset from Treatment of AMD with PDT Study [ TAP ] ) . PARTICIPANTS Sixty patients with subfoveal choroidal neovascularization ( CNV ) result ing from AMD . INTERVENTION Patients were r and omized in a ratio of 2:1 to a st and ard regimen using verteporfin therapy at a drug dose of 6 mg/m(2 ) body surface area and a light dose of 50 J/cm(2 ) or a sham treatment with placebo infusion and light exposure . Retreatments , if persistent fluorescein leakage from CNV was documented , were scheduled at 3-month intervals for up to 2 years . Confocal ICGA with tomographic sections was performed at baseline and continuously at the month 3 , 6 , 12 , and 24 examinations using a st and ardized protocol . MAIN OUTCOME MEASURES Analysis included the size of the neovascular net , the area of late hyperfluorescence , and choroidal hypofluorescence during early- and late-phase imaging . RESULTS In the verteporfin-treated group , the mean size of the CNV and the mean area of late leakage consistent with active leakage or staining showed no further enlargement at month 12 and were reduced at month 24 . In the placebo-treated group , new vessels grew threefold compared with baseline and exhibited persistent late hyperfluorescence result ing from leakage at 24 months . Associated choroidal hypofluorescence within the treated area was significantly increased in eyes treated with verteporfin PDT compared with the control group during the first year , persisted during all ICGA phases , and was irreversible during follow-up . Image analysis revealed choroidal hypoperfusion with choriocapillary dropout , which correlated with chorioretinal atrophy clinical ly . Progressive destruction of choroidal integrity by fibrosis in control eyes led to a similar extent of collateral hypofluorescence in both groups through the 24-month examination . CONCLUSIONS Indocyanine green angiography is an important adjunct in the identification of vascular effects associated with verteporfin PDT . Repeated treatments effectively arrested CNV growth and reduced leakage activity . The collateral impairment of choroidal perfusion appears to influence the visual outcome of the treatment PURPOSE To evaluate the effect of photodynamic therapy with verteporfin on the maintenance of central visual field function . DESIGN R and omized controlled clinical trial . PARTICIPANTS Forty-six consecutive patients with subfoveal choroidal neovascularization ( CNV ) caused by age-related macular degeneration including a classic component were r and omly assigned . Thirty-three participants received st and ard verteporfin therapy , and 13 received placebo and laser treatment . METHODS The trial was performed as a single-center , double-masked study . Patients were examined before therapy and continuously in 3-month intervals during 2 years of follow-up . A scanning laser ophthalmoscope ( SLO ) was used to perform macular microperimetry . Absolute and relative scotomas were documented at each visit , and size was measured in square millimeters . MAIN OUTCOME MEASURES The change in size of central scotoma in the verteporfin group compared with the placebo group . RESULTS An absolute scotoma was seen in 88 % , and a relative scotoma was seen in 100 % of eyes before therapy . Absolute defects were associated with the classic CNV component localized angiographically . In the verteporfin group , the absolute scotoma grew from 2.5 mm(2 ) at baseline to a final size of 7.3 mm(2 ) at month 24 . In the placebo group , the mean lesion size of the absolute scotoma enlarged from an initial size of 2.7 mm(2 ) to 31.5 mm(2 ) after 24 months . The relative scotoma increased from 7.9 mm(2 ) at baseline to 20.8 mm(2 ) at month 24 in the verteporfin group , whereas a progression from 8.5 mm(2 ) initially to 48.3 mm(2 ) at the final presentation was measured in the placebo group . Statistical analysis showed that both the mean absolute and relative scotoma sizes were significantly smaller in the verteporfin group than the placebo group for all intervals from 6 to 24 months ( P<0.001 ) . CONCLUSIONS Documentation of macular function with SLO perimetry demonstrated a significant benefit of verteporfin therapy for the preservation of the central visual field . Absolute and relative scotoma sizes remained smaller after therapy . This may influence reading ability and visual rehabilitation OBJECTIVE To determine intraobserver and interobserver variation for classifying types of choroidal neovascularizations ( CNV ) in exudative age-related macular degeneration ( ARMD ) . DESIGN Intraexaminer and interexaminer reliability study . PARTICIPANTS Digital high- quality fluorescein angiograms of 40 patients with neovascular ARMD were evaluated independently by 16 retinal specialists . MAIN OUTCOME MEASURES Fluorescein angiographies were presented in two r and omized sequences ( series A and B ) to each masked reader for classification of type of CNV into classic , occult , or mixed with classic component of less or greater 50 % . Agreement was evaluated by calculating kappa statistics ( kappa ) and intraclass correlation coefficients . RESULTS The mean kappa coefficient was 0.64 + /- 0.11 for intraobserver variation , with a range from 0.44 to 0.89 . For interobserver variation the intraclass correlation coefficients was calculated as 0.66 ( 95 % confidence interval [ CI ] 0.56 , 0.77 ) for series A and as 0.55 ( 95 % CI 0.43 , 0.67 ) for series B. CONCLUSIONS Angiographic classification of CNV secondary to ARMD can vary considerably not only between observers but also for repeated evaluation by the same observer . Because various current and emerging treatments including photodynamic therapy are based on specific angiographic characteristics , accurate interpretation will become more important OBJECTIVE To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin ( Visudyne ; CIBA Vision Corp , Duluth , Ga ) in patients with subfoveal choroidal neovascularization ( CNV ) caused by age-related macular degeneration ( AMD ) . DESIGN Two multicenter , double-masked , placebo-controlled , r and omized clinical trials . SETTING Twenty-two ophthalmology practice s in Europe and North America . PARTICIPANTS Patients with subfoveal CNV lesions caused by AMD with greatest linear dimension on the retina measuring 5400 micrometer or less , with evidence of classic CNV and best-corrected visual acuity ( approximate Snellen equivalent ) between 20/40 and 20/200 . METHODS The methods were similar to those described in our 1-year results , with follow-up examinations beyond 1 year continuing every 3 months ( except for Photograph Reading Center evaluations , which occurred only at month 18 and month 24 examinations ) . During the second year , the same regimen ( with verteporfin or placebo as applied at baseline ) was used if angiography showed fluorescein leakage from CNV . The primary outcome was the proportion of eyes with fewer than 15 letters ( approximately 3 lines ) of visual acuity loss at the month 24 examination , adhering to an intent-to-treat analysis . The last observation was carried forward to impute for any missing data . RESULTS Three hundred fifty-one ( 87 % ) of 402 patients in the verteporfin group compared with 178 ( 86 % ) of 207 patients in the placebo group completed the month 24 examination . Beneficial outcomes with respect to visual acuity and contrast sensitivity noted at the month 12 examination in verteporfin-treated patients were sustained through the month 24 examination . At the month 24 examination for the primary outcome , 213 ( 53 % ) of 402 verteporfin-treated patients compared with 78 ( 38 % ) of 207 placebo-treated patients lost fewer than 15 letters ( P<.001 ) . In subgroup analyses for predominantly classic lesions ( in which the area of classic CNV makes up at least 50 % of the area of the entire lesion ) at baseline , 94 ( 59 % ) of 159 verteporfin-treated patients compared with 26 ( 31 % ) of 83 placebo-treated patients lost fewer than 15 letters at the month 24 examination ( P<.001 ) . For minimally classic lesions ( in which the area of classic CNV makes up < 50 % but > 0 % of the area of the entire lesion ) at baseline , no statistically significant differences in visual acuity were noted . Few additional photosensitivity adverse reactions and injection site adverse events were associated with verteporfin therapy in the second year of follow-up . CONCLUSIONS The visual acuity benefits of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal lesions are safely sustained for 2 years , providing more compelling evidence to use verteporfin therapy for these cases . For AMD patients with subfoveal lesions that are minimally classic , there is insufficient evidence to warrant routine use of verteporfin therapy OBJECTIVE To summarize findings from three r and omized clinical trials of krypton laser treatment of juxtafoveal neovascular lesions regarding changes in visual acuity during 5 years of follow-up , rates of persistent and recurrent choroidal neovascularization , and status of macular lesions 5 years after enrollment . DESIGN , PATIENTS , AND PRIMARY OUTCOME MEASURES : Follow-up of patients enrolled in three r and omized trials of choroidal neovascularization secondary to age-related macular degeneration ( AMD ) , ocular histoplasmosis , or idiopathic causes ended in March 1991 . All patients were eligible to complete at least 3 years of follow-up examinations . Data on visual acuity , reading vision , and anatomic outcomes during 5 years of follow-up were available for 276 ( 92 % ) of 300 patients with AMD , 236 ( 92 % ) of 256 patients with ocular histoplasmosis , and 38 ( 97 % ) of 39 patients with idiopathic choroidal neovascularization enrolled 5 or more years earlier who were still living . RESULTS Among eyes with AMD , the estimated relative risk ( RR ) of a loss of 6 or more lines of visual acuity from baseline to any examination from 6 months through 5 years after enrollment for untreated eyes in comparison with treated eyes was 1.20 ( P = .04 ) . Normotensive patients with AMD realized the greatest benefit from laser treatment ( RR , 1.82 ) and hypertensive patients experienced little or no benefit ( RR , 0.93 ) . Untreated eyes with ocular histoplasmosis were at much greater risk of a 6-line decrease in visual acuity from the 1-year through the 5-year examination than were treated eyes ( unadjusted RR , 2.60 ; RR , 4.26 after adjustment for visual acuity and hypertension at baseline ; P < .001 for both ) . The treatment effect for eyes with idiopathic choroidal neovascularization was between the effects for eyes with AMD and eyes with ocular histoplasmosis . CONCLUSIONS The early beneficial effects of laser treatment on visual acuity persisted for at least 5 years in eyes with all three underlying conditions . Laser treatment of similar eyes with choroidal neovascularization in a juxtafoveal location is recommended for patients with these conditions , with the caveat that hypertensive patients with AMD may fare no better with laser treatment than without treatment OBJECTIVE To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization ( CNV ) . DESIGN AND SETTING Open-label extension of selected patients from 2 multicenter , double-masked , placebo-controlled , r and omized clinical trials , the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy ( TAP ) Investigation , at 22 ophthalmology practice s in Europe and North America . PARTICIPANTS Patients enrolled in the TAP Investigation and followed up for at least 24 months in whom verteporfin therapy to CNV might reduce the risk of further vision loss . METHODS Before receiving verteporfin therapy in the extension , eligible patients signed a written informed consent form accompanied by an oral consent process approved by local institutional review boards . Methods were similar to those described for 1- and 2-year results , with follow-up examinations beyond 2 years continuing at 3-month intervals with a few exceptions , including that extension patients with fluorescein leakage from CNV were to receive open-label verteporfin therapy irrespective of their original treatment assignment . RESULTS Of 402 patients in the verteporfin group , 351 ( 87.3 % ) completed the month 24 examination ; 320 ( 91.2 % ) of these enrolled in the extension study . The enrolled participants included 124 ( 78.0 % ) of the 159 verteporfin-treated patients with lesions composed of predominantly classic CNV at baseline , of whom 105 ( 84.7 % ) completed the month 36 examination . Verteporfin-treated patients with this lesion composition at baseline who participated in the extension study , with or without a month 36 examination , appeared more likely to have a younger age , better level of visual acuity , absence of fluorescein leakage from classic CNV , or no progression of classic CNV beyond the baseline boundaries of the lesion at the month 24 examination compared with those who did not enroll in the extension . For the 105 patients with a predominantly classic baseline lesion composition who completed the month 36 examination , an average of 1.3 treatments were given from the month 24 examination up to , but not including , the month 36 examination . A letter score loss in the study eye of at least 15 from baseline for these patients occurred in 39 ( 37.5 % ) at the month 24 examination compared with 44 ( 41.9 % ) of these patients at the month 36 examination . Visual acuity changed little from the month 24 examination ( mean , -1.9 lines ) to the month 36 examination ( mean , -2.0 lines ) for these eyes . Verteporfin-treated patients had little change in the mean visual acuity lost and few or no additional instances of infusion-related back pain or photosensitivity reactions from month 24 to month 36 . Two patients originally assigned to placebo had acute severe vision decrease within 7 days after verteporfin treatment during the extension . One patient originally assigned to verteporfin had acute severe vision decrease after verteporfin treatment of the fellow eye during the extension . CONCLUSIONS Vision outcomes for verteporfin-treated patients with predominantly classic lesions at baseline remained relatively stable from month 24 to month 36 , although only approximately one third of the verteporfin-treated patients originally enrolled with this lesion composition had a month 36 examination . From these results , the TAP Study Group identified no safety concerns to preclude repeating photodynamic therapy with verteporfin . Additional treatment was judged likely to reduce the risk of further vision loss . Caution appears warranted in the absence of comparison with an untreated group during the extension and since not all patients in the TAP Investigation participated in the TAP Extension Background In the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy ( TAP ) investigation , verteporfin therapy reduced the risk of at least moderate vision loss ( defined as a loss of at least 15 letters of visual acuity ) in patients with subfoveal choroidal neovascularization ( CNV ) secondary to age-related macular degeneration ( ARMD ) . This report presents detailed analyses of 24-month contrast sensitivity outcomes in these patients . Methods The patients included in the TAP investigation had subfoveal CNV secondary to ARMD and received verteporfin therapy ( n = 402 ) or placebo ( n = 207 ) at the first visit , with retreatment at each 3-month follow-up visit if angiography revealed fluorescein leakage from CNV . Contrast sensitivity was determined at each visit using a Pelli – Robson chart . Results At the month 24 examination , verteporfin-treated patients were less likely to lose at least 6 or 15 letters of contrast sensitivity than placebo-treated patients ( 86 [ 21 % ] versus 94 [ 45 % ] , and 27 [ 7 % ] versus 24 [ 12 % ] , respectively;P < 0.05 for both comparisons ) . The superiority of verteporfin therapy over placebo was greater in patients with predominantly classic CNV at baseline , although verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes . Conclusions Consistent with visual acuity outcomes , verteporfin therapy reduced the risk of a clinical ly relevant loss of contrast sensitivity in the total study population , with the greatest effect in patients with predominantly classic subfoveal CNV secondary to ARMD . Verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes than patients who received placebo . Given the association between contrast sensitivity and visual disability , the beneficial effects of verteporfin therapy on contrast sensitivity outcomes are expected to have a favorable impact on patients ’ daily activities PURPOSE To determine if oral hydration decreases the incidence of verteporfin infusion-associated pain and to find out if other factors play a role in predisposing to this undesired complication . METHODS Nonr and omized clinical trial . We prospect ively examined 250 consecutive patients who have been diagnosed with subfoveal choroidal neovascularization secondary to age-related macular degeneration and received photodynamic therapy using verteporfin . One hundred twenty-five patients were assigned to receive 500 ml of water orally administered 30 minutes before beginning the verteporfin infusion , and the remaining 125 consecutive patients were used as controls . Historical and clinical factors in these patients were evaluated for their association with the presence of verteporfin infusion-associated pain . RESULTS Out of 125 patients receiving water before treatment 12 ( 9.6 % ) experienced verteporfin infusion-associated pain . Among the 125 patients who did not get hydration before therapy 12(9.6 % ) experienced verteporfin infusion-associated pain . There was no statistical difference between the incidence of pain in the two groups ( P = 1.0 ) . No statistically significant association was evidence d between the presence of pain and participant 's baseline characteristics , except for pain on previous administration of verteporfin ( P < .001 ) . Out of 250 total patients 24 ( 9.6 % ) developed verteporfin infusion-associated pain . Back pain was the most common and occurred in 21 ( 8.4 % ) patients , but other sites included leg , groin , chest , buttock , arm , and shoulder pain concurrently or independently . All patients had resolution of their pain , including chest pain , on cessation of the infusion . CONCLUSIONS Verteporfin infusion-associated pain may be more common than has been previously reported and is not limited to the back area . It appears to be an idiosyncratic reaction to the drug . It does not seem to be prevented by oral hydration before infusion of verteporfin , and no baseline characteristics , other than a history of pain on previous infusion , seem to be predictive of verteporfin infusion-associated pain |
11,770 | 12,202,415 | RESULTS Luteal supplementation with either i.m .
hCG or i.m .
progesterone significantly improved fertility outcomes compared with no treatment .
When comparing i.m .
progesterone with i.m .
hCG , no fertility differences were found .
Intramuscular progesterone conferred the most benefit compared with oral or vaginal use .
Addition of oral estrogen to progesterone also improved implantation rates .
CONCLUSION Given the increased risk of ovarian hyperstimulation syndrome associated with hCG use , i.m .
progesterone is favoured for luteal phase supplementation with the addition of estrogen | BACKGROUND The addition of GnRH agonist to the treatment regimen in women undergoing IVF cycles is thought to create a luteal phase defect .
In an attempt to correct for this , many practitioners supplement with a variety of steroid hormones in the luteal phase . | OBJECTIVE --To evaluate the effect of support with human chorionic gonadotrophin in the luteal phase in women taking part in an in vitro fertilisation programme after buserelin and human menopausal gonadotrophin were used to hyperstimulate their ovaries . DESIGN --Controlled group comparison . SETTING --Outpatient department of a private hospital . PATIENTS --115 Women with indications for in vitro fertilisation , all of whom had at least one embryo transferred . INTERVENTIONS --After suppression of the pituitary with buserelin the ovaries of all the women were stimulated with human menopausal gonadotrophin on day 4 of the luteal phase . Human chorionic gonadotrophin ( 10,000 IU ) was given to induce ovulation , and oocytes were recovered 34 hours later . Embryos were transferred 46 to 48 hours after insemination . Women who had received the 10,000 IU of human chorionic gonadotrophin on a date that was an uneven number ( n = 61 ) were allocated to receive support doses of 2500 IU human chorionic gonadotrophin three and six days after that date . The remaining 54 women did not receive hormonal support . END POINT -- Determination of the rates of pregnancy . MEASUREMENTS and main results --Support with human chorionic gonadotrophin did not significantly alter the progesterone or oestradiol concentrations in the early or mid-luteal phase . The mean ( range ) progesterone concentrations in the late luteal phase in women who did not become pregnant were , however , significantly higher in those who received support ( 16(9 - 110 ) nmol/l nu 8(4 - 46 ) nmol/l ) , and the luteal phase was significantly longer in this group ( 14 days nu 12 days ) . The rate of pregnancy was significantly higher in the women who received support than in those who did not ( 25/61 nu 8/54 ) . CONCLUSIONS --When buserelin and human menopausal gonadotrophin are used to hyperstimulate ovaries support with human chorionic gonadotrophin in the luteal phase has a beneficial effect on in vitro fertilisation This study aim ed to compare the efficacy of micronized progesterone administered as luteal support following ovulation induction for in-vitro fertilization (IVF)- embryo transfer in cycles using gonadotrophin-releasing hormone agonist , either orally ( 200 mgx4/day ) or vaginally ( 100 mgx2/day ) and to characterize the luteal phase hormonal profile during such treatments . A total of 64 high responder patients requiring intracytoplasmic sperm injection due to male factor infertility were prospect ively r and omized into two treatment groups . Patients treated orally or vaginally were comparable in age ( 31.9 + /- 6.1 versus 30.6 + /- 5.2 ; mean + /- SD ) , number of oocytes retrieved ( 17 + /- 8.2 versus 18 + /- 7.0 ) , and number of embryos transferred ( 3.1 + /- 1.2 versus 2.7 + /- 0.9 ) per cycle . Following low dose vaginal treatment , a significantly higher implantation rate ( 30.7 versus 10.7 % , P < 0.01 ) , but similar clinical pregnancy rate ( 47.0 versus 33.3 % ) and ongoing pregnancy rate ( 41.1 versus 20.0 % ) was observed , compared with oral treatment . In conception cycles , luteal serum progesterone and oestrogen concentrations did not differ between the treatment groups . In non-conception cycles , late luteal progesterone concentrations were significantly lower following vaginal treatment . As low dose micronized progesterone administered vaginally is simple , easy and well tolerated , it could be recommended as the method of choice for luteal support , especially for high responder patients at risk for ovarian hyperstimulation syndrome Background . A prospect i ve study was done to compare the efficacy of luteal phase support ( LPS ) using either three times hCG ( group I , n=77 ) , hCG on the day of embryo transfer ( ET ) in combination with daily vaginal progesterone ( group II , n=62 ) or vaginal progesterone only ( group III , n=70 ) A total of 156 patients were r and omly treated with exogenous natural progesterone ( intramuscularly , 50 mg/day ) and vaginal gel ( 90 mg/day ) P or nothing ( Controls ) from the day before embryo transfer ( ET ) for two weeks . In case of positive beta-HCG , the treatment was continued for 12 weeks . Plasma P and 17 beta-Estradiol concentrations were estimated and compared with the control not supplemented group . Both treatments were able to increase significantly the luteal plasmatic values of P versus controls . The ongoing pregnancy and the living birth rates per transfer were significantly higher in the patients supplemented with intramuscular P than in those treated with vaginal gel P. The intramuscular natural P appears the most suitable route of administration for luteal phase support in IVF-ET procedures In an attempt to determine the best luteal support in in-vitro fertilization ( IVF ) cycles treated with gonadotrophin-releasing hormone agonist ( GnRHa ) and human menopausal gonadotrophin ( HMG ) by the ultrashort protocol , 60 patients were prospect ively r and omized for either i.m . progesterone or human chorionic gonadotrophin ( HCG ) luteal support . The two groups did not differ in the mean number of oocytes retrieved and embryos replaced , nor in the mean age of the patients and the amount of HMG used . HCG maintained higher levels of oestradiol and progesterone during the luteal phase . Conception rate was significantly higher in the HCG group . We conclude that HCG is superior to i.m . progesterone as luteal support in IVF cycles in which GnRHa is used in the ultrashort protocol Gonadotrophin-releasing hormone agonists ( GnRHa ) are widely used in in-vitro fertilization ( IVF ) for the prevention of a premature rise in luteinizing hormone ( LH ) concentrations . However , the administration of GnRHa during the follicular phase may also impair subsequent luteal function due to retarded recovery of pituitary gonadotrophin secretion . Therefore , luteal supplementation is generally applied . The present study was design ed to determine whether a premature LH surge would still be prevented after early cessation of GnRHa during ovarian stimulation and whether subsequent luteal phase LH production would be sufficient to support progesterone synthesis by the corpus luteum . Sixty patients were r and omized for three groups : ( i ) A long GnRHa/human menopausal gonadotrophin ( HMG ) protocol with luteal support by repeated human chorionic gonadotrophin ( HCG ) ( n = 20 ) , ( ii ) early follicular phase cessation of GnRHa without luteal support ( n = 20 ) , and ( iii ) a long GnRHa protocol without luteal support ( n = 20 ) . Frequent ultrasound and blood sampling was performed during the entire IVF cycle . Forty normo-ovulatory women served as controls . No premature LH surges were found after early cessation of GnRHa . In this group , some pituitary recovery occurred during the late luteal phase , but this did not affect corpus luteum function . Progesterone concentrations were shown to be dependent on disappearance of the pre-ovulatory bolus of HCG . Pregnancies occurred in all three groups . In conclusion , early follicular phase cessation of GnRHa is still effective in the prevention of a premature rise in LH . Although some pituitary recovery was observed thereafter , corpus luteum function is still abnormal due to early luteolysis This study was conducted to compare the endocrine milieu and pregnancy rates in an in-vitro fertilization and embryo transfer ( IVF-ET ) programme employing a gonadotrophin-releasing hormone agonist ( GnRHa ) and human menopausal gonadotrophin ( HMG ) when either human chorionic gonadotrophin ( HCG ) or progesterone were used for luteal phase support . A total of 121 IVF-ET treatment cycles were prospect ively studied . All patients started leuprolide acetate in the midluteal phase and it was continued for at least 10 days . When oestradiol levels were less than 150 pmol/l , HMG was started . When at least three follicles were greater than or equal to 17 mm in diameter , HCG 5000 IU i.m . was given . Oocytes were retrieved using transvaginal ultrasound and embryos were transferred 48 h later . The patients ' cycles were prospect ively r and omized to receive HCG ( 72 cycles ) or progesterone ( 49 cycles ) luteal support . The HCG group received 1500 IU i.m . on days 3 , 6 and 9 after the initial trigger . The progesterone group received 12.5 mg i.m . q.d . starting from the day after the HCG trigger . The dose of progesterone was increased to 25 mg i.m . q.d . starting on the day of embryo transfer and continued for 17 - 21 days . If the patient became pregnant , this dose of progesterone was continued until fetal heart activity was visualized by ultrasound . Mean ages , number of eggs retrieved , embryos transferred , oestradiol levels on the day of the HCG trigger , oestradiol and progesterone at the time of embryo transfer were the same in both groups . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To evaluate the possible role for estrogen supplementation to the P luteal phase support of GnRH agonists (GnRH-a)- and hMG-induced IVF-ET cycles . SETTING In vitro fertilization unit in a tertiary care university hospital . DESIGN A prospect ively r and omized study . PATIENTS One hundred consecutive patients undergoing ET after IVF were assigned into one of two luteal supplementation regimens . INTERVENTIONS In all patients enrolled in the study , ovulation was induced using the midluteal regimen for pituitary down regulation with GnRH-a followed by follicular stimulation with hMG . The first group received IM P 50 mg/d , as luteal phase support , starting the day of ET . The second group received the same dosage of P , combined with oral E2 valerate , 2 mg/d . Serum levels of P and E2 were monitored every 4 days for 16 days after ET . MAIN OUTCOME MEASURES Pregnancy rates ( PRs ) and live birth rates per ET . RESULTS No significant difference in E2 or P levels throughout the cycle was observed between groups . Similar PRs per ET and the live birth rates were also observed between group A and B ( 28 % versus 26.5 % and 78.6 % versus 76.1 % , respectively ) . CONCLUSION No advantage was found in the addition of E2 valerate to P luteal phase support of GnRH-a- and hMG-induced IVF-ET cycles The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization ( IVF ) program were compared . A control group ( group I ) consisted of 28 women ( 28 cycles ) who received our st and ard ovulation induction regimen ( no luteal phase support ) . The treatment group ( group II ) consisted of 40 women ( 42 cycles ) who were prospect ively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin ( hCG ) 5 days after the initial hCG dose . The groups were matched for age and cause of infertility . Estradiol ( E2 ) and progesterone ( P ) were measured on the day of embryo transfer and every 3 to 4 days thereafter . Luteal phase hCG support significantly augmented ( 1 ) E2 and P levels in the conception cycles of group II compared with group I and ( 2 ) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II . An ongoing pregnancy rate of 19 % was achieved in group II . This was not statistically different from the 13 % ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our st and ard ovulation induction regimen during the period of the study . In summary , the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG . It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri-implantation hormonal milieu Two progesterone presentations , a vaginal application of 90 mg progesterone per day ( Crinone ) or 300 mg progesterone administered orally ( Utrogestan ) , were compared for luteal phase support of patients undergoing an in-vitro fertilization ( IVF ) procedure . A total of 283 patients were r and omly allocated to either treatment . The treatment started within 24 h after the embryo transfer procedure and continued until day 30 in cases of implantation . Efficacy was assessed using the pregnancy and delivery rates . Safety was assessed through specific symptoms and usual safety monitoring . The pregnancy rates per transfer were not significantly different in the Crinone and Utrogestan groups at days 12 ( Crinone 35.3 % , Utrogestan 29.9 % , P = 0.55 ) , 30 ( Crinone 28.5 % , Utrogestan 25.0 % , P = 0.61 ) and 90 ( Crinone 25.9 % , Utrogestan 22.9 % , P = 0.69 ) . No differences in the spontaneous abortion rates were seen thereafter . The delivery rates ( number of deliveries per patient ; Crinone 23.0 % , Utrogestan 22.2 % , P = 1.00 ) , as well as the ratio of newborn babies per embryo transferred ( Crinone 11.7 % , Utrogestan 11.1 % , P = 0.91 ) , were not significantly different . Safety parameters were similar in both groups , except for drowsiness , which was more significantly frequent in the oral progesterone group than in the Crinone group at all time points . No serious adverse events were recorded in this study . The fact that Crinone matches the efficacy of the larger doses of progesterone used orally reflects an advantage of the transvaginal route of administration which avoids the metabolic inactivation of progesterone during its first liver pass BACKGROUND To compare local tolerance and patients compliance to intravaginal and intramuscular progesterone administration . METHODS Ninety-nine patients have been r and omised to receive either intravaginal Crinone , 90 mg/day ( n=51 ) or intramuscular Prontogest 50 mg/day ( n=48 ) for luteal supplementation in IVF/ICSI cycles . Local and systemic side effects as well as pattern of menstrual bleeding were reported on a self administered question naire . Progesterone levels were evaluated pre-treatment , in the mid-luteal phase and the day of pregnancy test . RESULTS Patients age , BMI , duration and causes of infertility were comparable in the two treatment groups . All parameters of ovarian response as well as pregnancy rates did not show significative difference in the two groups . A significative larger number of patients assigned to intravaginal support were free from side effects . Furthermore side effects , when reported , result ed significantly more severe in the intramuscular group . In the non pregnant patients menstrual flow appeared significantly earlier in those treated with vaginal progesterone ( p<0.001 ) . CONCLUSIONS Crinone 8 is a good alternative to parental progesterone for luteal support in ART cycles . It is well tolerated but it is linked to an earlier appearance of menstrual flow in non conceptional cycles OBJECTIVE To evaluate the effect of adding E(2 ) to progestin supplementation during the luteal phase on pregnancy and implantation rates in patients undergoing IVF cycles . DESIGN Prospect i ve , r and omized study . SETTING An IVF unit in a university hospital . PATIENT(S ) Patients who were undergoing IVF with controlled ovarian hyperstimulation using a GnRH analog and who had E(2)2,500 pg/dL at the time of hCG administration . INTERVENTION(S ) Serum concentrations of E(2 ) and progesterone were measured in all patients on days 7 , 10 , and 12 after ET . MAIN OUTCOME MEASURE(S ) The E(2 ) and progesterone profiles of the luteal phase and the pregnancy and implantation rates were documented . Data were analyzed for the entire study population and further stratified according to the GnRH analog protocol used ( short or long ) . RESULT ( S ) Significantly higher E(2 ) levels were found during the luteal phase in the group that received E(2 ) supplementation . This effect was more pronounced in the patients who were treated with the long GnRH analog protocol . Significantly higher pregnancy and implantation rates were recorded in the patients who received E(2 ) supplementation and were treated with the long GnRH analog protocol . CONCLUSION ( S ) For patients who are treated with the long GnRH analog protocol for controlled ovarian hyperstimulation and for whom luteal support with hCG is contraindicated , the addition of E(2 ) to the progestin support regimen may have a beneficial effect on pregnancy and implantation rates It has been reported that the pregnancy rate after in vitro fertilization ( IVF ) after pituitary desensitization with luteinizing hormone-releasing hormone agonist ( LH-RH-a ) is twice as low if the luteal phase is not supported . We therefore tested the respective advantages of luteal support using human chorionic gonadotropin ( hCG , 1,500 IU three times ) and progesterone ( P , micronized , oral administration , 400 mg/d ) after 171 embryo transfers ( ET ) in which the cycle was stimulated with the LH-RH-a triptoreline . The type of luteal phase support was r and omly selected except when the estradiol level exceeded 2,700 pg/mL. The clinical pregnancy rate and the ongoing pregnancy rate were significantly higher using hCG ( after the transfer of 3 embryos , 45 % and 43 % with hCG versus 23 % and 17 % with P ) . The same results were noted for the embryo implantation rate per ET ( 19 % of embryos are viable after 6 months of pregnancy after hCG versus 7.5 % after P ) . Adequate luteal support , therefore , significantly improves the results of IVF when LH-RH-a are used . The poor results obtained with P in this study might be related to its poor bioavailability after oral administration The use of luteal phase support has been demonstrated in patients undergoing IVF/ET in cycles stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists . However , it is still not clear which is the most suitable kind of supplementation . This study was design ed to compare the absorption and the efficacy of three different luteal support . We r and omly administered progesterone i.m . ( 50 mg/day ) , human chorionic gonadotrophin ( hCG ) ( 2000 IU every three days ) , progesterone vaginal cream ( 100 mg/day ) or nothing ( controls ) to 176 women treated for assisted procreation . We were not able to show any statistical differences for the percentage of pregnancy rate between groups . The serum progestrerone ( P ) and 17-ß-estradiol ( E2 ) and E2/P ratio levels of the luteal phase were compared with the control not supplemented group . All the treatments were able to increase significantly the luteal P values versus controls ( p<0.01 ) . Moreover , vaginal cream and natural P i m significantly decreased E2/P ratio ( p<0.05 ) . Serum P levels were more steady with P vaginal cream than i m injection . Vaginal cream for better bioavailability and acceptance appear the most suitable and comfortable method for luteal phase support Endometrial biopsies showing inadequate development were observed after ovarian stimulation with the GnRH agonist Buserelin and HMG for IVF or GIFT when luteal supplementation was omitted . Ninety-one patients were r and omly allocated to two luteal supplementation regimens : in 41 women HCG and in 50 women progesterone and oestradiol valerate . The pregnancy patients treated with a combination of the GnRH agonist and HMG a delay of implantation of 1.3 days was observed compared to pregnancies after clomiphene citrate-HMG stimulation . This delay was not due to slower preimplantation embryo development after GnRH agonist-HMG treatment . Temporarily defective function of the corpus luteum was evidence d by measuring serum progesterone , 17 beta-oestradiol and 17-hydroxyprogesterone in the patients receiving progesterone and oestradiol valerate . This inadequate corpus luteum function could be related to the prolonged blockage of pituitary gonadotrophic function after arrest of the GnRH agonist This prospect i ve r and omized study compared human chorionic gonadotropin ( hCG ) and micronized transvaginal progesterone for luteal support in 310 in vitro fertilization ( IVF ) patients treated with leuprolide acetate and gonadotropins in a long protocol , and showing normal ovarian response . Both treatment groups were homogeneous for age , BMI , stimulation treatment and ovarian response . Pregnancy rates per embryo transfer were not significantly different ( 33.1 % for the hCG group versus 38.7 % for the progesterone group ) . For IVF patients with a normal response to stimulation under pituitary supression , the use of hCG or progesterone for luteal support does not seem to have any effect on pregnancy rate . The choice of luteal treatment must balance medical hazard and patient convenience , as both therapeutic regimens seem equally effective Objective The purpose of the study was to determine the impact of two forms of luteal-phase supplementation , human chorionic gonadotropin ( hCG ) and progesterone ( P ) , during gonadotropin releasing hormone agonist (GnRha)/controlled ovarian hyperstimulation ( COH ) cycles . Design and Patients The study was a prospect i ve , r and omized evaluation of 77 patients . Group 1 patients ( n=38 ) received 2000 IU of hCG , injected subcutaneously , on days 3 , 6 , 9 , and 12 after transvaginal aspiration of the oocytes ( TVA = day 0 ) . Group 2 patients ( n=39 ) received 50-mg daily injections of intramuscular ( i.m . ) P from days 2 to 14 after TVA . Blood tests were performed on days 0 , 5 , 8 , and 12 after TVA . Setting The in vitro fertilization program of a tertiary care institution was the study setting .Main Outcome Measures The main outcome measures were ( 1 ) pregnancy and implantation rates ; ( 2 ) serum estradiol ( E ) , P , and hCG levels ; and ( 3 ) occurrence of side effects . Results Clinical pregnancy and implantation rates in group 1 versus group 2 were similar ( 36.7 vs 35.3 and 12 vs 14 % , respectively ) . Regardless of pregnancy occurrence , on days 8 and 12 after TVA , serum E and P levels were higher in group 1 than group 2 but the result ing E/P ratios were similar . Five of 38 patients ( group 1 ) developed moderate to severe ovarian hyperstimulation syndrome ( OHSS ) right after the first or second supplementary hCG injection . In these patients , the mean serum E level on the day of hCG trigger injection was about 3250 pg/ml and the number of follicles was between 9 and 17 . In 6 of 39 patients ( group 2 ) allergic reactions were observed at the P injection sites . Conclusions Based on our data , hCG administration as a form of luteal supplementation did not translate , in comparison to P , into significant benefits for the patients . At the same time , it significantly increased the risk of ovarian hyperstimulation . We suggest that whenever , during COH cycles , serum E levels are over 2500 pg/ml and the number of follicles exceeds 10 , luteal support with hCG should be excluded The effectiveness and the absorption of two progesterone ( P ) presentations have been compared for luteal phase support of patients aged < or = 37 years undergoing an in vitro fertilization ( IVF ) procedure for the first time , who were stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists ( GnRHa ) . All of them had two ovaries , normal ovarian functions and normal endometrial morphology : the indication for the assisted reproductive technique was the tubal factor . Two hundred and fifty patients were r and omly allocated to two groups in order to compare two treatment protocol s : Group A : natural i.m . P ( 50 mg/day , Prontogest , AMSA , Italy ) ; Group B : micronized vaginal P ( 200 mg/day Esolut , Angelini , Italy ) . We were able to show that the i.m . P result ed in a higher percentage of pregnancies than the vaginal preparation , with statistically significant differences . We recommend the use of injectable P , and suggest reserving intravaginal P as a second choice for patients who can not tolerate intramuscular administration Objective To examine the endometrial effects of three different doses of progesterone administered vaginally Methods Forty women 25–41 years old deprived of ovarian function received estradiol ( E2 ) for 28 days . From days 15 to 27 , a new mucus-like vaginal gel of progesterone was administered every other day , r and omly , dosed at 45 mg ( group A , n = 14 ) , 90 mg ( group B , n = 13 ) , or 180 mg ( group C , n = 13 ) . Plasma gonadotropins , estrone , E2 , and progesterone were measured . An endometrial biopsy was performed on day 20 ( n = 20 ) or 24 ( n = 20 ) for endometrial dating and for estrogen and progesterone receptor determinations . Results Plasma estrogen levels were in the menstrual cycle range . Mean progesterone levels were lower in group A ( 2.4 ± 0.2 ng/mL ) than in group B ( 3.6 ± 0.2 ng/mL ) or C ( 3.4 ± 0.4 ng/mL ) ( P < .005 ) . Plasma FSH and LH decreased significantly during progesterone treatment . In all groups , we observed secretory transformation in the gl and s ( day 20 ) and stroma ( day 24 ) and the distribution of estrogen and progesterone receptors seen in normal menstrual cycles . Conclusion Transvaginal administration of progesterone induced normal secretory transformation of the endometrium despite low plasma levels , suggesting a direct transit into the uterus or “ first uterine pass effect . OBJECTIVE To evaluate the efficacy of oral micronized progesterone compared with IM progesterone in oil for luteal support in patients undergoing IVF who are treated with a GnRH agonist . DESIGN R and omized prospect i ve clinical trial . SETTING University-based IVF center . PATIENT(S ) Women < 40 years of age who were undergoing IVF with luteal GnRH pituitary down-regulation . INTERVENTION(S ) Patients were r and omized to receive either oral micronized progesterone ( 200 mg three times daily ) or IM progesterone ( 50 mg daily ) . MAIN OUTCOME MEASURE(S ) Progesterone levels at st and ardized days 21 and 28 , and pregnancy and embryo implantation rates . RESULT ( S ) Day 21 progesterone levels were 77.6+/-13.2 ng/mL in the IM group and 81.5+/-16.2 ng/mL in the oral group . Day 28 progesterone levels were 76.3+/-15.0 ng/mL in the IM group and 53.6+/-10.1 ng/mL in the oral group . The clinical pregnancy rates were 57.9 % and 45.8 % for the IM and oral groups , respectively . The implantation rate per embryo was significantly higher in the IM group ( 40.9 % ) than in the oral group ( 18.1 % ) . CONCLUSION ( S ) When used according to our protocol s , oral progesterone and IM progesterone result in comparable levels of circulating progesterone . However , oral progesterone results in a reduced implantation rate per embryo Two different regimens of luteal support in gonadotrophin hormone-releasing hormone ( GnRH ) analogue/human menopausal gonadotrophin (GnRHa/HMG)-induced in-vitro fertilization cycle ( IVF ) were compared in a r and omized clinical trial . After embryo transfer , either vaginal progesterone alone was administered ( n = 89 , P group ) , or a combination of vaginal progesterone and human chorionic gonadotrophin ( n = 87 , P/HCG group ) . The primary aim of this study was to assess the effect of the different regimens of luteal support on the pregnancy rate . The secondary aim was to compare oestradiol and progesterone concentrations in the luteal phase between the two groups , and assess their effect on the pregnancy rate . A clinical pregnancy rate of 15 % was found in the P/HCG group in comparison with 26 % in the P group ( odds ratio 0.49 ; 99 % confidence interval : 0.18 - 1.3 ) . The luteal serum oestradiol and progesterone values in the P/HCG group were significantly higher when compared with the P group on the 6th , 9th and 12th day after oocyte retrieval ( Wilcoxon P < 0.001 ) . In accordance with the high oestradiol concentrations , more cases of ovarian hyperstimulation syndrome ( OHSS ) were found in the P/HCG group . Oestradiol values on the 9th day after oocyte retrieval , presumably the day of implantation , appeared to be higher in women who did not become clinical ly pregnant . We conclude that vaginal progesterone alone provides sufficient luteal support in GnRHa/HMG induced IVF cycles . The combination of vaginal progesterone and HCG as luteal support leads to significant high luteal oestradiol and progesterone concentrations . But a high concentration of oestradiol seems to have a deleterious effect on the implantation process , result ing in a low pregnancy rate The value of luteal phase supplementation with human chorionic gonadotropin ( hCG ) was assessed after a combined protocol of ovarian stimulation , using a long acting gonadotropin releasing hormone analog ( GnRH-a ) and human menopausal gonadotropins ( hMG ) , in a r and omized prospect i ve study of 36 consecutive cycles in an in vitro fertilization ( IVF ) program . The patients were allocated on the transfer day to either luteal phase supplementation with hCG ( Group A , n = 18 ) or none ( Group B , n = 18 ) . Nine patients of Group A conceived as compared with 3 in Group B. Five patients , all in Group A , developed ovarian hyperstimulation syndrome ( OHSS ) ( 3 moderate and 2 severe forms ) . Analysis of the hormonal profiles disclosed similar progesterone ( P ) , estradiol ( E2 ) , and E2/P ratio up to the 6th post ovum pick-up day . Then , E2 and mainly P levels decreased only in Group B result ing in a rising E2/P ratio . These findings stress the importance of luteal support in IVF cycles treated with GnRH-a . In light of the increased risk of OHSS among hCG treated patients , further studies are needed to assess the optimal preparation needed A prospect i ve r and omized study was conducted to evaluate the use of adding oestradiol valerate 6 mg per os daily to intravaginal micronized progesterone ( 600 mg daily ) as luteal supplements . The study comprised 378 infertile women superovulated with a gonadotrophin releasing-hormone agonist ( GnRHa ) and human menopausal gonadotrophins ( HMG ) for in-vitro fertilization ( IVF ) or zygote intra-Fallopian transfer ( ZIFT ) . The clinical pregnancy rate was similar ( 29 % ) whether or not oestradiol valerate was added to intravaginal progesterone . Eighteen out of twenty-two endometrial biopsies were in phase , and morphological evaluations of the two luteal supplementation groups were not different . Serum hormone profiles in singleton pregnancies showed a similar day of appearance of human chorionic gonadotrophin ( HCG ) in both protocol s but significantly lower oestradiol concentrations arose in the group without oestradiol valerate . In 32 % of the singleton pregnancies , the first appearance of HCG occurred later than day 12 after HCG injection ; in those ongoing pregnancies , corpus luteum rescue -- as measured by significantly lower serum oestradiol and progesterone concentrations -- was compromised . This study provided no evidence of any benefit of routinely supplementing GnRHa/HMG cycles with oestradiol valerate in addition to intravaginal micronized progesterone |
11,771 | 12,804,424 | REVIEW ER 'S CONCLUSIONS There is currently no evidence to support recommending vitamins such as alpha-tocopherol , beta-carotene or retinol , alone or in combination , to prevent lung cancer .
A harmful effect was found for beta-carotene with retinol at pharmacological doses in people with risk factors for lung cancer ( smoking and /or occupational exposure to asbestos ) . | BACKGROUND Some studies have suggested a protective effect of antioxidant nutrients on lung cancer .
Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta carotene and a lower risk of lung cancer .
OBJECTIVES To determine whether vitamins , minerals and other potential agents , alone or in combination , reduce incidence and mortality from lung cancer in healthy people . | CARET is a multicenter , two-armed , double-masked r and omized chemoprevention trial in Seattle , Portl and , San Francisco , Baltimore , Connecticut , and Irvine , to test whether oral administration of beta-carotene ( 30 mg/day ) plus retinyl palmitate ( 25,000 IU/day ) can decrease the incidence of lung cancer in high risk population s , namely , heavy smokers and asbestos-exposed workers . The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30 , 1993 , CARET had r and omized 1,845 participants in the 1985 - 1988 pilot phase plus 13,260 " efficacy " participants since 1989 ; of these , 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers ( 44 % female ) . Accrual is complete everywhere except Irvine , which was the last center added ( 1991 ) , and the safety profile of the regimen to date has been excellent . With 14,420 smokers , 4,010 asbestos-exposed participants , and 114,100 person-years through February 1998 , we expect CARET to be capable of detecting a 23 % reduction in lung cancer incidence in the two population s combined and 27 , 49 , 32 , and 35 % reductions in the smokers , female smokers , male smokers , and asbestos-exposed subgroups , respectively . CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finl and and the Harvard Physicians Health Study ( beta-carotene alone ) in the National Cancer Institute portfolio of major cancer chemoprevention trials BACKGROUND : In observational studies , individuals with high intakes of fruits and vegetables containing beta-carotene experience lower risks of developing cancer . However , the few r and omized trials of beta-carotene supplementation show no overall benefits ; some even suggest harm . This trial was design ed to test the effects of beta-carotene supplementation in women . METHODS : The Women 's Health Study is a r and omized , double-blind , placebo-controlled trial originally testing aspirin , vitamin E , and beta-carotene in the prevention of cancer and cardiovascular disease among 39 876 women aged 45 years or older . The beta-carotene component was terminated early after a median treatment duration of 2.1 years ( range = 0.00 - 2 . 72 years ) . Statistical tests were two-sided . RESULTS : Among women r and omly assigned to receive beta-carotene ( 50 mg on alternate days ; n = 19 939 ) or placebo ( n = 19 937 ) , there were no statistically significant differences in incidence of cancer , cardiovascular disease , or total mortality after a median of 4.1 years ( 2.1 years ' treatment plus another 2.0 years ' follow-up ) . There were 378 cancers in the beta-carotene group and 369 cancers in the placebo group ( relative risk [ RR ] = 1.03 ; 95 % confidence interval [ CI ] = 0.89 - 1 . 18 ) . There were no statistically significant differences for any site-specific cancer or during years 1 and 2 combined and years 3 and up combined . For cardiovascular disease , there were no statistically significant differences for myocardial infa rct ion ( 42 in the beta-carotene group versus 50 in the placebo group ) , stroke ( 61 versus 43 ) , deaths from cardiovascular causes ( 14 versus 12 ) , or the combined end point of these three events ( 116 versus 102 ; among women with more than one event , only the first was counted ) . Deaths from any cause were similar in the two groups ( 59 versus 55 ) . Among smokers at baseline ( 13 % of all women ) , there were no statistically significant differences in overall incidence of cancer ( RR = 1.11 ; 95 % CI = 0.78 - 1.58 ) or cardiovascular disease ( RR = 1.01 ; 95 % CI = 0 . 62 - 1.63 ) . CONCLUSION : Among apparently healthy women , there was no benefit or harm from beta-carotene supplementation for a limited period on the incidence of cancer and of cardiovascular disease BACKGROUND Evidence has accumulated from observational studies that people eating more fruits and vegetables , which are rich in beta-carotene ( a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver ) and retinol ( an alcohol chemical form of vitamin A ) , and people having higher serum beta-carotene concentrations had lower rates of lung cancer . The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ( vitamin A ) taken daily against placebo in 18314 men and women at high risk of developing lung cancer . The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm ; there were 28 % more lung cancers and 17 % more deaths in the active intervention group ( active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ) . Promptly after the January 18 , 1996 , announcement that the CARET active intervention had been stopped , we published preliminary findings from CARET regarding cancer , heart disease , and total mortality . PURPOSE We present for the first time results based on the pre-specified analytic method , details about risk factors for lung cancer , and analyses of subgroups and of factors that possibly influence response to the intervention . METHODS CARET was a r and omized , double-blinded , placebo-controlled chemoprevention trial , initiated with a pilot phase and then exp and ed 10-fold at six study centers . Cigarette smoking history and status and alcohol intake were assessed through participant self-report . Serum was collected from the participants at base line and periodically after r and omization and was analyzed for beta-carotene concentration . An Endpoints Review Committee evaluated endpoint reports , including pathologic review of tissue specimens . The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence , with weighting linearly to hypothesized full effect at 24 months after r and omization . Relative risks ( RRs ) were estimated by use of Cox regression models ; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake . O'Brien-Fleming boundaries were used for stopping criteria at interim analyses . Statistical significance was set at the .05 alpha value , and all P values were derived from two-sided statistical tests . RESULTS According to CARET 's pre-specified analysis , there was an RR of 1.36 ( 95 % confidence interval [ CI ] = 1.07 - 1.73 ; P = .01 ) for weighted lung cancer incidence for the active intervention group compared with the placebo group , and RR = 1.59 ( 95 % CI = 1.13 - 2.23 ; P = .01 ) for weighted lung cancer mortality . All subgroups , except former smokers , had a point estimate of RR of 1.10 or greater for lung cancer . There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake ( RR = 1.99 ; 95 % CI = 1.28 - 3.09 ; test for heterogeneity of RR among quartiles of alcohol intake has P = .01 , unadjusted for multiple comparisons ) and with large-cell histology ( RR = 1.89 ; 95 % CI = 1.09 - 3.26 ; test for heterogeneity among histologic categories has P = .35 ) , but not with base-line serum beta-carotene concentrations . CONCLUSIONS CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality . The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finl and CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome . Participants at high risk for lung cancer are drawn from two population s : asbestos-exposed workers and heavy smokers . The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate . Nearly 18,000 participants will be followed for a mean 6 years , yielding over 100,000 person-years of follow-up . We project that this sample size will have 80 % power to detect a 23 % decrease in the incidence of lung cancer cases . The purpose of this paper is to present the values of the key sample size parameters of CARET ; our schemes for monitoring CARET for sample size adequacy , incidence of side effects , and efficacy of the study vitamins ; an overview of the data collected ; and plans for the primary , secondary , and ancillary analyses to be performed at the end of the trial . These approaches to the design , monitoring , and analysis of CARET are applicable for many other prevention trials Despite numerous published studies , debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos , particularly those without radiographic or functional evidence of asbestosis . The beta-Carotene and Retinol Efficacy Trial ( CARET ) , a study of vitamin supplementation for chemoprevention of lung cancer , has followed 4,060 heavily exposed US men for 9 - 17 years . Lung cancer incidence for 1989 - 2002 was analyzed using a stratified proportional hazards model . The study confirmed excessive rates of lung cancer among men with radiographic asbestosis . Comparison of study arms revealed a strong , unanticipated synergy between radiographic profusion category and the active intervention . In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline , there was evidence of exposure-related lung cancer risk : Men with more than 40 years ' exposure in high-risk trades had a risk approximately fivefold higher than men with 5 - 10 years , after adjustment for covariates . The effect in these men was independent of study intervention arm , but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer . Residual confounding by sub clinical asbestosis , exposure to unmeasured lung carcinogens , or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se BACKGROUND The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the effect of daily beta-carotene ( 30 mg ) and retinyl palmitate ( 25,000 IU ) on the incidence of lung cancer , other cancers , and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure . CARET was stopped ahead of schedule in January 1996 because participants who were r and omly assigned to receive the active intervention were found to have a 28 % increase in incidence of lung cancer , a 17 % increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group . METHODS After the intervention ended , CARET participants returned the study vitamins to their study center and provided a final blood sample . They continue to be followed annually by telephone and mail self-report . Self-reported cancer endpoints were confirmed by review of pathology reports , and death endpoints were confirmed by review of death certificates . All statistical tests were two-sided . RESULTS With follow-up through December 31 , 2001 , the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 ( 95 % confidence interval [ CI ] = 0.97 to 1.31 ) and 1.08 ( 95 % CI = 0.99 to 1.17 ) , respectively . Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up . By contrast , the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped . During the post-intervention phase , females had larger relative risks of lung cancer mortality ( 1.33 versus 1.14 ; P = .36 ) , cardiovascular disease mortality ( 1.44 versus 0.93 ; P = .03 ) , and all-cause mortality ( 1.37 versus 0.98 ; P = .001 ) than males . CONCLUSIONS The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant . Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females , and cardiovascular disease mortality primarily to females and to former smokers Our aim was to describe a vitamin A-based cancer prevention program for former asbestos workers and to check for possible harmful effects by comparing rates of disease and death in study subjects with subjects who chose not to join . All subjects had been occupationally exposed to crocidolite at Wittenoom Gorge between 1943 and 1966 ; 1,677 subjects indicated interest in the program and 1,203 joined between June 1990 and May 1995 . Comparison subjects consisted of 996 former workers known to be alive in Western Australia in 1990 who did not join the program . Program subjects were provided with annual supplies of vitamin A ( either synthetic beta-carotene or retinol ) , help in quitting smoking and dietary advice . The comparison group received only mail contact . Both groups were followed up to December 1994 for vital status and cancer information , and rates of cancer and death from various causes were compared . Mortality in both groups was higher than expected ( st and ardised mortality ratio 1.23 in program subjects and 1.67 in comparison subjects ) . After adjustment for age , smoking and asbestos exposure , the relative rates in participants compared with non- participants was below I for all examined cancers and causes of death . For mesothelioma and lung cancer , group differences increased with time from entry , whereas other differences dissipated with time . No significant side effects were reported . In conclusion , program participants had significantly lower mortality than non- participants , but the rates of the 2 groups converged with time We measured serum etretinate to monitor compliance in an ongoing chemoprevention trial in which heavy smokers are r and omized to either etretinate or placebo orally for 6 months . Blood is collected for determination of etretinate levels before treatment and then at 2 , 4 , 8 , 16 , and 24 weeks after r and omization . The monitoring strategy was assessed by interim evaluation . There were 276 posttreatment sample s available from 75 r and omized subjects of whom 36 received etretinate and 39 placebo . The mean coefficient of variation for the internal st and ard retinyl acetate in serum was 4.16 % for the high-pressure liquid chromatography method used . Among positive sample s , the mean etretinate concentration was 25.7 ng/mL ( SD , 23.4 ) . Of the 131 sample s obtained from subjects r and omized to etretinate , 120 or 91.6 % had detectable levels compared with 4 of 145 or 2.8 % placebo sample s. Among the 36 subjects given etretinate , at least one positive test occurred . In 27 of these 36 participants , etretinate was detected in every sample obtained . In the other nine , the absence of drug could be explained by pill counts or a history of discontinuation of treatment for six . Among the 39 subjects given placebo , the four positive sample s were from four individuals , all of whom were negative on three other occasions . These data confirm the usefulness of the monitoring system we used and indicate that compliance and /or contamination will not be major problems in this trial BACKGROUND Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables , as well as high serum levels of vitamin E ( alpha-tocopherol ) and beta carotene , are associated with a reduced risk of lung cancer . METHODS We performed a r and omized , double-blind , placebo-controlled primary -prevention trial to determine whether daily supplementation with alpha-tocopherol , beta carotene , or both would reduce the incidence of lung cancer and other cancers . A total of 29,133 male smokers 50 to 69 years of age from southwestern Finl and were r and omly assigned to one of four regimens : alpha-tocopherol ( 50 mg per day ) alone , beta carotene ( 20 mg per day ) alone , both alpha-tocopherol and beta carotene , or placebo . Follow-up continued for five to eight years . RESULTS Among the 876 new cases of lung cancer diagnosed during the trial , no reduction in incidence was observed among the men who received alpha-tocopherol ( change in incidence as compared with those who did not , -2 percent ; 95 percent confidence interval , -14 to 12 percent ) . Unexpectedly , we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not ( change in incidence , 18 percent ; 95 percent confidence interval , 3 to 36 percent ) . We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer . Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not . Beta carotene had little or no effect on the incidence of cancer other than lung cancer . Alpha-tocopherol had no apparent effect on total mortality , although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not . Total mortality was 8 percent higher ( 95 percent confidence interval , 1 to 16 percent ) among the participants who received beta carotene than among those who did not , primarily because there were more deaths from lung cancer and ischemic heart disease . CONCLUSIONS We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene . In fact , this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects The Nutritional Prevention of Cancer Trial was a r and omized , clinical trial design ed to evaluate the efficacy of selenium as selenized yeast ( 200 microg daily ) in preventing the recurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States . Original secondary analyses through December 31 , 1993 showed striking inverse associations between treatment and the incidence of total [ hazard ratio ( HR ) = 0.61 , 95 % confidence interval ( CI ) = 0.46 - 0.82 ] , lung , prostate , and colorectal cancer and total cancer mortality . This report presents results through February 1 , 1996 , the end of blinded treatment . Effect modification by baseline characteristics is also evaluated . The effects of treatment overall and within subgroups of baseline age , gender , smoking status , and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models . Selenium supplementation reduced total ( HR = 0.75 , 95 % CI = 0.58 - 0.97 ) and prostate ( HR = 0.48 , 95 % CI = 0.28 - 0.80 ) cancer incidence but was not significantly associated with lung ( HR = 0.74 , 95 % CI = 0.44 - 1.24 ) and colorectal ( HR = 0.46 , 95 % CI = 0.21 - 1.02 ) cancer incidence . The effects of treatment on other site-specific cancers are also described . The protective effect of selenium was confined to males ( HR = 0.67 , 95 % CI = 0.50 - 0.89 ) and was most pronounced in former smokers . Participants with baseline plasma selenium concentrations in the lowest two tertiles ( < 121.6 ng/ml ) experienced reductions in total cancer incidence , whereas those in the highest tertile showed an elevated incidence ( HR = 1.20 , 95 % CI = 0.77 - 1.86 ) . The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence , although not all site-specific cancers exhibited a reduction in incidence . This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations Approximately 5 % of all cancers develop in the mucosa of the head and neck area ( Boyle et al. , 1990 ) . A substantial number of these patients present at a moment that curative treatment is possible , due to the fact that many head and neck cancers cause complaints in an early stage . The prognosis of TINO and T2NO glottic laryngeal cancer , for instance , is in the order of 90 and 70 % 5 year survival respectively . It is very likely that the pathogenesis of head and neck cancer is multifactorial . Both tobacco and alcohol are important risk factors in oral , oropharyngeal , hypopharyngeal and laryngeal cancer ( Wynder et al. , 1956 , 1976 ; Williams & Horn , 1977 ; Tuyns , 1979 ; Rothman et al. , 1980 ) . In addition , it is very likely that an individual genetic susceptibility ( de Vries et al. , 1987a , 1987b ; Schantz & Hsu , 1989 ; Spitz et al. , 1989 ; Schantz et al. , 1990 ) is important if only because so many individuals have been and are being exposed to tobacco and alcohol , whereas only relatively few actually develop cancer in the upper air and food passages . Patients with head and neck cancers are prone to develop multiple primary cancers ( see further ) , probably because the mucosa of the upper air and food passages is being exposed to the same carcinogens . The situation in lung cancer patients is different from that of head and neck cancer patients . Lung cancer is the leading cause of cancer deaths in men and the second leading cause of cancer deaths in women , after cancer of the breast . The major factor in the development of lung cancer is the inhalation of tobacco smoke , by susceptible hosts . In contrast to head and neck cancer patients , most lung cancer patients already have a poor prognosis at the time of diagnosis . The 5 year survival rate for all stages of lung cancer has been about 9 % for the last 20 years . This small sub population of patients that will be cured from their lung cancer are unfortunately prone to develop second primary cancers as well . Multiple primary tumours occurs in 10 - 30 % of all patients with head and neck cancer and in 10 % of patients with , lung cancer ( Vrabec , 1979 ; Gluckman & Crissman , 1983 ; Tepperman & Fitzpatrick , 1981 ; Gluckman , 1983 ; Wagenfeld et al. , 1981 ; Hordijk & de Jong , 1983 ; de Vries & Snow , 1986 ; de Vries et al. , 1986 ; De Vries , 1990 , and many others ) . The great majority of these second primary cancers occur metachronously in the respiratory tract and upper digestive tract . These second primary tumours usually carry a bad prognosis because they often occur either at notoriously bad sites , like ( again in ) the lung or esophagus , or within BACKGROUND It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer . To date , however , the published results of r and omized , placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect . We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population . METHODS The Supplementation en Vitamines et Mineraux Antioxydants ( SU.VI.MAX ) study is a r and omized , double-blind , placebo-controlled primary prevention trial . A total of 13 017 French adults ( 7876 women aged 35 - 60 years and 5141 men aged 45 - 60 years ) were included . All participants took a single daily capsule of a combination of 120 mg of ascorbic acid , 30 mg of vitamin E , 6 mg of beta carotene , 100 mug of selenium , and 20 mg of zinc , or a placebo . Median follow-up time was 7.5 years . RESULTS No major differences were detected between the groups in total cancer incidence ( 267 [ 4.1 % ] for the study group vs 295 [ 4.5 % ] for the placebo group ) , ischemic cardiovascular disease incidence ( 134 [ 2.1 % ] vs 137[2.1 % ] ) , or all-cause mortality ( 76 [ 1.2 % ] vs 98 [ 1.5 % ] ) . However , a significant interaction between sex and group effects on cancer incidence was found ( P = .004 ) . Sex-stratified analysis showed a protective effect of antioxidants in men ( relative risk , 0.69 [ 95 % confidence interval [ CI ] , 0.53 - 0.91 ] ) but not in women ( relative risk , 1.04 [ 95 % CI , 0.85 - 1.29 ] ) . A similar trend was observed for all-cause mortality ( relative risk , 0.63 [ 95 % CI , 0.42 - 0.93 ] in men vs 1.03 [ 95 % CI , 0.64 - 1.63 ] in women ; P = .11 for interaction ) . CONCLUSIONS After 7.5 years , low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women . Supplementation may be effective in men only because of their lower baseline status of certain antioxidants , especially of beta carotene BACKGROUND Fenretinide , a vitamin A analogue , has been shown to inhibit breast carcinogenesis in pre clinical studies . We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer . METHODS We r and omly assigned 2972 women , aged 30 - 70 years , with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally ( 200 mg/day ) or no treatment . The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after r and omization . Other end points considered post hoc were the same outcomes stratified by menopausal status , incidence of distant metastases , overall mortality , and tumors in other organs . The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis . Statistical tests were two-sided . RESULTS At a median observation time of 97 months , there were no statistically significant differences in the occurrence of contralateral breast cancer ( P = .642 ) or ipsilateral breast cancer ( P = .177 ) between the two arms . However , an interaction was detected between fenretinide treatment and menopausal status in both outcomes ( P for interaction in both outcomes = .045 ) , with a possible beneficial effect in premenopausal women ( contralateral breast cancer : adjusted hazard ratio [ HR ] = 0.66 , and 95 % confidence interval [ CI ] = 0.41 - 1.07 ; ipsilateral breast cancer : adjusted HR = 0.65 , and 95 % CI = 0.46 - 0 . 92 ) and an opposite effect in postmenopausal women ( contralateral breast cancer : adjusted HR = 1.32 , and 95 % CI = 0.82 - 2.15 ; ipsilateral breast cancer : adjusted HR = 1.19 , and 95 % CI = 0.75 - 1 . 89 ) . There were no statistically significant differences between the two arms in tumors in other organs , incidence of distant metastasis , and all-cause mortality . CONCLUSIONS Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall , although a possible benefit was detected in premenopausal women . These studies , particularly the post hoc analyses , are considered exploratory and need to be confirmed BACKGROUND Experimental and epidemiologic investigations suggest that alpha-tocopherol ( the most prevalent chemical form of vitamin E found in vegetable oils , seeds , grains , nuts , and other foods ) and beta-carotene ( a plant pigment and major precursor of vitamin A found in many yellow , orange , and dark-green , leafy vegetables and some fruit ) might reduce the risk of cancer , particularly lung cancer . The initial findings of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( ATBC Study ) indicated , however , that lung cancer incidence was increased among participants who received beta-carotene as a supplement . Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial ( CARET ) , which tested a combination of beta-carotene and vitamin A. PURPOSE We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics ( e.g. , age , number of cigarettes smoked , dietary or serum vitamin status , and alcohol consumption ) , by study compliance , and in relation to clinical factors , such as disease stage and histologic type . Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other population s. METHODS A total of 29,133 men aged 50 - 69 years who smoked five or more cigarettes daily were r and omly assigned to receive alpha-tocopherol ( 50 mg ) , beta-carotene ( 20 mg ) , alpha-tocopherol and beta-carotene , or a placebo daily for 5 - 8 years ( median , 6.1 years ) . Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry , along with measurements of serum levels of alpha-tocopherol and beta-carotene . Incident cases of lung cancer ( n = 894 ) were identified through the Finnish Cancer Registry and death certificates . Each lung cancer diagnosis was independently confirmed , and histology or cytology was available for 94 % of the cases . Intervention effects were evaluated by use of survival analysis and proportional hazards models . All P values were derived from two-sided statistical tests . RESULTS No overall effect was observed for lung cancer from alpha-tocopherol supplementation ( relative risk [ RR ] = 0.99 ; 95 % confidence interval [ CI ] = 0.87 - 1.13 ; P = .86 , logrank test ) . beta-Carotene supplementation was associated with increased lung cancer risk ( RR = 1.16 ; 95 % CI = 1.02 - 1.33 ; P = .02 , logrank test ) . The beta-carotene effect appeared stronger , but not substantially different , in participants who smoked at least 20 cigarettes daily ( RR = 1.25 ; 95 % CI = 1.07 - 1.46 ) compared with those who smoked five to 19 cigarettes daily ( RR = 0.97 ; 95 % CI = 0.76 - 1.23 ) and in those with a higher alcohol intake ( > or = 11 g of ethanol/day [ just under one drink per day ] ; RR = 1.35 ; 95 % CI = 1.01 - 1.81 ) compared with those with a lower intake ( RR = 1.03 ; 95 % CI = 0.85 - 1.24 ) . CONCLUSIONS Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke . beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers , and this effect may be associated with heavier smoking and higher alcohol intake . IMPLICATION S While the most direct way to reduce lung cancer risk is not to smoke tobacco , smokers should avoid high-dose beta-carotene supplementation Laboratory studies , and one previous uncontrolled trial , have suggested that retinoids may reverse bronchial atypia , a putatively premalignant condition . Sputum sampling is a simple , non-invasive method of assessing atypia . Smokers with at least a 15 pack-year history were screened for sputum atypia . One hundred and fifty subjects ' were r and omised to receive the synthetic retinoid etretinate 25 mg orally or identical placebo daily for 6 months . Compliance was measured by performing pill counts and serum sampling every 2 months for etretinate levels . The outcomes assessed were , improvements in sputum atypia and toxicity . At baseline there was no significant difference between the two groups with respect to gender , smoking history or extent of atypia . Four of 75 subjects on etretinate and six of 75 on placebo dropped out before 6 months . Compliance as measured by pill counts and etretinate levels was high . Eighty-six per cent of subjects on etretinate took 90 % or more of their prescribed medication and etretinate was detected in 245 of 264 sample s. By contrast etretinate was detected in only six of 266 sample s in the control group and probably did not represent true contamination . After 6 months on etretinate there was no difference in the degree of atypia between the two treatment arms . Toxicity was mild in both groups with considerable placebo effect noted . Etretinate , at the dose used in this study , had no impact on sputum atypia as detected by sputum sampling BACKGROUND Pre clinical evidence suggests that retinoids and antioxidants may prevent or delay the occurrence of cancer in the upper or lower airways , but such effects have not been reliably established in clinical studies . To assess the chemopreventive effects of vitamin A ( retinyl palmitate ) and N-acetylcysteine , we conducted a large r and omized intervention study in patients with head and neck cancer or with lung cancer , most of whom had a history of smoking . METHODS From June 1988 through July 1994 , a total of 2592 patients ( 60 % with head and neck cancer and 40 % with lung cancer ) were r and omly assigned to receive 1 ) retinyl palmitate ( 300000 IU daily for 1 year followed by 150000 IU for a 2(nd ) year ) , 2 ) N-acetylcysteine ( 600 mg daily for 2 years ) , 3 ) both compounds , or 4 ) no intervention . All statistical tests were two-sided . RESULTS Of the patients , 93.5 % had smoked tobacco at sometime in their lives ( and 25 % continued to smoke after cancer diagnosis ) . After a median follow-up of 49 months , 916 patients were reported with an event ( recurrence , second primary tumor , or death ) . No statistically significant difference was observed in overall survival or event-free survival between patients who received retinyl palmitate and patients who did not . Similarly , no difference was seen in overall survival or event-free survival between patients who received N-acetylcysteine and patients who did not . There was a lower incidence of second primary tumors in the no intervention arm , but the difference was not statistically significant . CONCLUSION A 2-year supplementation of retinyl palmitate and /or N-acetylcysteine result ed in no benefit-in terms of survival , event-free survival , or second primary tumors-for patients with head and neck cancer or with lung cancer , most of whom were previous or current smokers CONTEXT Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons , who self-select for high intakes of vitamin E through diet or supplements , have decreased risks of cardiovascular disease and cancer . R and omized trials do not generally support benefits of vitamin E , but there are few trials of long duration among initially healthy persons . OBJECTIVE To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women . DESIGN , SETTING , AND PARTICIPANTS In the Women 's Health Study conducted between 1992 and 2004 , 39 876 apparently healthy US women aged at least 45 years were r and omly assigned to receive vitamin E or placebo and aspirin or placebo , using a 2 x 2 factorial design , and were followed up for an average of 10.1 years . INTERVENTION Administration of 600 IU of natural- source vitamin E on alternate days . MAIN OUTCOME MEASURES Primary outcomes were a composite end point of first major cardiovascular event ( nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death ) and total invasive cancer . RESULTS During follow-up , there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group , a nonsignificant 7 % risk reduction ( relative risk [ RR ] , 0.93 ; 95 % confidence interval [ CI ] , 0.82 - 1.05 ; P = .26 ) . There were no significant effects on the incidences of myocardial infa rct ion ( RR , 1.01 ; 95 % CI , 0.82 - 1.23 ; P = .96 ) or stroke ( RR , 0.98 ; 95 % CI , 0.82 - 1.17 ; P = .82 ) , as well as ischemic or hemorrhagic stroke . For cardiovascular death , there was a significant 24 % reduction ( RR , 0.76 ; 95 % CI , 0.59 - 0.98 ; P = .03 ) . There was no significant effect on the incidences of total cancer ( 1437 cases in the vitamin E group and 1428 in the placebo group ; RR , 1.01 ; 95 % CI , 0.94 - 1.08 ; P = .87 ) or breast ( RR , 1.00 ; 95 % CI , 0.90 - 1.12 ; P = .95 ) , lung ( RR , 1.09 ; 95 % CI , 0.83 - 1.44 ; P = .52 ) , or colon cancers ( RR , 1.00 ; 95 % CI , 0.77 - 1.31 ; P = .99 ) . Cancer deaths also did not differ significantly between groups . There was no significant effect of vitamin E on total mortality ( 636 in the vitamin E group and 615 in the placebo group ; RR , 1.04 ; 95 % CI , 0.93 - 1.16 ; P = .53 ) . CONCLUSIONS The data from this large trial indicated that 600 IU of natural- source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer , did not affect total mortality , and decreased cardiovascular mortality in healthy women . These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women The hypothesis that a dietary supplement of selenium ( Se ) may reduce cancer risk was tested experimentally in humans . Patients with histories of basal/squamous cell carcinomas of the skin were assigned r and omly in double-blind fashion to daily oral supplements of either Se-enriched yeast ( 200 micrograms Se/day ) , or a low-Se yeast placebo . A total of 1312 patients recruited in 1983 - 1990 were followed with regular dermatologic examinations through 1993 for a total of 8269 person-years of observation . Skin cancer diagnoses were confirmed histologically . Plasma Se concentration was determined at 6 - 12 months intervals . All deaths and patient-reported illnesses were recorded ; reported cancers were confirmed and documented by consultation with the patient medical care providers . The results indicate that Se did not significantly affect the primary endpoints : incidences of recurrent basal/squamous cell carcinomas of the skin . However , Se-treatment was associated with reductions in several secondary endpoints : total mortality , mortality from all cancers combined , as well as the incidence of all cancers combined , lung cancer , colorectal cancer and prostate cancer . The consistencies of these associations over time , between study clinics and for the leading cancer sites strongly suggests benefits of Se-supplementation for this cohort of patients , supporting the hypothesis that supplemental Se can reduce cancer risk . Although Se did not shown protective effects against non-melanoma skin cancers , the suggested reductions in risks to other frequent cancers dem and further evaluation in well controlled clinical intervention trials Beta-carotene has established efficacy in animal models of oral carcinogenesis and has been shown to regress oral precancerous lesions in humans . The purpose of this study was to see whether these effects extended to the prevention of oral/pharyngeal/laryngeal ( head and neck ) cancer in humans . The subject population for this r and omized , placebo-controlled , double-blinded clinical trial included 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity , pharynx , or larynx . Patients were assigned r and omly to receive 50 mg of beta-carotene per day or placebo and were followed for up to 90 months for the development of second primary tumors and local recurrences . After a median follow-up of 51 months , there was no difference between the two groups in the time to failure [ second primary tumors plus local recurrences : relative risk ( RR ) , 0.90 ; 95 % confidence interval ( CI ) , 0.56 - 1.45 ] . In site-specific analyses , supplemental beta-carotene had no significant effect on second head and neck cancer ( RR , 0.69 ; 95 % CI , 0.39 - 1.25 ) or lung cancer ( RR , 1.44 ; 95 % CI , 0.62 - 3.39 ) . Total mortality was not significantly affected by this intervention ( RR , 0.86 ; 95 % CI , 0.52 - 1.42 ) . Whereas none of the effects were statistically significant , the point estimates suggested a possible decrease in second head and neck cancer risk but a possible increase in lung cancer risk . These effects are consistent with the effects observed in trials using intermediate end point biological markers in humans , in which beta-carotene has established efficacy in oral precancerous lesions but has no effect or slightly worsens sputum cytology , and in animal carcinogenicity studies , in which beta-carotene has established efficacy in buccal pouch carcinogenesis in hamsters but not in animal models of respiratory tract/lung carcinogenesis , with some suggestions of tumor-promoting effects in respiratory tract/lung . If our results are replicated by other ongoing/completed trials , this suggests a critical need for mechanistic studies addressing differential responses in one epithelial site ( head and neck ) versus another ( lung ) A r and omized , placebo-controlled clinical trial of beta-carotene and retinol was conducted with 755 former asbestos workers as study subjects . The targeted endpoint for the intervention study was a reduction in the incidence and prevalence of sputum atypia . The dosage of 50 mg beta-carotene/d and 25,000 IU retinol/d on alternate days result ed significant increases in serum concentrations of both agents with no clinical ly significant toxicity . Skin yellowing was observed in approximately 35 % of patients and may have contributed adversely to protocol adherence . Baseline analysis revealed that smoking and drinking were associated with lower concentrations of serum beta-carotene , even after dietary carotene intake was adjusted for ( P < 0.0001 ) . Baseline concentrations of retinol were apparently lowered by smoking ( P < 0.002 ) and increased by drinking ( P < 0.0001 ) . Drinking and smoking also were significantly related to lower beta-carotene concentrations after supplementation ( P < 0.001 ) . No significant reduction in sputum atypia was observed after treatment BACKGROUND Promising data have suggested that retinoid chemoprevention may help to control second primary tumors ( SPTs ) , recurrence , and mortality of stage I non-small-cell lung cancer ( NSCLC ) patients . METHODS We carried out a National Cancer Institute ( NCI ) Intergroup phase III trial ( NCI # I91 - 0001 ) with 1166 patients with pathologic stage I NSCLC ( 6 weeks to 3 years from definitive resection and no prior radiotherapy or chemotherapy ) . Patients were r and omly assigned to receive a placebo or the retinoid isotretinoin ( 30 mg/day ) for 3 years in a double-blind fashion . Patients were stratified at r and omization by tumor stage , histology , and smoking status . The primary endpoint ( time to SPT ) and the secondary endpoints ( times to recurrence and death ) were analyzed by log-rank test and the Cox proportional hazards model . All statistical tests were two-sided . RESULTS After a median follow-up of 3.5 years , there were no statistically significant differences between the placebo and isotretinoin arms with respect to the time to SPTs , recurrences , or mortality . The unadjusted hazard ratio ( HR ) of isotretinoin versus placebo was 1.08 ( 95 % confidence interval [ CI ] = 0.78 to 1.49 ) for SPTs , 0.99 ( 95 % CI = 0.76 to 1.29 ) for recurrence , and 1.07 ( 95 % CI = 0.84 to 1.35 ) for mortality . Multivariate analyses showed that the rate of SPTs was not affected by any stratification factor . Rate of recurrence was affected by tumor stage ( HR for T(2 ) versus T(1 ) = 1.77 [ 95 % CI = 1.35 to 2.31 ] ) and a treatment-by-smoking interaction ( HR for treatment-by-current-versus-never-smoking status = 3.11 [ 95 % CI = 1.00 to 9.71 ] ) . Mortality was affected by tumor stage ( HR for T(2 ) versus T(1 ) = 1.39 [ 95 % CI = 1.10 to 1.77 ] ) , histology ( HR for squamous versus nonsquamous = 1.31 [ 95 % CI = 1.03 to 1.68 ] ) , and a treatment-by-smoking interaction ( HR for treatment-by-current-versus-never-smoking = 4.39 [ 95 % CI = 1.11 to 17.29 ] ) . Mucocutaneous toxicity ( P<.001 ) and noncompliance ( 40 % versus 25 % at 3 years ) were higher in the isotretinoin arm than in the placebo arm . CONCLUSIONS Isotretinoin treatment did not improve the overall rates of SPTs , recurrences , or mortality in stage I NSCLC . Secondary multivariate and subset analyses suggested that isotretinoin was harmful in current smokers and beneficial in never smokers BACKGROUND Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease , and earlier basic research suggested plausible mechanisms . Because large r and omized trials of long duration were necessary to test this hypothesis directly , we conducted a trial of beta carotene supplementation . METHODS In a r and omized , double-blind , placebo-controlled trial of beta carotene ( 50 mg on alternate days ) , we enrolled 22,071 male physicians , 40 to 84 years of age , in the United States ; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982 . By December 31 , 1995 , the scheduled end of the study , fewer than 1 percent had been lost to follow-up , and compliance was 78 percent in the group that received beta carotene . RESULTS Among 11,036 physicians r and omly assigned to receive beta carotene and 11,035 assigned to receive placebo , there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease , or in overall mortality . In the beta carotene group , 1273 men had any malignant neoplasm ( except nonmelanoma skin cancer ) , as compared with 1293 in the placebo group ( relative risk , 0.98 ; 95 percent confidence interval , 0.91 to 1.06 ) . There were also no significant differences in the number of cases of lung cancer ( 82 in the beta carotene group vs. 88 in the placebo group ) ; the number of deaths from cancer ( 386 vs. 380 ) , deaths from any cause ( 979 vs. 968 ) , or deaths from cardiovascular disease ( 338 vs. 313 ) ; the number of men with myocardial infa rct ion ( 468 vs. 489 ) ; the number with stroke ( 367 vs. 382 ) ; or the number with any one of the previous three end points ( 967 vs. 972 ) . Among current and former smokers , there were also no significant early or late differences in any of these end points . CONCLUSIONS In this trial among healthy men , 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms , cardiovascular disease , or death from all causes The use of biomarkers is a promising approach to the study of human cancer risk . Bronchial metaplasia in sputum cytology may be a marker for potential premalignancy that can be used for population studies . We recently performed a r and omized , controlled trial in smokers on the effect of 14 weeks beta-carotene ( 20mg/day ) on markers for DNA damage . We now have evaluated the application of sputum cytology in this study and performed a preliminary evaluation of the effect of beta-carotene . Of the 150 potential participants in this trial 75 were not eligible because they failed to produce sputum sample s ( n = 29 ) , or because sample s were unsatisfactory ( n = 46 ) . The eligible group was older ( 41 vs 37 years ) and had smoked longer ( 23 vs 19 years ) , but had similar cigarette consumption ( mean 21/day ) and plasma cotinine levels . Metaplasia was grade d in seven categories . Only 11 subjects ( 15 % ) showed minor or mild atypia on study entry . Agreement within and between observers was 95 % within the same or an adjacent category . We observed no significant correlation between before and after treatment final metaplasia scores in either the beta-carotene ( Spearman R = 0.18 , P = 0.3 ) or placebo group ( Spearman R = 0.17 , P = 0.3 ) . Initial metaplasia scores were somewhat higher in the beta-carotene group ( n = 33 ) than in the placebo group ( n = 42 ) ( P = 0.06 ) . Final metaplasia scores were similar in both groups ( P = 0.69 ) , and there was no decrease in metaplasia scores in the beta-carotene group ( P = 0.75 ) . This study indicates that sputum cytology may not yet be a readily applicable marker in studies of a healthy asymptomatic population , because many smokers do not spontaneously produce sputum , more severe lesions are rare , and variation over time in the minor lesions in large . Therefore , the preliminary evidence that beta-carotene has no influence should be interpreted with care PURPOSE Vitamin A and retinoids are strong inhibitors of epithelial cancer promotion and progression in experimental carcinogenesis . This study examined whether they may prevent the occurrence of upper aerodigestive cancer in subjects heavily exposed to tobacco smoking , such as patients already cured of an early-stage lung cancer . PATIENTS AND METHODS The adjuvant effect of high-dose vitamin A was tested on 307 patients with stage I non-small-cell lung cancer . After curative surgery , patients were r and omly assigned to either a group prescribed retinol palmitate administration ( orally 300,000 IU daily for 12 months ) or a control group prescribed no treatment . RESULTS After a median follow-up of 46 months , the number of patients with either recurrence or new primary tumors was 56 ( 37 % ) in the treated arm and 75 ( 48 % ) in the control arm . Eighteen patients in the treated group developed a second primary tumor , and 29 patients in the control group developed 33 second primary tumors . A statistically significant difference in favor of treatment was observed concerning time to new primary tumors in the field of prevention ( P = .045 , log-rank test ) . The treatment difference in terms of disease-free interval was close to statistical significance ( P = .054 , log-rank test ) and just significant when adjusted for primary tumor classification ( P = .038 , Cox regression model ) . CONCLUSION Daily oral administration of high-dose vitamin A is effective in reducing the number of new primary tumors related to tobacco consumption and may improve the disease-free interval in patients curatively resected for stage I lung cancer . The impact of such a treatment on survival needs to be further explored Prostate cancer continues to be a major health threat , especially among African American men . The Selenium and Vitamin E Cancer Prevention Trial ( SELECT ) , which opened on July 25 , 2001 , was planned to study possible agents for the prevention of prostate cancer in a population of 32,400 men in the United States , including Puerto Rico , and Canada . SELECT is a phase III r and omized , placebo-controlled trial of selenium ( 200 microg/day from L-selenomethionine ) and /or vitamin E ( 400 IU/day of all rac alpha-tocopheryl acetate ) supplementation for a minimum of 7 years ( maximum of 12 years ) in non-African American men at least 55 years of age and African American men at least 50 years of age . SELECT is a large , simple trial that conforms as closely as possible with community st and ards of care . This commentary discusses the design problems the SELECT investigators had to resolve in developing the trial , including the role of prostate cancer screening , the best forms and doses of the study agents , and estimation of the event ( prostate cancer ) rate of men on the placebo arm The chemopreventive effects of antioxidants ( vitamin E , beta-carotene , vitamin C and red ginseng ) on oxidative DNA and protein ( globin ) damages were comparatively investigated in the peripheral blood of smokers ( > or = 20 cigarettes/day ) . Smokers showed a lower baseline level of plasma micronutrients ( vitamin C and beta-carotene ) ( P < 0.01 ) and higher baseline level of oxidative DNA or protein damage than non-smokers ( N = 5 ; P < 0.05 ) . During daily supplementation of antioxidants ( 200 IU vitamin of E , 9 mg of beta-carotene , 500 mg of vitamin C , or 1.8 g of red ginseng ) for 4 weeks , smokers plasma antioxidant concentrations increased linearly , while their mean levels of 8-hydroxydeoxyguanosine ( 8-OHdG ) and carbonyl contents decreased compared with those in smokers supplemented with a placebo ( P < 0.05 ) . Levels of urinary and plasma cotinine remained steady in smokers regardless of supplementation with antioxidants . 8-OHdG and carbonyl content decreased in a time-dependent manner ( as the total intake dose increased ) after supplementation with vitamin E ( 8-OHdG , 33.8 % ; carbonyl content , 43.6 % ) or red ginseng ( 8-OHdG , 31.7 % ; carbonyl content , 21.3 % ) . These preliminary data suggest that supplementation with antioxidants might protect smokers from oxidative damages and could reduce cancer risk or other diseases caused by free radicals associated with smoking Abstract Objectives : The Physicians ' Health Study ( PHS ) was a r and omized trial of beta-carotene ( 50 mg , alternate days ) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians . This report up date s results for beta-carotene and examines effect modification by baseline characteristics . Methods : Beta-carotene 's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models . Results : 2667 incident cancers were confirmed , with 1117 prostate , 267 colon , and 178 lung cancers . There were no significant differences with supplementation in total ( relative risk ( RR ) = 1.0 , 95 % confidence interval ( CI ) = 0.9–1.0 ) ; prostate ( RR = 1.0 , 95 % CI = 0.9–1.1 ) ; colon ( RR = 0.9 , 95 % CI = 0.7–1.2 ) ; or lung ( RR = 0.9 , 95 % CI = 0.7–1.2 ) cancer , and no differences over time . In subgroup analyses , total cancer was modestly reduced with supplementation among those aged 70 + years ( RR = 0.8 , 95 % CI = 0.7–1.0 ) , daily drinkers of alcohol ( RR = 0.9 , 95 % CI = 0.8–1.0 ) , and those in the highest BMI quartile ( RR = 0.9 , 95 % CI = 0.7–1.0 ) . Prostate cancer was reduced with supplementation among those in the highest BMI quartile ( RR = 0.8 , 95 % CI = 0.6–1.0 ) , and colon cancer was reduced among daily drinkers of alcohol ( RR = 0.5 , 95 % CI = 0.3–0.8 ) . Conclusions : The PHS found no overall effect of beta-carotene on total cancer , or the three most common site-specific cancers . The possibility of risk reduction within specific subgroups remains The " SUpplementation en VItamines et Minéraux AntioXidants " ( SU.VI.MAX ) study is a r and omized double-blind , placebo controlled , primary -prevention trial design ed to test the efficacy of a daily supplementation with antioxidant vitamins ( vitamin C , 120 mg ; vitamin E , 30 mg ; and beta-carotene , 6 mg ) and minerals ( selenium , 100 microg ; and zinc , 20 mg ) at nutritional doses ( one to three times the daily recommended dietary allowances ) , in reducing the frequency of cancers and cardiovascular diseases . The study involves 12,735 eligible subjects ( women aged 35 - 60 years , men aged 45 - 60 years ) included in 1994 in France . They will be followed up for 8 years . The targeted population is the general population . The aim of this specific analysis is to assess the effect of 2 years of supplementation on biochemical indicators of vitamin and trace element on a sub sample of 1000 subjects . The mean ( + /- st and ard deviation ) concentrations of plasma beta-carotene , alpha-tocopherol , vitamin C , selenium and zinc among participants who were r and omly assigned to receive a daily supplementation with beta-carotene , vitamin E , vitamin C , selenium and zinc for 2 years were significantly higher than those who were assigned to receive placebo . Specifically , the mean concentrations among men in the intervention group were 0.86 + /- 0.70 micromol/L for beta-carotene , 35.3 + /- 9.3 micromol/L for alpha-tocopherol , 11.5 + /- 4.7 microg/ mL for vitamin C , 1.65 + /- 0.33 micromol/L for selenium , and 16.2 + /- 3.9 micromol/L for zinc . The mean concentrations among women in the intervention were 1.25 + /- 0.90 micromol/L for beta-carotene , 34.9 + /- 8.4 micromol/L for alpha-tocopherol , 12.6 + /- 4.0 microg/mL for vitamin C , 1.68 + /- 0.37 micromol/L for selenium , and 15.3 + /- 3.9 micromol/L for zinc . The values observed for beta-carotene and vitamin E in the supplementation group after 2 years of intervention are those that have been associated with the lowest risk of cancer in observational studies . They are definitely lower than concentrations reported in intervention studies showing an apparent negative effect of high levels of beta-carotene supplementation on the lung cancer incidence rate in high-risk subjects ( initial level multiplied by 12 - 18 ) . Data from the follow-up will ascertain if any plausible reduction in the incidence rate of cancers may be associated with such amounts of antioxidant agents Tin miners in Yunnan Province in southern China have an extremely high rate of lung cancer , more than one percent per year among those at ‘ high risk ’ ( 40 + years old , with 10 + years of underground mining and /or smelting experience ) . The extraordinary lung cancer rates result from combined exposure to radon , arsenic , and tobacco smoking ( cigarettes and /or bamboo water pipe ) . A study to determine the feasibility of conducting a large-scale , lung-cancer chemoprevention trial was conducted in 1986 among currently employed or retired miners from the Yunnan Tin Corporation in the city of Gejiu . The study was design ed to answer four questions : ( i ) Could potentially eligible miners be identified and recruited ? ( ii ) Could intervention agents be shipped successfully from the United States to the study area and be appropriately distributed ? ( iii ) Would miners adequately adhere to the study protocol and comply with the intervention regimen ? ( iv ) Could potential adverse effects be monitored and documented ? The six-month feasibility study yielded affirmative answers to each of these questions . A roster of over 7,000 high-risk miners was compiled . Four agents ( vitamin A , 25,000 IU ; β-carotene , 50 mg ; vitamin E , 800 IU ; and selenium , 400 μg ) were administered daily with placebos to 350 miners according to a 24 factorial design . Adherence , assessed by pill counts and serum micronutrient levels , was approximately 90 percent . The findings from this preliminary study indicate that a full-scale , lung-cancer chemoprevention trial in this population is feasible Although dietary intake of vitamin A has little , if any , overall effect on blood retinol in generally well-nourished population s , subgroups may exist that would be responsive to supplementation . The hypothesis that vitamin A supplementation increases blood retinol in apparently well-fed individuals with lower than usual blood levels was tested in female health workers , with relatively low blood retinol values , who were r and omly assigned to receive vitamin A ( 10,000 IU daily ) or placebo . After 4 weeks the mean change in plasma retinol was -0.4 micrograms/dl for the group receiving placebo and + 4.1 micrograms/dl ( an increase of 9 % over base-line values ) for the group receiving vitamin A ( P = .02 ) . The results were similar when the base-line retinol level and several other covariates were considered . Thirteen women who had initially received placebo were then switched to vitamin A for 4 weeks . These women experienced a mean increase of 5.3 micrograms/dl in plasma retinol ( P = .04 ) . Responses to vitamin A supplementation tend to be greater among women with lower previous total vitamin A intake , as assessed by question naire [ Spearman rank correlation coefficient ( r ) = 0.50 ; P = .01 ] The " SUpplementation en VItamines et Minéraux AntioXydants " ( SU.VI.MAX ) Study is a r and omized double-blind , placebo-controlled , primary -prevention trial which started in 1994 in France . This epidemiologic study is design ed to test the efficacy of a daily supplementation with antioxidant vitamins ( vitamin C , 120 mg , vitamin E , 30 mg , and beta-carotene , 6 mg ) and minerals ( selenium , 100 microg , and zinc , 20 mg ) at nutritional doses , in reducing the main causes of premature death ( cancers and cardiovascular diseases ) ; 12,735 eligible subjects ( women aged 35 to 60 years , and men aged 45 to 60 years ) were included in 1994 and and will be followed up for 8 years . Participants undergo a yearly visit consisting , every other year , of either biological sampling or clinical examination . They also regularly provide information on health events and dietary intake by filling out computerized question naires using the Minitel Telematic Network . After 2 years of supplementation , biochemical indicators of vitamin and trace element status reach reasonable level without reaching concentrations as high as those observed in intervention studies , which tested relatively high doses of antioxidants , and ended up with higher risk of pathology On the basis of epidemiologic and experimental evidence of an anticancer activity of vitamin A , a r and omized clinical trial was activated in Milan with the aim of evaluating if retinol palmitate administration ( per os , 300,000 I.U. daily ) after complete resection of stage Ia non small-cell lung cancer could reduce the occurrence of cancer relapses ( within 3 years ) and /or the occurrence of new primary tumors ( beyond 3 years ) . By September 1987 , 181 patients had entered the trial : 87 in the treatment arm and 94 in the control arm . After a median follow-up of 14 months , the interim analysis was focused on the evaluation of toxicity , compliance , and early recurrences . Although the large majority of patients were affected by skin and mucous membrane desquamation and dryness during treatment , these symptoms were generally mild and well tolerated , and never induced the patient to stop the treatment . Other side effects like headache , hair loss , itching , or dyspepsia were detected at a much lower frequency . Only in 3 patients the treatment was interrupted , because of signs or symptoms potentially related to vitamin A administration . At the time of the analysis , a total of 42 ( 23 % ) patients had relapsed ; 16 ( 18 % ) in the treated arm , and 26 ( 28 % ) in the control arm . The largest difference between treated patients and controls was observed for bone metastases ( 2 vs. 7 ) and brain metastases ( 3 vs. 6 ) , and for squamous histology ( 6 vs. 11 ) . Only 2 cases of new primary cancer were detected , both in the control arm . These results are promising both in terms of tolerance and efficacy of treatment , but given the short median follow-up they must be very cautiously interpreted . A longer follow-up is necessary to establish whether a significant proportion of early recurrences could be prevented , or only delayed , by vitamin A administration CONTEXT Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events . Clinical trials have generally failed to confirm benefits , possibly due to their relatively short duration . OBJECTIVE To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer , cancer death , and major cardiovascular events . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled international trial ( the initial Heart Outcomes Prevention Evaluation [ HOPE ] trial conducted between December 21 , 1993 , and April 15 , 1999 ) of patients at least 55 years old with vascular disease or diabetes mellitus was extended ( HOPE-The Ongoing Outcomes [ HOPE-TOO ] ) between April 16 , 1999 , and May 26 , 2003 . Of the initial 267 HOPE centers that had enrolled 9541 patients , 174 centers participated in the HOPE-TOO trial . Of 7030 patients enrolled at these centers , 916 were deceased at the beginning of the extension , 1382 refused participation , 3994 continued to take the study intervention , and 738 agreed to passive follow-up . Median duration of follow-up was 7.0 years . INTERVENTION Daily dose of natural source vitamin E ( 400 IU ) or matching placebo . MAIN OUTCOME MEASURES Primary outcomes included cancer incidence , cancer deaths , and major cardiovascular events ( myocardial infa rct ion , stroke , and cardiovascular death ) . Secondary outcomes included heart failure , unstable angina , and revascularizations . RESULTS Among all HOPE patients , there were no significant differences in the primary analysis : for cancer incidence , there were 552 patients ( 11.6 % ) in the vitamin E group vs 586 ( 12.3 % ) in the placebo group ( relative risk [ RR ] , 0.94 ; 95 % confidence interval [ CI ] , 0.84 - 1.06 ; P = .30 ) ; for cancer deaths , 156 ( 3.3 % ) vs 178 ( 3.7 % ) , respectively ( RR , 0.88 ; 95 % CI , 0.71 - 1.09 ; P = .24 ) ; and for major cardiovascular events , 1022 ( 21.5 % ) vs 985 ( 20.6 % ) , respectively ( RR , 1.04 ; 95 % CI , 0.96 - 1.14 ; P = .34 ) . Patients in the vitamin E group had a higher risk of heart failure ( RR , 1.13 ; 95 % CI , 1.01 - 1.26 ; P = .03 ) and hospitalization for heart failure ( RR , 1.21 ; 95 % CI , 1.00 - 1.47 ; P = .045 ) . Similarly , among patients enrolled at the centers participating in the HOPE-TOO trial , there were no differences in cancer incidence , cancer deaths , and major cardiovascular events , but higher rates of heart failure and hospitalizations for heart failure . CONCLUSION In patients with vascular disease or diabetes mellitus , long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure The Women 's Health Study ( WHS ) is a r and omized , double-blind , placebo-controlled trial design ed to evaluate the balance of benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer in women . A total of 39,876 female health professionals , age 45 years or older and without a history of cardiovascular disease or cancer ( other than nonmelanoma skin cancer ) , were r and omized in a 2x2 factorial design to one of four treatment groups : active aspirin and vitamin E placebo , aspirin placebo and active vitamin E , both active agents , or both placebos . The process of r and omization was successful , as evidence d by the equal distribution of a large number of baseline demographic , lifestyle , and health history characteristics among the four treatment groups . Similar distribution of known potential confounders , as well as the large sample size , provides reassuring evidence that unmeasured or unknown potential confounders are also equally distributed . As expected in a clinical trial , the women in the study are healthier in some respects than the general population , but they have very comparable rates of obesity , hypertension , and elevated cholesterol . With adequate duration of treatment and follow-up , this trial will provide important and relevant information on the balance of benefits and risks of aspirin and vitamin E supplementation in the primary prevention of cardiovascular disease and cancer in women BACKGROUND Lung cancer and cardiovascular disease are major causes of death in the United States . It has been proposed that carotenoids and retinoids are agents that may prevent these disorders . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers , former smokers , and workers exposed to asbestos . The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol ( vitamin A ) in the form of retinyl palmitate per day on the primary end point , the incidence of lung cancer , were compared with those of placebo . RESULTS A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up ( mean length of follow-up , 4.0 years ) . The active-treatment group had a relative risk of lung cancer of 1.28 ( 95 percent confidence interval , 1.04 to 1.57 ; P=0.02 ) , as compared with the placebo group . There were no statistically significant differences in the risks of other types of cancer . In the active-treatment group , the relative risk of death from any cause was 1.17 ( 95 percent confidence interval , 1.03 to 1.33 ) ; of death from lung cancer , 1.46 ( 95 percent confidence interval , 1.07 to 2.00 ) ; and of death from cardiovascular disease , 1.26 ( 95 percent confidence interval , 0.99 to 1.61 ) . On the basis of these findings , the r and omized trial was stopped 21 months earlier than planned ; follow-up will continue for another 5 years . CONCLUSIONS After an average of four years of supplementation , the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer , cardiovascular disease , and any cause in smokers and workers exposed to asbestos Two nutrition intervention trials were conducted in Linxian , China , where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population 's chronic deficiencies of multiple nutrients are etiologically involved . Both trials were r and omized , double-blind , and placebo-controlled , and tested the effect of multiple-vitamin and multiple-mineral supplements in lowering the rates of cancer . In the first trial , the Dysplasia Trial , 3318 individuals with a cytologic diagnosis of esophageal dysplasia received daily vitamin and mineral supplements or placebos for 6 years . The second trial , the General Population Trial , involved 29,584 individuals and used a one-half replicate of a 2(4 ) fractional factorial design , which enabled the testing of daily supplementation of four different vitamin and mineral combinations and placebo for a period 5 1/4 years . This article describes the design and methods of these studies as well as the baseline characteristics and compliance behavior of the participants in these two trials , the largest cancer chemoprevention studies reported to date In preparation for a phase IV lung cancer chemoprevention trial , we conducted a pilot trial of beta-carotene and retinol in high-risk smokers . Eligibility criteria were ages of 50 - 69 years , a smoking history of at least 20 pack-years , and either being a current smoker or having quit within the past 6 years . Participants were recruited by mailing an interest survey to 29,928 age-selected members of King County Medical Blue Shield . We r and omized 1,029 women and men to one of four intervention arms : placebo , retinol , 25,000 international units/day ; beta-carotene , 30 mg/day ; or retinol plus beta-carotene . Participants were followed for side effects and adherence every 2 months either by a telephone call or a clinic visit . Blood was sample d for retinoid , carotenoid , and liver function analyses annually . beta-carotene and retinol were well tolerated during the follow-up period , which had a median of 1.5 years and a maximum of 3.3 years . Yellowing of the skin was seen in both beta-carotene arms . No differences were seen among arms or over time in incidence or severity of the other 15 monitored symptoms and signs or in serum liver function tests . Adherence was good : 83 % of participants remained active on study at 1 year and 75 % at 2 years . Serum beta-carotene increased from a prer and omization median concentration of 170 to 2100 ng/ml after 4 months of supplementation , and retinyl palmitate median levels more than tripled . ( ABSTRACT TRUNCATED AT 250 WORDS The Carotene and Retinol Efficacy Trial ( CARET ) was a double-blind , placebo-controlled trial of the daily administration of 25,000 IU vitamin A and 30 mg beta-carotene for the prevention of lung cancer . Of close to 18,500 participants , more than 4,000 were asbestos-exposed men recruited from shipyard and construction trades at five study centers in the United States . While the primary endpoint of the trial was the incidence of lung cancer , a number of questions about the natural history of asbestos-related disease will also be addressed . The mean age at entry into the trial was 57 years and the mean duration of follow-up on active intervention was 4 years . With the exception of 133 never-smoker pilot participants ( 3 % ) , all subjects recruited were by intention current ( 38 % ) or ex-smokers ( 58 % ) , with a mean cumulative smoking exposure at entry of 43 pack-years . Mean years from first asbestos exposure were 35 , and mean duration of asbestos exposure in a high-risk trade was 19 years . The distribution of radiographic abnormalities was as follows : normal , 34 % ; parenchymal opacities ( ILO profusion score > 1/0 ) alone , 18 % ; pleural thickening alone , 27 % ; both parenchymal opacities and pleural thickening , 21 % . The CARET cohort , when compared to previously reported asbestos-exposed cohorts , is characterized by substantial asbestos exposure and high proportion of asbestos-related radiographic findings . The active intervention was halted in 1996 , after a mean duration of 40 years . Passive follow-up of the cohort will continue until the year 2000 The evidence for a potential benefit of antioxidant vitamins in the prevention and therapy of atherosclerotic disease is derived from laboratory , clinical , and observational epidemiologic studies but remains inconclusive . Data from r and omized clinical trials are sparse , particularly for women . Therefore , it is both timely and important to conduct large-scale primary and secondary prevention trials of antioxidants and cardiovascular disease ( CVD ) . The Women 's Antioxidant and Cardiovascular Study ( WACS ) is a r and omized , double-blind , placebo-controlled secondary prevention trial of the balance of benefits and risks of antioxidant vitamins ( vitamins E and C , and beta-carotene ) among 8000 women with preexisting CVD . This secondary prevention trial will be conducted as a companion to the recently started Women 's Health Study , a primary prevention trial of vitamin E and beta-carotene , as well as aspirin . In the WACS , US female health professionals aged 40 years and older with a history of myocardial infa rct ion , angina pectoris , coronary revascularization , stroke , transient cerebral ischemia , carotid endarterectomy , or peripheral artery surgery will be r and omly assigned , utilizing a 2 x 2 x 2 factorial design , to receive vitamin E , vitamin C , beta-carotene , and /or placebo . Cardiovascular end points include nonfatal myocardial infa rct ion , nonfatal stroke , coronary revascularization procedures , and total CVD mortality . The present article describes the rationale , design , and methods of the trial BACKGROUND Patients with head- and -neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors . Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis . METHODS We prospect ively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx , pharynx , or oral cavity . After completion of surgery or radiotherapy ( or both ) , these patients were r and omly assigned to receive either isotretinoin ( 13-cis-retinoic acid ) ( 50 to 100 mg per square meter of body-surface area per day ) or placebo , to be taken daily for 12 months . RESULTS There were no significant differences between the two groups in the number of local , regional , or distant recurrences of the primary cancers . However , the isotretinoin group had significantly fewer second primary tumors . After a median follow-up of 32 months , only 2 patients ( 4 percent ) in the isotretinoin group had second primary tumors , as compared with 12 ( 24 percent ) in the placebo group ( P = 0.005 ) . Multiple second primary tumors occurred in four patients , all of whom were in the placebo group . Of the 14 second cancers , 13 ( 93 percent ) occurred in the head and neck , esophagus , or lung . CONCLUSIONS Daily treatment with high doses of isotretinoin is effective in preventing second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck , although it does not prevent recurrences of the original tumor Patients who are cured from head and neck carcinomas remain at high risk for developing a second primary in the head and neck area . It is now clear that retinoids exert a prophylactic action on the development of epithelial cancers when tested on laboratory animals and on human premalignant lesions . They are now used in the chemoprevention of epithelial cancers in r and omised trials evaluating their efficacy . We prospect ively studied 316 patients who developed squamous cell carcinoma of the head and neck , classified as T1/T2 , N0/N1 < or 3 cm , M0 according to the UICC TNM classification . Patients were r and omly assigned to receive orally , either etretinate ( a loading dose of 50 mg/day for the first month , followed by a dose of 25 mg/day in the following months ) or a placebo for 24 months . Adjuvant treatment began no later than 15 days after surgery and /or the initiation of radiotherapy . The 5-year survival rate and disease-free survival rate are similar in the two groups . There are no significant differences regarding either local , regional and distant relapses . After a median follow-up of 41 months ( range 0 - 81 ) , 28 patients in the etretinate group and 29 in the placebo group developed a second cancer with , respectively , 12 and 13 in the head and neck region . Adjuvant treatment was definitively discontinued mainly due to toxicity in 33 % of patients in the etretinate group versus 23 % in the placebo group ( P < 0.05 ) . Etretinate , a second-generation retinoid , does not prevent second primary tumours in patients who have been treated for squamous cell carcinoma of the oral cavity and oropharynx Former blue asbestos workers known to be at high risk of asbestos‐related diseases , particularly malignant mesothelioma and lung cancer , were enrolled in a chemo‐prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects r and omly assigned to β‐carotene or retinol . Subjects were assigned r and omly to take 30 mg/day β‐carotene ( 512 subjects ) or 25,000 IU/day retinol ( 512 subjects ) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995 . Comparison between groups was by Cox regression in both intention‐to‐treat analyses and efficacy analyses based on treatment actually taken . Median follow‐up time was 232 weeks . Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects r and omised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects r and omised to β‐carotene . The relative rate of mesothelioma ( the most common single cause of death in our study ) for those on retinol compared with those on β‐carotene was 0.24 ( 95 % CI 0.07–0.86 ) . In the retinol group , there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality . Similar results were found with efficacy analyses . Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic β‐carotene . The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation . Int . J. Cancer 75:362–367 , 1998 . © 1998 Wiley‐Liss , The SUpplementation en VItamines et Minéraux AntioXydants ( SU.VI.MAX ) Study is a r and omized , double-blind , placebo-controlled , primary -prevention trial design ed to test the efficacy of daily supplementation with antioxidant vitamins ( vitamin C , 120 mg ; vitamin E , 30 mg ; and beta-carotene , 6 mg ) and minerals ( selenium , 100 microg ; and zinc , 20 mg ) at nutrition-level doses ( one to three times the daily recommended dietary allowances ) in reducing several major health problems in industrialized countries , especially the main causes of premature death , cancers and cardiovascular diseases . The present report describes the design , implementation , and baseline characteristics of participants in this 8-year cohort study , which started in 1994 in France ; 12,735 eligible subjects ( women aged 35 - 60 , and men aged 45 - 60 ) were included in 1994 and will be followed for 8 years . Participants undergo a yearly visit consisting , every other year , of either biological sampling or clinical examination . They also regularly provide information on health events and dietary intake by filling out computerized question naires using the Minitel Telematic Network . Data on baseline characteristics of the participants suggest that the present sample is close to the national population in terms of geographic density , socioeconomic status , and the distribution of various major risk factors for the diseases under study . The choice of the study population should allow the results of this trial to apply to adult population s of both sexes in France and other industrialized countries Two r and omized nutrition intervention trials were conducted in Linxian , an area of north central China with some of the world 's highest rates of esophageal and stomach cancer and a population with a chronically low intake of several nutrients . One trial used a factorial design that allowed us to assess the effects in nearly 30,000 participants of daily supplementation with four nutrient combinations : retinol and zinc ; riboflavin and niacin ; vitamin C and molybdenum ; and beta-carotene , alpha-tocopherol , and selenium . The second trial provided daily multiple vitamin-mineral supplementation or placebo in 3318 persons with esophageal dysplasia , a precursor to esophageal cancer . After supplements were given for 5.25 y in the general population trial , small but significant reductions in total [ relative risk ( RR ) = 0.91 ] and cancer ( RR = 0.87 ) mortality were observed in subjects receiving beta-carotene , alpha-tocopherol , and selenium but not the other nutrients . The reductions were greater in women than men , and in those under compared with over the age of 55 ; however , differences by sex or age were not significant . After multiple vitamin and mineral supplements were given for 6 y in the smaller dysplasia trial , reductions in total ( RR = 0.93 ) and cancer ( RR = 0.96 ) mortality were observed but these were not significant . The largest reductions were for cerebrovascular disease mortality , but the effects differed by sex : a significant reduction was observed in men ( RR = 0.45 ) but not women ( RR = 0.90 ) . Restoring adequate intake of certain nutrients may help to lower the risk of cancer and other diseases in this high-risk population BACKGROUND Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers , including cancers of the esophagus and stomach . Vitamins and minerals in these foods may contribute to the reduced cancer risk . The people of Linxian County , China , have one of the world 's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients . PURPOSE We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian . METHODS Individuals of ages 40 - 69 were recruited in 1985 from four Linxian communes . Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period . The subjects were r and omly assigned to intervention groups according to a one-half replicate of a 2(4 ) factorial experimental design . This design enabled testing for the effects of four combinations of nutrients : ( A ) retinol and zinc ; ( B ) riboflavin and niacin ; ( C ) vitamin C and molybdenum ; and ( D ) beta carotene , vitamin E , and selenium . Doses ranged from one to two times U.S. Recommended Daily Allowances . RESULTS A total of 2127 deaths occurred among trial participants during the intervention period . Cancer was the leading cause of death , with 32 % of all deaths due to esophageal or stomach cancer , followed by cerebrovascular disease ( 25 % ) . Significantly ( P = .03 ) lower total mortality ( relative risk [ RR ] = 0.91 ; 95 % confidence interval [ CI ] = 0.84 - 0.99 ) occurred among those receiving supplementation with beta carotene , vitamin E , and selenium . The reduction was mainly due to lower cancer rates ( RR = 0.87 ; 95 % CI = 0.75 - 1.00 ) , especially stomach cancer ( RR = 0.79 ; 95 % CI = 0.64 - 0.99 ) , with the reduced risk beginning to arise about 1 - 2 years after the start of supplementation with these vitamins and minerals . No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc , riboflavin and niacin , or vitamin C and molybdenum . Patterns of cancer incidence , on the basis of 1298 cases , generally resembled those for cancer mortality . CONCLUSIONS The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults , particularly with the combination of beta carotene , vitamin E , and selenium , may effect a reduction in cancer risk in this population . IMPLICATION S The results on their own are not definitive , but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements PURPOSE To establish the incidence of abnormalities in the expression of retinoic acid receptor-beta ( RARbeta ) in bronchial cells and determine the capacity of 13-cis-retinoic acid ( 13-CRA ) to correct such abnormalities . PATIENTS AND METHODS One hundred eighty-eight smokers had a medical indication for bronchoscopy and were studied with bronchial brushings . Bronchial brushing sample s were obtained for cytology analysis and for molecular analysis . After RNA was extracted , RARbeta sequences were amplified by reverse transcriptase polymerase chain reaction and Southern blots were performed to assess RARbeta expression . Forty-four eligible individuals with diminished RARbeta expression consented to double-blind r and omization to receive a placebo or 13-CRA 30 mg orally daily for 6 months . A second bronchoscopy was performed at the end of the treatment period . An analysis of variance was used to analyze changes in RARbeta expression before and after treatment . RESULTS The 6-month treatment course was completed by 27 patients , and results were obtained for a total of 18 patients ( eight patients treated with 13-CRA and ten treated with the placebo ) . In the placebo group , there was no difference between the results of RARbeta expression before and after treatment ( P = .43 ) . In the 13-CRA group , there was an upregulation of RARbeta expression at the end of 13-CRA treatment ( P = .001 ) . Cytologic changes were uncommon . Toxicities were primarily of grade 1 . Palatal brushings were compared with bronchial brushings in 40 smokers . A perfect correlation of the results of RARbeta expression was obtained from 27 patients . CONCLUSION RARbeta expression is frequently decreased in the bronchial epithelium of smokers and is upregulated at the end of 13-CRA treatment . These results support undertaking a phase III chemoprevention trial of 13-CRA treatment for lung cancer |
11,772 | 31,442,601 | In a systematic review and meta- analysis , we found ESG to produce clinical ly significant weight loss that was reproducible among independent centers and to have a low rate of severe adverse events . | BACKGROUND & AIMS Bariatric surgery is the most successful treatment for obesity .
However , many patients avoid surgery due to its perceived invasive nature and fear of complications .
Endoscopic sleeve gastroplasty ( ESG ) is a seemingly less invasive option for patients with obesity .
We performed a systematic review and meta- analysis to evaluate the efficacy and safety of ESG in adults . | Background / objectives : This trial evaluated the safety and effectiveness of the Orbera Intragastric Balloon as an adjunct to lifestyle intervention . Subjects/ methods : In this multicenter , r and omized , open-label clinical trial , 255 adults with a body mass index of 30–40 kg m−2 were treated and outcomes were assessed up to 12 months . Participants were r and omized to endoscopic placement of an intragastric balloon plus lifestyle or lifestyle intervention alone . Balloons were removed at 6 months and lifestyle intervention continued for both groups through 12 months . At 9 months , co primary end points were two measures of weight loss . Results : At 6 months , weight loss was −3.3 % of total body weight ( −3.2 kg ) in the lifestyle arm vs −10.2 % ( −9.9 kg ) in the balloon plus lifestyle arm ( P<0.001 ) ; at 9 months ( 3 months postballoon removal ) , weight loss was −3.4 % ( −3.2 kg ) vs −9.1 % ( −8.8 kg , P⩽0.001 ) ; and at 12 months , −3.1 % ( −2.9 kg ) vs −7.6 % ( −7.4 kg , P⩽0.001 ) . For the primary end points , at 9 months , mean percent loss of weight in excess of ideal body weight ( s.d . ) at 9 months was 26.5 % ( 20.7 ) ( P=0.32 ) and 9.7 % ( 15.1 ) in the balloon and control groups , respectively . Also , 45.6 % ( 36.7 , 54.8 ) of the subjects r and omized to the balloon achieved at least 15 % loss of weight in excess of ideal body weight greater than the control group ( P<0.001 ) . The majority of balloon subjects experienced adverse events ; 86.9 % nausea , 75.6 % vomiting , 57.5 % abdominal pain and 18.8 % had their device removed before 6 months because of an adverse event or subject request . Five subjects ( 3.1 % ) in the balloon group had a gastric abnormality at the time of device removal , and no ulcers were found . Conclusions and relevance : Intragastric balloon achieved greater short-term weight loss at 3 and 6 months postballoon removal than lifestyle intervention alone . Adverse gastrointestinal events were common Objectives : The AspireAssist System ( AspireAssist ) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30 % of the calories consumed in a meal , in conjunction with lifestyle ( diet and exercise ) counseling . Methods : In this 52-week clinical trial , 207 participants with a body-mass index ( BMI ) of 35.0–55.0 kg/m2 were r and omly assigned in a 2:1 ratio to treatment with AspireAssist plus Lifestyle Counseling ( n=137 ; mean BMI was 42.2±5.1 kg/m2 ) or Lifestyle Counseling alone ( n=70 ; mean BMI was 40.9±3.9 kg/m2 ) . The co- primary end points were mean percent excess weight loss and the proportion of participants who achieved at least a 25 % excess weight loss . Results : At 52 weeks , participants in the AspireAssist group , on a modified intent-to-treat basis , had lost a mean ( ±s.d . ) of 31.5±26.7 % of their excess body weight ( 12.1±9.6 % total body weight ) , whereas those in the Lifestyle Counseling group had lost a mean of 9.8±15.5 % of their excess body weight ( 3.5±6.0 % total body weight ) ( P<0.001 ) . A total of 58.6 % of participants in the AspireAssist group and 15.3 % of participants in the Lifestyle Counseling group lost at least 25 % of their excess body weight ( P<0.001 ) . The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation in the postoperative period . Serious adverse events were reported in 3.6 % of participants in the AspireAssist group . Conclusions : The AspireAssist System was associated with greater weight loss than Lifestyle Counseling alone Background We would expect information on adverse drug reactions in r and omised clinical trials to be easily retrievable from specific search es of electronic data bases . However , complete retrieval of such information may not be straightforward , for two reasons . First , not all clinical drug trials provide data on the frequency of adverse effects . Secondly , not all electronic records of trials include terms in the abstract or indexing fields that enable us to select those with adverse effects data . We have determined how often automated search methods , using indexing terms and /or textwords in the title or abstract , would fail to retrieve trials with adverse effects data . Methods We used a sample set of 107 trials known to report frequencies of adverse drug effects , and measured the proportion that ( i ) were not assigned the appropriate adverse effects indexing terms in the electronic data bases , and ( ii ) did not contain identifiable adverse effects textwords in the title or abstract . Results Of the 81 trials with records on both MEDLINE and EMBASE , 25 were not indexed for adverse effects in either data base . Twenty-six trials were indexed in one data base but not the other . Only 66 of the 107 trials reporting adverse effects data mentioned this in the abstract or title of the paper . Simultaneous use of textword and indexing terms retrieved only 82/107 ( 77 % ) papers . Conclusions Specific search strategies based on adverse effects textwords and indexing terms will fail to identify nearly a quarter of trials that report on the rate of drug adverse effects BACKGROUND & AIMS The effects of bariatric surgery in patients with nonalcoholic fatty liver disease ( NASH ) are not well established . We performed a prospect i ve study to determine the biological and clinical effects of bariatric surgery in patients with NASH . METHODS From May 1994 through May 2013 , one hundred and nine morbidly obese patients with biopsy-proven NASH underwent bariatric surgery at the University Hospital of Lille , France ( the Lille Bariatric Cohort ) . Clinical , biological , and histologic data were collected before and 1 year after surgery . RESULTS One year after surgery , NASH had disappeared from 85 % of the patients ( 95 % confidence interval [ CI ] : 75.8%-92.2 % ) . Compared with before surgery , patients had significant reductions in mean ± SD body mass index ( BMI , from 49.3 ± 8.2 to 37.4 ± 7 ) and level of alanine aminotransferase ( from 52.1 ± 25.7 IU/L to 25.1 ± 20 IU/L ) ; mean levels of γ-glutamyltransferases were reduced from 51 IU/L before surgery ( interquartile range [ IQR ] , 34 - 87 IU/L ) to 23 IU/L afterward ( IQR , 14 - 33 IU/L ) and mean insulin resistance index values were reduced from 3.6 ± 0.5 to 2.9 ± 0.5 ( P < .01 for each comparison ) . NASH disappeared from a higher proportion of patients with mild NASH before surgery ( 94 % ) than severe NASH ( 70 % ) ( P < .05 ) according to Brunt score . In histologic analysis , steatosis was detected in 60 % of the tissue before surgery ( IQR , 40%-80 % ) but only 10 % 1 year after surgery ( IQR , 2.5%-21.3 % ) ; the mean nonalcoholic fatty liver disease score was reduced from 5 ( IQR , 4 - 5 ) to 1 ( IQR , 1 - 2 ) ( each P < .001 ) . Hepatocellular ballooning was reduced in 84.2 % of sample s ( n = 69 ; 95 % CI : 74.4 - 91.3 ) and lobular inflammation in 67.1 % ( n = 55 ; 95 % CI : 55.8 - 77.1 ) . According to Metavir scores , fibrosis was reduced in 33.8 % of patients ( 95 % CI : 23.6%-45.2 % ) . Patients whose NASH persisted 1 year after surgery ( n = 12 ) had lost significantly less weight ( change in BMI , 9.1 ± 1.5 ) than those without NASH ( change in BMI , 12.3 ± 0.6 ) ( P = .005 ) . Patients who underwent laparoscopic gastric b and ing lost less weight ( change in BMI , 6.4 ± 0.7 ) than those who underwent gastric bypass ( change in BMI , 14.0 ± 0.5 ) ( P < .0001 ) , and a higher proportion had persistent NASH ( 30.4 % vs 7.6 % of those with gastric bypass ; P = .015 ) . CONCLUSIONS Bariatric surgery induced the disappearance of NASH from nearly 85 % of patients and reduced the pathologic features of the disease after 1 year of follow-up . It could be a therapeutic option for appropriate morbidly obese patients with NASH who do not respond to lifestyle modifications . More studies are needed to determine the long-term effects of bariatric surgery in morbidly obese patients with NASH ABSTRACT Background : Bariatric endoscopic techniques are minimally invasive and induce gastric volume reduction to treat obesity . Aim : To evaluate endoscopic sleeve gastroplasty ( Apollo method ) using a suturing method directed at the greater curvature , as well as the perioperative care , two year safety and weight loss . Method : Prospect i ve single-center study over 154 patients ( 108 females ) using the endoscopic sleeve gastroplasty procedure under general anesthesia with overnight inpatient observation . Of the154 initial patients , 143 were available for 1-month of follow-up , 133 for 6-month , 64 for 12-month and 28 completed the 24 month assessment . Follow-up was carried out by a multidisciplinary team ( nutritionist and psychologist ) . Outcomes evaluated were : change in BMI ; change in body weight ( TBWL ) ; % of loss of initial body weight ( % TBWL ) ; % of excess body weight loss ( % EWL ) ( segregated in > or < 25 % and adverse effects . Voluntary oral contrasted radiological examinations were scheduled to assess the gastroplasty at different times post-procedure . Results : Mean age was 44.9 ( 23 - 69 ) years . At 24 months after the procedure baseline mean BMI change from 38.3 to 30.8 kg/m2 . TBWL , % TBWL and % EWL were of 21.3 kg , 19.5 % and 60.4 % respectively . 85.7 % of patients achieve the goal of > 25 % % EWL . There were no mayor adverse events intraprocedure or during the 24 months of follow-up . Conclusion : Endoscopic sleeve gastroplasty with regular monitoring by a multidisciplinary team can be considered an effective , safe and well tolerated procedure for obesity treatment , at least for two years of follow-up BACKGROUND & AIMS : Although bariatric surgery is the most effective therapy for obesity , only a small proportion of c and i date s undergo this surgery . Endoscopic sleeve gastroplasty ( ESG ) is a minimally invasive procedure that reduces the size of the gastric reservoir . We investigated its durability and effects on body weight and gastrointestinal function in a prospect i ve study of obese individuals . METHODS : Twenty‐five obese individuals ( 21 female ; mean body mass index , 35.5 ± 2.6 kg/m2 ; mean age , 47.6 ± 10 years ) underwent ESG with endoluminal creation of a sleeve along the gastric lesser curve from September 2012 through March 2015 at the Mayo Clinic in Rochester , Minnesota . Subjects were followed for a median period of 9 months . We measured changes in body weight and recorded adverse events ; patients were assessed by endoscopy after 3 months . Four participants underwent pre‐ESG and post‐ESG analyses to measure solid and liquid gastric emptying , satiation ( meal tolerance ) , and fasting and postpr and ial levels of insulin , glucose , and gut hormones . RESULTS : Subjects had lost 53 % ± 17 % , 56 % ± 23 % , 54 % ± 40 % , and 45 % ± 41 % of excess body weight at 6 , 9 , 12 , and 20 months , respectively , after the procedure ( P < .01 ) . Endoscopy at 3 months showed intact gastroplasty in all subjects . After ESG , physiological analyses of 4 participants showed a decrease by 59 % in caloric consumption to reach maximum fullness ( P = .003 ) , slowing of gastric emptying of solids ( P = .03 ) , and a trend toward increased insulin sensitivity ( P = .06 ) . Three patients had serious adverse events ( a perigastric inflammatory collection , a pulmonary embolism , and a small pneumothorax ) but made full recoveries with no need for surgical interventions . No further serious adverse events occurred after the technique was adjusted . CONCLUSIONS : ESG delays gastric emptying , induces early satiation , and significantly reduces body weight . ESG could be an alternative to bariatric surgery for selected patients with obesity . ClincialTrials.gov number : NCT 01682733 BACKGROUND Long‐term results from r and omized , controlled trials that compare medical therapy with surgical therapy in patients with type 2 diabetes are limited . METHODS We assessed outcomes 5 years after 150 patients who had type 2 diabetes and a body‐mass index ( BMI ; the weight in kilograms divided by the square of the height in meters ) of 27 to 43 were r and omly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux‐en‐Y gastric bypass or sleeve gastrectomy . The primary outcome was a glycated hemoglobin level of 6.0 % or less with or without the use of diabetes medications . RESULTS Of the 150 patients who underwent r and omization , 1 patient died during the 5‐year follow‐up period ; 134 of the remaining 149 patients ( 90 % ) completed 5 years of follow‐up . At baseline , the mean ( ±SD ) age of the 134 patients was 49±8 years , 66 % were women , the mean glycated hemoglobin level was 9.2±1.5 % , and the mean BMI was 37±3.5 . At 5 years , the criterion for the primary end point was met by 2 of 38 patients ( 5 % ) who received medical therapy alone , as compared with 14 of 49 patients ( 29 % ) who underwent gastric bypass ( unadjusted P=0.01 , adjusted P=0.03 , P=0.08 in the intention‐to‐treat analysis ) and 11 of 47 patients ( 23 % ) who underwent sleeve gastrectomy ( unadjusted P=0.03 , adjusted P=0.07 , P=0.17 in the intention‐to‐treat analysis ) . Patients who underwent surgical procedures had a greater mean percentage reduction from baseline in glycated hemoglobin level than did patients who received medical therapy alone ( 2.1 % vs. 0.3 % , P=0.003 ) . At 5 years , changes from baseline observed in the gastric‐bypass and sleeve‐gastrectomy groups were superior to the changes seen in the medical‐therapy group with respect to body weight ( ‐23 % , ‐19 % , and ‐5 % in the gastric‐bypass , sleeve‐gastrectomy , and medical‐therapy groups , respectively ) , triglyceride level ( ‐40 % , ‐29 % , and ‐8 % ) , high‐density lipoprotein cholesterol level ( 32 % , 30 % , and 7 % ) , use of insulin ( ‐35 % , ‐34 % , and ‐13 % ) , and quality ‐of‐life measures ( general health score increases of 17 , 16 , and 0.3 ; scores on the R AND 36‐Item Health Survey ranged from 0 to 100 , with higher scores indicating better health ) ( P<0.05 for all comparisons ) . No major late surgical complications were reported except for one reoperation . CONCLUSIONS Five‐year outcome data showed that , among patients with type 2 diabetes and a BMI of 27 to 43 , bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing , or in some cases resolving , hyperglycemia . ( Funded by Ethicon Endo‐Surgery and others ; STAMPEDE Clinical Trials.gov number , NCT00432809 . BACKGROUND Saline-filled intragastric balloon devices are reversible endoscopic devices design ed to occupy stomach volume and reduce food intake . OBJECTIVE To evaluate the safety and effectiveness of a dual balloon system plus diet and exercise in the treatment of obesity compared to diet and exercise alone . SETTING Academic and community practice , United States . METHODS Participants ( n = 326 ) with body mass index ( BMI ) 30 - 40 kg/m(2 ) were r and omized to endoscopic DBS treatment plus diet and exercise ( DUO , n = 187 ) or sham endoscopy plus diet and exercise alone ( DIET , n = 139 ) . Co- primary endpoints were a between-group comparison of percent excess weight loss ( % EWL ) and DUO subject responder rate , both at 24 weeks . Thereafter DUO patients had the DBS retrieved followed by 24 additional weeks of counseling ; DIET patients were offered DBS treatment . RESULTS Mean BMI was 35.4 . Both primary endpoints were met . DUO weight loss was over twice that of DIET . DUO patients had significantly greater % EWL at 24 weeks ( 25.1 % intent-to-treat ( ITT ) , 27.9 % completed cases ( CC , n = 167 ) compared with DIET patients ( 11.3 % ITT , P = .004 , 12.3 % CC , n = 126 ) . DUO patients significantly exceeded a 35 % response rate ( 49.1 % ITT , P<.001 , 54.5 % CC ) for weight loss dichotomized at 25%EWL . Accommodative symptoms abated rapidly with support and medication . Balloon deflation occurred in 6 % without migrations . Early retrieval for nonulcer intolerance occurred in 9 % . Gastric ulcers were observed ; a minor device change led to significantly reduced ulcer size and frequency ( 10 % ) . CONCLUSION The DBS was significantly more effective than diet and exercise in causing weight loss with a low adverse event profile BACKGROUND AND AIMS Endoscopic sleeve gastroplasty ( ESG ) is a novel , incisionless technique for gastric volume reduction to promote weight loss . Our aim was to describe the learning curve for performing ESG using a prospect i ve case series . METHODS Using a prospect i ve case series design , we analyzed the first 128 consecutive patients at a tertiary care academic medical center who underwent ESG performed by a single operator from August 2013 to December 2016 . Efficiency ( refining performance to decrease procedure time ) and mastery ( absence of outliers ) for performing ESG was evaluated by using a penalized basis-spline regression and cumulative sum analysis . RESULTS Efficiency for ESG was attained after 38 ESGs , with mastery after 55 procedures . At 12 months , the mean percent total body weight loss was 15.8 % ( st and ard deviation , 9.47 % ) . A total of 71.7 % of patients achieved successful weight loss . When using multiple linear regression analysis , both number of sutures and baseline weight were significantly associated with procedure time . Other patient characteristics , such as age , sex , and race , did not significantly affect procedure time . In addition , number of sutures , baseline weight , and endoscopist achieving efficiency were not correlated with successful weight loss at 12 months . CONCLUSIONS Mastery of ESG by a single operator is suggested after sufficient endoscopic experience and may help guide widespread clinical adaptability The profound effects of bariatric surgery on glycemic control are well established in many studies , including several r and omized trials that compared surgery versus intensive medical and lifestyle treatment of type 2 diabetes mellitus ( T2DM ) ( 17 ) . Remission of T2DM is common after bariatric surgery , and Roux-en-Y gastric bypass ( RYGB ) outperforms sleeve gastrectomy ( SG ) in most reports ( 4 , 8 , 9 ) . More important than improvements in glycemic control is whether these glycemic changes reduce the incidence of major complications , such as microvascular events . In the United States , T2DM is the primary cause of nephropathy , end-stage renal disease , adult blindness , and neuropathy , which together lead to significant downstream costs and decreased quality of life ( 1012 ) . Thus , a major goal of diabetes treatment is to mitigate the risk for these long-term sequelae ( 13 ) . We have previously shown that in patients with T2DM who have bariatric surgery , risk for incident microvascular disease is reduced for every year of remission from T2DMeven if patients eventually relapse back to T2DM ( indicating a legacy effect ) ( 14 ) . However , a detailed 2016 review of long-term microvascular outcomes of diabetes concluded that data were inadequate to support a superior effect of bariatric surgery compared with medical therapy ( 15 ) . Two recently published studies help inform this question ( 4 , 16 ) . The STAMPEDE ( Surgical Therapy and Medications Potentially Eradicate Diabetes Efficiently ) trial ( 4 ) r and omly assigned 150 patients with obesity and T2DM to have RYGB , SG , or an intensive medical and lifestyle intervention . After 5 years , urinary albumincreatinine ratios had decreased in the SG group only . Retinopathy did not change in any group , and neuropathy was not examined . STAMPEDE was limited by a relatively small sample size , which made it underpowered for rare outcomes . The prospect i ve SOS ( Swedish Obesity Subjects ) matched cohort study ( 16 ) followed 2010 patients who had bariatric surgery ( 13 % RYGB , 19 % gastric b and ing , and 68 % vertical-b and ed gastroplasty ) and 2037 matched patients who received usual care . The incidence of microvascular disease after 15 years of follow-up was significantly lower in the surgery group than the control group ( hazard ratio [ HR ] , 0.56 [ 95 % CI , 0.48 to 0.66 ] ) , including among subgroups with prediabetes ( HR , 0.18 [ CI , 0.11 to 0.30 ] ) , established diabetes ( HR , 0.54 [ CI , 0.40 to 0.72 ] ) , and normoglycemia ( HR , 0.63 [ CI , 0.48 to 0.81 ] ) at baseline . The SOS study was limited by the small number of RYGB procedures and lack of SG procedures , which are now the 2 most common bariatric procedures worldwide ( 17 ) . To address these gaps in the literature , we did a matched cohort study to determine whether bariatric surgery was associated with lower incidence of microvascular disease than usual care for severe obesity and T2DM . We hypothesized that patients having bariatric surgery would have lower risk for any incident microvascular disease ( composite of the first occurrence of retinopathy , neuropathy , or nephropathy ) . We further hypothesized that patients having bariatric surgery would have lower risk for incident retinopathy , nephropathy , and neuropathy than nonsurgical patients . Methods Setting s We did a retrospective observational cohort study of adults with T2DM who had bariatric surgery between 2005 and 2011 while enrolled in 1 of 4 integrated health care systems from the Health Care Systems Research Network : Kaiser Permanente ( KP ) Washington in Washington state , HealthPartners in Minnesota , KP Northern California , and KP Southern California . All study procedures were review ed and approved by the institutional review board at each site , and we were permitted to do the research without explicit consent from participants . Data Sources At each study site , staff used st and ardized electronic medical records , insurance cl aims , and other data systems ( 18 ) to extract enrollee data , including enrollment and insurance coverage ; demographics ; blood pressure ; height ; weight ; laboratory values ; medications dispensed ; deaths ; outpatient , inpatient , and emergency department use ; and inpatient and outpatient diagnosis and procedure codes . Surgical Participants The bariatric population included adults ( aged 19 to 79 years ) with severe obesity ( body mass index [ BMI ] 35 kg/m2 ) and T2DM who had a primary ( first observed ) bariatric surgical procedure between 1 January 2005 and 31 December 2011 . Following an approach adopted in prior studies ( 14 , 19 , 20 ) , we used a combination of bariatric registries ; review of medical records ; codes from the International Classification of Diseases , Ninth Revision ( ICD-9 ) ( 43.89 , 44.31 , 44.38 , 44.39 , 44.68 , 44.69 , and 44.95 ) ; and Current Procedural Terminology codes ( 43633 , 43644 , 43645 , 43659 , 43770 , 43775 , 43842 , 43843 , 43844 , 43845 , 43846 , and 43847 ) to identify bariatric procedures . Patients were classified as having T2DM if they had a hemoglobin A1c ( HbA1c ) level of at least 6.5 % or fasting plasma glucose level of at least 6.99 mmol/L ( 126 mg/dL ) at the most recent measurement within 2 years before surgery , or a current prescription for any diabetes medication . After selecting the population , we applied the following exclusion criteria based on information in the 2 years before surgery : less than 1 full year of continuous enrollment ; history of gastrointestinal surgery for cancer ; pregnancy in the year before surgery ; gestational diabetes as the sole diabetes diagnosis ; metformin as the sole indicator of possible T2DM ( that is , no other T2DM medications , laboratory values , or diagnoses ) ; preexisting neuropathy , retinopathy , or nephropathy ( defined in Outcome and Censoring Definitions ) ; and maximum preoperative BMI less than 35 kg/m2 . This left 4972 patients . We further excluded 850 patients who were missing values for BMI , HbA1c level , or serum creatinine concentration in the 2 years before surgery . Surgical patients who were missing these values differed from those who had complete data ( Appendix Table 1 ) . Specifically , they were more likely to be non-Hispanic white , to be from the HealthPartners site , to have had their procedure in the first year of our study ( 2005 ) , and to have had a shorter observed duration of T2DM at the time of surgery . Of the remaining 4122 patients , 4024 could be matched to at least 1 nonsurgical patient ( Figure 1 ) . Figure 1 . Flow diagram for identification of eligible patients with T2DM and no history of microvascular disease who had bariatric surgery . BMI = body mass index ; EHR= electronic health record ; HbA1c= hemoglobin A1c ; T2DM= type 2 diabetes mellitus . * Adults aged 2079 y who had a primary ( first observed ) bariatric surgical procedure between 1 January 2005 and 31 December 2011 . Bariatric procedures were identified using a combination of bariatric registries ; review of medical records ; International Classification of Diseases , Ninth Revision , codes ( 43.89 , 44.31 , 44.38 , 44.39 , 44.68 , 44.69 , and 44.95 ) ; and Current Procedural Terminology codes ( 43633 , 43644 , 43645 , 43659 , 43770 , 43775 , 43842 , 43843 , 43844 , 43845 , 43846 , and 43847 ) . We excluded patients with any of the following : < 1 y of continuous enrollment ; history of gastrointestinal surgery for cancer ; pregnancy in the year before surgery ; gestational diabetes as the sole diabetes diagnosis ; preexisting neuropathy , nephropathy , or retinopathy ; metformin as the sole indicator of possible T2DM ( no other T2DM medications , laboratory values , or diagnoses ) ; or maximum BMI < 35 kg/m2 . Patients may have > 1 type of missing data ( BMI , creatinine concentration , or HbA1c level ) or have no follow-up time after surgery . 98 surgical patients could not be matched to a nonsurgical patient on site , age , BMI , insulin use , HbA1c level , and sex . Appendix Table 1 . Comparison of Characteristics of Surgical Patients Who Were Missing Values for BMI , HbA1c , or Serum Creatinine at Baseline Versus Those Who Had Complete Information on These Values at Baseline Matched Nonsurgical Participants For each surgical patient , we identified up to 3 matched nonsurgical control participants via a 2-step process . First , among all patients with diabetes and at least 1 BMI measurement of 35 kg/m2 or greater who did not have bariatric surgery during the study ( n= 320345 ) , we identified a pool of potential control participants who were enrolled at the time of the surgery ; satisfied the study inclusion criteria ; and matched the surgical patient on the basis of study site , sex , age ( 10 years ) , BMI ( 5 kg/m2 ) , HbA1c level ( 1.5 percentage points ) , and insulin use . Second , for each control participant in the pool , we calculated Mahalanobis distance from the surgical patient on the basis of age , BMI , HbA1c level , diabetes duration , and total days of health care use in the 7 to 24 months before the date of surgery ( 21 ) . Finally , up to 3 control participants were selected on the basis of the shortest Mahalanobis distance . Throughout , nonsurgical patients could be used as a control for only 1 surgical patient ( matching without replacement ) . The Appendix gives additional details on the process we used to establish the matched cohort . Outcome and Censoring Definitions The primary outcome measure was time to incident microvascular disease ( composite of the first occurrence of retinopathy , neuropathy , or nephropathy ) . Retinopathy was defined by the first appearance of either ICD-9 code 362.0x ( diabetic retinopathy ) or both a retinal surgical procedure code or other retinopathic code ( Appendix Table 2 ) and ICD-9 code 250.5x ( diabetes with ophthalmic manifestations ) . Neuropathy was identified on the basis of the first occurrence of ICD-9 code 250.6 ( diabetes with neurologic manifestations ) or 357.2 ( polyneuropathy in diabetes ) . Finally , nephropathy was defined by at least 2 measures of estimated glomerular filtration rate less than 60 mL/min/1.73 m2 separated by at least 90 days without any intervening values of 60 mL/min/1.73 m2 or greater . We approximated Importance Macrovascular disease is a leading cause of morbidity and mortality for patients with type 2 diabetes , and medical management , including lifestyle changes , may not be successful at lowering risk . Objective To investigate the relationship between bariatric surgery and incident macrovascular ( coronary artery disease and cerebrovascular diseases ) events in patients with severe obesity and type 2 diabetes . Design , Setting , and Participants In this retrospective , matched cohort study , patients with severe obesity ( body mass index ≥35 ) aged 19 to 79 years with diabetes who underwent bariatric surgery from 2005 to 2011 in 4 integrated health systems in the United States ( n = 5301 ) were matched to 14 934 control patients on site , age , sex , body mass index , hemoglobin A1c , insulin use , observed diabetes duration , and prior health care utilization , with follow-up through September 2015 . Exposures Bariatric procedures ( 76 % Roux-en-Y gastric bypass , 17 % sleeve gastrectomy , and 7 % adjustable gastric b and ing ) were compared with usual care for diabetes . Main Outcomes and Measures Multivariable-adjusted Cox regression analysis investigated time to incident macrovascular disease ( defined as first occurrence of coronary artery disease [ acute myocardial infa rct ion , unstable angina , percutaneous coronary intervention , or coronary artery bypass grafting ] or cerebrovascular events [ ischemic stroke , hemorrhagic stroke , carotid stenting , or carotid endarterectomy ] ) . Secondary outcomes included coronary artery disease and cerebrovascular outcomes separately . Results Among a combined 20 235 surgical and nonsurgical patients , the mean ( SD ) age was 50 ( 10 ) years ; 76 % of the surgical and 75 % of the nonsurgical patients were female ; and the baseline mean ( SD ) body mass index was 44.7 ( 6.9 ) and 43.8 ( 6.7 ) in the surgical and nonsurgical groups , respectively . At the end of the study period , there were 106 macrovascular events in surgical patients ( including 37 cerebrovascular and 78 coronary artery events over a median of 4.7 years ; interquartile range , 3.2 - 6.2 years ) and 596 events in the matched control patients ( including 227 cerebrovascular and 398 coronary artery events over a median of 4.6 years ; interquartile range , 3.1 - 6.1 years ) . Bariatric surgery was associated with a lower composite incidence of macrovascular events at 5 years ( 2.1 % in the surgical group vs 4.3 % in the nonsurgical group ; hazard ratio , 0.60 [ 95 % CI , 0.42 - 0.86 ] ) , as well as a lower incidence of coronary artery disease ( 1.6 % in the surgical group vs 2.8 % in the nonsurgical group ; hazard ratio , 0.64 [ 95 % CI , 0.42 - 0.99 ] ) . The incidence of cerebrovascular disease was not significantly different between groups at 5 years ( 0.7 % in the surgical group vs 1.7 % in the nonsurgical group ; hazard ratio , 0.69 [ 95 % CI , 0.38 - 1.25 ] ) . Conclusions and Relevance In this observational study of patients with type 2 diabetes and severe obesity who underwent surgery , compared with those who did not undergo surgery , bariatric surgery was associated with a lower risk of macrovascular outcomes . The findings require confirmation in r and omized clinical trials . Health care professionals should engage patients with severe obesity and type 2 diabetes in a shared decision making conversation about the potential role of bariatric surgery in the prevention of macrovascular events BACKGROUND Obesity is a significant health problem and additional therapies are needed to improve obesity treatment . OBJECTIVE Determine the efficacy and safety of a 6-month swallowable gas-filled intragastric balloon system for weight loss . SETTING Fifteen academic and private practice centers in the United States . METHODS This was a double-blind , r and omized sham-controlled trial of the swallowable gas-filled intragastric balloon system plus lifestyle therapy compared with lifestyle therapy alone for weight loss at 6 months in participants aged 22 to 60 years with body mass index 30 to 40 kg/m2 , across 15 sites in the United States . The following endpoints were included : difference in percent total weight loss in treatment group versus control group was > 2.1 % , and a responder rate of > 35 % in the treatment group . RESULTS Three hundred eighty-seven patients swallowed at least 1 capsule . Of participants , 93.3 % completed all 24 weeks of blinded study testing . Nonserious adverse events occurred in 91.1 % of patients , but only .4 % were severe . One bleeding ulcer and 1 balloon deflation occurred . In analysis of patients who completed treatment , the treatment and control groups achieved 7.1 ± 5.0 % and 3.6 ± 5.1 % total weight loss , respectively , and a mean difference of 3.5 % ( P = .0085 ) . Total weight loss in treatment and control groups were 7.1 ± 5.3 and 3.6 ± 5.1 kg ( P < .0001 ) , and body mass index change in the treatment and control groups were 2.5 ± 1.8 and 1.3 ± 1.8 kg/m2 ( P < .0001 ) , respectively . The responder rate in the treatment group was 66.7 % ( P < .0001 ) . Weight loss maintenance in the treatment group was 88.5 % at 48 weeks . CONCLUSIONS Treatment with lifestyle therapy and the 6-month swallowable gas-filled intragastric balloon system was safe and result ed in twice as much weight loss compared with a sham control , with high weight loss maintenance at 48 weeks BACKGROUND AND AIMS Questions related to the safety and long-term efficacy of endoscopic sleeve gastroplasty ( ESG ) are not yet answered . Here we report weight loss , morbidity , revisions , and comorbidity resolution during the first 18 months after primary ESG . METHODS This is a consecutive case series from a prospect i ve observational study executed in a specialized center with a st and ardized pathway for multimodal management of obesity . RESULTS The 1000 patients in this study had a baseline body mass index of 33.3 ± 4.5 kg/m2 and age of 34.4 ± 9.5 years . Eight hundred ninety-seven patients ( 89.7 % ) were women . Mean percentage of total weight loss at 6 , 12 , and 18 months was 13.7 % ± 6.8 % ( n = 369 ; follow-up rate = 423 ; 87.2 % ) , 15.0 % ± 7.7 % ( n = 216 ; follow-up rate = 232 ; 93.1 % ) , and 14.8 % ± 8.5 % ( n = 54 ; follow-up rate = 63 ; 85.7 % ) , respectively . Lost to follow-up at the 12- and 18-month visits were 6.9 % and 14.3 % , respectively . Thirteen of 17 cases of diabetes , all 28 cases of hypertension , and 18 of 32 cases of dyslipidemia were in complete remission by the third month . With regard to postoperative complaints , 924 patients ( 92.4 % ) complained of nausea or abdominal pain that was controlled with medications during the first week after ESG . Twenty-four patients were readmitted : 8 for severe abdominal pain , of whom 3 had ESG reversal ; 7 for postprocedure bleeding , 2 of whom received 2 units of packed red blood cells each ; 4 for perigastric collection with pleural effusion , 3 of whom underwent percutaneous drainage ; and 5 for postprocedure fever with no sequelae . Eight patients were revised to sleeve gastrectomy , and 5 had redo-ESG . No patient required an emergency intervention , and there were no mortalities . CONCLUSIONS ESG appears to be well tolerated , safe , and effective . Significant weight loss occurs during the first 18 months without mortality or significant morbidity . Some patients require revision or reversal during the first year BACKGROUND AND AIMS Obesity is a p and emic effecting approximately 700 million adults worldwide with an additional 2 billion overweight . Endoscopic sleeve gastroplasty ( ESG ) is a minimally invasive endoscopic bariatric therapy that involves remodeling of the greater curvature , in an effort to reduce gastric capacity and delay gastric emptying . A variety of ESG suture patterns have been reported . This study is the first to use a uniform ' U ' stitch pattern across all centers to simplify technical aspects of the procedure and limit cost . This also uniquely assessed outcomes in all BMI categories and changes in metabolic rate , lean body mass , and adipose tissue composition . METHODS This is a multicenter analysis of prospect ively collected data from 7 centers including patients with overweight and obesity who underwent ESG . Primary outcomes included AWL , % TWL , change in BMI , % EWL at 6 and 12 months in overweight , obese class I , II , and III . Secondary outcomes included adipose tissue , lean body mass reduction , and metabolic rate analyzed by bioimpedance . Additionally , immediate or delayed adverse events were analyzed . Clinical success was defined as achieving ≥25 % EWL at 1 year with ≤ 5 % serious adverse event rate following the ASGE/ASMBS threshold . RESULTS A total of 193 patients underwent ESG during the study period . All groups had > 10 % TWL and > 25 % EWL at 6 months follow-up . On avarage , % TWL was 14.25 % ± 5.26 and 15.06 % ± 5.22 and the % EWL was 56.15 % ± 22.93 and 59.41 % ± 25.69 at 6 months and 1-year follow-up , respectively . % TWL was 8.91%±0.3 , 13.92%±5.76 , 16.22%±7.69 , and 19.01%±0.95 , and % EWL was 56.21%±2.0 , 62.03%±27.63 , 54.13%±23.46 , and 46.78%±2.43 for overweight , obesity class I , II , and III , respectively , at 1 year . Male , age < 41 years old , and higher BMI are predictors of achieving a TWL ≥10 % at 1-year follow-up . There was a significant reduction in adipose tissue from baseline . Severe adverse events occurred in 1.03 % including 2 perigastric collection s needing surgery . CONCLUSION Endoscopic sleeve gastroplasty appears to be feasible , safe , and effective in the treatment of patients with overweight and obesity according to the ASGE/ASMBS thresholds BACKGROUND AND AIMS Endoscopic sleeve gastroplasty ( ESG ) reduces the gastric lumen to a size comparable with that of laparoscopic sleeve gastrectomy ( LSG ) . However , there is a paucity of research comparing outcomes between the 2 procedures . Our study compared the 6-month weight loss outcomes and adverse events of ESG with LSG in a case-matched cohort . METHODS We retrospectively review ed prospect ively collected data for patients undergoing ESG or LSG at a single academic center . Weight was recorded at 1 and 6 months postprocedure , and percent total body weight loss ( % TBWL ) was calculated . Adverse events and new-onset Gastroesophageal Reflux Disease ( GERD ) were also recorded . RESULTS A total of 54 ESG patients were matched with 83 LSG patients by age , sex , and body mass index . The proportion of patients with GERD at baseline was similar in the 2 groups ( 16.7 % in ESG group vs 25.3 % in LSG group , P = .27 ) . At the 6-month follow-up , % TBWL ( compared with baseline ) was significantly lower in the ESG group compared with the LSG group ( 17.1 % ± 6.5 % vs 23.6 % ± 7.6 % , P < .01 ) . ESG patients had significantly lower rates of adverse events compared with LSG patients ( 5.2 % vs 16.9 % , P < .05 ) . New-onset GERD was also significantly lower in the ESG group compared with the LSG group ( 1.9 % vs 14.5 % , P < .05 ) . CONCLUSIONS ESG , a minimally invasive same-day procedure , achieved less weight loss at 6 months than LSG , with the caveat that LSG caused more adverse events and new-onset GERD than ESG BACKGROUND & AIMS It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis ( NASH ) . We examined the association between the magnitude of weight loss through lifestyle modifications and changes in histologic features of NASH . METHODS We conducted a prospect i ve study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks , from June 2009 through May 2013 , at a tertiary medical center in Havana , Cuba . Liver biopsies were collected when the study began and at week 52 of the diet and were analyzed histologically . RESULTS Paired liver biopsies were available from 261 patients . Among 293 patients who underwent lifestyle changes for 52 weeks , 72 ( 25 % ) achieved resolution of steatohepatitis , 138 ( 47 % ) had reductions in nonalcoholic fatty liver disease activity score ( NAS ) , and 56 ( 19 % ) had regression of fibrosis . At week fifty-two , 88 subjects ( 30 % ) had lost ≥5 % of their weight . Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters ( odds ratios = 1.1 - 2.0 ; P < .01 ) . A higher proportion of subjects with ≥5 % weight loss had NASH resolution ( 51 of 88 [ 58 % ] ) and a 2-point reduction in NAS ( 72 of 88 [ 82 % ] ) than subjects who lost < 5 % of their weight ( P < .001 ) . All patients who lost ≥10 % of their weight had reductions NAS , 90 % had resolution of NASH , and 45 % had regression of fibrosis . All patients who lost 7%-10 % of their weight and had few risk factors also had reduced NAS . In patients with baseline characteristics that included female sex , body mass index ≥35 , fasting glucose > 5.5 mmol/L , and many ballooned cells , NAS scores decreased significantly with weight reductions ≥10 % . CONCLUSIONS A greater extent of weight loss , induced by lifestyle changes , is associated with the level of improvement in histologic features of NASH . The highest rates of NAS reduction , NASH resolution , and fibrosis regression occurred in patients with weight losses ≥10 % |
11,773 | 22,895,944 | Three to six days of oral antibiotics had comparable efficacy compared to the st and ard duration 10-day course of oral penicillin in treating children with acute GABHS pharyngitis .
. | BACKGROUND The st and ard duration of treatment for children with acute group A beta hemolytic streptococcus ( GABHS ) pharyngitis with oral penicillin is 10 days .
Shorter duration antibiotics may have comparable efficacy .
OBJECTIVES To summarize the evidence regarding the efficacy of two to six days of newer oral antibiotics ( short duration ) compared to 10 days of oral penicillin ( st and ard duration ) in treating children with acute GABHS pharyngitis . | A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising studies for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as necessary ) . Limited time and re sources , however , may preclude such an approach . Construct and Pretest Selection Forms After deciding on selection criteria , review ers can prepare customized forms that contain checklists of the selection criteria ( Figure 1 ) . Using these forms can simplify the selection process , increase reliability , and provide a record of the judgments made about each study . After drafting form prototypes , review ers pretest these forms for clarity , ease of application , and reliability . To pretest the forms , two or more independent review ers typically apply them to a r and om sample of studies identified by the literature search . Review ers compare their results to identify sources of ambiguity and then revise the forms accordingly . If the revisions are substantial , this process may need to be repeated before the forms can be used . Figure 1 . Example of a form that might be developed for the selection of studies for a systematic review evaluating the efficacy of -blockers for secondary prevention of variceal bleeding . Write a Detailed Protocol Having a selection protocol as part of a larger protocol for the entire review helps review ers in two ways . First , it provides a document that explicitly states the review question and the selection criteria , making the process accountable . Review ers can later return to the protocol for guidance in resolving disagreements about article selection . Second , the selection protocol identifies what work will be done , by whom , in what manner , when , and for what reason ; thus , it provides a mode of communication within the review team . When review ers have a very large sample of studies from which to select , they can simplify this task by review ing all of the titles , then the abstract s , and then the full articles , excluding studies that do not meet one or more selection criteria at each step . In doing so , review ers should record ( on the selection forms ) the reasons for exclusion . After review ers have selected studies for the systematic review , they will move to the next task of critical appraisal . This procedure also requires careful planning . Appraising Studies for Systematic Review s Review ers appraise the studies selected for review with three objectives in mind : 1 ) to underst and the validity of the studies , 2 ) to uncover reasons for differences among study results other than chance , and 3 ) to provide readers with sufficient information with which to judge for themselves the applicability of the systematic review to their clinical practice . To achieve these goals , review ers use the strategies outlined in Table 2 and Table 3 to carefully reexamine many important features of the primary studies . Table 3 . Planning Study Appraisal Examine Important Clinical Features Although the selection criteria for a systematic review define the population , interventions , and outcomes of interest , the appraisal process involves a detailed assessment of the patients ( for example , high , medium , or low risk ) , the study interventions ( for example , frequency , degree , and duration ) , and the outcome measurements ( for example , definitions and degree of surveillance ) In a r and omized , prospect i ve , multicenter trial , 227 children ranging in age from 3 to 17 years who had tonsillopharyngitis and a throat culture positive for group A beta-hemolytic streptococci ( GABHS ) were treated with erythromycin estolate ( 40 mg/kg/d in two divided doses for five days ) or penicillin V ( 30 mg/kg/d in three divided doses for ten days ) . Clinical signs and symptoms of tonsillopharyngitis were recorded , and throat cultures were obtained before treatment as well as one to three days and six weeks after treatment . Clinical success ( cure and improvement ) was observed on days 6 to 8 in 100 of 102 ( 98 % ) assessable children treated with erythromycin estolate and on days 11 to 13 in 97 of 99 ( 98 % ) assessable children treated with penicillin V. Of all patients showing clinical success , 11 were rated as improved , all of whom were treated with erythromycin estolate . There was a trend towards increased use of analgesic treatment in the erythromycin estolate group ( 41 % vs 33 % ) . On completion of treatment , the rate of eradication of GABHS was 83.3 % in the erythromycin estolate group compared with 87.9 % in the penicillin V group . The difference is not significant but does not take into account patients excluded because of erythromycin resistance ( 3.7 % ) . Clinical recurrence was observed in 11 ( 10.8 % ) patients treated with erythromycin estolate and in 6 ( 6.1 % ) patients treated with penicillin V ( non-significant difference ) . Compliance in the erythromycin estolate group was statistically superior to that in the penicillin V group . The incidence and nature of adverse events were similar in both treatment groups Objective . To compare a 3-day azithromycin vs. a 10-day penicillin V regimen for treatment of acute group A streptococcal ( GAS ) pharyngitis in children and to determine whether viral infection and /or pharyngeal GAS carriage in patients and adult contacts affect clinical and bacteriologic efficacy . Methods . This multicenter , r and omized , comparative , open label study compared 3-day , once daily 10 mg/kg azithromycin oral suspension with a 10-day regimen of 100 000 IU/kg/day penicillin V oral suspension in three divided doses in children with acute GAS pharyngitis . Clinical and bacteriologic efficacy and tolerability of the antibiotics were evaluated . Recurrence of symptoms and infection was monitored for 6 months . Results . In total , 292 children ( age range , 2 to 12 years ) received at least one dose of study medication . Clinical success ( cure/improvement ) with either antibiotic was similar at the end of therapy ( Day 14 ; azithromycin , 95 % ; penicillin V , 97 % ) and at Day 28 ( azithromycin , 94 % ; penicillin V , 95 % ) . Bacteriologic eradication was significantly less with azithromycin than with penicillin V at Day 14 ( azithromycin , 38 % ; penicillin V , 81%;P < 0.001 ) and at Day 28 ( azithromycin , 31 % ; penicillin V , 68%;P < 0.001 ) . There was no associated increase in GAS-related sequelae . The lower incidence of bacteriologic eradication with azithromycin was not the result of possible concomitant viral infections in the patients , GAS carriage in one parent/guardian or any reduced susceptibility in pretreatment GAS isolates . Both antibiotics were equally well-tolerated . Conclusions . Treatment with 3-day , once daily 10 mg/kg azithromycin for GAS pharyngitis is associated with similar high levels of clinical efficacy , but lower levels of bacteriologic eradication , than with 10-day 100 000 IU/kg/day penicillin OBJECTIVE To estimate the incidence and risk factors of group A streptococcus ( GAS ) sore throat among school-aged children living in a periurban slum area of Ch and igarh , North India . METHODS A total of 536 children aged 5 - 15 years from 261 families identified by a systematic r and om selection method were enrolled in the study . Episodes of sore throat were recorded through fortnightly home visits over a one-year period . The local vernacular ( Hindi ) terms gala kharab ( bad throat ) and khansi jukam ( cough and cold ) were used to identify symptoms of sore throat , and throat swab specimens were collected from children who had these symptoms on the day of the home visit . Bacterial culture was carried out and the isolation of GAS was confirmed using group-A-specific antiserum . FINDINGS The incidences of sore throat and GAS sore throat were , respectively , 7.05 and 0.95 episodes per child-year . The incidence was higher in the following situations : among 11-year-olds , during the winter ( November to January ) and rainy ( August ) months ( a bimodal peak ) , among children living in houses where there was no separate room for the kitchen , and in homes that included a tobacco smoker . CONCLUSION The results show that the incidence of GAS sore throat was related to age , season , and indoor air pollution The efficacy and safety of a 3-day course of azithromycin oral suspension ( 10 mg/kg of body weight once daily ) were compared with those of penicillin V ( 50,000 U/kg/day in two divided doses ) in children aged 3 to 12 years for the treatment of symptomatic pharyngitis caused by the group A beta-hemolytic streptococcus ( GABHS ) . For the 154 evaluable patients , the original infecting strain of GABHS was eliminated at the end of follow-up ( 34 to 36 days after treatment started ) from 67 ( 85.8 % ) of 78 penicillin-treated patients and 41 ( 53.9 % ) of 76 azithromycin-treated patients ( P < 0.0001 ) . Overall clinical success was achieved in 71 ( 91.0 % ) of 78 penicillin V-treated patients and 57 ( 75.0 % ) of 76 azithromycin-treated patients ( P < 0.05 ) . Potential drug-related adverse events were reported for 5.5 and 8.6 % of the penicillin V- and azithromycin-treated patients , respectively ( P = 0.6 ) . In the present study , a once-daily ( 10 mg/kg ) , 3-day oral regimen of azithromycin was as safe as a 10-day course of penicillin but did not represent an effective alternative to penicillin for the treatment of GABHS pharyngitis , even for those children with azithromycin-susceptible strains OBJECTIVE To compare the efficacy and safety of amoxicillin ( 50 mg/kg/day divided twice daily ) for 6 days and penicillin V ( 45 mg/kg/day divided into three doses/day ) for 10 days in children with group A streptococcal ( GAS ) tonsillopharyngitis . METHODS In a prospect i ve , comparative , open , r and omized , multicenter trial , children were scheduled to return for visits 4 days ( main end point ) and 1 month after the completion of treatment for clinical and bacteriologic assessment . Total DNA restriction fragment length polymorphism was used to compare pre- and posttreatment GAS isolates . RESULTS Between September , 1993 , and February , 1995 , 321 children ( 161 amoxicillin , 160 penicillin V ) were enrolled , among whom 318 ( 160 amoxicillin , 158 penicillin V ) were evaluable for safety , and 277 were evaluable for efficacy . Four days after the completion of treatment , pretreatment GAS were eradicated from 118 of the 141 children receiving amoxicillin ( 83.7 % ) and 116 of the 136 ( 85.3 % ) taking penicillin . One month after the outset of treatment , bacteriologic relapses were observed in 9.9 % ( n = 11 ) of the children receiving amoxicillin and 5.7 % ( n = 6 ) of those treated with penicillin V , bacteriologic recurrences in 5 and 3 patients , respectively . Adverse events related to the study medications were reported in 4 patients in the amoxicillin group and 8 in the penicillin V group . Drug-related adverse events leading to treatment discontinuation occurred in 3 patients , all in the penicillin V group . Compliance , based on diary cards and the weight of study drugs returned , was significantly better in the amoxicillin group . CONCLUSIONS . The efficacy and safety of amoxicillin ( 50 mg/kg/day twice daily ) for 6 days were not statistically different from those of penicillin ( 45 mg/kg/d three times a day ) for 10 days in the treatment of GAS tonsillopharyngitis Oral penicillin V given three times daily in doses of 50,000 - 100,000 IU daily has been the st and ard treatment for tonsillopharyngitis for the last few decades . These regimens , initially recommended by the American Heart Association , were extrapolated from i.v . dosing with long-acting forms of penicillin which had been shown to prevent post-streptococcal sequelae . More recently , several antibiotics , including cefuroxime axetil , have been shown to be at least as effective as penicillin G in eradicating group A beta-haemolytic streptococci ( GABHS ) but their influence on post-streptococcal sequelae has never been assessed in a large-scale trial . The German Society for Pediatric Infectious Diseases ( DGPI ) undertook a large study of culture-proven tonsillopharyngitis involving several agents and included a 1 year follow-up to establish the effect on sequelae . In one arm of this study , cefuroxime 250 mg bid was compared with 50,000 IU penicillin V given in three divided doses . Cefuroxime axetil was more effective than oral penicillin V in eradicating GABHS at the assessment 2 - 4 days post-treatment ( 441/490 ( 90 % ) patients versus 1196/1422 ( 84 % ) patients ; P = 0.001 ) . Clinical ly , the two agents were equivalent in efficacy , and carriage rates were similar ( 11.1 % and 13.8 % , respectively ) in patients receiving cefuroxime axetil and penicillin V , 7 - 8 weeks post-treatment . One case of glomerular nephritis occurred in a patient given penicillin V. There were no post-streptococcal sequelae confirmed for patients treated with cefuroxime axetil . The findings confirm the previously reported efficacy of short-course ( 4 - 5 day ) treatments with cefuroxime axetil and indicate that short-course treatment is comparable to the st and ard oral penicillin V regimen in preventing post-streptococcal sequelae Background : Short course antimicrobial therapy is suggested for group A streptococcal tonsillopharyngitis . Methods : The bacteriologic and clinical efficacies of clarithromycin [ 30 or 15 mg/kg/day twice daily ( b.i.d . ) ] or amoxicillin/clavulanate ( 43.8/6.2 mg/kg/day b.i.d . ) for 5 days or penicillin V ( 30 mg/kg/day 3 times a day ) for 10 days were compared . In a r and omized , open label , parallel group , multicenter study , 626 children ( 2–16 years old ) with tonsillopharyngitis were enrolled ; 537 were evaluable for efficacy . Follow-up evaluations were performed at 4–8 and 21–28 days after therapy . Results : At enrollment , 26 % of the Streptococcus pyogenes isolates were clarithromycin-nonsusceptible . All regimens had an apparently similar clinical efficacy . The long term S. pyogenes eradication rates were 102 of 123 ( 83 % ) with amoxicillin/clavulanate and 88 of 114 ( 77 % ) with penicillin V. In the 30- and 15-mg/kg/day clarithromycin groups , eradication occurred in 71 of 86 ( 83 % ) and 59 of 80 ( 74 % ) of the clarithromycin-susceptible isolates ( P = 0.33 ) , and in 4 of 28 ( 14 % ) and 5 of 26 ( 19 % ) of the clarithromycin-resistant isolates , respectively ( clarithromycin-susceptible versus -resistant , P < 0.0001 ) . Both clarithromycin dosages were well-tolerated . Conclusions : In group A streptococcal tonsillopharyngitis , 5 days of clarithromycin or amoxicillin/clavulanate treatment had clinical efficacy comparable with that of 10 days of penicillin V treatment ; however , amoxicillin/clavulanate and penicillin V were bacteriologically more effective than clarithromycin because of its failure to eradicate the clarithromycin-resistant S. pyogenes isolates . The 5-day clarithromycin regimens are not recommended for treatment of streptococcal tonsillopharyngitis in areas where in vitro resistance of group A streptococci to clarithromycin is common Background . Three-day , 10 mg/kg/day azithromycin ( AZM ) studies in pediatric acute group A streptococcal tonsillopharyngitis have shown contradictory bacteriologic results . This study investigates the efficacy and tolerability of two dosages of 3-day azithromycin ( 20 mg/kg/day and 10 mg/kg/day ) compared with 10-day penicillin V. Methods . This was a prospect i ve , comparative , r and omized , multicenter trial . Children were scheduled to return for visits at 14 days ( main end point ) and 1 month after the onset of treatment for clinical and bacteriologic assessment . Molecular tools were used to compare pre- and posttreatment group A beta-hemolytic Streptococcus ( GABHS ) isolates . Results . Between November , 1997 , and July , 1998 , 501 patients ( 169 AZM 10 mg , 165 AZM 20 mg , 167 penicillin V ) between 2 and 12 years old were enrolled ; 500 were assessable for safety , 469 for intent to treat analysis and 420 for efficacy in the per protocol analysis . Before treatment 25 ( 7.9 % ) of 315 GABHS stains isolated from patients receiving AZM were resistant to this compound . On Day 14 pretreatment GABHS were eradicated from 78 ( 57.8 % ) of the 135 children receiving the AZM 10 mg regimen , 131 ( 94.2 % ) of the 139 receiving AZM 20 mg and 123 ( 84.2 % ) of the 146 taking penicillin . One month after the outset of treatment , bacteriologic relapses were observed in 40.5 % ( n = 30 ) of the children receiving AZM 10 mg , 14.8 % ( n = 18 ) of children taking AZM 20 mg and 13.2 % ( n = 15 ) of those treated with penicillin V. AZM 20 mg/kg/day was statistically superior to AZM 10 mg/kg/day microbiologically on Day 14 ( P = 0.0001 ) and Day 30 ( P = 0.0001 ) and clinical ly on Day 14 ( P = 0.0035 ) . AZM 20 mg/kg/day was statistically equivalent both microbiologically and clinical ly to st and ard therapy with penicillin V at all endpoints . The incidence of treatment-related adverse events was similar in the two azithromycin groups [ AZM 10 mg , 31 of 169 ( 18.3 % ) ; AZM 20 mg , 37 of 164 ( 23 % ) ] but significantly higher than those observed in the penicillin V group [ 5 of 166 (3%);P < 0.0001 ] . Most treatment-related adverse events were gastrointestinal and of mild-to-moderate severity . Fourteen patients withdrew from the trial because of adverse events ( 1 in the penicillin V group , 7 in the AZM 10 mg group and 6 in the AZM 20 mg group ) . Conclusion . This is the first study to demonstrate a daily dose-dependent difference in microbiologic efficacy of a regimen ; 3-day AZM 20 mg/kg/day is a more effective regimen than 3-day AZM 10 mg/kg/day for pediatric GABHS tonsillopharyngitis The efficacy and safety of azithromycin and penicillin V in the treatment of acute streptococcal pharyngitis/tonsillitis in paediatric patients were compared in a double-blind , double-dummy prospect i ve study . A total of 489 children ( age range , 2–13 years ) were r and omized to receive treatment with penicillin V ( 125–250 mg 4 × daily for 10 days ) or azithromycin in an oral suspension ( 10 or 20 mg/kg 1 × daily for 3 days ) . Only patients with baseline cultures positive forStreptococcus pyogenes and complete clinical and microbiological assessment s at the end of therapy and follow-up one month later were included in the efficacy analysis . A satisfactory clinical response ( cure or improvement ) was recorded in 99 % of the 10 mg/kg azithromycin group , 100 % of the 20 mg/kg azithromycin group , and 97 % of the penicillin V group at the end of therapy ( day 12–14 ) . At the follow-up evaluation ( day 28–30 ) , relapse rates in patients cured or improved at the end of therapy were 6 % , 5 % , and 2 % , respectively . Bacteriological eradication rates at the end of therapy were 98 % in both azithromycin groups and 92 % in patients who received penicillin V ( p=0.011 ) ; pathogen recurrence was recorded at follow-up in 4 % of the 20 mg/kg azithromycin group and in 6 % of both the 10 mg/kg azithromycin and penicillin V groups . Treatment-related adverse events , the majority of mild to moderate severity , occurred in 13 % of patients in the 20 mg/kg azithromycin group , 9 % in the 10 mg/kg azithromycin group , and 5 % in the penicillin V group . Azithromycin in a dosage of 10 or 20 mg/kg/day once daily for three days was as safe and effective as penicillin V administered four times daily in the treatment of paediatric patients with acute pharyngitis/tonsillitis In a prospect i ve r and omized multicenter study , 308 children , ages 2 to 15 years , were r and omized to receive either cefuroxime axetil suspension ( N = 152 ; 20 mg/kg/day twice daily ) for 4 days , penicillin suspension ( N = 156 ; 45 mg/kg/day divided three times daily ) for 10 days , of whom 97 and 103 , respectively , had culture-proved group A beta-hemolytic Streptococcus infection . Two to 4 days after completion of the treatment , group A beta-hemolytic Streptococcus were eradicated from 85 of 97 ( 87.6 % ) children taking cefuroxime and from 90 of 103 ( 87.4 % ) taking penicillin ; respective clinical cure rates were 94.8 % and 96.1 % . Clinical signs and symptoms resolved significantly more rapidly with cefuroxime ( P < 0.05 ) . At 28 to 32 days posttreatment the eradication of the primary isolate was confirmed in 94.4 and 91.9 % of cefuroxime axetil and penicillin-treated patients , respectively . Drug-related adverse events ( mainly gastrointestinal and cutaneous reactions ) were reported in 2.1 and 2.7 % of the cefuroxime- and penicillin-treated patients , respectively . Results indicated that a 4-day treatment with cefuroxime axetil was as effective and well-tolerated as the conventional 10-day treatment with penicillin in children with acute group A beta-hemolytic Streptococcus pharyngitis Of 96 children ( aged 2 - 12 years ) with either acute pharyngitis or acute tonsillitis , 49 received a single daily dose of azithromycin 10 mg/kg ( maximum 500 mg ) for three days , and 47 received penicillin V at a dose of 125 mg or 250 mg qid ( depending on body weight ) for ten days . Clinical assessment s and laboratory safety tests were performed during and after therapy . Before enrollment , all patients were screened for group A beta-haemolytic streptococci ( GABHS ) with a rapid test , and a throat swab was taken for confirmatory culture . The presence of GABHS at baseline was confirmed in 41 azithromycin- and 44 penicillin V-treated patients . Cure or improvement was seen in 98 % and 100 % of azithromycin- and penicillin V-treated patients , respectively . At day 11 , bacterial eradication was achieved in 39/41 ( 95 % ) azithromycin-treated patients , 38 ( 93 % ) of whom were considered clinical ly cured , while one patient ( 2 % ) relapsed . In the penicillin V group , 42/44 ( 95 % ) had GABHS eradicated , with 41 ( 93 % ) clinical ly cured and three patients ( 7 % ) improved . The remaining two patients in each group were clinical ly cured despite persistence of Streptococcus pyogenes . At follow-up evaluation ( day 30 ) , re-occurrence was observed in 5/37 ( 14 % ) and 3/40 ( 8 % ) of azithromycin- and penicillin V-treated patients , respectively ; all patients were asymptomatic . Both drugs were well-tolerated with only two patients in the azithromycin group complaining of side effects . Treatment related laboratory test abnormalities were observed in 6/47 ( 13 % ) and 4/45 ( 9 % ) azithromycin- and penicillin V-treated patients , respectively , but none was judged to be clinical ly significant . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND For many years alternatives to penicillin have been studied for the management of pediatric group A beta-hemolytic Streptococcus ( GABHS ) pharyngitis . As a result of its pharmacokinetic profile azithromycin is unique among these alternative antimicrobials in allowing once daily dosing and shorter duration of treatment . However , the optimum dose ( e.g. 10 or 12 mg/kg/day ) and duration ( e.g. 3 or 5 days ) of azithromycin therapy have not been defined yet . METHODS An open , comparative multicenter study was conducted in 343 children with clinical symptoms of GABHS pharyngitis and a positive culture to evaluate the efficacy and safety of azithromycin ( 10 mg/kg ) once daily for 3 days compared with penicillin V three times daily for 10 days . RESULTS Among the evaluable patients bacteriologic eradication documented at follow-up visits was inferior with azithromycin when compared with penicillin V therapy : at Days 9 to 20 ( mean , 12 days ) , negative cultures in 65 % ( 99 of 152 patients ) vs. 82 % ( 128 of 126 patients ) ( P < 0.001 ) ; and at Days 17 to 57 ( mean , 25 days ) , in 55 % vs. 80 % ( P < 0.001 ) . Overall clinical success ( cure or improvement ) was achieved in 93 % ( 149 of 160 patients ) of azithromycin-treated and in 89 % ( 143 of 160 patients ) of penicillin-treated patients ( P > 0.50 ) . There was no correlation between bacteriologic response and clinical outcome , as assessed shortly after completion of therapy or during 6-month follow-up . Both treatments were well-tolerated . CONCLUSIONS In the present study on GABHS pharyngitis in children , a once daily ( 10-mg/kg ) , 3-day oral regimen of azithromycin was as clinical ly effective and as safe as traditional penicillin but appeared inferior in eliminating GABHS from the throat OBJECTIVE To compare the safety and efficacy of a 5-day regimen of cefdinir with those a conventional 10-day regimen of penicillin V for the treatment of streptococcal pharyngitis in children . DESIGN Investigator-blind , r and omized controlled trial . SETTING Primary care , ambulatory . PATIENTS Children aged 1 to 12 years with signs and symptoms of pharyngitis and a positive result on a rapid screening test for Streptococcus pyogenes ( ie , a convenience sample ) . Four hundred eighty-two patients were enrolled in the study , and 440 were clinical ly and microbiologically evaluable . The most common reasons patients were nonevaluable were failure to return for specified visits and noncompliance with the administration of the medication ; 2 patients receiving penicillin V discontinued use of the drug because of adverse events . INTERVENTION Patients were r and omized to receive either 7-mg/kg cefdinir , twice daily , for 5 days or 10-mg/kg penicillin V potassium , 4 times daily , for 10 days . MAIN OUTCOME MEASURES The eradication of S pyogenes and the clinical cure of the signs and symptoms of pharyngitis , both determined 5 to 10 days after the completion of therapy . RESULTS Streptococcus pyogenes was eradicated in 201 ( 90 % ) of the 224 patients receiving cefdinir and 155 ( 72 % ) of the 216 patients receiving penicillin V ( 95 % confidence interval [ CI ] , 10.7%-25.1 % ; P < .001 ) . The clinical cure rates were 92 % and 91 % in the groups receiving cefdinir and penicillin V , respectively ( 95 % CI , -4.5 % to 6.1 % ; P = .80 ) . Adverse events , regardless of the opinion of the investigator about their relationship to the study medication , occurred in 12.5 % of the patients receiving cefdinir and 13.6 % of the patients receiving penicillin V ( P = .69 ) . CONCLUSIONS A 5-day regimen of cefdinir eradicated a higher proportion of S pyogenes than a 10-day regimen of penicillin V. No difference was noted between the regimens for clinical outcomes or adverse event rates OBJECTIVE To compare bacteriologic and clinical efficacy and safety of 10 vs 5 days of cefpodoxime proxetil vs 10 days of penicillin V potassium for the treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis in children . DESIGN Prospect i ve , r and omized , observer-blind , multicenter study . PATIENTS / INTERVENTIONS Four hundred eighty-four children ( age range , 2 to 17 years ) with signs and symptoms of acute tonsillopharyngitis were enrolled ; 377 had a positive throat culture for group A beta-hemolytic streptococci and were fully evaluable . One hundred twenty-one patients received cefpodoxime once a day for 10 days , 126 received cefpodoxime twice a day for 5 days , and 130 received penicillin V three times a day for 10 days . RESULTS Cefpodoxime for 10 days vs cefpodoxime for 5 days vs penicillin V for 10 days produced bacteriologic eradication at the end of therapy in 95 % , 90 % , and 78 % of the patients , respectively . The 10- and 5-day cefpodoxime treatment regimens were more efficacious than penicillin V ( P = .003 and P = .02 , respectively ) . The cumulative bacteriologic failure rate among assessable patients by the 32- to 38-day posttreatment visit was 20 ( 17 % ) of 121 patients who were treated with cefpodoxime for 10 days , 24 ( 19 % ) of 125 patients who were treated with cefpodoxime for 5 days , and 45 ( 35 % ) of 130 patients who were treated with penicillin V for 10 days ( P = .001 and P = .005 , respectively ) . Clinical cure or improvement was observed at the end of therapy in 96 % , 94 % , and 91 % of the patients , respectively ( P = not significant ) . Adverse events were infrequent and similar in all three treatment groups , with minor gastrointestinal side effects predominating . CONCLUSIONS Five days of treatment with cefpodoxime is as efficacious in bacteriologic eradication and clinical response ( cure plus improvement ) as 10 days of cefpodoxime therapy , and both cefpodoxime regimens produced superior bacteriologic efficacy compared with a 10-day regimen of penicillin V in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children Background : The recommended duration of antibiotic treatment of tonsillopharyngitis caused by group A β-hemolytic streptococci ( GABHS ) with penicillin V ( PenV ) is mostly 10 days . However , compliance with 10-day courses is bad . Shorter therapeutic courses are necessary , especially in young children . Methods : In a prospect i ve , r and omized , multi-center study , children aged 1–17 years with acute tonsillopharyngitis and a positive culture for GABHS were treated with cefuroxime axetil ( CAE ) 20 mg/kg/day ( max . 500 mg ) b.i.d . for 5 days or with PenV 50,000 IU/kg ( 30 mg/kg ) t.i.d . for 10 days . Patients were evaluated for clinical efficacy 2–4 and 7–9 days after the end of therapy . Throat swabs were taken 2–4 days after the end of therapy and at the first follow-up visit . Follow-up visits were carried out 7–8 weeks , 6 months and 12 months after study inclusion . Results : 1,952 patients ( CAE for 5 days , 496 patients /PenV for 10 days , 1,456 patients ) could be included in the intent-to-treat analysis . Two to 4 days after completion of the treatment course , the bacteriological eradication in group A ( 1–5 years ) and group B ( 6–17 years ) was 90.52 and 89.53 % ( CAE ) vs. 84.13 and 84.20 % ( PenV ) , respectively ; p = 0.0172 ; 0.0382 ; clinical success was 98.30 % ( CAE ) versus 93.25 % ( PenV ) , p = 0.0017 . Recurrent infections were significantly higher in younger children ( group A ) under both treatment regimens . Poststreptococcal sequelae ( glomerulonephritis ) were observed in only 1 case , in the PenV group . Conclusions : CAE b.i.d . for 5 days was at least as effective as PenV t.i.d . for 10 days . Incountries with a low incidence of rheumatic fever , CAE for 5 days can be recommended for the therapy of tonsillopharyngitis due to GABHS – also in young children Clarithromycin , an advanced-generation macrolide antibiotic , has demonstrated excellent in vitro activity against group A beta-hemolytic streptococcus ( GABHS ) . Potent activity againstStreptococcus pyogenes and a favorable pharmacokinetic profile have made it a reasonable alternative for treatment of patients with streptococcal pharyngitis . The safety and efficacy of clarithromycin and penicillin V were compared in a r and omized , investigator-blind study . Children 6 months to 12 years of age received 5 days of clarithromycin suspension 7.5 mg/kg twice daily ( n = 268 ) or 10 days of penicillin V suspension 13.3 mg/kg three times daily ( n = 260 ) . Patients were evaluated for signs and symptoms of pharyngitis , and throat swabs for culture were obtained prior to therapy , at the end of therapy , and at follow-up . Clarithromycin and penicillin V produced comparable rates of clinical success ( cure + improvement ) at the posttreatment ( 97 % and 94 % ) and follow-up ( 81 % and 82 % ) evaluations . The GABHS eradication rate , however , was significantly higher with clarithromycin ( 94 % vs 78%,P < .001 ) . Both drugs were well tolerated ; gastrointestinal complaints were similar and mild . Resistance did not occur with the short course of clarithromycin or the st and ard regimen of penicillin V. Five days ’ treatment with clarithromycin was superior to 10 daysof penicillin in eradicatingS. pyogenes The clinical efficacy , safety and bacteriological eradication of Group A beta-haemolytic streptococci ( GABHS ) from the throat was studied after treatment of streptococcal tonsillopharyngitis with three commonly used oral antibiotics in a prospect i ve , open labelled , comparative , r and omised trial of 265 evaluable patients seen in one centre . All three antibiotics were administered in the recommended doses ; penicillin V q8 hourly and clarithromycin q12 hourly were given for 10 days and cefprozil q12 hourly for 5 days . Clinical results and adverse events were similar for all three antibiotics used , with a prompt clinical outcome of > 95 % . Cefprozil had the best bacteriological eradication rate ( failed to eradicate : 13.2 , 15.1 , 2.3 ; relapses : 13.2 , 11.4 , 5.7 % , for penicillin , clarithromycin and cefprozil , respectively ) . Oral penicillin remains a clinical ly effective and safe antibiotic for the treatment of streptococcal pharyngitis . However , compliance and convenience for parents and children when they are asked to follow a 10 days course , especially when the patient has improved from the second or third day , together with the high incidence of bacteriological eradication failures , is an issue To determine the effectiveness of a short ( five-day ) course of penicillin V potassium therapy , 172 patients with group A beta-hemolytic streptococcal ( GABHS ) pharyngitis were r and omly assigned to receive 250 mg of penicillin V potassium three times daily for either five or ten days . The patients in the two treatment groups were comparable with respect to clinical findings , compliance , and serologic response to GABHS . A bacteriologic treatment failure was defined as the presence of the same serotype of GABHS in the follow-up as in the initial throat culture and occurred in 13 ( 18 % ) of the 73 patients in the five-day treatment group and in six ( 6 % ) of the 99 patients in the ten-day treatment group . These findings support the current recommendation for a full ten days of oral penicillin V therapy for the treatment of GABHS pharyngitis A large-scale study with a 1-year follow-up was performed to compare 10 days of penicillin V with a short-course treatment ( 5 days ) of other oral antibiotics in the treatment of group A beta-hemolytic streptococcus ( GABHS ) tonsillopharyngitis , to evaluate the efficacy and the incidence of poststreptococcal sequelae . The clinical response rates after completion of therapy were 94.5 % in the 5-day group and 93.4 % in the penicillin group ( P<.001 , equivalence test ) . The GABHS eradication rates were 83.3 % in the 5-day group and 84.4 % in the penicillin group ( P=.022 , equivalence test ) . Poststreptococcal sequelae were rare ( 5 patients ) and did not occur in the context of this study . The efficacy of 5-day antibiotic regimens was equivalent to 10 days of penicillin V , but resolution of clinical symptoms was faster in the 5-day group ( P<.001 , Fisher 's exact test ) . Recurrent tonsillopharyngitis occurs more frequently after treatment with penicillin ( P=.03 , Fisher 's exact test ) Summary In an open , controlled , r and omized multicenter study , 160 children suffering from pharyngitis and /or tonsillitis were treated with either 8 mg cefixime/kg body weight once daily for 5 days or 20,000 I.U. penicillin V/kg body weight t.i.d . for 10 days . One hundred fifty-one children were evaluable for clinical efficacy . In the cefixime group , 65 ( 86.7 % ) children were cured , seven ( 9.3 % ) were significantly improved , one ( 1.3 % ) relapsed and in two ( 2.7 % ) therapy failed . Of the patients treated with penicillin V , 69 ( 90.8 % ) were cured , five ( 6.6 % ) improved , one ( 1.3 % ) relapsed and in one ( 1.3 % ) therapy failed . Elimination of initial pathogens occurred in 57 ( 82.6 % ) patients treated with cefixime and in 60 ( 88.2 % ) treated with penicillin V. At 3 to 4 weeks after the end of treatment , six relapses were seen in the cefixime group and eight in the penicillin V group . Mild-to-moderate adverse events that were possibly related to the medication were seen in four children treated with cefixime and in five treated with penicillin V.ZusammenfassungIm Rahmen einer offenen , r and omisierten , kontrollierten Multizenterstudie wurden 160 Kinder mit Pharyngitis und/oder Tonsillitis entweder mit 8 mg Cefixim/kg Körpergewicht einmal täglich 5 Tage oder mit 20 000 IE Penicillin V/kg Körpergewicht dreimal täglich 10 Tage lang beh and elt . Die Beurteilung der klinischen Wirksamkeit war bei 51 Kindern möglich . In der Cefixim-Gruppe wurden 65 Kinder ( 86,7 % ) geheilt , bei sieben Kindern ( 9,3 % ) trat eine erhebliche Besserung ein , bei einem Kind ( 1,3 % ) kam es zu einem Rezidiv , bei zwei Kindern ( 2,7 % ) war die Beh and lung erfolglos . Unter Beh and lung mit Penicillin V trat in 69 Fällen ( 90,8 % ) Heilung ein , in fünf Fällen ( 6,6 % ) Besserung , in einem Fall ( 1,3 % ) trat ein Rezidiv auf , in einem Fall ( 1,3 % ) wurde die Beh and lung als erfolglos beurteilt . Bei 57 ( 82,6 % ) der mit Cefixim und bei 60 ( 88,2 % ) der mit Penicillin V beh and elten Kinder wurden die ursprünglichen Erreger eliminiert . 3–4 Wochen nach Beh and lungsende wurden in der Cefixim-Gruppe sechs und in der Penicillin V-Gruppe acht Rezidive festgestellt . Bei vier der mit Cefixim und fünf der mit Penicillin V beh and elten Kinder wurden Nebenwirkungen beobachtet , die möglicherweise auf die medikamentöse Therapie zurückzuführen sind |
11,774 | 28,947,079 | Evidence synthesis of studies with high method ological quality revealed that a high quality evidence level supported a significant increase for time-domain heart rate variability ( HRV ) analyses and the heart rate recovery ( HRR ) following AET .
The review also found that frequency domain HRV analyses were not significantly affected by AET .
CONCLUSION Aerobic exercise training demonstrated beneficial but limited effects on the AF in COPD .
Presently , it is not clear whether these effects are sustained in the long term . | OBJECTIVE To assess evidence for the effectiveness of aerobic exercise training ( AET ) on the autonomic function ( AF ) outcomes in patients with chronic obstructive pulmonary disease ( COPD ) . | Introduction Patients with chronic obstructive pulmonary disease ( COPD ) exhibit aerobic function , autonomic nervous system , and mucociliary clearance alterations . These parameters can be attenuated by aerobic training , which can be applied with continuous or interval efforts . However , the possible effects of aerobic training , using progressively both continuous and interval sessions ( ie , linear periodization ) , require further investigation . Aim To analyze the effects of 12-week aerobic training using continuous and interval sessions on autonomic modulation , mucociliary clearance , and aerobic function in patients with COPD . Methods Sixteen patients with COPD were divided into an aerobic ( continuous and interval ) training group ( AT ) ( n=10 ) and a control group ( CG ) ( n=6 ) . An incremental test ( initial speed of 2.0 km·h−1 , constant slope of 3 % , and increments of 0.5 km·h−1 every 2 minutes ) was performed . The training group underwent training for 4 weeks at 60 % of the peak velocity reached in the incremental test ( vVO2peak ) ( 50 minutes of continuous effort ) , followed by 4 weeks of sessions at 75 % of vVO2peak ( 30 minutes of continuous effort ) , and 4 weeks of interval training ( 5 × 3-minute effort at vVO2peak , separated by 1 minute of passive recovery ) . Intensities were adjusted through an incremental test performed at the end of each period . Results The AT presented an increase in the high frequency index ( ms2 ) ( P=0.04 ) , peak oxygen uptake ( VO2peak ) ( P=0.01 ) , vVO2peak ( P=0.04 ) , and anaerobic threshold ( P=0.02 ) . No significant changes were observed in the CG ( P>0.21 ) group . Neither of the groups presented changes in mucociliary clearance after 12 weeks ( AT : P=0.94 and CG : P=0.69 ) . Conclusion Twelve weeks of aerobic training ( continuous and interval sessions ) positively influenced the autonomic modulation and aerobic parameters in patients with COPD . However , mucociliary clearance was not affected by aerobic training 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 Abstract Objective : The aim of this study was to investigate the effects of moderate continuous training ( MCT ) and high intensity aerobic interval training ( AIT ) on systolic ventricular function and aerobic capacity in COPD patients . Methods : Seventeen patients with COPD ( 64 ± 8 years , 12 men ) with FEV1 of 52.8 ± 11 % of predicted , were r and omly assigned to isocaloric programs of MCT at 70 % of max heart rate ( HR ) for 47 minutes ) or AIT ( ∼90 % of max HR for 4 × 4 minutes ) three times per week for 10 weeks . Baseline cardiac function was compared with 17 age- and sex-matched healthy individuals . Peak oxygen uptake ( VO2-peak ) and left ( LV ) and right ventricular ( RV ) function examined by echocardiography , were measured at baseline and after 10 weeks of training . Results : At baseline , the COPD patients had reduced systolic function compared to healthy controls ( p < 0.05 ) . After the training , AIT and MCT increased VO2-peak by 8 % and 9 % and work economy by 7 % and 10 % , respectively ( all p < 0.05 ) . LV and RV systolic function both improved ( p < 0.05 ) , with no difference between the groups after the two modes of exercise training . Stroke volume increased by 17 % and 20 % , LV systolic tissue Doppler velocity ( S ’ ) by 18 % and 17 % and RV S ’ by 15 % after AIT and MCT , respectively ( p < 0.05 ) . Conclusion : Systolic cardiac function is reduced in COPD . Both AIT and MCT improved systolic cardiac function . In contrast to other patient groups studied , higher exercise intensity does not seem to have additional effects on cardiac function or aerobic capacity in COPD patients Objectives Chronic obstructive pulmonary disease ( COPD ) is associated with cardiac autonomic nervous system dysregulation . This study evaluates the effects of interval hypoxic training on cardiovascular and respiratory control in patients with mild COPD . Methods In 18 eucapnic normoxic mild COPD patients ( age 51.7 ± 2.4 years , mean ± SEM ) , r and omly assigned to either training or placebo group , and 14 age-matched healthy controls ( 47.7 ± 2.8 years ) , we monitored end-tidal carbon dioxide , airway flow , arterial oxygen saturation , electrocardiogram , and continuous noninvasive blood pressure at rest , during progressive hypercapnic hyperoxia and isocapnic hypoxia to compare baroreflex sensitivity to hypoxia and hypercapnia before and after 3 weeks of hypoxic training . In double-blind fashion , both groups received 15 sessions of passive intermittent hypoxia ( training group ) or normoxia ( placebo group ) . For the hypoxia group , each session consisted of three to five hypoxic ( 15–12 % oxygen ) periods ( 3–5 min ) with 3-min normoxic intervals . The placebo group inhaled normoxic air . Results Before training , COPD patients showed depressed baroreflex sensitivity , as compared with healthy individuals , without evident chemoreflex abnormalities . After training , in contrast to placebo group , the training group showed increased ( P < 0.05 ) baroreflex sensitivity up to normal levels and selectively increased hypercapnic ventilatory response ( P < 0.05 ) , without changes in hypoxic ventilatory response . Conclusion Eucapnic normoxic mild COPD patients already showed signs of cardiovascular autonomic abnormalities at baseline , which normalized with hypoxic training . If confirmed in more severe patients , interval hypoxic training may be a therapeutic strategy to rebalance early autonomic dysfunction in COPD patients BACKGROUND The chronic obstructive pulmonary disease ( COPD ) is associated with the strength and resistance decreasing in addition to the dysfunction on autonomic nervous system ( ANS ) . The aerobic training isolated or in association with the resistance training showed evidence of beneficial effects on an autonomic modulation of COPD ; however , there are no studies addressing the effect of isolated resistance training . AIMS This study aims at investigating the influence of resistance training on an autonomic modulation through heart rate variability ( HRV ) , functional capacity and muscle strength in individuals with COPD . DESIGN Clinical series study . SETTING Out patients . POPULATION The study involved 13 individuals with COPD . METHODS The experimental protocol was composed by an initial and final evaluation that consisted in autonomic evaluations ( HRV ) , cardiopulmonary functional capacity evaluation ( 6-minute walk test ) and strength evaluation ( dynamometry ) in addition by the resistance training performed by 24 sessions lasted 60 minutes each one and on a frequency of three times a week . The intensity was determined initially with 60 % of one maximum repetition and was progressively increased in each five sessions until 80 % . RESULTS The HRV temporal and spectral indexes analysis demonstrates improvement of autonomic modulation , with significant statistical increases to sympathetic and parasympathetic components of ANS representing by SDNN , LF and HF . In addition , it was observed significant statistical increases to shoulder abduction and knee flexion strength and functional capacity . CONCLUSION The exclusive resistance training performed was able to positively influence the autonomic modulation ; in addition it promoted benefits on cardiorespiratory functional capacity and strength benefits in individuals with COPD . CLINICAL REHABILITATION IMPACT This study could contribute to clinical and professionals research ers that act with COPD , even though the resistance component of pulmonary rehabilitation presents consensual benefits on several healthy indicators parameters . There is no evidence about the effects on HRV before . Moreover , this study showed , on clinical practice , the HRV uses as an ANS activity on sinus node evaluation and highlights further importance on scientific context Background : Pulmonary rehabilitation ( PR ) has emerged as a recommended st and ard of care in symptomatic COPD . Objectives : We now studied whether PR may affect cardiovascular response to exercise in these patients . Methods : Twenty-seven patients ( 9 females aged 69 ± 8 years ) with moderate-to-severe airflow obstruction admitted to a 9-week PR course performed a pre-to-post evaluation of lung function test and symptom-limited cardiopulmonary exercise test ( CPET ) . Oxygen uptake ( VO2 ) , tidal volume ( VT ) , dyspnea and leg fatigue scores were measured during CPET . Cardiovas-cular response was assessed by means of oxygen pulse ( O2Pulse ) , the oxygen uptake efficiency slope and heart rate recovery at the 1st min . Results : A significant increase in peak VO2 and in all cardiovascular parameters ( p < 0.05 ) was found following PR when compared to baseline . Leg fatigue ( p < 0.05 ) , but not dyspnea , was significantly reduced after PR . When assessed at metabolic and ventilatory iso levels [ % VCO2max and % minute ventilation ( VEmax ) ] , O2Pulse and VT were significantly higher ( p < 0.05 ) at submaximal exercise ( 75 and 50 % of VCO2max and VEmax ) after PR when compared to baseline . VT percent changes at 75 % VCO2max and 75 % VEmax after PR significantly correlated with corresponding changes in O2Pulse ( p < 0.01 ) . Conclusions : In COPD patients , a PR training program improved the cardiovascular response during exercise at submaximal exercise independent of the external workload . This change was associated with an enhanced ventilatory function during exercise BACKGROUND Current literature lacks solid evidence on the improvement of heart rate variability ( HRV ) after exercise training in patients with COPD . OBJECTIVES We aim ed to investigate changes in HRV after two exercise training programs in patients with COPD and to investigate the determinants of these eventual changes . METHODS Forty patients with COPD ( FEV(1 ) 39 ± 13%pred ) were r and omized into high ( n = 20 ) or low ( n = 20 ) intensity exercise training ( 3-month duration ) , and had their HRV assessed by the head-up tilt test before and after either protocol s. Baseline spirometry , level of daily physical activity , exercise capacity , body composition , functional status , health-related quality of life and muscle force were also assessed to investigate the determinants of improvement in HRV after the training program . RESULTS There was a significant improvement in HRV only after the high-intensity protocol ( pre versus post ; SDNN 29 ± 15 ms versus 36 ± 19 ms ; rMSSD 22 ± 14 ms versus 28 ± 22 ms ; p < 0.05 for both ) . Higher values of biceps brachialis strength , time spent walking in daily life and SDNN at baseline were determinants of improvement in HRV after the training program . CONCLUSIONS High-intensity exercise training improves HRV at rest and during orthostatic stimulus in patients with COPD . Better baseline total HRV , muscle force and daily physical activity level are predictors of HRV improvements after the training program BACKGROUND AND OBJECTIVES The present pilot study was undertaken to evaluate the efficacy of an aerobic exercise training ( AET ) program alone or combined with an antihypertensive agent ( irbesartan ) to reduce blood pressure ( BP ) and enhance heart rate variability ( HRV ) in chronic obstructive pulmonary disease patients . METHODS Twenty-one patients were r and omly assigned to a double-blind treatment with exercise and placebo ( n=11 ) or exercise and irbesartan ( n=10 ) . Subjects underwent 24 h BP monitoring and 24 h electrocardiographic recording before and after the 12-week AET . HRV was investigated using three indexes from the power spectral analysis and three indexes calculated from the time domain . The AET program consisted of exercising on a calibrated ergocycle for 30 min three times per week . Five patients in the placebo group were excluded during follow-up because they were not compliant . RESULTS There was no change in 24 h systolic and diastolic BP before ( 130+/-14 mmHg and 70+/-3 mmHg , respectively ) and after ( 128+/-8 mmHg and 70+/-8 mmHg , respectively ) exercise training in the placebo group , whereas in the irbesartan group systolic and diastolic BP decreased from 135+/-9 mmHg and 76+/-9 mmHg to 126+/-12 mmHg and 72+/-8 mmHg , respectively ( P<0.02 ) . There were no changes in HRV parameters in either group . CONCLUSIONS The present study suggests that a 12-week AET program is not associated with a significant reduction in BP or enhancement in HRV , whereas an AET program combined with irbesartan is associated with a reduction in 24 h BP OBJECTIVES Autonomic modulation is adversely impacted in patients with chronic obstructive pulmonary disease ( COPD ) . The purpose of the present investigation is to assess the effects of a 6-week aerobic exercise training program on autonomic modulation of heart rate in patients with COPD . METHODS Forty patients of both sexes with moderate-to-severe COPD were r and omly allocated to aerobic exercise training ( PT , n=20 ) or to usual care ( Control , n=20 ) . The training program consisted of lower and upper limb stretching and 30 min of treadmill exercise , 3 times per week for a 6-week period . Physiological data during symptom-limited exercise testing and the six-minute walk test ( 6MWT ) were assessed . In addition , R-R intervals were obtained at rest and during the 6MWT . Heart rate variability was analyzed by time ( rMSSD and SDNN index ) and frequency domains ( high frequency -- HF , low frequency -- LF and HF/LF ratio ) . RESULTS Peak oxygen consumption significantly improved in the training group only ( p<0.05 ) . Moreover , the training group demonstrated significant improvements ( p<0.05 ) in blood lactate , minute ventilation , dyspnea at peak exercise , sympathetic activity , and parasympathetic activity at rest and during submaximal exercise . Lastly , a positive and significant correlation was found between change in 6MWT distance and rMSSD index ( r=0.65 and p=0.001 ) . CONCLUSIONS Neural control of heart rate , in addition to other clinical ly valuable measures , is positively altered in moderate-severe COPD patients following 6 weeks of aerobic exercise training . The improvement in submaximal performance after exercise training was associated with parasympathetic activity Both interval ( IT ) and continuous ( CT ) exercise training results in an improvement of aerobic capacity in patients with chronic obstructive pulmonary disease ( COPD ) ; however , their effects on cardiac autonomic function remains unclear . The aim of our study was to evaluate the effect of a supervised CT vs IT on autonomic cardiac function in COPD patients BACKGROUND Heart rate recovery ( HRR ) is a marker of vagal tone that is associated with survival , but little is known about the effects of exercise training on HRR in patients with heart failure ( HF ) . METHODS Twenty-four patients with HF were r and omized to a 2-month residential rehabilitation program or to usual care . Symptom-limited exercise testing was performed at baseline and at discharge from the program . Heart rate recovery was expressed as the decline in heart rate from peak exercise through 6 minutes into recovery . In addition , HRR recovery curves were normalized to a range of 1 at peak heart rate and 0 at 6 minutes and adjusted for differences in heart rate reserve , facilitating the comparison of recovery curve shapes between groups . RESULTS Mean peak oxygen uptake and oxygen uptake at the lactate threshold increased 26 % ( P < .05 ) and 39 % ( P < .001 ) , respectively , in the exercise group , whereas neither of these responses changed significantly among controls . Heart rate recovery was significantly more rapid in the exercise group after training ( main effect 12.6 vs 2.6 beat/min in the trained and control groups , respectively , P = .005 ) . The normalized curves showed that the largest improvement in recovery curve shape occurred in the exercise group , but most of the HRR improvement was accounted for by a widening of the difference between peak and resting heart rate . CONCLUSION Exercise training results in a faster HRR in patients with HF . Heart rate recovery , as a simple marker of autonomic function , is an easily acquired response that may be useful for evaluating patient outcomes in cardiac rehabilitation BACKGROUND Exercise is an important part of chronic obstructive pulmonary disease ( COPD ) treatment . However , it is not know about the minimum effective time of physical training that could beneficially modify the cardiac autonomic modulation ( CAM ) and exercise capacity in these patients . AIM To contrast the potential effects of a physical training program ( PTP ) , for 6 versus 12 weeks , on CAM by linear and nonlinear heart rate variability ( HRV ) indices and exercise capacity in COPD patients . DESIGN Prospect i ve r and omized controlled trial . SETTING Outpatient pulmonary rehabilitation . POPULATION Twenty moderate-to-severe COPD patients were r and omly assigned to either a training group ( N.=10 ) or a control group ( N.=10 ) . METHODS HRV at rest and during submaximal test was determined by linear ( rMSSD and SDNN ) and non-linear indices ( SD1 , SD2 and sample entropy [ SE ] ) . In addition , key responses were obtained during cardiopulmonary exercise testing ( CPET ) , the walking distance ( WD ) during the six minute walking test and submaximal constant speed testing ( CST ) . PTP consisted of 30 minutes of aerobic exercise training on a treadmill , 3 times per week at 70 % of CPET peak speed rate . Patients were evaluated on baseline , 6 and 12 weeks . RESULTS Significant improvements in HRV indices , WD , as well as , other physiological responses were observed after 6 weeks of the PTP and maintained until 12 weeks ( P<0.05 ) . However , after 12 weeks , the SD1 index demonstrated an additional improvement compared with 6 weeks ( P<0.05 ) . Peak oxygen uptake and dioxide carbon production improved only after 12 weeks ( P<0.05 ) . Interestingly , the 6th week-baseline delta ( 6th week-baseline ) of WD , SDNN and SE were significantly higher than 12th week-6th week delta ( P<0.05 ) . CONCLUSION These results indicate that beneficial changes on cardiac autonomic modulation in conjunction with improvement in submaximal functional capacity occur in the first 6 weeks of PTP in moderate to severe COPD . CLINICAL REHABILITATION IMPACT Short-term rehabilitation ( 6 weeks ) is an effective sufficient time to beneficially modify important outcomes as cardiac modulation and exercise capacity in COPD patients BACKGROUND Chronic obstructive pulmonary disease ( COPD ) causes an impairment of respiratory function , well reflected by the progressive decrease in forced expiratory volume in 1 second ( FEV1 ) . The only interventions able to slow down the FEV1 decline are smoking cessation and drug treatment . Pulmonary rehabilitation ( PR ) , is cl aim ed to improve exercise tolerance , symptoms and quality of life , but its effects on lung function have been scantly investigated . AIM The aim of this paper was to evaluate , by the study named " FEV1 as an Index of Rehabilitation Success over Time " ( FIRST ) , the effects of PR on lung function in patients with COPD , under drug treatment with inhaled corticosteroids or long-acting β2-agonists and /or tiotropium in various combinations , according to guidelines , during a 3-year period . DESIGN Observational , prospect i ve , with two parallel groups study . SETTING PR setting in an urban hospital . POPULATION Two hundred fifty-seven COPD patients , 190 ( 103 males , mean age 71.1 ± 7.1 years range 57 - 86 years ) underwent PR and 67 ( 49 males , mean age 67.9 ± 7.9 years , range 58 - 79 years ) were treated only with drugs . METHODS Lung function was measured at baseline and at one-year intervals up to 3 years . The postbronchodilator FEV1 was used for statistical analysis . RESULTS In the PR group , FEV1 increased from 1240 mL ( 57.3 % of predicted value ) to 1252.4 mL ( 60.8 % ) after 3 years , whereas in the controls the values were 1367 mL ( 55 % of predicted ) at baseline and 1150 mL ( 51 % ) after 3 years . This difference was statistically significant ( P<0.001 ) . CONCLUSION In patients with COPD on st and ard pharmacotherapy , PR significantly affected the decline of FEV1 over time . CLINICAL REHABILITATION IMPACT The ability to substantially stop the FEV1 decline seems exclusive of PR when added to drug treatment . This finding warrants confirmation from r and omized trials In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Abstract Background : Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease . The effect of the exercise training in heart rate recovery ( HRR ) has not been established in patients with COPD . Objective : To assess the effects of 8-weeks ’ endurance training program on parasympathetic nervous system response measured as heart rate recovery in a sample of moderate-to-severe COPD patients . Methods : We recruited a consecutive sample of patients with COPD c and i date s to participate in a pulmonary rehabilitation program from respiratory outpatient clinics of a tertiary hospital . HRR was calculated , before and after training , as the difference in heart rate between end-exercise and one minute thereafter ( HRR1 ) in a constant-work rate protocol . Results : A total of 73 COPD patients were included : mean ( SD ) age 66 ( 8) years , median ( P25-P75 ) post-bronchodilator FEV1 39 (29–53)% . The prevalence of slow HRR1 ( ≤12 beats ) at baseline was 63 % , and was associated with spirometric severity ( mean FEV1 35 % in slow HRR1 vs 53 in normal HRR1 , p < 0.001 ) . After 8-weeks training , HRR1 improved from mean ( SD ) 10 ( 7 ) to 12 ( 7 ) beats ( p = 0.0127 ) . Multivariate linear regression models showed that the only variable related to post-training HRR1 was pre-training HRR1 ( p < 0.001 ) . Conclusions : These results suggest that training enhances HRR in patients with moderate-to-severe COPD . HRR is an easy tool to evaluate ANS such that it may be a useful clinical marker of parasympathetic nervous system response in patients with COPD |
11,775 | 32,297,973 | NSAIDs seemed slightly more effective than placebo for short-term pain reduction ( moderate certainty ) , disability ( high certainty ) , and global improvement ( low certainty ) , but the magnitude of the effects is small and probably not clinical ly relevant .
There was no clear difference in short-term pain reduction ( low certainty ) when comparing selective COX-2 inhibitors to non-selective NSAIDs .
We found very low evidence of no clear difference in the proportion of participants experiencing adverse events in both the comparison of NSAIDs versus placebo and selective COX-2 inhibitors versus non-selective NSAIDs . | BACKGROUND Acute low back pain ( LBP ) is a common health problem .
Non-steroidal anti-inflammatory drugs ( NSAIDs ) are often used in the treatment of LBP , particularly in people with acute LBP .
In 2008 , a Cochrane Review was published about the efficacy of NSAIDs for LBP ( acute , chronic , and sciatica ) , identifying a small but significant effect in favour of NSAIDs compared to placebo for short-term pain reduction and global improvement in participants with acute LBP .
This is an up date of the previous review , focusing on acute LBP .
OBJECTIVES To assess the effects of NSAIDs compared to placebo and other comparison treatments for acute LBP . | BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review 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 OBJECTIVES This study aim ed to assess analgesia provided by acupuncture , alone or in combination with pharmacotherapy , to patients presenting to emergency departments with acute low back pain , migraine or ankle sprain . DESIGN A pragmatic , multicentre , r and omised , assessor-blinded , equivalence and non-inferiority trial of analgesia , comparing acupuncture alone , acupuncture plus pharmacotherapy , and pharmacotherapy alone for alleviating pain in the emergency department . Setting , participants : Patients presenting to emergency departments in one of four tertiary hospitals in Melbourne with acute low back pain , migraine , or ankle sprain , and with a pain score on a 10-point verbal numerical rating scale ( VNRS ) of at least 4 . MAIN OUTCOME MEASURES The primary outcome measure was pain at one hour ( T1 ) . Clinical ly relevant pain relief was defined as achieving a VNRS score below 4 , and statistically relevant pain relief as a reduction in VNRS score of greater than 2 units . RESULTS 1964 patients were assessed between January 2010 and December 2011 ; 528 patients with acute low back pain ( 270 patients ) , migraine ( 92 ) or ankle sprain ( 166 ) were r and omised to acupuncture alone ( 177 patients ) , acupuncture plus pharmacotherapy ( 178 ) or pharmacotherapy alone ( 173 ) . Equivalence and non-inferiority of treatment groups was found overall and for the low back pain and ankle sprain groups in both intention-to-treat and per protocol ( PP ) analyses , except in the PP equivalence testing of the ankle sprain group . 15.6 % of patients had clinical ly relevant pain relief and 36.9 % had statistically relevant pain relief at T1 ; there were no between-group differences . CONCLUSION The effectiveness of acupuncture in providing acute analgesia for patients with back pain and ankle sprain was comparable with that of pharmacotherapy . Acupuncture is a safe and acceptable form of analgesia , but none of the examined therapies provided optimal acute analgesia . More effective options are needed . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry , ACTRN12609000989246 A double-blind , 18-center , balanced trial of diflunisal vs. cyclobenzaprine HCl vs. these two drugs combined vs. placebo produced complete results from 175 patients . They had sought treatment at the cooperating centers for acute painful spasms of the back within a day or two of trauma or strain . Global results over the 7 to 10 days of observations revealed a clinical ly and statistically significant superiority of the combined therapy by Day 4 ( P=0.006 ) and almost all patients recovered within a week to 10 days . A combination therapy with an effective safe analgesic and a true muscle relaxant for less than a week appears to be an excellent relief measure for acute back problems Pharmacological therapy of back pain with analgesics and anti-inflammatory drugs is frequently associated with adverse effects , particularly in the elderly . Aim of this study was to compare mesotherapic versus conventional systemic administration of nonsteroidal anti-inflammatory drugs ( NSAIDs ) and corticosteroids in patients with acute low back pain . Eighty-four patients were r and omized to receive anti-inflammatory therapy according to the following protocol s : ( a ) mesotherapy group received the 1st and 4th day 2 % lidocaine ( 1 mL ) + ketoprofen 160 mg ( 1 mL ) + methylprednisolone 40 mg ( 1 mL ) , then on 7th , 10th , and 13th day , 2 % lidocaine ( 1 mL ) + ketoprofen 160 mg ( 1 mL ) + methylprednisolone 20 mg ( 1 mL ) ( b ) conventional therapy group received ketoprofen 80 mg × 2/die and esomeprazole 20 mg/die orally for 12 days , methylprednisolone 40 mg/die intramuscularly for 4 days , followed by methylprednisolone 20 mg/die for 3 days , and thereafter , methylprednisolone 20 mg/die at alternate days . Pain intensity and functional disability were assessed at baseline ( T0 ) , at the end of treatment ( T1 ) , and 6 months thereafter ( T2 ) by using visual analogic scale ( VAS ) and Rol and -Morris disability question naire ( RMDQ ) . In both groups , VAS and RMDQ values were significantly reduced at the end of drug treatment and after 6 months , in comparison with baseline . No significant differences were found between the two groups . This suggests that mesotherapy may be a valid alternative to conventional therapy in the treatment of acute low back pain with corticosteroids and NSAIDs Study objective : In US emergency departments ( EDs ) , patients with low back pain are often treated with nonsteroidal anti‐inflammatory drugs and muscle relaxants . We compare functional outcomes among patients r and omized to a 1‐week course of naproxen+placebo versus naproxen+orphenadrine or naproxen+methocarbamol . Methods : This was a r and omized , double‐blind , comparative effectiveness trial conducted in 2 urban EDs . Patients presenting with acute , nontraumatic , nonradicular low back pain were enrolled . The primary outcome was improvement on the Rol and ‐Morris Disability Question naire ( RMDQ ) between ED discharge and 1 week later . All patients were given 14 tablets of naproxen 500 mg , to be used twice a day , as needed for low back pain . Additionally , patients were r and omized to receive a 1‐week supply of orphenadrine 100 mg , to be used twice a day as needed , methocarbamol 750 mg , to be used as 1 or 2 tablets 3 times per day as needed , or placebo . All patients received a st and ardized 10‐minute low back pain educational session before discharge . Results : Two hundred forty patients were r and omized . Baseline demographic characteristics were comparable . The mean RMDQ score of patients r and omized to naproxen+placebo improved by 10.9 points ( 95 % confidence interval [ CI ] 8.9 to 12.9 ) . The mean RMDQ score of patients r and omized to naproxen+orphenadrine improved by 9.4 points ( 95 % CI 7.4 to 11.5 ) . The mean RMDQ score of patients r and omized to naproxen+methocarbamol improved by 8.1 points ( 95 % CI 6.1 to 10.1 ) . None of the between‐group differences surpassed our threshold for clinical significance . Adverse events were reported by 17 % ( 95 % CI 10 % to 28 % ) of placebo patients , 9 % ( 95 % CI 4 % to 19 % ) of orphenadrine patients , and 19 % ( 95 % CI 11 % to 29 % ) of methocarbamol patients . Conclusion : Among ED patients with acute , nontraumatic , nonradicular low back pain , combining naproxen with either orphenadrine or methocarbamol did not improve functional outcomes compared with naproxen+placebo BACKGROUND Current worldwide clinical practice guidelines recommend acetaminophen as the first option for the treatment of acute low back pain . However , there is no concrete evidence regarding whether acetaminophen or nonsteroidal anti-inflammatory drugs ( NSAIDs ) is more effective for treating acute low back pain ( LBP ) in Japan . The present study aim ed to investigate whether acetaminophen treatment for acute musculoskeletal pain was comparable with loxoprofen ( a traditional NSAID in Japan ) treatment . METHODS Of the 140 patients with acute LBP who visited out-patient hospitals , 127 were considered eligible and were r and omly allocated to a group taking acetaminophen or one taking loxoprofen . As primary outcome measure , pain intensity was measured using a 0 - 10-numeric rating scale ( NRS ) . Moreover , pain disability , pain catastrophizing , anxiety , depression , and quality of life , as well as adverse events , were assessed as secondary outcomes . The primary outcome was tested with a noninferiority margin ( 0.84 on changes in pain-NRS ) , and the secondary outcomes were compared using conventional statistical methods at week 2 and week 4 . RESULTS Seventy patients completed the study ( acetaminophen : 35 , loxoprofen : 35 ) . The dropout rates showed no significant difference between the two medication-groups . We found that the mean differences of changes in pain-NRS from baseline to week 2 or 4 between the two medication groups were not statistically beyond the noninferiority margin ( mean [ 95 % confidence interval ] : -0.51 [ -1.70 , 0.67 ] , at week 2 and -0.80 [ -2.08 , 0.48 ] at week 4 ) . There were no consistent differences between the two medication groups in terms of secondary outcomes . CONCLUSIONS The results suggest that acetaminophen has comparable analgesic effects on acute LBP , based on at least a noninferiority margin , compared with loxoprofen at 4 weeks . Acetaminophen seems to be a reasonable first-line option for patients with acute LBP in Japan Background Low back pain is common and associated with a considerable burden to patients and society . There is uncertainty regarding the relative benefit of paracetamol and diclofenac and regarding the additional effect of pain medication compared with advice only in patients with acute low back pain . This trial will assess the effectiveness of paracetamol , diclofenac and placebo for acute low back pain over a period of 4 weeks . Furthermore , this trial will assess the additional effectiveness of paracetamol , diclofenac and placebo compared with advice only for acute low back pain over a period of 4 weeks . Methods The PACE Plus trial is a multi-center , placebo-blinded , superiority r and omized controlled trial in primary care , with a follow-up of 12 weeks . Patients with acute low back pain aged 18–60 years presenting in general practice will be included . Patients are r and omized into four groups : 1 ) Advice only ( usual care conforming with the clinical guideline of the Dutch College of General Practitioners ) ; 2 ) Advice and paracetamol ; 3 ) Advice and diclofenac ; 4 ) Advice and placebo . The primary outcome is low back pain intensity measured with a numerical rating scale ( 0–10 ) . Secondary outcomes include compliance to treatment , disability , perceived recovery , costs , adverse reactions , satisfaction , sleep quality , co- interventions and adequacy of blinding . Between group differences for low back pain intensity will be evaluated using a repeated measurements analysis with linear effects models . An economic evaluation will be performed using a cost-effectiveness analysis with low back pain intensity and a cost-utility analysis with quality of life . Explorative analyses will be performed to assess effect modification by predefined variables . Ethical approval has been granted . Trial results will be released to an appropriate peer-viewed journal . Discussion This paper presents the design of the PACE Plus trial : a multi-center , placebo-blinded , superiority r and omized controlled trial in primary care that will assess the effectiveness of advice only , paracetamol , diclofenac and placebo for acute low back pain . Trial registration Dutch Trial Registration NTR6089 , registered September 14th , 2016 . Protocol : Version 4 , June 2016 OBJECTIVE to estimate whether combination of ibuprofen and paracetamol is more effective than ibuprofen in monotherapy , in the treatment of acute low back pain . METHODS 80 adult patients with acute low back pain were r and omized into two subgroups . In the first subgroup , 40 patients were treated with ibuprofen 400 mg three times a day ( TID ) , whilst patients in the second subgroup ( n=40 ) were treated with a fixed-dose combination tablet of ibuprofen 200 mg plus paracetamol 325 mg TID , for three consecutive days . Patients were followed for another 7 days . Efficacy and tolerability of both treatment options was assessed . RESULTS A statistically significant decrease in pain intensity , assessed using a visual analogue scale ( p<0.001 ) , as well as the 5-point Likert scale , was noticed in both subgroups of patients . However , intensity of pain on Day 4 was significantly lower in patients treated with combined therapy ( t=2.05 , p=0.045 ) . Considerable improvement in mobility of the lumbar spine was noticed in both subgroup of patients ( p<0.001 ) , but at the end of the follow up period , finger-to-floor distance was lower in patients on combined therapy ( 4.7 cm vs. 8.3 cm , t=2.27 , p=0.03 ) . Improvement of functional ability on Day 4 and Day 10 was significant , regardless of treatment ( p<0.001 ) . One patient on combined therapy and two patients on ibuprofen monotherapy reported minor gastric intolerability . CONCLUSION compared to ibuprofen monotherapy , combination of ibuprofen and paracetamol may provide faster and longer analgesia in patients with acute low back pain , with equally favorable effect on mobility and functional ability and similar tolerability BACKGROUND Low back pain ( LBP ) is a common and costly illness . This r and omized , double-blind , placebo-controlled , cross-over study tested the hypothesis that periradicular injections of meloxicam would reduce LBP and improve physical activity compared to a saline injection at 3 months follow-up . METHODS After IRB approval , 80 consenting patients suffering LBP of < 6 months duration were r and omly assigned to the control ( C-group , N.=40 , receiving 10 mL of saline ) or the meloxicam ( M-group , N.=40 , receiving 10 mg in 10 mL saline ) . If the pain Numeric Rating Score ( NRS ) at 24 hours remained > 50 % of the pretreatment score , the patient was crossed-over to the other group . A successful treatment was NRS<3 at 3 months follow-up . Secondary outcome measures which were assessed included work-absence , physical-assistance , physical-activities limitations and pain-related insomnia . RESULTS The baseline NRS was 9.3 ( 95 % CI : 8.9 - 9.7 ) in the C-group and 9.2 ( 95 % CI : 8.8 - 9.6 ) in the M-group . At the 24 hours follow-up after the initial treatment , the mean NRS was 6.3 ( 95 % CI : 5.4 - 7.2 ) in the C-group vs. 3.5 ( 95 % CI : 2.6 - 4.4 ) in the M-group ( P<0.05 ) . The number of cross-over cases was significantly higher in the C-group ( N.=31 , 77.5 % vs. N.=5 , 12.5 % , P<0.001 ) . At the 3 months follow-up , 66 patients ( 35 + 31 ) were allocated in the M-group and 54 ( 82 % ) reported NRS Score <3 , while only 14 ( 9 + 5 ) patients remained in the C-group and eight patients had NRS<3 . CONCLUSIONS Periradicular injection of meloxicam is an effective analgesic treatment for acute/subacute LBP . This novel use of meloxicam also leads to an improvement in the level of physical activity at the 3-month follow-up Abstract The efficacy and tolerability of aceclofenac was compared with diclofenac resinate in a double-blind , multicentre r and omised study in patients with acute low back pain suffering from degenerative spinal disorders . The study included 227 patients r and omised to receive either aceclofenac 2 × 100 mg daily or diclofenac resinate 2 × 75 mg daily for up to 10 days . The primary objective was to demonstrate the clinical non-inferiority of the analgesic efficacy of aceclofenac compared with diclofenac resinate , as assessed by changes from baseline in the visual analogue scale ( 0–100 mm ) pain score , at rest and at visit 3 ( final visit on day 's 8–10 ) . Secondary objectives included the time to early cure ( resolution of pain ) and global assessment of tolerability . Mean change in pain score at rest , and as visit 3 , compared with baseline , was 61.6 mm ( SD 24.5 ) for the aceclofenac group ( n = 100 ) and 57.3 mm ( SD 22.8 ) for the diclofenac resinate group ( n = 105 ) in the per- protocol population . Similar changes were observed in the intention-to-treat population . Between-group differences of 4.5 mm and 5.5 mm for the per- protocol and intention-to-treat population s , respectively , demonstrated clinical non-inferiority of aceclofenac compared with diclofenac resinate . Furthermore , there was evidence for superiority of aceclofenac over diclofenac resinate in terms of statistical significance , as the one-sided 97.5 % confidence interval was above −10 mm and 0 mm . In the intention-to treat population , a total of six aceclofenac-treated patients discontinued their medication owing to early cure , compared with only one patient receiving diclofenac resinate . Seventeen aceclofenac- ( 14.9 % ) , and 18 diclofenac resinate-treated patients ( 15.9 % ) reported at least one adverse event . However , the total number of adverse events reported was lower in patients receiving aceclofenac ( 22 versus 31 in the diclofenac resinate group ) . In conclusion , non-inferiority of the analgesic efficacy of aceclofenac compared with diclofenac resinate was demonstrated in patients with localised , uncomplicated acute lumbosacral pain . For the reduction in pain levels from baseline there was also evidence for superiority of aceclofenac compared with diclofenac resinate in terms of statistical significance , although this difference was not considered clinical ly relevant . The results also showed a trend towards a better safety and tolerability profile of aceclofenac over diclofenac resinate from a clinical point of view This study reports on 105 patients with acute low-back pain given tizanidine ( 4 mg three times daily ) plus ibuprofen ( 400 mg three times daily ) or placebo plus ibuprofen ( 400 mg three times daily ) . Patients assessed their pain using visual analogue scales in a daily diary and the doctor assessed their condition at baseline and on days 3 and 7 . Both groups were treated effectively , but earlier improvement occurred in patients given tizanidine/ibuprofen , particularly regarding pain at night and at rest . Doctors assessed the helpfulness of treatment : tizanidine/ibuprofen was significantly better than placebo/ibuprofen at day 3 ( P = 0.05 ) . Significant differences between treatments in favour of tizanidine/ibuprofen occurred in patients with moderate and severe pain at night ( P<0.05 ) , at rest ( P<0.05 ) and those with moderate or severe sciatica ( P<0.05 ) . Significantly more patients given placebo/ibuprofen had gastro-intestinal side-effects compared with tizanidine/ibuprofen ( P = 0.002 ) . This supports previous work in animals showing that tizanidine mediates gastric mucosal protection against anti-inflammatory drugs . More patients given tizanidine/ibuprofen suffered drowsiness and other central nervous system effects ( P = 0.025 ) . In patients with severe acute low-back pain , however , some sedation and bed rest is advantageous . This study shows that tizanidine/ibuprofen is more effective in the treatment of moderate or severe acute low-back pain than placebo and ibuprofen alone Background Acute low back pain is a common condition result ing in pain and disability . Current national and international guidelines advocate general practitioner care including advice and paracetamol ( 4 g daily in otherwise well adults ) as the first line of care for people with acute low back pain . Non-steroidal anti-inflammatory drugs ( NSAIDs ) and spinal manipulative therapy ( SMT ) are advocated in many guidelines as second line management options for patients with acute low back pain who are not recovering . No studies have explored the role of NSAIDs and /or SMT in addition to first line management for acute low back pain . The primary aim of this study is to investigate if NSAIDs and /or SMT in addition to general practitioner advice and paracetamol results in shorter recovery times for patients with acute low back pain . The secondary aims of the study are to evaluate whether the addition of SMT and /or NSAIDs influences pain , disability and global perceived effect at 1 , 2 , 4 and 12 weeks after onset of therapy for patients with significant acute low back pain . Methods / design This paper presents the rationale and design of a r and omised controlled trial examining the addition of NSAIDs and /or SMT in 240 people who present to their general practitioner with significant acute low back pain Stopping r and omized trials early because of an apparent benefit is a growing phenomenon . A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) . To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment . If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ? In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances . If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change . Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical . We use this framework to identify and assess the ethical issues raised by stopping trials early because of apparent benefit ( Table ) . Table . Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading . This requires application of scientific procedures that yield valid and reliable data and thus minimize both systematic and r and om error . A systematic review of r and omized trials stopped early for apparent benefit ( 1 ) found that many of the trials yielded implausibly large treatment effects ; the median relative risk was 0.53 . Apparent large treatment effects occurred much more frequently when trials accrued only a small number of events . The odds of a treatment effect larger than the overall median relative risk of 0.53 was 28 times greater ( 95 % CI , 11 to 73 ) among trials in which fewer than the median of 66 events accrued than among trials in which more events accrued . These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects . The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment . For example , a trial of vitamin E supplementation in premature newborns that was stopped early because of an apparent reduction in intracranial hemorrhage ( 4 ) failed to detect the increase in sepsis associated with vitamin E supplementation that subsequent trials identified ( 5 ) . Social or Scientific Value and Favorable RiskBenefit Ratio It is underst and able that investigators focus their ethical obligations on research participants . Such focus , however , risks neglecting obligations to society . The tendency of truncated trials to overestimate the effect of a treatment on the end point that result ed in trial truncation and to yield insufficient data about other important outcomes endangers the wider community to whom the results will be applied ( 6 ) . On review ing the results of a truncated trial , astute clinicians might appropriately conclude that the benefits of the intervention remain uncertain . However , less skeptical clinicians might assume that the results are true and inappropriately expose patients to the intervention and its unknown harms . Consider the results of a trial in which the investigators continued to enroll patients even though prespecified criteria for early stopping were met . Two interim analyses of a r and omized trial of 5 versus 4 courses of chemotherapy in patients with acute myeloid leukemia ( 7 ) found apparent large benefits to the 5-course regimen ( relative odds reduction of 53 % [ CI , 23 % to 71 % ; P= 0.003 ] in the first analysis and 45 % [ CI , 20 % to 62 % ; P= 0.0002 ] in the second analysis ) . Finding these results too good to be true , the data monitoring committee recommended continuing the trial , which ultimately showed a trend in favor of the 4-course regimen . Had the investigators terminated the trial in accordance with their stopping rule , subsequent patients with leukemia may have experienced the toxicity of an additional course of chemotherapy without benefit . Harm result ing from the misleading findings of truncated trials can be compounded if the findings influence the recommendations of clinical practice guideline panels . Investigators conducting a trial that involved patients undergoing vascular surgery ( 8) stopped the trial early when 2 of 53 patients r and omly assigned to receive the -blocker bisoprolol and 18 of 59 control patients had major cardiovascular events ( relative risk reduction , 90 % [ CI , 59 % to 98 % ] ) . These results contributed to recommendations by the American Heart Association and the American College of Cardiology favoring administration of -blockers to patients with cardiac risk factors who were undergoing noncardiac surgery ( 9 ) . However , these results contradict those of 2 much larger subsequently published trials , neither of which suggested that -blockers reduce cardiac risk in patients undergoing noncardiac surgery ( 10 , 11 ) . Further social detriment may occur when clinicians compromise the ability of others to conduct more definitive studies by placing undue confidence in the results of a truncated trial . Investigators ( including 2 contributors to this article ) who obtained funding for a trial of -blockers in noncardiac surgery with an enrollment target of 10000 patients ( 12 ) faced challenges in persuading clinicians that the question remained unanswered . Participant Consent and Respect for Participants Key prerequisites for informed consent include the participant 's decision-making capacity and voluntariness and whether he or she had received adequate information to decide that participation in the research was in alignment with his or her values and goals . However , informed consent is not a single event , but it is an ongoing collaboration between participants and investigators . When important changes occur during a trial , investigators should inform participants of the changes . One justification for stopping a trial early for benefit is to inform study participants of the preliminary results and offer them the superior treatment . According to this argument , uncertainty about the relative merits of alternative interventions ( equipoise ) has been lost and informed clinicians and patients will overwhelmingly choose the superior treatment ( 13 ) . However , as we have pointed out , the astute clinician or patient may remain skeptical about a treatment 's apparent benefits if the findings come from a truncated trial . Unfortunately , many clinicians and even more patients probably will not have the knowledge and underst and ing to appropriately interpret the results . Disclosing interim results to study participants may therefore prove misleading . Furthermore , if investigators were to continue a trial after informing patients of the interim results , patients would be unblinded and may cross over or leave the trial . These behaviors create problems in interpreting trial results by further weakening inferences about the efficacy and safety of the intervention and compromising the ethical requirement of scientific validity . Finally , stopping a trial early does not guarantee that current and potential trial participants will receive the apparently beneficial treatment ( assuming that one believes they should ) . Studies of dissemination of new treatments reveal that long delays , such as those between reports of r and omized trials and recommendations of experts in review articles and textbooks , are common ( 14 ) . Continuing a 2-group trial gives participants at least a 50 % chance of receiving the experimental treatment , whereas if the trial is stopped early , the probability that participants will receive the treatment due to rapid dissemination is likely to be considerably less than 50 % . Independent Review Trials may have stopping rules that allow early termination because of genuine ( although misguided ) ethical concerns . However , investigators , trial sponsors , journals , and patients may all have additional motives for stopping trials early for apparent benefit . For example , truncated trials that report a large treatment effect tend to be published in the most prestigious medical journals ( 1 ) , which enhances the careers of the investigators and increases the likelihood that they will receive grants . Funding agencies have an interest in stopping trials early to minimize research costs . Pharmaceutical and for-profit sources that financially support trials are interested not only in controlling costs but also in the publicity and market share that result from reporting a trial stopped early for apparent benefit . Medical journals are interested in these trials because of publicity and citations , which result in increased journal impact factor , prestige , and advertising revenue . And patients and their advocates are motivated to stop a trial early when the experimental intervention is promising in order to hasten delivery of the intervention to clinical practice . All of these motives may affect investigators ' decisions and encourage an inappropriately early stop to a trial . These considerations m and ate that institutional review boards and data monitoring committees underst and the principles outlined in this article and insist on appropriate st and ards for stopping a trial early for apparent benefit to maintain the ethical integrity of clinical trials . Two hundred and sixty patients with lumbago or sciatic pain participated in a multicenter observer-blind r and omized trial to compare the efficacy and tolerability of dipyrone 2.5 g , diclofenac 75 mg , and placebo administered as an intramuscular injection once daily for the duration of one to two days . The effectiveness of the test treatments in relieving sciatic pain was measured by a visual analog scale ( VAS ) before and 30 minutes , 1 , 2 , 3 , 6 and 24 hours after each injection . In addition , the patient 's general well-being was measured on a 5-point rating scale on day 0 , 1 and 2 . At the end of the trial , the patients evaluated the overall efficacy of the study drugs on a 5-point rating scale . Minimal finger-toe distance was measured every day of the trial . Pain intensity on VAS ( primary endpoint ) showed a significantly greater reduction with dipyrone than with diclofenac or placebo between 1 and 6 hours after application ( p < 0.01 ) and at the end of the trial ( after 48 hours ) . Improvement in general well-being and minimal finger-toe distance was greatest in the dipyrone group . 59 % of the patients with dipyrone assessed the overall efficacy as " excellent " or " very good " , compared with 30 % with diclofenac , and 18 % with placebo . Adverse reactions were reported in only 7 patients ( 3 % ) , 4 ( 5 % ) in the dipyrone , 1 ( 1 % ) in the diclofenac , and 2 ( 2 % ) in the placebo group To study the safety and efficacy of a new medical food ( Theramine ) in the treatment of low back pain , we performed a 28-day double-blind r and omized controlled trial in 129 patients . Back pain was present for at least 6 weeks and was not mild . Patients were r and omly assigned to receive medical food alone ( n = 43 ) , naproxen alone ( 250 mg/d , n = 42 ) , or both medical food and naproxen ( n = 44 ) . All patients were assessed by using Rol and –Morris Disability Question naire , Oswestry Low Back Pain Scale , Visual Analog Scale Evaluation and laboratory analysis performed at baseline and at 28 days for assessing the safety and impact on inflammatory markers , which included complete blood counts , C-Reactive protein ( CRP ) , and liver function ( alkaline phosphatase , aspartate transaminase , and alanine transaminase ) . At baseline , there were no statistically significant differences in low back pain when assessed by Rol and –Morris function or Oswestry assessment s nor were there differences in the blood indices of inflammation . At day 28 , both the medical food group and combined therapy group ( medical food with naproxen ) were statistically significantly superior to the naproxen-alone group ( P < 0.05 ) . The medical food and naproxen group showed functional improvement when compared to the naproxen-alone group . The naproxen-alone group showed significant elevations in CRP , alanine transaminase , and aspartate transaminase when compared with the other groups . Medical food alone or with naproxen showed no significant change in liver function tests or CRP , with medical food potentially mitigating the effects seen with naproxen alone . The medical food ( Theramine ) appeared to be effective in relieving back pain without causing any significant side effects and may provide a safe alternative to presently available therapies A double-blind trial of azapropazone ( 300 mg . 4-times daily ) and ketoprofen ( 50 mg . 4-times daily ) was carried out in 50 patients with acute backache sufficiently severe to necessitate hospital admission . Of 39 patients who completed the full 3-weeks ' study period , 18 preferred azapropazone therapy , 10 preferred ketoprofen , and 11 showed either preference for the intermediate placebo period or no preference at all . Ten patients suffered from sufficiently severe side-effects with ketoprofen to necessitate their withdrawal from the trial . There were no similar episodes of withdrawal occurring during the azapropazone period & NA ; Motion style acupuncture treatment ( MSAT ) was more effective for pain relief and functional recovery than diclofenac injection in acute low back pain patients with disability . & NA ; Review s of the efficacy of acupuncture as a treatment for acute low back pain ( aLBP ) have shown that there is insufficient evidence for its effect and that more research is needed . Motion style acupuncture treatment ( MSAT ) is novel in that it requires a part of the patient ’s body to move passively or actively while acupuncture needles are retained . A multicenter , r and omized , comparative effectiveness trial was conducted to evaluate the effects of MSAT in aLBP with severe disability . A total of 58 aLBP patients with severe functional disability ( defined per Oswestry Disability Index [ ODI ] ≥60 % ) were recruited and assigned r and omly to receive 1 session of either conventional diclofenac injection ( n = 29 ) or MSAT ( n = 29 ) . The primary outcome measured improvement in LBP using the 10‐point numerical rating scale of LBP , and the secondary outcome assessed disability using the Oswestry Disability Index at 30 minutes and at 2 , 4 , and 24 weeks after treatment . Analyses were by intention to treat . The numerical rating scale of the MSAT group decreased 3.12 ( 95 % confidence interval = 2.26 , 3.98 ; P < .0001 ) more than that of the injection group and the Oswestry Disability Index of the MSAT group decreased 32.95 % ( 95 % confidence interval = 26.88 , 39.03 ; P < .0001 ) more than that of the injection group , respectively . The difference between the 2 groups maintained statistical significance at 2 and 4 weeks after treatment . These results suggest that MSAT has positive effects on immediate pain relief and the functional recovery of aLBP patients with severe disability 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 BACKGROUND Two generic bioequivalent copies of the same drug sometimes do not achieve therapeutic equivalence . This may produce adverse events in clinical practice if the therapeutic index of that drug is narrow . OBJECTIVE To compare the efficacy and safety of two generic copies of nimesulide Nimulid ( N ) and Tenaprost ( T ) . METHODS 60 out- patients with symptomatic low back pain or knee osteoarthritis were r and omized to take T or N ( 100 mg 2 x/day for 20 days ) in a prospect i ve double-blinded r and omized phase four clinical trial conducted at the Institute of Rheumatology , Bel grade , Serbia . Pain was evaluated by VAS . Paravertebral muscle spasm ( PVM ) , sagittal mobility , and the Lasegue 's test ( LT ) were estimated in low back pain . In knee osteoarthritis , knee circumference , motion , and knee tendons sensitivity ( KTS ) to palpation were assessed . Adverse events reported by the patients , or observed by the investigators were recorded . RESULTS T and N significantly reduced pain levels in patients with low back pain and knee osteoarthritis ( p<0.001 ) as well as knee circumference and KTS to palpation ( p<0.05 ) . Compared to N , T showed slightly better effects on the Lequesne functional index ( p<0.05 ) and PVM spasm in patients with lower back pain , but that was not of clinical relevance . Tolerability of T and N was good . CONCLUSION T and N are equally effective and safe forms of nimesulide for pain management in low back pain and knee osteoarthritis . Price per daily dose is a relevant parameter for making a choice . However , regulations regarding drug bioequivalence criteria should be met for drug marketing authorization su bmi ssion Background Acupuncture is widely-used to treat patients with low back pain , despite insufficient evidence of the technique 's efficacy for acute back pain . Motion style acupuncture treatment ( MSAT ) is a non-traditional acupuncture treatment requiring a patient to exercise while receiving acupuncture . In Korea , MSAT is used to reduce musculoskeletal pain and improve functional status . The study aims to evaluate the effect of MSAT on acute low back pain with severe disability . Methods / Design This study is a multicenter , r and omized , active-controlled trial with two parallel arms . Participants with acute low back pain and severe functional disability , defined as an Oswestry Disability Index ( ODI ) value > 60 % , will be r and omly allocated to the acupuncture group and the nonsteroidal anti-inflammatory drug ( NSAID ) injection group . The acupuncture group will receive MSAT and the NSAID injection group will receive an intramuscular injection of diclofenac . All procedures will be limited to one session and the symptoms before and after treatment will be measured by assessors blinded to treatment allocation . The primary outcome will be measured at 30 minutes after treatment using the numerical rating scale ( NRS ) of low back pain while the patient is moving . Secondary outcomes will be measured at 30 minutes after treatment using the NRS of leg pain , ODI , patient global impression of change , range of motion ( ROM ) of the lumbar spine , and degrees of straight leg raising ( SLR ) . Post-treatment follow-up will be performed to measure primary and secondary outcomes with the exception of ROM and SLR at 2 , 4 , and 24 weeks after treatment . Discussion The results of this trial will be discussed . Trial Registration Clinical Trial.gov Study objective The objective of this study was to determine the analgesic efficacy and safety of intravenous , single-dose paracetamol versus dexketoprofen versus morphine in patients presenting with mechanical low back pain ( LBP ) to the emergency department ( ED ) . Methods This r and omised double-blind study compared the efficacy of intravenous 1 gm paracetamol , 50 mg dexketoprofen and 0.1 mg/kg morphine in patients with acute mechanical LBP . Visual analogue scale ( VAS ) was used for pain measurement at baseline , after 15 and after 30 min . Results A total of 874 patients were eligible for the study , and 137 of them were included in the final analysis : 46 patients from the paracetamol group , 46 patients in the dexketoprofen group and 45 patients in the morphine group . The mean age of study subjects was 31.5±9.5 years , and 60.6 % ( n=83 ) of them were men . The median reduction in VAS score at the 30th minute for the paracetamol group was 65 mm ( 95 % CI 58 to 72 ) , 67 mm ( 95 % CI 60 to 73 ) for the morphine group and 58 mm ( 95 % CI 50 to 64 ) for the dexketoprophen group . Although morphine was not superior to paracetamol at 30 min ( difference : 3.8±4.9 ( 95 % CI −6 to 14 ) , the difference between morphine and dexketoprofen in reducing pain was 11.2±4.7 ( 95 % CI 2 to 21 ) . At least one adverse effect occurred in 8.7 % ( n=4 ) of the cases in the paracetamol group , 15.5 % ( n=7 ) of the morphine group , and 8.7 % ( n=4 ) of the dexketoprophen group ( p=0.482 ) . Conclusions Intravenous paracetamol , dexketoprofen and morphine are not superior to each other for the treatment of mechanical LBP in ED Study Design . A r and omized , double-blinded , placebo-controlled , parallel trial with 3 arms . Objective . To investigate in acute nonspecific low back pain ( LBP ) the effectiveness of spinal high-velocity low-amplitude ( HVLA ) manipulation compared with the nonsteroidal anti-inflammatory drug diclofenac and with placebo . Summary of Background Data . LBP is an important economical factor in all industrialized countries . Few studies have evaluated the effectiveness of spinal manipulation in comparison to nonsteroidal anti-inflammatory drugs or placebo regarding satisfaction and function of the patient , off-work time , and rescue medication . Methods . A total of 101 patients with acute LBP ( for < 48 hr ) were recruited from 5 outpatient practice s , exclusion criteria were numerous and strict . The subjects were r and omized to 3 groups : ( 1 ) spinal manipulation and placebo-diclofenac ; ( 2 ) sham manipulation and diclofenac ; ( 3 ) sham manipulation and placebo-diclofenac . Outcomes registered by a second and blinded investigator included self-rated physical disability , function ( SF-12 ) , off-work time , and rescue medication between baseline and 12 weeks after r and omization . Results . Thirty-seven subjects received spinal manipulation , 38 diclofenac , and 25 no active treatment . The placebo group with a high number of dropouts for unsustainable pain was closed praecox . Comparing the 2 active arms with the placebo group the intervention groups were significantly superior to the control group . Ninety subjects were analyzed in the collective intention to treat . Comparing the 2 intervention groups , the manipulation group was significantly better than the diclofenac group ( Mann-Whitney test : P = 0.0134 ) . No adverse effects or harm was registered . Conclusion . In a subgroup of patients with acute nonspecific LBP , spinal manipulation was significantly better than nonsteroidal anti-inflammatory drug diclofenac and clinical ly superior to placebo Pain syndromes of the lumbar spine are one of the main problems in orthopedic practice . The therapeutic effect of NSAIDs is not subject to doubt in this connection . But considering that the application of NSAIDs is frequently associated with side effects , a reduction of dosage would be to the patient 's benefit . Clinical studies have shown that concomitant treatment with vitamins B1 , B6 , B12 and diclofenac leads to a more efficient pain relief than treatment using diclofenac alone and thus provides the possibility of saving NSAIDs . This clinical trial was carried out in order to determine whether these results can also be achieved when a reduced dosage of diclofenac ( 75 mg daily ) is used . 123 patients with acute pain syndromes of the lumbar spine were treated with either B-vitamins and diclofenac or diclofenac alone for a maximum of 7 days . There was the option to terminate therapy in the trial after 3 - 4 days in the case of total pain relief . 45 patients could stop the treatment due to remission of symptoms . 30 patients belonged to the combination therapy group , the other 15 took diclofenac alone ; this difference is statistically significant ( p less than 0.05 ) . All parameters concerning pain relief and movement of the vertebral column showed statistically significant differences in favour of the B-vitamin-diclofenac-combination , too . The results document the positive influence of B-vitamins on painful vertebral syndromes and indicate that B-vitamins contribute to saving of NSAIDs by shortening the treatment time and reducing daily NSAID-dosage A short-term double-blind sequential trial of indomethacin against placebo in the treatment of low back pain , with and without nerve root pain such as sciatica , showed that indomethacin was significantly more effective than placebo in the group with nerve root pain . On the other h and , no difference was found between the treatments in the patients with uncomplicated low back pain . This difference may result from an effect of indomethacin on the inflammatory process around the nerve root which has been shown to be present when this is compressed Several clinical trials have shown that the duration of treatment of painful vertebral syndromes can be shortened by using a combination of vitamins B1 , B6 , B12 and diclofenac instead of diclofenac . In addition , a more efficient pain relief could be achieved by the combination therapy . In order to confirm these results , we compared the clinical efficacy of diclofenac ( 25 mg ) and a combination preparation with diclofenac ( 25 mg ) plus vitamins B1 ( thiamine nitrate 50 mg ) , B6 ( pyridoxine hydrochloride 50 mg ) and B12 ( cyanocobalamin 0.25 mg ) in a multicentric r and omized double-blind study including 418 patients . All patients received 3 x 2 capsules daily for a maximum of 2 weeks . In case of total pain relief , therapy should be discontinued after one week . Data of 376 patients could be evaluated . 53 out of 184 patients receiving the combination and 48 out of 192 patients treated with diclofenac alone could stop therapy due to sufficient pain relief after one week . The evaluation of the " Hoppe Pain Question naire " and the data concerning pain intensity also revealed better results for the combination preparation . The differences in favour of the B-vitamin-diclofenac-combination were statistically significant in patients with severe pain at the beginning of therapy . Considering undesirable side-effects ( symptoms in 70 out of 418 patients ) there were no significant differences between the two medications . This clinical trial provides further evidence that the combination therapy with diclofenac plus B-vitamins is more effective than diclofenac alone for the treatment of painful vertebral syndromes Objective To compare the efficacy of valdecoxib 40 mg q.d . ( with a second dose on day 1 ) with diclofenac 75 mg b.i.d . in the treatment of acute low back pain . Methods This was a multicenter , r and omized , double-blind study . Patients with acute low back pain , class 1a or 2a ( Quebec Task Force ) , with a visual analog scale score ≥50 mm ( on a 100-mm scale ) and moderate to severe pain on a categorical scale , were r and omized to valdecoxib 40 mg q.d . ( with a second dose on day 1 ) or diclofenac 75 mg b.i.d . for 7 days ( 170 patients per group ) . The primary efficacy end point was change in pain intensity ( visual analog scale , mm ) from baseline to day 3 for the per- protocol population . Results Least squares mean reductions in pain intensity from baseline to day 3 were similar for valdecoxib ( −42.02 mm ) and diclofenac ( −41.43 mm ) . Valdecoxib was comparable to diclofenac as the lower limit of the 95 % confidence interval of the estimated difference ( 0.59 mm ; 95 % confidence interval , −3.40 to 4.59 mm ) was within the prespecified noninferiority margin of –10 mm . The overall incidence of adverse events was similar for valdecoxib ( 28 % ) and diclofenac ( 26 % ) . No statistically different moderate or severe upper gastrointestinal adverse events were reported , although they were numerically greater for diclofenac ( 8) than for valdecoxib ( 3 ) . Discussion Valdecoxib 40 mg q.d . ( with a second dose on day 1 ) provides effective relief for acute low back pain , and was at least as efficacious as diclofenac 75 mg b.i.d . , with a nonsignificant but numerically lower incidence of gastrointestinal adverse events Abstract Background : NSAIDs are widely used for patients presenting with low back pain . A quick-release formulation of lornoxicam , a potent NSAID from the chemical class of oxicams , offers a faster onset of pain relief compared with the st and ard tablet formulation . Methods : Time to onset of pain relief with lornoxicam was compared with the quick-release formulation of diclofenac potassium in acute low back pain in a r and omised , double-blind , multicentre study . 220 patients received either lornoxicam 24 mg or diclofenac potassium 150 mg on day 1 followed by lornoxicam 8 mg twice daily or diclofenac potassium 50 mg twice daily for 5 days . Efficacy outcomes included time to onset of pain relief , as measured by the stopwatch method ( primary outcome ) , pain intensity , pain relief , rescue medication , ability to perform daily activities and global evaluation of the study medication . Results : The time to onset of pain relief ratios between diclofenac potassium/ lornoxicam was 1.03 ( 95 % CI 0.91 , 1.26 ) and 1.05 ( 95 % CI 0.93 , 1.29 ) in the intention-to-treat ( ITT ) and per- protocol ( PP ) analyses , respectively , demonstrating the non-inferiority of lornoxicam ( defined by lower limits of the 95 % CIs > 0.80 ) . Time to onset of pain relief was shorter with lornoxicam ( 30 minutes ) compared with diclofenac potassium ( 36 minutes ) . The difference was not statistically significant ( ITT analysis ) . A higher magnitude of analgesic effect associated with better global evaluation of the study medication for lornoxicam was also demonstrated . The drugs were equally well tolerated . Conclusion : Lornoxicam administered as a quick-release formulation was shown to be non-inferior to the equivalent formulation of diclofenac potassium in terms of onset of pain relief and more effective on most of the major st and ard efficacy outcomes Study Design . A prospect i ve , r and omized double-blind comparative trial . Objectives . To evaluate the efficacy and tolerability of nimesulide , a cyclooxygenase (COX)-2–selective anti-inflammatory agent versus ibuprofen in patients with acute lumbosacral back pain . Summary of Background Data . Nonsteroidal anti-inflammatory drugs ( NSAIDs ) have been more effective than placebo in patients with uncomplicated acute low back pain in previous r and omized controlled trials . The efficacy and tolerability of a new COX-2–selective anti-inflammatory drug have not yet been established . Methods . One hundred four patients aged 18–65 years with acute low back pain were enrolled . The patients were r and omly allocated either to oral nimesulide ( 100 mg twice daily for 10 days ) or oral ibuprofen ( 600 mg three times daily for 10 days ) . Outcome measures on a visual analog scale were an average of the pain intensity and the pain relief , stiffness in the back , functional status , and the results of physical examinations . All side effects were recorded at each visit . Results . With both study therapies , there was a clear improvement in all measured parameters of the pain and back function parameters measured from the third day of treatment onward . The patients ’ capacity for daily tasks , showed improvement in both groups ( P < 0.001 ) , but a statistically significant difference was found between the two groups in favor of the nimesulide group ( P < 0.05 ) after 10 days . Nimesulide was more effective than ibuprofen in improved lateral bending measurements ( P = 0.026 ) . Nimesulide and ibuprofen provided similar degrees of improvement in the modified Schober tests and in the pain intensity and back stiffness scores . More gastrointestinal side effects were reported with ibuprofen than nimesulide , and the comparison showed a trend ( P = 0.067 ) . Ten side effects occurred in the nimesulide group in 7 ( 13 % ) patients and 13 in the ibuprofen group in 11 ( 21 % ) patients . Conclusions . The results confirmed that the COX-2–selective inhibitor nimesulide is an effective and well-tolerated agent for use in general practice s to treat acutelow back pain . The incidence of gastrointestinal side effects seems to be lower with nimesulide than with ibuprofen In a 2-week , double-blind , parallel , multicenter study , piroxicam ( 20 mg once-daily ) and indomethacin ( 25 mg three times daily ) were compared in the treatment of painful lumbar disorders . A total of 230 patients were evaluated , 116 who received piroxicam and 114 who received indomethacin . While both drugs were highly effective in relieving symptoms , numerical superiority was evident for piroxicam in most efficacy parameters . The difference between treatments was most obvious at the end of the first week , when a greater percentage of patients receiving piroxicam was rated as ' very much improved ' . No serious adverse reactions or clinical laboratory abnormalities were noted for either drug , although fewer gastrointestinal side effects were observed with piroxicam Abstract Background : Low back pain is an important medical problem in Western industrialised countries . NSAIDs are one of the main options for symptomatic pain relief in the early management of this painful condition . Dexketoprofen is an NSAID belonging to the arylpropionic acid group that has demonstrated good analgesic efficacy and a good safety profile in different acute and chronic painful conditions . Methods : A r and omised , double-blind , parallel , active controlled , multicentre study that included 370 out patients with acute low back pain was conducted to compare the analgesic efficacy of dexketoprofen 50 mg twice daily versus diclofenac 75 mg twice daily administered intramuscularly for 2 days . Efficacy outcomes were assessment of pain intensity ( PI ) measured on a visual analogue scale , total PI scores from baseline to 6 hours after the first-dose administration ( primary efficacy endpoint ; SAPID0 - 6 ) , score on a physical disability scale using the Rol and Disability Question naire ( RDQ ) , and use of rescue medication . Tolerability and safety were also assessed as secondary variables . Results : The adjusted mean ( SAPID0 - 6 ) scores were very similar , 117.3 mm/h with dexketoprofen and 114.7 mm/h with diclofenac . The adjusted ratio of means was 1.023 and the lower 95 % confidence limit was 0.81 , demonstrating noninferiority of dexketoprofen ( defined by a lower limit of the 95 % CI > 0.80 ) in comparison with diclofenac ( per- protocol analysis ) . The median change in the RDQ was -6 points for both groups ( p = 0.69 ) , showing an overall improvement on the disability scale . No significant differences between groups were observed regarding the percentage of patients needing rescue medication or in the mean values of pain after repeated doses ( SAPID0-last ) . Dexketoprofen was well tolerated , with a reported incidence of adverse events similar to that of diclofenac . No serious adverse events were reported in either treatment group . Conclusion : From the results of this study it can be concluded that dexketoprofen 50 mg administered twice daily intramuscularly provides a clinical ly relevant analgesic effect with good tolerability after single and repeated doses in patients with acute severe low back pain The use of nonsteroidal anti-inflammatory drugs ( NSAID ) such as diclofenac for treatment of degenerative rheumatic disorders of the lumbar spine is of great significance in orthopedic practice . Clinical studies have shown that concomitant treatment with vitamins B1 , B6 , B12 and diclofenac provides more efficient pain relief than treatment using diclofenac alone . This study was undertaken in order to determine whether the duration of treatment with diclofenac for lower back pain can be shortened by adding B-vitamins to the therapeutic regimen . From September through December of 1986 , 256 patients participated in a multicenter , controlled , r and omized double-blind trial which compared the clinical efficacy of diclofenac ( 50 mg ) with a combined therapy of diclofenac ( 50 mg ) and vitamins B1 , B6 , and B12 ( thiamine nitrate , pyridoxine hydrochloride , and cyanocobalamine , resp . ; in dosages of 50 mg , 50 mg , and 0.25 mg , resp . ) . Patients were treated with 3 X 1 capsule daily for a maximum of two weeks , having the option to terminate participation in the trial after 1 week in the event of total pain relief . The data of 238 patients were able to be included in the evaluation . 29 patients opted to discontinue therapy due to remission on symptoms . Nineteen ( 65.6 % ) of these patients belonged to the combined therapy group , the other 10 ( 34.4 % ) having taken diclofenac alone ; this difference is statistically significant ( p less than 0.05 ) . An important aspect in the evaluation of therapy was the patient response regarding the improvement of painful symptoms which , in addition to their subjective feedback , was reflected in the test results of the " Hoppe Pain Question naire ( HPQ ) . " All parameters used as a measure of pain relief indicated superior results with the B-vitamin supplemented therapy when compared with results obtained with diclofenac alone . Moreover , after 3 days of therapy the " sensory " pain factor " sharpness " improved significantly . Undesirable side-effects were documented with 39 patients , 14 of them having discontinued therapy for this reason . No statistically significant difference could be determined within this group with regard to therapy . The study results document the positive influence of B-vitamins on painful symptoms and indicate that less NSAID is needed for pain relief when combined with B-vitamins Acute low back pain is a common problem in the emergency department ( ED ) . Effective management of acute pain enhances early rehabilitation and recovery . Given the importance of inflammatory mediators in pain generation and the adverse effects associated with opioids , it is logical to expect that a non-opioid agent with antiinflammatory and analgesic properties would provide excellent analgesia with fewer adverse effects . This double-blind , r and omized , multicenter clinical trial , performed in six university and community hospital EDs , compares the analgesic efficacy and adverse effects of ketorolac to those of acetaminophen-codeine in ED patients with acute musculoskeletal low back pain . Our hypothesis was that ketorolac would provide superior analgesia with fewer adverse effects . One hundred twenty-three patients with acute low back pain were r and omized to receive ketorolac ( KET , N = 63 ) or acetaminophen-codeine ( ACOD , N = 60 ) . Most ( 79 % ) were males , and the mean age was 34.5 years . After baseline clinical assessment , patients were treated with ketorolac ( 10 mg every 4 to 6 h as needed , up to four daily doses ) or acetaminophen-codeine ( 600 mg-60 mg , respectively , every 4 to 6 h as needed , up to six daily doses ) and followed for one week . Pain intensity was assessed on visual analogue and categorical scales . Functional capacity , overall pain relief , and overall medication rating were assessed on categorical scales . Adverse events were documented . Primary outcomes included : 1 ) Pain intensity differences , based on visual analogue scores , for the 0 to 6 h treatment phase . 2 ) Incidence of adverse events . Secondary outcomes included analgesic efficacy , functional capacity , and overall subjective drug evaluation at one week . Both drugs provided substantial pain relief , with maximal effect 2.2 h after oral dosing . There were no significant differences in analgesic efficacy , functional capacity , or overall pain relief between the two groups . Sixteen patients ( 10 KET vs. 6 ACOD , NS ) withdrew prematurely because of drug inefficacy . Patients in the ACOD group reported significantly more adverse drug events and serious adverse drug events . Seven patients --all in the ACOD group -- withdrew from the study because of adverse drug events . Based on comparable efficacy and a superior adverse event profile , ketorolac was preferable to acetaminophen with codeine for the treatment of acute low back pain in the ED Seventy out- patients with acute back pain participated in a double-blind comparative trial of the clinical efficacy and tolerance of orally administered meptazinol and diflunisal . Half of the patients received 200 mg meptazinol or 250 mg diflunisal 4-times daily for up to 3 weeks , depending on the duration of pain . Patients were examined 4 times at 1-week intervals for their capability to do daily tasks , for their capacity for forward bending , thoraco-lumbar torsion , straight leg raising , static hip flexion and sit-ups , and for subjective assessment of pain . Side-effects were recorded on a question naire . Both treatments produced marked improvement in most of the parameters assessed , often within the first week and , overall , the results were similar with the two drugs . Few side-effects were reported and those that were recorded were slight and similar in incidence apart from nausea in 5 meptazinol-treated patients and smarting and burning on urination in 2 patients receiving diflunisal Twenty-seven investigators participated in a double-blind , parallel placebo-controlled trial of piroxicam involving 278 patients with acute low back pain . Therapy commenced within 48 hours of the injury and continued for 7 days . The drug was given in the recommended regimen of 40 mg once daily for the first 2 days and 20 mg once daily thereafter . After 3 days of therapy , piroxicam patients showed a statistically greater amount of pain relief in the lying ( P<0.001 ) , sitting ( P<0.01 ) , and st and ing ( P<0.01 ) positions , but after 7 days the difference between treatments was no longer significant . After 1 week 's therapy , however , the requirement for additional analgesic was significantly lower in the piroxicam group ( P<0.05 ) , and more piroxicam than placebo patients ( 42 versus 28 ) had returned to work ( P<0.05 ) . Toleration was excellent in most patients , with only 13 % of the piroxicam and 17 % of the placebo group reporting adverse effects of mainly mild or moderate severity . The profile of the adverse effects was similar for both treatments . Piroxicam can provide effective relief of acute low-back pain with good toleration ; it should be considered for use in the initial treatment of this condition OBJECTIVE This r and omized , double-dummy , double-blind pilot study of acutely exacerbated low back pain was aim ed to inform a definitive comparison between Doloteffin , a proprietary extract of Harpagophytum , and rofecoxib , a selective inhibitor of cyclo-oxygenase-2 ( COX-2 ) . METHODS Forty-four patients ( phyto-anti-inflammatory drug-PAID-group ) received a daily dose of Doloteffin containing , inter alia , 60 mg of harpagoside for 6 weeks and 44 ( non-steroidal anti-inflammatory drug-NSAID-group ) received 12.5 mg/day of rofecoxib . All were allowed rescue medication of up to 400 mg/day of tramadol . Several outcome measures were examined at various intervals to obtain estimates of effect size and variability that might be used to decide the most suitable principal outcome measure and corresponding numbers required for a definitive study . RESULTS Forty-three PAID and 36 NSAID patients completed the study . Ten PAID and 5 NSAID patients reported no pain without rescue medication for at least 5 days of the 6th week of treatment . Eighteen PAID and 12 NSAID patients had more than a 50 % reduction in the week 's average of their pain scores between the 1st and 6th weeks . The mean percentage decrease from baseline in the pain component of the Arhus Index was 23 ( S.D. 52 ) in PAID and 26 ( S.D. 43 ) in NSAID . The corresponding measures for the overall Arhus Index were 11 ( 31 ) and 16 ( 24 ) and , for the Health Assessment Question naire , 7 ( 8) and 6 ( 7 ) . Tramadol was used by 21 PAID patients and 13 NSAID patients . Fourteen patients in each group experienced 39 adverse effects , of which 28 ( 13 in PAID ) were judged to some degree attributable to the study medications . CONCLUSION Though no significant intergroup differences were demonstrable , large numbers will be needed to show equivalence In a controlled multi-center single-blind study , the relative efficacy and tolerance of i.m . injectable preparations of etofenamat(e ) and diclofenac sodium were investigated in 96 patients with acute lumbago . Treatment result ed in obvious improvement in function and reduction in pain , no statistical difference being found between the two drugs . In 43 % of the patients treated with etofenamat(e ) and 27 % of those receiving diclofenac , the final medical report indicated very good therapeutic results . Under etofenamat(e ) i.m . therapy , no side effects occurred , and in no case did treatment have to be discontinued . Under diclofenac , two patients experienced adverse reactions , one allergic exanthema , and the other itching and a sensation of heat . A further patient experienced no improvement after the first injection and discontinued treatment The efficacy of an NSAID ( tenoxicam ) in the treatment of acute low back pain ( LBP ) was assessed in a double blind controlled study by using an objective functional evaluation . Seventy-three patients consulting for acute LBP were r and omized into two groups : Group I was treated with tenoxicam for 14 days and Group II was given a placebo . Trunk function was measured with a computerized isoinertial dynamometric trunk testing device ( Isostation B200 ) . Isometric and dynamic torques , range of motion and movement velocities were measured before treatment and after 14 days . Clinical evaluation was realized by the patient on a pain visual analogue scale ( VAS ) on days 1 , 8 and 15 and by the investigator on a five-point scale on days 8 and 15 . The functional evaluation showed significant differences in favour of the tenoxicam treatment for velocity and extension isometric torque . VAS and investigator evaluations showed a significant difference in favour of tenoxicam on day 8 but no difference on day 15 . This study shows that the use of tenoxicam in acute LBP is of interest . Tenoxicam has an effect on pain during the first part of the treatment and may help to restore full function even if the symptoms have disappeared The marketed formulations of 6 analgesic preparations were compared in the treatment of patients suffering from acute exacerbations of low back pain using a crossover trial of balanced incomplete block design . Sixty out- patients with symptoms result ing from a mechanical or degenerative condition were each prescribed 3 drugs which were administered consecutively for 1 week each . The medications ( and daily dosages ) were coded as A --aspirin ( 3600 mg ) , B --dextropropoxyphene plus paracetamol ( 260 mg plus 2600 mg ) , C --indomethacin ( 150 mg ) , D --mefenamic acid ( 1500 mg ) , E --paracetamol ( 4000 mg ) , and F --phenylbutazone ( 300 mg ) . Daily pain scores were significantly lower ( p less than 0.05 ) during treatment D than during treatments E and B , and significantly lower ( p less than 0.05 ) during treatment A than during treatment B. There were large and significant differences between treatments in the percentages of recommended doses acceptable to the patients and in the number of defaults from the prescribed regimens . The patients chose F and D significantly more ( p less than 0.05 ) often than A. Overall , there were consistently superior performances by mefenamic acid and phenylbutazone with little to choose between the two 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 A total of 395 male infantry recruits were evaluated in a prospect i ve study of possible risk factors for overexertional back pain and the efficacy of drug treatment regimens for this syndrome . Recruits were classified into subgroups of lumbar or thoracic , and paraspinal or spinous process pain . Recruits were divided into three treatment groups : Ibuprofen , Paracetamol , and no drug treatment . Of the recruits , 18 % were diagnosed as having overexertional back pain during the course of 14 weeks of training . By multivariate analysis low body mass index was found to be a risk factor for overexertional lumbar pain ( p = 0.005 ) and increased lumbar lordosis a risk factor for overexertional thoracic pain ( p = 0.005 ) . Of recruits with overexertional back pain , 65 % were asymptomatic by the end of basic training . There was no statistically significant difference between cure rates according to treatment groups Two groups of 20 patients each , with mild to moderate acute low back pain with associated muscle spasm of ten days ' duration or less , were treated with a combination of cyclobenzaprine and naproxen or naproxen alone in a r and omized , 14-day open-label trial . Cyclobenzaprine was added to the naproxen regimen as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute , painful , musculoskeletal conditions . The clinical characteristics of each study group , including the number of worker 's compensation patients , were comparable . Combination therapy was associated with less objective muscle spasm and tenderness and greater motion of the lumbosacral spine ( P less than 0.05 ) . There were trends toward faster resolution of functional deficits and pain with combined therapy . Combination therapy was associated with more side effects , due primarily to drowsiness from the cyclobenzaprine . The results of this study demonstrated that patients with muscle spasm associated with acute low back strain benefited from the use of combination therapy consisting of a nonsteroidal anti-inflammatory agent ( naproxen ) and a muscle relaxant ( cyclobenzaprine ) In this controlled , single-blind parallel group study , the effect of ibuprofen 1200 mg daily was compared with diclofenac 75 mg daily . Thirty patients entered the study , r and omized into two groups , each group receiving one tablet three times daily for two weeks . A one-week wash-out period ( i.e. a drug-free period during which only physiotherapy was given ) , preceded and followed the treatment on active drug . Assessment s were made by the same clinician throughout who was unaware of the treatment of individual patients . Statistically significant improvement was shown by patients receiving ibuprofen for the degree of pain relief at rest and improvement was also shown for the degree of pain at rest and during exercise , for pain relief during exercise and for spinal flexion . Patients who received diclofenac showed stastistically significant improvement for forward flexion , together with improvement for the degree of pain on exercise . Side-effects were very few Two multicenter , double-blind , r and omized studies were performed to determine the antihypertensive efficacy and effects on laboratory values of a new , shorter-acting formulation of metolazone in patients with mild to moderate hypertension . After baseline placebo-control periods , 105 patients were r and omly assigned to receive single daily doses of either placebo or 0.5 , 1.0 , or 2.0 mg of the new formulation of metolazone for six weeks in one study , and 164 patients were r and omized to receive 0.5 , 1.0 , or 2.0 mg of the new formulation of metolazone or 2.5 mg of the older , long-acting metolazone in the other . Mean blood pressure reductions in all three metolazone groups were statistically and clinical ly significant . Blood pressures of 51 % to 58 % of patients in the 0.5-mg metolazone group were controlled ( diastolic blood pressure less than 90 or a fall of greater than or equal to 10 mmHg from baseline ) . Reductions in mean serum potassium levels were dose-related . We conclude that 0.5 mg of metolazone is safe and effective therapy for hypertension ; it will significantly reduce systolic and diastolic blood pressure and minimizes changes in laboratory test values OBJECTIVE To assess efficacy and safety of diclofenac-K 12.5 mg tablets in the treatment of acute low back pain ( low back pain ) . MATERIAL / METHOD A multiple dose , double-blind , double-dummy , r and omized , placebo-controlled , parallel group trial compared diclofenac-K ( 12.5 mg ; n = 124 ) with ibuprofen ( 200 mg ; n = 122 ) and placebo ( n = 126 ) in patients with moderate-to-severe acute low back pain . The treatment consisted of an initial dose of 2 tablets followed by 1 or 2 tablets every 4 - 6 hours as needed ( maximum 6 tablets/day ) for 7 days . The primary efficacy outcome for the initial dose was TOTPAR-3 , the summed total pain relief over the first 3 hours . Secondary initial dose outcomes included TOTPAR-6 , summed pain intensity differences SPID-3 and SPID-6 , time to rescue medication or remedicate , and the End of First Dose global efficacy assessment . The primary efficacy outcome for the flexible multiple dosing regimen was the End of Study global efficacy assessment . Secondary outcomes for multiple dosing included time to rescue medication over the entire study , the End of Day global efficacy assessment s ( daily over Days 1 - 7 ) , pain intensity differences on the VAS measured at Visit 2 and 3 , and change in Eifel algofunctional index . Safety/tolerability was assessed by recording adverse events . RESULTS Diclofenac-K 12.5 mg demonstrated superiority vs placebo on the primary efficacy parameter and almost all secondary initial dose outcomes . With respect to the initial dose , diclofenac-K 12.5 mg was also significantly superior to ibuprofen 200 mg on SPID-3 . Ibuprofen 200 mg was superior to placebo only on the End of First Dose global efficacy assessment . The flexible multiple dosing regimens of diclofenac-K and ibuprofen were both significantly superior to placebo on the End of Study global efficacy assessment , time to rescue medication over the entire study period , the End of Day global efficacy assessment on Days 1 - 2 , pain intensity difference on the VAS at Visit 3 and the Eifel algofunctional index at Visit 3 ( also at Visit 2 in diclofenac-K 12.5 mg group ) . Both active treatments were as well tolerated as placebo . CONCLUSIONS The flexible multiple dosing regimen of diclofenac-K 12.5 mg ( initial dose of 2 tablets followed by 1 - 2 tablets every 4 - 6 hours , max . 75 mg/day ) is an effective and safe treatment of acute low back pain Abstract Background : Low back pain is a common and costly health care problem . This pilot study evaluated the sensitivity of the 2-stopwatch and Paris plinth method ologies for assessing time-to-onset of pain relief and flexibility , respectively , with continuous , low-level heatwrap therapy . Research Design and Methods : Subjects aged 18 to 55 years with at least moderate baseline acute low back pain were r and omly assigned to either heatwrap or oral placebo for 8 hours . Unheated wrap ( sham ) and oral ibuprofen were included for blinding purpose s only . Results : Sixty-one subjects were r and omly assigned to either heatwrap ( n = 26 ) , oral placebo ( n = 25 ) , sham wrap ( n = 5 ) , or oral ibuprofen ( n = 5 ) . Median time to confirmed first perceptible pain relief and to meaningful pain relief were significantly shorter for the heatwrap group compared with those assigned to oral placebo ( 96.5 vs < 240.0 min and 215.7 vs > 240.0 min , respectively ; P < 0.05 for both ) . Among subjects receiving the heatwrap , 53.8 % reported first perceptible and meaningful relief , compared with 28.0 % receiving oral placebo . Subjective measures of pain relief , back stiffness , and global evaluation were more sensitive in detecting treatment differences than the plinth assessment s of flexibility , range of motion , and pain . Three adverse events were reported as mild in severity and considered unrelated to study treatment . Conclusions : The 2-stopwatch methodology is a viable approach for assessing onset of analgesia in low back pain ; however , the plinth may not be a reliable method for assessing flexibility . Consistent with published studies involving much larger sample sizes , the heatwrap provided significantly faster and sustained pain relief than oral placebo in subjects with acute low back pain . Clinical Trial Identifier : NCT01045993 The use of flurbiprofen as an analgesic and anti-inflammatory agent in patients with soft tissue trauma induced by sports injuries , lumbar disk syndrome , or surgery was considered in three clinical trials . In the first study , soft tissue injuries to the lower limb in 51 professional soccer players were treated for six days with 150 mg of flurbiprofen per day or 3.6 g of aspirin per day . The second study compared three weeks of treatment with daily doses of 200 mg of flurbiprofen and 4 g of acetaminophen in 50 patients with acute low back pain . In the third study , 100 postoperative patients were given 400 mg of flurbiprofen per day or 4 g of acetaminophen per day for seven days following total or partial meniscectomy . In all of these trials , flurbiprofen showed excellent analgesic efficacy in reducing pain and swelling , and enhanced the recovery of patients with soft tissue trauma BACKGROUND Valdecoxib , a cyclooxygenase (COX)-2 specific inhibitor , is indicated for relief of the signs and symptoms of rheumatoid arthritis , osteoarthritis , and primary dysmenorrhea . Therapeutic doses of COX-2 specific inhibitors are as effective as nonspecific nonsteroidal anti-inflammatory drugs in reducing inflammatory pain while sparing the gastrointestinal and platelet toxicity associated with nonspecific COX-1 inhibition . OBJECTIVE The aim of this study was to assess the analgesic efficacy and tolerability of valdecoxib 40 mg/d compared with placebo in the treatment of chronic low back pain . METHODS This 4-week , prospect i ve , r and omized , double-blind placebo-controlled , parallel-group study was conducted at 37 centers across the United States and 5 centers in Canada . Patients aged > or = 18 years with chronic low back pain in flare were enrolled . Patients were r and omized to receive valdecoxib 40-mg/d or placebo tablets , once daily for 4 weeks . Patients rated low back pain intensity on a visual analog scale and completed the Rol and -Morris Disability Question naire and the modified Brief Pain Inventory-Short Form ( mBPI-SF ) at each visit . RESULTS Two hundred ninety-three patients were enrolled . The valdecoxib group comprised 148 patients ( 81 women , 67 men ; mean [ SD ] age , 48.6 [ 13.3 ] years ; mean [ SD ] body weight , 86.6 [ 20.9 ] kg ) , and the placebo group included 145 patients ( 85 women , 60 men ; mean [ SD ] age , 48.7 [ 12.6 ] years ; mean [ SD ] body weight , 85.6 [ 19.9 ] kg ) . Of the enrolled patients , 249 completed the study : 134 patients ( 91 % ) who received valdecoxib and 115 patients ( 79 % ) who received placebo . No statistically significant differences in patient baseline characteristics were noted between treatment groups , except in response to 1 mBPI-SF question ; patients in the valdecoxib group reported significantly greater interference in relations with other people due to pain than did those in the placebo group ( P = 0.048 ) . Changes from baseline in low back pain intensity were significantly greater in valdecoxib-treated patients at each assessment ( all , P < 0.001 vs placebo ) . Pain scores on the mBPI-SF indicated significantly greater pain relief with valdecoxib at each assessment ( all , P < or = 0.014 vs placebo ) . Improvements in mean Rol and -Morris Disability Question naire score with valdecoxib were significantly greater than with placebo at each assessment ( all , P < or = 0.003 ) . Although the overall incidence of adverse events ( AEs ) was significantly higher among patients receiving valdecoxib than those receiving placebo ( 35.1 % vs 24.1 % , respectively ; P = 0.042 ) , no significant differences were found between groups for the incidence of any individual AE . Most AEs ( 89 % [ 77/87 total events ] ) were mild or moderate in severity . CONCLUSIONS In this study of patients with chronic low back pain , valdecoxib 40 mg/d provided rapid relief ( within 1 week ) and consistent relief ( over 4 weeks ) . In addition , significant improvement in function and decreased disability were found with valdecoxib compared with placebo Summary A double-blind , between-patient comparison of alclofenac and indomethacin was carried out in 60 patients with low back pain and sciatica . Pain , functional disability and signs of dural irritation ( Lasegue 's sign ) were rated by the clinician before and at the end of each 7-day treatment period , and an overall assessment of treatment effectiveness was made by both clinician and patients .Response to treatment in terms of patient improvement was considered satisfactory with both drugs , but more erratic in those patients with an acute condition . Analysis of pain scores showed a significant tendency for patients with acute or chronic low back pain to improve more with alclofenac than with indomethacin treatment . Overall assessment s by the clinician and patients also indicated signiJcantly greater improvement with alclofenac HighlightsCombination of NSAID ’s and myorelaxants are frequently used in acute back pain . Clinical effectiveness of a topical agent obviously depends on its penetration through the epidermis into the deeper layers . Phonophoresis ( PP ) helps to introduce such agents with a wide range of molecular weight drugs through the skin and into the soft tissue below . Purpose : To investigate the effect of Phonophoresis ( PP ) with the combination of nonsteroidal anti‐inflammatory drugs ( NSAID ’s ) and myorelaxant versus routine Ultrasound ( US ) treatment with non‐therapeutic gel on the patients with acute low back pain ( ABP ) . Methods : Sixty patients with ABP were r and omly assigned into 2 groups . In Group 1 ( n = 30 ) US was applied using diclofenac + Thiocolchicoside gel for 10 min and for a total of 10 sessions . In Group 2 ( n = 30 ) the same US protocol was applied with the same setting and timing with Group 1 using US gel that does not contain any pharmaceutical ingredient . Evaluation parameters were Visual numeric scale ( VNS ) , Oswestry Disability Index ( ODI ) , and Shober test . Results : Comparison of the results obtained from the two groups before treatment and at second ( W2 ) and sixth weeks ( W6 ) posttreatment showed significant improvement in all parameters in both groups ( p < 0.05 ) . Comparison of the groups showed significantly superior improvement in Group 1 for ODI while there was no difference in other parameters at W2 . At W6 , there was significantly superior improvement in all parameters ( p < 0.05 ) except for Shober test in Group1 . Conclusion : Our results showed that PP treatment is superior than conventional US therapy at short term in ABP patients The present paper continues a more complex research related to the increased synergism in terms of both anti-inflammatory and analgesic effect obtained by the addition of chlorpheniramine ( CLF ) to the common acetylsalicylic acid ( ASA ) , acetaminophen ( PAR ) , and caffeine ( CAF ) combination . This synergistic effect was previously highlighted both in vitro in rat models and in vivo in the treatment of migraine . The aim of the research was to further evaluate the analgesic effect of a synergistic low-dose ASA – PAR – CAF – CLF combination in the treatment of low back pain , in a parallel , multiple-dose , double-blind , active controlled clinical trial . A number of 89 patients with low back pain of at least moderate intensity were r and omly assigned to receive Algopirin ® ( ALG ) , a combinational product containing 125 mg ASA , 75 mg PAR , 15 mg CAF , and 2 mg CLF , or PAR 500 mg , a drug recognized by American Pain Society as “ safe and effective ” in the treatment of low back pain . One tablet of the assigned product was administered three times a day for seven consecutive days . The patients evaluated their pain level using a Visual Analog Scale prior to administration , and at 1 , 2 , 4 , and 6 h after the morning dose . Time course of effect was similar in structure and size for both treatments . Pain relief appeared rapidly and steadily increased over 4 h after drug administration . Differential pain curves of ALG and PAR were very similar and comparable with the previously determined ALG analgesia pattern in migraine . Differences between the daily mean pain scores were not statistically significant for the two treatments . Similar results were obtained for the Sum of Pain Intensity Differences ( SPID ) for 0–4 h and 0–6 h intervals as well as for the time course of the proportion of patients with at least 30 % and at least 50 % pain relief . In conclusion , in spite of very small doses of active components , ALG proved equally effective to the st and ard low back pain treatment and therefore a viable therapeutic alternative , mainly for patients with gastrointestinal and hepatic sensitivity . Trial Registration : www . Clinical Trials.gov , identifier EudraCT No. : 2015–002314–74 IMPORTANCE Low back pain ( LBP ) is responsible for more than 2.5 million visits to US emergency departments ( EDs ) annually . These patients are usually treated with nonsteroidal anti-inflammatory drugs , acetaminophen , opioids , or skeletal muscle relaxants , often in combination . OBJECTIVE To compare functional outcomes and pain at 1 week and 3 months after an ED visit for acute LBP among patients r and omized to a 10-day course of ( 1 ) naproxen + placebo ; ( 2 ) naproxen + cyclobenzaprine ; or ( 3 ) naproxen + oxycodone/acetaminophen . DESIGN , SETTING , AND PARTICIPANTS This r and omized , double-blind , 3-group study was conducted at one urban ED in the Bronx , New York City . Patients who presented with nontraumatic , nonradicular LBP of 2 weeks ' duration or less were eligible for enrollment upon ED discharge if they had a score greater than 5 on the Rol and -Morris Disability Question naire ( RMDQ ) . The RMDQ is a 24-item question naire commonly used to measure LBP and related functional impairment on which 0 indicates no functional impairment and 24 indicates maximum impairment . Beginning in April 2012 , a total of 2588 patients were approached for enrollment . Of the 323 deemed eligible for participation , 107 were r and omized to receive placebo and 108 each to cyclobenzaprine and to oxycodone/acetaminophen . Follow-up was completed in December 2014 . INTERVENTIONS All participants were given 20 tablets of naproxen , 500 mg , to be taken twice a day . They were r and omized to receive either 60 tablets of placebo ; cyclobenzaprine , 5 mg ; or oxycodone , 5 mg/acetaminophen , 325 mg . Participants were instructed to take 1 or 2 of these tablets every 8 hours , as needed for LBP . They also received a st and ardized 10-minute LBP educational session prior to discharge . MAIN OUTCOMES AND MEASURES The primary outcome was improvement in RMDQ between ED discharge and 1 week later . RESULTS Demographic characteristics were comparable among the 3 groups . At baseline , median RMDQ score in the placebo group was 20 ( interquartile range [IQR],17 - 21 ) , in the cyclobenzaprine group 19 ( IQR,17 - 21 ) , and in the oxycodone/acetaminophen group 20 ( IQR,17 - 22 ) . At 1-week follow-up , the mean RMDQ improvement was 9.8 in the placebo group , 10.1 in the cyclobenzaprine group , and 11.1 in the oxycodone/acetaminophen group . Between-group difference in mean RMDQ improvement for cyclobenzaprine vs placebo was 0.3 ( 98.3 % CI , -2.6 to 3.2 ; P = .77 ) , for oxycodone/acetaminophen vs placebo , 1.3 ( 98.3 % CI , -1.5 to 4.1 ; P = .28 ) , and for oxycodone/acetaminophen vs cyclobenzaprine , 0.9 ( 98.3 % CI , -2.1 to 3.9 ; P = .45 ) . CONCLUSIONS AND RELEVANCE Among patients with acute , nontraumatic , nonradicular LBP presenting to the ED , adding cyclobenzaprine or oxycodone/acetaminophen to naproxen alone did not improve functional outcomes or pain at 1-week follow-up . These findings do not support use of these additional medications in this setting . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01587274 Study objective Low back pain causes more than 2.5 million visits to US emergency departments ( EDs ) annually . Low back pain patients are often treated with nonsteroidal anti‐inflammatory drugs and benzodiazepines . The former is an evidence ‐based intervention , whereas the efficacy of the latter has not been established . We compare pain and functional outcomes 1 week and 3 months after ED discharge among patients r and omized to a 1‐week course of naproxen+diazepam versus naproxen+placebo . Methods This was a r and omized , double‐blind , comparative efficacy clinical trial conducted in an urban health care system . Patients presenting with acute , nontraumatic , nonradicular low back pain of no more than a duration of 2 weeks were eligible for enrollment immediately before discharge from an ED if they had a score greater than 5 on the Rol and ‐Morris Disability Question naire , a vali date d 24‐item inventory of functional impairment caused by low back pain . Higher scores on the question naire indicate greater functional disability . The primary outcome in the trial was improvement in the score between ED discharge and 1 week later . Secondary outcomes included pain intensity 1 week and 3 months after ED discharge , as measured on a 4‐point descriptive scale ( severe , moderate , mild , and none ) . All patients were given 20 tablets of naproxen 500 mg , to be taken twice a day as needed for low back pain . Additionally , patients were r and omized to receive either 28 tablets of diazepam 5 mg or identical placebo , to be received as 1 or 2 tablets every 12 hours as needed for low back pain . All patients received a st and ardized 10‐minute low back pain educational session before discharge . Using a between‐group mean difference of 5 Rol and ‐Morris Disability Question naire points , a previously vali date d threshold for clinical significance , we calculated the need for at least 100 patients with primary outcome data . Results Enrollment began in June 2015 and continued for 9 months . Five hundred forty‐five patients were screened for eligibility . One hundred fourteen patients met selection criteria and were r and omized . Baseline demographic characteristics were not substantially different between the 2 groups . One hundred twelve patients ( 98 % ) provided 1‐week outcome data . The mean Rol and ‐Morris Disability Question naire score of patients r and omized to naproxen+diazepam improved by 11 ( 95 % confidence interval [ CI ] 9 to 13 ) , as did the mean score of patients r and omized to naproxen+placebo ( 11 ; 95 % CI 8 to 13 ) . At 1‐week follow‐up , 18 of 57 diazepam patients ( 32 % ; 95 % CI 21 % to 45 % ) reported moderate or severe low back pain versus 12 of 55 placebo patients ( 22 % ; 95 % CI 13 % to 35 % ) . At 3‐month follow‐up , 6 of 50 diazepam patients ( 12 % ; 95 % CI 5 % to 24 % ) reported moderate or severe low back pain versus 5 of 53 placebo patients ( 9 % ; 95 % CI 4 % to 21 % ) . Adverse events were reported by 12 of 57 diazepam patients ( 21 % ; 95 % CI 12 % to 33 % ) and 8 of 55 placebo patients ( 15 % ; 95 % CI 7 % to 26 % ) . Conclusion Among ED patients with acute , nontraumatic , nonradicular low back pain , naproxen+diazepam did not improve functional outcomes or pain compared with naproxen+placebo 1 week and 3 months after ED discharge Description The American College of Physicians ( ACP ) developed this guideline to present the evidence and provide clinical recommendations on noninvasive treatment of low back pain . Methods Using the ACP grading system , the committee based these recommendations on a systematic review of r and omized , controlled trials and systematic review s published through April 2015 on noninvasive pharmacologic and nonpharmacologic treatments for low back pain . Up date d search es were performed through November 2016 . Clinical outcomes evaluated included reduction or elimination of low back pain , improvement in back-specific and overall function , improvement in health-related quality of life , reduction in work disability and return to work , global improvement , number of back pain episodes or time between episodes , patient satisfaction , and adverse effects . Target Audience and Patient Population The target audience for this guideline includes all clinicians , and the target patient population includes adults with acute , subacute , or chronic low back pain . Recommendation 1 Given that most patients with acute or subacute low back pain improve over time regardless of treatment , clinicians and patients should select nonpharmacologic treatment with superficial heat ( moderate- quality evidence ) , massage , acupuncture , or spinal manipulation ( low- quality evidence ) . If pharmacologic treatment is desired , clinicians and patients should select nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants ( moderate- quality evidence ) . ( Grade : strong recommendation ) . Recommendation 2 For patients with chronic low back pain , clinicians and patients should initially select nonpharmacologic treatment with exercise , multidisciplinary rehabilitation , acupuncture , mindfulness-based stress reduction ( moderate- quality evidence ) , tai chi , yoga , motor control exercise , progressive relaxation , electromyography biofeedback , low-level laser therapy , operant therapy , cognitive behavioral therapy , or spinal manipulation ( low- quality evidence ) . ( Grade : strong recommendation ) . Recommendation 3 In patients with chronic low back pain who have had an inadequate response to nonpharmacologic therapy , clinicians and patients should consider pharmacologic treatment with nonsteroidal anti-inflammatory drugs as first-line therapy , or tramadol or duloxetine as second-line therapy . Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients . ( Grade : weak recommendation , moderate- quality evidence ) |
11,776 | 15,266,541 | Comparing routes of progesterone administration , reductions in clinical pregnancy rate with the oral route , compared to the intramuscular or vaginal routes , did not reach statistical significance , but there was evidence of benefit of the intramuscular over the vaginal route for the outcomes of ongoing pregnancy and live birth .
No significant difference in pregnancy rate was observed between vaginal progesterone gel and other types of vaginal progesterone .
REVIEW ERS ' CONCLUSIONS Luteal phase support with hCG or progesterone after assisted reproduction results in an increased pregnancy rate .
hCG does not provide better results than progesterone , and is associated with a greater risk of OHSS when used with GnRHa . | BACKGROUND The aspiration of the granulosa cells that surround the oocyte and the use of gonadotropin releasing hormone agonists ( GnRHa ) during assisted reproduction technology ( ART ) treatment can interfere with the production , during the luteal phase , of progesterone , which is necessary for successful implantation of the embryo .
Providing hormonal supplementation during the luteal phase with either progesterone itself , or human chorionic gonadotropin ( hCG ) , which stimulates progesterone production , may improve implantation and , thus , pregnancy rates .
OBJECTIVES To determine ( 1 ) if luteal phase support after assisted reproduction increases the pregnancy rate , ( 2 ) the optimal hormone for luteal phase support , i.e. hCG , progesterone , or a combination of both , and ( 3 ) the optimal route of progesterone administration . | OBJECTIVE --To evaluate the effect of support with human chorionic gonadotrophin in the luteal phase in women taking part in an in vitro fertilisation programme after buserelin and human menopausal gonadotrophin were used to hyperstimulate their ovaries . DESIGN --Controlled group comparison . SETTING --Outpatient department of a private hospital . PATIENTS --115 Women with indications for in vitro fertilisation , all of whom had at least one embryo transferred . INTERVENTIONS --After suppression of the pituitary with buserelin the ovaries of all the women were stimulated with human menopausal gonadotrophin on day 4 of the luteal phase . Human chorionic gonadotrophin ( 10,000 IU ) was given to induce ovulation , and oocytes were recovered 34 hours later . Embryos were transferred 46 to 48 hours after insemination . Women who had received the 10,000 IU of human chorionic gonadotrophin on a date that was an uneven number ( n = 61 ) were allocated to receive support doses of 2500 IU human chorionic gonadotrophin three and six days after that date . The remaining 54 women did not receive hormonal support . END POINT -- Determination of the rates of pregnancy . MEASUREMENTS and main results --Support with human chorionic gonadotrophin did not significantly alter the progesterone or oestradiol concentrations in the early or mid-luteal phase . The mean ( range ) progesterone concentrations in the late luteal phase in women who did not become pregnant were , however , significantly higher in those who received support ( 16(9 - 110 ) nmol/l nu 8(4 - 46 ) nmol/l ) , and the luteal phase was significantly longer in this group ( 14 days nu 12 days ) . The rate of pregnancy was significantly higher in the women who received support than in those who did not ( 25/61 nu 8/54 ) . CONCLUSIONS --When buserelin and human menopausal gonadotrophin are used to hyperstimulate ovaries support with human chorionic gonadotrophin in the luteal phase has a beneficial effect on in vitro fertilisation This study aim ed to compare the efficacy of micronized progesterone administered as luteal support following ovulation induction for in-vitro fertilization (IVF)- embryo transfer in cycles using gonadotrophin-releasing hormone agonist , either orally ( 200 mgx4/day ) or vaginally ( 100 mgx2/day ) and to characterize the luteal phase hormonal profile during such treatments . A total of 64 high responder patients requiring intracytoplasmic sperm injection due to male factor infertility were prospect ively r and omized into two treatment groups . Patients treated orally or vaginally were comparable in age ( 31.9 + /- 6.1 versus 30.6 + /- 5.2 ; mean + /- SD ) , number of oocytes retrieved ( 17 + /- 8.2 versus 18 + /- 7.0 ) , and number of embryos transferred ( 3.1 + /- 1.2 versus 2.7 + /- 0.9 ) per cycle . Following low dose vaginal treatment , a significantly higher implantation rate ( 30.7 versus 10.7 % , P < 0.01 ) , but similar clinical pregnancy rate ( 47.0 versus 33.3 % ) and ongoing pregnancy rate ( 41.1 versus 20.0 % ) was observed , compared with oral treatment . In conception cycles , luteal serum progesterone and oestrogen concentrations did not differ between the treatment groups . In non-conception cycles , late luteal progesterone concentrations were significantly lower following vaginal treatment . As low dose micronized progesterone administered vaginally is simple , easy and well tolerated , it could be recommended as the method of choice for luteal support , especially for high responder patients at risk for ovarian hyperstimulation syndrome There is disagreement among in vitro fertilization ( IVF ) programs as to the need to administer exogenous progesterone to support the luteal phase of patients undergoing embryo transfer after IVF . We examined the effect on pregnancy rates of Prolution , 50-mg daily injections given on days 7–16 following oocyte recovery , in 186 women undergoing IVF treatment using a combined stimulation regime of clomiphene and human menopausal gonadotropin ( hMG ) . One group was deliberately selected for treatment on the possible criterion of lutealphase deficiency and two other groups were r and omly selected into a treatment and a control group . No effect on pregnancy rate was noted in any of these groups . These results indicate that extension of the luteal phase with exogenous progesterone is unlikely to have a significant effect on increasing the pregnancy rate in IVF programs using similar treatment regimes Background . A prospect i ve study was done to compare the efficacy of luteal phase support ( LPS ) using either three times hCG ( group I , n=77 ) , hCG on the day of embryo transfer ( ET ) in combination with daily vaginal progesterone ( group II , n=62 ) or vaginal progesterone only ( group III , n=70 ) BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences A total of 156 patients were r and omly treated with exogenous natural progesterone ( intramuscularly , 50 mg/day ) and vaginal gel ( 90 mg/day ) P or nothing ( Controls ) from the day before embryo transfer ( ET ) for two weeks . In case of positive beta-HCG , the treatment was continued for 12 weeks . Plasma P and 17 beta-Estradiol concentrations were estimated and compared with the control not supplemented group . Both treatments were able to increase significantly the luteal plasmatic values of P versus controls . The ongoing pregnancy and the living birth rates per transfer were significantly higher in the patients supplemented with intramuscular P than in those treated with vaginal gel P. The intramuscular natural P appears the most suitable route of administration for luteal phase support in IVF-ET procedures In a consecutive series of 167 patients reaching the stage of embryo transfer after in vitro fertilization and embryo transfer , 19 clinical pregnancies ensued . The serum progesterone ( P ) levels were significantly greater on the first and second ( P less than 0.01 ) and third ( P less than 0.05 ) postaspiration days for those who conceived . Higher circulating levels of P were achieved on days 1 , 2 , and 3 ( P less than 0.05 ) by the daily injection of P , 50 mg in oil , given for 5 consecutive days , beginning immediately after follicle aspiration . Both pregnancy and nonpregnancy cycles demonstrated high circulating P levels , but the study implies that relatively higher levels are required for conception , and such levels can be achieved by the use of intramuscular Fifty-two women , who had 62 ovum aspiration cycles , received a progesterone ( P ) supplementation of 100 mg/day that was initiated 10 hours before human chorionic gonadotropin ( hCG ) administration and was continued over the following 6 days . Forty-eight women who had 74 ovum pick-ups , but did not get P , served as controls . Forty-four ( 84.6 % ) women of the treatment group , and 40 ( 83.3 % ) of the controls had ovum fertilization and embryo replacement . The fertilization and cleavage rates and the mean number of replaced embryos per embryo transfer ( ET ) cycle did not differ between the groups . Endometrial biopsies , from treatment group women with no fertilized eggs , which were taken 48 hours after ovum pick-up , mostly revealed an " advanced endometrial dating , " in relation to the " day of hCG . " Pregnancy rate per ET cycle for the treatment group was significantly higher than that of the controls ; 41.2 % versus 23.3 % , respectively . It is concluded that the higher pregnancy rate result ed from an improvement in uterine receptivity Replacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization ( IVF ) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant , because of the known rapid recovery of pituitary function after antagonist cessation . This r and omized two-center study was performed to compare nonsupplemented luteal phase characteristics after three different strategies for inducing final oocyte maturation . Forty patients underwent ovarian stimulation using recombinant (r-)FSH ( 150 IU/d , fixed ) combined with a GnRH antagonist ( antide ; 1 mg/d ) during the late follicular phase . When at least one follicle above 18 mm was observed , patients were r and omized to induce oocyte maturation by a single injection of either r-human (h)CG ( 250 microg ) ( n = 11 ) , r-LH ( 1 mg ) ( n = 13 ) , or GnRH agonist ( triptorelin ; 0.2 mg ) ( n = 15 ) . Retrieved oocytes were fertilized by either IVF or intracytoplasmatic sperm injection , depending on sperm quality . Embryo transfer was performed 3 - 4 d after oocyte retrieval . No luteal support was provided . Serum concentrations of FSH , LH , estradiol ( E(2 ) ) , progesterone ( P ) , and hCG were assessed at fixed intervals during the follicular and luteal phase . The median duration of the luteal phase was 13 , 10 , and 9 d for the r-hCG , the r-LH , and the GnRH agonist group , respectively ( P = 0.005 ) . The median area under the curve per day ( from 4 d post r and omization until the onset of menses ) for LH was 0.50 , 2.34 , and 1.07 for the r-hCG , the r-LH , and the GnRH agonist group , respectively ( P = 0.001 ) . The median area under the curve per day for P was 269 vs. 41 and 16 for the r-hCG , the r-LH , and the GnRH agonist group , respectively ( P < 0.001 ) . Low pregnancy rates ( overall , 7.5 % ; range , 0 - 18 % per started cycle ) were observed in all groups . In conclusion , the nonsupplemented luteal phase was insufficient in all three groups . In the patients receiving r-hCG , the luteal phase was less disturbed , compared with both other groups , presumably because of prolonged clearance of hCG from the circulation and the result ing extended support of the corpus luteum . Despite high P and E(2 ) concentrations during the early luteal phase in all three groups , luteolysis started prematurely , presumably because of excessive negative steroid feedback result ing in suppressed pituitary LH release . Hence , support of corpus luteum function remains m and atory after ovarian stimulation for IVF with GnRH antagonist cotreatment A polysyloxane vaginal ring containing 1 g of natural progesterone was developed as luteal supplementation for women treated with IVF-embryo transfer and for agonadal women participating in an oocyte donation programme . The ring provides continuous release of progesterone ( 10 - 20 nmol/l ) for 90 days . The efficacy of this form of progesterone supplementation was evaluated in two multicentre prospect i ve r and omized trials . IVF-embryo transfer trial : After oocyte aspiration , 505 women were r and omly allocated to progesterone supplementation with vaginal ring or i.m . progesterone ( 50 mg/day ) . The clinical pregnancy rate was 36.6 % in both groups . Implantation rate was 15.9 % in the vaginal ring and 16.0 % in i.m . progesterone . Oocyte donation trial : After endometrial proliferation with micronized oestradiol , 153 women were allocated to progesterone replacement with a vaginal ring or i.m . progesterone ( 100 mg/day ) . Clinical pregnancy rate was 39.8 and 28.6 % respectively . Implantation rate was significantly higher with the vaginal ring compared with i.m . progesterone ( 19.9 and 11.6 % respectively , P = 0.006 ) . The vaginal ring is a novel development which provides continuous release of progesterone for 90 days . In IVF-embryo transfer , its effectiveness is similar to daily i.m . injections . In oocyte donation the ring provides a progestative milieu which improves the implantation rate and eliminates the discomfort of daily i.m . injections A r and omized controlled study of luteal support therapy ( using intramuscular injections of progesterone and /or human chorionic gonadotropin ) was conducted in a trial design ed to minimize variables that might adversely affect the change of pregnancy . After applying rigid selection criteria , 207 women were recruited into one of four groups . Mathematical modeling was applied to the results to determine if there were degrees of improvement in uterine receptivity relative to various grade s of embryo quality ( " E " factor ) . Although the trial size was insufficient to enable the detection of significant improvements in the pregnancy rates that ranged from 27.5 % for non-treatment to 41.2 % for those receiving combined treatment , the birth rates were significantly better with luteal support ( 11.8 % versus 29.4 % ) . Similarly , the overall implantation rate just failed to reach statistical significance for luteal support , but the ongoing implantations were significantly better ( 3.6 % versus 9.0 % ) . Data modeling indicated that luteal support , particularly with the combined regimen , could improve the ongoing implantation rate by up to 2.5-fold when the E factor was poorest In an attempt to determine the best luteal support in in-vitro fertilization ( IVF ) cycles treated with gonadotrophin-releasing hormone agonist ( GnRHa ) and human menopausal gonadotrophin ( HMG ) by the ultrashort protocol , 60 patients were prospect ively r and omized for either i.m . progesterone or human chorionic gonadotrophin ( HCG ) luteal support . The two groups did not differ in the mean number of oocytes retrieved and embryos replaced , nor in the mean age of the patients and the amount of HMG used . HCG maintained higher levels of oestradiol and progesterone during the luteal phase . Conception rate was significantly higher in the HCG group . We conclude that HCG is superior to i.m . progesterone as luteal support in IVF cycles in which GnRHa is used in the ultrashort protocol Gonadotrophin-releasing hormone agonists ( GnRHa ) are widely used in in-vitro fertilization ( IVF ) for the prevention of a premature rise in luteinizing hormone ( LH ) concentrations . However , the administration of GnRHa during the follicular phase may also impair subsequent luteal function due to retarded recovery of pituitary gonadotrophin secretion . Therefore , luteal supplementation is generally applied . The present study was design ed to determine whether a premature LH surge would still be prevented after early cessation of GnRHa during ovarian stimulation and whether subsequent luteal phase LH production would be sufficient to support progesterone synthesis by the corpus luteum . Sixty patients were r and omized for three groups : ( i ) A long GnRHa/human menopausal gonadotrophin ( HMG ) protocol with luteal support by repeated human chorionic gonadotrophin ( HCG ) ( n = 20 ) , ( ii ) early follicular phase cessation of GnRHa without luteal support ( n = 20 ) , and ( iii ) a long GnRHa protocol without luteal support ( n = 20 ) . Frequent ultrasound and blood sampling was performed during the entire IVF cycle . Forty normo-ovulatory women served as controls . No premature LH surges were found after early cessation of GnRHa . In this group , some pituitary recovery occurred during the late luteal phase , but this did not affect corpus luteum function . Progesterone concentrations were shown to be dependent on disappearance of the pre-ovulatory bolus of HCG . Pregnancies occurred in all three groups . In conclusion , early follicular phase cessation of GnRHa is still effective in the prevention of a premature rise in LH . Although some pituitary recovery was observed thereafter , corpus luteum function is still abnormal due to early luteolysis BACKGROUND The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF . METHODS Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used . All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test . The study group ( n = 150 ) withdrew vaginal progesterone from the day of positive HCG . The control group ( n = 153 ) continued administration of vaginal progesterone during the next 3 weeks of pregnancy . RESULTS The number of miscarriages prior to and after week 7 of gestation was seven ( 4.6 % ) and 15 ( 10.0 % ) in the study group and five ( 3.3 % ) and 13 ( 8.5 % ) in the control group respectively . The number of deliveries was 118 ( 78.7 % ) in the study group and 126 ( 82.4 % ) in the control group . The differences were not significant . CONCLUSIONS Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate , and thus no effect on the delivery rate . Progesterone supplementation can safely be withdrawn at the time of a positive HCG test A simple programmed thaw cycle is described , during which the endometrium is prepared with oral oestradiol , followed by a natural progesterone source . This method involves minimal blood tests and uses inexpensive medications . Originally , an i.m . progesterone-in-oil preparation was used . Although highly successful in achieving high serum progesterone concentrations , the daily injections of the oily compound were found to be problematic from the patients ' perspective . To examine the possibility of replacing the injectable progesterone with a vaginal preparation we conducted a prospect i ve r and omized study of 1 year 's duration , during which time 170 and 184 thawing cycles were done with injectable and vaginal progesterone respectively . Although the progesterone blood concentrations obtained with the injectable preparation were more than twice those obtained with the vaginal progesterone , the clinical pregnancy rates ( defined as percentage thawing cycles with gestational sac(s)/embryo transfer as demonstrated on ultrasound , 4 weeks after embryo transfer ) were similar for both groups ( 15.9 and 16.8 % respectively ) . Implantation and abortion rates were also comparable . These results agree with previous reports of higher uterine progesterone concentrations after the vaginal application . We conclude that the combination of oral oestradiol and vaginal progesterone is an effective , simple and inexpensive approach for programmed thaw cycles This study was conducted to compare the endocrine milieu and pregnancy rates in an in-vitro fertilization and embryo transfer ( IVF-ET ) programme employing a gonadotrophin-releasing hormone agonist ( GnRHa ) and human menopausal gonadotrophin ( HMG ) when either human chorionic gonadotrophin ( HCG ) or progesterone were used for luteal phase support . A total of 121 IVF-ET treatment cycles were prospect ively studied . All patients started leuprolide acetate in the midluteal phase and it was continued for at least 10 days . When oestradiol levels were less than 150 pmol/l , HMG was started . When at least three follicles were greater than or equal to 17 mm in diameter , HCG 5000 IU i.m . was given . Oocytes were retrieved using transvaginal ultrasound and embryos were transferred 48 h later . The patients ' cycles were prospect ively r and omized to receive HCG ( 72 cycles ) or progesterone ( 49 cycles ) luteal support . The HCG group received 1500 IU i.m . on days 3 , 6 and 9 after the initial trigger . The progesterone group received 12.5 mg i.m . q.d . starting from the day after the HCG trigger . The dose of progesterone was increased to 25 mg i.m . q.d . starting on the day of embryo transfer and continued for 17 - 21 days . If the patient became pregnant , this dose of progesterone was continued until fetal heart activity was visualized by ultrasound . Mean ages , number of eggs retrieved , embryos transferred , oestradiol levels on the day of the HCG trigger , oestradiol and progesterone at the time of embryo transfer were the same in both groups . ( ABSTRACT TRUNCATED AT 250 WORDS Salivary oestradiol ( E2 ) and progesterone ( P ) levels have been shown to reflect the biologically active fractions in the serum . The luteal-phase status of stimulated cycles was investigated after in vitro fertilization and embryo transfer ( IVF-ET ) . Thirty patients were r and omly allocated to one of three luteal therapy groups : group A had no support , group B had intramuscular P and group C had intramuscular P and human chorionic gonadotrophin ( hCG ) . One pregnancy was achieved in group A , two in group B and three in group C. Significant correlations between salivary and serum levels of E2 and of P in matched sample s during luteal phase were found . Salivary E2 levels from luteal day 8 through day 14 and P levels from day 3 through day 14 were significantly higher in the pregnant than in the nonpregnant cycles . Among the nonpregnant cycles , salivary E2 and P levels were significantly higher in group C than in group A or B. These findings suggest that , in stimulated cycles for IVF-ET , determination of salivary E2 and P levels may be used as reliable alternatives to serum concentrations for assessing the luteal phase . Also , the additional hCG has an enhanced luteotrophic effect , as reflected by the higher salivary E2 and P levels , which may lead to a better pregnancy rate In order to determine the effect of early pregnancy support with intermittent injections of human chorionic gonadotropin ( hCG ) , 60 patients with positive serum pregnancy tests following in vitro fertilization ( IVF ) or gamete intra-fallopian transfer ( GIFT ) were r and omly allocated into 2 groups . Those in one group were given 5,000 IU of hCG twice weekly until they reached 12 weeks gestation , or miscarried . Those in the other group acted as controls . There was no difference in the serum progesterone level or in pregnancy outcome noted between the 2 groups . The miscarriage rate in each group was 26.6 % . It is concluded that exogenous hCG has no significant role to play once biochemical pregnancy has been achieved in patients with normal hormone profiles on an IVF program OBJECTIVE To compare the efficacy of Crinone 8 % intravaginal progesterone gel vs. IM progesterone for luteal phase and early pregnancy support after IVF-ET . DESIGN R and omized , open-label study . SETTING Academic medical center . PATIENT(S ) Two hundred and one women undergoing IVF-ET . INTERVENTION(S ) Women were r and omized to supplementation with Crinone 8 % ( 90 mg once daily ) or IM progesterone ( 50 mg once daily ) beginning the day after oocyte retrieval . MAIN OUTCOME MEASURE(S ) Pregnancy , embryo implantation , and live birth rates . RESULT ( S ) The women r and omized to luteal phase supplementation with IM progesterone had significantly higher clinical pregnancy ( 48.5 % vs. 30.4 % ; odds ratio [ OR ] , 2.16 ; 95 % confidence interval [ CI ] , 1.21 , 3.87 ) , embryo implantation ( 24.1 % vs. 17.5 % ; OR , 1.89 ; 95 % CI , 1.08 , 3.30 ) , and live birth rates ( 39.4 % vs. 24.5 % ; OR , 2.00 ; 95 % CI , 1.10 , 3.70 ) than women r and omized to Crinone 8 % . CONCLUSION ( S ) In women undergoing IVF-ET , once-a-day progesterone supplementation with Crinone 8 % , beginning the day after oocyte retrieval , result ed in significantly lower embryo implantation , clinical pregnancy , and live birth rates compared with women supplemented with IM progesterone Deficiency in the luteal phase has been shown during stimulated cycles using a protocol involving a GnRH agonist . The authors undertook a r and omised prospect i ve trial of supplementation by progesterone of the luteal phase and of early pregnancy in two hundred and seventy two patients requiring fertilisation in vitro ( FIV ) , gamete inter-fallopian transfer ( GIFT ) or zygote inter-fallopian transfer ( ZIFT ) . Either progesterone in solution in oil ( 50 mg/day ) administered by intramuscular injection or micronized progesterone administered intra-vaginally ( 600 mg/d ) were used as support for the luteal phase . Administration of progesterone in association with estradiol valerate was started on the day prior to oocyte puncture and was continued until the 12th week of pregnancy . The implantation rate was very close to the threshold of significance ( P = 0.07 ) in favour of the patients given vaginal progesterone . There was a higher rate of clinical pregnancies ( 33.6 versus 26.7 p. cent ) in the latter group , though this was not significant . While plasma progesterone ( Pg ) levels were lower in patients using vaginal progesterone , the abortion rate during the first three months was lower in this group ( P < 0.05 ) . Micronized progesterone administered vaginally was well tolerated by all patients . During stimulated cycles , notably by GnRHa , it thus proved to be more effective than Pg administered by intramuscular injection with regard to implantation and abortion rates Luteal support is essential in in-vitro fertilization ( IVF ) when long-acting gonadotrophin-releasing hormone agonist ( GnRHa ) is used . Because progesterone lacks luteotrophic stimulation , it seems to be the drug of choice in cases with an increased risk of ovarian hyperstimulation syndrome ( OHSS ) . The aim of this study was to assess the beneficial effect of the mid-luteal addition of human chorionic gonadotrophin ( HCG ) in IVF , using a down-regulation protocol and luteal support with progesterone , in a prospect i ve r and omized study . The study included 170 IVF cycles down-regulated with long-acting GnRHa which were supported with 50 mg/day progesterone i.m . during the luteal phase . Patients were evaluated in the mid-luteal period . Those without clinical signs of OHSS , oestradiol concentrations < 1000 pg.ml and progesterone concentrations < 50 ng/ml were r and omly allocated to either the addition of 2500 IU HCG ( HCG+ group ) or no HCG ( HCG- group ) . End luteal phase progesterone concentrations among non-pregnant patients were used to assess the contribution of exogenous progesterone and to categorize pregnancies according to their corpus luteum function . Similar low OHSS ( 2.7 and 1.8 % ) and pregnancy ( 30 and 29 % ) rates were observed in the HCG+ and HCG-groups respectively . Of the 26 pregnancies in the HCG+ cases , there was only one case with reduced corpus luteum function , compared with 12 or the 25 pregnancies among HCG- patients . Cases with reduced corpus luteum function required continuous progesterone support and presented lower betaHCG concentrations and a higher rate of adverse pregnancy outcome . We conclude that mid-luteal HCG addition does not affect pregnancy rate , but in fact helps to preserve corpus luteum function and avoids the need for further supplementation during early pregnancy OBJECTIVE To evaluate the possible role for estrogen supplementation to the P luteal phase support of GnRH agonists (GnRH-a)- and hMG-induced IVF-ET cycles . SETTING In vitro fertilization unit in a tertiary care university hospital . DESIGN A prospect ively r and omized study . PATIENTS One hundred consecutive patients undergoing ET after IVF were assigned into one of two luteal supplementation regimens . INTERVENTIONS In all patients enrolled in the study , ovulation was induced using the midluteal regimen for pituitary down regulation with GnRH-a followed by follicular stimulation with hMG . The first group received IM P 50 mg/d , as luteal phase support , starting the day of ET . The second group received the same dosage of P , combined with oral E2 valerate , 2 mg/d . Serum levels of P and E2 were monitored every 4 days for 16 days after ET . MAIN OUTCOME MEASURES Pregnancy rates ( PRs ) and live birth rates per ET . RESULTS No significant difference in E2 or P levels throughout the cycle was observed between groups . Similar PRs per ET and the live birth rates were also observed between group A and B ( 28 % versus 26.5 % and 78.6 % versus 76.1 % , respectively ) . CONCLUSION No advantage was found in the addition of E2 valerate to P luteal phase support of GnRH-a- and hMG-induced IVF-ET cycles A study was undertaken to compare the hormonal parameters [ serum concentrations of estradiol ( E2 ) , and progesterone ( P ) and P/E2 ratios ] of patients undergoing in vitro fertilization/embryo transfer to whom either progesterone in oil or human chorionic gonadotropin ( hCG ) was administered as luteal support . Seventeen patients were studied in 20 cycles . In 10 r and omly assigned cycles 25 mg of intramuscular progesterone in oil was administered daily from the day of embryo transfer ( day + 4 ) until day + 18 . In the other 10 cycles , 1500 IU of hCG was given intramuscularly on days + 4 , + 7 , + 10 , and + 13 . Even when accounting for the differences in recruitment in the two groups , the hCG-treated group had significantly higher concentrations of serum P ( P<0.01 ) and E2 ( P<0.05 ) during the luteal phase . The luteal P/E2 ratios were higher in the progesterone-treated group because of the lower E2 levels in that group , although the difference was not statistically significant . The ratio of the mean luteal P to the preovulatory serum E2 was significantly higher in the hCG-treated group ( P<0.01 ) . There were three clinical pregnancies in the hCG-treated group . We conclude that ( 1 ) higher P concentrations are achieved with hCG treatment than with progesterone treatment during the luteal phase ; ( 2 ) high luteal P/E2 ratios per se may not be an important determinant of implantation ; ( 3 ) progesterone production by the corpus luteum is not maximal in progesterone-treated cycles ; and ( 4 ) the usefulness of hCG as a luteal support agent should be further evaluated To evaluate any beneficial effect of progesterone supplementation during the luteal phase of GIFT or IVF cycles stimulated by clomiphene citrate and HMG , two r and om prospect i ve studies were performed . In the first study , a group of patients received a luteal phase supplement of 50 mg natural progesterone i.m . daily from the day of oocyte retrieval onwards . Initial results on 168 patients indicated that the pregnancy rate was similar in patients with or without progesterone supplements . No differences were found between the two groups in an analysis of pregnant and failed cycles . In a second study two different protocol s of luteal phase supplementation after Buserelin-HMG stimulation were compared : natural progesterone in combination with oestradiol valerate ( 50 patients ) or HCG supplements ( 41 patients ) . A 32 % pregnancy rate per cycle was encountered in both groups . Endometrial biopsies , taken during the luteal phase from patients who did not undergo embryo replacement , revealed retarded endometrial development in most of the biopsies A luteal phase defect has been demonstrated in cycles stimulated using a protocol including a gonadotrophin releasing hormone agonist ( GnRHa ) . We have conducted a r and omized prospect i ve study of luteal and early pregnancy supplementation in 262 women selected for in-vitro fertilization ( IVF ) , gamete intra-Fallopian transfer ( GIFT ) or zygote intra-Fallopian transfer ( ZIFT ) . Either intramuscular progesterone in oil ( 50 mg/day ) or intravaginal micronized progesterone ( 600 mg/day ) was used as luteal supplement . In association with oestradiol valerate , progesterone administration was initiated from the day before oocyte retrieval until the 12th week of pregnancy . The implantation rate just failed to reach statistical significance ( P = 0.07 ) in favour of the group receiving intravaginal progesterone . In the latter group , we observed a higher clinical pregnancy rate ( 33.6 versus 26.7 % , not significant ) . Despite lower plasma progesterone levels , a lower first trimester abortion rate ( P less than 0.05 ) was found in the intravaginally treated group . Intravaginal micronized progesterone was well tolerated by all patients and appeared more effective than intramuscular progesterone in improving the implantation rate , and in decreasing the incidence of abortions in stimulated cycles including GnRHa Two progesterone presentations , a vaginal application of 90 mg progesterone per day ( Crinone ) or 300 mg progesterone administered orally ( Utrogestan ) , were compared for luteal phase support of patients undergoing an in-vitro fertilization ( IVF ) procedure . A total of 283 patients were r and omly allocated to either treatment . The treatment started within 24 h after the embryo transfer procedure and continued until day 30 in cases of implantation . Efficacy was assessed using the pregnancy and delivery rates . Safety was assessed through specific symptoms and usual safety monitoring . The pregnancy rates per transfer were not significantly different in the Crinone and Utrogestan groups at days 12 ( Crinone 35.3 % , Utrogestan 29.9 % , P = 0.55 ) , 30 ( Crinone 28.5 % , Utrogestan 25.0 % , P = 0.61 ) and 90 ( Crinone 25.9 % , Utrogestan 22.9 % , P = 0.69 ) . No differences in the spontaneous abortion rates were seen thereafter . The delivery rates ( number of deliveries per patient ; Crinone 23.0 % , Utrogestan 22.2 % , P = 1.00 ) , as well as the ratio of newborn babies per embryo transferred ( Crinone 11.7 % , Utrogestan 11.1 % , P = 0.91 ) , were not significantly different . Safety parameters were similar in both groups , except for drowsiness , which was more significantly frequent in the oral progesterone group than in the Crinone group at all time points . No serious adverse events were recorded in this study . The fact that Crinone matches the efficacy of the larger doses of progesterone used orally reflects an advantage of the transvaginal route of administration which avoids the metabolic inactivation of progesterone during its first liver pass A r and omized control trial involving 42 superovulated in vitro fertilization ( IVF ) patients was carried out to investigate the effects of providing supplementary progesterone ( P ) around the time of laparoscopy . P was given 12 to 15 hours and 1 hour before and 24 hours after laparoscopy in one group ( group B ) ; human chorionic gonadotropin was given 12 hours before laparoscopy in another group ( group C ) ; and the remainder received no treatment in addition to normal IVF procedures ( group A ) . There was no difference in fertilization rate , the proportion of normally developing embryos , pregnancy rate , or birth rate between the treatment groups , We conclude that in the superovulation schedule used , P supplementation around the time of laparoscopy does not affect success rate of IVF BACKGROUND To compare local tolerance and patients compliance to intravaginal and intramuscular progesterone administration . METHODS Ninety-nine patients have been r and omised to receive either intravaginal Crinone , 90 mg/day ( n=51 ) or intramuscular Prontogest 50 mg/day ( n=48 ) for luteal supplementation in IVF/ICSI cycles . Local and systemic side effects as well as pattern of menstrual bleeding were reported on a self administered question naire . Progesterone levels were evaluated pre-treatment , in the mid-luteal phase and the day of pregnancy test . RESULTS Patients age , BMI , duration and causes of infertility were comparable in the two treatment groups . All parameters of ovarian response as well as pregnancy rates did not show significative difference in the two groups . A significative larger number of patients assigned to intravaginal support were free from side effects . Furthermore side effects , when reported , result ed significantly more severe in the intramuscular group . In the non pregnant patients menstrual flow appeared significantly earlier in those treated with vaginal progesterone ( p<0.001 ) . CONCLUSIONS Crinone 8 is a good alternative to parental progesterone for luteal support in ART cycles . It is well tolerated but it is linked to an earlier appearance of menstrual flow in non conceptional cycles OBJECTIVE To evaluate the effect of adding E(2 ) to progestin supplementation during the luteal phase on pregnancy and implantation rates in patients undergoing IVF cycles . DESIGN Prospect i ve , r and omized study . SETTING An IVF unit in a university hospital . PATIENT(S ) Patients who were undergoing IVF with controlled ovarian hyperstimulation using a GnRH analog and who had E(2)2,500 pg/dL at the time of hCG administration . INTERVENTION(S ) Serum concentrations of E(2 ) and progesterone were measured in all patients on days 7 , 10 , and 12 after ET . MAIN OUTCOME MEASURE(S ) The E(2 ) and progesterone profiles of the luteal phase and the pregnancy and implantation rates were documented . Data were analyzed for the entire study population and further stratified according to the GnRH analog protocol used ( short or long ) . RESULT ( S ) Significantly higher E(2 ) levels were found during the luteal phase in the group that received E(2 ) supplementation . This effect was more pronounced in the patients who were treated with the long GnRH analog protocol . Significantly higher pregnancy and implantation rates were recorded in the patients who received E(2 ) supplementation and were treated with the long GnRH analog protocol . CONCLUSION ( S ) For patients who are treated with the long GnRH analog protocol for controlled ovarian hyperstimulation and for whom luteal support with hCG is contraindicated , the addition of E(2 ) to the progestin support regimen may have a beneficial effect on pregnancy and implantation rates The use of luteal phase support has been demonstrated in patients undergoing IVF/ET in cycles stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists . However , it is still not clear which is the most suitable kind of supplementation . This study was design ed to compare the absorption and the efficacy of three different luteal support . We r and omly administered progesterone i.m . ( 50 mg/day ) , human chorionic gonadotrophin ( hCG ) ( 2000 IU every three days ) , progesterone vaginal cream ( 100 mg/day ) or nothing ( controls ) to 176 women treated for assisted procreation . We were not able to show any statistical differences for the percentage of pregnancy rate between groups . The serum progestrerone ( P ) and 17-ß-estradiol ( E2 ) and E2/P ratio levels of the luteal phase were compared with the control not supplemented group . All the treatments were able to increase significantly the luteal P values versus controls ( p<0.01 ) . Moreover , vaginal cream and natural P i m significantly decreased E2/P ratio ( p<0.05 ) . Serum P levels were more steady with P vaginal cream than i m injection . Vaginal cream for better bioavailability and acceptance appear the most suitable and comfortable method for luteal phase support Endometrial biopsies showing inadequate development were observed after ovarian stimulation with the GnRH agonist Buserelin and HMG for IVF or GIFT when luteal supplementation was omitted . Ninety-one patients were r and omly allocated to two luteal supplementation regimens : in 41 women HCG and in 50 women progesterone and oestradiol valerate . The pregnancy patients treated with a combination of the GnRH agonist and HMG a delay of implantation of 1.3 days was observed compared to pregnancies after clomiphene citrate-HMG stimulation . This delay was not due to slower preimplantation embryo development after GnRH agonist-HMG treatment . Temporarily defective function of the corpus luteum was evidence d by measuring serum progesterone , 17 beta-oestradiol and 17-hydroxyprogesterone in the patients receiving progesterone and oestradiol valerate . This inadequate corpus luteum function could be related to the prolonged blockage of pituitary gonadotrophic function after arrest of the GnRH agonist The Crinone 8 % preparation makes it possible to administer natural progesterone ( 90 mg ) vaginally once daily for luteal phase support ( LPS ) . Until now , no prospect i ve , r and omized studies have directly compared this new preparation with widely used Utrogest capsules , which were originally design ed for oral administration but are used routinely as a vaginal preparation . A prospect i ve , r and omized study investigated 126 patients undergoing cycles of in vitro fertilization ( IVF ) and IVF/intracytoplasmic sperm injection ( ICSI ) . Patients received either Crinone 8 % ( n = 73 ) vaginally once daily or two Utrogest capsules ( n=53 ) vaginally three times daily ( 600 mg ) . Clinical pregnancy rates were comparable ( 28.8 versus 18.9 % ) , as were clinical abortion rates until 12 weeks of gestation ( 14.3 versus 10.0 % ) and clinical ongoing pregnancy rates ( 24.7 versus 17.0 % ) in the Crinone 8 % and Utrogest groups , respectively . Forty-seven non-pregnant patients were r and omly selected to answer questions regarding comfort during LPS . Crinone 8 % had a clear advantage over Utrogest as it result ed in less vaginal discharge ( P < 0.01 ) and fewer application difficulties ( P<0.05 ) . Twenty patients familiar with the alternative preparation from a previous cycle also noted that Crinone 8 % was easier to apply ( P < 0.01 ) and less time consuming ( P < 0.05 ) to use than Utrogest This prospect i ve r and omized study compared human chorionic gonadotropin ( hCG ) and micronized transvaginal progesterone for luteal support in 310 in vitro fertilization ( IVF ) patients treated with leuprolide acetate and gonadotropins in a long protocol , and showing normal ovarian response . Both treatment groups were homogeneous for age , BMI , stimulation treatment and ovarian response . Pregnancy rates per embryo transfer were not significantly different ( 33.1 % for the hCG group versus 38.7 % for the progesterone group ) . For IVF patients with a normal response to stimulation under pituitary supression , the use of hCG or progesterone for luteal support does not seem to have any effect on pregnancy rate . The choice of luteal treatment must balance medical hazard and patient convenience , as both therapeutic regimens seem equally effective Objective The purpose of the study was to determine the impact of two forms of luteal-phase supplementation , human chorionic gonadotropin ( hCG ) and progesterone ( P ) , during gonadotropin releasing hormone agonist (GnRha)/controlled ovarian hyperstimulation ( COH ) cycles . Design and Patients The study was a prospect i ve , r and omized evaluation of 77 patients . Group 1 patients ( n=38 ) received 2000 IU of hCG , injected subcutaneously , on days 3 , 6 , 9 , and 12 after transvaginal aspiration of the oocytes ( TVA = day 0 ) . Group 2 patients ( n=39 ) received 50-mg daily injections of intramuscular ( i.m . ) P from days 2 to 14 after TVA . Blood tests were performed on days 0 , 5 , 8 , and 12 after TVA . Setting The in vitro fertilization program of a tertiary care institution was the study setting .Main Outcome Measures The main outcome measures were ( 1 ) pregnancy and implantation rates ; ( 2 ) serum estradiol ( E ) , P , and hCG levels ; and ( 3 ) occurrence of side effects . Results Clinical pregnancy and implantation rates in group 1 versus group 2 were similar ( 36.7 vs 35.3 and 12 vs 14 % , respectively ) . Regardless of pregnancy occurrence , on days 8 and 12 after TVA , serum E and P levels were higher in group 1 than group 2 but the result ing E/P ratios were similar . Five of 38 patients ( group 1 ) developed moderate to severe ovarian hyperstimulation syndrome ( OHSS ) right after the first or second supplementary hCG injection . In these patients , the mean serum E level on the day of hCG trigger injection was about 3250 pg/ml and the number of follicles was between 9 and 17 . In 6 of 39 patients ( group 2 ) allergic reactions were observed at the P injection sites . Conclusions Based on our data , hCG administration as a form of luteal supplementation did not translate , in comparison to P , into significant benefits for the patients . At the same time , it significantly increased the risk of ovarian hyperstimulation . We suggest that whenever , during COH cycles , serum E levels are over 2500 pg/ml and the number of follicles exceeds 10 , luteal support with hCG should be excluded OBJECTIVE To determine if pregnancy rates ( PRs ) for clomiphene citrate (CC)-stimulated IVF-ET can be increased by luteal support with E2 and P. DESIGN Prospect i ve r and omized crossover clinical study . SETTING Infertile women volunteers in an academic research environment . PATIENTS Ninety-three infertile women underwent a total of 143 IVF-ET cycle using CC for ovulation induction . INTERVENTIONS Each woman received either no luteal support ( control group ) or luteal support with both oral E2 ( 2 mg three times daily ) starting on the day of retrieval and vaginal P suppositories ( 100 mg twice daily ) starting on the day of ET . MAIN OUTCOME MEASURE Clinical PR . RESULTS In 79 of 143 ( 55 % ) of the cycles , at least one embryo was transferred . Compared with the control group ( n = 35 cycles ) , the luteal support group ( n = 44 cycles ) had a significantly higher PR per retrieval ( control : 2 % versus luteal support : 16 % ) and were older ( control : 33 + /- 4 versus luteal support : 35 + /- 4 years ; mean + /- SEM ) . They did not differ in terms of E2 or P levels , endometrial thickness on the day of hCG , number of follicles > 16 mm in diameter , mature oocytes retrieved , or embryos transferred . CONCLUSIONS Luteal support with both E2 and P significantly increase the clinical PRs for CC-stimulated IVF-ET The effectiveness and the absorption of two progesterone ( P ) presentations have been compared for luteal phase support of patients aged < or = 37 years undergoing an in vitro fertilization ( IVF ) procedure for the first time , who were stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists ( GnRHa ) . All of them had two ovaries , normal ovarian functions and normal endometrial morphology : the indication for the assisted reproductive technique was the tubal factor . Two hundred and fifty patients were r and omly allocated to two groups in order to compare two treatment protocol s : Group A : natural i.m . P ( 50 mg/day , Prontogest , AMSA , Italy ) ; Group B : micronized vaginal P ( 200 mg/day Esolut , Angelini , Italy ) . We were able to show that the i.m . P result ed in a higher percentage of pregnancies than the vaginal preparation , with statistically significant differences . We recommend the use of injectable P , and suggest reserving intravaginal P as a second choice for patients who can not tolerate intramuscular administration ABSTRACT HCG or human pituitary LH was administered to normal women during the luteal phase of the menstrual cycle . Functional activity of the corpora lutea was assessed by measurements of plasma progestogen levels by a competitive protein binding method . Both HCG and LH treatment produced significant elevations in progestogen levels . Levels in treatment cycles were 2–3 times those observed in control cycles . The interval between menses was lengthened 6 , 7 and 9 days in the 3 HCG-treated women and 3 , 7 and 8 days in the LH-treated women . These data suggest that both LH and HCG are capable of stimulating progesterone synthesis in a normal corpus luteum in vivo The effect of hCG and pregnancy on the circulating levels of relaxin was investigated in 48 women undergoing in vitro fertilization and embryo transfer ( ET ) for the treatment of infertility . Subjects were allocated r and omly to receive hCG ( Profasi ; 2000 IU , i m ) or placebo on the day of ET ( day 0 ) and on day 3 after ET ( day 3 ) . Sample s of peripheral blood were taken on days -4 , 6 , and 10 . An additional sample was taken on day 22 from women who became pregnant . The subjects were allocated retrospectively to 1 of 4 groups : no pregnancy , no hCG ( NP ) ; pregnancy , no hCG ( P ) ; no pregnancy , hCG ( NPH ) ; and pregnancy , hCG ( PH ) . Two patients with blighted ova and one with a tubal pregnancy were excluded from the analysis . The concentrations of relaxin were similar and rose significantly in all groups at each time point ( P less than 0.05 ) . On day 6 there was no significant difference in the increment between the groups , but by day 10 , circulating levels in the P compared to the NP and those in the PH compared to the NPH group were significantly greater ( P less than 0.05 ) . By day 22 the difference between the PH and the P groups was significant ( P less than 0.05 ) . Relaxin levels correlated with progesterone levels on day 10 in the NP and P groups ( r = 0.633 ; P less than 0.05 and r = 0.697 ; P less than 0.05 , respectively ) and with estradiol levels in the P group only on days 6 and 22 ( r = 0.659 ; P less than 0.05 and r = 0.783 ; P less than 0.05 , respectively ) . These data demonstrate that in women undergoing in vitro fertilization , relaxin levels increase during the luteal phase , and in those women who establish a pregnancy , the values are significantly greater by day 10 . The administration of hCG in the early luteal phase , before implantation , to women who subsequently become pregnant significantly increased the level of circulating relaxin on day 22 . The positive correlation between relaxin levels and ovarian steroid levels in the groups not receiving exogenous hCG suggests that a common factor may control the release of both OBJECTIVE To evaluate the efficacy of oral micronized progesterone compared with IM progesterone in oil for luteal support in patients undergoing IVF who are treated with a GnRH agonist . DESIGN R and omized prospect i ve clinical trial . SETTING University-based IVF center . PATIENT(S ) Women < 40 years of age who were undergoing IVF with luteal GnRH pituitary down-regulation . INTERVENTION(S ) Patients were r and omized to receive either oral micronized progesterone ( 200 mg three times daily ) or IM progesterone ( 50 mg daily ) . MAIN OUTCOME MEASURE(S ) Progesterone levels at st and ardized days 21 and 28 , and pregnancy and embryo implantation rates . RESULT ( S ) Day 21 progesterone levels were 77.6+/-13.2 ng/mL in the IM group and 81.5+/-16.2 ng/mL in the oral group . Day 28 progesterone levels were 76.3+/-15.0 ng/mL in the IM group and 53.6+/-10.1 ng/mL in the oral group . The clinical pregnancy rates were 57.9 % and 45.8 % for the IM and oral groups , respectively . The implantation rate per embryo was significantly higher in the IM group ( 40.9 % ) than in the oral group ( 18.1 % ) . CONCLUSION ( S ) When used according to our protocol s , oral progesterone and IM progesterone result in comparable levels of circulating progesterone . However , oral progesterone results in a reduced implantation rate per embryo OBJECTIVE To compare the efficacy of a vaginal progesterone preparation with our st and ard IM preparation within a donor egg program . DESIGN Prospect i ve r and omized trial . SETTING Donor egg program at a university assisted reproductive therapy program ( Jones Institute for Women 's Health ) . PATIENT(S ) Couples accepted into the donor egg program because of either premature ovarian failure or evidence of diminished ovarian reserve . INTERVENTION(S ) Women were r and omized into either a group receiving IM progesterone replacement or a group receiving vaginal progesterone replacement . Both groups underwent Estraderm patch/progesterone treatment in a mock cycle leading to an endometrial biopsy on day 26 followed by a second cycle in which ET was performed . Subjects with residual ovarian function received a GnRH agonist . In the IM treatment group , 100 mg was administered from cycle days 15 to 27 . In the vaginal treatment group , Crinone 8 % , a polycarbophil-based gel preparation containing 90 mg of micronized progesterone , was administered twice daily from the evening of day 14 . MAIN OUTCOME MEASURE(S ) Endometrial histology , serum levels of progesterone ( on days 13 , 17 , 20 , 24 , and 26 ) , the occurrence of pregnancy , implantation rate , and pregnancy outcome . RESULT ( S ) Fifty-four women r and omized into the vaginal progesterone treatment group and 18 women in the IM treatment group achieved ET . Mean serum progesterone levels were higher in the IM treatment group than in the Crinone group . Endometrial histology was " in phase " for all subjects in both groups . Clinical pregnancies were observed in 26 of 54 women and 5 of 18 women in the Crinone and IM progesterone groups , respectively . The ongoing pregnancy rate ( PR ) of 31 % ( 17/54 ) and implantation rate of 23 % in the subjects receiving Crinone was not statistically different from the IM progesterone group 's ongoing PR of 22 % ( 4/18 ) and implantation rate of 18 % . CONCLUSION Vaginal progesterone replacement with the polycarbophil gel preparation was as effective as IM progesterone in producing clinical and ongoing pregnancies within our donor egg program in the dosages administered The necessity of luteal-phase supplementation in an IVF programme is of continuing interest . After ovarian stimulation with clomiphene and human menopausal gonadotrophin ( HMG ) , the beneficial effect of supporting the luteal phase has never been scientifically demonstrated . After ovarian stimulation with GnRH agonist/HMG , the luteal phase seems to be inadequate , but in a previous study we did not find evidence to support the need for oral progesterone supplementation . To evaluate the beneficial effect of human chorionic gonadotrophin ( HCG ) supplementation , we performed a multicentre , double-blind , r and omized study with HCG ( 193 transfers ) against placebo ( 194 transfers ) . The ongoing pregnancy rate per transfer cycle was significantly better with HCG ( 18.7 versus 9.3 ) . This is the first truly objective ( r and omized ) study demonstrating the beneficial effect of supporting the luteal phase in an IVF programme Various treatments are given during the luteal phase by most IVF programmes , without any proof of their efficacy . We have performed a double-blind , r and omized study with dydrogesterone ( 125 transfers ) against placebo ( 133 transfers ) . The pregnancy rate was 21.6 versus 15.0 % per transfer cycle with dydrogesterone or placebo , respectively . There was no significant difference between these figures , but taking into account the usual success rate in IVF programmes ( 15 - 20 % ) a difference of 5 % would be significant only with two groups of 1500 subjects . This paper discusses the question of how we can come to a definite conclusion on the efficacy of hormonal supplementation during the luteal phase Summary . Vaginal administration of 200 or 400 mg of progesterone in a wax suppository every 12 h in normal women was effective in rapidly achieving and maintaining serum progesterone concentrations at physiological levels appropriate to the midluteal phase of the ovarian cycle and early pregnancy . Given in the follicular phase for 5 days in five subjects at each of two doses , progesterone reached concentrations in serum after 4 and 12 h o f 21–105 nmol/l ( mean 46·4 nmol/l SD 17·2 , n= 50 ) with 200 mg dosage and 21–101 nmol/l ( mean 53·8 nmol/l SD 16·6 , n= 49 ) with 400 mg dosage . There was no significant reduction in levels between 4 and 12 h after administration , in contrast to previously reported findings , suggesting that the wax base led to slow release of the hormone . The uptake of progesterone in the midluteal phase was assessed in 10 subjects by comparing successive cycles treated with progesterone or placebo in a r and omized double‐blind manner . Using only the 400 mg dosage , the mean serum progesterone level was raised by 69 % : the untreated level being normal ( 38·17 SD 10·01 compared with 64·49 SD 23·22 nmol/l , n= 10 ) . This was despite an assumed concomitant fall in endogenous hormone production as suggested by a 28 % reduction in oestradiol‐17β levels . Thus vaginal administration of progesterone in wax appears to be effective and convenient , and preferable to the use of other progestogens in various circumstances in which a fetus may be exposed to the drug This article reports on the effects of human chorionic gonadotropin ( hCG ) on progesterone ( P ) and estradiol ( E2 ) , luteal phase length , and conception in 116 cycles treated by in vitro fertilization and embryo transfer ( IVF-ET ) . In 60 cycles , the luteal phase was supported by hCG , 1500 IU three times at 2-day intervals from the day of ET . The remaining 56 cycles served as controls . hCG significantly increased the P level ( 93 + /- 53 versus 62 + /- 46 ng/ml ) , the P/E2 ratio , and the luteal phase length ( 17.4 + /- 1.3 versus 12.2 + /- 1.7 days ) . However , the total pregnancy rate did not significantly differ between the two groups , though the pregnancy rate after transfer of two or three embryos was slightly higher in the hCG group ( 26.9 versus 22 % in the control group ) , as was the rate of implanted embryo per transferred embryo after transfer of two or three embryos ( 25 versus 15.3 % ) . It was concluded that , while hCG increased the magnitude and duration of the luteal P secretion , it did not clearly improve the pregnancy rate Abstract Purpose : To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles , and to assess whether human chorionic gonadotropin ( hCG ) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels . Methods : The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed . Unsuccessful women with low late-midluteal estradiol levels ( < 100 pg/mL ) proceeded with the exploratory second IVF cycles where they were r and omly given with either progesterone alone ( P protocol ) or hCG + progesterone ( P+hCG protocol ) for luteal support . Results : Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium ( 100–500 pg/mL ) and high ( > 500 pg/mL ) levels ( 13.3 , 26.8 , and 36.3 % , respectively ) . P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate ( 31.7 % ) than P protocol ( 13.7 % ) . Conclusions : hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels Two different regimens of luteal support in gonadotrophin hormone-releasing hormone ( GnRH ) analogue/human menopausal gonadotrophin (GnRHa/HMG)-induced in-vitro fertilization cycle ( IVF ) were compared in a r and omized clinical trial . After embryo transfer , either vaginal progesterone alone was administered ( n = 89 , P group ) , or a combination of vaginal progesterone and human chorionic gonadotrophin ( n = 87 , P/HCG group ) . The primary aim of this study was to assess the effect of the different regimens of luteal support on the pregnancy rate . The secondary aim was to compare oestradiol and progesterone concentrations in the luteal phase between the two groups , and assess their effect on the pregnancy rate . A clinical pregnancy rate of 15 % was found in the P/HCG group in comparison with 26 % in the P group ( odds ratio 0.49 ; 99 % confidence interval : 0.18 - 1.3 ) . The luteal serum oestradiol and progesterone values in the P/HCG group were significantly higher when compared with the P group on the 6th , 9th and 12th day after oocyte retrieval ( Wilcoxon P < 0.001 ) . In accordance with the high oestradiol concentrations , more cases of ovarian hyperstimulation syndrome ( OHSS ) were found in the P/HCG group . Oestradiol values on the 9th day after oocyte retrieval , presumably the day of implantation , appeared to be higher in women who did not become clinical ly pregnant . We conclude that vaginal progesterone alone provides sufficient luteal support in GnRHa/HMG induced IVF cycles . The combination of vaginal progesterone and HCG as luteal support leads to significant high luteal oestradiol and progesterone concentrations . But a high concentration of oestradiol seems to have a deleterious effect on the implantation process , result ing in a low pregnancy rate The value of luteal phase supplementation with human chorionic gonadotropin ( hCG ) was assessed after a combined protocol of ovarian stimulation , using a long acting gonadotropin releasing hormone analog ( GnRH-a ) and human menopausal gonadotropins ( hMG ) , in a r and omized prospect i ve study of 36 consecutive cycles in an in vitro fertilization ( IVF ) program . The patients were allocated on the transfer day to either luteal phase supplementation with hCG ( Group A , n = 18 ) or none ( Group B , n = 18 ) . Nine patients of Group A conceived as compared with 3 in Group B. Five patients , all in Group A , developed ovarian hyperstimulation syndrome ( OHSS ) ( 3 moderate and 2 severe forms ) . Analysis of the hormonal profiles disclosed similar progesterone ( P ) , estradiol ( E2 ) , and E2/P ratio up to the 6th post ovum pick-up day . Then , E2 and mainly P levels decreased only in Group B result ing in a rising E2/P ratio . These findings stress the importance of luteal support in IVF cycles treated with GnRH-a . In light of the increased risk of OHSS among hCG treated patients , further studies are needed to assess the optimal preparation needed To determine whether luteal phase support with vaginal progesterone could improve pregnancy rates in our IVF/GIFT programme , we performed a prospect i ve r and omised controlled study . After stimulation with clomiphene citrate/human menopausal gonadotrophin , 123 women received no luteal support and 122 received progesterone pessaries 100 mg b.d . from 48 hours prior to embryo transfer and continued throughout the luteal phase . There was no difference in the pregnancy rate following IVF/ET ( 6/58 and 10/58 for the pessary and control group respectively ) , but a significantly higher rate was noted for GIFT ( 13/34 and 5/42 for the pessary and control group respectively ; P less than 0.05 ) . Of interest , only one of the 19 pregnancies using luteal support was extra-uterine , compared with 6/15 in the control group This study was design ed to determine the efficacy of 17α-hydroxyprogesterone caproate ( 17-OHPc ) for luteal phase support in in vitro fertilization ( IVF ) . For this purpose , a total of 86 IVF patients undergoing embryo transfer were r and omly allocated to two groups as follows : ( 1 ) group A , including 43 patients who received the support of luteal phase through the intramuscular administration of 17-OHPc at a dosage of 341 mg every 3 days , and ( 2 ) group B , including 43 patients who received the intramuscular administration of a saline solution as placebo every 3 days . In both groups , the treatment was started within 24 h after embryo transfer until β-HCG evaluation . In case of positive β-HCG , it was extended until 12 weeks . Efficacy was assessed using the pregnancy rates , which was , per transfer , statistically significantly higher in group A than in group B ( 32.5 vs. 18.3 % respectively ) . On the basis of our results , we emphasize the use of 17-OHPc for luteal phase support after IVF and embryo transfer Ovrian hyperstimulation syndrome ( OHSS ) is the major complication associated with artificial reproductive technologies . The aim of this study was to assess the potential of exogenous steroids to prevent OHSS without adversely affecting pregnancy rate . A prospect i ve and r and omized study including 945 consecutive cycles in 603 women ( mean age 28.6 years ) was carried out to evaluate the efficiency of high-dose progesterone and oestradiol administration during the luteal phase to prevent OHSS . After ovulation induction , patients were allocated by a series of computer-generated r and om numbers to receive either 5000 iu human chorionic gonadotrophin ( hCG ) 4 and 8 days after embryo transfer ( group 1 , n = 534 ) or 500 mg hydroxy-progesterone caproate and 10 mg oestradiol valerate on days 2 , 6 , 10 and 14 after embryo transfer ( group 2 , n = 411 ) , by i.m . injection . Total pregnancy rate was 24 % ( 97 of 411 ) and 23 % ( 121 of 534 ) , and median serum progesterone concentrations on day 15 after embryo transfer were 5.8 ng ml-1 ( range 0.1–298 ) and 0.1 ng ml-1 ( range 0.1–372 ) in groups 1 and 2 , respectively ( P = 0.001 ) . One hundred and sixty-three ( 30.5 % ) women in group 1 and 22 ( 5.4 % ) women in group 2 developed signs of OHSS ( P < 0.0001 ) . These results indicate that steroidal ovarian suppression during the luteal phase is a promising tool to reduce the incidence and severity of OHSS in a high-risk population without compromising the pregnancy rate A prospect i ve r and omized study was conducted to evaluate the use of adding oestradiol valerate 6 mg per os daily to intravaginal micronized progesterone ( 600 mg daily ) as luteal supplements . The study comprised 378 infertile women superovulated with a gonadotrophin releasing-hormone agonist ( GnRHa ) and human menopausal gonadotrophins ( HMG ) for in-vitro fertilization ( IVF ) or zygote intra-Fallopian transfer ( ZIFT ) . The clinical pregnancy rate was similar ( 29 % ) whether or not oestradiol valerate was added to intravaginal progesterone . Eighteen out of twenty-two endometrial biopsies were in phase , and morphological evaluations of the two luteal supplementation groups were not different . Serum hormone profiles in singleton pregnancies showed a similar day of appearance of human chorionic gonadotrophin ( HCG ) in both protocol s but significantly lower oestradiol concentrations arose in the group without oestradiol valerate . In 32 % of the singleton pregnancies , the first appearance of HCG occurred later than day 12 after HCG injection ; in those ongoing pregnancies , corpus luteum rescue -- as measured by significantly lower serum oestradiol and progesterone concentrations -- was compromised . This study provided no evidence of any benefit of routinely supplementing GnRHa/HMG cycles with oestradiol valerate in addition to intravaginal micronized progesterone A r and omized , prospect i ve blind study was carried out to investigate the need for luteal phase support in patients undergoing in-vitro fertilization ( IVF ) . One-hundred- and -fifty-six patients undergoing IVF in cycles stimulated with human menopausal gonadotropin ( HMG ) and human chorionic gonadotrophin ( HCG ) stimulated IVF , were divided into three different groups for luteal phase treatment . Fifty-four patients received dydrogesterone three times daily ( TID ) beginning on the day of embryo transfer ( ET ) . Fifty-one patients received HCG on days 3 , 6 and 10 following ET . Fifty-one patients received placebo p.o . TID beginning on the day of ET . There was no difference between the groups in pregnancy rate , rate of spontaneous abortion , proportion of normally developing fetuses or rate of chemical pregnancy . The data indicate that supplementation of the luteal phase may not improve the success rates of IVF-ET cycles OBJECTIVE To compare side effects and patient inconvenience of two vaginal progesterone ( P ) formulations for luteal support in in vitro fertilisation cycles . STUDY DESIGN Sixty infertile patients at risk of developing ovarian hyperstimulation syndrome were r and omised to receive either Cyclogest vaginal suppositories 400 mg twice daily or Crinone 8 % vaginal gel once daily for 14 days as the luteal support . On Day 6 and Day 16 after embryo transfer , they rated side effects and patient inconvenience into four grade s : none , mild , moderate and severe by completing a question naire . RESULTS Perineal irritation was reported by about 20 % of patients in each group . Significantly more patients using Cyclogest suppositories grade d inconvenience of administration , leaking out and interference with coitus as moderate or severe . CONCLUSION There was no difference in perineal irritation after Cyclogest suppositories or Crinone 8 % gel although significantly more patients found inconvenience of administration , leaking out and interference with coitus after Cyclogest Summary : Luteal phase lengths and hormonal profiles ( progesterone , oestra‐diol‐17 beta , beta HCG and prolactin ) have been documented in 77 cases derived from a series of patients undergoing IVF . Nineteen pregnancies were generated during this series and 12 healthy infants have already been delivered . Luteal phase lengths were 14.5pM 0.5 days with 14.3 % demonstrating mid‐luteal progesterone levels of less than 31 nmols/1 , considered to be low for successful conception . A r and om study of luteal support regimens comparing HCG or medroxyprogesterone acetate ( MPA ) with nil therapy was studied in a series of 44 consecutive embryo transfers during which 10 pregnancies were achieved . No difference was noted in the pregnancy rates for the 3 groups but the pregnancy outcome was better in those who had HCG support and this was more apparent in the overall series of 19 pregnancies . A significant luteotrophic effect was noted with HCG support regimens whilst MPA appeared to have a luteal suppressant action . Six pregnancies which aborted with blighted ova were derived from cycles in which the luteal phase progesterone levels were low raising the possibility that a poor hormonal environment may predispose to blighted ova OBJECTIVE To investigate the efficacy and safety of intravaginal Crinone 8 % ( Columbia Research Laboratories , Miami . FL ) versus IM progesterone for luteal phase support after IVF-ET . DESIGN Prospect i ve open trial with comparison to historical controls . SETTING University hospital . PATIENT(S ) Two hundred six women undergoing IVF-ET . INTERVENTION(S ) One hundred patients received Crinone vaginal progesterone gel ( 90 mg once daily ) and 106 patients received IM progesterone ( 50 mg once daily ) beginning on the evening of oocyte retrieval . MAIN OUTCOME MEASURE(S ) Pregnancy and miscarriage rates , and midluteal serum progesterone levels . RESULT ( S ) Positive beta-hCG pregnancy rates , clinical pregnancy rates per transfer , and ongoing pregnancy rates were similar for the Crinone and IM progesterone groups . Women who received Crinone had higher rates of biochemical pregnancy loss but lower rates of clinical pregnancy loss ( i.e. , spontaneous abortion ) than women who received IM progesterone . Midluteal serum progesterone concentrations were significantly higher in the IM progesterone group ( 94.3+/-8.8 ng/mL versus 57.7+/-7.4 ng/mL ) . Several women who received Crinone had vaginal bleeding 11 - 13 days after oocyte retrieval . CONCLUSION ( S ) For all age categories , positive beta-hCG and ongoing pregnancy rates were similar when Crinone or IM progesterone was given for luteal phase support in IVF-ET cycles , despite lower serum progesterone concentrations and higher rates of biochemical pregnancy loss with Crinone . Although the results of this study support the use of Crinone as an acceptable alternative for luteal support after IVF-ET , differences in bleeding patterns and rates of biochemical pregnancy loss demonstrate the need for a prospect i ve r and omized study |
11,777 | 25,899,251 | Probiotics may be beneficial in improving symptoms and quality of life in patients with allergic rhinitis ; however , current evidence remains limited due to study heterogeneity and variable outcome measures . | BACKGROUND Probiotics have proven beneficial in a number of immune-mediated and allergic diseases .
Several human studies have evaluated the efficacy of probiotics in allergic rhinitis ; however , evidence for their use has yet to be firmly established .
The current systematic review seeks to synthesize the results of available r and omized trials . | Background / objectives : An imbalance between Th1 and Th2 cells is involved in allergic rhinitis ( AR ) that may be improved by probiotics . To test the efficacy of the probiotic Lactobacillus paracasei subsp . paracasei LP-33 , a double-blind , placebo-controlled , r and omized trial was carried out in patients with AR to grass pollen treated with loratadine and presenting altered quality of life . Subjects/ methods : Subjects with persistent AR , symptomatic during the grass pollen season , and a positive skin test or specific immunoglobulin E to grass pollens were included by general practitioners ( GPs ) . All received loratadine for 5 weeks . The primary end point was the improvement in Rhinitis Quality of Life ( RQLQ ) global score at the fifth week of LP-33 consumption compared with placebo ( in addition to loratadine ) . Secondary end points included nasal and ocular symptoms ( individual and total symptom scores ) , visual analogue scale and time of first exacerbation of the symptoms when loratadine was stopped . Results : A total of 425 subjects were included . Using intent-to-treat analysis , the RQLQ global score decreased significantly more in the LP-33 group than in the placebo group ( P=0.0255 , difference=−0.286 ( 95 % confidence interval ( CI ) : −0.536 ; −0.035 ) ) . No significant differences were noted for the change of the rhinitis total symptom score 5 global score between groups ( P=0.1288 , difference=−0.452 ( 95 % CI : −1.036 ; 0.132 ) ) . Significant differences in ocular symptoms ( RQLQ ) were observed between groups ( P=0.0029 , difference=−0.4087 ( 95 % CI : −0.6768 ; −0.1407 ) ) . Conclusions : This study performed by GPs shows that LP-33 improves the quality of life of subjects with persistent AR who are currently being treated with an oral H1-antihistamine . Whereas nasal symptoms had not changed , ocular symptoms had consistently improved Background : A prospect i ve , cross‐sectional , international survey was conducted among patients and physicians to identify symptom perception and the impact of allergic rhinitis ( AR ) on health‐related quality of life ( HRQoL ) . This paper presents the results from the USA BACKGROUND The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier . We have previously shown that a human intestinal floral strain , Lactobacillus GG ( ATCC 53103 ) , promotes local antigen-specific immune responses ( particularly in the IgA class ) , prevents permeability defects , and confers controlled antigen absorption . OBJECTIVE The aim of this study was to evaluate the clinical and immunologic effects of cow 's milk elimination without ( n = 14 ) and with ( n = 13 ) the addition of Lactobacillus GG ( 5 x 10(8 ) colony-forming units/gm formula ) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow 's milk allergy . The second part of the study involved 10 breast-fed infants who had atopic eczema and cow 's milk allergy . In this group Lactobacillus GG was given to nursing mothers . METHODS The severity of atopic eczema was assessed by clinical scoring . The concentrations of fecal alpha 1- antitrypsin , tumor necrosis factor-alpha , and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention . RESULTS The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG . The concentration of alpha 1-antitrypsin decreased significantly in this group ( p = 0.03 ) but not in the group receiving the whey formula without Lactobacillus GG ( p = 0.68 ) . In parallel , the median ( lower quartile to upper quartile ) concentration of fecal tumor necrosis factor-alpha decreased significantly in this group , from 709 pg/gm ( 91 to 1131 pg/gm ) to 34 pg/gm ( 19 to 103 pg/gm ) ( p = 0.003 ) , but not in those receiving the extensively hydrolyzed whey formula only ( p = 0.38 ) . The concentration of fecal eosinophil cationic protein remained unaltered during therapy . CONCLUSION These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy , and by alleviating intestinal inflammation , may act as a useful tool in the treatment of food allergy Background : Oral probiotic bacteriotherapy with Lactobacillus rhamnosus has given promising results in small children with food allergy . We studied the effects of similar therapy in teenagers and young adults , who were allergic to birch pollen and apple food and had intermittent symptoms of atopic allergy and /or mild asthma BACKGROUND Japanese cedar pollinosis ( JCPsis ) affects nearly one in six Japanese . Oral administration of Bifidobacterium longum BB536 has been shown to be effective in relieving JCPsis symptoms during the pollen season . METHODS This double- two-way crossover study was design ed to evaluate the efficacy of BB536 on reducing symptoms in JCPsis patients exposed to Japanese cedar pollen ( JCP ) in an environmental exposure unit ( EEU ) outside of the normal JCP season . After a 1-week run-in period , subjects ( n=24 ) were r and omly allocated to receive BB536 powder ( approximately 5x1010 ) or placebo twice a day for 4 weeks . After a 2-week washout period , subjects were crossed over to another 4 weeks of intake . At the end of each intake period , subjects received controlled JCP exposure for 4 hours in the EEU . Symptoms were self-rated 30 minutes before and every 30 minutes during the exposures . From the first day of exposure through the next 5 successive days , participants self-rated their delayed symptoms and medication uses . Blood sample s were taken before the exposures . The mean JCP levels for exposures were 6500 to 7000 grains/m3 air . RESULTS In comparison with placebo , BB536 intake significantly reduced the ocular symptom scores during JCP exposures . Evaluating delayed symptoms after exposures indicated that scores for disruption of normal activities were significantly lower in the BB536 group compared with the placebo group . Prevalence of medication use was markedly reduced by BB536 intake . CONCLUSIONS These results suggest the potential beneficial effect of BB536 in relieving symptoms of JCP allergy Live Lactobacillus paracasi 33 ( LP33 ) may effectively improve the quality of life for patients with perennial allergic rhinitis . It has been demonstrated that heat-killed lactic acid bacteria ( LAB ) suppress specific immunoglobulin E synthesis and stimulate interleukin-12 production in animals . The aim of this study was , therefore , to evaluate the efficacy of heat-killed LP33 in the treatment of allergic rhinitis induced by house-dust-mite in human subjects . A total of 90 patients were enrolled in a r and omized , double blind , placebo-controlled trial and assigned to three treatment groups . Patients in groups A and B received two capsules per day of live or heat-killed LAB ( 5 x 10(9 ) colony-forming units/capsule ) , respectively , over a period of 30 days while those in Group C received placebo capsules . A modified question naire on pediatric rhinoconjunctivitis-related quality of life was administered to all subjects or their parents during each clinical visit . The overall quality of life score decreased for groups A and B , as compared with the placebo group , in terms of both frequency ( 9.47 + /- 2.89 , 6.30 + /- 2.19 , vs. -3.47 + /- 1.53 , respectively ; p < 0.0001 ) and level of bother ( 5.91 + /- 3.21 , 6.04 + /- 2.44 , vs. -2.80 + /- 1.64 , respectively ; p = 0.004 ) after the 30-day treatment . The efficacy of the heat-killed LP33 was not inferior to the live variant . No obvious side effects were reported for either active treatment group during the study period . Our results suggest that heat-killed LP33 can effectively improve the overall quality of life for patients with allergic rhinitis , and that it may be efficacious as an alternative treatment Japanese cedar pollinosis is an important contributor to allergic rhinitis in Japan . Lactobacillus may be useful as an immunomodulator and is used widely as a foodstuff . The purpose of the study was to examine the effects of daily intake of the Lactobacillus paracasei strain KW3110 in patients with cedar pollinosis . The effects of daily intake of KW3110 in patients with cedar pollinosis were investigated in 126 patients who received KW3110 or a placebo in a double-blind study . The study began 1 month before the start of the pollen season and lasted for 3 months . A significant reduction of nasal symptoms and the serum level of eosinophil cationic protein and improvement of quality of life scores occurred in the patients who received KW3110 when pollen scattering was low . However , the effects were limited during the peak period of pollen scattering . Intake of KW3110 may reduce allergic inflammation , but the effect is limited tion of both CP and cisplatin . Hypersensitivity to mannitol was reported as a cause of apparent hypersensitivity to cisplatin . 6 In case 2 the result of a skin test with mannitol was negative , whereas the result of a skin test with the commercial formulation containing CP and mannitol was positive , suggesting that CP was solely responsible for the hypersensitivity reaction . In addition to the clinical tolerance induced by the desensitization protocol , skin responses to intradermal CP diminished . As shown in Table I , the ratio between wheal sizes of CP and histamine decreased more than 3.5 times after the desensitization . The observation of wheal- and -flare responses becoming negative has already been described in penicillin desensitization . 7 This phenomenon supports an antigen-specific desensitization . The rate at which the drug concentration increases in the extracellular fluid seems to be the most important factor in a successful outcome of desensitization . As suggested by our two patients , this rate can differ in each individual case . We conclude that the 4-hour desensitization protocol may not be suitable for all patients allergic to CP , whereas a modified prolonged protocol seems to be more tolerable . Until further data have been accumulated , the short protocol may be at tempted initially but should be replaced by the prolonged protocol if adverse effects appear . The prolonged protocol seems to be both safe and efficacious with regard to anti tumor activity To examine whether long-term consumption of fermented milk containing a specific Lactobacillus casei may improve the health status of preschool children suffering from allergic asthma and /or rhinitis a r and omized , prospect i ve , double blind , controlled trial was conducted in 187 children 2–5 y of age . The children received for 12 mo either fermented milk ( 100 mL ) containing Lactobacillus casei ( 108 cfu/mL ) or placebo . The time free from and the number of episodes of asthma/rhinitis after starting intervention were the outcome measures . The number of fever or diarrhea episodes and the change in serum immunoglobulin were further assessed . No statistical difference between intervention and control group occurred in asthmatic children . In children with rhinitis , the annual number of rhinitis episodes was lower in the intervention group , mean difference ( 95 % CI ) , −1.6 ( −3.15 to −0.05 ) ; the mean duration of an episode of diarrhea was lower in the intervention group , mean difference −0.81 ( −1.52 to −0.10 ) days . While long-term consumption of fermented milk containing Lactobacillus casei may improve the health status of children with allergic rhinitis no effect was found in asthmatic children Objective To study , we examined the effect of Lactobacillus salivarius on the clinical symptoms and medication use among children with established allergic rhinitis ( AR ) . Design Double blind , r and omized , controlled trial . Setting Hualien Tzu-Chi General Hospital . Methods Atopic children with current allergic rhinitis received 4 × 109 colony forming units/g of Lactobacillus salivarius ( n=99 ) or placebo ( n=100 ) daily as a powder mixed with food or water for 12 weeks . The SCORing Allergic rhinitis index ( specific symptoms scores [ SSS ] and symptom medication scores [ SMS ] ) , which measures the extent and severity of AR , was assessed in each subject at each of the visits — 2 weeks prior to treatment initiation ( visit 0 ) , at the beginning of the treatment ( visit 1 ) , then at 4 ( visit 2 ) , 8 ( visit 3 ) and 12 weeks ( visit 4 ) after starting treatment . The WBC , RBC , platelet and , eosinophil counts as well as the IgE antibody levels of the individuals were evaluated before and after 3 months of treatment . Results The major outcome , indicating the efficacy of Lactobacillus salivarius treatment , was the reduction in rhinitis symptoms and drug scores . No significant statistical differences were found between baseline or 12 weeks in the probiotic and placebo groups for any immunological or blood cell variables . Conclusions Our study demonstrates that Lactobacillus salivarius treatment reduces rhinitis symptoms and drug usage in children with allergic rhinitis Many r and omized controlled trials ( RCTs ) have been done on role of probiotics as a treatment modality in allergic rhinitis . We conducted a review on the same . A systematic search of published literature was done . RCTs comparing effect of probiotics with placebo were included . A predefined set of outcome measures were assessed . Continuous data were expressed as pooled st and ardized mean difference ( SMD ) with 95 % confidence interval ( CI ) . Dichotomous data were expressed as odds ratio with 95 % CI . P value < 0.05 was considered significant . RevMan version 5 was used for all the analyses . Seven RCTs were eligible for inclusion . Probiotic intake improved quality of life score in patients with allergic rhinitis [ SMD -1.17 ( 95 % CI -1.47 , -0.86 ; P < 0.00001 ) ] . Other parameter that improved with probiotic intake was decrease in the number of episodes of rhinitis per year . There was no significant change in blood or immunologic parameters in the probiotic group , SMD -0.10 ( 95 % CI -0.26 , 0.06 ; P = 0.22 ) . Adverse events were not significant . Probiotic therapy might be useful in rhinitis , but the present data do not allow any treatment recommendations We conducted two r and omized , placebo-controlled , double-blind studies of Lactobacillus plantarum No. 14 ( LP14 ) in female students with seasonal allergic diseases . We also examined the mitogenic activity and cytokine inducibility of LP14 using Peyer ’s patch cells and mesenteric lymph node cells of swine . For subjects who took 8.7 × 108 of LP14 , a significant improvement in ocular symptom-medication score was observed . In the placebo group , the T helper type 1 (Th1)/T helper type 2 ( Th2 ) ratio tended to decrease after a 6-week intake period , while in the LP14 group , the percentage of Th1 cells significantly increased . Post-intake eosinophil counts significantly increased in comparison to those at intake cessation in the placebo group , but it appeared to be suppressed in the LP14 group . There were no changes in fecal microflora . LP14 strongly induced the gene expression of Th1-type cytokines . This study indicates the clinical effects of LP14 on seasonal allergic diseases Studies in animals have suggested that lactic acid bacteria alleviate allergic diseases , however , little information is available on their clinical effect on allergy in humans . Thus , we examined the efficacy of orally administered Lactobacillus acidophilus strain L-92 ( L-92 ) on perennial allergic rhinitis . In a r and omized , double-blind , placebo-controlled clinical trial , 49 patients with perennial allergic rhinitis were r and omized to receive either 100 mL of heat-treated fermented milk containing L-92 ( n = 25 ) or acidified milk without lactic acid bacteria ( placebo ; n = 24 ) for 8 wk . The severity of symptoms was evaluated based on the changes in the scores of clinical symptoms . Oral administration of milk fermented with L-92 result ed in a statistically significant improvement of nasal symptom-medication scores . Ocular symptom-medication scores of patients in the L-92 intervention group tended to improve compared with those in the placebo group . In addition , clear decreases of the scores of swelling and color of the nasal mucosa were observed in the L-92 intervention group at 6 and 8 wk after the start of ingestion of fermented milk . There were no significant differences in serum antihouse dust mite immunoglobulin E levels nor in T helper type 1/T helper type 2 ratio between the 2 groups . These results suggest that oral administration of L-92 can alleviate the symptoms of perennial allergic rhinitis , however , statistically significant changes were not shown in blood parameters Previous studies have suggested that probiotic administration may have therapeutic and /or preventive effects on atopic dermatitis in infants ; however , its role in allergic airway diseases remains controversial . To determine whether daily supplementation with specific Lactobacillus gasseri A5 for 8 weeks can improve the clinical symptoms and immunoregulatory changes in school children suffering from asthma and allergic rhinitis ( AR ) . We conducted a r and omized , double-blind , placebo-controlled study on school children ( age , 6 - 12 years ) with asthma and AR . The eligible study subjects received either L. gasseri A5 ( n = 49 ) or a placebo ( n = 56 ) daily for 2 months . Pulmonary function tests were performed , and the clinical severity of asthma and AR was evaluated by the attending physicians in the study period . Diary cards with records of the day- and nighttime peak expiratory flow rates ( PEFR ) , symptoms of asthma , and AR scores of the patients were used for measuring the outcome of the treatment . Immunological parameters such as the total IgE and cytokine production by the peripheral blood mononuclear cells ( P BMC s ) were determined before and after the probiotic treatments . Our results showed the pulmonary function and PEFR increased significantly , and the clinical symptom scores for asthma and AR decreased in the probiotic-treated patients as compared to the controls . Further , there was a significant reduction in the TNF-α , IFN-γ , IL-12 , and IL-13 production by the P BMC s following the probiotic treatment . In conclusion , probiotic supplementation may have clinical benefits for school children suffering from allergic airway diseases such as asthma and AR Probiotic microorganisms have been shown to be effective in the treatment of allergic inflammation and food allergy , but their efficacy remains controversial . This study tested the effect of a yogurt supplemented with a probiotic strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis ( JCPsis ) . Forty subjects with a clinical history of JCPsis were given yoghurt either containing BB536 ( BB536 yoghurt ) or without BB536 ( placebo yoghurt ) at 2 X 100 g per day for 14 weeks , in a r and omized , double-blind , placebo-controlled trial . Subjective symptoms and self-care measures were recorded daily and blood sample s were taken before and during the intervention ( at weeks 4 , 9 , and 14 ) to measure the blood parameter levels related to JCPsis . Yoghurt supplemented with BB536 significantly alleviated eye symptoms compared with placebo yoghurt ( odds ratio 0.31 ; 95 % confidence interval 0.10 - 0.97 ; p = 0.044 ) . Although no statistically significant differences were detected , nasal symptoms such as itching , rhinorrhea , and blockage , as well as throat symptoms tended to be relieved with the BB536 yoghurt . BB536 tended to suppress the decreasing blood levels of interferon-gamma ( IFN-y ) and the increasing blood eosinophil rates ; a significantly higher IFN-gamma level was observed for the difference from baseline at week 4 . A decreased trend in the difference from baseline levels of JCP-specific IgE levels was also observed at week 4 in the BB536 group compared with the placebo group . In conclusion , these results suggest that intake of BB536-supplemented yoghurt may relieve JCPsis symptoms , probably through a modulating effect on Th balance Objectives : To examine the immunological and clinical influence of 4 months ' feeding with either yoghurt or partially skimmed milk or nothing , on 20 volunteers . Subjects : Thirteen subjects had a demonstrated allergic rhinopathy and seven were healthy subjects and participated as controls . Research design : Either a group of seven or a group of six rhinopathic patients were fed either 450 g yoghurt or 450 g partially skimmed milk , respectively , for 4 months between March and October 1999 . All subjects maintained their usual diet throughout the study .Peripheral blood mononuclear cells ( P BMC ) were isolated before and after the experimental period and cultured for periods of 40 and 64 h. Proliferation index assay and release of IFNγ and IL-4 without and with PHA stimulation were assessed . Allergic rhinopathy was evaluated before and after the 4 months period by performing the nasal functionality tests ( Active Anterior Rhinomanometry , Acoustic Rhinometry ) , the prick test , the nasal specific provocation test ( NPT ) , the dosage of specific IgE blood levels , the evaluation of the symptomatological score and the nasal mucociliary transport test . Results : No significant change of the proliferation index was noted among the three groups . Cultured P BMC of the group fed with yoghurt released more IFNγ and less IL-4 . Cytokine plasma levels were at and remained at basal levels . Prick test , specific serum IgEs and NPT remained immodified . Muco-ciliary transport time ( MCTt ) and symptomatological score showed a definitive improvement after yoghurt feeding . Conclusion : Yoghurt feeding appears to improve or prevent allergic recurrences in rhinopatic patients .Sponsorship : This study was funded , in part , by a grant from Parmalat , Parma , Italy AIM To investigate whether birch pollen allergy symptoms are linked with gut microbiota changes and whether probiotics have an effect on these . METHODS Forty seven children with confirmed birch pollen allergy were r and omized to receive either a probiotic combination of Lactobacillus acidophilus ( L. acidophilus ) NCFM ( ATCC 700396 ) and Bifidobacterium lactis ( B. lactis ) Bl-04 ( ATCC SD5219 ) or placebo in a double-blind manner for 4 mo , starting prior to onset of the birch pollen season . Symptoms were recorded in a diary . Blood sample s were taken for analysis of cytokines and eosinophils . Fecal sample s were analysed for microbiota components , calprotectin and IgA. Nasal swabs were taken for analysis of eosinophils . RESULTS The pollen season induced a reduction in Bifidobacterium , Clostridium and Bacteroides which could not be prevented by the probiotic intervention . During the intervention , significantly higher numbers of B. lactis 11.2 x 10(7 ) + /- 4.2 x 10(7 ) vs 0.1 x 10(7 ) + /- 0.1 x 10(7 ) bacteria/g feces ( P < 0.0001 ) and L. acidophilus NCFM 3.5 x 10(6 ) + /- 1.3 x 10(6 ) vs 0.2 x 10(6 ) + /- 0.1 x 10(6 ) bacteria/g feces ( P < 0.0001 ) were observed in the probiotic group compared to the placebo group . During May , there was a tendency for fewer subjects , ( 76.2 % vs 95.2 % , P = 0.078 ) to report runny nose , while during June , fewer subjects , 11.1 % vs 33.3 % , reported nasal blocking in the probiotics group ( P = 0.101 ) . Concomitantly , fewer subjects in the probiotic group had infiltration of eosinophils in the nasal mucosa compared to the placebo group , 57.1 % vs 95 % ( P = 0.013 ) . Eye symptoms tended to be slightly more frequent in the probiotic group , 12.5 d [ interquartile range ( IQR ) 6 - 18 ] vs 7.5 d ( IQR 0 - 11.5 ) ( P = 0.066 ) during May. Fecal IgA was increased in the placebo group during the pollen season ; this increase was prevented by the probiotics ( P = 0.028 ) . CONCLUSION Birch pollen allergy was shown to be associated with changes in fecal microbiota composition . The specific combination of probiotics used was shown to prevent the pollen-induced infiltration of eosinophils into the nasal mucosa , and indicated a trend for reduced nasal symptoms BACKGROUND The role of probiotics in prevention of allergic disease is still not clearly established , although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years . OBJECTIVE To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years . METHODS Double-blind , r and omized placebo-controlled trial of infants at risk of allergic disease . Pregnant women were r and omized to take Lactobacillus rhamnosus HN001 ( L rhamnosus ) , Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding , and their infants were r and omized to receive the same treatment from birth to 2 years ( n = 474 ) . The infant 's cumulative prevalence of eczema and point prevalence of atopy , using skin prick tests to common allergens , was assessed at 2 years . RESULTS Infants receiving L rhamnosus had a significantly ( P = .01 ) reduced risk of eczema ( hazard ratio [ HR ] , 0.51 ; 95 % CI , 0.30 - 0.85 ) compared with placebo , but this was not the case for B animalis subsp lactis ( HR , 0.90 ; 95 % CI , 0.58 - 1.41 ) . There was no significant effect of L rhamnosus ( HR , 0.74 ; 95 % CI , 0.46 - 1.18 ) or B animalis subsp lactis ( HR , 0.82 ; 95 % CI , 0.52 - 1.28 ) on atopy . L rhamnosus ( 71.5 % ) was more likely than B animalis subsp lactis ( 22.6 % ) to be present in the feces at 3 months , although detection rates were similar by 24 months . CONCLUSION We found that supplementation with L rhamnosus , but not B animalis subsp lactis , substantially reduced the cumulative prevalence of eczema , but not atopy , by 2 years . Underst and ing how Lactobacilli act to prevent eczema requires further investigation Background / Objectives : Probiotics are defined as ‘ living micro-organisms that when administered in adequate amounts confer a health benefit to the host ’ . Different probiotic strains have been investigated for beneficial effects on allergic disorders . The purpose of the current study was to evaluate the effect of orally administering the probiotic Nestlé culture collection (NCC)2818 Bifidobacterium lactis strain on immune parameters and nasal symptom scores in subjects suffering from seasonal allergic rhinitis (SAR).Subjects/ Methods : The study was a double-blinded , parallel , r and omized placebo-controlled trial conducted during the peak of the pollen season . Adult subjects with clinical history of SAR and positive skin prick test to grass pollen were recruited . The subjects received B. lactis NCC2818 or placebo for 8 weeks and completed symptom question naires every week . Whole blood was collected at baseline ( V1 ) , 4 weeks ( V2 ) and 8 weeks ( V3 ) to measure immune parameters . Results : Concentrations of Th-2 cytokines , secreted by stimulated blood lymphocytes , were significantly lower in the probiotic group compared with the placebo group at V3 ( interleukin (IL)-5 , P=0.016 ; IL-13 , P=0.005 ) . Total nasal symptom scores were significantly lower in the second month of the study ( weeks 5–8 ) in the probiotic group compared with the placebo group ( P=0.03 ) . Also , percentages of activated CD63 expressing basophils were significantly lower in the probiotic group at V2 ( P=0.02 ) . Conclusions : Oral administration of the probiotic NCC2818 mitigates immune parameters and allergic symptoms during seasonal exposure . These promising results warrant that B. lactis NCC2818 be investigated further in large-scale trials for management of respiratory allergy BACKGROUND Recent studies suggest that oral bacteriotherapy with probiotics might be useful in the management of atopic dermatitis ( AD ) . OBJECTIVE The purpose of this investigation was to evaluate the clinical and anti-inflammatory effect of probiotic supplementation in children with AD . METHODS In a double-blind , placebo-controlled , crossover study , 2 probiotic Lactobacillus strains ( lyophilized Lactobacillus rhamnosus 19070 - 2 and Lactobacillus reuteri DSM 122460 ) were given in combination for 6 weeks to 1- to 13-year-old children with AD . The patients ' evaluations were registered after each intervention ( ie , better , unchanged , or worse ) . The clinical severity of the eczema was evaluated by using the scoring atopic dermatitis ( SCORAD ) score . As inflammatory markers , eosinophil cationic protein in serum and cytokine production by P BMC s were measured . RESULTS After active treatment , 56 % of the patients experienced improvement of the eczema , whereas only 15 % believed their symptoms had improved after placebo ( P = .001 ) . The total SCORAD index , however , did not change significantly . The extent of the eczema decreased during active treatment from a mean of 18.2 % to 13.7 % ( P = .02 ) . The treatment response was more pronounced in allergic patients ( at least one positive skin prick test response and elevated IgE levels ) , and in this group the SCORAD score decreased ( P = .02 compared with nonallergic patients ) . During active treatment , serum eosinophil cationic protein levels decreased ( P = .03 ) . No significant changes in the production of the cytokines IL-2 , IL-4 , IL-10 , or IFN-gamma were found . CONCLUSIONS A combination of L rhamnosus 19070 - 2 and L reuteri DSM 122460 was beneficial in the management of AD . The effect was more pronounced in patients with a positive skin prick test response and increased IgE levels BACKGROUND Few studies have been conducted to assess treatment options for patients with sensitivities to cypress pollens , important triggers of allergic rhinitis ( AR ) in the Mediterranean region . OBJECTIVE To evaluate the effect of desloratadine , a second-generation antihistamine , on AR symptoms caused by cypress pollens native to France . METHODS Adults ( N=233 ) with symptomatic cypress pollen allergies were r and omized to receive desloratadine , 5 mg , or placebo daily for 15 days during 2 consecutive cypress pollen seasons . The primary end point was the percentage change from baseline in morning total nasal symptom scores on day 14 ; secondary assessment s included total symptom score , peak nasal inspiratory flow , the Rhinoconjunctivitis Quality of Life Question naire , and global response to therapy . RESULTS On day 14 , the desloratadine group had a significantly greater percentage decrease in total nasal symptom score vs the placebo group ( -40 % vs. -30 % ; P < .04 ) . Similarly , on day 14 , there was a 47 % and 37 % respective decrease in total symptom score ( P = .01 ) . Mean peak nasal inspiratory flow scores showed numeric , albeit not statistically significant , improvements from baseline through day 14 with desloratadine . A significantly greater improvement in Rhinoconjunctivitis Quality of Life Question naire scores occurred with desloratadine vs placebo on day 14 ( -1.4 vs. -0.9 ; P = .004 ) . The mean global response to therapy was better with desloratadine vs placebo ( 3.4 vs. 3.9 ; P = .004 ) . The adverse event rate was similar in both groups . CONCLUSION Desloratadine is efficacious and safe for the treatment of AR induced by cypress pollens ; it also improved disease-related quality of life Background : Lactobacillus casei strain Shirota ( LcS ) has been found to exert antiallergic effects in animal experiments , but there is little information about its clinical effects in human patients with allergy . Methods : We performed a r and omized double-blind , placebo-controlled study to investigate the effects of LcS in patients with allergic rhinitis triggered by Japanese cedar pollen ( JCP ) . Participants were asked to drink fermented milk containing LcS ( LcS group ) or placebo ( control group ) for 8 weeks . Clinical symptoms and immunological parameters were compared between the two groups . Results : Symptom-medication scores ( SMS ) worsened in accordance with the increase in the amount of scattered JCP . In terms of the nasal and ocular SMS , there was no significant difference between the LcS group and the placebo group during the ingestion period . In the subgroup of patients with moderate-to-severe nasal symptom scores before starting the ingestion of test sample s , supplementation with LcS tended to reduce nasal SMS . Conclusion : These results indicate that fermented milk containing LcS does not prevent allergic symptoms in patients sensitive to JCP , but may delay the occurrence of allergic symptoms in patients with moderate-to-severe nasal symptom scores BACKGROUND Recently , some common foods in daily life , especially lactic acid bacteria , have been found to have anti-allergic effects . We previously isolated a halophilic lactic acid bacterium , Tetragenococcus halophilus Th221 , from soy sauce moromi , a mixture of koji and salt solution , and showed that it possesses an immunomodulatory activity that promotes T helper type 1 immunity . METHODS To evaluate the anti-allergic effects of Th221 , we performed a r and omized , double-blind , placebo-controlled study in 45 subjects with perennial allergic rhinitis ( PAR ) treated by oral administration of Th221 ( high dose , 60 mg/day , 15 subjects ; low dose , 20.4 mg/day , 15 subjects ) or a placebo ( 15 subjects ) for 8 weeks . RESULTS There were no significant differences among the groups that ingested Th221 and the placebo group regarding the disease severities , total nasal symptom scores and total nasal sign scores examined by physicians . However , the disease severity examined by physicians significantly improved in the high-dose group at the end of the trial compared with the beginning ( p < 0.05 ) . The total score for nasal symptoms of subjects who received a high dose of Th221 also showed a significant improvement at the end of the trial compared with the beginning ( p < 0.01 ) . According to the subjects ' diaries , significant improvements in sneezing and rhinorrhea were observed during some periods in the high-dose group . The change in serum total immunoglobulin E improved significantly at the end of the trial compared with the beginning in this group ( p < 0.05 ) . The safety of Th221 treatment was confirmed by laboratory tests and inspection of the general condition of each subject . CONCLUSIONS Th221 can be expected to safely improve the symptoms of PAR Background : Nonpathogenic Escherichia coli strain Nissle 1917 ( EcN ) has immunomodulatory properties and can act on different cells which are important for the allergic immune response . Herein , we investigated the efficacy and tolerability of EcN in subjects with grass pollen-dependent allergic rhinoconjunctivitis . Methods : Grass pollen-allergic subjects were r and omly allocated to receive EcN in a double-blind , placebo-controlled manner . The treatment was performed from 2 months before onset until the end of one grass pollen season ( in total : 6 months ) . The clinical symptom score and the intake of symptomatic medications were assessed . A skin prick test and grass pollen-specific immunoglobulin ( Ig ) E and IgA were evaluated before and after treatment . Results : Our results show that coseasonal treatment with EcN in grass pollen-allergic subjects was not superior to placebo as assessed using the symptom-medication score ( p = 0.257 ) . Interestingly , an increase [ median ( range ) ] in grass pollen-specific IgA was detectable in the EcN group [ 20,556 LU/ml ( 1,812 - 60,800 ) ] versus placebo [ 5,246 LU/ml ( 944 - 50,467 ) ] ( p = 0.048 ) . Conclusions : The results indicate that 6 months of coseasonal nonspecific immunomodulation by EcN is not sufficient to achieve clinical efficacy in grass pollen-allergic subjects . Future approaches in which such immunomodulators are combined with an allergen-specific protocol might enhance the clinical efficacy of the allergen-specific treatment Allergic rhinitis is characterized by T-helper (Th)2 polarization as elevated levels of Th2-derived cytokines , including interleukin (IL)-4 , IL-5 and IL-13 , have been evidence d at nasal level in allergic rhinitics ( 1 ) . Th2 cytokines play a pathogenic role as they induce IgE synthesis and eosinophil infiltration . Th2 polarization in allergic subjects may occur as consequence of reduced pressure of microbial agents in the gut : the so-called Hygiene Hypothesis ( 2 ) . Probiotics may stimulate immune system at all mucosal surfaces and exert a primary prevention of atopic diseases and reduce allergic symptoms and inflammatory parameters ( 3 ) . We previously found out that Bacillus clausii was capable of modulating cytokine pattern at nasal level in allergic children with recurrent respiratory infections ( 4 ) . Particularly , B. clausii restored physiological Th1 polarization and induced T-regulatory cell response , as documented by increased levels of IL-10 and tumor growth factor (TGF)b after treatment ( 4 ) . Therefore , we conducted a pilot study to investigate the potential effects exerted by B. clausii on nasal symptoms , eosinophils , and symptomatic use of antihistamines in children with allergic rhinitis . Twenty allergic children , 13 males and seven females , with an average age of 13.4 years ( range 12–15 ) were consecutively evaluated . A detailed clinical history and a complete physical examination , including allergy evaluation , were carried out for each patient . The diagnosis of allergic rhinitis due to pollen sensitization was made according to vali date d criteria ( 5 ) . The study was blinded both to the investigator who performed the nasal eosinophil assessment and the investigator who carried out statistical analysis . Symptomatic use of levocetirizine ( 5 mg tablets ) was prescribed for all children . Ten of them were r and omly treated with oral B. clausii ( EnterogerAL LERGY 2 0 0 5 : 6 0 : 7 0 2 – 7 1 0 • COPYRIGHT a 2005 BLACKWELL MUNKSGAARD • ALL R IGHTS RESERVED • CONTRIBUT IONS TO THIS SECT ION WILL NOT UNDERGO PEER REV IEW , BUT WILL BE REV IEWED BY THE ASSOCIATE ED ITORS INTRODUCTION Dietary supplementation with probiotics alters intestinal microflora of children and may have immunomodulatory effects in prevention of allergic diseases . The aim of this study was to evaluate the effects of Lactobacillus paracasei ( LP ) , strain HF.A00232 , as a supplementary agent to levocetirizine in treating children with perennial allergic rhinitis ( AR ) . METHODS This study was a 12-week , double-blind , r and omized , placebo-controlled trial . Sixty children with AR aged 6 - 13 years with nasal total symptoms score ( NTSS ) ≥5 who fulfilled the inclusion criteria were enrolled . Patients were r and omized into two groups with 28 participants receiving levocetirizine plus placebo and 32 participants receiving regular levocetirizine plus LP ( HF.A00232 ) for the first 8 weeks , with a shift to levocetirizine as rescue treatment during the following 4 weeks . Parameters evaluated , including nasal , throat , and eye TSS ( NTSS , TTSS , and ETSS , respectively ) , TSS and levocetirizine use , were recorded daily . Physical examinations and Pediatric Rhinoconjunctivitis Quality of Life Question naires ( PRQLQs ) were administered at each visit . In addition , blood sample s were obtained for evaluation of cytokines including interleukin-4 , interferon-γ , interleukin-10 , and transforming growth factor-β at baseline , Week 8 , and Week 12 . RESULTS The LP ( HF.A00232 ) group had significantly lower PRQLQ scores even after discontinuing regular levocetirizine from Week 9 to Week 12 ( p < 0.01 ) . There was more improvement in individual parameters in the PRQLQ , including sneezing ( p = 0.005 ) , itchy nose ( p = 0.040 ) , and swollen puffy eyes ( p = 0.038 ) , in the LP ( HF.A00232 ) group . No significant differences in TSS , NTSS , TTSS , ETSS , or cytokine levels were found between the two groups . CONCLUSION Dietary supplementation with LP ( HF.A00232 ) provided no additional benefit when used with regular levocetirizine in treating AR in the initial 8 weeks of our study , but there was a continuing decrease in PRQLQ scores , as well as a significant improvement in individual symptoms of sneezing , itchy nose , and swollen eyes , after discontinuing regular levocetirizine treatment Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases via modifying the gut ecosystem . The aim of this study was to assess whether ingestion of fermented milk containing Lactobacillus paracasei-33 ( LP-33 ) , a strain newly isolated from the human intestinal tract , can improve the quality of life of patients with perennial allergic rhinitis . In a r and omized , double-blind , placebo-controlled trial , we gave patients fermented milk with ( n = 60 ) or without ( n = 20 ) the addition of LP-33 ( 2 x 10(9 ) colony-forming units per bottle ) for 30 days . A modified question naire concerning pediatric rhinoconjunctivitis quality of life was administered to all subjects or their parents at each clinical visit . Scores for the overall quality of life significantly decreased in the LP-33 group as compared with the placebo group , in both frequency ( -16.02 + /- 2.14 vs. -7.27 + /- 3.55 , respectively ; p = 0.037 ) and level of bother ( -16.35 + /- 2.33 vs. -6.20 + /- 3.13 , respectively ; p = 0.022 ) after the 30-day treatment . Subjects reported no severe adverse effects such as fever , abdominal pain , or diarrhea . The results suggest that ingestion of LP-33-fortified fermented milk for 30 days can effectively and safely improve the quality of life of patients with allergic rhinitis , and may serve as an alternative treatment for allergic rhinitis BACKGROUND Supplementary consumption of probiotics may temporarily alter the intestinal microflora of infants and children , thereby preventing and treating allergic disorders . OBJECTIVE To compare the clinical efficacy of levocetirizine with that of levocetirizine plus Lactobacillus johnsonii EM1 ( Lj EM1 ) for treating perennial allergic rhinitis ( PAR ) in children . METHODS Sixty-three children aged 7 - 12 years fulfilled the entry criteria for the study and had moderate to severe PAR of at least 1 year 's duration . The treatment followed a r and omized , open-label crossover design : all subjects were r and omized to 2 crossover treatment regimens of levocetirizine with Lj EM1 ( group 1 ) or levocetirizine alone ( group 2 ) for 12 weeks ; subsequently , treatments were reversed for a further 12 weeks . The effects of the 2 regimens were compared using the Pediatric Rhinoconjunctivitis Quality of Life Question naire ( PRQLQ ) and the total symptom score ( TSS ) from diary cards . The parameters evaluated were nasal peak expiratory flow rate ( nPEFR ) , FVC , FEV1 , serum immunoglobulin E ( IgE ) , mite-specific IgE , eosinophilic cationic protein ( ECP ) , resistin , blood eosinophils , eosinophil percentage in nasal smears , IL-4 , IL-10 , interferon-γ ( IFN-γ ) , and transforming growth factor-β ( TGF-β ) . RESULTS After the first 12 weeks of treatment , TSS in both groups had improved progressively compared with that in the run-in period . Both groups had improved TSS at weeks 4 , 8 , and 12 ( P<0.05 ) , and group 1 was more efficacious than group 2 at week 4 ( P=0.014 ) , week 8 ( P=0.011 ) , and week 12 ( P<0.009 ) . During the second 12-week period , group 2 showed continual and progressive improvement , while group 1 did not . The PRQLQ scores were significantly decreased in both groups ( P<0.05 ) , but there was no statistically significant difference between the 2 groups ( P=0.446 ) . The eosinophil percentage in nasal smears decreased in both groups compared with that in the run-in period , and significant differences were detected in groups 2 and 1at 16 and 24 weeks of treatment , respectively ( P<0.05 ) . Both groups showed significant improvement in nPEFR at weeks 4 , 8 , 12 , 16 , and 24 ( P<0.01 ) , and the treatment for group 1 appeared to be more efficacious than that for group 2 at weeks 12 , 16 , and 20 ( P<0.05 ) . FVC and FEV1 were improved in both groups at weeks 8 through 24 ( P<0.05 ) , but there was no significant difference between the 2 groups . In cytokine measurements , IFN-γ and IL-10 increased significantly and IL-4 decreased significantly in both groups , while elevation of TGF-β was seen only in group 1 at 12 weeks ( P<0.001 ) . However , the difference in TGF-β disappeared after 24 weeks treatment . There was no difference in serum resistin levels . No serious adverse events were recorded in either treatment group . CONCLUSION The 24-week , 2-phase , crossover treatment program showed that levocetirizine plus Lj EM1 was more effective for PAR than levocetirizine and that this difference persisted for at least 3 months after discontinuation of Lj EM1 |
11,778 | 20,412,064 | Placebo response rates across RCTs of pharmacological therapies in IBS were high . | BACKGROUND Irritable bowel syndrome ( IBS ) is a functional disorder of the gastrointestinal tract with a significant placebo response .
AIM To conduct a systematic review and meta- analysis examining the magnitude of placebo response rate in treatment trials for IBS . | OBJECTIVES : Though the greatest proportion of irritable bowel syndrome ( IBS ) patients report a mixed bowel pattern ( IBS-Mixed ) , no available therapies have been rigorously evaluated in this subgroup . This study aim ed to evaluate the efficacy and safety of the 5-HT4 agonist tegaserod in women with IBS-Mixed and IBS with constipation ( IBS-C ) . METHODS : This prospect i ve , double-blind , r and omized , placebo-controlled , multicenter study was conducted in 100 centers in North America , South America , and Europe . Women with IBS-Mixed or IBS-C received tegaserod 6 mg or placebo twice daily . The primary efficacy variable was the patient 's assessment of satisfactory relief over the 4-wk treatment period . The proportion of patients reporting satisfactory relief for ≥3 of 4 treatment weeks ( 75 % rule ) and individual IBS symptoms were assessed . RESULTS : In total , 661 women were r and omized ( IBS-Mixed 324 , IBS-C 337 ) . Baseline symptom assessment s identified clear differences between the two cohorts . Tegaserod provided significant improvement in satisfactory relief of IBS symptoms over 4 wk ( OR 1.75 , 95 % CI 1.35–2.25 , P < 0.001 ) in both IBS-Mixed and IBS-C patients . Using the 75 % rule , 52.3 % of tegaserod-receiving IBS-M patients and 43.3 % of IBS-C patients were responders ( vs 36.3 , OR 1.88 , 95 % CI 1.16–3.04 , P < 0.010 ; and 28.9 , OR 1.90 , 95 % CI 1.19–3.05 , P < 0.008 for placebo , respectively ) . The most frequent adverse events leading to study discontinuation in tegaserod-treated patients were diarrhea ( 1.5 % ) and abdominal pain ( 0.9 % ) . Overall 7 % of IBS-C patients reported diarrhea compared to 12 % of IBS-Mixed ( placebo 2.4 % , 1.8 % , respectively ) . CONCLUSIONS : Tegaserod is effective in treating overall IBS symptoms in patients with IBS-Mixed and OBJECTIVES : To assess long-term safety and efficacy of alosetron in women with severe , chronic diarrhea-predominant IBS and in a subset having more frequent urgency ( i.e. , bowel urgency at least 10 of 14 days during screening ) . METHODS : R and omized patients received either alosetron 1 mg ( n = 351 ) or placebo ( n = 363 ) twice daily during a 48-wk , double-blind study . The primary endpoint was the 48-wk average rate of adequate relief of IBS pain and discomfort . Secondary endpoints included 48-wk average satisfactory control rates of urgency , stool frequency , stool consistency , and bloating . Other efficacy endpoints were average monthly adequate relief and urgency control rates and impact of provided rescue medication . RESULTS : Alosetron-treated patients had significantly greater 48-wk average adequate relief ( p = 0.01 ) and urgency control ( p < 0.001 ) rates , regardless of rescue medication use , compared with placebo . Results in subjects with more frequent urgency were more robust than those in the overall population ( p = 0.005 ) . In weeks without rescue medication use , satisfactory control rates for stool frequency and stool consistency were significantly greater in alosetron-treated patients than placebo . Alosetron-treated patients had significantly greater adequate relief than placebo-treated patients ( p < 0.05 ) in 9 of 12 months and significantly greater urgency control ( p < 0.001 ) in all months . Adequate relief and urgency control were maintained throughout the treatment . Adverse events and serious adverse events were similar between treatment groups , except for constipation . Neither ischemic colitis nor serious events related to bowel motor dysfunction was reported . CONCLUSIONS : Long-term use of alosetron is effective and well-tolerated in women with chronic , diarrhea-predominant IBS , including those with more frequent urgency : No currently available treatment provides consistent relief of irritable bowel syndrome . Colonic sensory and motor function are modulated partly through 5HT3‐receptors Herbal remedies , particularly peppermint , have been reported to be helpful in controlling symptoms of irritable bowel syndrome ( IBS ) . We conducted a r and omized double-blind placebo-controlled study on 90 out patients with IBS . Subjects took one capsule of enteric-coated , delayed-release peppermint oil ( Colpermin ) or placebo three times daily for 8 weeks . We visited patients after the first , fourth , and eighth weeks and evaluated their symptoms and quality of life . The number of subjects free from abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls ( P < 0.001 ) . The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls . Furthermore , Colpermin significantly improved the quality of life . There was no significant adverse reaction . Colpermin is effective and safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort OBJECTIVES : Bowel urgency is one of the most bothersome symptoms for nonconstipated IBS patients . The efficacy of alosetron in control of bowel urgency and Global Improvement of IBS symptoms were evaluated in a multicenter double-blind , r and omized , placebo-controlled study . METHODS : Female IBS patients with lack of satisfactory control of bowel urgency were r and omized 2:1 to alosetron 1 mg twice daily or placebo treatment groups . The primary endpoint was the proportion of days with satisfactory control of bowel urgency during the 12-wk treatment period and 2-wk follow-up period . Secondary endpoints included IBS Global Improvement ( responder defined as patient-reported moderate or substantial improvement in IBS symptoms ) and improvements in bowel function ( stool frequency , consistency , and sensation of incomplete evacuation ) . RESULTS : A total of 801 women were r and omized to the alosetron ( n = 532 ) or placebo groups ( n = 269 ) . Physicians classified 98 % of patients with diarrhea-predominant IBS . Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period ( 73 % vs 57 % , p < 0.001 ) . A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 ( 76 % vs 44 % , p < 0.001 ) . IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 ( 88 % vs 48 % ) as well as firmer stools , fewer stools/day , and fewer days with incomplete evacuation compared with nonresponders . Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients . Constipation was the most commonly reported adverse event . CONCLUSIONS : Alosetron is effective at managing bowel urgency in women with diarrhea-predominant IBS . The IBS Global Improvement assessment correlated with improvements in bowel function and may be a useful tool in future IBS clinical trials Are meta-analyses the brave new world , or are the critics of such combined analyses right to say that the biases inherent in clinical trials make them uncombinable ? Negative trials are often unreported , and hence can be missed by meta-analysts . And how much heterogeneity between trials is acceptable ? A recent major criticism is that large r and omised trials do not always agree with a prior meta- analysis . Neither individual trials nor meta-analyses , reporting as they do on population effects , tell how to treat the individual patient . Here we take a more rounded approach to meta-analyses , arguing that their strengths outweigh their weaknesses , although the latter must not be brushed aside A double-blind controlled therapeutic trial of factorial design was used to study the therapeutic effects of lorazepam , hyoscine butylbromide , and ispaghula husk in 12 r and omised blocks of eight patients with the irritable bowel syndrome ( IBS ) . Each of the three agents caused a sustained symptomatic improvement in some of the patients , although only with ispaghula was the difference between the real and dummy preparation statistically significant . When the eight possible combinations of treatment were analysed none of the 12 patients who received only dummy preparations of the three agents had maintained any improvement over the three months of the trial . Seven patients improved among the 12 who received potent preparations of all three agents , and between four and six patients improved in the groups receiving one or two of the potent preparations . These therapeutic results , though far from perfect , show that the types of drug commonly used to treat IBS are of some value and may be additive in their effects . Similar combinations of other therapeutic agents may be more effective , but it will be possible to determine this only by carrying out factorial therapeutic trials Background / objective In order to follow the most recent developments and recommendations in trial methodology for drug evaluation in patients with irritable bowel syndrome , we performed an extended analysis of a large clinical trial from a previously published study of otilonium bromide , using an assessment that integrates the key symptoms of irritable bowel syndrome . Material s and methods A large-scale clinical trial with a double-blind , placebo-controlled , parallel-group study design was conducted in 378 patients , treated for 15 weeks with the recommended st and ard dose of 40 mg otilonium bromide or placebo three times daily . The study was based on the collection of 12 single efficacy endpoints . The new efficacy assessment was based on the data reported by the patients . Rather than demonstrating score differences between the treatment groups of the study , we carried out an assessment that integrates the most frequent symptoms reported ( pain frequency and intensity , presence of meteorism and distension ) by the patient . Results The rate of response to treatment within 2–4 months ( the primary efficacy outcome measure ) was significantly higher in the otilonium bromide group ( 36.9 % ) than in the placebo group ( 22.5 % ; P = 0.007 ) . In each month of treatment , the rate of monthly response was higher in the otilonium bromide group as compared to the placebo group ( P < 0.05 ) . The total monthly and weekly responses to the single endpoints ( intensity and frequency of pain and discomfort , meteorism/abdominal distension , severity of diarrhoea or constipation and mucus in the stool ) were significantly more frequent in the group treated with otilonium bromide than in the placebo-treated group , with differences ranging from 10 % to 20 % . The subgroup analysis of the intestinal habits endpoint indicates that patients with diarrhoea have an additional benefit . Conclusion The present re-evaluation of a previously published study confirms that otilonium bromide is more effective than placebo for the treatment of irritable bowel syndrome , being very efficient in relieving pain and discomfort BACKGROUND AND AIM Previous studies with cisapride reported conflicting results in patients with constipation-predominant irritable bowel syndrome ( IBS ) . To gain further evidence , this r and omized double-blind study was carried out . METHODS Eighty-two symptomatic out patients were r and omized to receive either 5 mg oral cisapride or placebo three times daily for a period of 12 weeks . In patients without satisfactory improvement after 4 weeks , the dose was doubled . Symptom evaluation used visual analog scales ( VAS ) and the investigators ' global assessment . RESULTS After 4 weeks , in 18 ( 45 % ) cisapride and 24 ( 57 % ) placebo patients the dose was doubled because of insufficient improvement of symptoms . The mean VAS score for patients ' global rating of IBS symptoms at baseline was 67.5 mm for cisapride versus 70.7 mm for placebo , and improved to 38.4 mm versus 44.5 mm after 12 weeks of treatment . Investigators rated the overall effect of therapy as good or excellent in 70 % of the cisapride and 50 % of the placebo group . Neither these nor further efficacy parameter differences reached statistical significance . CONCLUSIONS These results indicate that the effect of 15 - 30 mg cisapride daily on symptoms of constipation-predominant IBS is not significantly superior to placebo . During the 12 week treatment of this trial cisapride proved to be safe and tolerable BACKGROUND : A r and omized , double blind , placebo-controlled dose-ranging study was conducted to assess the efficacy of alosetron in men with diarrhea-predominant irritable bowel syndrome ( IBS ) . METHODS : Six hundred and sixty-two men were r and omized to treatment with alosetron 0.5 , 1.0 , 2.0 , 4.0 mg , or placebo twice daily for 12 wk , followed by a 4-wk posttreatment period . Adequate relief of IBS pain and discomfort during week 5–12 of the treatment phase was the primary endpoint ; secondary endpoints included bowel urgency , stool frequency , and consistency , incomplete evacuation , bloating , and abdominal pain or discomfort . RESULTS : Subjects ranked urgency and abdominal pain as their most bothersome IBS symptoms . The average rate of adequate relief during week 5–12 was significantly higher in the alosetron 1.0 mg twice-daily group compared to placebo ( 53%vs 40 % , p= 0.04 ) , and all doses of alosetron significantly reduced stool consistency scores ( p < 0.001 ) indicating firmer stools . No significant effects of alosetron were seen with regard to urgency , number of bowel movements , bloating , and incomplete evacuation . Constipation was the most common adverse event and occurred in a dose-related manner among subjects receiving alosetron , 9 % ( 0.5 mg twice daily ) , 15 % ( 1.0 mg twice daily ) , 11 % ( 2.0 mg twice daily ) , and 21 % ( 4.0 mg twice daily ) . No serious adverse events of constipation were reported . One subject in the 0.5 mg twice-daily group had an episode of rectal bleeding suggestive of a possible diagnosis of ischemic colitis . CONCLUSION : Alosetron 1 mg twice daily provided adequate relief of IBS pain and discomfort , and improved stool consistency in men with diarrhea-predominant IBS Background Irritable bowel syndrome is the most common disorder diagnosed by gastroenterologists . Although several r and omized‐controlled trials have assessed the therapeutic role of antidepressant drugs , there is insufficient evidence to support their use BACKGROUND & AIMS Patients with irritable bowel syndrome ( IBS ) have high surgical rates . We investigated the demographic and medical factors independently associated with surgical histories of health examinees . METHODS We applied multiple stepwise logistic regression analysis to self-completed question naire data from 89,008 examinees , assessing 6 surgeries as outcomes . We assessed question naire/physician record agreement of physician-diagnosed IBS and surgical history on 201 r and omly selected examinees with > or =3 years of records . RESULTS Question naire/record agreement for IBS and surgery was 83.6 % ( kappa = 0.68 ) and 95.5%-100.0 % ( kappa = 0.82 - 1 ) , respectively . IBS was reported by 4587 examinees ( 5.2 % ) ( 1382 men [ 3.0 % ] and 3205 women [ 7.5 % ] ) . Subjects with and without IBS , respectively , reported the following surgical procedures : cholecystectomy , 569 ( 12.4 % ) versus 3428 ( 4.1 % ) , P < 0.0001 ; appendectomy , 967 ( 21.1 % ) versus 9906 ( 11.7 % ) , P < 0.0001 ; hysterectomy , 1063 ( 33.2 % ) versus 6751 ( 17.0 % ) , P < 0.0001 ; back surgery , 201 ( 4.4 % ) versus 2436 ( 2.9 % ) , P < 0.0001 ; coronary artery surgery , 127 ( 2.8 % ) versus 2033 ( 2.4 % ) , P > 0.05 ; peptic ulcer surgery , 22 ( 0.5 % ) versus 277 ( 0.3 % ) , P > 0.05 . Among independent surgery associations , IBS was associated with cholecystectomy ( adjusted odds ratio [ OR ] , 2.09 ; 95 % confidence interval [ CI ] , 1.89 - 2.31 ; P < 0.0001 ) , appendectomy ( OR , 1.45 ; 95 % CI , 1.33 - 1.56 ; P < 0.0001 ) , hysterectomy ( OR , 1.70 ; 95 % CI , 1.55 - 1.87 ; P < 0.0001 ) , and back surgery ( OR , 1.22 ; 95 % CI , 1.05 - 1.43 ; P = 0.0084 ) . CONCLUSIONS Health examinees with physician-diagnosed IBS report rates of cholecystectomy 3-fold higher , appendectomy and hysterectomy 2-fold higher , and back surgery 50 % higher than examinees without IBS ; IBS is independently associated with these surgical procedures Background The efficacy of antidepressants in irritable bowel syndrome ( IBS ) is controversial . No trials have directly compared a tricyclic with a selective serotonin reuptake inhibitor . Our aim was to determine whether imipramine and citalopram are efficacious in IBS . Methods This was a r and omized , double-blind , placebo-controlled , parallel group pilot trial with imipramine ( 50 mg ) and citalopram ( 40 mg ) . Results Of 51 IBS patients r and omized , baseline characteristics were comparable among the treatment arms ; the majority was diarrhea-predominant . Adequate relief of IBS symptoms ( primary endpoint ) was similar for each treatment arm . Improvements in bowel symptom severity rating for interference ( P = 0.05 ) and distress ( P = 0.02 ) were greater with imipramine versus placebo , but improvements in abdominal pain were not . There was a greater improvement in depression score ( P = 0.08 ) and in the SF-36 Mental Component Score ( P = 0.07 ) , with imipramine . Citalopram was not superior to placebo . Approximately 20 % of the variance in scores was explained by treatment differences for abdominal pain , bowel symptom severity disability , depression and the mental component of the SF-36 . Conclusion Neither imipramine nor citalopram significantly improved global IBS endpoints over placebo Background : Alverine citrate has been used in the treatment of irritable bowel syndrome for many years To investigate the efficacy and safety of tegaserod , a novel 5‐HT4 receptor partial agonist , in a r and omized , double‐blind , placebo‐controlled , 12‐week treatment , multicentre study Background : Irritable bowel syndrome ( IBS ) is a common gastrointestinal disorder . Serotonin type 3 ( 5-HT3 ) receptor antagonist alosetron hydrochloride is indicated for women with chronic , severe diarrhea-predominant IBS who have not responded adequately to conventional therapy . However , whether or not the therapeutic efficacy of 5-HT3 receptor antagonists has gender difference is uncertain . Methods : A double-blind , placebo-controlled , parallel-group , comparative study was conducted to evaluate the effect of novel 5-HT3 receptor antagonist , ramosetron hydrochloride , in male and female patients with diarrhea-predominant IBS . 418 subjects were r and omized ( 109 subjects : placebo , 105 subjects : 1 µg , 103 subjects : 5 µg , and 101 subjects : 10 µg ) and administered the study drug once daily . Results : The monthly responder rates of ‘ Patient-reported global assessment of relief of irritable bowel syndrome symptoms ’ in the 5- and 10-µg ramosetron hydrochloride-administered groups were higher than the placebo group ( 26.92 , 42.57 , and 43.01 % for placebo , 5 and 10 µg ) . Moreover , the difference of the responder rate in comparison with the placebo group was similar in males and females . As for safety , there was tolerability at doses up to 10 µg . Conclusion : Ramosetron is an effective and well-tolerated treatment not only for female IBS patients but also for male patients 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 The effects of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome ( IBS ) were evaluated in a r and omized , double-blind , placebo-controlled study . Sixty-nine IBS patients were assigned to a 12-week treatment with either 5 mg cisapride or placebo t.i.d . ; this dosage could be changed if necessary . The mean weekly number of days on which a stool was passed in the cisapride and placebo group increased to 5.3 and 4.4 ( p less than 0.05 ) during weeks 8 - 12 of treatment , and the number of days with stools of normal consistency increased to 3.5 and 1.9 ( p less than 0.05 ) , respectively . At week 12 , the reduction in severity and frequency scores for abdominal pain was significantly greater ( p less than or equal to 0.05 ) in the cisapride group ( 60 and 61 % ) than in the placebo group ( 40 and 32 % ) , as it was for abdominal distension ( p less than 0.05 ) . Cisapride tended to be better than placebo in diminishing flatulence . In 71 % versus 39 % of the patients the overall rating for the response to treatment was good or excellent at week 12 . Cisapride was well tolerated . These results suggest that the drug will be useful for the management of constipation-predominant IBS Background : Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome ( IBS ) in Western population s. However , little information is available regarding the use of tegaserod in the Asia-Pacific population . Aims : To evaluate the efficacy , safety , and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region . Patients : A total of 520 patients from the Asia-Pacific region with IBS , excluding those with diarrhoea predominant IBS . Methods : Patients were r and omised to receive either tegaserod 6 mg twice daily ( n=259 ) or placebo ( n=261 ) for a 12 week treatment period . The primary efficacy variable ( over weeks 1–4 ) was the response to the question : “ Over the past week do you consider that you have had satisfactory relief from your IBS symptoms ? ” Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS . Results : The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1–4 ( 56 % v 35 % , respectively ; p<0.0001 ) and weeks 1–12 ( 62 % v 44 % , respectively ; p<0.0001 ) . A clinical ly relevant effect was observed as early as week 1 and was maintained throughout the treatment period . Reductions in the number of days with at least moderate abdominal pain/discomfort , bloating , no bowel movements , and hard/lumpy stools were greater in the tegaserod group compared with the placebo group . Headache was the most commonly reported adverse event ( 12.0 % tegaserod v 11.1 % placebo ) . Diarrhoea led to discontinuation in 2.3 % of tegaserod patients . Serious adverse events were infrequent ( 1.5 % tegaserod v 3.4 % placebo ) . Conclusions : Tegaserod 6 mg twice daily is an effective , safe , and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea AIM To study the efficacy of low-dose imipramine in relieving symptoms associated with the irritable bowel syndrome ( IBS ) . METHODS A r and omized , double-blind trial of 25 mg imipramine vs matched placebo for 12 wk was performed . Doubling the dose was allowed once at week 2 in case of an unsatisfactory early response . Primary efficacy variables were subjective global symptom relief and quality of life ( QoL ) using SF-36 at week 12 . RESULTS One hundred and seven patients were enrolled by advertisement or referral by general practitioners and 56 ( 31 imipramine : 25 placebo ) completed the 16-wk study . Baseline characteristics were comparable . A high overall dropout rate was noted in the imipramine and placebo arms ( 47.5 % vs 47.9 % , P > 0.05 ) , a mean of 25.0 and 37.4 d from enrollment , respectively ( P < 0.05 ) . At the end of 12 wk , there was a significant difference in global symptom relief with imipramine over placebo ( per- protocol : 80.6 % vs 48.0 % , P = 0.01 ) and a trend on intent-to-treat ( ITT ) analysis ( 42.4 % vs 25.0 % , P = 0.06 ) . This improvement was evident early and persisted to week 16 ( P = 0.024 and 0.053 by per- protocol and ITT analyses , respectively ) . Mean cumulative and component-specific SF-36 scores improved in the imipramine group only ( per- protocol , P < 0.01 ) . Drug-related adverse events leading to patient dropout were more common in the imipramine group ( 25.4 % vs 12.5 % , P > 0.05 ) . CONCLUSION Imipramine may be effective in the treatment of IBS patients and is associated with improved QoL. Careful patient selection , initiation of a low dose with gradual escalation and monitoring for side effects may result in an improved therapeutic response Background : Irritable bowel syndrome has been treated with selective serotonin reuptake inhibitors but there is not enough evidence from controlled trials to prove their effectiveness BACKGROUND & AIMS Studies of antidepressants and psychological treatments in functional bowel disorders ( FBD ) are method ologically limited . The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy ( CBT ) against education ( EDU ) and desipramine ( DES ) against placebo ( PLA ) in female patients with moderate to severe FBD ( irritable bowel syndrome , functional abdominal pain , painful constipation , and unspecified FBD ) . We also evaluated the amenability of clinical ly meaningful subgroups to these treatments . METHODS This r and omized , comparator-controlled , multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD . Participants received psychological ( CBT vs. EDU ) or antidepressant ( DES vs. PLA ) treatment for 12 weeks . Clinical , physiologic , and psychosocial assessment s were performed before and at the end of treatment . RESULTS The intention-to-treat analysis showed CBT as significantly more effective than EDU ( P = 0.0001 ; responder rate , 70 % CBT vs. 37 % EDU ; number needed to treat [ NNT ] , 3.1 ) . DES did not show significant benefit over PLA in the intention-to-treat analysis ( P = 0.16 ; responder rate , 60 % DES vs. 47 % PLA ; NNT , 8.1 ) but did show a statistically significant benefit in the per- protocol analysis ( P = 0.01 ; responder rate , 73 % DES vs. 49 % PLA ; NNT , 5.2 ) , especially when participants with nondetectable blood levels of DES were excluded ( P = 0.002 ) . Improvement was best gauged by satisfaction with treatment . Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms , abuse history , no depression , and diarrhea-predominant symptoms ; CBT was beneficial over EDU for all subgroups except for depression . CONCLUSIONS For female patients with moderate to severe FBD , CBT is effective and DES may be effective when taken adequately . Certain clinical subgroups are more or less amenable to these treatments Irritable bowel syndrome is a common gastrointestinal disorder characterized by abdominal pain and discomfort and altered bowel habit . Antagonism at the 5‐HT3 receptor may be of benefit in the treatment of irritable bowel syndrome BACKGROUND & AIMS The aim of this study was to evaluate the dose-ranging pharmacodynamic effects of renzapride , a 5-hydroxytryptamine 4 ( 5-HT4 ) receptor full agonist/5-HT3 receptor antagonist , on gastrointestinal transit and symptoms in patients with constipation-predominant irritable bowel syndrome ( C-IBS ) . METHODS Forty-eight patients ( 46 women ) with C-IBS underwent recording of baseline symptoms for 1 week . Twelve patients per group were r and omized ( double-blind , parallel design ) to 11 - 14 days of renzapride ( 1 , 2 , or 4 mg ) or placebo , once daily . Daily bowel habits and weekly satisfactory relief of IBS symptoms were recorded . At the end of treatment , gastric emptying ( GE ) , small bowel transit ( SBT ) , and colon transit ( CT ) were measured by scintigraphy . The relationship between CT and bowel function was evaluated . RESULTS A statistically significant linear dose response to renzapride was detected for CT ( GC8 h , P = 0.004 ; GC24 h , P = 0.056 ) , and ascending colon ( AC ) emptying t1/2 ( P = 0.019 ) , but not for GE ( t1/2 , P = 0.088 ; or SBT , P = 0.41 ) . AC half-time transit ( t1/2 ) for placebo and 4 mg of renzapride were ( median ) 17.5 vs. 5.0 hours , respectively . Improved bowel function scores ( stool form and ease of passage , but not frequency ) were significantly ( P < 0.05 ) associated with accelerated CT . Pharmacokinetic analysis showed linear kinetics of renzapride with a mean t1/2 in plasma of 10 hours . Bowel function and satisfactory relief were not significantly altered by renzapride , although a type II error can not be excluded . No significant adverse clinical , laboratory , or electrocardiogram ( ECG ) effects were observed . CONCLUSIONS Renzapride causes clinical ly significant dose-related acceleration of CT , particularly ascending colonic emptying ; this acceleration of transit is associated with improvement of bowel function in female C-IBS patients OBJECTIVE : Alosetron is indicated for women with chronic , severe diarrhea-predominant IBS ( d-IBS ) who have not responded adequately to conventional therapy . Constipation is the most common adverse event with alosetron treatment . Multiple dosing regimens were assessed in a r and omized , double-blind , placebo-controlled study ( S3B30040 ) to determine efficacy , tolerability , and evaluate constipation rate . METHODS : 705 women with severe d-IBS were r and omized to placebo , alosetron 0.5 mg once daily , 1 mg once daily , or 1 mg twice daily for 12 wk . The primary end point was the proportion of week 12 responders ( patients with moderate or substantial improvement in IBS symptoms ) on the 7-point Likert Global Improvement Scale ( GIS ) . Secondary end points were average rate of adequate relief of IBS pain and discomfort , and bowel symptom improvements . RESULTS : The proportion of GIS responders at week 12 ( primary time point ) was significantly greater in all alosetron groups compared with placebo ( 54/176 [ 30.7 % ] , 90/177 [ 50.8 % ] , 84/175 [ 48 % ] , and 76/177 [ 42.9 % ] for placebo , 0.5 , 1 mg once daily , and 1 mg twice daily alosetron groups , respectively ; P ≤ 0.02 ) . Results were similar for the average adequate relief rate ( treatment effects ≥12 % , P ≤ 0.038 ) . Bowel symptoms were improved in all alosetron groups . Constipation was the most common adverse event ( 9 % , 16 % , and 19 % patients in the 0.5 mg , 1 mg once daily , and 1 mg twice daily groups , respectively ) . One event of intestinal obstruction and one of ischemic colitis occurred in the 0.5 mg group , and one event of fecal impaction occurred in the 1 mg twice-daily group . All were self-limited and resolved without sequelae . CONCLUSION : Alosetron 0.5 mg and 1 mg once daily as well as 1 mg twice daily are effective in providing global improvement in IBS symptoms , adequate relief of IBS pain and discomfort , and improvement in bowel symptoms in women with severe d-IBS . Lower dosing regimens result ed in a decreased constipation rate Background : Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20 % of the population , with a predominance in females . This was an exploratory study of renzapride in 168 male and female patients with non-D , non-C irritable bowel syndrome ( IBS ) . Patients were r and omized to placebo or renzapride ( 1 , 2 , or 4 mg/day ) for 8 weeks . The primary efficacy variable was patient-reported satisfactory relief of IBS symptoms . Secondary variables included relief of abdominal pain/discomfort . The proportion of patients reporting satisfactory relief of their IBS symptoms for at least 50 % of the time did not differ significantly from those on placebo . However , post hoc analysis in women showed differences in responder rate on renzapride versus placebo of 18.2 % ( 95 % CI −5 % to 42 % ; P = 0.066 ) during weeks 1–4 and 6 % ( 95 % CI −21 % to 33 % ; P = 0.339 ) during weeks 5–8 . Renzapride was well tolerated and most adverse events were mild to moderate in intensity . Further studies are warranted to determine whether renzapride is beneficial in this patient population BACKGROUND AND AIMS Tegaserod is approved for the treatment of constipation-predominant irritable bowel syndrome ( C-IBS ) in females . The aim of this study was to evaluate the effect of tegaserod on colonic transit time ( CTT ) and symptoms in male patients with C-IBS . METHODS Forty-four males with C-IBS ( Rome II ) were enrolled . After a baseline washout period of 2 weeks , 40 patients were r and omized to 6 mg twice daily of tegaserod or placebo for 12 weeks . Daily bowel habits and weekly satisfactory relief of symptoms were recorded . Total and segmental CTT were measured using radiopaque markers at baseline and after treatment . RESULTS The mean + /- SD for the total colonic , right colonic , left colonic and rectosigmoid transit time ( in hours ) were 18.96 + /- 3.92 , 7.74 + /- 1.55 , 5.64 + /- 1.51 and 5.58 + /- 2.2 in the tegaserod group compared to 22.47 + /- 3.73 , 9.69 + /- 2.33 , 6.6 + /- 1.32 and 6.18 + /- 2.22 in the placebo group at the end of 12 weeks . There was a statistically significant difference in the total , right and left CTT in the tegaserod group ( P < 0.05 ) at the end of treatment . Global satisfactory relief at the end of 12 weeks was 75 % in the tegaserod group and 50 % in the placebo group ( P > 0.05 ) . Greater stool frequency occurred in the tegaserod group ( P > 0.05 ) . There was a significant decrease in the stool consistency at the end of 12 weeks in patients treated with tegaserod ( P < 0.05 ) . CONCLUSIONS Tegaserod causes significant acceleration of CTT in male patients with C-IBS . Although there was a trend towards improvement in bowel symptoms in the treated group , this effect was not statistically significant Background : It has been proposed that treatments for irritable bowel syndrome with constipation ( IBS-C ) should provide rapid symptomatic relief , be intermittent , and effective upon repeated use . Aims : To evaluate the efficacy and safety of tegaserod on IBS symptoms , and its impact on quality of life and health economic measures . Patients : Women ( ⩾18 years of age ) with IBS-C according to the Rome II criteria . Methods : Prospect i ve , double blind , placebo controlled , r and omised trial . Women with IBS-C either received tegaserod 6 mg twice daily or placebo for one month . Patients with at least a partial response entered a treatment free interval . Upon symptom recurrence , tegaserod treated patients were re-r and omised to tegaserod or placebo for an additional month . Primary efficacy variables were response ( overall IBS symptoms and abdominal discomfort/pain ) to first and repeated treatment . Analysis was by intention to treat . Results : 2660 patients and 1191 patients were r and omised for first and repeated treatment respectively . Tegaserod was superior to placebo for each primary efficacy variable ( first treatment : 33.7 % v 24.2 % responders respectively for relief of IBS symptoms and 31.3 % v 22.1 % for relief of abdominal discomfort/pain ; repeated treatment : 44.9 % v 28.7 % , and 42.4 % v 27.1 % , all p<0.0001 ) . Tegaserod was superior to placebo for every secondary efficacy variable ( relief of abdominal discomfort/pain , bloating and constipation ; stool frequency and consistency ) . A response to tegaserod was observed within the first treatment week . Tegaserod produced greater satisfaction , work productivity , and improved quality of life than placebo ( p<0.05 ) . Conclusion : Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment BACKGROUND & AIMS Although widely prescribed , the evidence for the use of antidepressants for the treatment of irritable bowel syndrome ( IBS ) is limited . In this study , we hypothesized that fluoxetine ( Prozac ) , a selective serotonin reuptake inhibitor , has visceral analgesic properties , leading to increased sensory thresholds during rectal distention and improvement of symptoms , in particular in IBS patients with visceral hypersensitivity . METHODS Forty non-depressed IBS patients underwent a rectal barostat study to assess the sensitivity to rectal distention before and after 6 weeks of treatment with fluoxetine 20 mg or placebo . Abdominal pain scores , individual gastrointestinal symptoms , global symptom relief , and psychologic symptoms were assessed before and after the intervention . RESULTS At baseline , 21 of 40 patients showed hypersensitivity to rectal distention . Fluoxetine did not significantly alter the threshold for discomfort/pain relative to placebo , either in hypersensitive ( 19 + /- 3 vs. 22 + /- 2 mm Hg above MDP ) or in normosensitive ( 34 + /- 2 vs. 39 + /- 4 mm Hg above MDP ) IBS patients . Overall , 53 % of fluoxetine-treated patients and 76 % of placebo-treated patients reported significant abdominal pain scores after 6 weeks ( not significant ) . In contrast , in hypersensitive patients only , fluoxetine significantly reduced the number of patients reporting significant abdominal pain . Gastrointestinal symptoms , global symptom relief , and psychologic symptoms were not altered . CONCLUSIONS Fluoxetine does not change rectal sensitivity in IBS patients . Possible beneficial effects on pain perception need to be confirmed in larger trials Summary No subjective or objective evidence of beneficial effect was observed from the use of Pirenzipine in irritable bowel syndrome ( TBS ) patients who had not responded to a high fibre diet BACKGROUND Irritable bowel syndrome ( IBS ) is a functional gastrointestinal ( GI ) disease that causes significant impairment in quality of life and accounts for $ 8 billion per year to the healthcare system and loss of productivity in the workplace . OBJECTIVE The authors examined the efficacy and safety of paroxetine controlled-release ( paroxetine-CR ) in patients with IBS . METHOD Seventy-two patients with IBS participated in a 12-week , double-blind , r and omized , placebo-controlled study of paroxetine-CR ( 12.5 mg-50 mg/day ) . Efficacy was measured by Composite Pain Scores ( primary outcome ) and the Clinical Global Impression-Improvement ( CGI-I ) and Severity ( CGI-S ) ratings . RESULTS In intent-to-treat analyses , there were no significant differences between paroxetine-CR ( N=36 ) and placebo ( N=36 ) on reduction in Composite Pain Scores , although the proportion of responders on CGI-I was significantly higher in the paroxetine-CR group . The treatment was well tolerated . CONCLUSION The study did not demonstrate a statistically significant benefit for paroxetine-CR over placebo on the primary outcome measure , although there was improvement in secondary outcome measures . Overall , paroxetine-CR seems to have potential benefit in IBS . Studies with adequate sample s may clarify the role of paroxetine-CR in IBS Until recently many clinical trials of functional gastrointestinal disorders ( FGIDs ) suffered from important weaknesses in trial design , study execution , and data analysis . This makes it difficult to determine whether truly efficacious therapies exist for these disorders . One of the important method ologic problems is the absence of vali date d outcome measures and lack of consensus among stakeholders on how to measure outcome . Currently much of the effort is being put into the development of vali date d outcome measures for several of the FGIDs . The r and omized , controlled trial with parallel groups is the design of choice . In this report , guidelines are given for the basic architecture of intervention studies of FGIDs . Further studies on design issues are required to ensure the recommendations will become evidence based in the future After organic disease had been excluded as far as possible by clinical examination , including laboratory tests , analysis of faeces , and X-ray examination or endoscopy of the upper and lower gastrointestinal tract , 61 patients were given either 50 mg trimipramine at bedtime or identically looking coded placebo in a prospect i ve study for 4 weeks . The complaints were grade d on an analogue scale by both the patients and the physicians . The results showed that the complaint scores were significantly reduced to about half in the placebo group . In the group treated with trimipramine a significantly greater reduction was found for the scores of vomiting , sleeplessness , depression , and for the mucus content of stools . The scores for tiredness during treatment had decreased less in the group receiving trimipramine than in the one receiving placebo . These improvements occurred already during the first week of treatment . No adverse side effect was recorded BACKGROUND Irritable bowel syndrome ( IBS ) is a common gastrointestinal disorder with symptoms of abdominal pain , discomfort , and altered bowel function . Antagonists of the type 3 serotonin receptor ( 5-HT3 ) have shown promising results in the relief of IBS-associated symptoms . We aim ed to confirm these findings by doing a r and omised , placebo-controlled trial . METHODS We studied 647 female IBS patients with diarrhoea-predominant or alternating bowel patterns ( diarrhoea and constipation ) . 324 patients were assigned 1 mg alosetron and 323 placebo orally twice daily for 12 weeks , followed by a 4-week post-treatment period . Adequate relief of abdominal pain and discomfort was the primary endpoint ; secondary endpoints included improvements in urgency , stool frequency , and stool consistency . Analysis was by intention to treat . FINDINGS 79 ( 24 % ) of patients in the alosetron group and 53 ( 16 % ) in the placebo group dropped out . The difference in the drop-out rate between groups was mainly due to a greater occurrence of constipation in the alosetron group . A greater proportion of alosetron-treated patients than placebo-treated patients ( 133 [ 41 % ] vs 94 [ 29 % ] , respectively ) reported adequate relief for all 3 months of treatment ( difference 12 % [ 4.7 - 19.2 ] ) . Alosetron also significantly decreased urgency and stool frequency , and increased stool firmness . Constipation occurred in 30 % and 3 % of patients in the alosetron and placebo groups , respectively . INTERPRETATION Alosetron was well tolerated and clinical ly effective in alleviating pain and bowel-related symptoms in this population of women with IBS OBJECTIVE : The purpose of the trial was to determine whether a high-fiber diet ( HFD ) alone or in combination with paroxetine or placebo was effective treatment for patients with irritable bowel syndrome ( IBS ) . METHODS : Design : Trial of HFD alone ( Group 1 ) followed by a r and omized , double-blind trial of HFD with paroxetine or placebo ( Group 2 ) . Setting : Gastroenterology office in a 524-bed university-affiliated community hospital in Pittsburgh . Patients : Men and women , aged 18–65 yr , previously diagnosed with IBS but otherwise healthy . Intervention : Institution of HFD in 98 participants consuming low- or average-fiber diets . Allocation of paroxetine to 38 and placebo to 43 symptomatic participants consuming HFDs . Measurements : Overall well-being , abdominal pain , and abdominal bloating ( Groups 1 and 2 ) ; food avoidance , work functioning , and social functioning ( Group 2 ) . RESULTS : In Group 1 , overall well-being improved in 26 % patients , and abdominal pain and bloating decreased in 22 % and 26 % patients , respectively , with an HFD . In Group 2 , overall well-being improved more with paroxetine than with placebo ( 63.3%vs 26.3 % ; p= 0.01 ) , but abdominal pain , bloating , and social functioning did not . With paroxetine , food avoidance decreased ( p = 0.03 ) and work functioning was marginally better ( p = 0.08 ) . Before unblinding , more paroxetine recipients than placebo recipients wanted to continue their study medication ( 84%vs 37 % ; p < 0.001 ) . CONCLUSIONS : The difference in overall well-being found in our paroxetine/placebo trial is greater than that found in previously published drug/placebo trials for IBS . Moreover , the difference in well-being applied to nondepressed recipients of paroxetine Aim : To study the effect of prokinetic treatment with cisapride in patients with constipation‐predominant irritable bowel syndrome BACKGROUND Irritable bowel syndrome ( IBS ) is a common gastrointestinal disorder seen in primary care practice . The symptoms of IBS , including abdominal pain , discomfort , and abnormal bowel function , may be modulated by activity of the serotonin type 3 receptor ( 5-HT(3 ) ) . The efficacy and tolerability of the 5-HT(3 ) receptor antagonist alosetron hydrochloride in nonconstipated female patients with IBS were evaluated in a double-blind , r and omized , placebo-controlled trial . METHODS Patients received either 1 mg of alosetron hydrochloride ( n = 309 ) or placebo ( n = 317 ) twice daily for 12 weeks , followed by a 4-week posttreatment period . Adequate relief of IBS pain and discomfort was the primary end point . Secondary end points included improvements in urgency , stool frequency , stool consistency , incomplete evacuation , and bloating . RESULTS Seventy-one percent of patients were classified as having diarrhea-predominant IBS . Forty-three percent of alosetron-treated patients with diarrhea-predominant IBS reported adequate relief for all 3 months compared with 26 % of placebo-treated patients ( P<.001 ; percentage point difference = 17 ; 95 % confidence interval , 8.0 - 25.4 ) . Improvement with alosetron compared with placebo was observed by the end of the fourth week of treatment and persisted throughout the remainder of treatment . Alosetron significantly decreased urgency and stool frequency and caused firmer stools within 1 week of starting treatment . Effects were sustained throughout treatment and symptoms returned following treatment cessation . No significant improvement in the percentage of days with sense of incomplete evacuation or bloating was observed compared with placebo during the first month of treatment . Constipation was the most commonly reported adverse event . CONCLUSION Alosetron hydrochloride , 1 mg twice daily for 12 weeks , is effective in relieving pain and some bowel-related symptoms in diarrhea-predominant female patients with IBS Background : Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome ( IBS ) in Western and Asia‐Pacific population s. This study evaluated the efficacy , safety and tolerability of tegaserod versus placebo in patients with IBS . Methods : Patients with IBS ( excluding those whose primary bowel symptom was diarrhoea ) were r and omized to receive either tegaserod 6 mg b.i.d . ( n = 327 ) or placebo ( n = 320 ) for a 12‐week double‐blind treatment period . The primary efficacy variable ( over weeks 1 to 4 ) was the response to the question : ‘ Over the past week do you consider that you have had satisfactory relief from your IBS symptoms ? ’ Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and the individual IBS symptoms . Results : Overall satisfactory relief was greater in the tegaserod group than in the placebo group . Over weeks 1 to 4 , the odds ratio was 1.54 , that is , the odds of satisfactory relief were 54 % higher in the tegaserod group than in the placebo group ( 95 % confidence interval for odds ratio ( CI ) ( 1.14 , 2.08 ) , P = 0.0049 ) . Over weeks 1 to 12 , the odds ratio was 1.78 , that is , the odds of satisfactory relief were 78 % higher in the tegaserod group than in the placebo group ( 95 % CI ( 1.35 , 2.34 ) , P < 0.0001 ) . A statistically significant therapeutic gain over placebo was observed for the majority of weeks from week 1 to week 12 ( except weeks 1 and 4 ) , with a mean therapeutic gain of 7.3 and 10.6 percentage points over weeks 1–4 and weeks 1–12 , respectively . Headache was the most commonly reported adverse event ( 8.0 % tegaserod versus 4.7 % placebo ) . Diarrhoea was reported by 9.2 % of patients on tegaserod ( 1.3 % on placebo ) and led to discontinuation in 2.8 % of tegaserod patients . Conclusion : Tegaserod 6 mg b.i.d . is an effective , safe and well‐tolerated treatment in patients suffering from IBS without diarrhoea as primary bowel symptom Most drugs are ineffective for the long-term treatment of irritable bowel syndrome ( IBS ) . The beneficial effects of medical treatment of IBS are poor and last for only a relative short time . Over a period of 6 months , we investigated the effectiveness of cimetropium bromide , a new antimuscarinic compound , in patients with IBS . Forty-eight patients were treated at r and om and in double-blind fashion with cimetropium bromide ( 50 mg , tid ) or placebo for 6 months . Personal diary cards and monthly check-ups guaranteed the monitoring of symptoms ( mainly pain ) . In addition , personality patterns ( MHQ-CBA tests ) were obtained for the patients before and after therapy , both to detect possible psychoneurotic traits and to observe the changes in these traits in relation to the changes in pain symptoms . Three patients on placebo and one on cimetropium dropped out . At the end of therapy , pain scores had decreased an average of 16 % in the placebo group and 87 % in the cimetropium group ( p less than 0.01 ) . Twenty patients ( 87 % ) on cimetropium versus five patients ( 24 % ) on placebo considered themselves to be globally improved ( p less than 0.01 ) . The MHQ test showed significant improvement in the anxiety score in the cimetropium group only . The CBA test confirmed a significant decrease in anxiety state ( STAI-X-1 ) after cimetropium treatment . Eleven patients ( 48 % ) on cimetropium reported side effects ( mainly dry mouth and sleepiness ) , but none withdrew from the study . The results of this trial indicate that long-term treatment of IBS with cimetropium bromide significantly improves symptoms and associated psychological disorders Cimetropium bromide is a new antimuscarinic compound with strong antispasmodic activity . The aim of this study was to evaluate the effects of oral cimetropium bromide on total gut transit time in patients with irritable bowel syndrome . Forty patients , divided according to their initial total gastrointestinal transit times and presenting symptoms , were treated with cimetropium bromide 50 mg t.d.s . or placebo for 1 month according to a double‐blind , parallel group design . Before and after treatment all subjects ingested 24 radio‐opaque markers . The total intestinal transit time was determined by evaluating the rate of disappearance of markers from plain X‐ray films of the abdomen taken every 24 h for 4 days . Pain and bowel habits were also monitored . Seven patients did not complete the study . Cimetropium bromide significantly ( P < 0.01 ) shortened the whole gut transit time in patients with prolonged transit time ( 80.8 ± 4.0 h before vs 60.8 ± 6.7 h after treatment ) and improved the global clinical condition significantly compared with placebo ( P= 0.029 ) . In patients with a short total intestinal transit time , cimetropium bromide had no effect on whole gut transit time and did not significantly improve symptoms . The results of this study indicate that oral cimetropium bromide is effective both objective ly and subjectively in a subgroup of irritable bowel syndrome patients with constipation A double-blind , r and omized parallel group trial comparison involving 712 patients with irritable bowel syndrome was performed . Over a treatment period of 4 weeks hyoscine-N-butylbromide ( 30 mg/day p.o . ) plus paracetamol ( 1 500 mg/day p.o . ) , hyoscine-N-butylbromide ( 30 mg/day p.o . ) , paracetamol ( 1 . 500 mg/day p.o . ) or placebo ( 3 tablets/day p.o . ) were administered . Patients kept a diary and entered a daily rating of their symptoms ( visual analogue scale ) . At the end of the four weeks 81 % of the patients in the Buscopan plus group were deemed " responder " ( marked or some improvement in symptoms ) . In the Buscopan group 76 % , in the paracetamol group 72 % and in the placebo group 64 % of the patients were responders . The differences between the Buscopan plus group and the placebo group , and between the Buscopan group and the placebo group were statistically significant . The daily rating on the analogue scale showed a statistically significant improvement in abdominal pain intensity in the Buscopan plus group versus the placebo group and in the Buscopan plus group versus the paracetamol group . Thirty-eight patients ( = 5 % , no differences between the treatment groups ) experienced adverse effects , that did not require treatment . Buscopan plus and Buscopan are suitable for the treatment of the irritable bowel syndromes Twenty adult Indian patients suffering from the spastic form of irritable colon , i.e. abdominal pain and constipation , were given trimebutine ( Mebutin ) , 2-phenyl , 2-dimethylamino-n-butyl 3 , 4 , 5-trimethoxybenzoate . Patients were given treatment with 200 mg trimebutine three times daily , or placebo for 4 weeks , and then crossed over . In addition , stool transit times were assessed by the single stool transit time ( SST ) method of Cummings . Results showed a statistical improvement in abdominal pain and constipation with both trimebutine and placebo after 4 weeks , but only with trimebutine after 8 weeks . Single stool transit time was significantly reduced after trimebutine BACKGROUND Cisapride improves symptoms in patients with idiopathic constipation . This trial compares the effect of cisapride with that of placebo in patients with irritable bowel syndrome ( IBS ) and constipation . METHODS Seventy patients were r and omized to 12 weeks ' treatment with 5 mg cisapride three times daily or placebo in a double-blind trial . The dose could be doubled after 4 weeks in patients without satisfactory improvement . The patients scored their symptoms on a 100-mm visual analogue scale ( VAS ) ( 0 = best , 100 = worst ) , and the investigators evaluated the symptomatic effect . RESULTS The dose was doubled in 17 and 23 patients in the cisapride and placebo groups , respectively , after 4 weeks . The patients ' mean VAS score for global evaluation of IBS symptoms in the cisapride and placebo groups was 73 and 71 mm , respectively , at the start of treatment and 47 and 41 mm at the end . The difference between cisapride and placebo at the end was 6 mm in favour of placebo ( 95 % confidence interval ( CI ) , -6 , 18 ) ( NS ) . The investigators evaluated the effect as good or excellent in 39.2 % and 58.8 % in the cisapride and placebo groups , respectively . The difference in favour of placebo was 19.5 % ( 95 % CI , -5 , 44 ) ( NS ) . Nor were any statistically significant differences seen between cisapride and placebo in the other effect factors . CONCLUSIONS The trial seems to exclude a clinical ly significant effect of 15 - 30 mg cisapride daily in patients with IBS and constipation during a 12-week treatment period Abstract Numerous attempts have been made to relate specific emotional conflicts to colonic symptoms in the irritable colon syndrome . Depression has been described as an accompaniment of the illness . This paper investigates the relationship between irritable colon and depression using self-rating symptom scales and the Zung Self-Rating Depression Scale . Thirty-one subjects were followed for two months in a double-blind study employing a tricyclic antidepressant and an inactive placebo . The study demonstrates the frequency of depression in patients with the syndrome ; it shows a clearly positive treatment effect with placebo alone for both depressive symptoms and gastrointestinal complaints , and suggests that tricyclic antidepressant therapy results in moderately greater improvement in symptoms than does treatment with placebo alone |
11,779 | 28,621,712 | Pre clinical trials have shown that HCQ alone and in combination therapy leads to enhancement of tumor shrinkage . | Eukaryotes use autophagy as a mechanism for maintaining cellular homeostasis by degrading and recycling organelles and proteins .
This process assists in the proliferation and survival of advanced cancers .
There is mounting pre clinical evidence that targeting autophagy can enhance the efficacy of many cancer therapies .
Hydroxychloroquine ( HCQ ) is the only clinical ly-approved autophagy inhibitor , and this systematic review focuses on HCQ use in cancer clinical trials . | The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance , which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation . Pre clinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib . We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma . We enrolled 25 patients , including 11 ( 44 % ) refractory to prior bortezomib . No protocol -defined dose-limiting toxicities occurred , and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with st and ard doses of bortezomib , at which we observed dose-related gastrointestinal toxicity and cytopenias . Of 22 patients evaluable for response , 3 ( 14 % ) had very good partial responses , 3 ( 14 % ) had minor responses , and 10 ( 45 % ) had a period of stable disease . Electron micrographs of bone marrow plasma cells collected at baseline , after a hydroxychloroquine run-in , and after combined therapy showed therapy-associated increases in autophagic vacuoles , consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity . Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy Pre clinical studies indicate autophagy inhibition with hydroxychloroquine ( HCQ ) can augment the efficacy of DNA-damaging therapy . The primary objective of this trial was to determine the maximum tolerated dose ( MTD ) and efficacy of HCQ in combination with radiation therapy ( RT ) and temozolomide ( TMZ ) for newly diagnosed glioblastoma ( GB ) . A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection . Patients received HCQ ( 200 to 800 mg oral daily ) with RT and concurrent and adjuvant TMZ . Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles ( AVs ) in peripheral blood mononuclear cells ( P BMC ) . Population pharmacokinetic ( PK ) modeling enabled PK-pharmacodynamic correlations . Sixteen phase I subjects were evaluable for dose-limiting toxicities . At 800 mg HCQ/d , 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia , 1 with sepsis . HCQ 600 mg/d was found to be the MTD in this combination . The phase II cohort ( n = 76 ) had a median survival of 15.6 mos with survival rates at 12 , 18 , and 24 mo of 70 % , 36 % , and 25 % . PK analysis indicated dose-proportional exposure for HCQ . Significant therapy-associated increases in AV and LC3-II were observed in P BMC and correlated with higher HCQ exposure . These data establish that autophagy inhibition is achievable with HCQ , but dose-limiting toxicity prevented escalation to higher doses of HCQ . At HCQ 600 mg/d , autophagy inhibition was not consistently achieved in patients treated with this regimen , and no significant improvement in overall survival was observed . Therefore , a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ Blocking autophagy with hydroxychloroquine ( HCQ ) augments cell death associated with alkylating chemotherapy in pre clinical models . This phase I study evaluated the maximum tolerated dose ( MTD ) , safety , preliminary activity , pharmacokinetics , and pharmacodynamics of HCQ in combination with dose-intense temozolomide ( TMZ ) in patients with advanced solid malignancies . Forty patients ( 73 % metastatic melanoma ) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m2 daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed . An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ . Common toxicities included grade 2 fatigue ( 55 % ) , anorexia ( 28 % ) , nausea ( 48 % ) , constipation ( 20 % ) , and diarrhea ( 20 % ) . Partial responses and stable disease were observed in 3/22 ( 14 % ) and 6/22 ( 27 % ) patients with metastatic melanoma . In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response , and prolonged stable disease , respectively . A significant accumulation in autophagic vacuoles ( AV ) in peripheral blood mononuclear cells was observed in response to combined therapy . Population pharmacokinetics ( PK ) modeling , individual PK simulations , and PK-pharmacodynamics ( PD ) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation . This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable , and is associated with autophagy modulation in patients . Prolonged stable disease and responses suggest antitumor activity in melanoma patients , warranting further studies of this combination , or combinations of more potent autophagy inhibitors and chemotherapy in melanoma Introduction : This investigator-initiated study explores the safety , maximum tolerated dose , clinical response , and pharmacokinetics of hydroxychloroquine ( HCQ ) with and without erlotinib in patients with advanced non – small-cell lung cancer . Methods : Patients with prior clinical benefit from an epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor were r and omized to HCQ or HCQ plus erlotinib in a 3 + 3 dose-escalation schema . Results : Twenty-seven patients were treated , eight with HCQ ( arm A ) and 19 with HCQ plus erlotinib ( arm B ) . EGFR mutations were detected in 74 % of the patients and 85 % had received two or more prior therapies . Arm A had no dose-limiting toxicities , but the maximum tolerated dose was not reached as this arm closed early to increase overall study accrual . In arm B , one patient each experienced grade 3 rash , nail changes , skin changes , nausea , dehydration , and neutropenia ; one had grade 4 anemia ; and one developed fatal pneumonitis , all considered unrelated to HCQ . There were no dose-limiting toxicities , therefore the highest tested dose for HCQ with erlotinib 150 mg was 1000 mg daily . One patient had a partial response to erlotinib/HCQ , for an overall response rate of 5 % ( 95 % confidence interval , 1–25 ) . This patient had an EGFR mutation and remained on therapy for 20 months . Administration of HCQ did not alter the pharmacokinetics of erlotinib . Conclusions : HCQ with or without erlotinib was safe and well tolerated . The recommended phase 2 dose of HCQ was 1000 mg when given in combination with erlotinib 150 mg Autophagy enables cells to de grade and recycle cytoplasmic material s both as a housekeeping mechanism and in response to extracellular stress such as nutrient deprivation . Recent studies indicate that autophagy also functions as a protective mechanism in response to several cancer therapy agents , making it a prospect i ve therapeutic target . Few pharmacological inhibitors suitable for testing the therapeutic potential of autophagy inhibition in vivo are known . An automated microscopy assay was used to screen > 3,500 drugs and pharmacological agents and identified one drug , verteporfin , as an inhibitor of autophagosome accumulation . Verteporfin is a benzoporphyrin derivative used in photodynamic therapy , but it inhibits autophagy without light activation . Verteporfin did not inhibit LC3/Atg8 processing or membrane recruitment in response to autophagic stimuli , but it inhibited drug- and starvation-induced autophagic degradation and the sequestration of cytoplasmic material s into autophagosomes . Transient exposure to verteporfin in starvation conditions reduced cell viability whereas cells in nutrient-rich medium were unaffected by drug treatment . Analysis of structural analogs indicated that the activity of verteporfin requires the presence of a substituted cyclohexadiene at ring A of the porphyrin core but that it can tolerate a number of large substituents at rings C and D. The existence of an autophagy inhibitor among FDA -approved drugs should facilitate the investigation of the therapeutic potential of autophagy inhibition in vivo Autophagy is a lysosomal degradation process that may act as a mechanism of survival in a variety of cancers . While pharmacologic inhibition of autophagy with hydroxychloroquine ( HCQ ) is currently being explored in human clinical trials , it has never been evaluated in canine cancers . Non-Hodgkin lymphoma ( NHL ) is one of the most prevalent tumor types in dogs and has similar pathogenesis and response to treatment as human NHL . Clinical trials in canine patients are conducted in the same way as in human patients , thus , to determine a maximum dose of HCQ that can be combined with a st and ard chemotherapy , a Phase I , single arm , dose escalation trial was conducted in dogs with spontaneous NHL presenting as patients to an academic , tertiary-care veterinary teaching hospital . HCQ was administered daily by mouth throughout the trial , beginning 72 h prior to doxorubicin ( DOX ) , which was given intravenously on a 21-d cycle . Peripheral blood mononuclear cells and biopsies were collected before and 3 d after HCQ treatment and assessed for autophagy inhibition and HCQ concentration . A total of 30 patients were enrolled in the trial . HCQ alone was well tolerated with only mild lethargy and gastrointestinal-related adverse events . The overall response rate ( ORR ) for dogs with lymphoma was 93.3 % , with median progression-free interval ( PFI ) of 5 mo . Pharmacokinetic analysis revealed a 100-fold increase in HCQ in tumors compared with plasma . There was a trend that supported therapy-induced increase in LC3-II ( the cleaved and lipi date d form of microtubule-associated protein 1 light chain 3/LC3 , which serves as a maker for autophagosomes ) and SQSTM1/p62 ( sequestosome 1 ) after treatment . The superior ORR and comparable PFI to single-agent DOX provide strong support for further evaluation via r and omized , placebo-controlled trials in canine and human NHL We previously reported that inhibition of autophagy significantly augmented the anticancer activity of the histone deacetylase ( HDAC ) inhibitor vorinostat ( VOR ) through a cathepsin D-mediated mechanism . We thus conducted a first-in-human study to investigate the safety , preliminary efficacy , pharmacokinetics ( PK ) , and pharmacodynamics ( PD ) of the combination of the autophagy inhibitor hydroxychloroquine ( HCQ ) and VOR in patients with advanced solid tumors . Of 27 patients treated in the study , 24 were considered fully evaluable for study assessment s and toxicity . Patients were treated orally with escalating doses of HCQ daily ( QD ) ( d 2 to 21 of a 21-d cycle ) in combination with 400 mg VOR QD ( d one to 21 ) . Treatment-related adverse events ( AE ) included grade 1 to 2 nausea , diarrhea , fatigue , weight loss , anemia , and elevated creatinine . Grade 3 fatigue and /or myelosuppression were observed in a minority of patients . Fatigue and gastrointestinal AE were dose-limiting toxicities . Six-hundred milligrams HCQ and 400 mg VOR was established as the maximum tolerated dose and recommended phase II regimen . One patient with renal cell carcinoma had a confirmed durable partial response and 2 patients with colorectal cancer had prolonged stable disease . The addition of HCQ did not significantly impact the PK profile of VOR . Treatment-related increases in the expression of CDKN1A and CTSD were more pronounced in tumor biopsies than peripheral blood mononuclear cells . Based on the safety and preliminary efficacy of this combination , additional clinical studies are currently being planned to further investigate autophagy inhibition as a new approach to increase the efficacy of HDAC inhibitors |
11,780 | 29,564,404 | Conclusion This report showed that astigmatism was the most common refractive errors in children and adults followed by hyperopia and myopia .
The highest prevalence of myopia and astigmatism was seen in South-East Asian adults . | Purpose The aim of the study was a systematic review of refractive errors across the world according to the WHO regions . | PURPOSE To determine the prevalence of refractive errors and their distribution according to age and sex in a Brazilian population . METHODS This population -based cross-sectional study involved 7654 Brazilian inhabitants of nine municipalities of Sao Paulo State , Brazil , between March 2004 and July 2005 . Participants aged > 1 year were selected using a r and om , stratified , household cluster sampling technique , excluding individuals with previous refractive or cataract surgery . Myopia was defined as spherical equivalent ( SE ) ≤-0.5D , high myopia as SE ≤-3.0D , hyperopia as SE ≥+0.5D , high hyperopia as SE ≥+3D , astigmatism as ≤-0.5DC and anisometropia as ≥1.0D difference between eyes . Age , sex , complaints and a comprehensive eye examination including cycloplegic refraction test were collected and analysed using descriptive analysis , univariate and multivariate methods . RESULTS The prevalence of astigmatism was 59.7 % , hyperopia 33.8 % and myopia was 25.3 % . Astigmatism had a progressive increase with age . With-the-rule ( WTR ) axes of astigmatism were more frequently observed in the young participants and the against-the-rule ( ATR ) axes were more frequent in the older subjects . The onset of myopia occurred more frequently between the 2nd and 3rd decades of life . Anisometropia showed a prevalence of 13.2 % ( 95 % CI 12.4 - 13.9 ; p < 0.001 ) . There was an association between age and all types of refractive error and hyperopia was also associated with sex . Hyperopia was associated with WTR axes ( odds ratio 0.73 ; 95 % CI : 0.6 - 0.8 ; p < 0.001 ) and myopia with ATR axes ( odds ratio 0.66 ; 95 % CI : 0.6 - 0.8 ; p < 0.001 ) . CONCLUSIONS Astigmatism was the most prevalent refractive error in a Brazilian population . There was a strong relationship between age and all refractive errors and between hyperopia and sex . WTR astigmatism was more frequently associated with hyperopia and ATR astigmatism with myopia . The vast majority of participants had low- grade refractive error , which favours planning aim ed at correction of refractive error in the population PURPOSE To describe the prevalence of hyperopia and associated factors in a representative sample of Australian schoolchildren 6 and 12 years old . DESIGN Population -based cross-sectional study . PARTICIPANTS Schoolchildren ages 6 ( n = 1765 ) and 12 ( n = 2353 ) from 55 r and omly selected schools across Sydney . METHODS Detailed eye examinations included cycloplegic autorefraction , ocular biometry , cover testing , and dilated fundus examination . Information on birth and medical history were obtained from a parent question naire . MAIN OUTCOME MEASURES Moderate hyperopia defined as spherical equivalent ( SE ) refraction of > or = + 2.00 diopters ( D ) , and eye conditions including amblyopia , strabismus , astigmatism , and anisometropia . RESULTS Prevalences of moderate hyperopia among children ages 6 and 12 were 13.2 % and 5.0 % , respectively ; it was more frequent in children of Caucasian ethnicity ( 15.7 % and 6.8 % , respectively ) than in children of other ethnic groups . Compared with children without significant ametropia ( -0.49 < or = SE refraction < or = + 1.99 D ) , the prevalence of eye conditions including amblyopia , strabismus , abnormal convergence , and reduced stereoacuity was significantly greater in children with moderate hyperopia ( all Ps < 0.01 ) . Maternal smoking was significantly associated with moderate hyperopia among 6-year-olds ( P = 0.03 ) , but this association was borderline among 12-year-olds ( P = 0.055 ) . Early gestational age ( < 37 weeks ) and low birth weight ( < 2500 g ) were not statistically significant predictors of moderate hyperopia in childhood . CONCLUSIONS Moderate hyperopia was strongly associated with many common eye conditions , particularly amblyopia and strabismus , in older children . Birth parameters did not predict moderate hyperopia PURPOSE To determine the prevalence of refractive error types in Singaporean Chinese children aged 6 to 72 months . METHODS The Strabismus , Amblyopia and Refractive Error in Singaporean Children ( STARS ) is a population -based study in southwest Singapore . Door-to-door recruitment of participants was used , with disproportionate r and om sampling in 6-month increments . Parental question naires were administered . Participant eye examinations included logMAR visual acuity , cycloplegic autorefraction , and ocular biometry . Overall and age-specific prevalences of myopia ( spherical equivalence [ SE ] < or= -0.50 D ) , high myopia ( SE < or= -6.00 D ) , hyperopia ( SE > or= + 3.00 D ) , astigmatism ( cylinder > or= + 1.50 D ) , and anisometropia ( SE difference between each eye > or=2.00 D ) were calculated . RESULTS A total of 3009 children were examined ( participation rate , 72.3 % ) . Right eye ( OD ) cycloplegia data were available for 1375 boys and 1264 girls ( mean age , 41 months ) . Mean OD SE was + 0.69 D ( SD 1.15 ) . Overall myopia prevalence was 11.0 % with no variance between the sexes ( P = 0.91 ) . The prevalence of high myopia ( at least -6.00 D ) was 0.2 % . The prevalences of hyperopia , astigmatism , and anisometropia were 1.4 % , 8.6 % , and 0.6 % , respectively . Most astigmatism ( > 95 % ) was with-the-rule ( cylinder axes between 1 degrees and 15 degrees or 165 degrees and 180 degrees ) . Myopia was present in 15.8 % , 14.9 % , 20.2 % , 8.6 % , 7.6 % , and 6.4 % of children aged 6 to 11 , 12 to 23 , 24 to 35 , 36 to 47 , 48 to 59 , and 60 to 72 months , respectively . Prevalence increased with age for astigmatism ( P < 0.001 ) , but not for hyperopia or anisometropia ( P = 0.55 and P = 0.37 ) , respectively . CONCLUSIONS The prevalences of myopia and astigmatism in young Singaporean Chinese children are high , but that of hyperopia is low . Age effects were observed for each refractive error category , but differences between the sexes were not significant . Age-related variation in myopia prevalence may be influenced by ocular development , environment , and /or testability Background Due to its high prevalence and associated sight-threatening pathologies , myopia has emerged as a major health issue in East Asia . The purpose was to test the impact on myopia development of a school-based intervention program aim ed at increasing the time student spent outdoors . Methods A total of 3051 students of two primary ( grade s 1 - 5 , aged 6 - 11 ) and two junior high schools ( grade s 7 - 8 , aged 12 - 14 ) in both urban and rural Northeast China were enrolled . The intervention group ( n = 1735 ) unlike the control group ( n = 1316 ) was allowed two additional 20-min recess programs outside the classroom . A detailed question naire was administered to parents and children . Uncorrected visual acuity ( UCVA ) was measured using an E St and ard Logarithm Vision Acuity Chart ( GB11533 - 2011 ) at baseline , 6-month and 1-year intervals . A r and om sub sample ( n = 391 ) participated in the clinic visits and underwent cycloplegia at the beginning and after 1 year . Results The mean UCVA for the entire intervention group was significantly better than the entire control group after 1 year ( P < 0.001 ) . In the subgroup study , new onset of myopia and changes in refractive error towards myopia were direction during the study period was significantly lower in the intervention group than in the control group ( 3.70 % vs. 8.50 % , P = 0.048 ; -0.10 ± 0.65 D/year vs. -0.27 ± 0.52 D/year , P = 0.005 ) . Changes in axial length and IOP were also significantly lower following the intervention group ( 0.16 ± 0.30 mm/year vs. 0.21 ± 0.21 mm/year , P = 0.034 ; -0.05 ± 2.78 mmHg/year vs. 0.67 ± 2.21 mmHg/year , P = 0.006 ) . Conclusions Increasing outdoor activities prevented myopia onset and development , as well as axial growth and elevated IOP in children . Trial registration Current controlled trials NCT02271373 Purpose : To determine the prevalence of amblyopia and refractive errors among 7 to 12-year-old primary school children in Tehran , Iran . Methods : This population -based cross-sectional study included 2,410 r and omly selected students . Visual acuity was tested using an E-chart on Yang vision tester . Refractive errors were measured by photorefractometry and cycloautorefraction . Strabismus was checked using cover test . Direct ophthalmoscopy was used to assess the anterior segment , lens opacities , red reflex and fundus . Functional amblyopia was defined as best corrected visual acuity ≤20/40 in one or both eyes with no anatomical problems . Results : Amblyopia was present in 2.3 % ( 95 % CI : 1.8 % to 2.9 % ) of participants with no difference between the genders . Amblyopic subjects were significantly younger than non-amblyopic children ( P=0.004 ) . Overall , 15.9 % of hyperopic and 5.9 % of myopic cases had amblyopia . The prevalence of hyperopia ≥+2.00D , myopia ≤-0.50D , astigmatism ≥0.75D , and anisometropia ( ≥1.00D ) was 3.5 % , 4.9 % , 22.6 % , and 3.9 % , respectively . With increasing age , the prevalence of myopia increased ( P<0.001 ) , that of hyperopia decreased ( P=0.007 ) , but astigmatism showed no change . Strabismus was found in 2.3 % of cases . Strabismus ( OR=17.9 ) and refractive errors , especially anisometropia ( OR=12.87 ) and hyperopia ( OR=11.87 ) , were important amblyogenic risk factors . Conclusion : The high prevalence of amblyopia in our subjects in comparison to developed countries reveals the necessity of timely and sensitive screening methods . Due to the high prevalence of amblyopia among children with refractive errors , particularly high hyperopia and anisometropia , provision of glasses should be specifically attended by parents and supported by the Ministry of Health and insurance organizations INTRODUCTION Refractive error remains one of the primary causes of visual impairment in children worldwide , and the prevalence of refractive error varies widely . The objective of this study was to determine the prevalence of refractive error and study the possible associated factors inducing refractive error among primary school children of Malay ethnicity in the suburban area of Kota Bharu , Kelantan , Malaysia . MATERIAL S AND METHODS A school-based cross-sectional study was performed from January to July 2006 by r and om selection on St and ard 1 to St and ard 6 students of 10 primary schools in the Kota Bharu district . Visual acuity assessment was measured using logMAR ETDRS chart . Positive predictive value of uncorrected visual acuity equal or worse than 20/40 , was used as a cut-off point for further evaluation by automated refraction and retinoscopic refraction . RESULTS A total of 840 students were enumerated but only 705 were examined . The prevalence of uncorrected visual impairment was seen in 54 ( 7.7 % ) children . The main cause of the uncorrected visual impairment was refractive error which contributed to 90.7 % of the total , and with 7.0 % prevalence for the studied population . Myopia is the most common type of refractive error among children aged 6 to 12 years with prevalence of 5.4 % , followed by hyperopia at 1.0 % and astigmatism at 0.6 % . A significant positive correlation was noted between myopia development with increasing age ( P < 0.005 ) , more hours spent on reading books ( P < 0.005 ) and background history of siblings with glasses ( P < 0.005 ) and whose parents are of higher educational level ( P < 0.005 ) . Malays in suburban Kelantan ( 5.4 % ) have the lowest prevalence of myopia compared with Malays in the metropolitan cities of Kuala Lumpur ( 9.2 % ) and Singapore ( 22.1 % ) . CONCLUSION The ethnicity-specific prevalence rate of myopia was the lowest among Malays in Kota Bharu , followed by Kuala Lumpur , and is the highest among Singaporean Malays . Better socio-economic factors could have contributed to higher myopia rates in the cities , since the genetic background of these ethnic Malays are similar PURPOSE To assess the prevalence of refractive errors and vision impairment in school-age children in Shunyi District , northeast of Beijing , the Peoples Republic of China . METHODS R and om selection of village-based clusters was used to identify a sample of children 5 to 15 years of age . Resident registration books were used to enumerate eligible children in the selected villages and identify their current school . Ophthalmic examinations were conducted in 132 schools on children from 29 clusters during May 1988 to July 1998 , including visual acuity measurements , cycloplegic retinoscopy , cycloplegic autorefraction , ocular motility evaluation , and examination of the external eye , anterior segment , media , and fundus . Independent replicate measurements of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in three schools . RESULTS A total of 6,134 children from 4,338 households were enumerated , and 5,884 children ( 95.9 % ) were examined . The prevalence of uncorrected , presenting , and best visual acuity 0.5 ( 20/40 ) or worse in at least one eye was 12.8 % , 10.9 % , and 1.8 % , respectively ; 0.4 % had best visual acuity 0.5 or worse in both eyes . Refractive error was the cause in 89.5 % of the 1,236 eyes with reduced vision , amblyopia in 5 % , other causes in 1.5 % , with unexplained causes in the remaining 4 % . Myopia -0.5 diopter or less in either eye was essentially absent in 5-year-old children , but increased to 36.7 % in males and 55.0 % in females by age 15 . Over this same age range , hyperopia 2 diopters or greater decreased from 8.8 % in males and 19.6 % in females to less than 2 % in both . Females had a significantly higher risk of both myopia and hyperopia . CONCLUSIONS Reduced vision because of myopia is an important public health problem in school-age children in Shunyi District . More than 9 % of children could benefit from prescription glasses . Further studies are needed to determine whether the upward trend in the prevalence of myopia continues far beyond age 15 and whether the development of myopia is changing for more recent birth cohorts OBJECTIVE To determine the prevalence of refractive error and associated risk factors in the Meiktila District of central rural Myanmar . DESIGN Population -based cross-sectional study . PARTICIPANTS R and omized stratified cluster sampling of the inhabitants 40 years or older from villages in Meiktila was performed ; 2481 eligible participants were identified , 2076 participated in the study , and adequate refractive data were obtained on 1863 individuals ( 75.1 % ) . METHODS Demographic data including age , gender , and education level were obtained from all participants . The ophthalmic examination included autorefraction , nuclear opalescence ( NO ) grading at the slit lamp , and applanation tonometry . MAIN OUTCOME MEASURES Refractive errors were classified by type of ametropia and their prevalence was determined . Univariate and multivariate analyses were performed and odds ratios were calculated for the predictors of refractive error within the statistical models . RESULTS Mean refractive error measured -1.3 diopters ( D ) ( st and ard deviation [ SD ] , 2.9 ) and mean cylindrical error measured 1.1 D ( SD , 1.5 ) . Myopia of > -1.0 and > -6.0 D occurred in 42.7 % ( 95 % confidence interval [ CI ] , 40.4%-44.9 % ) and 6.5 % ( 95 % CI , 5.4%-7.6 % ) of subjects , respectively . Myopic refractive error was associated significantly with a higher degree of NO ( P<0.001 ) and age . Hypermetropia of > + 1.0 D occurred in 15 % ( 95 % CI , 5.4%-7.6 % ) of the population and was associated with higher education levels ( P<0.001 ) . Astigmatism worse than 1.0 D occurred in 30.6 % ( 95 % CI , 28.5%-32.7 % ) of the population and was associated with age ( P<0.001 ) and NO ( P<0.001 ) . CONCLUSION Myopia was more prevalent in older subjects and in those with increased NO . The prevalence rates of myopia in the > or = 40 age group are higher than those found in other Asian regions and are likely to contribute to visual impairment BACKGROUND This study determined the importance of including tests for refractive errors in vision screening . METHODS In this cross-sectional study , we performed a r and om cluster sampling of schoolchildren in the city of Dezful , Iran . After sampling and obtaining informed written consents from their parents , children underwent examinations at the school sites . Students underwent tests of visual acuity , cover tests and cycloplegic refractions . Elementary and middle school students who had a visual acuity of 20/20 or better in both eyes were included in the study . RESULTS From 3673 elementary and middle school students , 2957 ( 80.5 % ) had 20/20 vision or better . Of these , 16.1 % [ 95 % confidence interval ( CI ) : 14.8 - 17.4 ] were ametropic , 0.4 % had myopia and 10.1 % had hyperopia . Mean sphere in those with hyperopia was + 2.6±0.7 ( range : + 2.0 to + 7.28 ) diopter ( D ) . Astigmatism was detected in 6.6 % and the mean cylinder was -0.9 ( range : -0.75 to -3.25 ) D. The rate of anisometropia was 1.5 % ( 95 % CI : 0.8 - 2.0 ) . CONCLUSION Screening results of 20/20 vision for schoolchildren does not necessarily indicate normal eye status because hyperopia and astigmatism may still be sources of visual discomfort . To identify these cases and increase the sensitivity of screening tests , measurement of refractive errors by cycloplegic refraction tests might be included in vision screening PURPOSE To evaluate the prevalence of refractive errors associated with age , gender , and central corneal thickness and to evaluate astigmatism in the refraction and keratometry in a r and omly sample d elderly Japanese population . DESIGN Population -based epidemiologic survey . PARTICIPANTS A r and om sampling of residents of Tajimi , Japan , aged 40 years or older . A total of 3021 residents ( participation rate , 78.1 % ) participated . METHODS Each subject underwent screening examinations including autokeratorefractometry , subjective refraction , best-corrected visual acuity , central corneal thickness measurement , intraocular pressure measurement , slit-lamp examination , fundus photography , and visual field testing . MAIN OUTCOME MEASURES The prevalence of myopia ( spherical equivalent [ SE ] , < -0.5 diopters [ D ] ) , high myopia ( SE , < -5 D ) , hyperopia ( SE , > 0.5 D ) , refractive astigmatism ( cylinder , > 0.5 D ) , and anisometropia ( difference in SE between eyes , > 1.0 D ) , and the correlation of refractive errors with age , gender , and central corneal thickness . Astigmatism in the refraction and keratometry was analyzed using polar value analysis and the vector calculation method . RESULTS The crude prevalence of myopia , high myopia , hyperopia , refractive astigmatism in the refraction , and anisometropia was 41.8 % ( 95 % confidence interval [ CI ] , 40.0%-43.6 % ) , 8.2 % ( 95 % CI , 7.2%-9.2 % ) , 27.9 % ( 95 % CI , 26.3%-29.6 % ) , 54.0 % ( 95 % CI , 52.1%-55.8 % ) , and 15.1 % ( 95 % CI , 13.7%-16.4 % ) , respectively . The prevalence of myopia decreased with age up to 70 to 79 years but increased slightly in patients 80 years and older ; the prevalence of hyperopia showed the opposite trend . The prevalence of astigmatism and anisometropia was higher in the older age groups . No significant gender difference was found associated with the refractive status except for keratometric readings . Polar value analysis and the vector calculation method showed a trend toward against-the-rule astigmatism with increasing age in both refractive and keratometric astigmatism , with a discrepancy between the two . CONCLUSIONS The overall prevalence of myopia ( SE , < -0.5 diopters ) was 41.8 % in the study population , which is higher than that in population -based studies previously reported Purpose We assessed changes in age-specific prevalence of refractive error at the time of starting school , by comparing preschool and school age cohorts in Shanghai , China . Methods A cross-sectional study was done in Jiading District , Shanghai during November and December 2013 . We r and omly selected 7 kindergartens and 7 primary schools , with probability proportionate to size . Chinese children ( n = 8398 ) aged 3 to 10 years were enumerated , and 8267 ( 98.4 % ) were included . Children underwent distance visual acuity assessment and refraction measurement by cycloplegic autorefraction and subjective refraction . Results The prevalence of uncorrected visual acuity ( UCVA ) , presenting visual acuity , and best-corrected visual acuity in the better eye of ≤20/40 was 19.8 % , 15.5 % , and 1.7 % , respectively . Among those with UCVA ≤ 20/40 , 93.2 % could achieve visual acuity of ≥20/32 with refraction . Only 28.7 % ( n = 465 ) of children with UCVA in the better eye of ≤20/40 wore glasses . Prevalence of myopia ( spherical equivalent ≤-0.5 diopters [ D ] in at least one eye ) increased from 1.78 % in 3-year-olds to 52.2 % in 10-year-olds , while prevalence of hyperopia ( spherical equivalent ≥+2.0 D ) decreased from 17.8 % among 3-year-olds to 2.6 % by 10 years of age . After adjusting for age , attending elite " high-level " school was statistically associated with greater myopia prevalence . Conclusions The prevalence of myopia was lower or comparable to that reported in other population s from age 3 to 5 years , but increased dramatically after 6 years , consistent with a strong environmental role of schooling on myopia development PURPOSE To provide data on prevalence and types of refractive error and the spectacle-wearing rate among adults in Nigeria and the degree to which the need for distance correction could be met by off-the-shelf spectacles . METHODS Multistage , stratified , cluster r and om sampling with probability proportional to size was used to identify a nationally representative sample of 15,027 persons aged ≥40 years . Distance vision was measured using a reduced logMAR tumbling-E chart . All participants underwent autorefraction , and those with presenting acuity of < 6/12 in one or both eyes had their corrected acuity measured and underwent detailed clinical examination to determine the cause . RESULTS Included in the survey were 13,599 ( 89.9 % ) of the 15,122 persons aged ≥40 years who were enumerated . Uncorrected refractive error was responsible for 77.9 % of mild visual impairment ( < 6/12 - 6/18 ) , 57.1 % of moderate visual impairment ( < 6/18 - 6/60 ) , 11.3 % of severe visual impairment ( < 6/60 - 3/60 ) , and 1.4 % of blindness ( < 3/60 ) . The crude prevalence of myopia ( ≤0.5 D ) and high myopia ( ≤5.0 D ) were 16.2 % and 2.1 % , respectively . Spectacles could improve the vision of 1279 ( 9.4 % ) and 882 ( 6.5 % ) participants at the 6/12 and 6/18 level , respectively , but only 3.4 % and 4.4 % of these individuals wore spectacles to the examination site . Approximately 2,140,000 adults in Nigeria would benefit from spectacles that improved their vision from < 6/12 to ≥6/12 . More than a third of the need could be met by low-cost , off-the-shelf spectacles . CONCLUSIONS Uncorrected refractive errors are an important cause of visual impairment in Nigeria , and services must be dramatically improved to meet the need purpose To determine the age- and gender-specific prevalences of refractive errors in Tehran through a population -based study . methods A total of 6497 citizens representing a cross-section of the population of Tehran were sample d from 160 clusters using a stratified , r and om , cluster sampling strategy . Eligible people were enumerated through a door-to-door household survey in the selected clusters and were invited to participate . All participants were transferred to a clinic for an extensive eye examination and interview . Refractive error was determined using manifest and cycloplegic refraction . Myopia was defined as the spherical equivalent of −0.5 diopters ( D ) or more and hyperopia was defined as the spherical equivalent of more than + 0.5 D. results Of those sample d , 4565 ( 70.3 % ) people participated in the study . Refraction data for 4354 participants aged five years and over are presented . The age- and gender-st and ardized prevalence of myopia based on manifest refraction was 21.8 % ( 95 % confidence interval [ CI ] , 20.1 to 23.5 ) and that for hyperopia was 26.0 % ( 95 % CI , 24.5 to 27.6 ) . The prevalences based on cycloplegic refraction were 17.2 % ( 95 % CI , 15.6 to 18.8 ) and 56.6 % ( 95 % CI , 54.7 to 58.6 ) , respectively . Prevalences of myopia and hyperopia differed significantly among the age and gender groups ( P < 0.001 ) . Astigmatism of 0.75 cylinder diopter or greater was present in 29.6 % ( 95 % CI , 28.0 to 31.3 ) of right eyes with manifest refraction and in 30.3 % ( 95 % CI , 28.5 to 32.1 ) with cycloplegic refraction . Among the study population , 6.1 % ( 95 % CI , 5.3 to 6.8 % ) had anisometropia of 1 D or more . conclusions This report has provided details of the refractive status in the population . We have documented prevalences of myopia , hyperopia , astigmatism and anisometropia by age and gender , identifying more affected age- and gender-groups for prevention programs in the community PURPOSE To determine the prevalence of refractive errors in the public and private school system in the city of Natal , Northeastern Brazil . METHODS Refractometry was performed on both eyes of 1,024 r and omly selected students , enrolled in the 2001 school year and the data were evaluated by the SPSS Data Editor 10.0 . Ametropia was divided into : 1- from 0.1 to 0.99 diopter ( D ) ; 2- 1.0 to 2.99 D ; 3- 3.00 to 5.99 D and 4- 6D or greater . Astigmatism was regrouped in : I- with-the-rule ( axis from 0 to 30 and 150 to 180 degrees ) , II- against-the-rule ( axis between 60 and 120 degrees ) and III- oblique ( axis between > 30 and < 60 and > 120 and < 150 degrees ) . The age groups were categorized as follows , in : 1- 5 to 10 years , 2- 11 to 15 years , 3- 16 to 20 years , 4- over 21 years . RESULTS Among refractive errors , hyperopia was the most common with 71 % , followed by astigmatism ( 34 % ) and myopia ( 13.3 % ) . Of the students with myopia and hyperopia , 48.5 % and 34.1 % had astigmatism , respectively . With respect to diopters , 58.1 % of myopic students were in group 1 , and 39 % distributed between groups 2 and 3 . Hyperopia were mostly found in group 1 ( 61.7 % ) as well as astigmatism ( 70.6 % ) . The association of the astigmatism axes of both eyes showed 92.5 % with axis with-the-rule in both eyes , while the percentage for those with axis against-the-rule was 82.1 % and even lower for the oblique axis ( 50 % ) . CONCLUSION The results found differed from those of most international studies , mainly from the Orient , which pointed to myopia as the most common refractive error , and corroborates the national ones , with the majority being hyperopia Objective : This study investigated the distribution pattern of refractive status and prevalence of refractive errors in school-age children in Western China to determine the possible environmental factors . Methods : A r and om sampling strategy in geographically defined clusters was used to identify children aged 6 - 15 years in Yongchuan , a socio-economically representative area in Western China . We carried out a door-to-door survey and actual eye examinations , including visual acuity measurements , stereopsis examination , anterior segment and eyeball movements , fundus examinations , and cycloplegic retinoscopy with 1 % cyclopentolate . Results : A total of 3469 children living in 2552 households were selected , and 3070 were examined . The distributions of refractive status were positively-skewed for 6 - 8-year-olds , and negatively-skewed for 9 - 12 and 13 - 15-year-olds . The prevalence of hyperopia ( ≥+2.00 D spherical equivalent [ SE ] ) , myopia ( ≤-0.50 D SE ) , and astigmatism ( ≥1.00 diopter of cylinder [ DC ] ) were 3.26 % , 13.75 % , and 3.75 % , respectively . As children 's ages increased , the prevalence rate of hyperopia decreased ( P<0.001 ) and that of myopia increased significantly ( P<0.001 ) . Children in academically challenging schools had a higher risk of myopia ( P<0.001 ) and astigmatism ( ≥1.00DC , P = 0.04 ) than those in regular schools . Conclusion : The distribution of refractive status changes gradually from positively-skewed to negatively-skewed distributions as age increases , with 9-year-old being the critical age for the changes . Environmental factors and study intensity influence the occurrence and development of myopia PURPOSE To determine the prevalence of refractive conditions in the adult population that visited primary care optometry clinics in Puerto Rico . METHODS A retrospective cross-sectional study of patients examined at the Inter American University of Puerto Rico School of Optometry Eye Institute Clinics between 2004 and 2010 . Subjects considered had best corrected visual acuity by st and ardized subjective refraction of 20/40 or better . The refractive errors were classified by the spherical equivalent ( SE ) : sphere+½ cylinder . Myopia was classified as a SE>-0.50D , hyperopia as a SE>+0.50 D , and emmetropia as a SE between -0.50 and + 0.50 , both included . Astigmatism equal or higher than 0.25 D in minus cylinder form was used . Patients with documented history of cataract extraction ( pseudophakia or aphakia ) , amblyopia , refractive surgery or other corneal/ocular surgery were excluded from the study . RESULTS A total of 784 r and omly selected subjects older than 40 years of age were selected . The estimated prevalence ( 95 % , confidence interval ) among all subjects was hyperopia 51.5 % ( 48.0 - 55.0 ) , emmetropia 33.8 % ( 30.5 - 37.2 ) , myopia 14.7 % ( 12.1 - 17.2 ) and astigmatism 69.6 % ( 68.8 - 73.3 ) . Hyperopia was more common in females than males although the difference was not statistically significant . The mean spherical equivalent values was hyperopic until 70 y/o and decreased slightly as the population ages . CONCLUSION Hyperopia is the most common refractive error and its prevalence and seems to increase among the aging population who visited the clinics . Further programs and studies must be developed to address the refractive errors needs of the adult Puerto Rican population Aim To investigate the prevalence of , and demographic associations with , uncorrected refractive error ( URE ) in an older British population . Methods Data from 4428 participants , aged 48–89 years , who attended an eye examination in the third health check of the European Prospect i ve Investigation into Cancer-Norfolk study and had also undergone an ophthalmic examination were assessed . URE was defined as ≥1 line improvement of visual acuity with pinhole-correction in the better eye in participants with LogMar presenting visual acuity ( PVA ) < 0.3 ( PVA < 6/12 ) . Refractive error was measured using an autorefractor without cycloplegia . Myopia was defined as spherical equivalent ≤−0.5 dioptre , and hypermetropia ≥0.5 dioptre . Results Adjusted to the 2010 midyear British population , the prevalence of URE in this Norfolk population was 1.9 % ( 95 % CI 0.6 % to 3.1 % ) . Lower self-rated distance vision was correlated with higher prevalence of URE ( ptrend<0.001 ) . In a multivariate logistic regression model adjusting for age , gender , retirement status , educational level and social class , independent significant associations with URE were increasing age ( ptrend<0.001 ) and having hypermetropic or myopic refractive error . Wearing distance spectacles was inversely associated with URE ( OR 0.34 , 95 % CI 0.21 to 0.55 , p<0.001 ) . There were 3063 people ( 69.2 % ) who wore spectacles/contact lenses for distance vision . Spectacle wear differed according to type of refractive error ( p<0.001 ) , and use rose with increasing severity of refractive error ( ptrend<0.001 ) . Conclusion Although refractive error is common , the prevalence of URE was found to be low in this population reflecting a low prevalence of PVA<0.3 BACKGROUND Refractive error is an important cause of preventable visual impairment and blindness worldwide . Population -based studies will continue to be a key part in identification ofthe magnitude and the importance of this common eye disease . OBJECTIVE To assess the prevalence of the refractive error in primary school-aged children in Bangkok and Nakhonpathom together with the provision of the appropriately free of charge spectacles . MATERIAL AND METHOD A Population -based cross-sectional analytic study was conducted between October 2008 and September 2009 . R and om selection of geographically defined clusters was used to identify the study sample . The examination included visual acuity ( VA ) by Snellen chart and pinhole correction , autorefraction under cycloplegic refraction , ocular motility evaluation , examination of the external eye , anterior segment , media , and fundus . Ophthalmologists screened for ocular abnormalities . RESULTS Among 2340 children , 1100 in Bangkok and 1240 in Nakhonpathom were examined The prevalence of refractive error in Bangkok and Nakhornpathom were 12.7 % and 5.7 % respectively . Refractive error was the cause in 97.6 % of eyes with reduced vision , amblyopia in 0.5 % , other causes in 0.8 % , and unexplained causes in 1.1 % . CONCLUSION The present study showed a relative high prevalence of uncorrected refractive error in the central part of Thail and especially in Bangkok . Eye health education and screening is recommended to evaluate the need for refractive correction with appropriate prescription of spectacles The prevalence of refractive errors in urban preschool children in Xuzhou , China remains unknown . Children attending twelve r and omly selected kindergartens participated in this study . Visual acuity , ocular alignment , cover-uncover test , cycloplegic refraction , slit-lamp and funduscopy were performed under a st and ardized testing environment . Cycloplegic streak retinoscopy was performed for all subjects . The mean spherical equivalent ( SE ) refractive error was the main outcome measure . Emmetropia was defined as refractive status between + 1.75 diopters ( D ) and -0.75D . Myopia , hyperopia , astigmatism and anisometropia were defined as SE < -0.50D , SE > + 2.0 D , cylindrical error > 1.0 D and SE difference ≥ 1 D between fellow eyes , respectively . Out of 2349 eligible children , 2255 ( 96 % ) children completed a refractive examination . Of the 2255 children , the mean SE of right eyes was + 1.14 ± 0.95 diopters ( D ) . Mean SE of the right eyes did not decline with age ( r = -0.01 ; P = 0.56 ) . The majority ( 86.6 % ) of children were emmetropia . The prevalence of myopia and hyperopia was 0.9 % and 14.3 % , respectively . The mean astigmatism for the right eyes was 0.87 ± 0.62 D. The prevalence of With-the-rule , against the rule and oblique astigmatism was 93.8 % , 4.7 % and 1.5 % , respectively . The mean anisometropia between two eyes was 0.14 ± 0.38 D. The most common type of refractive error was hyperopia ( 14.3 % ) , followed by astigmatism ( 8.8 % ) , anisometropia ( 3.2 % ) , and myopia ( 0.9 % ) . The refractive status in this population of urban Xuzhou preschool children was stable and there was no evidence of a myopic refractive shift over this age range in our cross-sectional study Aim : To report the prevalence , risk factors and associated population attributable risk percentage ( PAR ) for refractive errors in the South Indian adult population . Methods : A population -based cross-sectional epidemiologic study was conducted in the Indian state of And hra Pradesh . A multistage cluster , systematic , stratified r and om sampling method was used to obtain participants ( n = 10293 ) for this study . Results : The age-gender-area-adjusted prevalence rates in those ≥40 years of age were determined for myopia ( spherical equivalent [ SE ] < −0.5 D ) 34.6 % ( 95 % confidence interval [ CI ] : 33.1–36.1 ) , high-myopia ( SE < −5.0 D ) 4.5 % ( 95 % CI : 3.8–5.2 ) , hyperopia ( SE > + 0.5 D ) 18.4 % ( 95 % CI : 17.1–19.7 ) , astigmatism ( cylinder < −0.5 D ) 37.6 % ( 95 % CI : 36–39.2 ) , and anisometropia ( SE difference between right and left eyes > 0.5 D ) 13.0 % ( 95 % CI : 11.9–14.1 ) . The prevalence of myopia , astigmatism , high-myopia , and anisometropia significantly increased with increasing age ( all p < 0.0001 ) . There was no gender difference in prevalence rates in any type of refractive error , though women had a significantly higher rate of hyperopia than men ( p < 0.0001 ) . Hyperopia was significantly higher among those with a higher educational level ( odds ratio [ OR ] 2.49 ; 95 % CI : 1.51–3.95 ) and significantly higher among the hypertensive group ( OR 1.24 ; 95 % CI : 1.03–1.49 ) . The severity of lens nuclear opacity was positively associated with myopia and negatively associated with hyperopia . Conclusions : The prevalence of myopia in this adult Indian population is much higher than in similarly aged white population s. These results confirm the previously reported association between myopia , hyperopia , and nuclear opacity PURPOSE This study was initiated to compare the refractive state in a population sample to that among university students in Norway and to that among the general population in other Nordic countries . METHODS A population sample of 112 individuals and 224 engineering students were r and omly selected and examined using automated and clinical refraction in cycloplegia . RESULTS Statistically significant differences were found in prevalences of myopia ( population sample : 33 % , students : 47 % , p : 0.016 ) and prevalences of hyperopia ( population sample : 47 % , students : 30 % , p : 0.001 ) between the two groups . The mean refractive error among the population sample was -0.1+/-2.0 D compared to -0.6+/-2.2 D among the students ( p=0.0013 ) . CONCLUSIONS The population sample had a significantly lower prevalence of myopia and a higher prevalence of hyperopia than the student population . The state of refraction in the population sample was found to be in agreement with results reported from other Nordic countries BACKGROUND Uncorrected refractive errors are a leading cause of visual disability globally . This population -based study was done to estimate the prevalence of uncorrected refractive errors in adults aged 30 years and above of village Pawakah , Khyber Pakhtunkhwa ( KPK ) , Pakistan . METHODS It was a cross-sectional survey in which 1000 individuals were included r and omly . All the individuals were screened for uncorrected refractive errors and those whose visual acuity ( VA ) was found to be less than 6/6 were refracted . In whom refraction was found to be unsatisfactory ( i.e. , a best corrected visual acuity of < 6/6 ) further examination was done to establish the cause for the subnormal vision . RESULTS A total of 917 subjects participated in the survey ( response rate 92 % ) . The prevalence of uncorrected refractive errors was found to be 23.97 % among males and 20 % among females . The prevalence of visually disabling refractive errors was 6.89 % in males and 5.71 % in females . The prevalence was seen to increase with age , with maximum prevalence in 51 - 60 years age group . Hypermetropia ( 10.14 % ) was found to be the commonest refractive error followed by Myopia ( 6.00 % ) and Astigmatism ( 5.6 % ) . The prevalence of Presbyopia was 57.5 % ( 60.45 % in males and 55.23 % in females ) . Poor affordability was the commonest barrier to the use of spectacles , followed by unawareness . Cataract was the commonest reason for impaired vision after refractive correction . The prevalence of blindness was 1.96 % ( 1.53 % in males and 2.28 % in females ) in this community with cataract as the commonest cause . CONCLUSIONS Despite being the most easily avoidable cause of subnormal vision uncorrected refractive errors still account for a major proportion of the burden of decreased vision in this area . Effective measures for the screening and affordable correction of uncorrected refractive errors need to be incorpora'ted into the health care delivery system Purpose To assess the prevalence of refractive error and visual impairment in private school children in Ghana . Methods A r and om selection of geographically defined classes in clusters was used to identify a sample of school children aged 12 to 15 years in the Ashanti Region . Children in 60 clusters were enumerated and examined in classrooms . The examination included visual acuity , retinoscopy , autorefraction under cycloplegia , and examination of anterior segment , media , and fundus . For quality assurance , a r and om sample of children with reduced and normal vision were selected and re-examined independently . Results A total of 2454 children attending 53 private schools were enumerated , and of these , 2435 ( 99.2 % ) were examined . Prevalence of uncorrected , presenting , and best visual acuity of 20/40 or worse in the better eye was 3.7 , 3.5 , and 0.4 % , respectively . Refractive error was the cause of reduced vision in 71.7 % of 152 eyes , amblyopia in 9.9 % , retinal disorders in 5.9 % , and corneal opacity in 4.6 % . Exterior and anterior segment abnormalities occurred in 43 ( 1.8 % ) children . Myopia ( at least −0.50 D ) in one or both eyes was present in 3.2 % of children when measured with retinoscopy and in 3.4 % measured with autorefraction . Myopia was not significantly associated with gender ( P = 0.82 ) . Hyperopia ( + 2.00 D or more ) in at least one eye was present in 0.3 % of children with retinoscopy and autorefraction . Conclusions The prevalence of reduced vision in Ghanaian private school children due to uncorrected refractive error was low . However , the prevalence of amblyopia , retinal disorders , and corneal opacities indicate the need for early interventions INTRODUCTION The uncorrected refractive error is an important cause of childhood blindness and visual impairment . OBJECTIVE To study the patterns of refractive errors among the urban and rural school going children of Nepal . SUBJECTS AND METHODS A total of 440 school children of urban and rural schools within the age range of 7 - 15 years were selected for this study using multi-stage r and omization technique . RESULTS The overall prevalance of refractive error in school children was 19.8 % . The commonest refractive error among the students was myopia ( 59.8 % ) , followed by hypermetropia ( 31.0 % ) . The children of age group 12 - 15 years had the higher prevalence of myopia as compared to the younger counterparts ( 42.5 % vs 17.2 % ) . The prevalence of myopia was 15.5 % among the urban students as compared to 8.2 % among the rural ones ( RR = 1.89 , 95 % CI = 1.1 - 3.24 ) . The hypermetropia was more common in urban students than in rural ones ( 6.4 % ) vs 5.9 % , RR = 1.08 ( 95 % CI : 0.52 - 2.24 ) . CONCLUSION The prevalence of refractive error in the school children of Nepal is 19.8 % . The students from urban setting s are more likely to have refractive error than their rural counterparts PURPOSE To assess the prevalence of refractive error and visual impairment in school-age children in Gombak District , a suburban area near Kuala Lumpur city . DESIGN Population -based , cross-sectional survey . PARTICIPANTS Four thous and six hundred thirty-four children 7 to 15 years of age living in 3004 households . METHODS R and om selection of geographically defined clusters was used to identify the study sample . Children in 34 clusters were enumerated through a door-to-door survey and examined in 140 schools between March and July 2003 . The examination included visual acuity measurements ; ocular motility evaluation ; retinoscopy and autorefraction under cycloplegia ; and examination of the external eye , anterior segment , media , and fundus . MAIN OUTCOME MEASURES Distance visual acuity and cycloplegic refraction . RESULTS The examined population was 70.3 % Malay , 16.5 % Chinese , 8.9 % Indian , and 4.3 % of other ethnicity . The prevalence of uncorrected ( unaided ) , presenting , and best-corrected visual impairment ( visual acuity < or = 20/40 in the better eye ) was 17.1 % , 10.1 % , and 1.4 % , respectively . More than half of those in need of corrective spectacles were without them . In eyes with reduced vision , refractive error was the cause in 87.0 % , amblyopia in 2.0 % , other causes in 0.6 % , and unexplained causes in 10.4 % , mainly suspected amblyopia . Myopia ( spherical equivalent of at least -0.50 diopter [ D ] in either eye ) measured with retinoscopy was present in 9.8 % of children 7 years of age , increasing to 34.4 % in 15-year-olds ; and in 10.0 % and 32.5 % , respectively , with autorefraction . Myopia was associated with older age , female gender , higher parental education , and Chinese ethnicity . Hyperopia ( > or = 2.00 D ) with retinoscopy varied from 3.8 % in 7-year-olds , 5.0 % with autorefraction , to less than 1 % by age 15 , with either measurement method . Hyperopia was associated with younger age and " other " ethnicity . Astigmatism ( > or = 0.75 D ) was present in 15.7 % of children with retinoscopy and in 21.3 % with autorefraction . CONCLUSIONS Visual impairment in school-age children in urban Gombak District is overwhelmingly caused by myopia , with a particularly high prevalence among children of Chinese ethnicity . Eye health education and screening may help address the unmet need for refractive correction PURPOSE To assess the prevalence of refractive error and related visual impairment in school-aged children in the rural population of the Mahabubnagar district in the southern Indian state of And hra Pradesh . METHODS R and om selection of village-based clusters was used to identify a sample of children 7 to 15 years of age . From April 2000 through February 2001 , children in the 25 selected clusters were enumerated in a door-to-door survey and examined at a rural eye center in the district . The examination included visual acuity measurements , ocular motility evaluation , retinoscopy and autorefraction under cycloplegia , and examination of the anterior segment , media , and fundus . Myopia was defined as spherical equivalent refractive error of at least -0.50 D and hyperopia as + 2.00 D or more . Children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance in seven clusters . RESULTS A total of 4414 children from 4876 households was enumerated , and 4074 ( 92.3 % ) were examined . The prevalence of uncorrected , baseline ( presenting ) , and best corrected visual acuity of 20/40 or worse in the better eye was 2.7 % , 2.6 % , and 0.78 % , respectively . Refractive error was the cause in 61 % of eyes with vision impairment , amblyopia in 12 % , other causes in 15 % , and unexplained causes in the remaining 13 % . A gradual shift toward less-positive values of refractive error occurred with increasing age in both boys and girls . Myopia in one or both eyes was present in 4.1 % of the children . Myopia risk was associated with female gender and having a father with a higher level of schooling . Higher risk of myopia in children of older age was of borderline statistical significance ( P = 0.069 ) . Hyperopia in at least one eye was present in 0.8 % of children , with no significant predictors . CONCLUSIONS Refractive error was the main cause of visual impairment in children aged between 7 and 15 years in rural India . There was a benefit of spectacles in 70 % of those who had visual acuity of 20/40 or worse in the better eye at baseline examination . Because visual impairment can have a significant impact on a child 's life in terms of education and development , it is important that effective strategies be developed to eliminate this easily treated cause of visual impairment PURPOSE To determine the prevalence and risk factors for refractive errors in middle-aged to elderly Singaporeans of Indian ethnicity . METHODS A population -based , cross-sectional study of Indians aged over 40 years of age residing in Southwestern Singapore was conducted . An age-stratified ( 10-year age group ) r and om sampling procedure was performed to select participants . Refraction was determined by autorefraction followed by subjective refraction . Myopia was defined as spherical equivalent ( SE ) < -0.50 diopters ( D ) , high myopia as SE < -5.00 D , astigmatism as cylinder < -0.50 D , hyperopia as SE > 0.50 D , and anisometropia as SE difference > 1.00 D. Prevalence was adjusted to the 2000 Singapore census . RESULTS Of the 4497 persons eligible to participate , 3400 ( 75.6 % ) were examined . Complete data were available for 2805 adults with right eye refractive error and no prior cataract surgery . The age-adjusted prevalence was 28.0 % ( 95 % confidence interval [ CI ] , 25.8 - 30.2 ) for myopia and 4.1 % ( 95 % CI , 3.3 - 5.0 ) for high myopia . There was a U-shaped relationship between myopia and increasing age . The age-adjusted prevalence was 54.9 % ( 95 % CI , 52.0 - 57.9 ) for astigmatism , 35.9 % ( 95 % CI , 33.7 - 38.3 ) for hyperopia , and 9.8 % ( 95 % CI , 8.6 - 11.1 ) for anisometropia . In a multiple logistic regression model , adults who were female , younger , taller , spent more time reading and writing per day , or had astigmatism were more likely to be myopic . Adults who were older or had myopia or diabetes mellitus had higher risk of astigmatism . CONCLUSIONS In Singapore , the prevalence of myopia in Indian adults is similar to those in Malays , but lower than those in Chinese . Risk factors for myopia are similar across the three ethnic groups in Singapore PURPOSE To determine the prevalence of refractive errors and to investigate factors associated with refractive error in adults 30 years of age and older in Bangladesh . DESIGN Cross-sectional study . PARTICIPANTS A nationally representative sample of 12 782 adults 30 years of age and older . METHODS The sample of subjects was selected based on multistage , cluster r and om sampling with probability-proportional-to-size procedures . The examination protocol consisted of an interview that included measures of literacy , education , occupation , and refractive correction . Visual acuity testing ( logarithm of the minimum angle of resolution [ logMAR ] ) , automated refraction , and optic disc examination were performed for all subjects . Subjects with < 6/12 ( 0.3 logMAR ) acuity in either eye were grade d additionally for cataract and underwent a dilated fundal examination . Subjects for whom no refractive error was recorded ( 312 subjects ; 2.7 % ) or who had undergone cataract surgery ( 123 subjects ; 1.1 % ) were excluded from the analysis . MAIN OUTCOME MEASURES Refractive error and socioeconomic variables ( literacy , education , occupation ) . RESULTS Eleven thous and six hundred twenty-four subjects were examined ( 90.9 % response rate ; mean age+/-st and ard deviation , 44+/-12.6 years ) . Five thous and four hundred eighty-nine subjects ( 49.1 % ) were men and 5700 subjects ( 50.9 % ) were women . Mean spherical equivalent was -0.19 diopters ( D ; + /-1.50 D ) . Six thous and four hundred twelve subjects ( 57.3 % ) were emmetropic , 2469 ( 22.1 % ) were myopic ( < -0.5 D ) , and 2308 ( 20.6 % ) were hypermetropic ( > + 0.5 D ) . Two hundred six subjects ( 1.8 % ) were highly myopic ( < -5 D ) . Myopia was more common in men ( 26.3 % ) than in women ( 21.0 % ) , whereas hyperopia was more common in women ( 27.4 % ) than in men ( 15.8 % ) . Overall , myopia increased with age ( 17.5 % of those aged 30 - 39 years were myopic , compared with 65.5 % of those age 70 years and older ) . A sub analysis of subjects without cataract showed increasing hyperopia with age and an association between myopia and higher education . Myopia was more common among the employed than in unemployed subjects . Astigmatism ( > 0.5 D ) , present in 3625 subjects ( 32.4 % ) , was more common among women , illiterate subjects , and unschooled subjects . Against-the-rule astigmatism was more common ( 58.7 % ) than oblique astigmatism ( 29.3 % ) , which was more common than with-the-rule ( WTR ) astigmatism ( 12.1 % ) . Against-the-rule astigmatism and oblique astigmatism increased with age , unlike WTR astigmatism . Of 830 ( 7.5 % ) subjects , women were more commonly anisometropic ( > 1.0 D ) . Anisometropia increased with age . CONCLUSIONS Refractive error data are described for a country and region that previously have lacked population -based data . Prevalence and factors associated with refractive error are presented , with a detailed comparison with other population -based surveys regionally and internationally Background : The latest WHO report indicates that refractive errors are the leading cause of visual impairment throughout the world . The aim of this study was to determine the prevalence of myopia , hyperopia , and astigmatism in 7 yr old children in Iran . Methods : In a cross-sectional study in 2013 with multistage cluster sampling , first grade rs were r and omly selected from 8 cities in Iran . All children were tested by an optometrist for uncorrected and corrected vision , and non-cycloplegic and cycloplegic refraction . Refractive errors in this study were determined based on spherical equivalent ( SE ) cyloplegic refraction . Results : From 4614 selected children , 89.0 % participated in the study , and 4072 were eligible . The prevalence rates of myopia , hyperopia and astigmatism were 3.04 % ( 95 % CI : 2.30–3.78 ) , 6.20 % ( 95 % CI : 5.27–7.14 ) , and 17.43 % ( 95 % CI : 15.39–19.46 ) , respectively . Prevalence of myopia ( P=0.925 ) and astigmatism ( P=0.056 ) were not statistically significantly different between the two genders , but the odds of hyperopia were 1.11 ( 95 % CI : 1.01–2.05 ) times higher in girls ( P=0.011 ) . The prevalence of with-the-rule astigmatism was 12.59 % , against-the-rule was 2.07 % , and oblique 2.65 % . Overall , 22.8 % ( 95 % CI : 19.7–24.9 ) of the schoolchildren in this study had at least one type of refractive error . Conclusion : One out of every 5 schoolchildren had some refractive error . Conducting multicenter studies throughout the Middle East can be very helpful in underst and ing the current distribution patterns and etiology of refractive errors compared to the previous decade Purpose To determine the prevalence of refractive errors in Yazd , central Iran . Methods This population -based study was performed in 2010 - 2011 and targeted adults aged 40 to 80 years . Multi-stage r and om cluster sampling was applied to select sample s from urban and rural residents of Yazd . Manifest refraction , visual acuity measurement , retinoscopy and funduscopy were performed for all subjects . Myopia , hyperopia , astigmatism and anisometropia were defined as spherical equivalent ( SE ) < -0.50 diopters ( D ) , SE > + 0.50 D , cylindrical error > 0.5 D and SE difference ≥1 D between fellow eyes , respectively . Results From a total of 2,320 selected individuals , 2,098 subjects ( 90.4 % ) participated out of which 198 subjects were excluded due to previous eye surgery . The prevalence ( 95 % confidence interval ) for myopia , hyperopia , astigmatism , anisometropia , -6 D myopia or worse , and 4 D hyperopia or worse was 36.5 % ( 33.6 - 39.4 % ) , 20.6 % ( 17.9 - 23.3 % ) , 53.8 % ( 51.3 - 56.3 % ) , 11.9 % ( 10.4 - 13.4 % ) , 2.3 % ( 1.6 - 2.9 % ) and 1.2 % ( 0.6 - 1.8 % ) , respectively . The prevalence of hyperopia , astigmatism and anisometropia increased with age . The prevalence of myopia was significantly higher in female subjects . The prevalence of with-the-rule , against-the-rule and oblique astigmatism was 35.7 % , 13.4 % and 4.6 % , respectively . The prevalence of against-the-rule astigmatism increased with age ( P<0.001 ) ; with-the-rule astigmatism was more common in women ( P=0.038 ) . Conclusion More than half of the study population had refractive errors ; the prevalence of myopia and astigmatism was higher than earlier studies in Iran . Since refractive errors are a major cause of avoidable visual impairment , their high prevalence in this survey is important from a public health perspective Background Uncorrected Refractive Error is one of the leading cause amblyopia that exposes children to poor school performance . It refrain them from productive working lives result ing in severe economic and social loses in their latter adulthood lives . The objective of the study was to assess the prevalence of uncorrected refractive error and its associated factors among school children in Debre Markos District . Method A cross section study design was employed . Four hundred thirty two students were r and omly selected using a multistage stratified sampling technique . The data were collected by trained ophthalmic nurses through interview , structured question naires and physical examinations . Snellens visual acuity measurement chart was used to identify the visual acuity of students . Students with visual acuity less than 6/12 had undergone further examination using auto refractor and cross-checked using spherical and cylindrical lenses . The data were entered into epi data statistical software version 3.1 and analyzed by SPSS version 20 . The statistical significance was set at α ≤ 0.05 . Descriptive , bivariate and multivariate analyses were done using odds ratios with 95 % confidence interval . Result Out of 432 students selected for the study , 420 ( 97.2 % ) were in the age group 7–15 years . The mean age was 12 ± 2.1SD . Overall prevalence of refractive error was 43 ( 10.2 % ) . Myopia was found among the most dominant 5.47 % followed by astigmatism 1.9 % and hyperopia 1.4 % in both sexes . Female sex ( AOR : 3.96 , 95 % CI : 1.55 - 10.09 ) , higher grade level ( AOR : 4.82 , 95 % CI : 1.98 - 11.47 ) and using computers regularly ( AOR : 4.53 , 95 % CI : 1.58 - 12.96 ) were significantly associated with refractive error . Conclusion The burden of uncorrected refractive errors is high among primary schools children . Myopia was common in both sexes . The potential risk factors were sex , regular use of computers and higher grade level of students . Hence , school health programs should work on health information dissemination and eye health care services provision PURPOSE To assess the prevalence of refractive error and related visual impairment in school-aged children in an urban population in New Delhi , India . METHODS R and om selection of geographically defined clusters was used to identify a sample of children 5 to 15 years of age . From December 2000 through March 2001 , children in 22 selected clusters were enumerated through a door-to-door survey and examined at a local facility . The examination included visual acuity measurements , ocular motility evaluation , retinoscopy and autorefraction under cycloplegia , and examination of the anterior segment , media , and fundus . Myopia was defined as spherical equivalent refractive error of at least -0.50 D and hyperopia as + 2.00 D or more . Children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance in four of the clusters . RESULTS A total of 7008 children from 3426 households were enumerated , and 6447 ( 92.0 % ) examined . The prevalence of uncorrected , baseline ( presenting ) , and best corrected visual acuity of 20/40 or worse in the better eye was 6.4 % , 4.9 % , and 0.81 % , respectively . Refractive error was the cause in 81.7 % of eyes with vision impairment , amblyopia in 4.4 % , retinal disorders in 4.7 % , other causes in 3.3 % , and unexplained causes in the remaining 5.9 % . There was an age-related shift in refractive error from hyperopia in young children ( 15.6 % in 5-year-olds ) toward myopia in older children ( 10.8 % in 15-year-olds ) . Overall , hyperopia was present in 7.7 % of children and myopia in 7.4 % . Hyperopia was associated with female gender . Myopia was more common in children of fathers with higher levels of education . CONCLUSIONS Reduced vision because of uncorrected refractive error is a major public health problem in urban school-aged children in India . Cost-effective strategies are needed to eliminate this easily treated cause of vision impairment PURPOSE To describe the prevalence of refractive errors in a black adult population . METHODS The Barbados Eye Study , a population -based study , included 4709 Barbados-born citizens , or 84 % of a r and om sample , 40 to 84 years of age . Myopia and hyperopia were defined as a spherical equivalent < -0.5 diopters and > + 0.5 diopters , respectively , based on automated refraction . Analyses included 4036 black participants without history of cataract surgery . Associations with myopia and hyperopia were evaluated in logistic regression analyses . RESULTS The prevalence of myopia was 21.9 % and was higher in men ( 25.0 % ) than in women ( 19.5 % ) . The prevalence of hyperopia was 46.9 % and was higher in women ( 51.8 % ) than in men ( 40.5 % ) . The prevalence of myopia decreased from 17 % in persons 40 to 49 years of age to 11 % in those 50 to 59 years of age , but increased after 60 years of age . The prevalence of hyperopia increased from 29 % at 40 to 49 years of age to 65 % at 50 to 59 years of age , and tended to decline thereafter . A higher prevalence of myopia was positively associated ( P < 0.05 ) with lifetime occupations requiring nearwork , nuclear opacities , posterior subcapsular opacities , glaucoma , and ocular hypertension . Factors associated with hyperopia were the same as for myopia , except for occupation , and in the opposite direction . CONCLUSIONS High prevalences of myopia and hyperopia were found in this large black adult population . The prevalence of myopia ( hyperopia ) increased ( decreased ) after 60 years of age , which is inconsistent with data from other studies . The high prevalence of age-related cataract , glaucoma , and other eye conditions in the Barbados Eye Study population may contribute to the findings PURPOSE To determine the prevalence of refractive errors among schoolchildren in Northeastern Iran by age and gender . METHODS Using multistage r and om cluster sampling , 2020 schoolchildren 6 - 17 years of age were selected for this cross-sectional study . The participants totalled 1551 ( response rate 76.8 % ) elementary and junior high school children ( 41.5 % boys and 58.5 % girls ) from the northeast of Iran . Cycloplegic autorefraction was used to determine refractive error . Myopia was defined as a spherical equivalent ( SE ) of -0.50 dioptre ( D ) or worse , hyperopia as a SE of + 2.00 D or more , and astigmatism as cylinder equal to or worse than -0.75 D. RESULTS The prevalence of uncorrected , habitual and optimal visual acuity of 6/12 ( 0.30 logMAR ) or worse in the better eye was 2.2 % , 1.0 % , and 0.2 % respectively . The prevalence rates of myopia , hyperopia and astigmatism were 4.3 % ( 95%CI : 3.3 - 5.3 ) , 5.4 % ( 95%CI : 4.3 - 6.5 ) and 11.5 % ( 95%CI : 9.9 - 13.1 ) respectively and were not related to gender . The prevalence of myopia and against-the-rule astigmatism increased significantly with age ( p < 0.0001 ) . The prevalence of hyperopia significantly decreased with age ( p < 0.0001 ) . CONCLUSIONS The prevalence of myopia in schoolchildren in Northeastern Iran is considerably lower than that of East Asian population s , but similar to many other population s , including South Africa , Chile and other countries of the Middle East . Whilst comparisons with other studies show that the prevalence of hyperopia and astigmatism in Northeastern Iran is higher than that of some countries , it is lower compared with others Purpose : To measure the changes of corneal curvature during contraction of the ciliary muscle . Setting : Department of Ophthalmology , St. Luke 's International Hospital , Tokyo , Japan . Methods : Twenty‐eight eyes of 14 healthy volunteers under 40 years old were enrolled in this prospect i ve r and omized controlled study and divided into pilocarpine and control groups . Intraocular pressure ( IOP ) , pupil diameter , and corneal topography were measured before and 40 minutes after instillation of topical pilocarpine 4 % or balanced salt solution . Corneal topography was analyzed for the mean ring‐power of Placido rings 1 through 25 , average corneal power ( ACP ) , and for spherical equivalent , regular astigmatism , asymmetry , and high‐order irregularity by Fourier analysis . Results : Pilocarpine had no effect on IOP , but it did cause a significant decrease in mean pupil diameter . Simultaneously , pilocarpine increased the mean ring powers for Placido rings 1 through 4 and the ACP ( + 0.13 diopters ( D ) ± 0.17 [ SD ] ; P = .017 ) . By Fourier analysis , the mean spherical component for the central 3.0 mm of the cornea increased in the pilocarpine group ( + 0.08 ± 0.15 D ; P = .020 ) . There were no changes in components of regular astigmatism , asymmetry , and high‐order irregularity . Conclusions : The central cornea steepened in curvature and increased in power owing to contraction of the ciliary muscle . The results suggest that changes in corneal curvature increase refractive power during accommodation PURPOSE To assess the prevalence of refractive error and describe the distribution of ocular biometry and its association with refraction in adult Chinese . METHODS R and om clustering sampling was used to identify adults aged > or = 50 years in Liwan District , Guangzhou . Refraction was determined by subjective refraction that achieved the best corrected vision based on monocular measurement . Ocular biometry was measured by A-mode ultrasound using a h and held applanation probe . RESULTS Among 1405 participants in the study , data from 1269 phakic right eyes were available for analysis . The prevalence of myopia ( SE < -0.5 D ) , hyperopia ( SE > + 0.5 D ) , and astigmatism ( cylinder > 0.75 D ) was 32.3 % ( 95 % confidence interval [ CI ] , 27.8%-34.6 % ) , 40.0 % ( 95 % CI , 37.3%-42.7 % ) , and 48.3 % ( 95 % CI , 45.6%-51.1 % ) , respectively . The spherical equivalent tended to become hyperopic at 60 years and shifted toward myopia at 75 years . Axial length did not change with age but was consistently shorter in women . Lens thickness increased with age and tended to be greater in women . CONCLUSIONS The prevalence of myopia and biometric distribution in this urban Chinese cohort are similar to those observed in Singaporean Chinese but greater than in Mongolians and Europeans . Further studies are needed to clarify the role of environmental factors in the myopia rates OBJECTIVE To estimate the prevalence of refractive error in school-aged children in urban setting of Southern China . METHODS In this population -based cross-sectional study , children aged 5 to 15 years old were r and omly selected by clustering sampling and door-to-door survey , and were examined in 71 schools and 19 community stations from October 2002 to January 2003 . The examination included visual acuity measurement , ocular motility evaluation , retinoscopy , autorefraction under cycloplegia and examination of the external eye , anterior segment , media , and fundus . RESULTS Of 5053 children living in 4814 households enumerated , 4364 ( 86.4 % ) were examined . The prevalence of myopia ( spherical equivalent , SE < -0.50 D ) was 35.1 % ( 95 % CI : 33.2%-36.9 % ) with retinoscopy , this rate increased from 3 . 3 % in 5-year-old to 73.1 % in 15-year-old . Females had a significantly higher risk of myopia ( adjusted odds ratio : 1.29 , 95 % CI : 1.11 - 1.51 ) . The prevalence of hyperopia ( SE > or = + 2.00 D ) was 5.8 % ( 95 % CI : 5.3%-6.3 % ) and decreased from 16.7 % in 5-year-old to less than 1 % in 15-year-old . Astigmatism ( cylinder > or = 0.75 D ) was presented in 33.6 % of children examined with retinoscopy and in 42.7 % with autorefraction . CONCLUSIONS The prevalence of myopia is high in Chinese school-age children living in urban Guangzhou , representing an important public health problem . The coverage and quality of refractive correction in the children need to be improved Purpose : To determine the prevalence and demographic associations of refractive error in Botucatu , Brazil . Methods : A population -based , cross-sectional prevalence study was conducted , which involved r and om , household cluster sampling of an urban Brazilian population in Botucatu . There were 3000 individuals aged 1 to 91 years ( mean 38.3 ) who were eligible to participate in the study . Refractive error measurements were obtained by objective refraction . Results : Objective refractive error examinations were performed on 2454 residents within this sample ( 81.8 % of eligible participants ) . The mean age was 38 years ( st and ard deviation ( SD ) 20.8 years , Range 1 to 91 ) and females comprised 57.5 % of the study population . Myopia ( spherical equivalent ( SE ) < − 0.5 dropters ( D ) ) was most prevalent among those aged 30–39 years ( 29.7 % ; 95 % confidence interval ( CI ) 24.8–35.1 ) and least prevalent among children under 10 years ( 3.8 % ; 95 % confidence interval ( CI ) 1.6–7.3 ) . Conversely hypermetropia ( SE > 0.5D ) was most prevalent among participants under 10 years ( 86.9 % ; 95 % CI 81.6–91.1 ) and least prevalent in the fourth decade ( 32.5 % ; 95 % CI 28.2–37.0 ) . Participants aged 70 years or older bore the largest burden of astigmatism ( cylinder at least −0.5D ) and anisometropia ( difference in SE of > 0.5D ) with a prevalence of 71.7 % ( 95 % CI 64.8–78.0 ) 55.0 % ( 95 % CI 47.6–62.2 ) respectively . Myopia and hypermetropia were significantly associated with age in a bimodal manner ( P < 0.001 ) , whereas anisometropia and astigmatism increased in line with age ( P < 0.001 ) . Multivariate modeling confirmed age-related risk factors for refractive error and revealed several gender , occupation and ethnic-related risk factors . Conclusions : These results represent previously unreported data on refractive error within this Brazilian population . They signal a need to continue to screen for refractive error within this population and to ensure that people have adequate access to optical correction PURPOSE Few epidemiologic data are available on refractive status in elderly Asians . The purpose of the study was to determine prevalence and risk factors associated with refractive errors in a metropolitan elderly Chinese population in Taiwan . METHODS A population -based survey was conducted in the Shihpai district of Taipei , Taiwan . A total of 2045 residents aged 65 years or more were r and omly selected and invited to complete a comprehensive question naire and undertake a detailed ocular examination , including best corrected visual acuity and measurements of refractive error , using autorefraction . Of the subjects , 1361 ( 66.6 % ) participated in the ocular examination . Spherical equivalent ( SE ) was calculated in diopters ( D ) , and data from right eyes were reported . RESULTS The age- and sex-adjusted prevalence rates were determined for myopia ( SE<-0.5 D , 19.4 % ; SE<-1.0 D , 14.5 % ) , high myopia ( SE<-6.0 D , 2.4 % ) , hyperopia ( SE>+0.5 D , 59.0 % ; SE>+1.0 D , 44.2 % ) , astigmatism ( cylinder<-0.5 D , 74.0 % ; cylinder<-1.0 D , 45.3 % ) , and anisometropia ( SE difference between right and left eyes>0.5 D , 45.2 % ; SE difference>1.0 D , 21.8 % ) . The prevalence of myopia , astigmatism , and anisometropia significantly increased with age ( all P<0.01 ) . The prevalence of hyperopia tended to decrease with age . There was no gender difference in prevalence rates in any type of refractive error , except that women had a higher rate of hyperopia ( SE>+1.0 D ) than men ( P=0.004 ) . Multivariate regression analysis showed that myopia was weakly associated with higher educational level . The severity of lens nuclear opacity was positively associated with the rates of myopia and negatively associated with the rates of hyperopia . CONCLUSIONS The prevalence of myopia in this elderly Chinese population is not much higher than in similarly aged elderly white population s , compared with a much greater difference in prevalence among younger Chinese versus white people . This suggests that changing environmental factors may account for the increased prevalence of myopia in younger cohorts of Chinese PURPOSE To assess the prevalence of refractive error and vision impairment in school age children in the terai area of the Mechi zone in Eastern Nepal . METHODS R and om selection of village-based clusters was used to identify a sample of children 5 to 15 years of age . Children in the 25 selected clusters were enumerated through a door-to-door household survey and invited to village sites for examination . Visual acuity measurements , cycloplegic retinoscopy , cycloplegic autorefraction , ocular motility evaluation , and anterior segment , media , and fundus examinations were done from May 1998 through July 1998 . Independent replicate examinations for quality assurance monitoring took place in all children with reduced vision and in a sample of those with normal vision in seven villages . RESULTS A total of 5,526 children from 3,724 households were enumerated , and 5,067 children ( 91.7 % ) were examined . The prevalence of uncorrected , presenting , and best visual acuity 0.5 ( 20/40 ) or worse in at least one eye was 2.9 % , 2.8 % , and 1.4 % , respectively ; 0.4 % had best visual acuity 0.5 or worse in both eyes . Refractive error was the cause in 56 % of the 200 eyes with reduced uncorrected vision , amblyopia in 9 % , other causes in 19 % , with unexplained causes in the remaining 16 % . Myopia -0.5 diopter or less in either eye or hyperopia 2 diopters or greater was observed in less than 3 % of children . Hyperopia risk was associated with female gender and myopia risk with older age . CONCLUSIONS The prevalence of reduced vision is very low in school-age children in Nepal , most of it because of correctable refractive error . Further studies are needed to determine whether the prevalence of myopia will be higher for more recent birth cohorts Purpose . To study and analyze astigmatism and its characteristics in a cross-sectional study of schoolchildren from Dezful , Iran . Methods . In a cross-sectional study using r and om cluster sampling on 460 schools in Dezful ( clusters ) , 39 clusters were selected . The study was conducted after coordinating with schools and obtaining written consent from students ' parents . Cycloplegic refraction was done for primary and junior high school students and non-cycloplegic refraction was done for high school students . Astigmatism was defined as the cylinder power of 0.75 diopter ( D ) or more . Results . Of 5726 selected students , 5544 ( 96.8 % ) participated in the study . The prevalence of astigmatism was 13.47 % ( 95 % confidence interval : 11.90 to 15.04 ) and was not significantly related to age and gender . Regarding axis , 45.76 , 48.14 , and 6.09 % of astigmatic schoolchildren had with-the-rule ( WTR ) , against-the-rule ( ATR ) , and oblique astigmatism , respectively . An increase in age was accompanied by a decrease in the prevalence of WTR astigmatism and an increase in the prevalence of ATR astigmatism ( p < 0.001 ) . The association between astigmatism and myopia [ odds ratio = 8.81 ] was stronger than its association with hyperopia ( odds ratio = 3.81 ) . Those with high values of spherical error had high values of cylindrical error , as well . Mean sphere in WTR , ATR , and oblique astigmatism was 1.93 , 1.37 , and 0.88 D , respectively ( p < 0.001 ) . The highest values of spherical refractive error were observed in WTR astigmatism group . Conclusions . The prevalence of ATR astigmatism was high in this study . It appears that the decrease in the prevalence of WTR and the increase in the prevalence of ATR astigmatism as a result of aging happened earlier in our study compared with other studies . Astigmatism was found to have a strong correlation with myopia , although individuals with high hyperopia also had high astigmatism . Individuals with high ametropia mostly had WTR astigmatism although the percentage of ATR astigmatism was high in those with low ametropia PURPOSE To assess the prevalence of refractive error and visual impairment in school-aged African children in South Africa . METHODS R and om selection of geographically defined clusters was used to identify a sample of children 5 to 15 years of age in the Durban area . From January to August 2002 , children in 35 clusters were enumerated through a door-to-door survey and examined in temporary facilities . The examination included visual acuity measurements , ocular motility evaluation , retinoscopy and autorefraction under cycloplegia , and examination of the anterior segment , media , and fundus . In nine clusters , children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance . RESULTS A total of 5599 children living in 2712 households were enumerated , and 4890 ( 87.3 % ) were examined . The prevalence of uncorrected , presenting , and best-corrected visual acuity of 20/40 or worse in the better eye was 1.4 % , 1.2 % , and 0.32 % , respectively . Refractive error was the cause in 63.6 % of the 191 eyes with reduced vision , amblyopia in 7.3 % , retinal disorders in 9.9 % , corneal opacity in 3.7 % , other causes in 3.1 % , and unexplained causes in the remaining 12.0 % . Exterior and anterior segment abnormalities were observed in 528 ( 10.8 % ) children , mainly corneal and conjunctival . Myopia ( at least -0.50 D ) in one or both eyes was present in 2.9 % of children when measured with retinoscopy and in 4.0 % measured with autorefraction . Beginning with an upward trend at age 14 , myopia prevalence with autorefraction reached 9.6 % at age 15 . Myopia was also associated with increased parental education . Hyperopia ( + 2.00 D or more ) in at least one eye was present in 1.8 % of children when measured with retinoscopy and in 2.6 % measured with autorefraction , with no significant predictors of hyperopia risk . CONCLUSIONS The prevalence of reduced vision is low in school-age African children , most of it because of uncorrected refractive error . The high prevalence of corneal and other anterior segment abnormalities is a reflection of the inadequacy of primary eye care services in this area PURPOSE To describe racial variations in the prevalence of refractive errors among adult white , Chinese , Hispanic , and black subjects in the United States . DESIGN Cross-sectional data from a prospect i ve cohort study -the Multi-Ethnic Study of Atherosclerosis ( MESA ) . METHODS A total of 6000 adults aged 45 to 84 years living in the United States participated in the study . Refractive error was assessed , without cycloplegia , in both eyes of all participants using an autorefractor . After excluding eyes with cataract , cataract surgery , or previous refractive surgery , the eye with the larger absolute spherical equivalent ( SE ) value for each participant was used to classify refractive error . Any myopia was defined as SE of -1.0 diopters ( D ) or less ; high myopia was defined as SE of -5.0 D or less ; any hyperopia was defined as SE of + 1.0 D or more ; clinical ly significant hyperopia was defined as SE of + 3.0 D or more . Astigmatism was defined as a cylinder value of + 1.0 D or more . RESULTS After excluding 508 participants with cataracts in both eyes , 838 participants with cataract surgery , 90 participants with laser refractive surgery , and 134 participants who refused to remove their contact lenses for the refraction measurement , 4430 adults with refractive error assessment in at least 1 eye contributed to the analysis . The prevalence of myopia among MESA participants was 25.1 % , with lowest rates in Hispanic participants ( 14.2 % ) , followed by black ( 21.5 % ) and white participants ( 31.0 % ) , and highest rates in Chinese participants ( 37.2 % ) . The overall rates of high myopia and astigmatism were 4.6 % and 45.0 % , respectively , with Chinese subjects also having the highest rates of high myopia ( 11.8 % ) and astigmatism ( 53.4 % ) . The overall prevalence of any hyperopia was 38.2 % and clinical ly significant hyperopia was 6.1 % , with Hispanic participants having the highest rates of hyperopia ( 50.2 % ) and clinical ly significant hyperopia ( 8.8 % ) . In multivariate analyses adjusting for age , sex , race , and study site , higher education level , being employed , and being taller were associated with a higher prevalence of myopia . In contrast , lower educational level and being shorter were associated with a higher prevalence of hyperopia . CONCLUSIONS Myopia and astigmatism were most prevalent in the Chinese population , with Chinese subjects having 3 times the prevalence of myopia as Hispanic subjects . Hyperopia was most common in Hispanic subjects . These findings provide further insights into variations in refractive errors among different racial groups and have important implication s for the eye care services in the United States IMPORTANCE Myopia has reached epidemic levels in parts of East and Southeast Asia . However , there is no effective intervention to prevent the development of myopia . OBJECTIVE To assess the efficacy of increasing time spent outdoors at school in preventing incident myopia . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized trial of children in grade 1 from 12 primary schools in Guangzhou , China , conducted between October 2010 and October 2013 . INTERVENTIONS For 6 intervention schools ( n = 952 students ) , 1 additional 40-minute class of outdoor activities was added to each school day , and parents were encouraged to engage their children in outdoor activities after school hours , especially during weekends and holidays . Children and parents in the 6 control schools ( n = 951 students ) continued their usual pattern of activity . MAIN OUTCOMES AND MEASURES The primary outcome measure was the 3-year cumulative incidence rate of myopia ( defined using the Refractive Error Study in Children spherical equivalent refractive error st and ard of ≤-0.5 diopters [ D ] ) among the students without established myopia at baseline . Secondary outcome measures were changes in spherical equivalent refraction and axial length among all students , analyzed using mixed linear models and intention-to-treat principles . Data from the right eyes were used for the analysis . RESULTS There were 952 children in the intervention group and 951 in the control group with a mean ( SD ) age of 6.6 ( 0.34 ) years . The cumulative incidence rate of myopia was 30.4 % in the intervention group ( 259 incident cases among 853 eligible participants ) and 39.5 % ( 287 incident cases among 726 eligible participants ) in the control group ( difference of -9.1 % [ 95 % CI , -14.1 % to -4.1 % ] ; P < .001 ) . There was also a significant difference in the 3-year change in spherical equivalent refraction for the intervention group ( -1.42 D ) compared with the control group ( -1.59 D ) ( difference of 0.17 D [ 95 % CI , 0.01 to 0.33 D ] ; P = .04 ) . Elongation of axial length was not significantly different between the intervention group ( 0.95 mm ) and the control group ( 0.98 mm ) ( difference of -0.03 mm [ 95 % CI , -0.07 to 0.003 mm ] ; P = .07 ) . CONCLUSIONS AND RELEVANCE Among 6-year-old children in Guangzhou , China , the addition of 40 minutes of outdoor activity at school compared with usual activity result ed in a reduced incidence rate of myopia over the next 3 years . Further studies are needed to assess long-term follow-up of these children and the generalizability of these findings . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00848900 Purpose : Many children with poor vision due to refractive error remain undiagnosed and perform poorly in school . The situation is worse in the Sub-Saharan Africa , including Ethiopia , and current information is lacking . The objective of this study is to determine the prevalence of refractive error among children enrolled in elementary schools in Gondar town , Ethiopia . Material s and Methods : This was a cross-sectional study of 1852 students in 8 elementary schools . Subjects were selected by multistage r and om sampling . The study parameters were visual acuity ( VA ) evaluation and ocular examination . VA was measured by staff optometrists with the Snellen E-chart while students with subnormal vision were examined using pinhole , retinoscopy evaluation and subjective refraction by ophthalmologists . Results : The study cohort was comprised of 45.8 % males and 54.2 % females from 8 r and omly selected elementary schools with a response rate of 93 % . Refractive errors in either eye were present in 174 ( 9.4 % ) children . Of these , myopia was diagnosed in 55 ( 31.6 % ) children in the right and left eyes followed by hyperopia in 46 ( 26.4 % ) and 39 ( 22.4 % ) in the right and left eyes respectively . Low myopia was the most common refractive error in 61 ( 49.2 % ) and 68 ( 50 % ) children for the right and left eyes respectively . Conclusions : Refractive error among children is a common problem in Gondar town and needs to be assessed at every health evaluation of school children for timely treatment OBJECTIVE Vientiane Province is an urbanizing region in Southeast Asia . We aim ed to determine the prevalence of refractive error and visual impairment in primary school-aged children in this region . DESIGN Prospect i ve , cross-sectional survey . PARTICIPANTS A total of 2899 schoolchildren from Vientiane Province , Lao People 's Democratic Republic ( Lao PDR ) . METHODS Ten districts from Vientiane were r and omly selected and 2 primary schools were r and omly selected from each district . All children aged 6 to 11 years at selected schools were eligible to participate . The examination included visual acuity ( VA ) testing , cycloplegic retinoscopy with subjective refinement if indicated , ocular motility testing , and anterior segment and fundus examinations in visually impaired children . MAIN OUTCOME MEASURES Cycloplegic refraction and VA . RESULTS There was an estimated total of 3330 children who were eligible to participate , and data were recorded from 2899 ( 87 % ) of these children . Complete refractive data were available on 2842 children ( 85 % of eligible population ) . The mean spherical equivalent ( SE ) in the right eyes was + 0.60 diopter ( D ) ( 95 % confidence interval [ CI ] , 0.49 - 0.72 ) , and the mean SE in the left eyes was + 0.59 ( 95 % CI , 0.50 - 0.68 ) . The prevalence of hyperopia was 2.8 % ( 95 % CI , 1.9 - 3.7 ; 88 subjects ) , and the prevalence of myopia was 0.8 % ( 95 % CI , 0.3 - 1.4 ; 24 subjects ) . The majority of children ( 98 % ; 95 % CI , 97.0 - 99.0 ) had normal unaided binocular VA ( at least 20/32 in their better eye ) . The overall prevalence of any visual impairment ( presenting VA < 20/32 in the better eye ) was 1.9 % ( 95 % CI , 1.0 - 2.9 ; 55 subjects ) . In multivariate logistic regression analysis , age ( P = 0.001 ) was a significant predictor , and female gender ( P = 0.08 ) and Yao ethnicity ( P = 0.09 ) were borderline significant predictors of the presence of any visual impairment . CONCLUSIONS Visual impairment is not a public health concern in this primary school-aged population ; however , visually impaired children in the community were not studied . From this baseline , future surveys could determine the effect of increasing urbanization on myopia prevalence in this population PURPOSE To assess the prevalence of refractive errors and vision impairment in school-age children in a suburban area ( La Florida ) of Santiago , Chile . METHODS R and om selection of geographically defined clusters was used to identify a representative sample of children 5 to 15 years of age . Children in the 26 selected clusters were enumerated through a door-to-door survey and invited to report to a community health clinic for examination . Visual acuity measurements , cycloplegic retinoscopy , cycloplegic autorefraction , ocular motility evaluation , and examination of the external eye , anterior segment , media , and fundus were done from April through August 1998 . Independent replicate examinations of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in six clusters . RESULTS A total of 6,998 children from 3,830 households were enumerated , and 5,303 children ( 75.8 % ) were examined . The prevalence of uncorrected , presenting , and best visual acuity 0.50 ( 20/40 ) or worse in at least one eye was 15.8 % , 14.7 % , and 7.4 % , respectively ; 3.3 % had best visual acuity 0.50 or worse in both eyes . Refractive error was the cause in 56.3 % of the 1,285 eyes with reduced vision , amblyopia in 6.5 % , other causes in 4.3 % , with unexplained causes in the remaining 32.9 % . Myopia -0.50 diopter or less in either eye was present in 3.4 % of 5-year-old children , increasing to 19.4 % in males and 14.7 % in females by age 15 . Over this same age range , hyperopia 2.00 diopters or greater decreased from 22.7 % to 7.1 % in males and from 26.3 % to 8.9 % in females . Females had a significantly higher risk of hyperopia than males . CONCLUSIONS Refractive error , associated primarily with myopia , is a major cause of reduced vision in school-age children in La Florida . More than 7 % of children could benefit from the provision of proper spectacles . Efforts are needed to make existing programs that provide free spectacles for school children more effective . Further studies are needed to determine whether the upward trend in myopia continues far beyond 15 years of age PURPOSE To determine the epidemiology of refractive errors in an adult Chinese population in Singapore . METHODS A disproportionate , stratified , clustered , r and om-sampling procedure was used to select names of 2000 Chinese people aged 40 to 79 years from the 1996 Singapore electoral register in the Tanjong Pagar district in Singapore . These people were invited to a central ized clinic for a comprehensive eye examination , including refraction . Refraction was also performed on nonrespondents in their homes . Myopia , high myopia , and hyperopia were defined as a spherical equivalent ( SE ) in the right eye of less than -0.5 D , less than -5.0 D , and more than + 0.5 D , respectively . Astigmatism was defined as less than -0.5 D of cylinder . Anisometropia was defined as a difference in SE of more than 1.0 D between the two eyes . Only phakic eyes were analyzed . RESULTS From 1717 eligible people , 1232 ( 71.8 % ) were examined . Adjusted to the 1997 Singapore population , the overall prevalence of myopia , hyperopia , astigmatism , and anisometropia was 38.7 % ( 95 % confidence interval [ CI ] : 35.5 , 42.1 ) , 28.4 % ( 95 % CI : 25.3 , 31.3 ) , 37.8 % ( 95 % CI : 34.6 , 41.1 ) , and 15.9 % ( 95 % CI : 13.5 , 18.4 ) , respectively . The prevalence of high myopia was 9.1 % ( 95 % CI : 7.2 , 11.2 ) , with women having significantly higher rates than men . The age pattern of myopia was bimodal , with higher prevalence in the 40 to 49 and 70 to 81 age groups and lower prevalence between those age ranges . Prevalence was reversed in hyperopia , with a higher prevalence in subjects aged 50 to 69 . There was a monotonic increase in prevalence with age for both astigmatism and anisometropia . Increasing educational levels , higher individual income , professional or office-related occupations , better housing , and greater severity of nuclear opacity were all significantly associated with higher rates of myopia , after adjustment for age and sex . CONCLUSIONS The results indicate that whereas myopia is 1.5 to 2.5 times more prevalent in adult Chinese residing in Singapore than in similarly aged European-derived population s in the United States and Australia , the sociodemographic associations are similar Purpose : To determine the prevalence of refractive error ( RE ) and spectacle wear and to explore the need for spectacle correction in adults ( 30 years or older ) in Pakistan . Methods : Multi-stage , cluster r and om sampling national survey . Each subject had their medical history taken , visual acuity measured , and underwent autorefraction , biometry and fundus examination . Those that presented with visual acuity of less than 6/12 in either eye underwent more detailed examination , including corrected distance visual acuity measurement ( autorefraction results placed in a trial lens frame ) . Myopia was defined as a spherical equivalent of worse than –0.5D , hypermetropia as greater than + 0.5D , and astigmatism as greater than 0.75D . Spectacle need ( i.e. , those that improved from unaided VA with spectacle correction ) was determined along with the spectacle coverage , defined as the proportion of need that was met ( by the participant 's own spectacles ) . Results : The crude prevalence of myopia , hypermetropia and astigmatism was 36.5 % , 27.1 % , and 37 % , respectively . The prevalence of spectacle wear in phakic participants was 4.0 % , significantly lower than for those who were pseudo/aphakic ( 41.7 % ) . Just over a quarter ( 25.8 % ) of spectacle wearers presenting with visual impairment ( < 6/12 ) were able to improve their vision when retested with their autorefraction prescription . The overall spectacle coverage ( 6/12 cutoff ) was 15.1 % . Conclusions : This survey provides the first reliable national estimates . RE services are not covering the majority of the population in need and the provision of spectacle correction , as a highly cost effective treatment for visual impairment , needs addressing within the country 's national eye care program PURPOSE To evaluate visual acuity , visual function , and prevalence of refractive error among Chinese secondary -school children in a cross-sectional school-based study . METHODS Uncorrected , presenting , and best corrected visual acuity , cycloplegic autorefraction with refinement , and self-reported visual function were assessed in a r and om , cluster sample of rural secondary school students in Xichang , China . RESULTS Among the 1892 subjects ( 97.3 % of the consenting children , 84.7 % of the total sample ) , mean age was 14.7 + /- 0.8 years , 51.2 % were female , and 26.4 % were wearing glasses . The proportion of children with uncorrected , presenting , and corrected visual disability ( < or = 6/12 in the better eye ) was 41.2 % , 19.3 % , and 0.5 % , respectively . Myopia < -0.5 , < -2.0 , and < -6.0 D in both eyes was present in 62.3 % , 31.1 % , and 1.9 % of the subjects , respectively . Among the children with visual disability when tested without correction , 98.7 % was due to refractive error , while only 53.8 % ( 414/770 ) of these children had appropriate correction . The girls had significantly ( P < 0.001 ) more presenting visual disability and myopia < -2.0 D than did the boys . More myopic refractive error was associated with worse self-reported visual function ( ANOVA trend test , P < 0.001 ) . CONCLUSIONS Visual disability in this population was common , highly correctable , and frequently uncorrected . The impact of refractive error on self-reported visual function was significant . Strategies and studies to underst and and remove barriers to spectacle wear are needed AIMS To characterize ophthalmological findings in a sample of Swedish children aged 4 - 15 years . METHODS A prospect i ve cross-sectional comprehensive ophthalmological investigation was performed on a sample of 143 children ( 67 girls , 76 boys ) aged 4 - 15 years . RESULTS Visual acuity ( VA ) in the better eye > or=1.0 ( < or=0.0 logMAR ) was found in 79 % of subjects . None of the children had VA in the better eye < 0.5 ( > 0.3 logMAR ) . Amblyopia was found in 0.7 % of subjects . A total of 68 % of the children had no refractive errors . Hyperopia ( > or=2.0 dioptres [ D ] in spherical equivalent [ SE ] ) was found in 9 % and myopia ( > or=0.5 D SE ) in 6 % of children . Astigmatism ( > or=0.75 D ) was recorded in 22 % and anisometropia ( > or=1.0 D SE ) in 3 % . A total of 8 % were optically corrected . Strabismus was recorded in 3.5 % . Signs of visuoperceptual problems were reported in 3 % of the children . CONCLUSION This sample of Swedish children may serve as a comparison group regarding ophthalmological findings in children aged 4 - 15 years PURPOSE To describe the prevalence of and risk factors for myopia and other refractive errors in a rural , adult , Chinese population . DESIGN Population -based , cross-sectional study . PARTICIPANTS A clustered , r and om sampling procedure was used to select 7557 Chinese people aged > or=30 years from H and an , China . METHODS All eligible subjects were invited to undergo a comprehensive eye examination , including st and ardized refraction . Myopia , high myopia , and hyperopia were defined as a spherical equivalent ( SE ) in the right eye of more than -0.5 diopter ( D ) , less than -5.0 D , and 0.5 D or more , respectively . Astigmatism was less than -0.5 D of cylinder . Anisometropia was defined as a difference in SE of > 1.0 D between the 2 eyes . Only phakic eyes were analyzed . MAIN OUTCOME MEASURES Myopia and other refractive errors . RESULTS We included 6491 ( 85.9 % participation rate ) eligible subjects in this study . Adjusted to the 2000 China population census , the prevalence rate of myopia was 26.7 % ( 95 % confidence interval [ CI ] , 25.6 - 27.8 ) , hyperopia 15.9 % ( 95 % CI , 15.0 - 16.8 ) , astigmatism 24.5 % ( 95 % CI , 23.5 - 25.5 ) , and anisometropia 7.7 % ( 95 % CI , 7.0 - 8.4 ) . The prevalence of high myopia was 1.8 % ( 95 % CI , 1.5 - 2.1 ) . Using a multivariate regression model , current smoking ( odds ratio [ OR ] , 0.7 , 95 % CI , 0.5 - 0.9 ) , hours of reading ( OR , 1.2 ; 95 % CI , 1.1 - 1.4 ) , diabetes ( OR , 8.4 ; 95 % CI , 2.2 - 32.5 ) , and number of family members with myopia ( OR , 1.3 ; 95 % CI , 1.1 - 1.7 , for each family member ) were associated with myopia in younger persons ( 30 - 49 years ) . High school or higher education ( OR , 1.8 ; 95 % CI , 1.1 - 3.1 ) , diabetes ( OR , 1.6 ; 95 % CI , 1.2 - 2.7 ) , nuclear opacity ( OR , 1.7 ; 95 % CI , 1.2 - 2.3 ) , and number of family members with myopia ( OR , 1.5 ; 95 % CI , 1.2 - 1.9 ) were risk factors in persons > or=50 years of age . CONCLUSIONS Myopia affects more than one quarter of rural Chinese persons > or=30 years of age . Myopia is more common in younger people and is associated with different risk factors than in older people Purpose . To determine the prevalence of amblyopia , strabismus , and refractive errors in children entering school . Methods . In this cross-sectional population -based study , 6-year-old children enrolling in Shahrood schools were r and omly sample d. Those with organic blindness or mental retardation were excluded . Ocular alignment , visual acuity , stereopsis , cover testing , and cycloplegic refraction were recorded for all children by an optometrist . A diagnosis of amblyopia was based on a best-corrected visual acuity of 6/12 or less in one or both eyes , or a bilateral difference of at least two best-corrected visual acuity lines . Results . A total of 902 children were invited for optometry examinations , among which 827 ( 91.7 % ) responded and 815 children ( 98.5 % ) were included in the study . The prevalence of significantly reduced visual acuity ( uncorrected VA ≤6/12 in either eye ) and amblyopia was 3.6 and 1.7 % , respectively . The prevalence of hyperopia ( + 2.00 D or worse ) , myopia ( −0.50 D or worse ) , astigmatism ( 0.75 D or worse ) , and anisometropia ( 1.00 D or more ) were 20.5 , 1.7 , 19.6 , and 2.2 % , respectively . Significant refractive error , defined as hyperopia > + 3.50 D , myopia > −3.00 D , astigmatism > 1.50 D in the orthogonal meridian or > 1.00 D in the oblique meridian , or anisometropia ( hyperopic > 1.00 D , myopic > 3.00 D ) was detected in 2.1 , 0.1 , 5.0 , and 0.9 % of the sample , respectively . Strabismus was diagnosed in 1.2 % of children . Overall , 52 children ( 6.4 % ; 95 % confidence interval [ CI ] , 4.7–8.1 % ) were at risk of amblyopia ; of these , 81 % had significant refractive errors , 11 % had strabismus , and 8 % had both . Conclusion . A considerable proportion of 6-year-old children have strabismus and /or significant , potentially amblyogenic refractive errors . The relatively high rate of hyperopia and astigmatism in the studied population needs more attention . The results of the study emphasize the need for adequate diagnostic and therapeutic eye care services for preschool children Purpose : To assess the prevalence of refractive error in schoolchildren aged 12–14 years in urban and rural setting s in Cambodia ’s Phnom Penh and K and al provinces . Methods : Ten schools from Phnom Penh Province and 26 schools from K and al Province were r and omly selected and surveyed in October 2010 . Children were examined by teams of Australian and Cambodian optometrists , ophthalmic nurses and ophthalmologists who performed visual acuity ( VA ) testing and cycloplegic refraction . Results : A total of 5527 children were included in the study . The prevalence of uncorrected , presenting and best-corrected VA ≤ 6/12 in the better eye were 2.48 % ( 95 % confidence interval [ CI ] 2.02–2.83 % ) , 1.90 % ( 95 % CI 1.52–2.24 % ) and 0.36 % ( 95 % CI 0.20–0.52 % ) , respectively ; 43 children presented with glasses whilst a total of 315 glasses were dispensed . The total prevalence of refractive error was 6.57 % ( 95 % CI 5.91–7.22 % ) , but there was a significant difference between urban ( 13.7 % , 95 % CI 12.2–15.2 % ) and rural ( 2.5 % , 95 % CI 2.03–3.07 % ) schools ( P < 0.0001 ) . Refractive error accounted for 91.2 % of visually impaired eyes , cataract for 1.7 % , and other causes for 7.1 % . Myopia ( spherical equivalent ≤ −0.50 diopters [ D ] in either eye ) was associated with increased age , female gender and urban schooling . Conclusions : The prevalence of refractive error was significantly higher in urban Phnom Penh schools than rural schools in K and al Province . The prevalence of refractive error , particularly myopia was relatively low compared to previous reports in Asia . The majority of children did not have appropriate correction with spectacles , highlighting the need for more effective screening and optical intervention PURPOSE Determine the epidemiologic aspects and the degree of severity of different refractive errors in primary schoolchildren . PATIENTS AND METHODS A prospect i ve and descriptive study was conducted from 1 December 2005 to 31 March 2006 on schoolchildren ranging from 4 to 16 years of age in a public primary school in Cotonou , Benin . The refraction was evaluated for any visual acuity lower than or equal to 0.7 . RESULTS The study included 1057 schoolchildren . The average age of the study population was 8.5+/-2.6 years with a slight predominance of females ( 51.8 % ) . The prevalence of refractive error was 10.6 % and astigmatism accounted for the most frequent refractive anomaly ( 91.9 % ) . Myopia and the hyperopia were associated with astigmatism in 29.4 % and 16.1 % of the cases , respectively . The age bracket from 6 to 11 years accounted for the majority of refractive errors ( 75.9 % ) , without age and sex being risk factors ( p=0.811 and p=0.321 , respectively ) . The average vision of the ametropic eye was 0.61 , with a clear predominance of slight refractive errors ( 89.3 % ) and particularly of low-level simple astigmatism ( 45.5 % ) . CONCLUSION The relatively low prevalence of refractive error observed does not obviate the need for implementing actions to improve the ocular health of schoolchildren PURPOSE The purpose of the present study was to report the prevalence of refractive ( RA ) , corneal ( CA ) , and internal astigmatism ( IA ) in a population of 6-year-old children ; examine their variation with gender , ethnicity , and refraction ; and examine the effects of gender , ethnicity , and spherical equivalent refraction on the relationship between CA and RA in this population . METHODS The Sydney Myopia Study is a population -based survey of refraction and eye health in 6-year-old children . A r and om cluster design was used to recruit children from schools across Sydney , Australia , during 2003 to 2004 . Data collection used a detailed question naire and comprehensive eye examination . Keratometric and cycloplegic autorefraction data from right eyes were analyzed . RESULTS Of 2238 eligible children , 1765 ( 78.9 % ; 50.7 % boys ) had parental consent to participate . Overall prevalence of RA ( > or = 1.0 diopter [ D ] ) was 4.8 % ( 95 % confidence interval [ CI ] 3.8%-6.1 % ) , CA ( > or = 1.0 D ) 27.7 % ( CI 23.8%-32.3 % ) , and IA ( > or = 1.0 D ) 21.1 % ( CI 19.0%-23.5 % ) . The RA axis was fairly evenly distributed , with predominance of oblique axis ( 39.1 % ; CI 35.9%-42.6 % ) . CA axis was mainly with the rule ( 75.1 % ; CI 72.6%-77.8 % ) , while IA axis was mainly against the rule ( 76.7 % ; CI 74.2%-79.3 % ) . After adjustment for multiple variables , girls had significant , marginally greater mean CA and IA than boys . East Asian and South Asian children had significantly greater prevalence and mean RA and CA than European Caucasian children . There were no significant ethnic differences of mean IA . Compared to reference ( spherical equivalent [ SEq ] 1.01 - 1.50 D ) , mean RA and CA increased significantly with more hyperopic and more myopic refractions . Mean IA was significantly greater only for hyperopic refractions ( SEq > 2.00 D ) . CONCLUSIONS The prevalence of astigmatism found in this population of 6-year-old children was relatively low , and showed significant variation with ethnicity . The data suggest that emmetropization for RA occurs by a compensatory process between CA and IA OBJECTIVE To investigate the distribution of spherical equivalent and ocular biometric parameters in a population of grade 7 children in central China . METHODS 2 363 grade 7 students of junior high schools were r and omly sample d. The students have been examined at baseline and followed up annually . Detailed question naires and most of the ocular examinations were performed . Spherical equivalent ( Seq ) was calculated as sphere + 1/2 cylinder from cycloplegic autorefraction . Myopia was defined as spherical equivalent ≤ -0.5D , hyperopia as spherical equivalent ≥ + 0.5D and emmetropia between -0.5D and + 0.5D . The Lensar LS900 was used to measure corneal curvatures , axial length and anterior chamber depth . Right eyes results were analyzed . RESULTS Among 2 267 children who have the baseline examination , 1 839 children participated the follow up examination(response rate , 81.1 % ) , with an mean age of 14.7 years ( range , 12.9 - 17.6 ) and male ratio of 48.4 % . The mean spherical equivalent refraction was ( -2.62 ± 2.19)D. The prevalence rates of myopia , high myopia , emmetropia and hyperopia were 82.7 % , 7.1 % , 9.8 % and 7.5 % . The cumulative incidence rates of myopia and high myopia were 47.1 % and 4.5 % respectively . Axial length , anterior chamber depth , and corneal curvature were normally distributed . The mean axial length , anterior chamber depth , and corneal curvature were ( 24.8 ± 1.1)mm , ( 3.18 ± 0.25)mm , ( 42.8 ± 1.4)D and ( 43.9 ± 1.6)D respectively . Axial length was longer , anterior chamber depth was deeper , and corneal were flatter in the male(P = 0.000 ) . Axial length and anterior chamber depth correlated negatively with refraction . CONCLUSIONS A moderate myopic distribution of refraction was present in the grade 9 students in central China . The prevalence rates of myopia and high myopia were relatively high in this 14-year-old population compared to other countries . It is necessary to strengthen the prevention of juvenile myopia PURPOSE To assess the prevalence of refractive error and visual impairment in school children in a rural area of southern China . DESIGN Prospect i ve cross-sectional survey . PARTICIPANTS Two thous and four hundred children from junior high schools in Yangxi County . METHODS R and om selection of classes from the 3 junior high school grade levels was used to identify the study sample . Children from 36 classes in 13 schools were examined in April 2005 . The examination included visual acuity ( VA ) testing ; ocular motility evaluation ; cycloplegic autorefraction ; and examination of the external eye , anterior segment , media , and fundus . MAIN OUTCOME MEASURES Distance VA and cycloplegic refraction . RESULTS Among 2515 enumerated children , 2454 ( 97.6 % ) were examined . The study population consisted of the 2400 children between 13 and 17 years old . Prevalences of uncorrected , presenting , and best-corrected VA < or = 20/40 in the better eye were 27.0 % , 16.6 % , and 0.46 % , respectively . Sixty percent of those who could achieve acuity > or = 20/32 in at least one eye with best correction were without the necessary spectacles . Refractive error was the cause in 97.1 % of eyes with reduced vision ; amblyopia , 0.81 % ; other causes , 0.67 % ; and unexplained causes , 1.4 % . Myopia ( spherical equivalent , -0.50 diopters [ D ] or more in either eye ) affected 36.8 % of 13-year-olds , increasing to 53.9 % of 17-year-olds . Myopia was associated with higher grade level , female gender , schooling in the county urban center , and higher parental education . Hyperopia ( + 2.00 D or more ) affected approximately 1.0 % in all age groups . Astigmatism ( > or = 0.75 D ) was present in 25.3 % of all children . CONCLUSIONS Reduced vision because of uncorrected myopia is a public health problem among school-age children in rural China . Effective VA screening strategies are needed to eliminate this easily treated cause of visual impairment ABSTRACT Purpose : To determine the prevalence of refractive errors in Segovia , Spain . Methods : A cohort of 569 subjects was r and omly selected in a stratified manner according to gender and age in a cross-sectional , population -based epidemiologic study , the target population of which was urban residents aged 40 to 79 years . All participants underwent an ophthalmic examination that included measurement of visual acuity ( VA ) and refraction , tonometry , anterior segment biomicroscopy , funduscopy , optic nerve head photography , and visual field testing . Of those , 417 subjects were enrolled who met the inclusion criteria of a phakic right eye and VA over 20/40 . The prevalence of spherical errors was assessed after calculating the spherical equivalent and defining myopia as −0.5 diopters ( D ) or less and hyperopia as + 0.50 D or more . The prevalence of astigmatism over 0.50 D was evaluated in minus cylinder form . Results : The estimated prevalences ( 95 % confidence interval ) of myopia , hyperopia , and astigmatism , in the population were 25.4 % ( 21.5–29.8 % ) 43.6 % ( 39–48.4 % ) , and 53.5 % ( 48.7–58.2 % ) , respectively . No significant gender difference was found in the prevalence of any refractive errors . The prevalence of myopia or the mean value did not change significantly with age . The mean hyperopia and the mean astigmatism ( p < 0.01 for both ) and the prevalence increased with increasing age ( p < 0.01 for both ) . Anisometropia of 1 D or more was present in 12.3 % ( 49/396 subjects ) . Conclusion : More than 60 % of the Segovia population over 40 years of age has a refractive error , with 25.4 % myopic and 43.6 % hyperopic . Astigmatism is present in over half of the population and the types change with age Purpose . To determine the prevalence of myopia and hyperopia and the associated risk factors in the presbyopic age group of the population in Shahroud , Iran . Methods . Through a multistage r and om cluster sampling approach , 6311 people of the 40- to 64-year-old population residing in Shahroud were invited to this study . The prevalence of a cycloplegic spherical equivalent ( SE ) ≥−0.5 diopter ( D ) and hyperopia > + 0.50 D was determined by age and gender . Results . Of the invitees , 5190 ( 82.2 % ) participated in the study and data from 4864 people was used in the analyses . On the basis of cycloplegic refraction , the prevalence of myopia and hyperopia was 30.2 % [ 95 % confidence interval ( CI ) : 28.9 to 31.5 ] and 35.6 ( 95 % CI : 34.1 to 37.1 ) , respectively . In the multiple logistic regression model , the odds of myopia significantly increased with higher education [ odds ratio ( OR ) = 1.02 , p < 0.001 ] and nuclear cataract ( OR = 3.23 , p < 0.001 ) . After the age of 54 years , the odds of hyperopia significantly increased compared with the 40- to 44-year age group , whereas higher education and nuclear cataract had negative association with hyperopia . The prevalence of high myopia ( SE > −6.0 D ) and high hyperopia ( SE > 4.0 D ) was 1.9 % ( 95 % CI : 1.5 to 2.3 ) and 1.1 % ( 95 % CI : 0.8 to 1.4 ) , respectively . Nuclear cataract significantly correlated with high myopia ( OR = 6.44 ) and older age significantly correlated with high hyperopia ( OR = 1.12 ) . Conclusions . The prevalence of myopia was unexpectedly higher than that found in other parts of the Middle East . The prevalence of hyperopia was lower than that previously reported in Iran . Education correlated directly with myopia and inversely with hyperopia ; however , nuclear cataract was the most important risk factor for myopia . Adjusted for other variables , the prevalence of hyperopia still increased with age PURPOSE To assess the prevalence of refractive error and visual impairment in school-age children in a metropolitan area of southern China . METHODS R and om selection of geographically defined clusters was used to identify children 5 to 15 years of age in Guangzhou . Children in 22 clusters were enumerated through a door-to-door survey and examined in 71 schools and 19 community facilities from October 2002 to January 2003 . The examination included visual acuity measurements , ocular motility evaluation , retinoscopy , and autorefraction under cycloplegia and examination of the external eye , anterior segment , media , and fundus . RESULTS A total of 5053 children living in 4814 households were enumerated , and 4364 ( 86.4 % ) were examined . The prevalence of uncorrected , presenting , and best-corrected visual acuity 20/40 or worse in the better eye was 22.3 % , 10.3 % , and 0.62 % , respectively . Refractive error was the cause in 94.9 % of the 2335 eyes with reduced vision , amblyopia in 1.9 % , other causes in 0.4 % , and unexplained causes in the remaining 2.8 % . External and anterior segment abnormalities were seen in 1496 ( 34.3 % ) children , mainly minor conjunctival abnormalities . Media and fundus abnormalities were observed in 32 ( 0.73 % ) children . Myopia ( spherical equivalent of at least -0.50 D in either eye ) measured with retinoscopy affected 73.1 % of children 15 years of age , 78.4 % with autorefraction . The prevalence of myopia was 3.3 % in 5-year-olds with retinoscopy and 5.7 % with autorefraction . Females had a significantly higher risk of myopia . Hyperopia ( + 2.00 D or more ) measured with retinoscopy was present in 16.7 % of 5-year-olds , 17.0 % with autorefraction . The prevalence of hyperopia was below 1 % in 15-year-olds , with both methods . Astigmatism ( cylinder of > or = 0.75 D ) was present in 33.6 % of children with retinoscopy and in 42.7 % with autorefraction . CONCLUSIONS The prevalence of reduced vision because of myopia is high in school-age children living in metropolitan Guangzhou , representing an important public health problem . One third of these children do not have the necessary corrective spectacles . Effective strategies are needed to eliminate this easily treated cause of significant visual impairment |
11,781 | 10,320,860 | CONCLUSIONS : There is lack of data on cost effectiveness of cholesterol lowering interventions in the general practice setting .
The cost effectiveness of cholesterol lowering in general practice deteriorates when all relevant costs are taken into account and when efficacy is corrected for community effectiveness .
Cholesterol lowering intervention is more cost effective in men compared with women and in patients with coronary heart disease compared with persons without coronary heart disease . | STUDY OBJECTIVE : To investigate and evaluate published data on cost effectiveness of cholesterol lowering interventions , and how this information could be interpreted in a rational approach of cholesterol management in general practice . | This study set out to determine whether screening can be psychologically harmful to healthy adults . A prospect i ve controlled study was carried out on 215 healthy adults attending a by-invitation coronary heart disease screening clinic in general practice . The general health question naire was used as an indicator of recent psychological distress . Patients attending the screening clinic had significantly lower subjective psychological distress than an unscreened group of 225 age-matched controls , indicating that we may well be screening an already psychologically healthy sub-group . The main finding was that patients ' own assessment of their psychological distress was significantly increased three months after screening compared with that of controls , who showed a non-significant decrease . It is concluded that there is a real risk of causing distress by screening healthy adults and that this possibility has largely been ignored by previous studies . Possible explanations and implication s of these findings are discussed , particularly in the light of increased pressure from many quarters for more screening services to be set up in general practice A total of 96 patients with moderate elevations of low-density lipoprotein ( LDL ) cholesterol were r and omly assigned to 4 different double-blind treatment regimens : placebo ; colestipol 5 g and lovastatin 20 mg/day ( C5 + L20 ) ; colestipol 10 g and lovastatin 20 mg/day ( C10 + L20 ) ; and lovastatin 40 mg/day ( L40 ) . During 12 weeks of therapy , C10 + L20 achieved the greatest reduction in total cholesterol ( -32 % ) and LDL cholesterol ( -48 % ) levels from baseline . This combination also exhibited significantly greater reductions in LDL cholesterol levels than the C5 + L20 and L40 groups ( p < 0.01 ) . The differences in total and LDL cholesterol reduction between the C5 + L20 and L40 groups were not significant . Similar changes and differences between treatments were seen in apolipoprotein B levels . Whereas mean total apolipoprotein A-I levels increased with all treatments ( p < 0.05 ) , lipoprotein particles A-I were significantly increased in the C10 + L20 group ( p < 0.01 ) only . Results demonstrate that the combination of low-dose lovastatin ( 20 mg/day ) with low-dose colestipol ( 5 or 10 g/day ) produces LDL cholesterol reductions equal to or greater than higher doses of lovastatin ( 40 mg/day ) . In addition , low-dose combinations are > 25 % more cost-effective than high-dose monotherapy The cost of screening for hypercholesterolaemia in a clinical trial was investigated at a primary health care centre . A convenience sample of the population was screened for inclusion in a study of the effectiveness of a lipid lowering programme . Included in the study were adults 30 - 59 years of age with a S-Cholesterol of 6.50 - 7.79 mmol l-1 at r and omization , plus two previous values > or = 6.50 mmol l-1 at screening and selection , with at least two other cardiovascular risk factors . In total 447 persons were screened and 37 were r and omized into the lipid lowering programme . The mean cost per r and omized person was estimated at about SEK 7500 ( Swedish Crowns ) . An analysis of different inclusion criteria for treatment was also carried out . The cost of finding a patient to treat in the clinical trial was estimated to be more than three times as high with a total cholesterol cut-off point of 7.80 mmol l-1 compared with a cut-off point of 5.20 mmol l-1 This cost-benefit analysis attempts to translate the clinical findings of the Helsinki Heart Study ( HHS ) and published results regarding additional cardiovascular conditions into economic terms meaningful to US managed care providers . The study has the following 3 key objectives : to define the cost effectiveness of gemfibrozil in the prevention of coronary heart disease ( CHD ) ; to assess the net impact of gemfibrozil on total treatment costs for CHD ; and to identify those patient groups for whom gemfibrozil therapy is most cost effective . In order to reach these findings a cost-effectiveness model was constructed based on original clinical data provided by the HHS , published findings for CHD risk and cost of treatment in the US , expert opinion and extension of HHS to other cardiovascular conditions , and documented costs and treatment protocol s of US Medicaid and privately managed health care programmes . The model was applied to the California Medicaid ( Medi-Cal ) programme to estimate costs of hyperlipidaemia therapy using gemfibrozil . In parallel , savings to Medi-Cal from averted coronary events were estimated . From these data , the net expected savings to Medi-Cal were calculated . The probability of experiencing CHD varies with cholesterol level , age , sex and risk factors such as smoking , hypertension and diabetes . Therefore , it is possible to use risk-factor profiles to define groups of individuals with low , moderate or high risk of experiencing acute myocardial infa rct ion ( AMI ) or sudden cardiac death . The probability of a cardiac event within 5 years ranges from 1.1 % in a 45-year-old low risk male to over 36 % in a 55-year-old high risk male . The average total cost of CHD care was found to be US$ 22,271 within 5 years . Using the probability of a CHD event to calculate the expected 5-year cost of CHD care produces a range from US$ 242 in the 45-year-old low risk male to US$ 8084 in the 55-year-old high risk male . Treatment with gemfibrozil reduces the probability of AMI and sudden cardiac death events by 34 % , as demonstrated in the HHS . Therefore , the corresponding probability ranges are reduced to 0.7 % in the 45-year-old low risk male and 27.3 % in the 55-year-old high risk male after treatment with gemfibrozil . The expected cost of a coronary event is reduced by US$ 82 and US$ 1997 , respectively . ( ABSTRACT TRUNCATED AT 400 WORDS Over the past decade the efficacy and cost of medical interventions have been subject to increasing scrutiny with quantitative techniques , such as the r and omized controlled trial and cost-effectiveness analysis . Such studies provide invaluable guidance for the clinician choosing from a limited range of options in caring for an individual patient . However , in the field of health policy myriad competing programs , services , institutions , and interests must be weighed . Unfortunately , quantitative methods are virtually always used to compare two , or at most a few , alternative strategies . Since the relative cost effectiveness of an intervention may appear radically different depending on the alternative . . Twenty-four factories or other occupational groups , employing 18 210 men aged 40 to 59 , were formed into matched pairs . One of each pair was allocated r and omly to receive a five to six year programme of medical examinations and intervention to reduce the levels of the main coronary risk factors . Men at factories in the intervention group were given advice on dietary reduction of plasma cholesterol concentrations , stopping or reducing cigarette smoking , regular exercies for the sedentary and reduced energy intake for the overweight , and hypertension was treated . The programme was delivered mainly through existing occupational medical services , helped by a small central staff . Personal consultations were largely confined to men with a high risk of developing coronary heart disease . Changes in risk factors were assessed by regular st and ardised examinations of r and om sample s of men . The spread of information by general propag and a proved easy , but a change in habits seemed to require personal contact . Small but significant reductions occurred , mainly in the high-risk group , but these were not sustained when pressure was relaxed STUDY OBJECTIVE : To evaluate the cost effectiveness and equity of a community based cardiovascular disease prevention programme . DESIGN : A prospect i ve cross sectional design . SETTING : A community based intervention to reduce cardiovascular disease in the district of Norsjö ( n = 5500 ) , Sweden . The intervention was aim ed at both the general population and at individuals thought to be at special risk , the emphasis being on changing dietary habits and reducing cholesterol concentrations . PARTICIPANTS : The participants were men and women aged 30 - 60 years . MAIN RESULTS : The mean serum cholesterol concentration in the Norsjö population was reduced by nearly 20 % during the first six years of intervention . It was estimated that the programme 's overall total societal costs were 363,000 pounds and estimates of the cost per year of life saved ranged from 14,900 pounds to net savings , according to different assumptions . Taking only health care costs and savings into account , the cost per year of life saved ranged from 1100 pounds to 4050 pounds . The results varied between different sex and age groups , but not between social classes . Even if a causal relationship exists between low cholesterol concentrations and excess mortality , the estimated side effects of lowering cholesterol values in Norsjö were negligible in comparison with the expected benefits . CONCLUSIONS : The community based intervention in Norsjö seems to be cost effective even under conservative assumptions . The approach used seems to have benefited all social classes . Cost effectiveness analyses that take consequences for equity into account are valuable tools in decision making BACKGROUND Advances in the treatment of cardiovascular disease have increased costs ; annual cardiovascular healthcare expenditure in the United States currently exceeds $ 100 billion . Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality . METHODS AND RESULTS The Sc and inavian Simvastatin Survival Study is a r and omized , double-blind , placebo-controlled trial in which simvastatin reduced the risk of death by 30 % ( P=.0003 ) over the median follow-up period of 5.4 years in patients with previous myocardial infa rct ion or stable angina pectoris as a result of a 42 % reduction in the risk of coronary deaths ( P=.00001 ) . In the present report , data prospect ively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare re source use and perform a cost-minimization analysis . In the placebo group ( n=2223 ) , there were 1905 hospitalizations ( average duration , 7.9 days ) for acute cardiovascular events or coronary revascularization procedures among 937 patients , whereas in the simvastatin group ( n=2221 ) , there were 1403 such hospitalizations ( average duration , 7.1 days ) among 720 patients ( all differences , P<.0001 ) . The corresponding number of hospital days was 15089 and 9951 in the two groups , respectively ( 34 % reduction , P<.0001 ) . In the United States , the result ing reduction in hospitalization costs over the 5.4 years of the trial would be $ 3872 per patient , reducing the effective cost of simvastatin by 88 % to $ 0.28 per day . CONCLUSIONS In addition to reducing mortality and morbidity in coronary heart disease patients , simvastatin markedly reduces use of hospital services , thus off setting most of its cost Abstract Objective : To measure the costs and cost effectiveness of the Oxcheck cardiovascular risk factor screening and intervention programme . Design : Cost effectiveness analysis of a r and omised controlled trial using clinical and economc data taken from the trial . Setting : Five general practice s in Luton and Dunstable , Engl and . Subjects : 2205 patients who attended a health check in 1989 - 90 and were scheduled for re-examination in 1992 - 3 ( intervention group ) ; 1916 patients who attended their initial health check in 1992 - 3 ( control group ) . Participants were men and women aged 35 - 64years . Intervention : Health check conducted by nurse , with health education and follow up according to degree of risk . Main outcome measures : Cost of health check programme ; cost per 1 % reduction in coronary risk . Results : Health check and follow up cost £ 29.27 per patient . Estimated programme cost per 1 % reduction in coronary risk per participant was between £ 1.46 and £ 2.25 ; it was nearly twice as much for men as women . Conclusions : The cost to the practice of implementing Oxcheck-style health checks in an average sized practice of 7500 patients would be £ 47 000 , a proportion of which could be paid for through staff pay reimbursements and B and Three health promotion target payments . This study highlights the considerable difficulties faced when calculating the costs and benefits of a health promotion programme . Economic evaluations should be integrated into the protocol s of r and omised controlled trials to enable judgments to be made on the relative cost effectiveness of different prevention strategies . Key messages Research was undertaken to estimate the cost of the health checks and relate the cost to changes in the relative risk of cardiovascular disease The immediate cost of implementing Oxcheck-style health checks in an average sized practice of 7500 patients would be £ 47 000 , which is comparable with the immediate cost of a cervical screening programme The actual costs to the practice would be substantially reduced by staff pay reimbursements and health promotion target payments Further research is required to estimate the wider costs of health checks result ing from the additional use of health care BACKGROUND The National Cholesterol Education Program recommends achievement of a defined target level of low-density lipoprotein cholesterol ( LDL-C ) for the treatment of hypercholesterolemia . They endorse the use of niacin and /or sequestrants as the first line of therapy to achieve such target LDL-C level . This recommendation has not been compared with the use of lovastatin as initial therapy if multidrug regimens are required to achieve goal LDL-C. METHODS Prospect ively collected data on tolerance and effectiveness for niacin , sequestrants , and lovastatin were obtained from a lipid clinic at a large midwestern Veterans Affairs medical center . We used a decision tree to compare the complexity and cost of three sequential drug algorithms used for the following initial LDL-C levels : 4.14 , 4.91 , 5.69 , and 6.47 mmol/L ( 160 , 190 , 220 , and 250 mg/dL ) . Algorithm 1 was niacin followed by a sequestrant and then lovastatin ; algorithm 2 , a sequestrant followed by niacin and then lovastatin ; and algorithm 3 , lovastatin followed by niacin and a sequestrant . Drug and laboratory costs were obtained from the pharmacy and pathology services at the same institution . Sensitivity analyses were performed on the tolerance and effectiveness of each drug as well as drug and laboratory cost estimates . RESULTS The probability of achieving target LDL-C level ( 3.36 mmol/L [ 130 mg/dL ] ) decreased as initial LDL-C level increased . As a rule , algorithm 3 required fewer drugs in combination to achieve the target level for all initial LDL-C levels modeled . In addition , the use of lovastatin was high across all algorithms at all initial LDL-C levels modeled . Algorithm 1 was less expensive than algorithm 2 or 3 at a low initial LDL-C level ( 4.14 mmol/L [ 160 mg/dL ] ) , with an average cost of $ 375 vs $ 454 vs $ 585 , respectively . At all other initial LDL-C levels ( 4.91 , 5.69 , and 6.47 mmol/L [ 190 , 220 , and 250 mg/dL ] ) , algorithm 2 was slightly less expensive than algorithm 1 . Algorithm 3 became relatively less expensive as initial LDL-C level increased : 56 % more expensive than algorithm 1 at an initial LDL-C level of 4.14 mmol/L ( 160 mg/dL ) as compared with 7 % more expensive than algorithm 1 at an initial LDL-C level of 6.47 mmol/L ( 250 mg/dL ) . CONCLUSIONS Fulfillment of the target LDL-C approach recommended by the National Cholesterol Education Program often requires the use of multiple drugs . When lovastatin is used initially , the regimen becomes simpler , albeit more expensive . At initial LDL-C levels of 4.91 mmol/L ( 190 mg/dL ) or higher , this difference in cost becomes progressively smaller ( 7 % at 6.47 mmol/L [ 250 mg/dL ] ) , making algorithm 3 the better alternative ; at low initial LDL-C levels ( 4.14 mmol/L [ 160 mg/dL ] ) , a niacin-first regimen is reasonably simple and substantially less expensive . At moderate and severe initial LDL-C levels ( 4.91 and 5.69 mmol/L [ 190 and 220 mg/dL ] ) , the lovastatin-first regimen may be advantageous OBJECTIVE To compare the costs and effects of two different intervention strategies for the nonpharmacological treatment of hypercholesterolaemia . DESIGN R and omized , controlled trial . Subjects were r and omly allocated to one of two intervention models and followed up for 1 year . SETTING Vårby Health Centre , a primary care practice located in a suburb of Stockholm . SUBJECTS Subjects with a total serum cholesterol in the range 7.0 - 7.8 mmol L-1 and no signs of ischaemic heart disease or diabetes mellitus , r and omized to a low-intensity ( n = 35 ) or medium-intensity ( n = 41 ) intervention . INTERVENTION Two strategies were used , one labelled medium-intensity strategy which followed national current guidelines for nonpharmacological treatment of hypercholesterolaemia , the other was a low-intensity strategy . MAIN OUTCOME MEASURES Total serum cholesterol and intervention costs . RESULTS Both intervention strategies result ed in small ( mean 3.5 % ) decreases in total cholesterol with no significant difference between the groups . The cost per subject in the low-intensity group was SEK 753 and in the medium-intensity group SEK 3614 . CONCLUSIONS Because the effect of the two intervention programmes did not differ , the low-intensity programme is to be preferred from a cost-effectiveness point of view . If only one-third of the population in Stockholm county with cholesterol levels > or = 6.5 mmol L-1 are discovered by the primary health care system , and follow the treatment advice , the net savings in the low-intensity model compared to the current guidelines here presented as the moderate-intensity model , would be SEK 93 million To compare the effectiveness and costs of two alternative approaches to the treatment of hypercholesterolemia , a prospect i ve r and omized trial is being undertaken at Southern California Kaiser Permanente , a large health maintenance organization . Six hundred and twelve patients with postdiet LDL cholesterol ( LDL-C ) levels in the range of 190 - 230 mg/dl ( or 160 - 230 mg/dl for those with coronary heart disease or two or more coronary risk factors ) were r and omized to a stepped-care regimen ( initial treatment with niacin followed by other agents if needed ) or to initial use of lovastatin , an HMG-CoA reductase inhibitor . All patients are being followed for 1 year . The study seeks to approximate conditions of typical clinical practice : provider compliance with these plans of treatment is encouraged but not enforced and patients pay for medication as they customarily would . Principal outcomes of interest include the proportion of participants who achieve goal LDL-C at one year , the mean change in total cholesterol and LDL-C levels between baseline and the end of follow-up , and the costs of cholesterol-lowering therapy BACKGROUND The 1988 US National Cholesterol Education Program Expert Panel Report recommended initial treatment with niacin or bile acid sequestrants , followed by other agents if needed , to lower low-density lipoprotein cholesterol ( LDL-C ) levels in hypercholesterolemic patients who require drug therapy . It is unknown how the effectiveness and costs of such an approach ( " stepped care " ) compare in typical clinical practice to those of initial therapy with lovastatin . PATIENTS AND METHODS We r and omly assigned 612 patients , aged 20 to 70 years , who met 1988 National Cholesterol Education Program guidelines for drug treatment of elevated LDL-C level and had not previously used cholesterol-lowering medication , to either a stepped-care regimen or initial therapy with lovastatin ( both n=306 ) . The study , conducted at Southern California Kaiser Permanente , was design ed to approximate typical practice : provider compliance with treatment plans was encouraged but not enforced , and patients paid for medication as they customarily would . RESULTS At 1 year , the decline in mean LDL-C level was significantly greater among patients assigned to initial treatment with lovastatin ( 22 % vs 15 % for stepped care ; P<.001 ) , as was the number who attained goal LDL-C level ( < /= 4.14 mmol/L [ < /= 160 mg/dL ] , or < /= 3.36 mmol/L [ < /= 130 mg/dL ] if coronary heart disease or two or more risk factors were present ) ( 40 % vs 24 % ; P<.001 ) . The increase in mean high-density lipoprotein cholesterol levels was significantly greater in the stepped-care group , however ( 8 % vs 1 % for lovastatin ; P<.001 ) . Patients who were r and omized to stepped care were more likely to report substantial bother caused by side effects ( 30 % vs 16 % for lovastatin ; P<.001 ) and discontinuation of therapy at 1 year ( 28 % vs 18 % , respectively ; P<.01 ) . Costs of care were $ 333 higher per patient in the lovastatin group ( $ 786 vs $ 453 ; P<.001 ) . CONCLUSIONS A stepped-care regimen beginning with niacin is less costly than initial therapy with lovastatin , but also less effective in lowering LDL-C level . While it is more effective in increasing high-density lipoprotein cholesterol levels , the tolerability of such a regimen may be a problem STUDY OBJECTIVE : To investigate the cost effectiveness of personal health education for angina patients being treated in general practice . DESIGN : A r and omised controlled trial in which people were r and omised to intervention and control groups . All were assessed at the start and end of the study , with details recorded of disease status , coronary heart disease risk factors , and self assessed quality of life . A note was taken of their current use of drugs and over the course of the study their use of all health services . Those in the intervention group had three visits per year from a health visitor , whose brief was discuss ways of living more easily with their disease and in which risks of further events might be reduced . PATIENTS : Altogether 688 patents in the Greater Belfast area aged less than 75 years and known to have angina for at least six months . MAIN RESULTS : Significant improvements in survival and self assessed quality of life were found between the study and control groups . The intervention was associated with a reduction in drug usage and there was no significant difference between the intervention and control groups in terms of their use of other health services . CONCLUSION : Given the improvement in survival and self assessed quality of life and no significant differences in costs to the health service between the two groups , the intervention was deemed to be cost effective A cardiovascular disease screening and education campaign was conducted throughout the North Coast Region of New South Wales from 1987 to 1991 . Objectives were : to screen 20 per cent of the adult population for blood cholesterol and other heart disease risk factors ; to raise awareness of the risks associated with a high-fat diet ; to provide nutrition counselling and referral advice for those with elevated cholesterol ; and to monitor these participants ' cholesterol levels with a follow-up test at three months . During the five years , 42,869 individuals or 18 per cent of North Coast adults participated , with some overrepresentation of women aged 40 to 60 years . Initially , 65 per cent of participants had elevated cholesterol levels ( > or = 5.5 mmol/L ) and 46 per cent were overweight ( body mass index over 25 ) . A three-month retest was offered to all participants with elevated cholesterol , of whom 53 per cent attended . Participants who received nutrition counselling generally reported dietary changes which were reflected in significant cholesterol and weight reductions . Of participants who attended retest , 63 to 87 per cent had reduced cholesterol levels and 57 to 71 per cent reduced weight . A stratified r and om sample of participants was retested at one and three years . Reductions in cholesterol were well maintained for one year but showed signs of relapse after three years . There was a tendency for initially lower cholesterol levels to increase over a three-year period . Contributing factors included aging , regression to the mean and complacency . Maintenance may be enhanced by regular reinforcement of nutrition changes and development of more supportive environments Imprecise measurement of risk factors causes misclassification of individuals , limits sensitivity to detect those with high true levels , and dilutes associations between risk factors and disease . The implication s of these effects for two particular examples were explored using data from a large prospect i ve study relating plasma cholesterol to coronary heart disease ( CHD ) mortality and diastolic blood pressure ( DBP ) to fatal stroke . The absolute and relative effectiveness of three " high-risk " strategies of screening and treatment and a " population -based " shift in the risk factor distribution were compared , assuming different degrees of measurement error . The absolute benefits of each strategy were greater than suggested by unadjusted estimates from survey data . For cholesterol and CHD ( a linear relationship in this cohort ) , uncorrected estimates tended to exaggerate the effectiveness of " high-risk " strategies relative to the " population -based " approach . For DBP and stroke ( an exponential relationship ) , the relative effectiveness of screening and treatment was underestimated if no allowance was made for measurement error . These findings are strictly applicable only to the middle-aged men from whom they were derived , but the effects of misclassification and regression dilution need to be considered in any assessment of preventive strategies |
11,782 | 9,150,293 | The results confirm that paracetamol is an effective analgesic , and that codeine 60 mg added to paracetamol produces worthwhile additional pain relief even in single oral doses | null | null |
11,783 | 29,744,960 | RESULTS This study review ed mainly the effect of tepid massage on temperature compared with the use of antipyretics , along with other adverse effects in relation with fever management .
The results revealed no significant effect of tepid massage on temperature in febrile children .
In addition , incidence rates of adverse effects including chills , goose pimples , and discomfort were higher in tepid massage groups . | AIM This study aim ed to examine the effect of tepid massage in febrile children comparing with other fever management . | AIMS AND OBJECTIVES This study examined effectiveness of a theoretically based education programme in reducing inappropriate antipyretic use in fever management . BACKGROUND Paediatric nurses ' inconsistent , ritualistic antipyretic use in fever management is influenced by many factors including inconsistent beliefs and parental requests . Determinants of antipyretic administration , identified by the theory of planned behaviour , were belief-based attitudes and subjective norms . DESIGN A quasi-experiment explored group effects of a peer education programme , based on the theory of planned behaviour , on factors influencing paediatric nurses ' antipyretic administration . Surveys and chart audits collected data from medical wards at experimental and control hospitals one month pre and one and four months postpeer education programme . METHODS All nurses employed in targeted wards were eligible to participate in surveys and all eligible charts were audited . The peer education programme consisted of four one-hour sessions targeting evidence -based knowledge , myths and misconceptions , normative , attitudinal and control influences over and rehearsal of evidence -based fever management . All nurses in experimental hospital targeted wards were eligible to attend . Peer education and support facilitated session information reaching those unable to attend sessions . RESULTS Two-way univariate anovas explored between subject , experimental and control group and within subject factors , pre , post and latency data . Significant interactions in normative influence ( p = 0.01 ) and intentions ( p = 0.01 ) , a significant main group effect in control influence ( p = 0.01 ) and a significant main effect between audit data across time points ( p = 0.03 ) highlight peer education programme effectiveness in behaviour change . Normative , control and intention changes postpeer education programme were maintained in latency data ; mean temperature was not . CONCLUSION The peer education programme , based on a behaviour change theory , initiated and maintained evidence -based intentions for antipyretics use in fever management . RELEVANCE TO CLINICAL PRACTICE The promotion of evidence -based change in organizational unit intentions and behaviour highlights the crucial role peer support and education can play in continuing educational programmes OBJECTIVE To compare the effectiveness of tepid sponging and antipyretic drug versus only antipyretic drug among febrile children . DESIGN R and omized controlled trial . SETTING Tertiary care hospital . PARTICIPANTS 150 children 6 mo - 12 yr age with axillary temperature 101F . INTERVENTION Tepid sponging and antipyretic drug ( Paracetamol ) ( n=73 ) or only antipyretic drug ( Paracetamol ) ( n=77 ) . MAIN OUTCOME MEASURES Reduction of body temperature and level of comfort . RESULTS The reduction of body temperature in the tepid sponging and antipyretic drug group was significantly faster than only antipyretic group ; however , by the end of 2 hours both groups had reached the same degree of temperature . The children in tepid sponging and antipyretic drug had significantly higher discomfort than only antipyretic group , but the discomfort was mostly mild . CONCLUSION Apart from the initial rapid temperature reduction , addition of tepid sponging to antipyretic administration does not offer any advantage in ultimate reduction of temperature ; moreover it may result in additional discomfort A controlled clinical study compared the antipyretic effectiveness of acetaminophen administered at regular 4 h intervals ( group 1,n=53 ) versus sproadic usage contingent upon a body temperature above 37.9 ° C ( group 2,n=51 ) in 104 children presenting with simple febrile convulsions . The incidence of febrile episodes or temperature values were similar in spite of significantly larger amounts of acetaminophen administered to patients in group 1 . Four and 4 children in groups 1 and 2 , respectively , had a second episode of febrile seizures , in all of them within the first 24 h of admission . We conclude that the prophylactic administration of acetaminophen in children with febrile seizures is not effective in the prevention of fever , the reduction of its degree , or in preventing the early recurrence of febrile seizures A controlled clinical study compared the effectiveness of sponging with tepid water , ice water , and equal parts of 70 per cent isopropyl alcohol and water in addition to orally administered acetaminophen to reduce fever in children . More rapid reduction of fever was demonstrated when sponging was combined with the oral antipyretic drug . Sponging with ice water or with alcohol in water were equally effective and significantly superior to sponging with tepid water ; however , sponging with tepid water afforded significantly better comfort during the sponging procedure OBJECTIVES --To compare the acceptability and effects on temperature of advice to unwrap children and give paracetamol or warm sponging treatments in the management of feverish illness at home . DESIGN --A r and omised , open , parallel group study using factorial design comparison of unwrapping , warm sponging plus unwrapping , paracetamol plus unwrapping , and paracetamol and warm sponging plus unwrapping . SETTING --Homes of willing families with a feverish child recruited after consulting one of 21 participating general practitioners in Southampton . SUBJECTS--52 children aged from 3 months to 5 years with axillary temperatures before treatment of > or = 37.8 degrees C and < 40 degrees C. MAIN OUTCOME MEASURES --Response to advice assessed over four hours ; temperature assessed by continuous data logging from an axillary thermistor ; acceptability of treatment to child and parent scored on Likert scales immediately after treatment and on return to health . RESULTS --Response to treatment advice varied ; unwrapping alone had little effect on temperature . Paracetamol increased the time below 37.2 degrees C in four hours by 109 ( 95 % confidence interval 74 to 145 ) minutes compared with unwrapping ; warm sponging caused the fastest reduction in temperature . Parents discriminated between treatments , preferring paracetamol . CONCLUSION --Advice to give paracetamol is more effective than sponging or unwrapping in controlling temperature in children at home and is more acceptable to parents . Warm sponging has an additive effect and reduces fever more quickly than paracetamol BACKGROUND Routine antipyretic therapy in children with infectious diseases has long been the source of controversy . Each year , in addition to antimalarial medication , millions of children with Plasmodium falciparum malaria receive paracetamol to reduce fever . However , the usefulness of this practice has not been proven . METHODS In a r and omised trial in Lambaréné , Gabon , 50 children with P falciparum malaria were treated with intravenous quinine , and received either mechanical antipyresis alone , or in combination with paracetamol . Rectal body temperature and parasitaemia were recorded every 6 h for 4 days . Plasma concentrations and inducible concentrations of tumour necrosis factor ( TNF ) and interleukin-6 were measured every 24 h. In addition , production of oxygen radicals was measured in both groups . FINDINGS The mean fever clearance time was 32 h for children treated with paracetamol and 43 h for those who received mechanical antipyresis alone ; however , this 11 h difference was not significant ( 95 % CI -2 to 24 h ; p = 0.176 ) . Parasite clearance time was significantly prolonged in patients who received paracetamol with a difference of 16 h ( 8 - 24 h ; p = 0.004 ) . Plasma concentrations of TNF and interleukin-6 were similar in both groups during the study . However , the induced concentrations of TNF , and the production of oxygen radicals , were significantly lower in children treated with paracetamol than those who received mechanical antipyresis alone . INTERPRETATION These data suggest that paracetamol has no antipyretic benefits over mechanical antipyresis alone in P falciparum malaria . Moreover , paracetamol prolongs parasite clearance time , possibly by decreased production of TNF and oxygen radicals CONTEXT AND OBJECTIVE The role of tepid sponging to promote fever control in children is controversial . We did not find any studies reporting on the effectiveness of tepid sponging in addition to dipyrone . The aim of this study was to compare the effects of tepid sponging plus dipyrone with dipyrone alone for reducing fever . DESIGN AND SETTING A r and omized clinical trial was undertaken at Instituto Materno-Infantil Professor Fern and o Figueira , Recife , Pernambuco . METHODS Children from six months to five years old with axillary temperature greater than 38 masculineC in the emergency ward between January and July 2006 were eligible . One hundred and twenty children were r and omly assigned to receive oral dipyrone ( 20 mg/kg ) or oral dipyrone and tepid sponging for 15 minutes . The primary outcome was mean temperature reduction after 15 , 30 , 60 , 90 and 120 minutes . Secondary outcomes were crying and irritability . RESULTS 106 children finished the study . After the first 15 minutes , the fall in axillary temperature was significantly greater in the sponged group than in the control group ( p < 0.001 ) . From 30 to 120 minutes , better fever control was observed in the control group . Crying and irritability were observed respectively in 52 % and 36 % of the sponged children and in none and only two of the controls . CONCLUSIONS Tepid sponging plus dipyrone cooled faster during the first 15 minutes , but dipyrone alone presented better fever control over the two-hour period . Tepid sponging caused mild discomfort , crying and irritability for most of the children . CLINICAL TRIAL REGISTRATION NUMBER ACTRN12608000083392 Tepid sponge baths distress febrile children , and their efficacy at reducing fever has not been established . This study compared fever reduction and with ( 1 ) acetaminophen alone and ( 2 ) acetaminophen plus a 15-minute tepid sponge bath . Twenty children , ages 5 to 68 months , who presented to the emergency department or urgent care center with fever of > or = 38.9 degrees C were r and omized to receive ( 1 ) acetaminophen alone or ( 2 ) acetaminophen plus a 15-minute tepid sponge bath . All subjects received a 15-mg/kg dose of acetaminophen . Tympanic temperature was monitored every 30 minutes for 2 hours . Subjects were monitored for signs of discomfort ( crying , shivering , goosebumps ) . Sponge-bathed subjects cooled faster during the first hour but there was no significant temperature difference between the groups over the 2-hour study period ( P = .871 ) . Subjects in the sponge bath group had significantly higher discomfort scores ( P = .009 ) Two hundred and twenty-four children aged 6 months to 5 years , with rectal temperatures greater than or equal to 30 degrees ( 104 degrees F ) , were r and omly treated with sponging alone or with medication including a single oral dose of aspirin 15 mg/kg , or paracetamol 15 mg/kg , or ibuprofen 8 mg/kg . Twenty-three children were excluded from the final analysis because they did not complete the study . Demographic characteristics of the patients were found to be comparable in all groups . Rectal temperatures were recorded every 30 min for a 3 h period . During the first 30 min of intervention , sponging was found to be more effective than all of the three medications . After 60 min , the effects of each medication became superior to sponging with tepid water in reducing body temperature . Twenty-three children were excluded from the final analysis because they did not complete the study . Comparing the effect of the three different medications , it was seen that the antipyretic efficacy of aspirin and ibuprofen were significantly more than paracetamol 3 h after intervention ( P < 0.05 ) . For the management of fever over 39 degrees C , it is therefore recommended to give children an antipyretic drug , preferably ibuprofen , and at the same time to begin sponging to provide a rapid and sustained Several commonly used antipyretic therapies were compared in a series of 67 children . All regimens were more effective than exposure alone . Paracetamol and aspirin were comparable in antipyretic effect and superior to tepid sponging alone . The addition of tepid sponging to paracetamol therapy did not further improve the antipyretic response A block r and omized clinical trial to compare the efficacy of tepid sponging with the use of paracetamol in febrile children was undertaken at the Queen Elizabeth Central Hospital , Blantyre . Eighty children aged between 6 and 54 months with axillary temperatures of between > or = 38.5 degrees C and < or = 40 degrees C and a clinical diagnosis consistent with upper respiratory tract infection and /or malaria were block r and omized to receive either oral paracetamol ( 15 mg/kg ) or tepid sponging . Children receiving tepid sponging were sponged from head to toe ( except the scalp ) by leaving a thin layer of water on the body . If the body became dry it was repeated and continued until the axillary temperature fell to < 38.5 degrees C. Axillary temperature and assessment of discomfort ( convulsions , crying , irritability , vomiting and shivering ) were recorded every 30 minutes for 2 hours . A significantly greater and more rapid reduction of fever was demonstrated with paracetamol than with tepid sponging . Tepid sponging without antipyretics is often used to reduce fever , but our results suggest that this is effective only during the 1st 30 minutes . Paracetamol is clearly more effective than tepid sponging in reducing body temperature in febrile children in a tropical climate The effectiveness of tepid sponging , in addition to antipyretic medication , in the reduction of temperature in febrile children living in a tropical environment , was assessed in a prospect i ve , r and omized , open trial . Seventy-five children aged between 6 and 53 months who attended the casualty department of the Children 's Hospital , Bangkok , Thail and , with fever ( rectal temperature ≥38.5 ° C ) of presumed viral origin were r and omized to receive either tepid sponging and oral paracetamol ( sponged group ) or paracetamol alone ( control group ) . Rectal temperature and the occurrence of crying , irritability , and shivering were recorded over the following 2 hours . A greater and more rapid fall in mean rectal temperature occurred in the sponged group than in the control group . Temperature fell below 38.5 ° C sooner in children in the sponged group than in control children ( P < 0.001 ) . At 60 minutes , 38 ( 95.0 % ) of the controls still had a temperature of 38.5 ° C or greater , compared with only 15 children ( 42.9 % ) in the sponged group ( P<1 × 10 - 5 ) . Crying was associated with sponging , but shivering and irritability occurred in only one child who was being sponged . It is concluded that tepid sponging , in addition to antipyretic medication , is clearly more effective than antipyretic medication alone in reducing temperature in febrile children living in a tropical climate |
11,784 | 25,052,373 | Clinical ly significant restraint of maxillary growth was not found .
Although the m and ibular body length is increased , the facial impact of it is reduced by the simultaneous increment of the face height .
Changes of lower face height and occlusal plane inclination varied , suggesting that vertical dimension can be manipulated in patients who would benefit from lower molar extrusion .
As for lip position , there is not enough evidence to suggest clear lip position changes .
Changes associated with a Class II correction were identified .
Most of the changes individually were of limited clinical significance , but when combined reached clinical importance . | OBJECTIVE To evaluate dental , skeletal , and soft tissue effects during Twin-block treatment . | The aim of this study was to evaluate and compare the effects of activator and Twin Block ( TB ) appliances on the soft tissue profile . The study included 50 skeletal Class II patients ( 25 girls and 25 boys , mean age : 11.9 + /- 0.16 years ) who were r and omly allocated to one of two functional appliance treatment groups . The control group included 25 untreated skeletal Class II patients ( 13 boys and 12 girls , mean age : 10.11 + /- 0.91 years ) . Data were obtained from st and ardized lateral cephalograms taken at the beginning ( T0 ) and end ( T1 ) of appliance wear . The mean treatment time was 9 months for the activator group and 8 months for the TB group . The observation period of the control group was 8 months . Soft tissue profile changes were evaluated by means of 12 linear and five angular measurements . The groups were compared at T0 and T1 using analysis of variance , and treatment/observation differences ( T1-T0 ) were evaluated with the Kruskal-Wallis test . Treatment changes in both appliance groups differed significantly ( P < or = 0.001 ) from those in the control group , except for Ss-y , Ls-y , Li-E , and A-y measurements in the TB group and Ls-y , Li-E , nasolabial angle , and A-y measurements in the activator group . When the effects of the two appliances were compared , significant differences were observed only for SS-y ( P < or = 0.05 ) , Ss-E ( P < or = 0.05 ) , Si-E ( P < or = 0.05 ) , and nasolabial angle ( P < or = 0.01 ) . The effects of the activator and TB appliances on the soft tissue profile were similar ; both significantly changed the soft tissue profile This study evaluated the effectiveness of early orthodontic treatment with the Twin-block appliance for the developing Class II Division 1 malocclusion . This multicenter trial was carried out in the United Kingdom . A total of 174 children , aged 8 to 10 years old , with Class II Division 1 malocclusion were r and omly allocated to receive treatment with a Twin-block appliance or to an untreated , control group . Data were collected at the start of the study and 15 months later . Results showed that early treatment with Twin-block appliances result ed in reduction of overjet , correction of molar relationships , and reduction in severity of malocclusion . Most of this correction was due to dentoalveolar change , but some was due to favorable skeletal change . Early treatment with the Twin-block appliance is effective in reducing overjet and severity of malocclusion . The small change in the skeletal relationship might not be considered clinical ly significant A prospect i ve clinical study with a r and om allocation of 47 adolescent patients to three different functional appliance groups was established and compared with an untreated control group over a 9-month period . Treatment was undertaken with either a Bionator , Twin Block , or Bass appliance . Pre- and post-treatment cephalograms were used to quantify the skeletal and dentoalveolar changes produced by the appliances and compared with those observed in the control group as a result of growth . Both the Bionator and Twin Block appliances demonstrated a statistically significant increase in m and ibular length ( 3.9 + /- 2.7 mm ; 3.7 + /- 2.1 mm , respectively ) compared with the control group ( P < 0.05 ) , with an anterior movement of pogonion and point B. Highly statistically significant increases ( P < 0.01 ) were seen in lower face heights for all the appliance groups compared with the control group . The Twin Block group showed the least forward movement of point A due to a change in the inclination of the maxillary plane . The Bionator and Twin Block groups showed statistically significant reductions in the inclination of the upper incisors to the maxillary plane ( P < 0.05 ) . The Bass group showed minimal change in the inclination of the lower labial segment to the m and ibular plane . The Bionator group demonstrated the greatest proclination of the lower labial segment ( 4.0 + /- 3.6 degrees ) . Clinical ly important changes were measured in all the appliance groups when compared with the control group . Differences were also identified between the functional appliance groups . The Twin Block appliance and , to a lesser extent , the Bionator appeared the most effective in producing sagittal and vertical changes A prospect i ve clinical study with a r and om allocation of 47 patients to three different functional appliance groups was established and compared with a slightly younger control group over a 9-month period . The cephalometric hard tissue changes were assessed in relation to the soft tissue changes produced and the patients were also assessed by three-dimensional ( 3D ) laser scanning of the facial soft tissues . Each ' averaged ' appliance group scan was compared with the ' averaged ' control group face . Statistically and clinical ly significant changes occurred in the group treated with the Twin Block appliance , and to a lesser extent in the group treated with the Bionator appliance . No statistically significant facial soft tissue changes could be demonstrated in the Bass appliance group . Upper lip position remained stable despite the significant overjet reduction attained in the three appliance groups . Lower lip protrusion ( up to 3.8 mm ) , lower lip length ( up to 4.0 mm ) , and soft tissue lower and total face height increased significantly in all appliance groups by varying amounts . The long-term effect of these changes needs to be fully evaluated . The laser scanning system was found to be a sensitive and accurate method of quantitatively assessing small changes in the soft tissue facial form . Significant changes of the facial tissues in the transverse plane were highlighted by this technique INTRODUCTION The purpose of this study was to evaluate the skeletal and dentoalveolar effects of the Twin-block and bionator appliances in the treatment of Class II Division 1 malocclusions . METHODS Fifty-five girls from North India with Class II Division 1 malocclusion and the same physical growth maturation status were selected for the study . The subjects were divided among a Twin-block group ( n = 25 ) , a bionator group ( n = 20 ) , and a control group ( n = 10 ) . Pretreatment and posttreatment lateral cephalometric radiographs of the treatment group subjects , and prefollow-up and postfollow-up radiographs of the control group subjects , were traced manually and subjected to the pitchfork analysis . RESULTS Statistical software was used for 1-way analysis of variance and multiple comparisons ( post-hoc test , Bonferroni ) . A P value of .05 was considered statistically significant . Neither the Twin-block nor the bionator appliance significantly restricted forward growth of the maxilla ( P = .476 ) . M and ibular growth in the Twin-block subjects was significantly greater than in controls ( P = .005 ) . M and ibular growth was comparable in the control and the bionator subjects . Molar correction , overjet reduction , and proclination of the m and ibular incisors were significantly greater ( P = .000 ) in the treated subjects compared with the controls . CONCLUSIONS Both the Twin-block and bionator appliances were effective in correcting molar relationships and reducing overjets in Class II Division 1 malocclusion subjects . However , the Twin-block was more efficient than the bionator in the treatment of Class II Division 1 malocclusion This prospect i ve controlled study investigated the net effects of the Twin Block functional appliance taking into account the effects of normal growth in an untreated control group . The treatment group consisted of 36 subjects , mean age of 12.4 years , consecutively treated with Twin Block appliances for an average period of 0.9 years . Each subject had immediate pre- and posttreatment lateral cephalograms . The control group consisted of 27 subjects with a mean age of 12.1 years . These patients were observed for a mean time of 1.2 years and had radiographic investigation at the initial consultation and immediately before the start of Twin Block therapy . The data were then annualized and subjected to multiple regression analysis . In the treatment group , a reduction in ANB of 2.0 degrees ( p < 0.001 ) was observed largely because of an increase in SNB of 1.9 degrees ( p < 0.001 ) . No statistically significant restraint in the maxillary growth was observed . Treatment result ed in an increase in Ar-Pog of 5.1 mm ( p < 0.001 ) compared with the control group increase in Ar-Pog of 2.7 mm , result ing in a net gain of 2.4 mm . The overjet was reduced by combination of a net maxillary incisor retroclination of 10.8 degrees ( p < 0.001 ) , net m and ibular incisor proclination of 7.9 degrees ( p < 0.001 ) and forward movement of the m and ible . Buccal segment relationships were corrected by means of lower molar eruption , restraint in the eruption of the upper molars and forward growth or repositioning of the m and ible . Any possible fossa adaption was not assessed |
11,785 | 25,041,084 | However , high levels of heterogeneity were found that were not explained by the meta-regression .
Smoking status of doctors may affect their delivery of smoking cessation treatments to patients , with smokers being less likely than non-smokers or ex-smokers to advise and counsel their patients to quit but more likely to refer them to smoking cessation programmes | AIMS To assess the association between doctors ' smoking status and the use of the ' 5As ' of smoking cessation . | BACKGROUND Disease prevention and health promotion are important tasks in the daily practice of all general practitioners ( GPs ) . The objective of this study was to explore the knowledge and attitudes of European GPs in implementing evidence -based health promotion and disease prevention recommendations in primary care , to describe GPs ' perceived barriers to implementing these recommendations and to assess how GPs ' own health behaviors affect their work with their patients . METHODS A postal multinational survey was carried out from June to December 2000 in a r and om sample of GPs listed from national colleges of each country . RESULTS Eleven European countries participated in the study , giving a total of 2082 GPs . Although GPs believe they should advise preventive and health promotion activities , in practice , they are less likely to do so . About 56.02 % of the GPs answered that carrying-out prevention and health promotion activities are difficult . The two most important barriers reported were heavy workload/lack of time and no reimbursement . Associations between personal health behaviour and attitudes to health promotion or activities in prevention were found . GPs who smoked felt less effective in helping patients to reduce tobacco consumption than non-smoking GPs ( 39.34 % versus 48.18 % , P < 0.01 ) . GPs who exercised felt that they were more effective in helping patients to practice regular physical exercise than sedentary GPs ( 59.14 % versus 49.70 % , P < 0.01 ) . CONCLUSIONS Significant gaps between GP 's knowledge and practice s persist in the use of evidence -based recommendations for health promotion and disease prevention in primary care INTRODUCTION Smoking cessation counseling by health professionals is an effective approach to increase cessation rates among smokers . To guide the development of training and educational interventions , we surveyed six health professional groups including general practitioners ( GPs ) , pharmacists , dentists , dental hygienists , nurses , and respiratory therapists , in order to describe current practice s and identify the correlates of smoking cessation counseling . METHODS Self-administered question naires were mailed to 500 persons r and omly selected from the membership lists of active licensed professionals in each health professional group in Québec . RESULTS Response proportions ranged from 52 % ( nurses ) to 70 % ( dental hygienists ) . Compared with other groups , GPs and pharmacists undertook more counseling with patients ready to quit . GPs and respiratory therapists undertook more counseling with patients not ready to quit . Three factors emerged consistently across most groups as positively associated with counseling , including the belief that counseling is the role of health professionals , perceived self-efficacy to engage in effective counseling , and knowledge of community cessation re sources . DISCUSSION The correlates of cessation counseling are similar across health professional groups . Interventions that address beliefs that cessation counseling is the role of health professionals , self-efficacy to provide effective counseling , and knowledge of community re sources may result in improved cessation counseling practice s among health professionals Over the years we have been working to develop , test , and implement tobacco control interventions as a part of routine care within Kaiser Permanente . Most of our work has been in Kaiser Permanente 's northwest division , based in Portl and , Oregon , but we have also implemented similar approaches in several other divisions , including Ohio , Hawaii , and Georgia . I will first describe our general approach , which we call the TRAC model ( “ tobacco reduction , assessment , and care ” ) , and then share both our progress and some very real difficulties we have encountered in trying to implement the program throughout the health care system . The rationale for delivering brief tobacco intervention during routine care is familiar to those who work in cessation.1 Tobacco remains the most important cause of preventable disease . We know that most smokers see clinicians frequently , and that these visits create teachable moments when patients are receptive to advice and intervention . When we routinely ignore these intervention opportunities , we are , in effect , failing our patients . Indeed , meta-analyses from the Agency for Health Care Policy and Research ( AHCPR ) clinical guideline 2 show that brief advice and support lead to modest but consistent long term effects on smoking cessation . We also know that brief tobacco interventions are among the most cost effective of all medical care procedures we routinely offer.3 4 It is for these reasons that the Health Plan Employer Data Information Set ( HEDIS ) and other quality monitoring groups are holding health care systems accountable for addressing tobacco during clinical care . For me , however , the most important reasons to offer cessation advice and assistance are that our patients want , need , and expect this kind of support . How are we doing as a nation in delivering cessation advice during medical care visits ? Figure 1 displays time trend data 5 from the National Household BACKGROUND China has the most smokers among the world 's nations . Physicians play a key role in smoking cessation , but little is known about Chinese physicians and smoking . METHODS This 2004 clustered r and omized survey of 3552 hospital-based physicians from six Chinese cities measured smoking attitudes , knowledge , personal behavior , and cessation practice s for patients . Descriptive statistics and multivariate analysis of factors associated with asking about or advising against smoking were conducted in 2005 and 2006 . RESULTS Smoking prevalence was 23 % among all Chinese physicians , 41 % for men and 1 % for women . Only 30 % report good implementation of smoke-free workplace policies and 37 % of current smokers have smoked in front of their patients . Although 64 % usually advise smokers to quit , only 48 % usually ask about smoking status , and 29 % believe most smokers will follow their cessation advice . Less than 7 % set quit date s or use pharmacotherapy when helping smokers quit . Although 95 % and 89 % , respectively , know that active or passive smoking causes lung cancer , only 66 % and 53 % , respectively , know that active or passive smoking causes heart disease . Physicians were significantly more likely to ask about or advise against smoking if they believed that counseling about health harms helps smokers quit and that most smokers would follow smoking-cessation advice . CONCLUSIONS Physician smoking cessation , smoke-free workplaces , and education on smoking-cessation techniques need to be increased among Chinese physicians . Strengthening counseling skills may result in more Chinese physicians helping smoking patients to quit . These improvements can help reduce the Chinese and worldwide health burden from smoking OBJECTIVE To investigate the smoking habits and associated risk factors among Greek physicians . STUDY DESIGN Cross-sectional survey of a r and omly selected sample of Greek physicians . METHODS A national sample of 1284 physicians ( 718 men , 566 women ) participated in the study , which was conducted between September 2003 and June 2005 . Data were collected through an anonymous self-completed question naire . Logistic regression was used to analyse the influence of different factors on the probability of a physician being a current or former smoker . RESULTS Overall , 38.6 % of the physicians ( 40 % of men ; 37 % of women ) currently smoked , 13.8 % were former smokers , and 47.6 % had never smoked . Eighty-three per cent of smokers reported starting smoking before the age of 25 years , with half of them during medical school ( aged 19 - 24 years ) . Multivariate analyses revealed that physicians who were male , unmarried , divorced or widowed , surgeons or anaesthetists , and residents were more likely to be current smokers . Former smokers were more likely to be older , male and born in a rural area . Moreover , the odds of being a current or former smoker were significantly higher among physicians with a history of parents who smoked . The proportion of physicians who reported counselling patients ( often or always ) to stop smoking was lower among current smokers compared with those who never smoked or those who were former smokers ( 74.4 % vs. 85.3 % vs. 84.7 % , P<0.0001 ) . CONCLUSIONS The prevalence of smoking among Greek physicians is exceedingly high and similar to that of the general population . More effective interventions that reduce smoking in the medical community should be implemented immediately so that physicians will be better able to fulfil their function as role models for the general population BACKGROUND While cardiologists are very active in the prevention of cardiovascular disease , their attitudes towards patients ' smoking habits are poorly studied . AIMS In a nationwide French survey , we assessed cardiologists ' levels of knowledge and management of smoking cessation . METHODS We sent out a question naire to a r and om sample of 1000 cardiologists . RESULTS A total of 371cardiologists agreed to participate in the survey ; 8.1 % were current smokers and 32.4 % were past smokers . Most classified smoking cessation as the top priority for patients with coronary artery disease ( 56.5 % ) and peripheral arterial disease ( 88.5 % ) . Cardiologists routinely assessed active and passive smoking in 96.2 % and 43 % of their patients , respectively . Only 29.2 % considered themselves well informed about smoking-cessation management . While 39.9 % declared they knew about the minimal counselling 7.3 % described it correctly . Only 17.5 % used the Fagerström question naire . Smoking cessation was advised systematic ally by 85 % but only 5.4 % of cardiologists followed up their patients specifically on this issue . They referred smokers to either their general practitioner or to smoking-cessation centres and /or quitlines in 16.0 % and 67.0 % of cases , respectively ; 31.8 % never referred their patients to a smoking-cessation centre , and 25 % declared being unaware of any such centre in their area . Cardiologists who smoked were less likely to ask about patients ' smoking status than non-smokers ( 90 % vs 98.2 % , p=0.039 ) . Similarly , they were more passive in offering smoking-cessation counselling ( 23 % vs 7 % , p=0.011 ) , and referred less frequently their patients to a smoking-cessation centre ( 37 % vs 64 % , p=0.028 ) . CONCLUSION French cardiologists are rarely involved in the management of smoking cessation . Their own smoking status influences their attitudes towards the management of smoking cessation CONTEXT The World Health Organization has advocated that physicians should not smoke cigarettes and surveys on this issue should be conducted among medical professionals . However , no nationally representative surveys of smoking among physicians in Japan have been reported . OBJECTIVES To estimate the nationwide prevalence of smoking and determine the attitudes toward smoking among Japanese physicians . DESIGN , SETTING , AND PARTICIPANTS Descriptive study in which anonymous question naires were mailed to 4500 r and omly selected physician members of the Japan Medical Association in the year 2000 , which represents 63 % of all Japanese physicians ; 3771 ( 84 % ) respondents were included in the analysis . MAIN OUTCOME MEASURES Smoking prevalence among physicians , history of smoking , and attitudes toward smoking . RESULTS The prevalence of cigarette smoking among physicians was 27.1 % for men and 6.8 % for women , about half the age-adjusted prevalences among the general Japanese population . Smoking prevalence was higher among male physicians in Japan than those in the United States ( 3%-10 % ) and the United Kingdom ( 4%-5 % ) . Smoking prevalence differed by age , with the highest prevalence among male past smokers aged 70 years or older ( 51.8 % ; 95 % confidence interval [ CI ] , 47.4%-56.2 % ) . Among male current smokers , the highest rates were for those aged 40 to 49 years ( 31 % ; 95 % CI , 27.5%-34.5 % ) ; rates for female past smokers were highest among those aged 50 to 59 years ( 10.7 % ; 95 % CI , 6.6%-14.8 % ) and for female current smokers were highest among those aged 70 years or older ( 8.2 % ; 95 % CI , 4.8%-11.6 % ) . Nonsmoking physicians had more unfavorable views toward smoking and were more active in encouraging patients not to smoke than those physicians who smoked . CONCLUSION Smoking cessation programs should be introduced among Japanese physicians to reduce the number of smoking physicians . Also , a continuing education program should be instituted to motivate physicians about their role in society OBJECTIVES Several countries have followed the US example in publishing national guidelines on smoking cessation interventions . Gauging responses to these guidelines can provide important lessons for future implementation and revision internationally . This study sought to assess General Practitioners ' ( GPs ' ) views on recently published English smoking cessation guidelines that form the foundation of the UK National Health Service 's smoking cessation strategy . DESIGN Postal survey in which GPs were asked to judge the appropriateness , effectiveness and practicability of key recommendations for primary care in recent national smoking cessation guidelines . SETTING General practice , Engl and and Wales . SUBJECTS R and om national sample of GPs ; 236 GPs completed the question naire ; effective response rate : 62 % . RESULTS Only 16 % of GPs accepted that all the recommendations in the guidelines were appropriate ; 43 % accepted that it was appropriate to check the smoking status of known smokers when they visit the surgery and only 30 % thought it was practicable to advise smokers to stop at every opportunity . However , 77 % of GPs thought that they should provide assistance for smokers wanting to stop ; 74 % believed that they should refer smokers to specialist services if appropriate and a similar proportion ( 77 % ) believed that it was appropriate to recommend nicotine replacement therapy . CONCLUSIONS There was greater acceptance by GPs that they should assist smokers wanting to stop than that they should routinely monitor smoking status and give opportunistic advice to patients to stop . Given that opportunistic advice is a cornerstone of the national guidelines there is a need to find ways of reconciling what is being recommended and what GPs feel is appropriate |
11,786 | 28,762,635 | A robotic approach has favourable clinical outcomes but is more expensive | BACKGROUND Evidence has been systematic ally assessed comparing robotic with st and ard laparoscopy for treatment of endometrial cancer . | OBJECTIVE To compare outcomes between robotic versus laparoscopic hysterectomy and lymphadenectomy in patients with endometrial cancer . METHODS A cohort study was performed by prospect ively identifying all patients with clinical stage I or occult stage II endometrial cancer who underwent robotic hysterectomy and lymphadenectomy from 2006 - 2008 and retrospectively comparing data using the same surgeons ' laparoscopic hysterectomy and lymphadenectomy cases from 1998 - 2005 , prior to our robotic experience . Patient demographics , operative times , complications , conversion rates , pathologic results , and length of stay were analyzed . RESULTS 181 patients ( 105 robotic and 76 laparoscopic ) met inclusion criteria . There was no significant difference between the two groups in median age , uterine weight , bilateral pelvic or aortic lymph node counts , or complication rates in patients whose surgeries were completed minimally invasively . Despite a higher BMI ( 34 vs. 29 , P<0.001 ) , the estimated blood loss ( 100 vs. 250 mL , P<0.001 ) , transfusion rate ( 3 % vs. 18 % , RR 0.18 , 95%CI 0.05 - 0.64 , P=0.002 ) , laparotomy conversion rate ( 12 % vs. 26 % , RR 0.47 , 95%CI 0.25 - 0.89 , P=0.017 ) , and length of stay ( median : 1 vs. 2 nights , P<0.001 ) were lower in the robotic patients compared to the laparoscopic cohort . The odds ratio of conversion to laparotomy based on BMI for robotics compared to laparoscopy is 0.20 ( 95 % CI 0.08 - 0.56 , P=0.002 ) . The mean skin to skin time ( 242 vs. 287 min , P<0.001 ) and total room time ( 305 vs. 336 min , P<0.001 ) was shorter for the robotic cohort . CONCLUSION Robotic hysterectomy and lymphadenectomy for endometrial carcinoma can be accomplished in heavier patients and results in shorter operating times and hospital length of stay , a lower transfusion rate , and less frequent conversion to laparotomy when compared to laparoscopic hysterectomy and lymphadenectomy PURPOSE To demonstrate the feasibility of robot-assisted staging surgery using three arms in patients with endometrial cancer . METHODS One hundred nine patients with clinical stage I endometrial cancer who underwent staging surgery at Yonsei University Health System were enrolled from May 2006 to January 2009 . Patient demographics and operative outcomes were prospect ively collected . RESULTS Robotic surgery using three arms was performed in 28 patients , laparoscopy in 25 , and laparotomy in 56 . There were no differences among the three groups in terms of patient demographics . The number of harvested pelvic lymph nodes was lower in the laparoscopy group than in the laparotomy group ( 18.36 + /- 7.25 vs. 24.39 + /- 10.08 , respectively , P = 0.025 ) , but there was no difference between the robot and laparotomy groups . The number of resected para-aortic lymph nodes and operative time did not differ among the three groups . The average hospital stay was longer for the laparotomy group than the robot and laparoscopy groups ( 10.78 days vs. 7.92 days vs. 7.67 days , respectively , P < 0.001 ) . Operative complications and transfusions developed more frequently in the laparotomy group than in the robot and laparoscopy groups ( 25.0 % vs. 7.1 % vs. 8.0 % , respectively , P = 0.049 ; 42.9 % vs. 14.3 % vs. 16.0 % , respectively , P = 0.006 ) . CONCLUSION Robot-assisted surgery using three arms is a feasible method for surgical staging in patients with clinical stage I endometrial cancer OBJECTIVE : To evaluate the effect of introducing a robotic program on cost and patient outcome . METHODS : This was a prospect i ve evaluation of clinical outcome and cost after introducing a robotics program for the treatment of endometrial cancer and a retrospective comparison to the entire historical cohort . RESULTS : Consecutive patients with endometrial cancer who underwent robotic surgery ( n=143 ) were compared with all consecutive patients who underwent surgery ( n=160 ) before robotics . The rate of minimally invasive surgery increased from 17 % performed by laparoscopy to 98 % performed by robotics in 2 years . The patient characteristics were comparable in both eras , except for a higher body mass index in the robotics era ( median 29.8 compared with 27.6 ; P<.005 ) . Patients undergoing robotics had longer operating times ( 233 compared with 206 minutes ) , but fewer adverse events ( 13 % compared with 42 % ; P<.001 ) , lower estimated median blood loss ( 50 compared with 200 mL ; P<.001 ) , and shorter median hospital stay ( 1 compared with 5 days ; P<.001 ) . The overall hospital costs were significantly lower for robotics compared with the historical group ( Can$7,644 compared with Can$10,368 [ Canadian dollars ] ; P<.001 ) even when acquisition and maintenance cost were included ( Can$8,370 compared with Can$10,368 ; P=.001 ) . Within 2 years after surgery , the short-term recurrence rate appeared lower in the robotics group compared with the historic cohort ( 11 recurrences compared with 19 recurrences ; P<.001 ) . CONCLUSION : Introduction of robotics for endometrial cancer surgery increased the proportion of patients benefitting from minimally invasive surgery , improved short-term outcomes , and result ed in lower hospital costs . LEVEL OF EVIDENCE : Purpose Laparoscopy ( LSC ) offers superior patient outcomes compared to laparotomy . Small retrospective/ prospect i ve series have suggested robotics offers further reduction in postoperative pain and pain medication use compared to st and ard LSC . Our objective was to compare postoperative pain in patients undergoing robotically assisted ( RBT ) versus st and ard LSC for newly diagnosed endometrial cancer . Methods All preoperative endometrial cancer cases scheduled for RBT and LSC from May 1 , 2007 to June 9 , 2010 were identified . For this analysis , we only included cases not requiring conversion to laparotomy . All patients were offered intravenous ( IV ) patient-controlled analgesia ( PCA ) postoperatively . Intraoperative equivalent fentanyl doses ( IEFDs ) and pain scores in the postanesthesia care unit ( PACU ) were assessed . Results IV PCA was used in 206 RBTs ( 86 % ) and 208 LSCs ( 88 % ) . Median IEFD was 425 μg for LSCs and 500 μg for RBTs ( P = 0.03 ) . Median pain scores on PACU arrival were similar in both groups . Median highest pain score was 5 for LSCs and 4 for RBTs ( P = 0.007 ) . Linear regression demonstrated that the IEFD was not correlated with the highest pain score ( R = 0.09 ; P = 0.07 ) . Fentanyl was used postoperatively in 196 of 206 RBTs ( 95 % ) and 187 of 208 LSCs ( 90 % ) . The total fentanyl doses were 242.5 ( range 0–2705 ) μg and 380 ( range 0–2625 ) μg , respectively ( P < 0.001 ) . The median hourly fentanyl doses were 16.7 ( range 0–122.5 ) μg and 23.5 ( range 0–132.4 ) μg , respectively ( P = 0.005 ) . Simultaneous multiple regression analysis further demonstrated RBT was independently associated with a lower total fentanyl dose compared to LSC ( P = 0.02 ) . Conclusions RBT is independently associated with significantly lower postoperative pain and pain medication requirements compared to LSC . The amount of intraoperative fentanyl analgesia does not appear to correlate with postoperative pain BACKGROUND Evaluation of the impact of a new robotic surgery programme on perioperative outcomes for endometrial cancer METHODS A prospect i ve data base of all patients undergoing staging for endometrial cancer during July 2007-July 2008 was collected and analysed . Demographic data and perioperative outcomes were compared between cases performed via laparotomy , laparoscopy and robotics . RESULTS Sixty-five patients underwent staging during the time of data collection ( LAP-26 , LSC-7 , ROB-32 ) . No difference in surgical volume in the year before vs. after robotics was identified . Median operative time for robotics and laparotomy was significantly less than for laparoscopy ( p = 0.023 ) . There was no significant difference in lymph node yields between the three groups ( p = 0.92 ) . Robotics was associated with significantly less blood loss ( p < 0.0001 ) . Complication rates were significantly lower in the robotic group compared to the laparotomy group ( p = 0.05 ) . Median hospital stay was 1 day for the minimally invasive groups . Total number of perioperative inpatient days decreased from 331 to 150 in one year . Practice management of endometrial cancer transitioned from a predominantly open approach ( 5.6 % LSC ) to robotics ( 11 % LSC , 49 % ROB ) within 12 months . CONCLUSIONS Robotic surgery dramatically altered our management of endometrial cancer and was associated with a significant improvement in several perioperative outcomes when compared to laparotomy and laparoscopy INTRODUCTION Comparison of perioperative outcomes and recurrence in patients undergoing primary surgical treatment for endometrial cancer by robotics , laparoscopy , vaginal/laparoscopy , or laparotomy approaches . METHODS Prospect i ve analysis of 67 patients undergoing robotic surgery for endometrial cancer between March 2004 and December 2007 . Comparison was made with similar patients operated between November 1999 and December 2006 by laparoscopy ( 37 cases ) , laparotomy ( 99 cases ) and vaginal/laparoscopy approach ( vaginal hysterectomy , bilateral adnexectomy/laparoscopic lymphadenectomy ) ( 47 cases ) and matched by age , body mass index ( BMI ) , histological type and International Federation of Gynecologists and Obstetricians ( FIGO ) staging . RESULTS Mean operating times for patients undergoing robotic , laparoscopy , vaginal/laparoscopy or laparotomy approach were 181.9 , 189.5 , 202.7 and 162.7 min , respectively ( p = 0.006 ) ; mean blood loss was 141.4 , 300.8 , 300.0 and 472.6 ml , respectively ( p < 0.001 ) ; mean number of nodes was 24.7 , 27.1 , 28.6 , and 30.9 , respectively ( p = 0.008 ) ; mean length of hospital stay was 1.9 , 3.4 , 3.5 and 5.6 days , respectively ( p < 0.001 ) . There were no significant differences in intra- or postoperative complications among the four groups . The conversion rate was 2.9 % for robotics and 10.8 % for the laparoscopy group ( 0.001 ) . There were no differences relative to recurrence rates among the four groups : 9 % , 14 % , 11 % and 15 % for robotics , laparoscopy , vaginal/laparoscopy , and laparotomy , respectively . CONCLUSION Robotics , laparoscopy and vaginal/laparoscopy techniques are preferable to laparotomy for suitable patients with endometrial cancer . Robotics is preferable to laparoscopy due to a shorter hospital stay and lower conversion rate and preferable to vaginal/laparoscopy due to a reduced hospitalization BACKGROUND Previous studies comparing robotic-assisted laparoscopic surgery to traditional laparoscopic or open surgery in gynecologic oncology have been retrospective . To our knowledge , no prospect i ve r and omized trials have thus far been performed on endometrial cancer . OBJECTIVE We sought to prospect ively compare traditional and robotic-assisted laparoscopic surgery for endometrial cancer . STUDY DESIGN This was a r and omized controlled trial . From December 2010 through October 2013 , 101 endometrial cancer patients were r and omized to hysterectomy , bilateral salpingo-oophorectomy , and pelvic lymphadenectomy either by robotic-assisted laparoscopic surgery or by traditional laparoscopy . The primary outcome measure was overall operation time . The secondary outcome measures included total time spent in the operating room , and surgical outcome ( number of lymph nodes harvested , complications , and recovery ) . The study was powered to show at least a 25 % difference in the operation time using 2-sided significance level of .05 . The differences between the traditional laparoscopy and the robotic surgery groups were tested by Pearson χ2 test , Fisher exact test , or Mann-Whitney test . RESULTS In all , 99 patients were eligible for analysis . The median operation time in the traditional laparoscopy group ( n = 49 ) was 170 ( range 126 - 259 ) minutes and in the robotic surgery group ( n = 50 ) was 139 ( range 86 - 197 ) minutes , respectively ( P < .001 ) . The total time spent in the operating room was shorter in the robotic surgery group ( 228 vs 197 minutes , P < .001 ) . In the traditional laparoscopy group , there were 5 conversions to laparotomy vs none in the robotic surgery group ( P = .027 ) . There were no differences as to the number of lymph nodes removed , bleeding , or the length of postoperative hospital stay . Four ( 8 % ) vs no ( 0 % ) patients ( P = .056 ) had intraoperative complications and 5 ( 10 % ) vs 11 ( 22 % ) ( P = .111 ) had major postoperative complications in the traditional and robotic surgery groups , respectively . CONCLUSION In patients with endometrial cancer , robotic-assisted laparoscopic surgery was faster to perform than traditional laparoscopy . Also total time spent in the operation room was shorter in the robotic surgery group and all conversions to laparotomy occurred in the traditional laparoscopy group . Otherwise , the surgical outcome was similar between the groups . Robotic surgery offers an effective and safe alternative in the surgical treatment of endometrial cancer STUDY OBJECTIVE To compare surgical costs for endometrial cancer staging between robotic-assisted and traditional laparoscopic methods . DESIGN Retrospective chart review from November 2005 to July 2006 ( Canadian Task Force classification II-3 ) . SETTING Non-university-affiliated teaching hospital . PATIENTS Thirty-three women with diagnosed endometrial cancer undergoing hysterectomy , bilateral salpingo-oophorectomy , and pelvic and paraaortic lymph node resection . INTERVENTIONS Patients underwent either robotic or traditional laparoscopic surgery without r and omization . MEASUREMENTS AND MAIN RESULTS Hospital cost data were obtained for operating room time , instrument use , and disposable items from hospital billing records and provided by the finance department . Separate overall hospital stay costs were also obtained . Mean operative costs were higher for robotic procedures ( $ 3323 vs $ 2029 ; p<.001 ) , due in part to longer operating room time ( $ 1549 vs $ 1335 ; p=.03 ) . The more significant cost difference was due to disposable instrumentation ( $ 1755 vs $ 672 ; p<.001 ) . Total hospital costs were also higher for robotic-assisted procedures ( $ 5084 vs $ 3615 ; p=.002 ) . CONCLUSION Robotic surgery costs were significantly higher than traditional laparoscopy costs for staging of endometrial cancer in this small cohort of patients AIM To study inflammatory response and nutritional biomarkers in operated endometrial cancer ( EC ) patients . MATERIAL S AND METHODS A total 109 consecutive EC patients undergoing open laparotomy ( LT ) , laparoscopic ( LS ) or robot-assisted surgery ( RS ) were studied . Twenty four patients served as controls . Pre- and postoperative levels of inflammatory and nutritional biomarkers were analyzed prospect ively . RESULTS The estimated blood loss was significantly lower in RS compared to all other groups . C-reactive protein ( CRP ) and interleukin-6 ( IL-6 ) correlated with each other and exhibited positive correlation with age , body-mass index ( BMI ) , leukocyte count , platelet count , kynurenine , kynurenine/tryptophan ratio and urinary neopterin and a negative correlation with vitamin D and retinol . Hemoglobin , retinol , alpha-tocopherol , vitamin D and citrulline concentrations decreased and inflammatory biomarkers increased after surgery to a different extent in LT , LS , RS and control groups . CONCLUSION The present data demonstrate a differential response to surgical trauma in patients with endometrial carcinoma The aim of this study was to compare the financial and clinical outcomes in robotic-assisted laparoscopic surgery for primary endometrial cancer between obese and nonobese women . The hospital finance department assessed the total admission costs for robotic surgery for endometrial cancer in 54 women . This included a sub analysis for costs over nine areas ( ward and clinics , drugs and pharmacy , medical staff , theaters , blood products , imaging , pathology , rehabilitation therapy , and high dependency costs ) . Furthermore , a prospect i ve collection of morbidity and surgical outcome data was performed . The study group included 21 nonobese and 33 obese women ( body mass index > 30 ) . Obese women were more likely to stay for more than one night in hospital ( 20/33 [ 60.6 % ] compared to 4/21 [ 19.0 % ] , P=0.032 ) and to have high dependency care ( 25/33 [ 75.8 % ] compared to 10/21 [ 47.6 % ] , P=0.032 ) . Theater time was on average 35 min longer ( 95 % confidence interval [ CI ] 5–65 min , P=0.0252 ) . Both the groups were comparable for comorbidities except for the presence of diabetes being present in the obese group ( 13/33 [ 39.4 % ] compared to 0/21 [ 0.0 % ] , P=0.007 ) . There were six Clavien-Dindo grade II complications in the obese group and two in the nonobese group . The average overall costs were £ 1,852 greater ( 95 % CI £ 431–£3,277 , P=0.012 ) in the obese group . Diabetes and hypertension were associated with increased costs , but obesity was the only independent variable . In conclusion , greater re source should be allocated to obese women undergoing primary surgery for endometrial cancer |
11,787 | 28,102,899 | Authors ' conclusions In patients with heart failure low‐ quality evidence showed a reduction in heart failure admission with NP‐guided treatment while low‐ quality evidence showed uncertainty in the effect of NP‐guided treatment for all‐cause mortality , heart failure mortality , and all‐cause admission .
Uncertainty in the effect was further shown by very low‐ quality evidence for patient 's quality of life . | Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body .
Symptoms of heart failure include breathlessness , fatigue and fluid retention .
Outcomes for patients with heart failure are highly variable ; however on average , these patients have a poor prognosis .
Prognosis can be improved with early diagnosis and appropriate use of medical treatment , use of devices and transplantation .
Patients with heart failure are high users of healthcare re sources , not only due to drug and device treatments , but due to high costs of hospitalisation care .
B‐type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure , but could offer to clinicians a possible tool to guide drug treatment .
This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance .
Objectives To assess whether treatment guided by serial BNP or NT‐proBNP ( collectively referred to as NP ) monitoring improves outcomes compared with treatment guided by clinical assessment alone . | OBJECTIVES The purpose of this study was to compare the effects of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy with those of intensive clinical management and with usual care ( UC ) on clinical outcomes in chronic symptomatic heart failure . BACKGROUND Initial trial results suggest titration of therapy guided by serial plasma B-type natriuretic peptide levels improves outcomes in patients with chronic heart failure , but the concept has not received widespread acceptance . Accordingly , we conducted a longer-term study comparing the effects of NT-proBNP-guided therapy with those of intensive clinical management and with UC of patients with heart failure . METHODS Three hundred sixty-four patients admitted to a single hospital with heart failure were r and omly allocated 1:1:1 ( stratified by age ) to therapy guided by NT-proBNP levels or by intensive clinical management , or according to UC . Treatment strategies were applied for 2 years with follow-up to 3 years . RESULTS One-year mortality was less in both the hormone- ( 9.1 % ) and clinical ly-guided ( 9.1 % ) groups compared with UC ( 18.9 % ; p = 0.03 ) . Three-year mortality was selectively reduced in patients < or=75 years of age receiving hormone-guided treatment ( 15.5 % ) compared with their peers receiving either clinical ly managed treatment ( 30.9 % ; p = 0.048 ) or UC ( 31.3 % ; p = 0.021 ) . CONCLUSIONS Intensive management of chronic heart failure improves 1-year mortality compared with UC . Compared with clinical ly guided treatment and UC , hormone-guided treatment selectively improves longer-term mortality in patients < or=75 years of age . ( NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death [ BATTLESCARRED ] ; Australian New Zeal and Clinical Trials Registry 12605000735651 ) OBJECTIVES The aim of this multicenter study was to evaluate the prognostic impact of a therapeutic strategy using plasma brain natriuretic peptide ( BNP ) levels . BACKGROUND The prognosis of chronic heart failure ( CHF ) remains poor , even among patients treated in specialized departments . METHODS A total of 220 New York Heart Association functional class II to III patients considered optimally treated with angiotensin-converting enzyme inhibitors ( ACEIs ) , beta-blockers , and diuretics by CHF specialists were r and omized to medical treatment according to either current guidelines ( clinical group ) or a goal of decreasing BNP plasma levels < 100 pg/ml ( BNP group ) . Outpatient visits were scheduled every month for 3 months , then every 3 months . The primary combined end point was CHF-related death or hospital stay for CHF . RESULTS Both groups were similar for baseline clinical and biological characteristics . Left ventricular ejection fraction was slightly lower in the BNP group than in the clinical group ( 29.9 + /- 7.7 % vs. 31.8 + /- 8.4 % , p = 0.05 ) . At the end of the first 3 months , all types of drugs were changed more frequently in the BNP group . Mean dosages of ACEIs and beta-blockers were significantly higher in the BNP group ( p < 0.05 ) , whereas the mean increase in furosemide dosage was similar in both groups . During follow-up ( median 15 months ) , significantly fewer patients reached the combined end point in the BNP group ( 24 % vs. 52 % , p < 0.001 ) . CONCLUSIONS In optimally treated CHF patients , a BNP-guided strategy reduced the risk of CHF-related death or hospital stay for CHF . The result was mainly obtained through an increase in ACEI and beta-blocker dosages BACKGROUND Heart failure ( HF ) treatment guided by amino-terminal pro-B type natriuretic peptide ( NT-proBNP ) may reduce cardiovascular event rates compared to st and ard-of-care ( SOC ) management . Comprehensive underst and ing regarding effect of NT-proBNP guided care on patient-reported quality of life ( QOL ) remains unknown . METHODS One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were r and omized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Question naire ( MLHFQ ) quarterly , with change ( Δ ) in score assessed across study procedures and as a function of outcome . RESULTS Overall , baseline MLHFQ score was 30 . Across study visits , QOL improved in both arms , but was more improved and sustained in the NT-proBNP arm ( repeated measures P = .01 ) ; NT-proBNP patients showing greater reduction in MLHFQ score ( -10.0 vs -5.0 ; P = .05 ) , particularly in the physical scale of the question naire . Baseline MLHFQ scores did not correlate with NT-proBNP ; in contrast , ∆MLHFQ scores modestly correlated with ∆NT-proBNP values ( ρ = .234 ; P = .006 ) as did relative ∆ in MLHFQ score and NT-proBNP ( ρ = .253 ; P = .003 ) . Considered in tertiles , less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization , worsening HF , and cardiovascular death ( P = .001 ) . CONCLUSIONS We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care . Compared to SOC HF management , NT-proBNP guided care was associated with greater and more sustained improvement in QOL ( Clinical Trial Registration : www . clinical trials.govNCT00351390 ) Heart failure has been named “ the growing epidemic . ” Over the last decade , the annual number of heart failure hospitalizations has almost doubled with approximately 50 % of patients being rehospitalized within 6 months of discharge [ 1 ] . The complex array of physiologic , psychological , social , and health care delivery issues makes it a challenging chronic disease to manage . Underst and ing the epidemiology and pathophysiology of the syndrome , identifying the predictors and their strength of association with outcomes , and using the available diagnostic modalities cost-effectively are essential in order to devise effective prevention interventions and implement novel therapeutic approaches to curb this epidemic . In this special issue , we have invited a few papers that address such issues and explain why despite the emergence of novel therapeutic approaches , that promise life prolongation and hospital length reduction , this patient population will still be needing rehospitalization and will often have a poor prognosis . This special issue is the extension of an effort that was initiated in 2011 with the first heart-failure-focused issue [ 2 ] . In the pathophysiology section , S. M. R. Kazemi-Bajestani et al. describe the opportunities and challenges of targeting the angiotensin converting enzyme 2 (ACE2)/Ang II/Ang1–7 and apelin/APJ pathways as novel therapeutic modalities in heart failure [ 3 ] . ACE2 and the apelin/APJ are two important peptide systems which exert diverse effects on the cardiovascular system . Dysregulation of such systems may be involved in the predisposition to cardiovascular diseases whereas enhancing their action may have important therapeutic effects . In the same section , D. Lindner et al. provide a comprehensive review on the protective function of signal transducer and activator of transcription 3 ( STAT3 ) in CVB3-induced myocarditis [ 4 ] . The transcription factor ( STAT3 ) is an important mediator of the inflammatory process , and in this original research the investigators examine the role of STAT3 in viral myocarditis and its possible role in the development to dilated cardiomyopathy . Considering the high mortality rate and the availability of life-saving therapies like transplantation and left ventricular assist devices , accurate prognosis determination in HF is clinical ly important . Taking into account the mediocre performance of current established prediction models , such as the Seattle Heart Failure Model [ 5–7 ] , the work by H. Fukuta et al. [ 8 ] on the prognostic value of left ventricular diastolic dysfunction in patients undergoing cardiac catheterization for coronary artery disease sheds light on this extremely important topic . A shared underst and ing of medical conditions between patients and their health care providers has been shown to improve self-care and outcomes [ 9 ] . In the comorbidity section , we demonstrate how certain comorbid conditions may affect patients ' decision-making capacity and interfere with their ability to comply with treatment requirements , recognize and self-manage disease worsening symptoms . Among others , cognitive impairment is increasingly recognized as a common adverse consequence of HF , whereby phenomena such as microembolism , chronic or intermittent cerebral hypoperfusion , and /or impaired cerebral vessel reactivity may lead to cerebral hypoxia and ischemic brain damage . Cognitive decline in HF is characterized by deficits in one or more cognition domains , including attention , memory , executive function , and psychomotor speed . E. Dardiotis et al. [ 10 ] , in a comprehensive review , underscore the importance for healthcare professionals to become familiar with assessment of cognitive performance using st and ardized screening instruments in their routine evaluations of HF patients . Another comorbidity gaining increasing attention in HF patients is depression . There are several pathophysiological mechanisms as well as behavioral processes linking depression and HF . Equally important is screening for depression and there are several valid and reliable screening tools to identify patients at greater risk . Consultation should be provided by a multidisciplinary team , consisting of cardiologists , psychiatrists , and hospital or community nurses so as to carefully plan , execute , and evaluate medical intervention and implement lifestyle changes . D. Mastrogiannis et al. [ 11 ] systematic ally review the existing knowledge regarding current definitions , prognostic implication s , pathophysiological mechanisms , and current and future treatment options in patients with depression and HF . Evidence from the literature supports the possibility of a pathophysiological relationship between cognitive impairment , depression , and HF . Yet , very few studies have sought to investigate this relationship . The paper by Z. N. Sohani and Z. Samaan review s current literature on the association between depression and cognitive impairment in persons with HF and explores possible mechanisms explaining this complex triad [ 12 ] . Heart failure through neurohumoral activation induces alterations of cardiac metabolism , such as insulin resistance , and promotes increased utilization of noncarbohydrate substrates for energy production [ 13 , 14 ] . Fasting blood ketone bodies as well as fat oxidation have been shown to be increased in this patient population . The result is depletion of myocardial ATP , phosphocreatine , and creatine kinase , leading to decreased efficiency of mechanical work . A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart . Trimetazidine , perhexiline , and ranolazine directly inhibit fatty acid oxidation and have been used to increase the ischemic threshold in patients with effort angina . Current research is supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with HF . These agents have been shown to improve both glucose metabolism and left ventricular function in diabetic patients with left ventricular dysfunction . In the pharmacotherapy section , we provide a systematic review , in which N. Signoretta et al. [ 15 ] discuss the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilization in patients with HF . In the advanced heart failure section , we provide a thorough review on the current status of mechanical circulatory support in patients with advanced HF . Management of the advanced HF patients with the numerous comorbidities [ 16 , 17 ] requires a significant amount of health care re sources and is becoming a major public health problem . As therapeutical strategies for HF have been refined , the number of patients suffering from the end-stage disease has exp and ed dramatically . Although heart transplantation still represents the gold st and ard therapeutical approach , the shortage of donors universally has made the implantation of mechanical circulatory support devices a well-established management for this disease . The systematic review by K. Spiliopoulos et al. [ 18 ] , outlines the current status of mechanical circulatory support in this patient population . In the chronic follow-up section , we deal with telemonitoring , a novel diagnostic modality that has been suggested to be beneficial for HF patients , targeting optimization of their chronic followup . Telemonitoring is viewed as a means of recording physiological data ( such as body weight , heart rate , arterial blood pressure electrocardiogram recordings , and other data ) by portable devices and transmitting these data remotely ( via a telephone line , a mobile phone , or a computer ) to a server where they can be stored , review ed , and analyzed by the research team . In a systematic review of all r and omized clinical trials evaluating telemonitoring in chronic HF , G. Giamouzis et al. [ 19 ] assess whether telemonitoring provides any substantial benefit in this patient population . We hope that the readers of the journal will find the topics as interesting and important as we did . Gregory Giamouzis George Giannakoulas Javed Butler John A. Elefteriades Carsten Tschope Filippos OBJECTIVES We sought to examine whether measurements of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , in addition to cardiac troponin T ( cTnT ) and interleukin-6 ( IL-6 ) , improve the ability to identify high-risk patients who benefit from an early invasive strategy . BACKGROUND Biochemical indicators of cardiac performance ( e.g. , NT-proBNP ) , inflammation ( e.g. , IL-6 ) , and myocardial damage ( e.g. , cTnT ) predict mortality in unstable coronary artery disease ( UCAD ) ( i.e. , unstable angina or non-ST-segment elevation myocardial infa rct ion [ MI ] ) . In these patients , an early invasive treatment strategy improves the outcome . METHODS Levels of NT-proBNP , cTnT , and IL-6 were measured in 2,019 patients with UCAD r and omized to an invasive or non-invasive strategy in the FRagmin and fast revascularization during InStability in Coronary artery disease ( FRISC-II ) trial . Patients were followed up for two years to determine death and MI . RESULTS Patients in the third NT-proBNP tertile had a 4.1-fold ( 95 % confidence interval [ CI ] 2.4 to 7.2 ) and 3.5-fold ( 95 % CI 1.8 to 6.8 ) increased mortality in the non-invasive and invasive groups , respectively . An increased NT-proBNP level was independently associated with mortality . In patients with increased levels of both NT-proBNP and IL-6 , an early invasive strategy reduced mortality by 7.3 % ( risk ratio 0.46 , 95 % CI 0.21 to 1.00 ) . In patients with lower NT-proBNP or IL-6 levels , the mortality was not reduced . Only elevated cTnT was independently associated with future MI and a reduction of MI by means of an invasive strategy . CONCLUSIONS N-terminal proBNP is independently associated with mortality . The combination of NT-proBNP and IL-6 seems to be a useful tool in the identification of patients with a definite survival benefit from an early invasive strategy . Only cTnT is independently associated with future MI and a reduction of MI by an invasive strategy AIM to compare efficacy of treatment of high risk patients after acute decompensation ( AD ) of chronic heart failure ( CHF ) based on monitoring of NT-proBNP concentration and st and ard treatment . MATERIAL AND METHODS Patients ( n=100 ) with class III-IV CHF and left ventricular ejection fraction ( LV EF ) < 40 % due to ischemic heart disease ( IHD ) , dilated cardiomyopathy ( DCMP ) , or arterial hypertension ( AH ) after compensation of HF before discharge were distributed into groups of low ( NT-proBNP < 1400 picog/ml , n=30 ) or high ( NT-proBNP more or equal 1400 picog/ml , n=70 ) risk . High risk patients were r and omized into 2 treatment groups : NT-proBNP based ( group I , n=35 ) and st and ard ( group II , n=35 ) therapy . At study closure we formed another group consisting of group I and II participants noncomplaint with study protocol ( group NC , n=10 ) . Groups practically did not differ by main clinical functional characteristics . Aim of treatment was lowering of NT-proBNP level below 1000 picog/ml or more or equal 50 % from baseline . At discharge median NT-proBNP concentration was 3750.0 ( 2224.0 ; 6613.0 ) , 2783.0 ( 2021.5 ; 4827.5 ) , and 2162.0 ( 1684.5 ; 5750.0 ) picog/ml in groups I , II , and NC , respectively ( = 0.315 ) . RESULTS At study entry all group I and II patients received combination of angiotensin converting enzyme inhibitors or angiotensin receptor blockers , -adrenoblockers , antagonists of mineralocorticoid receptors . After 6 months changes of doses of neuro-hormonal modulators in group I were more pronounced than in group II . NT-proBNP concentration decreased by 53 % down to 1585.5 ( 976,6 ; 2742,5 ) picog/ml , = 0.001 , and by 10.2 % in groups I and II , respectively ( between group = 0.001 ) . In group I compared with II we observed more pronounced improvement of clinical functional indicators , quality of life , and parameters of systolic and diastolic LV function ( < 0.05 ) , fewer cardiovascular deaths ( 4 vs. 10 , = 0.033 ) and repeat decompensations and rehospitalizations because CHF ( 4 vs. 14 , = 0.007 ) . CONCLUSION Compared with st and ard therapy long-term NT-proBNP guided treatment of high risk patients significantly significantly decreased rate of CV deaths and repeat decompensations and rehospitalizations because CHF , and more effectively influenced clinical and functional state , quality of life and main echocardiographical parameters of LV systolic and diastolic function BACKGROUND R and omized clinical trials have shown that newly discharged and symptomatic patients with chronic heart failure ( CHF ) benefit from follow-up in a specialized heart failure clinic ( HFC ) . Clinical stable and educated patients are usually discharged from the HFC when on optimal therapy . It is unknown if risk stratification using natriuretic peptides could identify patients who would benefit from longer-term follow-up . Furthermore , data on the use of natriuretic peptides for monitoring of stable patients with CHF are sparse . AIMS The aims of this study are to test the hypothesis that clinical stable , educated , and medical optimized patients with CHF with N-terminal pro-brain natriuretic peptide ( NT-proBNP ) levels > or = 1,000 pg/mL benefit from long-term follow-up in an HFC and to assess the efficacy of NT-proBNP monitoring . METHODS A total of 1,250 clinical ly stable , medically optimized , and educated patients with CHF will be enrolled from 18 HFCs in Denmark . The patients will be r and omized to treatment in general practice , to a st and ard follow-up program in the HFC , or to NT-proBNP monitoring in the HFC . The patients will be followed for 30 months ( median ) . RESULTS Data will be collected from 2006 to 2009 . At present ( March 2008 ) , 720 patients are r and omized . Results expect to be presented in the second half of 2010 . CONCLUSIONS This article outlines the design of the NorthStar study . If our hypotheses are confirmed , the results will help cardiologists and nurses in HFCs to identify patients who may benefit from long-term follow-up . Our results may also indicate whether patients with CHF will benefit from adding serial NT-proBNP measurements to usual clinical monitoring OBJECTIVES The aim of this study was to evaluate whether chronic heart failure ( HF ) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide ( NT-proBNP ) is superior to st and ard of care ( SOC ) management . BACKGROUND It is unclear whether st and ard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with st and ard management alone . METHODS In a prospect i ve single-center trial , 151 subjects with HF due to left ventricular ( LV ) systolic dysfunction were r and omized to receive either st and ard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management . The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations . Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function , assessed with echocardiography . RESULTS Through a mean follow-up period of 10 ± 3 months , a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC ( 58 events vs. 100 events , p = 0.009 ; logistic odds for events 0.44 , p = 0.02 ) ; Kaplan-Meier curves demonstrated significant differences in time to first event , favoring NT-proBNP-guided care ( p = 0.03 ) . No age interaction was found , with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects . Compared with SOC , NT-proBNP-guided patients had greater improvements in quality of life , demonstrated greater relative improvements in LV ejection fraction , and had more significant improvements in both LV end-systolic and -diastolic volume indexes . CONCLUSIONS In patients with HF due to LV systolic dysfunction , NT-proBNP-guided therapy was superior to SOC , with reduced event rates , improved quality of life , and favorable effects on cardiac remodeling . ( Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting ; NCT00351390 ) AIMS Heart failure ( HF ) is reported to have an essentially malignant prognosis that can be modified by several interventions . Most outcome data on HF are available from r and omized controlled treatment trials and longitudinal epidemiological studies . However , for a number of reasons , neither type of study have , to date , provided generalizable data on HF mortality . Furthermore , data on the prognosis of borderline left ventricular systolic dysfunction ( LVSD ) are even more limited . METHODS AND RESULTS ECHOES ( Echocardiographic Heart of Engl and Screening Study ) screened a total of 6,162 patients from a total of 10,161 invited ( 61 % response rate ) . Patients were r and omly selected from four pre-specified cohorts : the general population , diuretic users , those with a prior clinical label of HF , and a population with risk factors for HF , to identify the prevalence of HF and LVSD based on clinical assessment , ECG , and echocardiography . Causes of death during a 5 - 9 year follow-up period were recorded from routine mortality statistics . The 5-year survival rate of the general population was 93 % , compared with 69 % of those with LVSD without HF , 62 % with HF and no LVSD , and 53 % with HF plus LVSD . Survival improved significantly with increasing ejection fraction ( EF ) ( log rank test for trend , chi(2 ) = 534.5 , 1 , P < 0.0001 ) . CONCLUSION The ECHOES mortality data confirm the poor prognosis of patients suffering prevalent HF across the community with a mortality risk estimate of 9 % per year . Borderline systolic dysfunction ( EF 40 - 50 % ) on echocardiography carries a poor prognosis Hyperkalemia is a concern in heart failure ( HF ) , especially in older patients with co-morbidities . Previous studies addressing this issue have focused mainly on younger patients . This study was aim ed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy . Frequency and predictors of hyperkalemia were defined in patients ( n = 566 ) participating in the Trial of Intensified versus St and ard Medical Therapy in Elderly Patients with Congestive Heart Failure , in which patients ≥60 years of age were r and omized to a st and ard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy . During an 18-month follow-up 76 patients ( 13.4 % ) had hyperkalemia ( ≥5.5 mmol/L ) and 28 ( 4.9 % ) had severe hyperkalemia ( ≥6.0 mmol/L ) . Higher baseline serum potassium ( odds ratio [ OR ] 2.92 per mmol/L ) , baseline creatinine ( OR 1.11 per 10 μmol/L ) , gout ( OR 2.56 ) , New York Heart Association ( NYHA ) class ( compared to NYHA class II , IV OR 3.08 ) , higher dosage of spironolactone at baseline ( OR 1.20 per 12.5 mg/day ) , and higher dose changes of spironolactone ( compared to no dose change : 12.5 mg , OR 1.45 ; 25 mg , OR 2.52 ; > 25 mg , OR 3.24 ) were independent predictors for development of hyperkalemia ( p < 0.05 for all comparisons ) . In conclusion , hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy . Risk is increased in patients treated with spironolactone , in addition to patient-specific risk factors such as chronic kidney disease , higher serum potassium , advanced NYHA class , and gout . Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia OBJECTIVES This study was design ed to investigate whether the addition of N-terminal pro-B-type natriuretic peptide-guided , intensive patient management ( BM ) to multidisciplinary care ( MC ) improves outcome in patients following hospitalization due to heart failure ( HF ) . BACKGROUND Patients hospitalized due to HF experience frequent rehospitalizations and high mortality . METHODS Patients hospitalized due to HF were r and omized to BM , MC , or usual care ( UC ) . Multidisciplinary care included 2 consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse . In addition , BM included intensified up-titration of medication by HF specialists in high-risk patients . NT-proBNP was used to define the level of risk and to monitor wall stress . This monitoring allowed for anticipation of cardiac decompensation and adjustment of medication in advance . RESULTS A total of 278 patients were r and omized in 8 Viennese hospitals . After 12 months , the BM group had the highest proportion of antineurohormonal triple-therapy ( difference among all groups ) . Accordingly , BM reduced days of HF hospitalization ( 488 days ) compared with the hospitalization for the MC ( 1,254 days ) and UC ( 1,588 days ) groups ( p < 0.0001 ; significant differences among all groups ) . Using Kaplan-Meier analysis , the first HF rehospitalization ( 28 % ) was lower in the BM versus MC groups ( 40 % ; p = 0.06 ) and the MC versus UC groups ( 61 % ; p = 0.01 ) . Moreover , the combined end point of death or HF rehospitalization was lower in the BM ( 37 % ) than in the MC group ( 50 % ; p < 0.05 ) and in the MC than in the UC group ( 65 % ; p = 0.04 ) . Death rate was similar between the BM ( 22 % ) and MC groups ( 22 % ) , but was lower compared with the UC group ( 39 % ; vs. BM : p < 0.02 ; vs. MC : p < 0.02 ) . CONCLUSIONS Compared with MC alone , additional BM improves clinical outcome in patients after HF hospitalization . ( BNP Guided Care in Addition to Multidisciplinary Care ; NCT00355017 ) STUDY OBJECTIVES Pulmonary arterial hypertension ( PAH ) leads to substantial morbidity and mortality . Noninvasive parameters in the follow-up assessment of PAH could be helpful in clinical decision making . The brain natriuretic peptide ( BNP ) has been shown to correlate with the functional status and prognosis of these patients and could be a valuable parameter in this respect . The aim of our study was to investigate whether BNP levels could reflect clinical and hemodynamic changes , including the response to therapy during long-term follow-up in patients with PAH . STUDY DESIGN We measured pulmonary hemodynamics , functional parameters including the 6-min walk distance ( 6MWD ) , and plasma BNP levels at baseline and after a mean ( + /- SEM ) follow-up period of 12.6 + /- 1.5 months in patients with PAH . RESULTS In group A ( n = 18 ) , with decreasing BNP levels mean pulmonary artery pressure ( PAP ) and pulmonary vascular resistance ( PVR ) decreased ( PAP , 60.89 + /- 3.44 to 53.47 + /- 3.24 mm Hg ; PVR , 1,207.47 + /- 111.75 to 942.35 + /- 103.15 dyne.s.cm(-5 ) ; p < 0.01 ) and 6MWD increased ( 408.24 + /- 29.57 to 470 + /- 25.54 m ; p < 0.01 ) . In group B ( n = 12 ) , with increasing BNP levels mean PAP and PVR increased ( PAP , 52 + /- 3.31 to 60.17 + /- 5.03 mm Hg ; PVR , 946.13 + /- 115.35 to 1,236.6 + /- 180.23 dyne . s . cm(-5 ) ; p < 0.01 ) and mean 6MWD decreased from 463.64 + /- 27.77 to 367.27 + /- 38.87 m ( p < 0.05 ) . Comparing groups revealed statistically significant differences regarding changes in PAP ( group A , -11.58 + /- 3.57 % ; group B , + 13.29 + /- 5.44 % ; p = 0.001 ) and PVR ( group A , -19.21 + /- 5.87 % , group B , + 30.35 + /- 7.72 % ; p < 0.001 ) . Correlations existed between the changes in BNP levels and pulmonary hemodynamics . CONCLUSION We concluded that BNP levels parallel changes in pulmonary hemodynamics and functional parameters , including the 6MWD , in PAH patients . Consequently , we suggest BNP as a parameter for the follow-up assessment of PAH patients BACKGROUND Heart failure and left ventricular systolic dysfunction ( LVSD ) are increasingly common disorders , with outcomes worse than many cancers . Evidence -based therapies , such as ACE inhibitors and beta-blockers , improve prognosis and symptoms , and reduce healthcare expenditure . However , despite the high prevalence and malignant prognosis , few studies have reported the impact of heart failure and LVSD on overall quality of life and , more crucially , have not research ed the elderly or those in the community . METHODS All patients attending the Echocardiographic Heart of Engl and Screening ( ECHOES ) study of the prevalence of heart failure and LVSD in the community were assessed by clinical history and examination , electrocardiogram and echocardiography , and also completed the SF36 health status question naire . Quality of life in patients found to have heart failure , LVSD , and other cardiac and medical conditions are compared with the r and omly selected general population sample . Data are generalisable to the UK . RESULTS 6162 people in the community were screened in the ECHOES study , of whom 5961 ( 97 % ) completed the SF36 . The health perceptions of 3850 people aged 45 years or older selected r and omly from the population were compared with those of 426 patients diagnosed as having definite heart failure . Those with heart failure had significant impairment of all the measured aspects of physical and mental health , in addition to declines in physical functioning . Significantly worse impairment was found in those with more severe heart failure by NYHA class : indeed , NYHA functional class was closely correlated to SF36 score . Patients with asymptomatic left ventricular dysfunction and patients rendered asymptomatic by treatment had similar scores to the r and om population sample . Those with heart failure reported more severe physical impairment of quality of life than people giving a history of chronic lung disease or arthritis , with less impact on mental health than patients reporting depression . CONCLUSIONS Patients with heart failure have statistically significant impairment of all aspects of quality of life , not simply physical functioning . The physical ( role and functioning ) health burden was significantly greater than that suffered in other serious common chronic disorders , whether cardiac or other systems . Optimising treatment to improve NYHA class appears to improve perceptions of quality of life for patients with heart failure . Given the dramatic decline in quality of life with heart failure , this end-point should be a much more important target for healthcare interventions , especially treatments such as ACE inhibitors and beta-blockers that are shown to improve quality of life Background To investigate whether B-type natriuretic peptide (NP)-guided treatment of heart failure ( HF ) patients improved their health related quality of life ( Hr-QoL ) compared to routine HF treatment , and whether changes in Hr-QoL differed depending on whether the patient was a responder to NP-guided therapy or not . Methods A secondary analysis of the UPSTEP- study , a Sc and inavian multicentre study using a prospect i ve , r and omized , open , blinded evaluation design on patients with HF with New York Heart Association ( NYHA ) class II-IV . NP-guiding was aim ed to reduce BNP < 150 ng/L if < 75 years or BNP < 300 ng/L if > 75 years . A responder was defined as a patient with a BNP < 300 ng/L and /or a decrease in BNP of at least 40 % in week 16 compared to study start . Short form-36 ( SF-36 ) was used to measure Hr-QoL. At the study start , 258 patients presented evaluable SF-36 question naires , 131 in the BNP group and 127 in the control group . At the study end 100 patients in the NP-guided group and 98 in the control group , presenting data from both the study start and the study end . Results There were no significant differences in Hr-QoL between NP-guided HF treatment and control group ; however significant improvements could be seen in four of the eight domains in the NP-guided group , whereas in the control group improvements could be seen in six of the domains . Among the responders improvements could be noted in four domains whereas in the non-responders improvements could be seen in only one domain evaluating within group changes . Conclusions Improved Hr-QoL could be demonstrated in several of the domains in both the NP-guided and the control group . In the responder group within group analyses showed more increased Hr-QoL compared to the non-responder group . However , all groups demonstrated increase in CONTEXT It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide ( BNP ) is superior to symptom-guided therapy . OBJECTIVE To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy . DESIGN , SETTING , AND PATIENTS R and omized controlled multicenter Trial of Intensified vs St and ard Medical Therapy in Elderly Patients With Congestive Heart Failure ( TIME-CHF ) of 499 patients aged 60 years or older with systolic heart failure ( ejection fraction < or = 45 % ) , New York Heart Association ( NYHA ) class of II or greater , prior hospitalization for heart failure within 1 year , and N-terminal BNP level of 2 or more times the upper limit of normal . The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerl and and Germany between January 2003 and June 2008 . INTERVENTION Uptitration of guideline -based treatments to reduce symptoms to NYHA class of II or less ( symptom-guided therapy ) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less ( BNP-guided therapy ) . MAIN OUTCOME MEASURES Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured vali date d question naires . RESULTS Heart failure therapy guided by N-terminal BNP and symptom-guided therapy result ed in similar rates of survival free of all-cause hospitalizations ( 41 % vs 40 % , respectively ; hazard ratio [ HR ] , 0.91 [ 95 % CI , 0.72 - 1.14 ] ; P = .39 ) . Patients ' quality -of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies . Compared with the symptom-guided group , survival free of hospitalization for heart failure , a secondary end point , was higher among those in the N-terminal BNP-guided group ( 72 % vs 62 % , respectively ; HR , 0.68 [ 95 % CI , 0.50 - 0.92 ] ; P = .01 ) . Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older ( P < .02 for interaction ) CONCLUSION Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N43596477 Aims Heart failure ( HF ) management is complicated by difficulties in clinical assessment . Biomarkers may help guide HF management , but the correspondence between clinical evaluation and biomarker serum levels has hardly been studied . We investigated the correlation between biomarkers and clinical signs and symptoms , the influence of patient characteristics and comorbidities on New York Heart Association ( NYHA ) classification and the effect of using biomarkers on clinical evaluation . Methods and results This post-hoc analysis comprised 622 patients ( 77 ± 8 years , 76 % NYHA class ≥3 , 80 % LVEF ≤45 % ) participating in TIME-CHF , r and omising patients to either NT-proBNP-guided or symptom-guided therapy . Biomarker measurements and clinical evaluation were performed at baseline and after 1 , 3 , 6 , 12 and 18 months . NT-proBNP , GDF-15 , hs-TnT and to a lesser extent hs-CRP and cystatin-C were weakly correlated to NYHA , oedema , jugular vein distension and orthopnoea ( ρ-range : 0.12–0.33 ; p < 0.01 ) . NT-proBNP correlated more strongly to NYHA class in the NT-proBNP-guided group compared with the symptom-guided group . NYHA class was significantly influenced by age , body mass index , anaemia , and the presence of two or more comorbidities . Conclusion In HF , biomarkers correlate only weakly with clinical signs and symptoms . NYHA classification is influenced by several comorbidities and patient characteristics . Clinical judgement seems to be influenced by a clinician ’s awareness of NT-proBNP concentrations OBJECTIVES The aim of this research was to describe N-terminal part of the pro-B-type natriuretic peptide ( NT-proBNP ) levels over time in non-ST-segment elevation acute coronary syndromes ( NSTEACS ) , to eluci date factors associated with changes of NT-proBNP levels , and to examine association with long-term mortality . BACKGROUND The NT-proBNP levels are associated with mortality . Long-term temporal changes of NT-proBNP levels and their relation to other factors have not been examined . METHODS The NT-proBNP was analyzed at r and omization and at 48 h , after 6 weeks , 3 and 6 months in NSTEACS patients enrolled in the Fragmin and fast Revascularisation during InStability in Coronary artery disease (FRISC)-II trial . The NT-proB-type natriuretic peptide was analyzed at least three time points in 1,216 patients . RESULTS The median NT-proBNP level , which at r and omization was 529 ng/l , decreased throughout the whole sampling period to 238 ng/l at six months . Elevated troponin T , C-reactive protein , and female gender were associated with higher reduction rates , and high age , diabetes , previous myocardial infa rct ion , treatment with diuretics , and nitrates on admission with lower reduction rates . At each time point , the NT-proBNP level was predictive of the two-year mortality . However , the adjusted odds ratio increased for each time point . CONCLUSIONS The initial rise of NT-proBNP in NSTEACS is mainly reversible . Factors associated with less reversibility are related to chronically impaired left ventricular function , and factors associated with greater reversibility are related to the acute myocardial damage . The NT-proBNP level measured during a chronic , relatively stable phase is a better predictor of mortality than during an acute unstable phase . The clinical setting and timing of measurement will be important to consider when using NT-proBNP for risk assessment BACKGROUND Little is known about the management of elderly patients with congestive heart failure ( CHF ) although they represent the majority of the CHF population . Therefore , the TIME-CHF study was set up ( 1 ) to evaluate the medical management of very old patients ( > or = 75 years ) with CHF compared with younger patients ( 60 - 74 years ) , ( 2 ) to compare an intensified with a st and ard treatment approach , and ( 3 ) to differentiate between systolic and diastolic dysfunction ( ejection fraction < or = 45 % vs > 45 % ) . METHODS In a prospect i ve single-blinded multicenter trial , 824 symptomatic patients , CHF hospitalization within the last year and elevated NT-BNP , are r and omized to an intensified versus a st and ard medical therapy . Treatment strategies follow the published guidelines with the aim to reduce symptoms to NYHA class < or = II ( st and ard ) or , additionally , NT-BNP levels below twice the upper limit of normal ( intensified ) . The primary end points are 18-month hospitalization-free survival and quality of life . RESULTS By the end of 2004 , 297 patients have been included , 147 r and omized to intensified and 150 to st and ard therapy . Mean age in the older age group was 82 + /- 4 years ( n = 174 ) and 69 + /- 4 years in the younger group ( n = 123 ) , respectively . Ejection fraction was > 45 % in 26 % and 10 % , respectively . Significant comorbidities were present in 93 % of patients . CONCLUSION TIME-CHF will be the first prospect i ve r and omized trial to comprehensively study the management of elderly patients with CHF . It will provide unique information comparing two treatment strategies in two age groups irrespective of ejection fraction regarding prognosis , quality of life , as well as re source utilization and costs BACKGROUND Although brain natriuretic peptide ( BNP ) and E/Ea are closely related in heart failure ( HF ) patients and may be helpful to guide HF therapy , the response of E/Ea to changes in BNP over several weeks of intensive HF treatment optimisation is unknown . This study was design ed to investigate this relationship . METHODS AND RESULTS In 17 patients with decompensated HF , treatment was titrated to reduce the NT-proBNP level to < 200pg/mL over 10 weeks . Paired NT-proBNP measurements and echocardiograms were performed at two weekly intervals during the study . Treatment titration was associated with a reduction in E/Ea ( 17.6+/-6.8S.D. to 13.7+/-5.0S.D. , p=0.018 ) in keeping with the reduction in NT-proBNP ( median 603 [ S.E. 561 ] to 311 [ S.E. 235 ] , p=0.045 ) . This relationship remained in those who responded to titration ( reduction in NT-proBNP of > or=50 % ) , and those who did not . The overall change in E/Ea was similar to the changes observed in NT-proBNP in each group however there appeared to be temporal differences in the changes in E/Ea and NT-proBNP . CONCLUSION This pilot study demonstrates that the E/Ea decreases after NT-proBNP guided HF therapy . E/Ea may be a complementary target for HF therapy optimisation ; this hypothesis should be further evaluated in larger scale r and omised trials BACKGROUND Accurate data for prevalence rates for heart failure due to various causes , and for left-ventricular systolic dysfunction in all adults are unavailable . Our aim was to assess prevalence of left-ventricular systolic dysfunction and heart failure in a large representative adult population in Engl and . METHODS Of 6286 r and omly selected patients aged 45 years and older , 3960 ( 63 % ) participated in the study . They came from 16 r and omly selected general practice s. We assessed patients by history and examination , electrocardiography , and echocardiography . Prevalence of left-ventricular systolic dysfunction ( defined as ejection fraction < 40 % ) and heart failure was calculated for the overall population on the basis of strict criteria and , when necessary , adjudication by a panel . FINDINGS Left-ventricular systolic dysfunction was diagnosed in 72 ( 1.8 % [ 95 % CI 1.4 - 2.3 ] ) participants , half of whom had no symptoms . Borderline left-ventricular function ( ejection fraction 40 - 50 % ) was seen in 139 patients ( 3.5 % [ 3.0 - 4.1 ] ) . Definite heart failure was seen in 92 ( 2.3 % , [ 1.9 - 2.8 ] ) and was associated with an ejection fraction of less than 40 % in 38 ( 41 % ) patients , atrial fibrillation in 30 ( 33 % ) , and valve disease in 24 ( 26 % ) . Probable heart failure was seen in a further 32 ( 0.8 % [ 0.6 - 1.1 ] ) patients . In total , 124 ( 3.1 % [ 2.6 - 3.7 ] ) patients aged 45 years or older had definite or probable heart failure . INTERPRETATION Heart failure is often misdiagnosed or underdiagnosed in primary care . Our results suggest that assessment of left-ventricular function in patients with suspected heart failure could lead to more effective diagnosis and treatment of this disorder We aim ed to study the potential influence of the variability in the assessment of echocardiographically measured left ventricular ejection fraction ( LVEF ) on indications for the implantation of internal cardioverter defibrillator and /or cardiac resynchronization devices in heart failure patients . TIME-CHF was a multicenter trial comparing NT-BNP versus symptom-guided therapy in patients aged ≥60 years . Patients had their LVEF assessed at the recruiting centre using visual assessment , the area-length or biplane Simpson ’s method . Echocardiographic data were transferred to the study core-lab for re- assessment . Re- assessment in the core-lab was done with biplane Simpson ’s method , and included an appraisal of image quality . 413 patients had the LVEF analyzed at the recruiting centre and at the core lab . Image quality was optimal in 191 and suboptimal in 222 . Overall , the correlation between LVEF at the recruiting centres and at the core-lab was good , independent of image quality ( R² = 0.62 ) . However , when a LVEF ≤30 % or ≥30 % was used as a cut-off , about 20 % of all patients would have been re-assigned to having either a LVEF above or below the cut-off , this proportion was not significantly influenced by image quality . We conclude that correlation between LVEF assessed by different centres based on the same ultrasound data is good , regardless of image quality . However , one fifth of patients would have been re-assigned to a different category when using the clinical ly important cut-off of 30 % BACKGROUND STARBRITE , a multicenter r and omized pilot trial , tested whether outpatient diuretic management guided by B-type natriuretic peptide ( BNP ) and clinical assessment result ed in more days alive and not hospitalized over 90 days compared with clinical assessment alone . METHODS AND RESULTS A total of 130 patients from 3 sites with left ventricular ejection fraction ≤35 % were enrolled during hospitalization for heart failure ( HF ) and r and omly assigned to therapy guided by BNP and clinical assessment ( BNP strategy ) or clinical assessment alone . The clinical goal was resolution of congestion without hypotension or renal dysfunction . In the BNP arm , therapy was adjusted to achieve optimal fluid status , defined as the BNP level and congestion score obtained at the time of discharge . In the clinical assessment arm , therapy was titrated to achieve optimal fluid status , represented by the patient 's signs and symptoms at the time of discharge . Exclusion criteria were serum creatinine > 3.5 mg/dL and acute coronary syndrome . Follow-up was done in HF clinics . BNP was measured with the use of a rapid assay test . There was no significant difference in number of days alive and not hospitalized ( hazard ratio 0.72 , 95 % confidence interval 0.41 - 1.27 ; P = .25 ) , change in serum creatinine , or change in systolic blood pressure ( SBP ) . BNP strategy was associated with a trend toward a lower blood urea nitrogen ( 24 mg/dL vs 29 mg/dL ; P = .07 ) ; BNP strategy patients received significantly more angiotensin-converting enzyme ( ACE ) inhibitors , beta-blockers , and the combination of ACE inhibitor or angiotensin receptor blocker plus beta-blockers . CONCLUSIONS BNP strategy was not associated with more days alive and not hospitalized , but the strategy appeared to be safe and was associated with increased use of evidence -based medications OBJECTIVES This study aim ed to assess cost-effectiveness of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided versus symptom-guided therapy in heart failure ( HF ) patients ≥60 years old . BACKGROUND Cost-effectiveness of NT-proBNP guidance in HF patients is unclear . It may create additional costs with uncertain benefits . METHODS In the TIME-CHF ( Trial of Intensified versus St and ard Medical Therapy in Elderly Patients with Congestive Heart Failure ) , patients with left ventricular ejection fraction ( LVEF ) of ≤45 % were r and omized to receive intensified NT-proBNP-guided therapy or st and ard , symptom-guided therapy . For cost-effectiveness analysis , 467 ( 94 % ) patients ( age 76 ± 7 years , 66 % male ) were eligible . Incremental cost-effectiveness was calculated as incremental costs per gained life-year and quality -adjusted life-year ( QALY ) within the 18-month trial period , as defined per protocol . RESULTS NT-proBNP-guided therapy was dominant ( i.e. , more effective and less costly ) over symptom-guided therapy , saving $ 2,979 USD ( 2.5 to 97.5 % confidence interval [ CI ] : $ 8,758 to $ 3,265 ) per patient , with incremental effectiveness of + 0.07 life-years and + 0.05 QALYs . The probability of NT-proBNP-guided therapy being dominant was 80 % , and the probability of saving 1 life-year or QALY at a cost of $ 50,000 was 97 % and 93 % , respectively . Exclusion of residence costs result ed in an incremental cost-effectiveness ratio ( ICER ) of $ 5,870 per life-year gained . Cost-effectiveness of NT-proBNP-guided therapy was most pronounced in patients < 75 years old and in those with < 2 significant comorbidities , being dominant in all sensitivity analyses . In the worst-case scenario ( excluding residence costs in those with ≥2 comorbidities ) , the ICER was $ 11,935 per life-year gained . CONCLUSIONS NT-proBNP-guided therapy has a high probability of being cost effective in HF patients with reduced LVEF , particularly in patients age 60 to 75 years or with less than 2 comorbidities . ( Trial of Intensified versus st and ard Medical therapy in Elderly patients with Congestive Heart Failure [ TIME-CHF ] ; IS RCT N43596477 ) BACKGROUND Serious adverse events ( SAEs ) from heart failure ( HF ) therapy are frequent ; however , techniques to identify at-risk patients are inadequate . Furthermore , the relationship between SAEs , quality of life ( QOL ) , and cardiac structure are unknown . METHODS AND RESULTS 151 symptomatic patients with systolic HF were followed for a mean of 10 months . In this post hoc analysis , treatment-related SAEs included acute renal failure , dizziness , hypo/hyperkalemia , hypotension , and syncope . At 1 year , 21 treatment-related SAEs occurred . No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the st and ard of care arm ( P = .20 ) . At baseline , patients who suffered SAEs were less likely to be receiving beta-blockers ( 85.7 % vs 97.7 % ; P = .009 ) and had worse functional class and lower chloride levels . Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Question naire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period . Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction ; patients in the highest risk quartile had the shortest time to first cardiovascular event ( P = 0.01 ) . CONCLUSIONS NT-proBNP-guided HF care is safe . Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling . A risk score to prospect ively predict SAEs in aggressive HF management was developed BACKGROUND This study aim ed to explore the feasibility of guiding the application of metoprolol succinate in patients with moderate to severe heart failure ( HF ) through monitoring plasma brain natriuretic peptide ( BNP ) levels . METHODS A total of 195 patients with moderate to severe HF ( NYHA Functional Class III to IV ) were selected and r and omized into two groups : an observation group and a BNP group . The groups were established to observe the clinical conditions and establish plasma BNP levels to guide the application of metoprolol succinate . The average start-up of metoprolol succinate and average dose of metoprolol succinate after one month , as well as the recurrence rate and mortality of HF during hospital stay were compared between the two groups . RESULTS Start-up of metoprolol succinate was shorter in the BNP group than in the observation group [ ( 5.89 ± 1.76 ) d vs. ( 7.03 ± 2.08 ) d , p < 0.01 ] , but no significant differences in recurrence rate ( 26.60 % vs. 23.91 % , p > 0.05 ) and mortality ( 6.38 % vs. 5.43 % , p > 0.05 ) of HF were observed between the two groups . The average dose of metoprolol succinate after one month was higher in the BNP group compared with that of the observation group [ ( 47.65 ± 13.09 ) mg/d vs. ( 35.08 ± 11.08 ) mg/d , p < 0.01 ] . CONCLUSIONS Although monitoring plasma BNP might have limited the clinical impact on the change of left ventricular ejection fraction , recurrence of HF or mortality within 1 month , it could safely facilitate early use and up-titration of the metoprolol succinate in patients with moderate to severe HF . KEY WORDS BNP ; Heart failure ; β receptor blocker BACKGROUND Serial measurements of N-terminal pro-B type natriuretic peptide ( NT-proBNP ) provide prognostic information in patients with chronic heart failure ( HF ) . Changes in NT-proBNP concentrations parallel prognosis ; however , it remains unclear whether HF care with a goal to maximize medical therapy and also lower NT-proBNP concentrations is superior to st and ard HF care alone . AIMS The aim of the study was to evaluate the hypothesis that an HF strategy guided by NT-proBNP reduces cardiovascular events compared to st and ard of care HF management . METHODS In a prospect i ve r and omized single-center trial , subjects with New York Heart Association class II to IV systolic HF ( left ventricular ejection fraction < or = 40 % ) will be enrolled . Both groups will receive st and ard HF management ( with a goal for minimizing HF symptoms and achieving maximal dosages of therapies with proven mortality benefit in HF ) , whereas one group ( " NT-proBNP " ) will also have treatment adjustments to reduce NT-proBNP concentrations < or = 1,000 pg/mL. The primary end point of the trial is total cardiovascular events for a 1-year period ; secondary end points will include effects of NT-proBNP-guided care on cardiac structure and function , quality of life , and total costs of care . RESULTS Enrollment began in 2006 ; of the original 300 planned , thus far , 151 subjects have been r and omized . Interim analysis in November 2009 indicated significant reduction of events in the NT-proBNP arm . Full results are expected in 2010 . CONCLUSIONS The Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy ( PROTECT ) Study will test the hypothesis that therapy guided by NT-proBNP concentrations will be superior to st and ard of care HF management ( www . clinical trials.gov identifier NCT00351390 ) AIMS We sought to determine if heart failure ( HF ) care with a goal to lower N-terminal pro B-type natriuretic peptide ( NT-proBNP ) concentrations , compared with st and ard of care ( SOC ) management , is associated with improvement in echocardiographic parameters of cardiac structure and function . METHODS AND RESULTS Of 151 subjects with HF due to left ventricular systolic dysfunction ( LVSD ) prospect ively r and omized to NT-proBNP-guided vs. SOC HF care , 116 had serial echocardiographic data . Endpoints in this echocardiographic study included the relationship between change in NT-proBNP and LV reverse remodelling , as well as associations between biomarker-guided therapy and measures of diastolic function , right ventricular ( RV ) size and function , estimates of LV filling pressure and RV systolic pressure ( RVSP ) , and the degree of mitral regurgitation ( MR ) . After a mean of 10 months of study procedures , in adjusted analyses , final NT-proBNP concentrations predicted risk of remodelling [ hazard ratio ( HR ) ↑LV end-diastolic volume index = 1.43 , 95 % confidence interval ( CI ) 1.10 - 1.86 , P = 0.007 ; HR ↑LV end-systolic volume index = 1.54 , 95 % CI 1.10 - 1.91 , P = 0.01 ; HR ↓LV ejection fraction ( LVEF ) = 1.53 , 905 % CI 1.12 - 1.89 , P = 0.02 ] . In addition to greater improvement in LVEF and reductions in LV volume , compared with SOC , NT-proBNP-guided patients showed significant decreases in the ratio of early transmitral peak velocity to early diastolic peak annular velocity ( E/E ' ) , pulmonary vein peak S velocity , RV fractional area change , RVSP , and MR severity . CONCLUSION NT-proBNP concentrations may serve as a non-invasive indicator of the state of cardiac structure and function in HF due to LVSD . Multiple , prognostically meaningful echocardiographic variables improved more significantly in patients treated with NT-proBNP-guided care vs. SOC AIMS This study was design ed to evaluate a new NT-proBNP monitoring concept in out patients with systolic heart failure ( HF ) . METHODS AND RESULTS This was a multicentre , prospect i ve r and omized open-label blinded endpoint study . A total of 407 systolic HF patients were allocated to either clinical management ( n = 208 ) or clinical management + NT-proBNP monitoring ( n = 199 ) and followed for 2.5 years . If NT-proBNP increased > 30 % , a clinical checklist was completed and treatment initiated . The patients were matched at r and omization and were 73 years old , 25 % were females , 85 % were NYHA class I-II , LVEF was 30 % , and NT-proBNP 1955 pg/mL. NT-proBNP monitoring did not improve outcome , the hazard ratio for the primary composite endpoint ( death or a cardiovascular admission ) being 0.96 [ 95 % confidence interval ( CI ) 0.71 - 1.29 , P = 0.766 ] . NT-proBNP monitoring did not induce a significant change in the pharmacological strategy ( P > 0.05 for all comparisons ) . In patients in whom NT-proBNP increased > 30 % ( 25 % of the patients ) during follow-up , a higher frequency of admission ( 69 % vs. 47 % , P = 0.002 ) , a higher number of admission days ( 14 vs. 5 days , P = 0.003 ) and number of admissions ( 2 vs. 1 , P = 0.009 ) , and a lower quality of life ( P = 0.032 ) and a poorer functional class ( 37 % vs. 18 % in NYHA class III-IV , P < 0.001 ) were observed . CONCLUSIONS Adding serial measurements of NT-proBNP to optimal clinical management was not associated with a change in pharmacological strategy and did not improve outcome . However , survivors in whom NT-proBNP increased > 30 % showed a poorer functional class , clinical outcome , and quality of life . TRIAL REGISTRATION www.centerwatch : 173491 ( NorthStar ) BACKGROUND Although echocardiography is the gold st and ard test for suspected left ventricular dysfunction , its cost and availability limits its use as a routine screening tool . The high negative predictive value of B-natriuretic peptide ( BNP ) in dyspneic patients suggests its possible utility in screening patients prior to echocardiography . Determining an appropriate BNP level below which the need for echocardiography is precluded would be valuable . We hypothesized that a fixed plasma BNP level of 20 pg/mL and simple clinical parameters are an effective pre-echocardiographic screening tool for left ventricular dysfunction . METHODS Two hundred and two patients at a Veterans Administration facility with symptoms suggestive of heart disease ( male to female ratio 193:9 , mean age 65 years ) were screened prior to echocardiography . Patients with known cardiac dysfunction were excluded . RESULTS BNP levels of > or = 20 pg/mL were 79 % sensitive and 44 % specific in screening for any abnormality of ventricular function . The negative predictive value was 69 % . When broken down into categories of dysfunction , the cutoff point of 20 pg/mL had a better negative predictive value for those with systolic dysfunction ( 96 % ) or systolic plus diastolic dysfunction ( 100 % ) if patients with diastolic dysfunction were excluded . The majority of patients with falsely low BNP levels ( < 20 pg/mL with positive echocardiographic findings ) had mild diastolic dysfunction , with 3 patients exhibiting mild systolic dysfunction . CONCLUSIONS BNP may be a useful screening tool for left ventricular dysfunction in patients with history suggestive of heart disease and be used to assist in forming a pretest probability , which in turn could greatly assist in appropriateness of patient referral and in optimization of drug therapy B-type natriuretic peptide ( BNP ) is a cardiac neurohormone used as a noninvasive tool for diagnosing and monitoring heart failure . Beta blockers have beneficial effects in patients with heart failure as well as a direct effect on BNP plasma levels . The aim of this study is to compare the efficacy of a BNP-guided approach vs. st and ard care on beta-blocker titration in heart failure patients . Forty-one patients with heart failure were r and omized into a clinical trial . Bisoprolol was started , and the dose was regularly up-titrated . BNP was measured monthly . The clinical group had beta-blocker dosage increased according to st and ard care , whereas the BNP group had beta-blocker dosage up-titrated according to plasma BNP levels plus st and ard care . The primary outcome was mean beta-blocker dose achieved after 3 months . BNP levels , left ventricular ejection fraction , clinical score , quality of life , and hospitalization were collected in all patients . BNP-guided up-titration of beta blocker in ambulatory patients with heart failure did not result in higher doses of beta blocker at the end of 3 months+/-SD ( 5.9+/-4.3 mg vs. 4.4+/-3.4 mg , p=0.22 ) . Left ventricular ejection fraction was significantly improved in both groups by 7.3 % ( 95 % confidence interval , 4.1%-10.4 % ; p<0.0001 ) . A trend toward better quality of life was seen in the BNP group IMPORTANCE Prevention strategies for heart failure are needed . OBJECTIVE To determine the efficacy of a screening program using brain-type natriuretic peptide ( BNP ) and collaborative care in an at-risk population in reducing newly diagnosed heart failure and prevalence of significant left ventricular ( LV ) systolic and /or diastolic dysfunction . DESIGN , SETTING , AND PARTICIPANTS The St Vincent 's Screening to Prevent Heart Failure Study , a parallel-group r and omized trial involving 1374 participants with cardiovascular risk factors ( mean age , 64.8 [ SD , 10.2 ] years ) recruited from 39 primary care practice s in Irel and between January 2005 and December 2009 and followed up until December 2011 ( mean follow-up , 4.2 [ SD , 1.2 ] years ) . INTERVENTION Patients were r and omly assigned to receive usual primary care ( control condition ; n=677 ) or screening with BNP testing ( n=697 ) . Intervention-group participants with BNP levels of 50 pg/mL or higher underwent echocardiography and collaborative care between their primary care physician and specialist cardiovascular service . MAIN OUTCOMES AND MEASURES The primary end point was prevalence of asymptomatic LV dysfunction with or without newly diagnosed heart failure . Secondary end points included emergency hospitalization for arrhythmia , transient ischemic attack , stroke , myocardial infa rct ion , peripheral or pulmonary thrombosis/embolus , or heart failure . RESULTS A total of 263 patients ( 41.6 % ) in the intervention group had at least 1 BNP reading of 50 pg/mL or higher . The intervention group underwent more cardiovascular investigations ( control , 496 per 1000 patient-years vs intervention , 850 per 1000 patient-years ; incidence rate ratio , 1.71 ; 95 % CI , 1.61 - 1.83 ; P<.001 ) and received more renin-angiotensin-aldosterone system-based therapy at follow-up ( control , 49.6 % ; intervention , 56.5 % ; P=.01 ) . The primary end point of LV dysfunction with or without heart failure was met in 59 ( 8.7 % ) of 677 in the control group and 37 ( 5.3 % ) of 697 in the intervention group ( odds ratio [ OR ] , 0.55 ; 95 % CI , 0.37 - 0.82 ; P = .003 ) . Asymptomatic LV dysfunction was found in 45 ( 6.6 % ) of 677 control-group patients and 30 ( 4.3 % ) of 697 intervention-group patients ( OR , 0.57 ; 95 % CI , 0.37 - 0.88 ; P = .01 ) . Heart failure occurred in 14 ( 2.1 % ) of 677 control-group patients and 7 ( 1.0 % ) of 697 intervention-group patients ( OR , 0.48 ; 95 % CI , 0.20 - 1.20 ; P = .12 ) . The incidence rates of emergency hospitalization for major cardiovascular events were 40.4 per 1000 patient-years in the control group vs 22.3 per 1000 patient-years in the intervention group ( incidence rate ratio , 0.60 ; 95 % CI , 0.45 - 0.81 ; P = .002 ) . CONCLUSION AND RELEVANCE Among patients at risk of heart failure , BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction , diastolic dysfunction , and heart failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00921960 AIMS N-terminal pro brain natriuretic peptide ( NT-proBNP ) is a potent marker of heart failure and other cardiac diseases . The value of NT-proBNP testing in the medical emergency department ( ED ) was assessed in patients > 65 years old . METHODS AND RESULTS This large , prospect i ve , r and omized , controlled , multicentre trial was conducted in six medical EDs . Data for evaluation of the primary endpoint of hospitalization were available for 1086 patients . Median NT-proBNP was 582 pg/mL. A total of 16 % of patients presented with NT-proBNP < 150 pg/mL ( low ) , 55 % with NT-proBNP between 150 and 1800 pg/mL ( intermediate ) , and 29 % with NT-proBNP > 1800 pg/mL ( high ) . NT-proBNP was positively correlated with hospital admission [ odds ratio ( OR ) for high vs. low 2.9 , P < 0.0001 ] , length of stay ( 8.5 days vs. 3.5 days for high vs. low , P < 0.01 ) , in-hospital death ( 3.9 % vs. 0 % for high vs. low , P < 0.01 ) , 6 months re-hospitalization ( OR for high vs. low 5.1 , P < 0.0001 ) , and 6 months death or re-hospitalization ( OR for high vs. low 5.7 , P < 0.0001 ) . Knowledge of NT-proBNP had no significant effect on the primary endpoint hospital admission and the secondary endpoints intermediate/intensive care unit ( IMC/ICU ) admission , length of stay , re-hospitalization and death , or re-hospitalization in the total cohort . However , patients with high open NT-proBNP ( > 1800 pg/mL ) were more likely to be admitted to the hospital ( P < 0.05 ) and IMC/ICU ( P < 0.05 ) , whereas patients with low open NT-proBNP ( < 150 pg/mL ) were less likely to be admitted ( P < 0.05 ) compared with patients with blinded NT-proBNP . CONCLUSION Although NT-proBNP does not affect overall hospitalization , it is associated with better stratification of patient care and is strongly correlated with subsequent utilization of hospital re sources and prognosis The drug treatment of heart failure , once simple , has become complex . Apart from a loop diuretic and digoxin , most patients should now be receiving an angiotensin-converting enzyme inhibitor ( or angiotensin II receptor blocker ) , a beta-blocker and spironolactone . Newer drugs , such as endothelin-receptor antagonists and combined blockers of converting-enzyme and neutral endopeptidase , might soon become available . When to introduce these drugs and what dose is optimal for any individual , are questions that currently vex clinicians . We proposed that plasma levels of the cardiac hormone brain natriuretic peptide ( BNP , or better , its 1 - 76 amino-acid N-terminal fragment , N-BNP ) , would provide an objective index for guiding drug treatment in patients with established , stable cardiac failure . In a pilot study , 69 patients were r and omized to drug treatment based on clinical criteria , or based on plasma levels of N-BNP . After a median follow-up of 9.6 months , those in the N-BNP group had fewer clinical end-points than those in the group managed by clinical criteria alone ( 19 vs 54 ; P= 0.02 ) . These preliminary data encourage the concept that the increasingly complex pharmacotherapy for heart failure , both chronic ( as in this trial ) and acute , might best be guided by an objective measure such as plasma levels of BNP or N-BNP BACKGROUND There is currently no objective practical guide to intensity of drug treatment for individuals with heart failure . We hypothesised that pharmacotherapy guided by plasma concentrations of the cardiac peptide aminoterminal brain natriuretic peptide ( N-BNP ) would produce a superior outcome to empirical trial-based therapy dictated by clinical acumen . METHODS 69 patients with impaired systolic function ( left-ventricular ejection fraction < 40 % ) and symptomatic heart failure ( New York Heart Association class II-IV ) were r and omised to receive treatment guided by either plasma N-BNP concentration ( BNP group ) or st and ardised clinical assessment ( clinical group ) . FINDINGS During follow-up ( minimum 6-months , median 9.5 months ) , there were fewer total cardiovascular events ( death , hospital admission , or heart failure decompensation ) in the BNP group than in the clinical group ( 19 vs 54 , p=0.02 ) . At 6 months , 27 % of patients in the BNP group and 53 % in the clinical group had experienced a first cardiovascular event ( p=0.034 ) . Changes in left-ventricular function , quality of life , renal function , and adverse events were similar in both groups . INTERPRETATION N-BNP-guided treatment of heart failure reduced total cardiovascular events , and delayed time to first event compared with intensive clinical ly guided treatment OBJECTIVES The GUIDE-IT ( Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure ) study is design ed to determine the safety , efficacy , and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) level of < 1,000 pg/ml compared with usual care in high-risk patients with systolic heart failure ( HF ) . BACKGROUND Elevations in natriuretic peptide ( NP ) levels provide key prognostic information in patients with HF . Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs , and observational data show that decreases in NP levels over time are associated with favorable outcomes . Results from smaller prospect i ve , r and omized studies of this strategy thus far have been mixed , and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF . METHODS GUIDE-IT is a prospect i ve , r and omized , controlled , unblinded , multicenter clinical trial design ed to r and omize approximately 1,100 high-risk subjects with systolic HF ( left ventricular ejection fraction ≤40 % ) to either usual care ( optimized guideline -recommended therapy ) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of < 1,000 pg/ml . Patients in either arm of the study are followed up at regular intervals and after treatment adjustments for a minimum of 12 months . The primary endpoint of the study is time to cardiovascular death or first hospitalization for HF . Secondary endpoints include time to cardiovascular death and all-cause mortality , cumulative mortality , health-related quality of life , re source use , cost-effectiveness , and safety . CONCLUSIONS The GUIDE-IT study is design ed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinical ly relevant endpoints of mortality , hospitalization , quality of life , and medical re source use . ( Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [ GUIDE-IT ] ; NCT01685840 ) BACKGROUND Most patients with chronic heart failure ( CHF ) receive the same dose of angiotensin-converting enzyme ( ACE ) inhibitors because there is currently no measure of treatment efficacy . We sought to determine whether titration of vasodilator therapy according to plasma brain natriuretic peptide ( BNP ) concentration may be of value in the individual optimization of vasodilator therapy in CHF . METHODS AND RESULTS Twenty patients with mild to moderate CHF receiving stable conventional therapy including an ACE inhibitor were r and omly assigned to titration of ACE inhibitor dosage according to serial measurement of plasma BNP concentration ( BNP group ) or optimal empirical ACE inhibitor therapy ( clinical group ) for 8 weeks . Only the BNP-driven approach was associated with significant reductions in plasma BNP concentration throughout the duration of the study and a significantly greater suppression when compared with empiric therapy after 4 weeks [ -42.1 % ( -58.2 , -19.7 ) vs -12.0 % ( -31.8 , 13.8 ) , P = .03 ] . Both treatment strategies were well tolerated and associated with favorable neurohormonal and hemodynamic effects ; however , in comparison between groups , mean heart rate fell ( P = .02 ) and plasma renin activity rose ( P = .03 ) in the BNP group when compared with the clinical group . CONCLUSIONS Plasma BNP concentration may be chronically reduced by tailored vasodilator therapy in CHF . Furthermore , titration of vasodilator therapy according to plasma BNP was associated with more profound inhibition of the renin-angiotensin-aldosterone system and significant fall in heart rate when compared with empiric therapy Multibiomarker paradigms have been proposed to diagnose , define progression , and to monitor therapy of heart failure ( HF ) patients . The aim of this study was to evaluate the prognostic and therapy-monitoring potential of four novel biomarkers ( copeptin , midregional proatrial natriuretic peptide ( MR-proANP ) , neopterin , and procalcitonin ) which have been shown to be elevated in the plasma of patients with HF and reported to have prognostic value . In a prospect i ve study of 40 patients hospitalized for decompensated HF and who received nesiritide infusions as part of their care , blood was drawn before , during , and postinfusion and assayed for the novel biomarkers . B-type natriuretic peptide ( BNP ) and N-terminal pro-BNP ( NT-proBNP ) which were previously measured and reported in this cohort were also included in the analyses . All biomarkers were elevated at baseline prior to nesiritide infusion , but copeptin , MR-proANP , and NT-proBNP demonstrated significant acute reductions in plasma levels in response to therapy . Copeptin levels were higher in posthospital nonsurvivors and by proportional hazards model were associated with an increased mortality risk ( p = 0.04 ) . Procalcitonin and neopterin added no incremental information on response to therapy or risk stratification . In contrast , copeptin and MR-proANP appear to have potential for monitoring acute responses to therapy . Only copeptin and BNP contributed to risk stratification in this cohort of advanced HF patients , but the conjoint use of BNP or NT-proBNP does not appear to impact the prognostic value of copeptin alone . These results are hypothesis generating to stimulate additional investigation AIMS Treatment of chronic heart failure ( CHF ) guided by natriuretic peptides has been studied in clinical trials with conflicting results . The aim of this study was to investigate if N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy in symptomatic heart failure patients in primary care would improve clinical outcomes over and above treatment according to guidelines . METHODS AND RESULTS SIGNAL-HF was a 9 month , r and omized , single-blind , parallel group study in patients with CHF in NYHA class II-IV , ejection fraction (EF)<50 % and elevated NT-proBNP levels ( males>800 , females>1000 ng/L ) . All investigators underwent a pre- study educational programme about current CHF guidelines . A control group managed by non-trained investigators was considered not possible for ethical and practical reasons . Patients were r and omized to structured treatment of CHF according to guidelines with or without NT-proBNP monitoring . The choice and dose of therapy for CHF was at the investigator 's discretion . The primary outcome variable was the composite endpoint of days alive , days out of hospital , and symptom score from the Kansas City Cardiomyopathy Question naire . In all , 252 patients were r and omized . The allocation groups were well balanced with regards to age , NT-proBNP , and EF . Treatment doses of beta-blockers and blockers of the renin-angiotensin-aldosterone system were markedly increased towards target doses and to a similar degree in both groups . There were no differences between the groups concerning either the primary endpoint ( P=0.28 ) or its components [ cardiovascular ( CV ) death , P=0.93 ; CV hospitalization , P=0.88 ; or symptom score , P=0.28 ] . CONCLUSION NT-proBNP-guided CHF treatment did not result in important improvements in clinical outcomes in patients with CHF in primary care above and beyond what could be achieved by education and structured CHF treatment according to guidelines AIMS To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure ( HF ) and preserved LVEF ( HFpEF ) . METHODS AND RESULTS Patients with HFpEF ( LVEF > 45 % ; n = 123 ) and HF with reduced LVEF ( HFrEF ; LVEF ≤45 % ; n = 499 ) with age ≥60 years , NYHA class ≥ II , and elevated NT-proBNP ( > 400 ng/L or > 800 ng/L depending on age ) were r and omized to medical therapy titrated only to reduce symptoms to NYHA ≤II ( symptom-guided ) or also to reduce NT-proBNP below the inclusion threshold ( NT-proBNP-guided ) during a 6-month period . Patients were followed for an additional 12 months . Despite similar treatment escalation , NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF . Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF ( P = 0.02 ) , while survival and HF hospitalization-free survival did not differ . Among HFpEF patients , NT-proBNP reduction and symptom relief were similar in the symptom-guided ( n = 59 ) and NT-proBNP-guided ( n = 64 ) group despite more aggressive treatment in the NT-proBNP-guided group . In contrast to effects in HFrEF , NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF , with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival , 0.03 for survival , and 0.01 for HF hospitalization-free survival . CONCLUSIONS Outcomes in HFpEF were not better than in HFrEF , and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF . These preliminary findings suggest that , in contrast to HFrEF , NT-proBNP-guided therapy may not be beneficial in HFpEF . Trial registration IS RCT N43596477 BACKGROUND Heart failure management programmes have been shown to reduce re-hospitalizations . We recently investigated a new disease management programme comparing usual care ( UC ) to home-based nurse care ( HNC ) and a HNC group in which decision-making was based on NT-proBNP levels ( BNC ) . As re-hospitalization is the main contributing economic factor in heart failure expenditures , we hypothesized that this programme might be able to reduce costs and could be conducted cost effectively compared to UC . METHODS One hundred and ninety congestive heart failure patients , who were included in a r and omized trial to receive UC , HNC or BNC at discharge , were analysed in a cost-effectiveness model . Different models were applied to perform analysis of all medical costs , and the costs per year survived were chosen as an effectiveness parameter . RESULTS Per patient costs because of heart failure treatment in the UC and the BNC group were € 7109 ± 11,687 and € 2991 ± 4885 ( P=0·027 ) , respectively . Corrected for death as a competing risk , the costs in the UC group were € 7893 ± 11,734 and were reduced by BNC to € 3148 ± 4949 ( P=0·012 ) . Considering costs because of all-cause re-hospitalizations , calculated costs per year survived after discharge were € 19,694 ± 26,754 for UC , € 14,262 ± 25 330 for HNC ( P > 0·05 ) and € 8784 ± 14,728 for BNC ( t-test-based contrast P=0·015 ) . In all models calculated , HNC was cost neutral . CONCLUSIONS NT-BNP-guided heart failure specialist care in addition to home-based nurse care is cost effective and cheaper than st and ard care , whereas HNC is cost neutral BACKGROUND Hospital admissions for acute decompensated heart failure ( ADHF ) are frequent and are accompanied by high percentages of mortality and readmissions . Brain natriuretic peptide ( BNP ) and the inactive N-terminal fragment of its precursor proBNP ( NT-proBNP ) are currently the best predictors of prognosis in heart failure ( HF ) patients . In the setting of chronic HF , studies that performed guidance of therapy by NT-proBNP have had only limited success . For patients with ADHF , retrospective studies have shown that a reduction in NT-proBNP of ≤30 % during admission is a significant predictor of HF readmissions and mortality . These data suggest a role for NT-proBNP guidance in the setting of ADHF admissions . STUDY DESIGN The PRIMA II is an investigator-initiated , multicenter , r and omized , controlled , prospect i ve 2-arm trial that investigates the impact of inhospital guidance for ADHF treatment by a predefined NT-proBNP target ( > 30 % reduction during admission ) on the reduction of readmission and mortality rates within 180 days . Consenting ADHF patients with NT-proBNP levels of > 1,700 ng/L are eligible . After achieving clinical stability , a total of 340 patients are r and omized to either NT-proBNP-guided or conventional treatment ( 1:1 ) . The primary end point is dual , that is , a composite of all-cause mortality and readmission for HF in 180 days and the number of days alive out of hospital in 180 days . Secondary end points are readmissions and /or mortality in 180 days , cost effectiveness of hospitalization days in 180 days , readmissions and mortality in 90 days , and quality of life . CONCLUSION The PRIMA II trial aims at providing scientific evidence for the use of NT-proBNP-guided therapy compared with conventional treatment in patients admitted for ADHF OBJECTIVES The purpose of this study was to assess whether management of heart failure ( HF ) guided by an individualized N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) target would lead to improved outcome compared with HF management guided by clinical assessment alone . BACKGROUND Natriuretic peptides may be attractive biomarkers to guide management of heart failure ( HF ) and help select patients in need of more aggressive therapy . The PRIMA ( Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality ? ) study is , to our knowledge , the first large , prospect i ve r and omized study to address whether management of HF guided by an individualized target NT-proBNP level improves outcome . METHODS A total of 345 patients hospitalized for decompensated , symptomatic HF with elevated NT-proBNP levels at admission were included . After discharge , patients were r and omized to either clinical ly-guided outpatient management ( n = 171 ) , or management guided by an individually set NT-proBNP ( n = 174 ) defined by the lowest level at discharge or 2 weeks thereafter . The primary end point was defined as number of days alive outside the hospital after index admission . RESULTS HF management guided by this individualized NT-proBNP target increased the use of HF medication ( p = 0.006 ) , and 64 % of HF-related events were preceded by an increase in NT-proBNP . Nevertheless , HF management guided by this individualized NT-proBNP target did not significantly improve the primary end point ( 685 vs. 664 days , p = 0.49 ) , nor did it significantly improve any of the secondary end points . In the NT-proBNP-guided group mortality was lower , as 46 patients died ( 26.5 % ) versus 57 ( 33.3 % ) in the clinical ly-guided group , but this was not statistically significant ( p = 0.206 ) . CONCLUSIONS Serial NT-proBNP measurement and targeting to an individual NT-proBNP value did result in advanced detection of HF-related events and importantly influenced HF-therapy , but failed to provide significant clinical improvement in terms of mortality and morbidity . ( Effect of NT-proBNP Guided Treatment of Chronic Heart Failure [ PRIMA ] ; NCT00149422 ) OBJECTIVES This study was a multicenter , single-arm , double-blinded observational prospect i ve clinical trial design ed to monitor daily concentrations of B-type natriuretic peptide ( BNP ) and to determine how these concentrations correlate with acute clinical heart failure decompensation ( ADHF ) and related adverse clinical outcomes in at-risk HF patients . BACKGROUND Although BNP at discharge is predictive of 30-day outcomes , outpatient serial testing may improve the risk of detecting early decompensation . METHODS A total of 163 patients with HF signs and symptoms of ADHF discharged from the hospital or in an outpatient setting measured their weight and BNP levels daily for 60 days with a finger-stick test . Patients and physicians were blinded to BNP levels . The composite outcome was ADHF events : cardiovascular death , admission for decompensated HF , or clinical HF decompensation requiring either parenteral HF therapy or changes in oral HF medications . RESULTS A total of 6,934 daily BNP values were recorded , with a median of 46 measures per patient over a monitoring period of 65 days . Forty patients had 56 events . Correlations between BNP measures weakened over time , and the dispersion between BNP measures grew . During 10,035 patient-days , there were 494 ( 4.9 % ) days of weight gain ( ≥5 lbs ) . The hazard ratio per unit increase of ln BNP was 1.84 , and the hazard ratio on a day of weight gain was 3.63 . These effects retained significance when controlling for symptoms . When the monitoring period for each subject was broken into intervals based on ADHF events , there were 39 ( 18.4 % ) intervals of upward trending BNP corresponding to a risk increase of 59.8 % and 64 ( 30.2 % ) downward trending intervals corresponding to a risk decrease of 39.0 % . There were 94 ( 44.3 % ) intervals with 1 or more days of weight gain corresponding to a risk increase of 26.1 % . CONCLUSIONS This pilot study demonstrates that home BNP testing is feasible and that trials using home monitoring for guiding therapy are justifiable in high-risk patients . Daily weight monitoring is complementary to BNP , but BNP changes correspond to larger changes in risk , both upward and downward . ( Heart Failure [ HF ] Assessment with B-type Natriuretic Peptide [ BNP ] In the Home [ HABIT ] ; NCT00946231 ) AIMS The optimal duration of a public heart failure ( HF ) clinic programme is unknown . This sub study of the NT-proBNP stratified follow-up in outpatient heart failure clinics ( NorthStar ) trial was design ed to evaluate the effect of extended follow-up in an outpatient HF clinic on long-term adherence to guideline -based therapy . METHODS AND RESULTS Patients with HF with reduced EF on optimal medical therapy ( n = 921 ) were r and omized to either extended follow-up in the HF clinic ( n = 461 ) or discharge to primary care ( n = 460 ) and followed for a median of 4.1 years ( range : 13 months to 6.1 years ) . The effect of the HF clinic intervention on treatment adherence ( time to at least a 90 day break in treatment ) was estimated by drug dispensing from pharmacies of an ACE inhibitor/ARB , beta-blocker ( BB ) , or mineralocorticoid receptor antagonist ( MRA ) . Median age was 69 years , 25 % were females , LVEF was 30 % , and 90 % were in NYHA class II-III . The HF clinic intervention did not reduce time to a 90 day break in treatment with either an ACE inhibitor/ARB [ hazard ratio ( HR ) 0.82 , 95 % confidence interval ( CI ) 0.34 - 1.97 , P = 0.650 ] , a BB ( HR 1.09 , 95 % CI 0.53 - 2.66 , P = 0.820 ) , or an MRA ( HR 1.30 , 95 % CI 0.85 - 2.00 , P = 0.238 ) . CONCLUSIONS Extended follow-up in an outpatient HF clinic did not improve long-term adherence to guideline -based therapy , and adherence did not deteriorate when follow-up was shifted from the HF clinic to primary care Background — Therapy guided by N-terminal-pro-B-type natriuretic peptide ( NT-proBNP ) levels may improve outcomes in patients with chronic heart failure ( HF ) , especially in younger patients with reduced left ventricular ejection fraction . It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP – guided treatment strategy . Methods and Results — Trial of Intensified versus st and ard Medical therapy in Elderly patients with Congestive Heart Failure r and omized 499 patients with HF aged ≥60 years with left ventricular ejection fraction ⩽45 % to intensified , NT-proBNP – guided versus st and ard , symptom-guided therapy into prespecified age groups ( 60–74 and ≥75 years ) during 18 months . A total of 329 patients ( 92 % ) alive at 18 months agreed to long-term follow-up . HF medication was intensified to a larger extent in the NT-proBNP – guided group . During long-term , NT-proBNP – guided therapy did not improve hospital-free ( primary end point : hazard ratio , 0.87 ; 95 % confidence interval , 0.71–1.06 ; P=0.16 ) or overall survival ( hazard ratio , 0.85 ; 95 % confidence interval , 0.64–1.13 ; P=0.25 ) but did improve HF hospitalization-free survival ( hazard ratio , 0.70 ; 95 % confidence interval , 0.55–0.90 ; P=0.005 ) . Patients aged 60 to 74 years had benefit from NT-proBNP – guided therapy on the primary end point and HF hospitalization-free survival , whereas patients aged ≥75 years did not ( P<0.10 for interaction ) . In l and mark analysis , there was no regression to the mean after cessation of the NT-proBNP – guided strategy . More intensified HF medication at month 12 was associated with better long-term HF hospitalization-free and overall survival . Conclusions — Intensified , NT-proBNP – guided therapy did not improve the primary end point compared with symptom-guided therapy but did improve HF hospitalization-free survival . Within the subgroup of patients aged 60 to 74 years , it improved clinical outcome including the primary end point . These effects did not disappear after cessation of the NT-proBNP – guided strategy on the long-term . This is possibly attributable to a more intensified HF medical therapy in the NT-proBNP – guided group . Clinical Trial Registration — URL : http://www.is rct n.org . Unique identifier : IS RCT N43596477 |
11,788 | 29,935,493 | Results have indicated aerobic exercise , resistance exercise , stretching , yoga , qigong , and pilates can be safe and effective in the management of symptoms for those with , or at risk for , BCRL .
Conclusion Several forms of exercise appear to be safe interventions for clinicians to use when treating this population and offer benefits such as improved quality of life , strength , body mass index , and mental health and decreased pain and lymphatic swelling . | Background Breast cancer‐related lymphedema ( BCRL ) affects many areas of daily living .
Individuals with lymphedema may experience chronic and progressive swelling , recurrent skin infections , and decreased self‐image and quality of life .
For many years , it was considered best practice for this population to avoid exercise ; however , in recent years , research has begun to challenge this belief .
This systematic review and meta‐analyses examined the recent literature on the effects of exercise for patients with , or at risk for , BCRL to inform best practice . | Introduction Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors . This study examines the incidence of self-reported lymphedema , timing of lymphedema onset , and associations between sociodemographic , clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter , multiethnic prospect i ve cohort study of breast cancer survivors , the Health , Eating , Activity and Lifestyle Study . Methods A total of 666 women diagnosed with breast cancer staged as in situ , localized or regional disease at ages 35 to 64 years were recruited through the Surveillance , Epidemiology , and End Results registries in New Mexico ( non-Hispanic white and Hispanic white ) , Los Angeles County ( black ) , and Western Washington ( non-Hispanic white ) and followed for a median of 10.2 years . We evaluated sociodemographic factors , breast cancer- and treatment-related factors , comorbidities , body mass index ( BMI ) , hormonal factors , and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models , estimating hazard ratios ( HR ) and 95 % confidence intervals ( CI ) . Results Over the follow-up period , 190 women ( 29 % ) reported lymphedema . The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months ( range : 0.5 to 134.9 months ) . Factors independently associated with lymphedema were total/modified radical mastectomy ( versus partial/less than total mastectomy ; HR = 1.37 , 95 % CI : 1.01 to 1.85 ) , chemotherapy ( versus no chemotherapy ; HR = 1.48 , 95 % CI : 1.09 to 2.02 ) , no lymph nodes removed ( versus ≥10 lymph nodes removed ; HR = 0.17 , 95 % CI : 0.08 to 0.33 ) , pre-diagnostic BMI ≥30 kg/m2 ( versus BMI < 25 kg/m2 ; HR = 1.59 , 95 % CI : 1.09 to 2.31 ) , and hypertension ( versus no hypertension ; HR = 1.49 , 95 % CI : 1.06 to 2.10 ) . After adjusting for demographics and breast cancer- and treatment-related factors , no significant difference in lymphedema risk was observed across racial/ethnic groups . Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women . Conclusions Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection , or who have a higher BMI should be closely monitored for detection and treatment of lymphedema . Further studies are needed to underst and the roles of chemotherapy and hypertension in the development of lymphedema Goals of workOur aim was to compare the effects of l and versus water multimodal exercise programs on body composition and breast cancer-specific quality of life in breast cancer survivors . Patients and methods Ninety-eight breast cancer survivors were assigned to three groups : control , l and exercise , and water exercise . Both exercise groups participated in an 8-week multimodal program . Adiposity was measured by anthropometry ( body mass index , waist circumference ) and bioelectrical impedance ( body fat and muscle lean body mass ) . Incidence of clinical ly significant secondary lymphedema was also assessed . Finally , specific quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life BR-23.Main Results Using ANCOVA , significant group × time interactions for body fat percentage ( F = 3.376 ; P = 0.011 ) and lean body mass ( F = 3.566 ; P = 0.008 ) were found . Breast cancer survivors in the l and exercise group exhibited a greater decrease in percentage of body fat than those in the water exercise ( P < 0.001 ) and control ( P = 0.002 ) groups . The ANCOVA revealed a significant group × time interaction for waist circumference ( F = 4.553 ; P = 0.002 ) : breast cancer survivors in the control group showed a greater waist circumference when compared to water ( P = 0.003 ) and l and ( P < 0.001 ) exercise groups . A significant group × time interaction was also found for breast symptoms ( F = 9.048 ; P < 0.001 ) : participants in the water exercise group experienced a greater decrease of breast symptoms than those in the l and exercise ( P < 0.01 ) and control ( P < 0.05 ) groups . Conclusion L and exercise produced a greater decrease in body fat and an increase in lean body mass , whereas water exercise was better for improving breast symptoms Objective The aim of this study was to evaluate the feasibility and effect of a water-based exercise program on lymphedema status and shoulder range of motion among women with breast cancer – related lymphedema . Design This was a single-blinded , r and omized controlled pilot trial . Twenty-nine eligible breast cancer survivors ( median , 10 yrs after surgery ) with arm lymphedema ( median , 21 % interlimb difference ) were included and r and omized into the intervention ( n = 15 ) or control ( n = 14 ) group . Twenty-five participants completed the study . The intervention was at least twice-weekly water-based exercise for 8 wks , initially supervised but performed independently during the study period . Outcomes of interest were feasibility as measured by retention and adherence ; lymphedema status as measured by optoelectronic perometry , bioimpedance spectroscopy , and tissue dielectric constant ; and shoulder range of motion as measured by goniometer . Results Four participants were not measured at postintervention and were not included in the analysis ( retention ) . Four participants in the intervention group did not perform the minimum water-based exercise criteria set ( adherence ) . No effect was found on lymphedema status . Compared with the control group , median range of motion change for flexion was 6 ( 1–10 ) degrees ( P < 0.001 ) and 6 ( 0–15.5 ) degrees ( P = 0.07 ) for external rotation . A clinical ly relevant increase in the intervention group was found for 36 % in flexion ( P ⩽ 0.05 ) and 57 % in external rotation ( P ⩽ 0.05 ) compared with controls . Conclusions This study shows that water-based exercise is feasible for breast cancer survivors with arm lymphedema and that shoulder range of motion can be improved years after cancer treatment has been completed The aim of this study was to determine whether an exercise program , commencing 4–6 weeks post-operatively , reduces upper limb impairments in women treated for early breast cancer . Women ( n = 160 ) were r and omized to either an 8-week exercise program ( n = 81 ) or to a control group ( n = 79 ) following stratification for axillary surgery . The exercise program comprised a weekly session and home program of passive stretching and progressive resistance training for shoulder muscles . The control group attended fortnightly assessment s but no exercises were provided . The primary outcome was self-reported arm symptoms derived from the EORTC breast cancer-specific question naire ( BR23 ) , scored out of 100 with a low score indicative of fewer symptoms . The secondary outcomes included physical measures of shoulder range of motion , strength , and swelling ( i.e. , lymphedema ) . Women were assessed immediately following the intervention and at 6 months post-intervention . The change in symptoms from baseline was not significantly different between groups immediately following the intervention or at 6 m post-intervention . The between group difference immediately following the intervention was 4 ( 95 % CI −1 to 9 ) and 6 months post-intervention was 4 ( −2 to 10 ) . However , the change in range of motion for flexion and abduction was significantly greater in the exercise group immediately following the intervention , as was change in shoulder abductor strength . In conclusion , a supervised exercise program provided some , albeit small , additional benefit at 6 months post-intervention to women who had been provided with written information and reminders to use their arm . Both the groups reported few impairments including swelling immediately following the intervention and 6 months post-intervention . Notably , resistance training in the post-operative period did not precipitate lymphedema BACKGROUND Weight lifting has generally been proscribed for women with breast-cancer-related lymphedema , preventing them from obtaining the well-established health benefits of weight lifting , including increases in bone density . METHODS We performed a r and omized , controlled trial of twice-weekly progressive weight lifting involving 141 breast-cancer survivors with stable lymphedema of the arm . The primary outcome was the change in arm and h and swelling at 1 year , as measured through displaced water volume of the affected and unaffected limbs . Secondary outcomes included the incidence of exacerbations of lymphedema , number and severity of lymphedema symptoms , and muscle strength . Participants were required to wear a well-fitted compression garment while weight lifting . RESULTS The proportion of women who had an increase of 5 % or more in limb swelling was similar in the weight-lifting group ( 11 % ) and the control group ( 12 % ) ( cumulative incidence ratio , 1.00 ; 95 % confidence interval , 0.88 to 1.13 ) . As compared with the control group , the weight-lifting group had greater improvements in self-reported severity of lymphedema symptoms ( P=0.03 ) and upper- and lower-body strength ( P<0.001 for both comparisons ) and a lower incidence of lymphedema exacerbations as assessed by a certified lymphedema specialist ( 14 % vs. 29 % , P=0.04 ) . There were no serious adverse events related to the intervention . CONCLUSIONS In breast-cancer survivors with lymphedema , slowly progressive weight lifting had no significant effect on limb swelling and result ed in a decreased incidence of exacerbations of lymphedema , reduced symptoms , and increased strength . ( Clinical Trials.gov number , NCT00194363 . Background This study was to investigate the effects of complex exercise on shoulder range of motion and pain for women with breast cancer-related lymphedema . Methods 69 women participated in this study and then they were r and omly allocated to complex exercise group ( n = 35 ) or the conventional decongestive therapy group ( n = 34 ) . All subjects received 8 sessions for 4 weeks . To identify the effects on shoulder range of motion and pain , goniometer and visual analog scale were used , respectively . The outcome measurements were performed before and after the 4 week intervention . Results After 4 weeks , complex exercise group had greater improvements in shoulder range of motion and pain compared with the conventional decongestive therapy group ( p < 0.05 ) . Conclusion These results suggest that complex exercise is beneficial to improve shoulder range of motion as well as pain of the women with breast cancer-related lymphedema . Complex exercise would be useful to improve shoulder range of motion and pain of the women with breast cancer-related lymphedema Background We aim ed to evaluate the effect of an 8-week yoga intervention on the shoulder and spinal actions of women with breast cancer-related arm lymphoedema . Method A r and omised controlled pilot trial . The intervention group ( n = 12 ) completed eight weeks of daily yoga sessions while the control group ( n = 11 ) continued with best current care including information on compression sleeves , skin care , risks of temperature variations and recommended safe use of affected arm . Lumbo-pelvic posture , range of motion ( ROM ) in the shoulder and spine , and strength in shoulder and pectoral major and minor , and serratus anterior were taken at baseline , week 8 and after a 4-week follow-up . Outcome assessors were blinded to allocation . Results At week eight the intervention group had an improvement in lumbo-pelvic posture , as indicated by a reduction in pelvic obliquity compared to the control group ( mean difference = −8.39 ° , 95 % CI : −15.64 to −1.13 ° , p = 0.023 ) . A secondary finding was that strength in shoulder abduction significantly increased following the yoga intervention in both the affected ( 9.5 kg ; CI : 0.34 to 18.66 , p = 0.042 ) and non-affected arm ( 11.58 kg ; CI : 0.25 to 22.91 ; p = 0.045 ) . There were no significant between group changes in any ROM measures as a result of the yoga intervention . Conclusion This pilot study demonstrates that participation in yoga may provide benefits for posture and strength in women with Breast Cancer Related Lymphoedema . The improvements may be attributed to the focus of yoga on overall postural and functional movement patterns . Further trials with longer intervention that follow this methodology are warranted . Trial registration The Australian New Zeal and Clinical Trials Registry ACTRN12611000202965 Exercise for Health was a r and omized , controlled trial design ed to evaluate two modes of delivering ( face-to-face [ FtF ] and over-the-telephone [ Tel ] ) an 8-month translational exercise intervention , commencing 6-weeks post-breast cancer surgery ( PS ) . Outcomes included quality of life ( QoL ) , function ( fitness and upper body ) and treatment-related side effects ( fatigue , lymphoedema , body mass index , menopausal symptoms , anxiety , depression and pain ) . Generalised estimating equation modelling determined time ( baseline [ 5 weeks PS ] , mid-intervention [ 6 months PS ] , post-intervention [ 12 months PS ] ) , group ( FtF , Tel , Usual Care [ UC ] ) and time-by-group effects . 194 women representative of the breast cancer population were r and omised to the FtF ( n = 67 ) , Tel ( n = 67 ) and UC ( n = 60 ) groups . There were significant ( p < 0.05 ) interaction effects on QoL , fitness and fatigue with differences being observed between the treatment groups and the UC group . Trends observed for the treatment groups were similar . The treatment groups reported improved QoL , fitness and fatigue over time and changes observed between baseline and post-intervention were clinical ly relevant . In contrast , the UC group experienced no change , or worsening QoL , fitness and fatigue , mid-intervention . Although improvements in the UC group occurred by 12-months post-surgery , the change did not meet the clinical ly relevant threshold . There were no differences in other treatment-related side effects between groups . This translational intervention trial , delivered either FtF or Tel , supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment Resistance exercise has great potential to aid in the management of breast cancer – related lymphedema ( BCRL ) , but little is known regarding the acute response of performing resistance exercises with the affected limb . Purpose . To examine the acute impact of upper body resistance exercise on the amount of swelling and severity of symptoms in women with BCRL and to compare these effects between resistance exercise involving high and low loads ( heavier vs lighter weights ) . Methods . Seventeen women aged 61 ± 9 years with mild to severe BCRL participated in this study . Participants completed a high load ( 6 - 8 repetition maximum ) and low load ( 15 - 20 repetition maximum ) exercise session consisting of 2 sets of 5 upper body resistance exercises in a r and omized order separated by a 10- to 12-day wash-out period . The extent of swelling was assessed using bioimpedance spectroscopy , dual-energy x-ray absorptiometry , and arm circumference measurements . The severity symptoms were assessed using the visual analogue scale ( pain , heaviness , and tightness ) and a modified Brief Pain Inventory . Measurements were taken pre-exercise , immediately post-exercise , 24 hours post-exercise , and 72 hours post-exercise . Results . No changes in the extent of swelling or the severity of symptoms were observed between pre-exercise and immediately post-exercise , 24 hours post-exercise , or 72 hours post-exercise . No differences in the response to the high or low load exercise were observed . Conclusions . Upper body resistance exercise does not acutely increase swelling or feelings of discomfort/pain , heaviness tightness in the affected limb of BCRL patients when performed at either high or low loads PURPOSE To examine the effect of a progressive upper-body exercise program on lymphedema secondary to breast cancer treatment . METHODS Fourteen breast cancer survivors with unilateral upper extremity lymphedema were r and omly assigned to an exercise ( n = 7 ) or control group ( n = 7 ) . The exercise group followed a progressive , 8-week upper-body exercise program consisting of resistance training plus aerobic exercise using a Monark Rehab Trainer arm ergometer . Lymphedema was assessed by arm circumference and measurement of arm volume by water displacement . Patients were evaluated on five occasions over the experimental period . The Medical Outcomes Trust Short-Form 36 Survey was used to measure quality of life before and after the intervention . Significance was set at alpha < or = 0.01 . RESULTS No changes were found in arm circumference or arm volume as a result of the exercise program . Three of the quality -of-life domains showed trends toward increases in the exercise group : physical functioning ( P = .050 ) , general health ( P = .048 ) , and vitality ( P = .023 ) . Mental health increased , although not significantly , for all subjects ( P = .019 ) . Arm volume measured by water displacement was correlated with calculated arm volume ( r = .973 , P < .001 ) , although the exercise and control group means were significantly different ( P < .001 ) . CONCLUSIONS Participation in an upper-body exercise program caused no changes in arm circumference or arm volume in women with lymphedema after breast cancer , and they may have experienced an increase in quality of life . Additional studies should be done in this area to determine the optimum training program Purpose Resistance exercise has great potential to aid in the management of breast cancer-related lymphedema ( BCRL ) ; however , little is known regarding optimal exercise prescription . The pervasive view is that resistance exercise with heavy loads may be contraindicated , disregarding the dose – response relationship that exists between the load utilised in resistance exercise and the magnitude of structural and functional improvements . No previous research has examined various resistance exercise prescriptions for the management of BCRL . This study compared the effects of high load and low load resistance exercise on the extent of swelling , severity of symptoms , physical function and quality of life in women with BCRL . Methods Sixty-two women with a clinical diagnosis of BCRL ( > 5 % inter-limb discrepancy ) were r and omly assigned to a high-load resistance exercise ( n = 22 ) , low-load resistance exercise ( n = 21 ) or usual care ( n = 19 ) group . Participants in the experimental groups completed a 3-month moderate- to high-intensity resistance exercise program in which the load of the exercises was manipulated from 10–6 repetition maximum ( 75–85 % of one repetition maximum [ 1RM ] ) for the high-load group or from 20–15 repetition maximum ( 55–65 % 1RM ) for the low-load group . Outcome measures included the extent of swelling in the affected arm , symptom severity , physical function and quality of life . Results There were no differences between groups in the extent of affected arm swelling or severity of symptoms . The change in muscle strength , muscle endurance and quality of life – physical functioning was significantly greater in both high-load and low-load groups compared with the control group ( p < 0.040 ) . Change in quality of life – physical function was significantly associated with the change in symptom severity and muscle strength . No lymphedema exacerbations or other adverse events occurred during this trial . Conclusion Women with BCRL can safely lift heavy weights during upper body resistance exercise without fear of lymphedema exacerbation or increased symptom severity . Implication s for Cancer SurvivorsWomen with breast cancer-related lymphedema can be informed that appropriately prescribed and supervised upper body resistance exercise is safe and can aid in the management of lymphedema through improvements in physical function and quality of life OBJECTIVE To investigate the differences between the effects of complex decongestive physiotherapy with and without active resistive exercise for the treatment of patients with breast cancer-related lymphedema ( BCRL ) . DESIGN R and omized control-group study . SETTING An outpatient rehabilitation clinic . PARTICIPANTS Patients ( N=40 ) with diagnosed BCRL . INTERVENTIONS Patients were r and omly assigned to either the active resistive exercise group or the nonactive resistive exercise group . In the active resistive exercise group , after complex decongestive physiotherapy , active resistive exercise was performed for 15min/d , 5 days a week for 8 weeks . The nonactive resistive exercise group performed only complex decongestive physiotherapy . MAIN OUTCOME MEASURES The circumferences of the upper limbs ( proximal , distal , and total ) for the volume changes , and the Short Form-36 version 2 question naire for the quality of life ( QOL ) at pretreatment and 8 weeks posttreatment for each patient . RESULTS The volume of the proximal part of the arm was significantly more reduced in the active resistive exercise group than that of the nonactive resistive exercise group ( P<.05 ) . In the active resistive exercise group , there was significantly more improvement in physical health and general health , as compared with that of the nonactive resistive exercise group ( P<.05 ) . CONCLUSIONS For the treatment of patients with BCRL , active resistive exercise with complex decongestive physiotherapy did not cause additional swelling , and it significantly reduced proximal arm volume and helped improve QOL PURPOSE Lymphedema is a common condition that breast cancer survivors face . Despite a lack of supporting evidence from prospect i ve observational studies , occupational and leisure time physical activity are feared to be possible risk factors for lymphedema onset or exacerbation . We examined effects of supervised upper- and lower-body weight training on the incidence and symptoms of lymphedema in 45 breast cancer survivors who participated in the Weight Training for Breast Cancer Survivors study . METHODS Participants were on average 52 years old , 4 to 36 months post-treatment , and had axillary dissection as part of their treatment . Thirteen women had prevalent lymphedema at baseline . The intervention was twice-a-week weight training over a period of 6 months . Lymphedema was monitored at baseline and 6 months by measuring the circumference of each arm , and by self-report of symptoms and clinical diagnosis . RESULTS None of the intervention-group participants experienced a change in arm circumferences > or = 2.0 cm after a 6-month exercise intervention . Self-reported incidence of a clinical diagnosis of lymphedema or symptom changes over 6 months did not vary by intervention status ( P = .40 and P = .22 , respectively ) . CONCLUSION This is the largest r and omized controlled trial to examine associations between exercise and lymphedema in breast cancer survivors . The results of this study support the hypotheses that a 6-month intervention of resistance exercise did not increase the risk for or exacerbate symptoms of lymphedema . These results herald the need to start reevaluating common clinical guidelines that breast cancer survivors avoid upper body resistance activity for fear of increasing risk of lymphedema Objectives This study aim ed to determine the effect of a moderate , tailored exercise program on health-related quality of life , physical function , and arm volume in women receiving treatment for nonmetastatic breast cancer . Methods Women who were within 4–12 weeks of surgery for stage I – III breast cancer were r and omized to center-based exercise and lymphedema education intervention or patient education . Functional Assessment of Cancer Therapy – Breast Cancer ( FACT-B ) , 6-min walk , and arm volume were performed at 3-month intervals through 18 months . Repeated measures analysis of covariance was used to model the total meters walked over time , FACT-B scores , and arm volume . Models were adjusted for baseline measurement , baseline affected arm volume , number of nodes removed , age , self-reported symptoms , baseline SF-12 mental and physical component scores , visit , and treatment group . Results Of the recruited 104 women , 82 completed all 18 months . Mean age ( range ) was 53.6 ( 32–82 ) years ; 88 % were Caucasian ; 45 % were employed full time ; 44 % were overweight ; and 28 % obese . Approximately , 46 % had breast-conserving surgery ; 79 % had axillary node dissection ; 59 % received chemotherapy ; and 64 % received radiation . The intervention result ed in an average increase of 34.3 ml ( SD = 12.8 ) versus patient education ( p = 0.01 ) . Changes in FACT-B scores and arm volumes were not significantly different . Conclusions With this early exercise intervention after breast cancer diagnosis , a significant improvement was achieved in physical function , with no decline in health-related quality of life or detrimental effect on arm volume . Implication s for cancer survivorsStarting a supervised exercise regimen that is tailored to an individual 's strength and stamina within 3 months following breast cancer surgery appears safe and may hasten improvements in physical functioning Objective Chronic lymphedema occurs frequently in breast cancer patients and is associated with significant morbidity and reduced quality -of-life . In this pilot study , the authors ( 1 ) addressed whether conducting a larger r and omized controlled trial of aqua lymphatic therapy ( ALT ) would be feasible and ( 2 ) estimated the extent to which ALT combined with home-based exercise compared with home-based exercise alone would reduce arm disability in patients with breast cancer – related lymphedema . Design Twenty-five women with breast cancer – related lymphedema were r and omized to either ALT in addition to a home l and -based exercise program ( ALT group ; n = 13 ) or to a home l and -based exercise program alone ( control group ; n = 12 ) . The participants were evaluated before and after a 12-wk intervention period composed of weekly pool exercise sessions . Main outcome measures were arm volume , arm disability , pain , and quality -of-life . Results At follow-up , there was no statistical difference between the control and ALT groups in any of the outcomes , except for present pain intensity . At the end of the study period , there was no change in the lymphedematous limb volume in either group . Grip strength was improved in both groups . Only the ALT group showed a statistically significant difference with a reduction in pain intensity score and arm disability . Furthermore , quality -of-life significantly improved only in the ALT group . Conclusions Conducting a larger r and omized controlled trial would be feasible . In comparison with the beginning of the intervention , the participants in the ALT group showed significant beneficial changes after 12 wks of treatment , whereas the control group did not improve . ALT did not make the lymphedema volume worse and therefore may serve as a safe alternative to l and -based treatments of breast cancer – related lymphedema OBJECTIVE The aim of the present study was to compare the effects of clinical Pilates exercises with those of the st and ard lymphedema exercises on lymphedema developing after breast cancer treatment . MATERIAL S AND METHODS The study comprised 60 female patients with a mean age of 53.2±7.7 years who developed lymphedema after having breast cancer treatment . The patients were r and omized into two groups : the clinical Pilates exercise group ( n=30 ) , and the control group ( n=30 ) . Before , and at the 8th week of treatment , the following parameters were measured : the severity of lymphedema , limb circumferences , body image using the Social Appearance Anxiety Scale , quality of life with the European Organization for Research and Treatment of Cancer ( EORTC ) quality of life question naire ( QLQ-BR23 ) , and upper extremity function using the Disabilities of the Arm , Shoulder and H and ( DASH ) outcome measure . Both groups performed one-hour exercises three days a week for 8 weeks . RESULTS After treatment , the symptoms recovered significantly in both groups . Reductions in the severity of lymphedema , improvements in the social appearance anxiety scale scores , quality of life scores , and upper extremity functions scores in the clinical Pilates exercise group were greater than those in the control group . Clinical Pilates exercises were determined to be more effective on the symptoms of patients with lymphedema than were st and ard lymphedema exercises . CONCLUSIONS Clinical Pilates exercises could be considered a safe model and would contribute to treatment programs Abstract The benefit of exercise for breast cancer-treated women is well documented . However , studies of cardiovascular fitness training for women with breast cancer-related arm lymphedema are rare . The purpose of this study was to investigate the effects of intensive pole walking on arm lymphedema in women treated for breast cancer . Thirty-five women with unilateral lymphedema were included and twenty-three completed an eight-week exercise intervention consisting of pole walking 3–5 times per week , for 30–60 min , at 70%–80 % of their maximum heart rate , preceded by a two-week control period . Measurements of arm lymphedema ( water displacement method ) , body weight , cardiovascular fitness ( sub-maximal bicycle ergometer test ) and subjective assessment s ( disability of the arm , shoulder and h and ( DASH ) question naire ; heaviness and tightness using a visual analogue scale ( VAS ) ; and well-being ) were performed before the control period and before and after the exercise intervention . The results indicated a significant reduction in total arm volume of the lymphedema arm ( p = 0.001 ) , in lymphedema absolute volume ( p = 0.014 ) and lymphedema relative volume ( p = 0.015 ) . Significant decreases of heart rate ( p = 0.004 ) , DASH score ( p = 0.053 ) and rating of tightness in the arm ( p = 0.043 ) were found . Positive and negative influences on well-being were reported . The conclusion of this study is that pole walking is feasible for breast cancer-treated women with arm lymphedema OBJECTIVE To investigate the safety and efficacy of arm crank ergometry in breast cancer patients after axillary lymph node dissection , with regard to changes in bioelectrical impedance analysis , arm circumference , muscular strength , quality of life and fatigue . DESIGN R and omized controlled clinical intervention trial . SUBJECTS Forty-nine patients with breast cancer after axillary lymph node dissection . METHODS Arm crank ergometer training twice-weekly was compared with usual care over 12 weeks . RESULTS The arm crank ergometer group improved significantly in terms of lean body mass and skeletal muscle mass , and showed a significant decrease in body fat . In the arm crank ergometer group , as well as the usual care group , a significant increase in armpit circumference was detected during the training period . The magnitude of the gain was higher in the usual care group . For all other measured regions of the arm a significant decrease in circumference was seen in both groups . Muscular strength of the upper extremity increased significantly in both groups , with a greater improvement in the arm crank ergometer group . In both groups a non-significant trend towards improvement in quality of life was observed . The arm crank ergometer group showed significant improvements in physical functioning , general fatigue and physical fatigue . CONCLUSION These results confirm the feasibility of arm crank ergometer training after axillary lymph node dissection and highlight improvements in strength , quality of life and reduced arm symptoms with this training Hypothesis . Qigong exercise is a popular method for relieving the side effects of conventional cancer treatments in survivors of breast cancer , yet its effects are not empirically assessed . This study aim ed to investigate the effects of qigong exercise on upper limb lymphedema , arterial resistance , and blood flow velocity in survivors with breast cancer and mastectomy . Study Design . This study was conducted as a prospect i ve clinical trial . Methods . Eleven survivors of breast cancer with qigong experience ( mean age = 58.3 ± 10.1 years ) were assigned to the experimental group and 12 survivors of breast cancer without qigong experience ( mean age = 53.8 ± 4.2 years ) were assigned to the control group . They all had breast cancer – related lymphedema . All procedures were completed within one session . After baseline measurements were taken , the experimental group performed 18 Forms Tai Chi Internal Qigong for approximately 6 minutes while the control group rested for similar duration in a sitting position . Both groups were then reassessed . All participants were measured on their affected upper limb circumference ( by using tape measures ) , peripheral arterial resistance , and blood flow velocities ( using a Doppler ultrasound machine ) . Results . The between-group differences were not significant for all outcome measures at baseline ( P > .05 ) . The circumferences of the affected upper arm , elbow , forearm and wrist decreased after qigong exercise ( P < .05 ) . However , no significant difference was found in the circumference measures between the 2 groups posttest ( P > .0125 ) . In terms of vascular outcomes , the resistance index decreased and the maximum systolic arterial blood flow velocity ( SV ) and minimum diastolic arterial blood flow velocity ( DV ) increased significantly after qigong exercise ( P < .05 ) . The between-group difference was close to significant for SV ( P = .018 ) and was significant for DV ( P < .001 ) posttest . Conclusion . Qigong exercise could reduce conventional cancer therapy side effects such as upper limb lymphedema and poor circulatory status in survivors of breast cancer . However , such effects may be temporary , and further studies must be conducted to explore longer term effects Evidence -based exercise and relaxation recommendations for people with breast cancer-related lymphedema ( BCRL ) are needed . We report a r and omized controlled study of one program , design ed to achieve synergistic improvements in physical and emotional BCRL symptoms . People in the treatment group received an exercise and relaxation program , The Breast Cancer Recovery Program ( N=16 ) . The control participants ( N=16 ) continued with health professionals ' recommendations . Participants were tested at entry , 2.5 weeks , 5 weeks , and 3 months . Treatment group participants , compared with control participants , demonstrated significant treatment effects for improved bioimpedance z , arm flexibility , quality of life , mood at 3 months , and weight loss . Adherence was high for this safe and effective program , which improved lymphedema physical and emotional symptoms |
11,789 | 28,430,611 | Sensitivity analyses and subgroup analyses demonstrated the stability of our conclusion .Our analysis showed that EGFR mutations in ctDNA predicted a better PFS , in particular in advanced NSCLC patients treated by EGFR-TKIs .
KRAS mutations in ctDNA indicated a worse PFS and OS in patients treated by chemotherapy | EGFR ( exon 19 and exon 21 ) mutations in patients with advanced non-small cell lung cancer ( NSCLC ) treated by EGFR-TKIs are associated with a better survival ; while KRAS mutations predict a worse prognosis .
However , there are divergent findings regarding the prognostic value of EGFR and KRAS mutations in circulating tumor DNA ( ctDNA ) . | Purpose : Elevated levels or increases in circulating tumor cells ( CTC ) portend poor prognosis in patients with epithelial cancers . Less is known about CTCs as surrogate endpoints or their use for predictive biomarker evaluation . This study investigated the utility of CTC enumeration and characterization using the Cell Search platform , as well as mutation detection in circulating tumor DNA ( ctDNA ) , in patients with advanced non – small cell lung cancer ( NSCLC ) . Experimental Design : Forty-one patients were enrolled in a single-arm phase II clinical trial of erlotinib and pertuzumab . Peripheral blood was analyzed for CTC enumeration , EGFR expression in CTCs , and detection of oncogenic mutations in CTCs and ctDNA . Changes in CTC levels were correlated with 2[18F]fluoro-2-deoxy-d-glucose – positron emission tomographic ( FDG-PET ) and computed tomographic ( CT ) imaging and survival endpoints . Results : CTCs were detected ( ≥1 CTC ) at baseline in 78 % of patients . Greater sensitivity for mutation detection was observed in ctDNA than in CTCs and detected mutations were strongly concordant with mutation status in matched tumor . Higher baseline CTC counts were associated with response to treatment by Response Evaluation Criteria in Solid Tumors ( RECIST , P = 0.009 ) and decreased CTC counts upon treatment were associated with FDG-PET and RECIST response ( P = 0.014 and P = 0.019 ) and longer progression-free survival ( P = 0.050 ) . Conclusion : These data provide evidence of a correlation between decreases in CTC counts and radiographic response by either FDG-PET or RECIST in patients with advanced NSCLC . These findings require prospect i ve validation but suggest a potential role for using CTC decreases as an early indication of response to therapy and ctDNA for real-time assessment of mutation status from blood . Clin Cancer Res ; 18(8 ) ; 2391–401 . © 2012 AACR Purpose : Activating mutations in the epidermal growth factor receptor ( EGFR ) are associated with enhanced response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer ( NSCLC ) , whereas KRAS mutations translate into poor patient outcomes . We hypothesized that analysis of plasma for EGFR and KRAS mutations from shed tumor DNA would have clinical utility . Methods : An allele-specific polymerase chain reaction assay using Scorpion-amplification refractory mutation system ( DxS , Ltd ) was used to detect mutations in plasma DNA from patients with advanced stage NSCLC treated as second- or third-line therapy on a phase I/II trial of docetaxel plus intercalated erlotinib . Results : EGFR mutations were detected in 10 of 49 patients ( 20 % ) . Six ( 12 % ) had single activating mutations in EGFR , associated with improved progression-free survival ( median , 18.3 months ) , compared with all other patients ( median , 3.9 months ; p = 0.008 ) , or those with wild-type EGFR ( median , 4.0 months ; p = 0.012 ) . Four of 49 patients harbored a de novo T790 M resistance mutation ( median progression-free survival , 3.9 months ) . EGFR mutational status was associated with clinical response ( 45 assessable , p = 0.0001 ) ; in the six patients with activating mutations , all achieved complete ( 33 % ) or partial ( 67 % ) response . All CR patients had E19del detectable in both tumor and plasma . KRAS mutations were detected in two of 49 ( 4 % ) patients , both of whom had rapid progressive disease . Conclusions : Activating EGFR mutations detected in shed DNA in plasma are significantly associated with favorable outcomes in patients with advanced NSCLC receiving docetaxel plus intercalated erlotinib . The addition of docetaxel in this schedule did not diminish the efficacy of erlotinib against patients with EGFR activating mutations BACKGROUND Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality . New agents targeting the epidermal growth factor system are emerging , but only a subgroup of the patients will benefit from the therapy . Cell free DNA ( cfDNA ) in the blood allows for tumour specific analyses , including KRAS-mutations , and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS ( pmKRAS ) in patients with non-small cell lung cancer ( NSCLC ) . MATERIAL AND METHODS Patients with newly diagnosed , advanced NSCLC eligible for chemotherapy were enrolled in a prospect i ve biomarker trial . A pre-treatment blood sample was drawn and subsequently DNA was extracted and pmKRAS analysed . The patients received carboplatin ( AUC5 ) i.v . day 1 and vinorelbine ( 30mg/m(2 ) i.v . day 1 and 60mg/m(2 ) p.o . day 8) for a maximum of six cycles . Response to chemotherapy was evaluated according to RECIST v.1.0 by CT scans of the chest and upper abdomen . The presence of pmKRAS at baseline was assessed by an in-house qPCR method . The primary endpoint was overall survival ( OS ) . Secondary end-points were progression free survival ( PFS ) and overall response rate . RESULTS The study included 246 patients receiving a minimum of 1 treatment cycle , and all but four were evaluable for response according to RECIST . Forty-three patients ( 17.5 % ) presented with a KRAS mutation . OS was 8.9 months and PFS by intention to treat 5.4 months . Patients with a detectable plasma-KRAS mutation had a significantly shorter OS and PFS compared to the wild type ( WT ) patients ( median OS 4.8 months versus 9.5 months , HR 1.87 , 95 % CI 1.23 - 2.84 , p=0.0002 and median PFS 3.0 months versus 5.6 months , HR 1.60 , 95 % CI 1.09 - 2.37 , p=0.0043 ) . A multivariate Cox regression analysis confirmed the independent prognostic value of pmKRAS in OS but not in PFS . The response rate to chemotherapy was significantly lower in the group of patients with a mutation compared to WT ( p<0.0001 ) . CONCLUSION The presence of KRAS mutations in plasma may be a marker of poor prognosis and may also hold predictive value . Further validation in an independent cohort is highly needed PURPOSE Mutations in the epidermal growth factor receptor ( EGFR ) kinase domain can predict tumor response to tyrosine kinase inhibitors ( TKIs ) in non-small-cell lung cancer ( NSCLC ) . However , obtaining tumor tissues for mutation analysis is challenging . We hypothesized that plasma-based EGFR mutation analysis is feasible and has value in predicting tumor response in patients with NSCLC . PATIENTS AND METHODS Plasma DNA sample s and matched tumors from 230 patients with stages IIIB to IV NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography . We compared the mutations in the plasma sample s and the matched tumors and determined an association between EGFR mutation status and the patients ' clinical outcomes prospect ively . RESULTS In 230 patients , we detected 81 EGFR mutations in 79 ( 34.3 % ) of the patients ' plasma sample s. We detected the same mutations in 63 ( 79.7 % ) of the matched tumors . Sixteen plasma ( 7.0 % ) and fourteen tumor ( 6.1 % ) sample s showed unique mutations . The mutation frequencies were significantly higher in never-smokers and in patients with adenocarcinomas ( P = .012 and P = .009 , respectively ) . In the 102 patients who failed platinum-based treatment and who were treated with gefitinib , 22 ( 59.5 % ) of the 37 with EGFR mutations in the plasma sample s , whereas only 15 ( 23.1 % ) of the 65 without EGFR mutations , achieved an objective response ( P = .002 ) . Patients with EGFR mutations had a significantly longer progression-free survival time than those without mutations ( P = .044 ) in plasma . CONCLUSION EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs |
11,790 | 27,490,100 | A statistically significant trial-level correlation was identified between EFA slope and ACM at 2 weeks , but is likely misleading , as there was no treatment effect on ACM .
CONCLUSIONS Mortality remains high in short time periods in CM clinical trials . | BACKGROUND Cryptococcal meningitis ( CM ) is a leading cause of HIV-associated mortality .
In clinical trials evaluating treatments for CM , biomarkers of early fungicidal activity ( EFA ) in cerebrospinal fluid ( CSF ) have been proposed as c and i date surrogate endpoints for all- cause mortality ( ACM ) .
However , there has been no systematic evaluation of the group-level or trial-level evidence for EFA as a c and i date surrogate endpoint for ACM . | BACKGROUND Treatment with low-dose amphotericin B ( 0.4 mg per kilogram of body weight per day ) or oral azole therapy in patients with the acquired immunodeficiency syndrome ( AIDS ) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization . METHODS In a double-blind multicenter trial we r and omly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B ( 0.7 mg per kilogram per day ) with or without flucytosine ( 100 mg per kilogram per day ) for two weeks ( step one ) , followed by eight weeks of treatment with itraconazole ( 400 mg per day ) or fluconazole ( 400 mg per day ) ( step two ) . Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinical ly stable at 2 weeks and asymptomatic at 10 weeks . RESULTS At two weeks , the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone ( P=0.06 ) . Elevated intracranial pressure was associated with death in 13 of 14 patients during step one . The clinical outcome did not differ significantly between the two groups . Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks ( 95 percent confidence interval for the difference in percentages , -100 to 21 ) . The proportion of patients who had clinical responses was similar with fluconazole ( 68 percent ) and itraconazole ( 70 percent ) . Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks , with no significant difference between the groups . In a multivariate analysis , the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization . CONCLUSIONS For the initial treatment of AIDS-associated cryptococcal meningitis , the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks , as compared with regimens used in previous studies . Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization , itraconazole may be a suitable alternative for patients unable to take fluconazole BACKGROUND HIV-associated cryptococcal meningitis is associated with an estimated 600 000 deaths worldwide per year . Current st and ard initial therapy consists of amphotericin B ( AmB ) plus flucytosine ( 5-FC ) , but 5-FC remains largely unavailable in Asia and Africa . Alternative , more widely available , and /or more effective antifungal combination treatment regimens are urgently needed . METHODS Eighty HIV-seropositive , antiretroviral naive patients presenting with cryptococcal meningitis were r and omized to 4 treatment arms of 2 weeks duration : group 1 , AmB ( 0.7 - 1 mg/kg ) and 5-FC ( 25 mg/kg 4 times daily ) ; group 2 , AmB ( 0.7 - 1 mg/kg ) and fluconazole ( 800 mg daily ) ; group 3 , AmB ( 0.7 - 1 mg/kg ) and fluconazole ( 600 mg twice daily ) ; and group 4 , AmB ( 0.7 - 1 mg/kg ) and voriconazole ( 300 mg twice daily ) . The primary end point was the rate of clearance of infection from the cerebrospinal fluid ( CSF ) or early fungicidal activity ( EFA ) , as determined by results of serial , quantitative CSF cryptococcal cultures . RESULTS There were no statistically significant differences in the rate of clearance of cryptococcal colony-forming units ( CFU ) in CSF sample s among the 4 treatment groups ; the mean ( ±st and ard deviation ) EFA for treatment groups 1 , 2 , 3 , and 4 were -0.41 ± 0.22 log CFU/mL CSF/day , -0.38 ± 0.18 log CFU/mL CSF/day , -0.41 ± 0.35 log CFU/mL CSF/day , and -0.44 ± 0.20 log CFU/mL CSF/day , respectively . Overall mortality was 12 % ( 9 of 78 patients died ) at 2 weeks and 29 % ( 22 of 75 patients died ) at 10 weeks , with no statistically significant differences among groups . There were few laboratory abnormalities related to the second agents given ; in particular , there were no statistically significant ( ≥ grade 3 ) increases in alanine transaminase level or decreases in neutrophil count . CONCLUSIONS There was no statistically significant difference in EFA between AmB in combination with fluconazole and AmB plus 5-FC for the treatment of HIV-associated cryptococcal meningitis . AmB plus fluconazole ( 800 - 1200 mg/day ) represents an immediately implementable alternative to AmB plus 5-FC . AmB plus voriconazole is an effective alternative combination in patients not receiving interacting medications In a prospect i ve observational study of 54 patients with human immunodeficiency virus-associated cryptococcal meningitis , the early fungicidal activity of amphotericin B ( 1 mg/kg/day ) was significantly greater than that of fluconazole ( 400 mg/day ) . Compared with antiretroviral therapy-naive patients , patients developing cryptococcal meningitis while already receiving antiretroviral therapy had lower baseline fungal burdens and a longer median duration of survival , but there were no differences observed in fungal clearance , cerebrospinal fluid proinflammatory cytokines , or 10-week mortality BACKGROUND The st and ard therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis of amphotericin B ( AmB ; 0.7 mg/kg per day ) plus flucytosine frequently takes > 2 weeks to sterilize the cerebral spinal fluid , and acute mortality remains high . A dosage range for AmB of 0.7 - 1 mg/kg per day is noted in current guidelines , but there are no data comparing 0.7 mg/kg per day with 1 mg/kg per day . METHODS Sixty-four HIV-seropositive , antiretroviral therapy-naive patients in Cape Town , South Africa , who experienced their first episode of cryptococcal meningitis during the period May 2005-June 2006 were r and omized to receive either ( 1 ) AmB , 0.7 mg/kg per day , plus flucytosine , 25 mg/kg 4 times per day ( group 1 ; 30 patients ) ; or ( 2 ) AmB , 1 mg/kg per day , plus flucytosine , 25 mg/kg 4 times per day ( group 2 ; 34 patients ) . Regimens were given for 2 weeks , followed by treatment with oral fluconazole . The primary outcome measure was early fungicidal activity , as determined by results of serial , quantitative cerebral spinal fluid cryptococcal cultures . Secondary outcome measures were safety and mortality . The median duration of follow-up was 1 year . RESULTS Early fungicidal activity was significantly greater for group 2 than for group 1 ( mean + /- SD , -0.56 + /- 0.24 vs. -0.45 + /- 0.16 log cfu/mL of cerebral spinal fluid per day ; P = .02 ) . The incidence of renal impairment did not significantly differ between the 2 groups . Anemia was associated with female sex and , less strongly , with membership in group 2 . Renal impairment and anemia reversed after the regimen was switched to fluconazole . Two- and 10-week mortality rates were 6 % and 24 % , respectively , with no difference between groups . CONCLUSIONS AmB , 1 mg/kg per day , plus flucytosine is more rapidly fungicidal than is st and ard-dose AmB plus flucytosine . Because of its size , this study provides limited data on any difference in toxicity between the regimens , but toxicities were manageable and reversible . CLINICAL TRIALS REGISTRATION NUMBER IS RCT N68133435 ( http://www.controlled-trials.com ) The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B ( AmB ) lipid complex ( ABLC ) in the treatment of AIDS-associated cryptococcal meningitis . Of 55 patients r and omly assigned to 6 weeks of therapy with ABLC ( 1.2 - 5.0 mg/[kg.d ] , with ascending doses for three sequential cohorts ) or AmB ( 0.7 - 1.2 mg/[kg.d ] ) , 46 received > or = 12 doses . Transfusion requirements , mean decreases in hemoglobin level , and mean increases in creatinine level were significantly greater with AmB than with ABLC . The total number of adverse events , infusion-related events , and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar . Among 21 recipients of ABLC at a dosage of 5 mg/kg ( daily for 2 weeks and then thrice weekly for 4 weeks ) , symptoms and signs resolved for 18 ( 86 % ) . Of those receiving > or = 12 doses of ABLC , cultures converted to negative for 8 ( 42 % ) , were undeterminable for 3 ( 16 % ) , and remained positive for 8 ( 42 % ) despite resolution of symptoms . Although preliminary , these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis . Because this formulation has less hematologic and renal toxicity than does AmB , further evaluation of ABLC is warranted Background : Cryptococcal meningitis in Africa is associated with up to 70 % mortality at 3 months and 500 000 deaths annually . We examined strategies to improve on fluconazole ( FLU ) monotherapy : addition of flucytosine ( 5-FC ) and /or addition of short-course amphotericin B ( AmB ) . Methods : In step 1 , previously reported , patients were r and omized to receive FLU 1200 mg per day with or without 5-FC 100 mg/kg per day for 14 days . In step 2 , 43 patients were similarly r and omized , with addition of AmB 1 mg/kg per day for 7 days to both arms . After 2 weeks , patients received FLU monotherapy and were followed to 10 weeks . The primary endpoint was rate of clearance of infection ( early fungicidal activity , EFA ) . Secondary endpoints related to safety and mortality . Results : Forty patients ( 25 % with Glasgow Coma Scale < 15 ) were analyzed . EFA for the triple combination arm was greater than that for AmB – FLU : −0.50 ± 0.15 log CFU/day vs. −0.38 ± 0.19 log colony forming units per day ( P = 0.03 ) ; and greater than that for step 1 with FLU–5-FC ( −0.28 ± 0.17 ) or FLU alone ( −0.11 ± 0.09 ) . Combined analysis across steps revealed that addition of 5-FC and AmB had significant , independent additive effects on EFA , with trends toward fewer early deaths with addition of 5-FC ( 4/41 vs. 11/39 , P = 0.05 ) and fewer deaths overall with addition of AmB ( 13/39 vs. 20/40 , P = 0.1 ) . Conclusion : Addition of 5-FC and short-course AmB to high-dose FLU significantly enhanced EFA and may be associated with favorable trends in survival . Both these strategies should be tested in a larger phase III study 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 . It is generally acknowledged that amphotericin B is the most effective treatment for cryptococcal meningitis . However , administration of this drug is accompanied by substantial adverse effects . This double-blind study , performed before the routine availability of highly active antiretroviral therapy , was design ed to compare the efficacy and safety of liposomal amphotericin B to conventional amphotericin deoxycholate in patients with acquired immunodeficiency syndrome ( AIDS ) and acute cryptococcal meningitis . METHODS . Patients were r and omized ( ratio , 1:1:1 ) from multiple sites in the United States and Canada to receive either amphotericin B at 0.7 mg/kg/day ( n = 87 ) , liposomal amphotericin B at 3 mg/kg/day ( n = 86 ) , or liposomal amphotericin B at 6 mg/kg/day ( n = 94 ) . RESULTS . Efficacy was similar among all 3 treatment groups . The overall incidence of infusion-related reactions was significantly lower for both the 3 mg/kg/day and 6 mg/kg/day dosages of liposomal amphotericin B , compared with conventional amphotericin B ( P < .001 ) . Significantly fewer patients who received the 3 mg/kg/day dosage of liposomal amphotericin B developed nephrotoxicity , indicated by a doubling of the serum creatinine value , compared with recipients of conventional amphotericin B ( P = .004 ) . Overall mortality at 10 weeks was 11.6 % , with no significant differences among the treatment groups . CONCLUSIONS . Liposomal amphotericin B provides an equally efficacious alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis . Liposomal amphotericin B at a dosage of 3 mg/kg/day is accompanied by significantly fewer adverse effects BACKGROUND Cryptococcal meningitis is a major cause of human immunodeficiency virus (HIV)-associated morbidity and mortality in Africa . Improved oral treatment regimens are needed because amphotericin B is neither available nor feasible in many centers . Fluconazole at a dosage of 1200 mg per day is more fungicidal than at a dosage of 800 mg per day , but mortality rates remain unacceptably high . Therefore , we examined the effect of adding oral flucytosine to fluconazole . METHODS From 13 February through 2 December 2008 , HIV-seropositive , antiretroviral-naive patients experiencing their first episode of cryptococcal meningitis were r and omized to receive ( 1 ) 14 days of fluconazole ( 1200 mg per day ) alone or ( 2 ) in combination with flucytosine ( 100 mg/kg per day ) followed by fluconazole ( 800 mg per day ) , with both groups undergoing 10 weeks of follow-up . The primary end point was early fungicidal activity , derived from quantitative cerebrospinal fluid cultures on days 1 , 3 , 7 , and 14 . Secondary end points were safety and 2- and 10-week mortality . RESULTS Forty-one patients were analyzed . Baseline mental status , cryptococcal burden , opening pressure , CD4(+ ) cell count , and HIV load were similar between groups . Combination therapy was more fungicidal than fluconazole alone ( mean early fungicidal activity + /- st and ard deviation -0.28 + /- 0.17 log colony-forming units [CFU]/mL per day vs -0.11 + /- 0.09 log CFU/mL per day ; P < .001 ) . The combination arm had fewer deaths by 2 weeks ( 10 % vs 37 % ) and 10 weeks ( 43 % vs 58 % ) . More patients had grade III or IV neutropenia with combination therapy ( 5 vs 1 , within the first 2 weeks ; P = .20 ) , but there was no increase in infection-related adverse events . CONCLUSIONS The results suggest that optimal oral treatment for cryptococcal meningitis is high-dose fluconazole with flucytosine . Efforts are needed to increase availability of flucytosine in Africa . Clinical trials registration . is rct n.org Identifier : IS RCT N02725351 BACKGROUND It frequently takes more than 2 weeks for drug treatments for cryptococcal meningitis to sterilise cerebrospinal fluid ( CSF ) . In-vitro and animal studies lend support to the use of combinations of amphotericin B , flucytosine , and fluconazole for treatment of cryptococcosis . We compared the fungicidal activity of combinations of these drugs for initial treatment of patients with cryptococcal meningitis . METHODS 64 patients with a first episode of HIV-associated cryptococcal meningitis were r and omised to initial treatment with : amphotericin B ( 0.7 mg/kg daily ) ; amphotericin B plus flucytosine ( 100 mg/kg daily ) ; amphotericin B plus fluconazole ( 400 mg daily ) ; or triple therapy with amphotericin B , flucytosine , and fluconazole . Our primary endpoint was fungicidal activity , measured by the rate of reduction in CSF cryptococcal colony-forming units ( CFU ) from serial quantitative CSF cultures on days 3 , 7 , and 14 of treatment . FINDINGS Baseline CSF CFU counts were an important prognostic factor . Clearance of cryptococci from the CSF was exponential and was significantly faster with amphotericin B plus flucytosine than with amphotericin B alone ( p=0.0006 ) , amphotericin B plus fluconazole ( p=0.02 ) , or triple therapy ( p=0.02 ) . INTERPRETATION At these doses , amphotericin B plus flucytosine is the most rapidly fungicidal regimen . Quantification of CSF cultures provides a powerful new means to accurately assess the fungicidal activity of new treatment regimens for cryptococcal meningitis BACKGROUND Combination antifungal therapy ( amphotericin B deoxycholate and flucytosine ) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality , as compared with amphotericin B alone . We performed a r and omized , controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days . METHODS We conducted a r and omized , three-group , open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection . All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day ; patients in group 1 were treated for 4 weeks , and those in groups 2 and 3 for 2 weeks . Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks , and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks . RESULTS A total of 299 patients were enrolled . Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone ( 15 vs. 25 deaths by day 14 ; hazard ratio , 0.57 ; 95 % confidence interval [ CI ] , 0.30 to 1.08 ; unadjusted P=0.08 ; and 30 vs. 44 deaths by day 70 ; hazard ratio , 0.61 ; 95 % CI , 0.39 to 0.97 ; unadjusted P=0.04 ) . Combination therapy with fluconazole had no significant effect on survival , as compared with monotherapy ( hazard ratio for death by 14 days , 0.78 ; 95 % CI , 0.44 to 1.41 ; P=0.42 ; hazard ratio for death by 70 days , 0.71 ; 95 % CI , 0.45 to 1.11 ; P=0.13 ) . Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid ( -0.42 log10 colony-forming units [ CFU ] per milliliter per day vs. -0.31 and -0.32 log10 CFU per milliliter per day in groups 1 and 3 , respectively ; P<0.001 for both comparisons ) . Rates of adverse events were similar in all groups , although neutropenia was more frequent in patients receiving a combination therapy . CONCLUSIONS Amphotericin B plus flucytosine , as compared with amphotericin B alone , is associated with improved survival among patients with cryptococcal meningitis . A survival benefit of amphotericin B plus fluconazole was not found . ( Funded by the Wellcome Trust and the British Infection Society ; Controlled-Trials.com number , IS RCT N95123928 . ) Objective We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment . Design The trial was a prospect i ve , r and omized , and non-blinded study . Setting : The study was performed at an academic centre for AIDS , Amsterdam , The Netherl and s. Patients , participants Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis , r and omized between 5 February 1987 and 1 January 1990 , were included for analysis . Interventions Oral itraconazole ( 200 mg twice daily ) , versus amphotericin B ( 0.3 mg/kg daily ) intravenously plus oral flucytosine ( 150 mg/kg daily ) was administered for 6 weeks followed by maintenance therapy with oral itraconazole ( 200 mg daily ) to all patients . Main outcome measures Outcome measures were a complete or partial response , recrudescence and relapse . Results A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine ( P = 0.009 ) . A partial response was observed in seven out of the 14 patients assigned to itraconazole . During maintenance therapy , recrudescence ( n = 6 ) or relapse ( n = 1 ) occurred in seven out of the 12 patients initially assigned to itraconazole , whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine ( P = 0.22 ) ; recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks ( P = 0.003 ) . Conclusion Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis BACKGROUND Progress in therapy for cryptococcal meningitis has been slow because of the lack of a suitable marker of treatment response . Previously , we demonstrated the statistical power of a novel endpoint , the rate of clearance of infection , based on serial quantitative cultures of cerebrospinal fluid , to differentiate the fungicidal activity of alternative antifungal drug regimens . We hypothesized that the rate of clearance of infection should also be a clinical ly meaningful endpoint . METHODS We combined data from cohorts of patients with human immunodeficiency virus-associated cryptococcal meningitis from Thail and , South Africa , and Ug and a , for whom the rate of clearance of infection was determined , and clinical and laboratory data prospect ively collected , and explored the association between the rate of clearance of infection and mortality by Cox survival analyses . RESULTS The combined cohort comprised 262 subjects . Altered mental status at presentation , a high baseline organism load , and a slow rate of clearance of infection were independently associated with increased mortality at 2 and 10 weeks . Rate of clearance of infection was associated with antifungal drug regimen and baseline cerebrospinal fluid interferon-gamma levels . CONCLUSIONS The results support the use of the rate of clearance of infection or early fungicidal activity as a means to explore antifungal drug dosages and combinations in phase II studies . An increased underst and ing of how the factors determining outcome interrelate may help clarify opportunities for intervention BACKGROUND Intravenous amphotericin B , with or without flucytosine , is usually st and ard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome ( AIDS ) . Fluconazole , an oral triazole agent , represents a promising new approach to the treatment of cryptococcal disease . METHODS In a r and omized multicenter trial , we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis . Eligible patients , in all of whom the diagnosis had been confirmed by culture , were r and omly assigned in a 2:1 ratio to receive either fluconazole ( 200 mg per day ) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period . RESULTS Of the 194 eligible patients , 131 received fluconazole and 63 received amphotericin B ( mean daily dose , 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure ; P = 0.34 ) . Treatment was successful in 25 of the 63 amphotericin B recipients ( 40 percent ; 95 percent confidence interval , 26 percent to 53 percent ) and in 44 of the 131 fluconazole recipients ( 34 percent ; 95 percent confidence interval , 25 percent to 42 percent ) ( P = 0.40 ) . There was no significant difference between the groups in overall mortality due to cryptococcosis ( amphotericin vs. fluconazole , 9 of 63 [ 14 percent ] vs. 24 of 131 [ 18 percent ] ; P = 0.48 ) ; however , mortality during the first two weeks of therapy was higher in the fluconazole group ( 15 percent vs. 8 percent ; P = 0.25 ) . The median length of time to the first negative cerebrospinal fluid culture was 42 days ( 95 percent confidence interval , 28 to 71 ) in the amphotericin B group and 64 days ( 95 percent confidence interval , 53 to 67 ) in the fluconazole group ( P = 0.25 ) . Multivariate analyses identified abnormal mental status ( lethargy , somnolence , or obtundation ) as the most important predictive factor of a high risk of death during therapy ( P less than 0.0001 ) . CONCLUSIONS Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS . Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure . The optimal therapy for patients at high risk remains to be determined We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine . In 50 patients with 51 courses of therapy adherent to the protocol , 27 courses were with amphotericin B and 24 with the combination . Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks , the combination cured or improved more patients ( 16 vs 11 ) , produced fewer failures or relapses ( three vs. 11 ) , more rapid sterilization of the cerebrospinal fluid ( P less than 0.001 ) and less nephrotoxicity ( P less than 0.05 ) than did amphotericin B alone . The number of deaths was the same ( five ) with each regimen . Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening . We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis BACKGROUND Amphotericin B treatment in cryptococcosis requires daily hospital visits or admission . Its toxicities and hospital costs have been concerned . Short course amphotericin B regimen warrants to be evaluated . OBJECTIVE To compare the safety and efficacy of one-week ( AmB1 ) with two-week ( AmB2 ) amphotericin B both followed by fluconazole . MATERIAL AND METHOD 57 AIDS with cryptococcal meningitis were r and omly assigned to either AmB1 or AmB2 . Microbiological and clinical clearances were the outcomes of the study . RESULTS The treatment success at 6 weeks was 63.3 % in AmB1 and 70.4 % in AmB2 ( p = 0.574 ) . Clinical assessment at week 10 and renal toxicities were not significantly different between both regimens . Mortality rate was 14 % however , 75 % of deaths were in AmB2 . CONCLUSION AmB1 was comparably effective and safe as the st and ard AmB2 regimen in the treatment of AIDS related cryptococcal meningitis . It can be an alternative regimen to lower hospital based care and improve cost effective for source limiting health care centers We performed a r and omized trial in which combination therapy with fluconazole and short-term flucytosine was compared with fluconazole monotherapy in 58 patients with AIDS-associated cryptococcal meningitis ( CM ) . Thirty of these patients were r and omized to receive combination therapy with fluconazole , 200 mg once a day for 2 months , and flucytosine , 150 mg/(kg.d ) for the first 2 weeks , and 28 were r and omized to receive monotherapy with fluconazole at the same dose for 2 months . Patients in both groups who survived for 2 months received fluconazole as maintenance therapy at a dose of 200 mg three times per week for 4 months . The combination therapy prevented death within 2 weeks and significantly increased the survival rate among these patients ( 32 % ) at 6 months over that among patients receiving monotherapy ( 12 % ) ( P = .022 ) . The combination therapy also result ed in a significant decrease in the severity of headache after 1 month of treatment , compared with monotherapy ( P = .005 ) . No serious adverse reactions were observed in patients receiving either regimen . These data indicate that treatment with fluconazole and short-term flucytosine is a cost-effective and safe regimen that improves the quality of life for patients with AIDS-associated CM in developing countries where human immunodeficiency virus is endemic BACKGROUND . Cryptococcal meningitis ( CM ) remains a leading cause of acquired immunodeficiency syndrome-related death in sub-Saharan Africa . The timing of the initiation of antiretroviral therapy ( ART ) for human immunodeficiency virus (HIV)-associated CM remains uncertain . The study aim ed to determine the optimal timing for initiation of ART in HIV-positive individuals with CM . METHODS . A prospect i ve , open-label , r and omized clinical trial was conducted at a tertiary teaching hospital in Zimbabwe . Participants were aged > or = 18 years , were ART naive , had received a first CM diagnosis , and were r and omized to receive early ART ( within 72 h after CM diagnosis ) or delayed ART ( after 10 weeks of treatment with fluconazole alone ) . Participants received 800 mg of fluconazole per day . The ART regimen used was stavudine , lamivudine , and nevirapine given twice daily . The duration of follow-up was up to 3 years . The primary end point was all-cause mortality . RESULTS . Fifty-four participants were enrolled in the study ( 28 in the early ART arm and 26 in the delayed ART arm ) . The median CD4 cell count at enrollment was 37 cells/mm(3 ) ( interquartile range , 17 - 69 cells/mm(3 ) ) . The 3-year mortality rate differed significantly between the early and delayed ART groups ( 88 % vs 54 % ; P < .006 ) ; the overall 3-year mortality rate was 73 % . The median duration s of survival were 28 days and 637 days in the early and delayed ART groups , respectively ( P = .031 , by log-rank test ) . The risk of mortality was almost 3 times as great in the early ART group versus the delayed ART group ( adjusted hazard ratio , 2.85 ; 95 % confidence interval , 1.1 - 7.23 ) . The study was terminated early by the data safety monitoring committee . CONCLUSIONS . In re source -limited setting s where CM management may be suboptimal , when compared with a delay of 10 weeks after a CM diagnosis , early initiation of ART results in increased mortality . Trial registration . Clinical Trials.gov identifier : NCT00830856 BACKGROUND A trial-level surrogate end point for a r and omized clinical trial may allow assessment of the relative benefits of the treatment to be performed at an earlier time point and potentially with a smaller sample size . However , determining whether an end point is a reliable trial-level surrogate based on results of previous trials is not straightforward . The question of trial-level surrogacy is easily confused with the question of individual-level surrogacy , and this confusion can lead to controversy . A recent example concerns the evaluation of pathologic complete response ( pCR ) as a surrogate for event-free survival ( EFS ) and overall survival ( OS ) in early-stage breast cancer . MATERIAL S AND METHODS The differences between individual-level surrogacy ( i.e. for patients receiving a specific treatment , the surrogate end point predicts the definitive end point ) and trial-level surrogacy ( the results of the trial for the surrogate end point predict the results of the trial for the definitive end point ) are discussed . Trial-level data used in two previous meta-analyses evaluating pCR as a trial-level surrogate for EFS and OS were re-analyzed using methods that appropriately account for the variability in pCR rates as well as the variability in the hazard ratios for EFS and OS . RESULTS There is no evidence that pCR is a trial-level surrogate for EFS or OS , nor is there evidence that pCR could be used reliably to screen out nonpromising agents from further drug development . CONCLUSIONS At present , neoadjuvant RCTs should continue to follow patients to observe EFS and OS to assess clinical benefit , and they should be design ed with sufficient sample size to reliably assess EFS . However , one can not rule out the possibility that future meta-analyses involving more trials and in which the patient population or class of treatments is restricted could suggest the validity of pCR as a trial-level surrogate for EFS or OS in some focused setting To evaluate HIV-1 RNA and CD4 + cell responses to therapy as predictors of clinical progression and to evaluate levels and trends of these markers prior to clinical failure , HIV-1 RNA measurements were retrospectively obtained on subjects who progressed to AIDS or death and a r and om sample of subjects who did not . Sample s were taken from AIDS Clinical Trials Group Study 175 , a r and omized trial comparing nucleoside analog therapies in subjects with CD4 + cell counts of between 200 and 500 cells/mm3 . HIV-1 RNA and CD4 + cell count independently predicted clinical progression . Risk of subsequent progression is best captured by the change to the last measured value for CD4 + cell count and the area under the curve minus baseline , a measure of viral replication over time , for HIV-1 RNA . Subjects who failed had lower CD4 + cell counts , greater rates of CD4 + cell decline , and higher HIV-1 RNA levels , but not greater rates of HIV-1 RNA increase than subjects who did not . Subjects who maintained more than 200 CD4 + cells/mm3 and fewer than 10,000 copies of HIV-1 RNA per milliliter had low risk of progression . During the first few months of therapy , treatments are best monitored by regular HIV-1 RNA and less frequent CD4 + cell measurements . Thereafter , both markers should be monitored on a similar schedule to identify rapidly declining CD4 + cell counts , or adverse levels of either . These results further delineate the prognostic significance of HIV-1 RNA and CD4 + cell count and should help to better define their utility in the practice setting One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter , prospect i ve , r and omized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy . Among 91 patients who met preestablished criteria for r and omization , cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks . The estimated relapse rate for the four-week regimen was higher--27 as compared with 16 percent -- whereas the incidence of toxic effects for the two regimens was similar--44 as compared with 43 percent . Among 23 transplant recipients , 4 of 5 treated for four weeks relapsed , leading to the decision to treat the rest of the group for six weeks . Only 3 of the 18 treated for six weeks relapsed . In a third group of 80 patients , the protocol was not followed during the initial four weeks , and these patients were not r and omized . Thirty-eight died or relapsed . Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors ( P less than 0.05 ) of a favorable response : headache as a symptom , normal mental status , and a cerebrospinal fluid white-cell count above 20 per cubic millimeter . These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications , underlying disease , or immunosuppressive therapy ; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32 ; and at four weeks of therapy , a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8 . Patients who do not meet these criteria should receive at least six weeks of therapy The comparison of initial treatment with amphotericin B ( 0.7 mg/kg/d ) plus rifampin ( 600 mg/d ) with amphotericin B ( 0.7 mg/kg/d ) alone for 2 weeks , both followed by fluconazole ( 400 mg/ d ) for 8 weeks in the acute treatment of cryptococcal meningitis in AIDS by an open- r and omized , controlled , prospect i ve clinical trial is reported . Twenty patients were enrolled in each group . There were no significant differences between the groups in regard to a negative CSF culture for Cryptococcus neoformans in the 2nd and 10th weeks of treatment , time until normal body temperature after treatment , number of patients who died , and persistence of high CSF pressure after completion of treatment . Elevated intracranial pressure was an important factor associated with the patients who died . These results indicate that the combination of amphotericin B plus rifampin is not superior to amphotericin B alone BACKGROUND There is need to investigate the use of liposomal amphotericin B in cryptococcal meningitis in India . AIMS To compare the efficacy , safety , duration of treatment and cost of two doses of liposomal amphotericin B ( Amp B ) ( Fungisome ) in cryptococcal meningitis in HIV/AIDS patients . SETTING S AND DESIGN Prospect i ve , r and omized , multicenter study in tertiary care hospitals across India . MATERIAL S AND METHODS Adult patients with culture-proven cryptococcal meningitis with HIV/AIDS were r and omized to receive either 1 ( Group A ) or 3 mg/kg/day of Fungisome ( Group B ) . Clinical efficacy and tolerability , laboratory evaluations and mycological response were assessed daily , twice weekly and weekly respectively . The patients were assessed at four and eight-week follow-up . STATISTICS We calculated average and st and ard deviation for the various parameters . RESULTS The time to show clinical response was 13.66 days ( 1 mg ) and 9.55 days ( 3 mg ) . In Group B ( n=6 complete response ) , 50 % patients responded within one week by microbial conversion , 83 % in two weeks and 100 % in three weeks . Patients with 1 mg dose ( n=4 complete response ) , none showed microbial conversion within one week , 75 % responded in two weeks , whereas one patient took four weeks . The average duration of treatment was 36.5+/-14.4 and 26.5+/-5.89 ( S.D. ) days in 1 and 3 mg/kg/day respectively . Drug was tolerated with little renal , hepatic or hematological toxicity . The cost was found to be 3.81 lacs and 1.74 lacs with 3mg/kg/day and 1mg/kg/day respectively . CONCLUSION Higher dose showed better efficacy and quicker microbial conversion of Cerebrospinal fluid ( CSF ) ( cerebrospinal fluid ) than 1 mg/kg/day . It shortened the duration of treatment in days by 27 % while drug cost almost doubled ( CLINICAL TRIAL REGISTRATION NUMBER IS RCT N 52812742 ) The optimal regimen for treatment of Mycobacterium avium complex ( MAC ) disease has not been established . Eighty-five AIDS patients with disseminated MAC disease were r and omized to receive a three-drug regimen of clarithromycin , rifabutin or clofazimine , and ethambutol . Two dosages of clarithromycin , 500 or 1,000 mg twice daily ( b.i.d . ) , were compared . The Data and Safety Monitoring Board recommended discontinuation of the clarithromycin dosage comparison and continuation of the rifabutin vs. clofazimine comparison . After a mean follow-up of 4.5 months , 10 ( 22 % ) of 45 patients receiving clarithromycin at 500 mg b.i.d . had died ( 70 deaths per 100 person-years ) compared with 17 ( 43 % ) of 40 patients receiving clarithromycin at 1,000 mg b.i.d . ( 158 deaths per 100 person-years ) ( relative risk , 2.43 ; 95 % confidence interval , 1.11 - 5.34 ; P = .02 ) . After 10.4 months , 20 ( 49 % ) of 41 patients receiving rifabutin had died ( 81 deaths per 100 person-years ) compared with 23 ( 52 % ) of 44 patients receiving clofazimine ( 94 deaths per 100 person-years ) ( relative risk , 1.20 ; 95 % confidence interval , 0.65 - 2.19 ; P = .56 ) . Bacteriologic outcomes were similar among treatment groups . In treating MAC disease in AIDS patients , the maximum dose of clarithromycin should be 500 mg b.i.d Animal studies and case series have demonstrated the dose-dependent efficacy and long half-life of amphotericin B deoxycholate ( ABd ) , providing the rationale for our r and omized controlled study to compare once-daily ( OD ) ( 1 mg/kg ) and alternate-d ( AD ) ( 2 mg/kg ) administration of ABd in the treatment of cryptococcal meningitis in patients with AIDS hospitalized at King Chulalongkorn Memorial Hospital , Thail and , from 2003 to 2004 . Of 28 patients , 15 and 13 received OD and AD administration , respectively . There was no significant difference between the 2 groups regarding the demography , clinical features , and laboratory data . After 2 weeks of the intensive-phase treatment , there was no significant difference in the clinical response between the OD ( 80 % ) and AD ( 76.9 % ) groups . Mycological response was observed in 33.3 % and 10 % of patients in the OD and AD groups , respectively ( p=0.3 ) . There was no difference in nephrotoxicity and infusion-related events . In conclusion , this is the first r and omized controlled study comparing OD and AD administration of ABd in the treatment of cryptococcal meningitis . Although our study was not sufficiently powered to draw conclusions on clinical efficacy and toxicities , the results are encouraging and should warrant further clinical trials evaluating the efficacy and adverse effects with a larger sample size OBJECTIVE To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis . DESIGN Patients were r and omly assigned to oral fluconazole , 400 mg/d , for 10 weeks or to amphotericin B , 0.7 mg/kg body weight daily for 1 week , then three times weekly for 9 weeks combined with flucytosine , 150 mg/kg d , in four divided doses . SETTING Los Angeles County-University of Southern California Medical Center . PATIENTS Between 15 February and 7 December 1988 , 42 patients had evidence of their first episode of cryptococcal meningitis , of whom 21 participated in the trial . All patients enrolled were men with the acquired immunodeficiency syndrome ( AIDS ) except one woman who was receiving prednisone therapy and was excluded from the final analysis . RESULTS Of 14 patients with AIDS assigned to fluconazole , 8 ( 57 % ; 95 % CI , 29 % to 82 % ) failed ; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy ( 0 % ; CI , 0 % to 46 % ) ( Fisher exact test , P = 0.04 ) . The mean duration of positive cerebrospinal fluid cultures was 40.6 + /- 5.4 days in patients receiving fluconazole and 15.6 + /- 6.6 days in patients receiving amphotericin B plus flucytosine ( Mann-Whitney test , P = 0.02 ) . Overall , 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died ( Fisher exact test , P = 0.27 ) . CONCLUSION Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS We compared amphotericin B ( 0.3 mg/kg/d ) plus flucytosine ( 150 mg/kg/d ) plus itraconazole ( 400 mg/d ) ( study group ) with amphotericin B plus flucytosine ( control group ) by an open-r and omized trial . In the study group , after CSF mycological cultures disclosed nothing , itraconazole was administrated alone through six weeks of treatment . Treatment was considered successful if the patient had two consecutive negative CSF cultures by the end of the 6-week treatment period . Fifty patients were enrolled in each group . There were significant differences between the study group and the control group in the successful treatment ( 100 % vs 90 % ; P = 0.03 ) , the mean length of time until normal body temperature after treatment ( 5.9 + /- 3.7 days vs 8.8 + /- 5.1 days ; P = 0.02 ) and the adverse effects . The mean length of time to the first negative CSF culture was 13.9 + /- 6.1 days in the study group and 13.3 + /- 6.5 days in the control group ( P = 0.66 ) . Relapse rate with itraconazole 200 mg/day was higher in the study group We conducted a phase 2 , double-blind , placebo-controlled study to evaluate the safety and antifungal activity of adjuvant recombinant interferon (rIFN)- gamma 1b in patients with acquired immunodeficiency syndrome and acute cryptococcal meningitis . Patients received 100 or 200 microg of rIFN- gamma 1b or placebo , thrice weekly for 10 weeks , plus st and ard therapy with intravenous amphotericin B , with or without flucytosine , followed by therapy with fluconazole . End points included conversion of cerebrospinal fluid fungal cultures from positive to negative at 2 weeks , resolution of symptoms , and survival . Among 75 patients , 2-week culture conversion occurred in 13 % of placebo recipients , 36 % of rIFN- gamma 1b ( 100 microg ) recipients , and 32 % of rIFN- gamma 1b ( 200 microg ) recipients . There was a trend toward improved combined mycologic and clinical success in rIFN- gamma 1b recipients ( 26 % vs. 8 % ; P=.078 ) . Therapy with rIFN- gamma 1b was well tolerated , and there was no apparent influence on serial CD4 cell counts and human immunodeficiency virus load measurements . Adjunctive therapy with rIFN- gamma 1b holds promise for patients with acute cryptococcal meningitis and warrants further study BACKGROUND The burden of Cryptococcus neoformans in cerebrospinal fluid ( CSF ) predicts clinical outcomes in human immunodeficiency virus (HIV)-associated cryptococcal meningitis ( CM ) and is lower in patients on antiretroviral therapy ( ART ) . This study tested the hypothesis that initiation of ART during initial treatment of HIV/CM would improve CSF clearance of C. neoformans . METHODS A r and omized treatment- strategy trial was conducted in Botswana . HIV-infected , ART-naive adults aged≥21 years initiating amphotericin B treatment for CM were r and omized to ART initiation within 7 ( intervention ) vs after 28 days ( control ) of r and omization , and the primary outcome of the rate of CSF clearance of C. neoformans over the subsequent 4 weeks was compared . Adverse events , including CM immune reconstitution inflammatory syndrome ( CM-IRIS ) , and immunologic and virologic responses were compared over 24 weeks . RESULTS Among 27 subjects enrolled ( 13 intervention and 14 control ) , [ corrected ] the median times to ART initiation were 7 ( interquartile range [ IQR ] , 5–10 ) and 32days ( IQR , 28–36 ) , respectively . The estimated rate of CSF clearance did not differ significantly by treatment strategy ( -0.32 log10 colony-forming units [CFU]/mL/day±0.20 intervention and -0.52 log10 CFUs/mL/day ( ±0.48 ) control , P=.4 ) . Two of 13 ( 15 % ) and 5 of 14 ( 36 % ) subjects died in the intervention and control arms , respectively ( P=0.39 ) . Seven of 13 subjects ( 54 % ) in the intervention arm vs 0 of 14 in the control arm experienced CM-IRIS ( P=.002 ) . CONCLUSIONS Early ART was not associated with improved CSF fungal clearance , but result ed in a high risk of CM-IRIS . Further research on optimal incorporation of ART into CM care is needed . CLINICAL TRIALS REGISTRATION NCT00976040 Clinical trials that compare strategies to optimize antibiotic use are of critical importance but are limited by competing risks that distort outcome interpretation , complexities of noninferiority trials , large sample sizes , and inadequate evaluation of benefits and harms at the patient level . The Antibacterial Resistance Leadership Group strives to overcome these challenges through innovative trial design . Response adjusted for duration of antibiotic risk ( RADAR ) is a novel methodology utilizing a superiority design and a 2-step process : ( 1 ) categorizing patients into an overall clinical outcome ( based on benefits and harms ) , and ( 2 ) ranking patients with respect to a desirability of outcome ranking ( DOOR ) . DOORs are constructed by assigning higher ranks to patients with ( 1 ) better overall clinical outcomes and ( 2 ) shorter duration s of antibiotic use for similar overall clinical outcomes . DOOR distributions are compared between antibiotic use strategies . The probability that a r and omly selected patient will have a better DOOR if assigned to the new strategy is estimated . DOOR/RADAR represents a new paradigm in assessing the risks and benefits of new strategies to optimize antibiotic use |
11,791 | 26,320,031 | Overall , the evidence suggests that yoga and meditation have favourable effects on prisoners | null | null |
11,792 | 28,114,374 | Our findings suggested that p-mTOR overexpression was not significantly related to prognosis in breast carcinoma regarding OS and disease recurrence . | OBJECTIVE Phosphorylated mammalian target of rapamycin ( p-mTOR ) is a promising prognostic marker in many types of cancer .
However , its survival benefit in patients with breast carcinoma remains unknown .
The aim of the present study was to assess the relationship between p-mTOR expression and prognosis in breast carcinoma based on a systematic review and meta- analysis . | Introduction Activation of the phosphatidylinositol-3-kinase ( PI3 K ) and /or mitogen-activated protein kinase ( MAPK ) pathways results in anti-estrogen resistance in vitro , but a biomarker with clinical validity to predict intrinsic resistance has not been identified . In metastatic breast cancer patients with previous exposure to endocrine therapy , the addition of a mammalian target of rapamycine ( mTOR ) inhibitor has been shown to be beneficial . Whether or not patients on adjuvant endocrine treatment might benefit from these drugs is currently unclear . A biomarker that predicts intrinsic resistance could potentially be used as companion diagnostic in this setting . We tested the clinical validity of different downstream-activated proteins in the PI3 K and /or MAPK pathways to predict intrinsic tamoxifen resistance in postmenopausal primary breast cancer patients . Methods We recollected primary tumor tissue from patients who participated in a r and omized trial of adjuvant tamoxifen ( 1–3 years ) versus observation . After constructing a tissue micro-array , cores from 563 estrogen receptor α positive were immunostained for p-AKT(Thr308 ) , p-AKT(Ser473 ) , p-mTOR , p-p706SK and p-ERK1/2 . Cox proportional hazard models for recurrence free interval were used to assess hazard ratios and interactions between these markers and tamoxifen treatment efficacy . Results Interactions were identified between tamoxifen and p-AKT(Thr308 ) , p-mTOR , p-p70S6 K and p-ERK1/2 . Applying a conservative level of significance , p-p70S6 K remained significantly associated with tamoxifen resistance . Patients with p-p70S6 K negative tumors derived significant benefit from tamoxifen ( HR 0.24 , P < 0.0001 ) , while patients whose tumor did express p-p70S6 K did not ( HR = 1.02 , P = 0.95 ) , P for interaction 0.004 . In systemically untreated breast cancer patients , p-p70S6 K was associated with a decreased risk for recurrence . Conclusions Patients whose tumor expresses p-p70S6 K , as a marker of downstream PI3 K and /or MAPK pathway activation , have a favorable prognosis , but do not benefit from adjuvant tamoxifen . A potential benefit from inhibitors of the PI3K/Akt/mTOR pathway in these patients needs to be further explored Background and purpose There are scarce data available on the prognostic/predictive value of p-Akt and p-mTOR protein expression in patients with high-risk early breast cancer . Patients and methods Formalin-fixed paraffin-embedded ( FFPE ) tumor tissue sample s from 997 patients participating in two adjuvant phase III trials were assessed for EGFR , PTEN , p-Akt , p-mTOR protein expression , and PIK3CA mutational status . These markers were evaluated for associations with each other and with selected patient and tumor characteristics , immunohistochemical subtypes , disease-free survival ( DFS ) , and overall survival ( OS ) . Results p-mTOR protein expression was negatively associated with EGFR and positively associated with PTEN , with p-Akt473 , and with the presence of PIK3CA mutations . EGFR expression was positively associated with p-Akt473 , p-Akt308 , and PIK3CA wild-type tumors . Finally , p-Akt308 was positively associated with p-Akt473 expression . In univariate analysis , EGFR ( p = 0.016 ) and the coexpression of EGFR and p-mTOR ( p = 0.015 ) were associated with poor OS . Among patients with p-Akt308-negative or low-expressing tumors , those treated with hormonal therapy were associated with decreased risk for both relapse and death ( p = 0.013 and p < 0.001 , respectively ) . In the subgroup of patients with locoregional relapse , positive EGFR and mTOR protein expression was found to be associated with increased ( p = 0.034 ) and decreased ( p < 0.001 ) risk for earlier relapse , respectively . In multivariate analysis , low levels of p-Akt308 and the coexpression of EGFR and p-mTOR retained their prognostic value . Conclusion Low protein expression of p-Akt308 was associated with improved DFS and OS among patients treated with hormonal therapy following adjuvant chemotherapy . Coexpression of EGFR and p-mTOR was associated with worse OS.ZusammenfassungHintergrundGeringe Date n existieren über den prognostischen/prädiktiven Wert der p-Akt- und p-mTOR-Proteinexpression bei Patienten mit “ High-risk”-Mammakarzinom i m Frühstadium . Patienten und Method enFormalinfixierte und in Paraffin eingebettete ( FFPE ) Tumorgewebeproben von 997 Patienten , welche i m Rahmen von 2 adjuvanten Phase-III-Studien zytostatisch beh and elt wurden , wurden auf EGFR , PTEN , p-Akt , pmTOR und PIK3CA-Mutationsstatus untersucht . Diese Marker wurden in Assoziation mit ausgewählten Patienten- und Tumorcharakteristika , immunhistochemischen Mammakarzinomsubtypen , dem krankheitsfreien Überleben ( DFS ) sowie dem Gesamtüberleben ( OS ) evaluiert . ErgebnisseDie Expression von p-mTOR war negativ mit der Expression von EGFR , jedoch signifikant positiv mit PTEN und p-Akt473 sowie dem Nachweis von PIK3CA-Mutationen assoziiert . Die EGFR-Expression war signifikant positiv mit der Proteinexpression von p-Akt473 und p-Akt308 sowie PIK3CA-Wildtyp-Tumoren assoziiert . Die p-Akt308-Expression war ebenfalls signifikant positiv mit der Expression von p-Akt473 assoziiert . In der univariaten Analyse war sowohl die EGFR ( p = 0,016 ) , als auch die Koexpression von EGFR und p-mTOR ( p = 0,015 ) mit einem schlechteren OS assoziiert . Unter den Patienten mit p-Akt308-negativen oder gering exprimierenden Tumoren konnte bei denjenigen , die mit einer Hormontherapie beh and elt wurden , ein signifikant vermindertes Risiko für ein Rezidiv als auch für den Tod ( jeweils p = 0,013 und p < 0,001 ) nachgewiesen werden . In der Subgruppenanalyse von Patienten mit lokoregionärem Rezidiv konnte eine Assoziation von positivem EGFR-Status sowie mTOR-Expression mit einem jeweils erhöhten ( p = 0,034 ) bzw . verminderten ( p < 0,001 ) Risiko für das Auftreten von Frührezidiven nachgewiesen werden . In der multivariaten Analyse behielten die niedrigen p-Akt308-Werte und die Koexpression von EGFR und p-mTOR ihren prognostischen Wert . FazitEine niedrige Expression von p-Akt308 bei Patienten , die eine Hormontherapie nach einer adjuvanten Chemotherapie erhielten , war mit einem verbesserten DFS und OS assoziiert . Die Koexpression von EGFR und p-mTOR war mit einem schlechteren OS assoziiert In a phase 3 , double-blind , r and omized , international study ( the BOLERO-2 ) , the addition of mTOR inhibitor everolimus to exemestane was evaluated in postmenopausal women with estrogen-receptor-positive ( ER⁺ ) advanced/recurrent breast cancer that was refractory to any nonsteroidal aromatase inhibitor ( NSAI ) . This report presents the safety and up date d ( 18- month ) efficacy results from the Japanese subset ( n=106 ) of BOLERO-2 . After a median follow-up of 18 months , the median progression-free survival time was 8.5 months with everolimus plus exemestane compared to 4.2 months with placebo plus exemestane . The most common adverse events ( AEs ) with everolimus plus exemestane were stomatitis , rash , dysgeusia , and non-infectious lung disease . The AEs reported with the combination therapy were mostly of grade 1 or 2 and manageable with appropriate intervention . In conclusion , this combination could be a useful addition to the armamentarium of treatments for Japanese postmenopausal women with ER⁺ advanced/recurrent breast cancer progressing on NSAIs BACKGROUND Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin ( mTOR ) intracellular signaling pathway . In early studies , the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity . METHODS In this phase 3 , r and omized trial , we compared everolimus and exemestane versus exemestane and placebo ( r and omly assigned in a 2:1 ratio ) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease ( or both ) . The primary end point was progression-free survival . Secondary end points included survival , response rate , and safety . A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed . RESULTS Baseline characteristics were well balanced between the two study groups . The median age was 62 years , 56 % had visceral involvement , and 84 % had hormone-sensitive disease . Previous therapy included letrozole or anastrozole ( 100 % ) , tamoxifen ( 48 % ) , fulvestrant ( 16 % ) , and chemotherapy ( 68 % ) . The most common grade 3 or 4 adverse events were stomatitis ( 8 % in the everolimus-plus-exemestane group vs. 1 % in the placebo-plus-exemestane group ) , anemia ( 6 % vs. < 1 % ) , dyspnea ( 4 % vs. 1 % ) , hyperglycemia ( 4 % vs. < 1 % ) , fatigue ( 4 % vs. 1 % ) , and pneumonitis ( 3 % vs. 0 % ) . At the interim analysis , median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane , according to assessment s by local investigators ( hazard ratio for progression or death , 0.43 ; 95 % confidence interval [ CI ] , 0.35 to 0.54 ; P<0.001 ) . Median progression-free survival was 10.6 months and 4.1 months , respectively , according to central assessment ( hazard ratio , 0.36 ; 95 % CI , 0.27 to 0.47 ; P<0.001 ) . CONCLUSIONS Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors . ( Funded by Novartis ; BOLERO-2 Clinical Trials.gov number , NCT00863655 . ) BACKGROUND Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway . We aim ed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab . METHODS In this r and omised , double-blind , placebo-controlled , phase 3 trial , we recruited women with HER2-positive , trastuzumab-resistant , advanced breast carcinoma who had previously received taxane therapy . Eligible patients were r and omly assigned ( 1:1 ) using a central patient screening and r and omisation system to daily everolimus ( 5 mg/day ) plus weekly trastuzumab ( 2 mg/kg ) and vinorelbine ( 25 mg/m(2 ) ) or to placebo plus trastuzumab plus vinorelbine , in 3-week cycles , stratified by previous lapatinib use . The primary endpoint was progression-free survival ( PFS ) by local assessment in the intention-to-treat population . We report the final analysis for PFS ; overall survival follow-up is still in progress . This trial is registered with Clinical Trials.gov , number NCT01007942 . FINDINGS Between Oct 26 , 2009 , and May 23 , 2012 , 569 patients were r and omly assigned to everolimus ( n=284 ) or placebo ( n=285 ) . Median follow-up at the time of analysis was 20.2 months ( IQR 15.0 - 27.1 ) . Median PFS was 7.00 months ( 95 % CI 6.74 - 8.18 ) with everolimus and 5.78 months ( 5.49 - 6.90 ) with placebo ( hazard ratio 0.78 [ 95 % CI 0.65 - 0.95 ] ; p=0.0067 ) . The most common grade 3 - 4 adverse events were neutropenia ( 204 [ 73 % ] of 280 patients in the everolimus group vs 175 [ 62 % ] of 282 patients in the placebo group ) , leucopenia ( 106 [ 38 % ] vs 82 [ 29 % ] ) , anaemia ( 53 [ 19 % ] vs 17 [ 6 % ] ) , febrile neutropenia ( 44 [ 16 % ] vs ten [ 4 % ] ) , stomatitis ( 37 [ 13 % ] vs four [ 1 % ] ) , and fatigue ( 34 [ 12 % ] vs 11 [ 4 % ] ) . Serious adverse events were reported in 117 ( 42 % ) patients in the everolimus group and 55 ( 20 % ) in the placebo group ; two on-treatment deaths due to adverse events occurred in each group . INTERPRETATION The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated , HER2-positive , advanced breast cancer . The clinical benefit should be considered in the context of the adverse event profile in this population |
11,793 | 21,926,155 | RESULTS Vascular function and morphology was impaired in RA relative to healthy controls .
The majority of studies reported no associations between systemic inflammation and vascular function .
CONCLUSION The link between systemic inflammation and vascular function and morphology is not wholly supported by the available literature . | OBJECTIVES RA associates with significantly increased morbidity and mortality from cardiovascular disease ( CVD ) .
This may be due to complex interactions between traditional CVD risk factors , systemic rheumatoid inflammation and the vasculature .
We review ed the current literature to answer : ( i ) whether there is sufficient evidence that patients with RA have altered vascular function and morphology compared with normal controls ; ( ii ) whether there is sufficient evidence to determine if such changes relate predominantly to systemic inflammation ; and ( iii ) whether any changes of vascular function and morphology in RA can be modified with therapy . | BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements . Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events Increased cardiovascular mortality has been associated with rheumatoid arthritis ( RA ) . There have been reports indicating that tumor necrosis factor blockers may exert favorable but transient effects on lipid profile , flow-mediated vasodilation ( FMD ) of the brachial artery , and common carotid intima – media thickness ( ccIMT ) in RA . In this study , we assessed the effects of rituximab on FMD , ccIMT , and lipid profile . Five female RA patients received two infusions of 1000 mg rituximab i.v . High-resolution B-mode ultrasound was used to assess brachial FMD and ccIMT . We also determined plasma total cholesterol ( TC ) , HDL-C , LDL-C , and triglyceride ( Tg ) levels . Assessment s were performed at baseline , as well as at weeks 2 , 6 , and 16 after the first infusion . Rituximab ( RTX ) treatment result ed in a rapid and sustained improvement in FMD . The mean improvement was 30 % , 22 % , and 81 % at weeks 2 , 6 , and 16 , respectively . RTX had little effect on atherosclerosis within this short period of time ; however , we observed 10 % , 9 % , and 2 % decreases in ccIMT at weeks 2 , 6 , and 16 , respectively . RTX therapy result ed in 3–11 % decrease in TC , as well as 14–35 % increase in HDL-C levels . Two infusions of RTX exerted early and sustained favorable effects on endothelial dysfunction , as well as plasma TC and HDL-C levels . RTX may also decrease ccIMT ; however , longer follow-up is needed to assess the prolonged effects of RTX on vascular function and lipid profile in RA patients Objectives : Rheumatoid arthritis ( RA ) is associated with increased cardiovascular disease ( CVD ) risk that has been attributed to endothelial dysfunction and inflammation . Non‐steroidal anti‐inflammatory drugs ( NSAIDs ) and cyclo‐oxygenase (COX)‐2 inhibitors have been shown in some studies to improve endothelial function in subjects without RA . The aim of this study was to investigate the effects of COX inhibition on endothelial function in patients with RA . Methods : Patients with RA ( n = 37 ) were r and omized to receive a 2‐week course of either indomethacin ( 75 mg bd ) , rofecoxib ( 12.5 mg bd ) , or placebo in a double‐blind study . Endothelial function was measured using flow‐mediated dilation ( FMD ) of the brachial artery in response to reactive hyperaemia . Arterial stiffness was also assessed using pulse wave analysis ( PWA ) through the measurement of the aortic augmentation index ( AIx ) . Measurements of vascular function and inflammatory markers were taken before and at the end of the treatment period . Results : There were no significant differences in changes in FMD , AIx , blood pressure ( BP ) , serum creatinine , erythrocyte sedimentation rate ( ESR ) , or high‐sensitivity C‐reactive protein ( hsCRP ) between groups . However , compared with the other treatment groups , there was a tendency for systolic BP to decrease in the placebo group ( p = 0.063 ) and for creatinine to increase in the indomethacin and rofecoxib groups after treatment ( p = 0.054 ) . Conclusions : This study suggests that COX inhibition by indomethacin or rofecoxib do not improve endothelial function in patients with RA BACKGROUND Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis . Therefore , we prospect ively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates . METHODS AND RESULTS Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine , sympathetic activation by cold pressor testing , dilator responses to increased blood flow , and dilation in response to nitroglycerin . Cardiovascular events ( cardiovascular death , unstable angina , myocardial infa rct ion , percutaneous transluminal coronary angioplasty , coronary bypass grafting , ischemic stroke , or peripheral artery revascularization ) served as outcome variables over a median follow-up period of 7.7 years . Patients suffering from cardiovascular events during follow-up ( n=16 ) had significantly increased vasoconstrictor responses to acetylcholine infusion ( P=0 . 009 ) and cold pressor testing ( P=0.002 ) , as well as significantly blunted vasodilator responses to increased blood flow ( P<0.001 ) and the intracoronary injection of nitroglycerin ( P=0.001 ) . Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis . By multivariate analysis , all tests of coronary vasoreactivity were significant , independent predictors of a poor prognosis , even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself . CONCLUSIONS Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates . Thus , the assessment of coronary endothelial vasoreactivity can provide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease Objectives : Vascular endothelial function and common carotid artery intima – medial thickness ( CCA‐IMT ) are well‐established surrogate markers for early atherosclerotic disease , which accounts for 30–40 % of excess mortality in rheumatoid arthritis ( RA ) patients . Our aim was to investigate whether long‐term treatment with anti‐tumour necrosis factor (TNF)α agents can modulate endothelial function and CCA‐IMT . Methods : Twelve patients with RA ( mean age 54.8±15 years ) on anti‐TNFα treatment ( seven adalimumab , five infliximab ) due to uncontrolled disease activity , with mean Disease Activity Score ( DAS28 ) 5.7 ( range 4.6–6.9 ) despite disease‐modifying anti‐rheumatic drugs ( DMARDs ) , were studied prospect ively . Patients were assessed at baseline and after 3 and 18 months for endothelial‐dependent vasodilatation , assessed by flow‐mediated vasodilatation ( FMD ) , endothelial‐independent vasodilatation and CCA‐IMT . RA disease activity and response to therapy were assessed by the DAS28 index . Results : After 18 months of treatment , 67 % of the patients were responders according to European League Against Rheumatism ( EULAR ) response criteria . Anti‐TNFα treatment improved FMD ( from 7±4.3 % to 11.1±3.8 % , p = 0.026 ) whereas CCA‐IMT did not change significantly [ from 0.67 ( 0.4–1 ) to 0.68 ( 0.39–1.2 ) mm ; mean change 0.01 ( −0.06 to 0.08 ) mm ] . Endothelial‐independent vasodilatation remained stable ( 20.4±7.3 % to 22.9±6.5 % , p = 0.4 ) . Conclusions : In this small cohort of patients with RA and no clinical ly overt cardiovascular disease ( CVD ) , after 18 months of treatment with anti‐TNFα agents , endothelial function improved significantly while CCA‐IMT remained stable . Longitudinal studies using more patients are needed to determine the clinical significance of these findings in relation to the risk of atherosclerosis OBJECTIVE To vali date the European League Against Rheumatism ( EULAR ) , the American College of Rheumatology ( ACR ) , and the World Health Organization (WHO)/International League Against Rheumatism ( ILAR ) response criteria for rheumatoid arthritis ( RA ) . METHODS EULAR response criteria were developed combining change from baseline and level of disease activity attained during follow up . In a trial comparing hydroxychloroquine and sulfasalazine , we studied construct ( radiographic progression ) , criterion ( functional capacity ) , and discriminant validity . RESULTS EULAR response criteria had good construct , criterion , and discriminant validity , ACR and WHO/ILAR criteria showed only good criterion validity . CONCLUSION EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA NG monomethyl-L-arginine ( L-NMMA ) , a specific inhibitor of the synthesis of endothelium-derived nitric oxide ( NO ) , was infused into the brachial arteries of healthy volunteers to study the role of NO in the control of forearm blood flow . L-NMMA caused a 50 % fall in basal blood flow and attenuated the dilator response to infused acetylcholine but not that to glyceryl trinitrate . These results indicate that the dilator action of endothelium-derived NO contributes to the control of basal and stimulated regional blood flow in man . Impairment of production of NO might account for the abnormalities in vascular reactivity that characterise a wide variety of disease states Introduction In this study we aim ed to investigate whether there are indications of premature atherosclerosis , as measured by endothelial dependent flow-mediated dilation ( ED-FMD ) and intima media thickness ( IMT ) , in patients with very early RA , and to analyze its relation to biomarkers of endothelial dysfunction , taking inflammation and traditional cardiovascular disease ( CVD ) risk factors into account . Methods Patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospect i ve study of CVD co-morbidity . Of these , all patients aged ≤60 years were consecutively included in this survey of CVD risk factors ( n = 79 ) . Forty-four age and sex matched controls were included . IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography . Blood was drawn for analysis of lipids , erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , plasminogen activator inhibitor-1 ( PAI-1 ) , tissue plasminogen activator (tPA)-mass , VonWillebr and factor ( VWF ) , soluble intercellular adhesion molecule-1 ( sICAM ) , soluble vascular cell adhesion molecule-1 ( sVCAM ) , sE-selectin , sL-selectin and monocyte chemotactic protein-1 ( MCP-1 ) . In a subgroup of 27 RA patients and their controls the ultrasound measurements were reanalysed after 18 months . Results There were no significant differences between RA patients and controls in terms of IMT or ED-FMD at the first evaluation . However after 18 months there was a significant increase in the IMT among the patients with RA ( P < 0.05 ) . Patients with RA had higher levels of VWF , sICAM-1 ( P < 0.05 ) and of MCP-1 ( P = 0.001 ) compared with controls . In RA , IMT was related to some of the traditional CVD risk factors , tPA-mass , VWF ( P < 0.01 ) and MCP-1 and inversely to sL-selectin ( P < 0.05 ) . In RA , ED-FMD related to sL-selectin ( P < 0.01 ) . DAS28 at baseline was related to PAI-1 , tPA-mass and inversely to sVCAM-1 ( P < 0.05 ) and sL-selectin ( P = 0.001 ) . Conclusions We found no signs of atherosclerosis in patients with newly diagnosed RA compared with controls . However , in patients with early RA , IMT and ED-FMD were , to a greater extent than in controls , related to biomarkers known to be associated with endothelial dysfunction and atherosclerosis . After 18 months , IMT had increased significantly in RA patients but not in controls 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 OBJECTIVE To investigate the effects of angiotensin-converting enzyme ( ACE ) inhibitors and statins ( hydroxy-methyl-glutaryl-CoA reductase inhibitors ) on inflammatory markers and endothelial functions in patients with rheumatoid arthritis ( RA ) . METHODS A total of 45 patients with longterm RA were r and omized into 3 groups to receive 8 weeks of treatment with placebo ( n = 15 ) , simvastatin ( 20 mg/day , n = 15 ) , or quinapril ( 10 mg/day , n = 15 ) as an adjunct to existing antirheumatic drug treatment . Factors with a role in the development of endothelial dysfunction , such as C-reactive protein ( CRP ) , fibrinogen , nitric oxide ( NO ) , and serum cytokine concentrations including interleukin 1beta ( IL-1beta ) , IL-6 , and tumor necrosis factor-alpha ( TNF-alpha ) were measured at baseline and in the posttreatment period . Brachial artery vasodilator responses were assessed by high resolution ultrasound to evaluate endothelial functions . RESULTS Simvastatin treatment significantly decreased serum CRP and TNF-a [ from 14 + /- 6 to 7 + /- 3 mg/l ( p = 0.025 ) and 30 + /- 5 to 16 + /- 4 pg/ml ( p = 0.012 ) , respectively ] , while quinapril had no significant changes in these 2 measures . IL-1beta and IL-6 showed insignificant changes in patients in the 2 drug groups . Endothelium-dependent vasodilatation was improved significantly in the simvastatin group [ from 5.3 + /- 1.1 % to 8.9 + /- 1.4 % ( p = 0.025 ) ] , while there was no difference in endothelium-independent vasodilatation [ 9.0 + /- 1.8 % to 11.2 + /- 2.5 % ( p = 0.17 ) ] . The quinapril group showed no significant changes in both types of vasodilation although there was a tendency to an increase in endothelium-dependent vasodilatation [ from 6.1 + /- 0.8 % to 7.8 + /- 0.7 % ( p = 0.06 ) ] . Treatment with the 2 drugs had no significant effects on resting arterial diameter . CONCLUSION We show that simvastatin 20 mg daily improves endothelial function in patients with RA . Its beneficial effect may be attributed to lowering CRP and TNF-alpha concentrations . ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response Patients with rheumatoid arthritis ( RA ) have endothelial dysfunction , which may predispose them to the risk of premature atherosclerosis . This study investigated the involvement of tumor necrosis factor ( TNF ) α in the pathophysiologic characteristics of this abnormality by use of the TNF‐α‐neutralizing antibody infliximab Background — The excess in cardiovascular risk in patients with rheumatoid arthritis provides a strong rationale for early therapeutical interventions . In view of the similarities between atherosclerosis and rheumatoid arthritis and the proven benefit of angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease , it was the aim of the present study to delineate the impact of ramipril on endothelial function as well as on markers of inflammation and oxidative stress in patients with rheumatoid arthritis . Methods and Results — Eleven patients with rheumatoid arthritis were included in this r and omized , double-blind , crossover study to receive ramipril in an uptitration design ( 2.5 to 10 mg ) for 8 weeks followed by placebo , or vice versa , on top of st and ard antiinflammatory therapy . Endothelial function assessed by flow-mediated dilation of the brachial artery , markers of inflammation and oxidative stress , and disease activity were investigated at baseline and after each treatment period . Endothelial function assessed by flow-mediated dilation increased from 2.85±1.49 % to 4.00±1.81 % ( P=0.017 ) after 8 weeks of therapy with ramipril but did not change with placebo ( from 2.85±1.49 % to 2.84±2.47 % ; P=0.88 ) . Although systolic blood pressure and heart rate remained unaltered , diastolic blood pressure decreased slightly from 78±7 to 74±6 mm Hg ( P=0.03 ) . Tumor necrosis factor-&agr ; showed a significant inverse correlation with flow-mediated dilation ( r=−0.408 , P=0.02 ) , and CD40 significantly decreased after ramipril therapy ( P=0.049 ) . Conclusions — Angiotensin-converting enzyme inhibition with 10 mg/d ramipril for 8 weeks on top of current antiinflammatory treatment markedly improved endothelial function in patients with rheumatoid arthritis . This finding suggests that angiotensin-converting enzyme inhibition may provide a novel strategy to prevent cardiovascular events in these patients OBJECTIVE Endothelial dysfunction has been found in patients with rheumatoid arthritis ( RA ) . In this study we aim ed to assess whether adalimumab , a fully human monoclonal antibody directed against TNF-alpha , was able to improve endothelial function in RA patients with long-st and ing disease refractory to infliximab . METHODS Eight RA patients ( 7 women ; range : 24- 74 years ) were studied . They had been treated with the chimeric monoclonal anti-TNF-alpha antibody-infliximab for at least 1 year and were switched to adalimumab therapy because of loss of efficacy following periodical treatment with infliximab . Endothelial dependent ( EDV ) and independent vasodilatation ( EIV ) were measured by brachial ultrasonography . Patients were assessed prior to ( day 0 ) and at day 2 , and weeks 2 and 12 after the onset of adalimumab therapy . RESULTS Following adalimumab administration a rapid increase in the percentage ( % ) of EDV was found in all patients ( mean + /- SD : 10.1 + /- 5.1 % at day 2 compared to 5.8 + /- 4.1 % at day 0 ) . At weeks 2 and 12 the % EDV was also significantly increased compared to day 0 . All patients showed decrease in the disease activity score 28 and C-reactive protein levels ( P = 0.012 ) . Moreover , at week 12 the atherogenic index was reduced in all patients ( P = 0.012 ) . CONCLUSION Our study confirms that short-term adalimumab therapy yields an active and positive effect on endothelial function in long-st and ing RA patients with severe disease . This observation emphasizes the potential role of the TNF-alpha blockade in the mechanisms implicated in the development of atherogenesis in RA & NA ; Current methods for assessing vasomotor endothelial function are impractical for use in large studies . We tested the hypothesis that pulse‐wave analysis ( PWA ) combined with provocative pharmacological testing might provide an alternative method . Radial artery waveforms were recorded and augmentation index ( AIx ) was calculated from derived aortic waveforms . Thirteen subjects received sublingual nitroglycerin ( NTG ) , inhaled albuterol , or placebo . Twelve subjects received NTG , albuterol , and placebo separately during an infusion of NG‐monomethyl‐L‐arginine ( LNMMA ) or norepinephrine . Twenty‐seven hypercholesterolemic subjects and 27 controls received NTG followed by albuterol . Endothelial function was assessed by PWA and forearm blood flow in 27 subjects . Albuterol and NTG both significantly and repeatably reduced AIx ( P<0.001 ) . Only the response to albuterol was inhibited by LNMMA ( −9.8±5.5 % vs −4.7±2.7 % ; P=0.02 ) . Baseline AIx was higher in the hypercholesterolemic subjects , who exhibited a reduced response to albuterol ( P=0.02 ) but not to NTG when compared with matched controls . The responses to albuterol and acetylcholine were correlated ( r=0.5 , P= 0.02 ) . Consistent with an endothelium‐dependent effect , the response to albuterol was substantially inhibited by LNMMA . Importantly , the response to albuterol was reduced in subjects with hypercholesterolemia and was correlated to that of intra‐arterial acetylcholine . This methodology provides a simple , repeatable , noninvasive means of assessing endothelial function in vivo Background —Endothelial dysfunction plays a key role in atherogenesis . We prospect ively investigated the impact of noninvasive measurement of endothelial function on cardiovascular risk in peripheral arterial disease ( PAD ) . The study was specially aim ed at assessing whether brachial artery flow-mediated dilation ( FMD ) added to the predictive value of ankle-brachial pressure index ( ABPI ) . Methods and Results —Of 131 patients monitored for a mean of 23±10 months , 18 had a coronary event , 12 a cerebrovascular event , and 9 a peripheral event . The median FMD was lower in patients with an event than in those without ( 5.8 % versus 7.6 % , P < 0.05 ) , whereas vasodilation to nitroglycerin was similar in the two groups . The cardiovascular event rate was higher in patients with FMD below the median versus those with FMD above the median ( P < 0.001 by log-rank test ) . In a Cox proportion hazard model , independent predictors of events were FMD below the median ( P < 0.01 ) , ABPI below the median ( P < 0.01 ) , and previous stroke ( P < 0.02 ) . Similar results were obtained when peripheral events were excluded from the analysis . Below-median ABPI and FMD combined was more accurate in predicting risk ( relative risk [ RR ] 13.0 ; 95 % CI , 3.0 to 56.2 ; P < 0.01 ) than ABPI ( RR , 6.4 ; 95 % CI , 1.4 to 29.1 ; P < 0.02 ) and FMD ( RR , 4.8 ; 95 % CI , 1.1 to 23.3 ; P < 0.05 ) alone . Conclusions —A low brachial artery FMD is an independent predictor of cardiovascular risk in patients with PAD and adds to the prognostic value of ABPI , which is currently the most powerful prognostic indicator in PAD OBJECTIVES Our aim was to investigate mechanisms of inflammation-induced endothelial dysfunction in humans . METHODS Endothelial function in twenty-one healthy human volunteers was measured using forearm venous plethysmography before and 8 h after administration of typhoid vaccination to generate an inflammatory response . Basal and stimulated endothelial nitric oxide ( NO ) bioavailability was assessed by measurement of the responses to intra-arterial N(G)-monomethyl-l-arginine ( l-NMMA ) and bradykinin , respectively . The effects of supplementation with l-arginine or ascorbic acid were assessed to probe the effects of substrate deficiency and oxidative stress , respectively . Systemic effects were determined by measuring cytokine response , total anti-oxidant status ( TAOS ) and urinary protein excretion . RESULTS Vaccination induced a cytokine response , a fall in total anti-oxidant status and increased urinary albumin excretion ( UAE ) . There was a reduction in the response to bradykinin ( BK , P<0.005 ) and l-NMMA ( P<0.0001 ) with no effect on the response to glyceryl trinitrate ( GTN ) and norepinephrine ( NE ) . Following vaccination blood flow response to BK ( but not GTN ) was partially returned to pre-vaccine levels by infusion of ascorbic acid ( P=0.01 ) . Supplementation with l-arginine had no effect . CONCLUSION Inflammation causes widespread endothelial dysfunction , reduces vascular NO bioavailability and increases oxidative stress . These actions are partially reversible with local anti-oxidants . These findings suggest a role for reactive oxygen species in inflammation-induced endothelial dysfunction OBJECTIVE To determine the influence of low-dose prednisolone on atherosclerosis , endothelial function , and risk factors for atherosclerosis in patients with early rheumatoid arthritis ( RA ) . METHODS At start of the first disease modifying antirheumatic drug , 67 patients with early , active RA were r and omized to either 7.5 mg prednisolone daily ( n = 34 ) or no prednisolone ( n = 33 ) . In the prednisolone group , 21 were treated for 2 years and 13 continuously . After a mean of 5 years intima-media thickness ( IMT ) and calculated intima-media area ( cIMa ) of the carotid arteries were determined by B-mode ultrasound . Endothelial function was determined by flow-mediated dilatation ( FMD ) of the brachial artery . RESULTS IMT [ median ( interquartile range ) 0.675 mm ( 0.58 - 0.82 ) vs 0.673 mm ( 0.0.62 - 0.80 ) ] , cIMa [ 13.7 mm2 ( 11.45 - 20.37 ) vs 14.1 mm2 ( 12.34 - 17.38 ) ] , prevalence of atherosclerotic plaques ( 82.3 % vs 81.9 % ) , and endothelial function [ FMD% ( mean + /- SD ) 3.88 % + /- 2.8 vs 3.74 % + /- 2.9 ] did not differ between patients treated with and those not treated with prednisolone . There were no differences in lumen diameter of carotid arteries , or levels of lipoproteins , glucose , and blood pressure . Patients treated for at least 4 years ( and currently treated ) with prednisolone had a trend to higher systolic blood pressure ( 157 + /- 29 mm Hg ) compared with untreated patients ( 141 + /- 28 mm Hg ; p = 0.06 ) and had higher cholesterol levels ( 5.6 mmol/L + /- 1.39 vs 4.9 + /- 28 ; p = 0.03 ) . In the whole cohort , age and HDL were independently associated with IMT ; age , HDL , and blood pressure with cIMa ; and age and serum creatinine with presence of atherosclerotic plaques . CONCLUSION Low-dose prednisolone did not influence endothelial function and atherosclerosis in patients with RA . However , total cholesterol was higher in patients treated with prednisolone Objective : Chronic inflammation in rheumatoid arthritis ( RA ) is associated with vascular endothelial dysfunction . The aim of this study was to determine the effect of spironolactone on endothelial function in anti‐tumour necrosis factor (TNF)‐naive RA patients . Methods : Twenty‐four anti‐TNF‐naive RA patients ( mean age 49±1.8 years ; disease duration 8.5±5.8 years ) with high disease activity [ Disease Activity Score including a 28‐joint count ( DAS28>5.1 ) ] despite treatment with stable doses of conventional disease‐modifying anti‐rheumatic drugs ( DMARDs ) were investigated . Inflammatory disease activity [ DAS28 and Health Assessment Question naire‐Disability Index ( HAQ‐DI ) scores , erythrocyte sedimentation rate ( ESR ) , and C‐reactive protein ( CRP ) ] , serum markers of endothelial dysfunction , serum nitrite concentration , and endothelium‐dependent and ‐independent vasodilation of the brachial artery were measured before and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day . Results : After treatment with spironolactone , flow‐mediated vasodilation ( FMD ) improved from 3.18±0.46 % to 3.95±0.49 % ( p<0.001 ) whereas there was no significant change in endothelium‐independent vasodilation with nitroglycerin and baseline diameter ( 18.4±1.15 % vs. 18.3±1.13 % , p = 0.046 , and 3.5±0.1 vs. 3.52±0.1 mm , p = 0.952 , respectively ) ; serum nitrite concentration was reduced significantly from 6.9±0.34 to 6.8±0.33 µmol/L ( p<0.001 ) , ESR from 59.90±4.86 to 51.22±4.26 mm in the first hour ( p<0.001 ) , and CRP level from 15.2±3.8 to 9.4±2.6 mg/dL ( p = 0.019 ) . DAS28 and HAQ‐DI scores were significantly reduced , from 6.9±0.25 to 4.1±0.31 ( p<0.05 ) and from 1.47±0.09 to 0.69±0.1 ( p<0.05 ) , respectively . Conclusions : The study suggests that , in RA , endothelial dysfunction is part of the disease process and treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in RA Premature atherosclerosis is linked to inflammation . Arterial stiffness is a marker of vascular dysfunction . We tested the hypothesis that treatment with infliximab , which is effective in reducing inflammation in rheumatoid arthritis ( RA ) and ankylosing spondylitis ( AS ) , also lowers the augmentation index ( AIx ) in patients with active disease . We also analyzed the subendocardial viability ratio ( SEVR ) , which is a measure of myocardial perfusion relative to cardiac workload . Included in the study were 30 patients ( 17 RA , 13 AS ) . Conventional treatment failed in all patients . The AIx and SEVR were determined by radial applanation tonometry before and after treatment with infliximab , at baseline and at week 7 . After treatment with infliximab , Disease Activity Score for 28 joints ( RA patients ) , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index ( AS patients ) , erythrocyte sedimentation rate ( ESR ) , and C-reactive protein ( CRP ) improved significantly ( p < 0.001 ) . The AIx for all patients increased from 22.0 ± 14.0 % to 24.6 ± 13.0 % ( p = 0.03 ) . The increase in the RA sub-group ( p = 0.01 ) was also significant . The SEVR decreased from 148.6 ± 23.7 % to 141.2 ± 23.7 % ( p = 0.04 ) . Infliximab did not reduce the AIx in patients with RA and AS , although there were clinical improvements and CRP and ESR decreased . Instead , the AIx increased . This could negatively influence cardiac workload OBJECTIVE To determine whether the interleukin (IL)6 -174 gene polymorphism may influence the development of sub clinical atherosclerosis manifested by the presence of endothelial dysfunction in RA patients . PATIENTS AND METHODS 311 patients ( 228 [ 73.3 % ] women ; 243 [ 78.1 % ] rheumatoid factor positive ) who fulfilled the 1987 ACR classification criteria for RA seen at the Rheumatology outpatient clinic of Hospital Xeral-Calde , Lugo between March 1996 and December 2006 and 226 matched controls were included in this study . Between March and December 2007 , a subgroup of 98 patients r and omly selected was assessed for the presence of endothelial dysfunction . Patients and controls were genotyped for a single biallelic ( G/C ) nucleotide polymorphism ( rs1800795 ) in the promoter region at the position -174 of the IL6 gene using a TaqMan 5 ' allele discrimination assay . RESULTS No significant differences in the IL6 -174 allele or genotype frequency between RA patients and controls were found . However , RA patients homozygous for the IL6 -174 GG genotype had more severe endothelial dysfunction ( flow-mediated endothelium-dependent vasodilatation-FMD% : 4.2 + or - 6.6 ) than those carrying the IL6 -174 GC ( FMD% : 6.3 + or - 8.1 ) or IL6 -174 CC ( FMD% : 6.0 + or - 3.3 ) genotypes . In this regard , significant differences were observed when FMD% values in RA patients carrying the IL6 -174 GG genotype were compared with that observed in those carrying the IL6 -174 GC and the IL6 -174 CC genotypes ( FMD% : 6.3 + or - 4.6 ) ( p=0.02 ) . CONCLUSIONS Our results support a role of IL6 -174 gene polymorphism in the development of sub clinical atherosclerosis in patients with RA OBJECTIVES The aim of this study was to investigate the effect of simvastatin and ezetimibe on inflammation , disease activity , endothelial dysfunction , and arterial stiffness in a cohort of rheumatoid arthritis ( RA ) patients . BACKGROUND Rheumatoid arthritis is a chronic inflammatory condition associated with increased cardiovascular risk . Statins reduce inflammation and disease activity in RA patients , but whether this is due to pleiotropism or cholesterol lowering per se is unclear . METHODS Twenty patients received 20 mg simvastatin or 10 mg ezetimibe each for 6 weeks in a r and omized double-blind crossover study . Disease activity , blood pressure , aortic pulse wave velocity ( PWV ) , brachial artery flow-mediated dilation ( FMD ) , and serum inflammatory markers were measured before and after each treatment . RESULTS Both ezetimibe and simvastatin significantly reduced total cholesterol ( -0.62 + /- 0.55 mmol/l and -1.28 + /- 0.49 mmol/l , respectively ; p < 0.001 ) , low-density lipoprotein cholesterol ( -0.55 + /- 0.55 mmol/l and -1.28 + /- 0.49 mmol/l ; p < 0.0001 ) , and C-reactive protein ( -5.35 + /- 9.25 mg/l and -5.05 + /- 6.30 mg/l ; p < 0.001 ) . Concomitantly , Disease Activity Score ( -0.55 + /- 1.01 and -0.67 + /- 0.91 ; p = 0.002 ) , aortic PWV ( -0.69 + /- 1.15 m/s and -0.71 + /- 0.71 m/s ; p = 0.001 ) , and FMD ( 1.37 + /- 1.17 % and 2.51 + /- 2.13 % ; p = 0.001 ) were significantly improved by both drugs . CONCLUSIONS This study demonstrates that both ezetimibe and simvastatin reduce disease activity and inflammatory markers to a similar extent in patients with RA . Therapy is also associated with a concomitant reduction in aortic PWV and improvement in endothelial function . This suggests that cholesterol lowering per se has anti-inflammatory effects and improves vascular function in RA OBJECTIVE To establish whether carotid intima-media wall thickness ( IMT ) may be a good predictor for the development of cardiovascular ( CV ) events in patients with rheumatoid arthritis ( RA ) . METHODS A series of 47 RA patients who at the time of recruitment did not have traditional CV risk factors or CV disease were assessed by carotid ultrasonography . Carotid IMT and carotid plaques were measured in the right common carotid artery . Then , a prospect i ve assessment of the CV outcome was performed over a 5-year period . Logistic regression models and receiver operating characteristic curves were performed to evaluate the ability of different variables to predict CV events . RESULTS Carotid IMT was greater in RA patients who over the extended follow-up experienced CV events ( 1.01 + /- 0.16 mm ) compared with the remaining RA patients who did not have CV complications ( 0.74 + /- 0.12 mm ) ( P < 0.001 ) . Also , carotid IMT categorized in quartiles was strongly associated with CV events . In this regard , none of the patients with carotid IMT less than 0.77 mm had CV events . However , 6 of the 10 patients with carotid IMT greater than 0.91 mm experienced CV events ( P value for the trend < 0.001 ) . Carotid IMT yielded a high predictive power for the development of CV events over the 5-year follow-up period . The area under the receiver operating characteristic curve was 0.93 for a model that only included carotid IMT and 0.90 for carotid plaque . CONCLUSIONS The results from the present study support the use of carotid ultrasonography as a predictor of CV events in RA Background Recent findings imply prognostic significance of intracoronary acetylcholine infusion for endothelial function testing . We evaluated whether routine use of this test in coronary angiography patients is safe . Methods Patients undergoing a first diagnostic coronary angiography were selected to receive intracoronary acetylcholine for endothelial function evaluation . The relation between adverse reactions during infusion and risk factors was analyzed with a logistic regression model . Included in the multiple logistic regression model were the variables with a univariate P value < 0.20 . Results Adverse reactions occurred in 16 % ( 49/299 ) of the patients . This included two life-threatening events caused by occlusive spasm and flow limitation in the left coronary artery . Other adverse events were chest pain ( n = 38 ) , AV block or sinus bradycardia ( n = 10 ) , dyspnea ( n = 3 ) . Adverse reactions were more likely to occur in patients younger than 60 years of age ( relative risk , 5.6 [ 2.2–14.3 ] ) . Conclusion Intracoronary acetylcholine infusion is safe , but may lead to serious adverse reactions . Care should be taken especially in patients younger than 60 years of age . Routine use of acetylcholine infusion can thus only be justified if it has important prognostic significance . This has to be proven further in large prospect i ve studies OBJECTIVE Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis ( RA ) . Atherosclerosis and RA share similar inflammatory mechanisms that include involvement of tumor necrosis factor alpha ( TNF alpha ) . Anti-TNF alpha antibody improved endothelial function in RA patients after a 12-week treatment . The aim of the present study was to assess whether improvement of endothelial function is still effective in long-term infliximab-treated RA patients . METHODS Seven RA patients ( 5 women ; age range 25 - 73 years ) were studied . They had been treated with infliximab for at least 1 year and were currently being treated with this drug every 8 weeks . Endothelial-dependent and independent vasodilatation were measured by brachial ultrasonography . RESULTS Following infliximab infusion , a rapid increase in the percentage of endothelial-dependent vasodilatation was found in all patients ( mean + /- SD 9.4 + /- 5.5 % 2 days postinfusion compared with 2.8 + /- 2.5 % 2 days before infusion ) . However , values returned to baseline by 4 weeks after infusion . There were no differences in the percentage of endothelial-independent vasodilatation prior to and after infusion . A decrease in the individual disease activity score for each patient was observed at day 7 postinfusion ( P = 0.02 ) . CONCLUSION Our study confirms an active but transient effect of infliximab on endothelial function in RA patients treated periodically with this drug . It may support long-term use of drugs that block TNF alpha function to reduce the high incidence of cardiovascular complications in RA OBJECTIVES The goal of this study was to prospect ively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events . BACKGROUND Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors . The prospect i ve relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown . METHODS We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery . Patients were prospect ively followed with an average follow-up of 1.2 years after surgery . RESULTS Thirty-five patients had an event during follow-up , including cardiac death ( 5 patients ) , myocardial infa rct ion ( 17 patients ) , unstable angina ( 10 patients ) , or stroke ( 3 patients ) . Preoperative endothelium-dependent flow-mediated dilation ( FMD ) was significantly lower in patients with an event ( 4.4 + /- 2.8 % ) compared with those without an event ( 7.0 + /- 4.9 % , p < 0.001 ) , whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups . In a Cox proportional-hazards model , independent predictors of events included age ( p = 0.003 ) , more invasive surgery ( surgery other than carotid endarterectomy , p = 0.02 ) , and impaired brachial-artery endothelial function ( p = 0.002 ) . Risk was approximately nine-fold higher in patients with FMD < 8.1 % ( lower two tertiles ) compared with those in the upper tertile ( odds ratio 9.5 ; 95 % confidence interval 2.3 to 40 ) . CONCLUSIONS Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease . The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk OBJECTIVE Inflammation appears to play a central role in atherosclerosis , and endothelial damage mediated by systemic inflammation may contribute to the increased cardiovascular mortality in rheumatoid arthritis ( RA ) . Brachial artery flow-mediated dilatation ( FMD ) and pulse wave analysis ( PWA ) are measures of vascular function . The aim of this study was to determine if FMD and PWA are abnormal in patients with RA . METHODS Twenty-five RA patients and 25 matched healthy controls were studied . All were free of traditional cardiovascular risk factors . FMD was measured in all subjects . PWA was performed in 18 RA patients and 18 controls , with results expressed as large and small artery compliance ( C1 and C2 ) . Modified Sharp scores were calculated in 13 RA patients . RESULTS Results ( mean + /- SD ) in RA patients and controls , respectively , were as follows : FMD 107.6 + /- 4.6 % versus 108.5 + /- 4.1 % ( P = 0.49 ) , C1 14.8 + /- 2.8 ml/mm Hg x 10 versus 17.9 + /- 3.1 ml/mm Hg x 10 ( P = 0.0033 ) , C2 4.5 + /- 2.3 ml/mm Hg x 100 versus 7.7 + /- 3.7 ml/mm Hg x 100 ( P = 0.0039 ) . There was an inverse correlation between C2 and modified Sharp scores in the RA patients ( Spearman 's rho -0.69 , P = 0.0085 ) . CONCLUSION FMD was normal in these RA patients , whereas arterial compliance was markedly reduced . PWA appears to be a more sensitive measure of vascular dysfunction than FMD in RA and may be the preferred surrogate marker of vascular dysfunction in longitudinal studies of RA patients . The inverse correlation between C2 and the modified Sharp score , a measure that reflects disease activity over time , supports the notion that chronic inflammation plays a role in RA-associated atherosclerosis Abstract Aim : It is well known that increased insulin resistance is associated with the development of cardiovascular disease in patients with rheumatoid arthritis and that tumour necrosis factor- alpha plays an important role in this process . Infliximab is a chimeric monoclonal anti- tumour necrosis factoralpha antibody . This study investigates the effects of long term infliximab treatment on insulin resistance in patients with rheumatoid arthritis . Material s and Methods : Seven rheumatoid arthritis patients ( 6 female and 1 male ; mean age : 44.6±12.3 , mean duration of disease : 6.8 y ) for whom infliximab treatment had been planned at the rheumatology and internal medicine clinics were included . Patients were evaluated during and at the end of the study with a mean follow-up duration of 9.6 months . Fasting plasma glucose , fasting plasma insulin levels and serum lipid profile were assessed at baseline and throughout the treatment period ( prior to every infusion ) . Homeostasis Model Assessment of Insulin Resistance model was used for the assessment of insulin sensitivity . Results : Fasting insulin and Homeostasis Model Assessment of Insulin Resistance levels decreased after treatment ( from 19.4±7.7 μU/ml to 8.9±4.1 μU/ml and from 2.4±1 to 1.1±0.5 , respectively ; p<0.05 for both ) . No significant change was observed in other parameters . Conclusion : An improvement in insulin sensitivity was observed in patients receiving long term infliximab treatment for rheumatoid arthritis Rheumatoid arthritis ( RA ) is associated with cardiovascular morbidity and mortality and inflammation contributes to related endothelial dysfunction . We aim ed to investigate the effect of anti-TNFα therapy on endothelial function in subjects with rheumatoid arthritis . We measured flow-mediated ( FMD ) and GTN-mediated dilation of the brachial artery before and following 36 weeks of anti-TNFα therapy in nine RA patients and in a group of RA patients on conventional therapy . Thirty-six weeks of anti-TNFα therapy improved FMD relative to those on conventional therapy ( 8.65 ± 1.50 vs. 1.70 ± 1.36 % , P = 0.02 ) . No significant changes in GTN responses were evident . Significant improvements in tender ( P = 0.03 ) and swollen ( P = 0.02 ) joint counts , patients ’ global self- assessment ( P = 0.01 ) and DAS-28 scores ( P = 0.04 ) were observed in the anti-TNFα treated group . The addition of anti-TNFα treatment to conventional therapy , in those with severe RA , reduces inflammatory symptoms and improves endothelial function , potentially lowering future atherosclerotic This study compared the rapidity of onset , the magnitude , and the duration of action of 2 short-acting nitroglycerin preparations using high-resolution brachial ultrasound . Both sublingual tablet and lingual spray formulations caused maximal vasodilation at 3 minutes ; however , the spray provided faster ( at 2 minutes ) , greater , and more prolonged ( 15 minutes ) vasodilation than the tablet OBJECTIVES Increased arterial stiffness , an independent risk factor for premature coronary artery disease , has been reported in patients with RA . The objectives of this study were first to assess , in patients with RA , the relationship between disease activity , inflammation and augmentation index , which is a combined measure of arterial stiffness and pulse wave reflection . The second objective was to establish any effect anti-rheumatic treatment may have on augmentation index . METHODS One hundred and forty-eight RA patients with no previous history of cardiovascular disease ( CVD ) had their augmentation index corrected for a heart rate of 75 beats per minute ( AIx@75 ) , and parameters of RA disease activity and CV risk measured . Forty-seven patients were then treated with either MTX ( n = 21 ) or etanercept ( ETAN ) ( n = 26 ) , and assessment s were repeated at 2 and 4 months . RESULTS Patients with high CRP ( > 10 mg/l ) showed significantly higher mean AIx@75 than those with low CRP ( < or = 10 mg/l ) ( 33 + /- 8 vs 30 + /- 8 % ; P = 0.033 ) . On regression analysis , log(10 ) CRP ( beta = 0.298 ; P = 0.002 ) , gender ( beta = 0.257 ; P = 0.007 ) , BMI ( beta = -0.292 ; P = 0.004 ) , diastolic blood pressure ( beta = 0.260 ; P = 0.009 ) and age ( beta = 0.194 ; P = 0.046 ) were independently associated with AIx@75 . Treatment with ETAN ( 35 + /- 9 , 32.5 + /- 1 and 32.5 + /- 8 % ; P = 0.025 ) but not MTX ( 31 + /- 1 , 31 + /- 1 and 31 + /- 1 % ; P = 0.971 ) attenuated the AIx@75 significantly from baseline to Visits 2 and 3 . CONCLUSIONS Systemic inflammation ( CRP ) is an independent predictor of arterial stiffness and pulse wave reflection in patients with RA . ETAN but not MTX therapy reduces arterial stiffness and pulse wave reflection and may thus improve CV morbidity in RA Rheumatoid arthritis ( RA ) is associated with greater risk of cardiovascular morbidity and mortality , the inflammatory component of RA being strongly linked to this excess risk . Endothelial dysfunction is linked to atherosclerosis and has been demonstrated in larger vessels in RA . In this pilot study , we determined for the first time whether skin microvascular function was impaired in patients with active RA and also determined its response to anti-inflammatory treatment . This was assessed non-invasively using laser Doppler imaging combined with iontophoresis of the vasodilators acetylcholine ( ACh , endothelium dependent ) and sodium nitroprusside ( SNP , endothelium independent ) to the forearm . Eight RA patients admitted for acute flare-ups were assessed before and following anti-inflammatory treatment . St and ard laboratory indices were obtained along with pain perception ( VAS ) . A control group of eight subjects was included for baseline comparison . Compared to this group , vascular function was substantially and significantly ( P<0.00001 ) lower in RA patients . Following treatment , as CRP and VAS decreased , vascular function improved for both ACh ( P<0.00001 ) and SNP ( P=0.001 ) , this improvement being significantly greater for ACh ( P<0.001 ) . Vascular dysfunction is evident in RA patients , even at the level of the cutaneous microcirculation , but improves as inflammation regresses . Assessment of cutaneous vascular function may be a useful , non-invasive surrogate indicator of vascular risk in RA , inclusive of myocardial microvascular abnormalities BACKGROUND Rheumatoid arthritis ( RA ) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality . Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis . Indeed , adhesion molecules and cytokines , tumor necrosis factor (TNF)-alpha in particular , are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease . Hence , the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-alpha antibody infliximab on disease activity and endothelial function in patients with active RA . METHODS AND RESULTS Eleven RA patients ( mean age 46+/-5 years ; disease duration 9+/-2 years ) with high disease activity despite treatment with stable doses of methotrexate ( < or=25 mg/wk ) and prednisone ( < or=10 mg/d ) were investigated . Clinical status and endothelium-dependent and -independent vasodilation of the brachial artery as assessed by high-resolution ultrasound were measured before and after 12 weeks of infliximab therapy . Flow-mediated vasodilation improved from 3.2+/-0.4 % to 4.1+/-0.5 % ( P=0.018 ) , whereas endothelium-independent vasodilation with nitroglycerin and baseline diameter remained unchanged ( 13.6+/-1.2 % versus 12.8+/-1.4 % , P=0.98 , and 3.74+/-0.15 versus 3.66+/-0.11 mm , P=0.54 , respectively ) . Disease activity score ( DAS28 ) was significantly reduced , from 5.6+/-0.3 to 3.5+/-0.6 ( P=0.002 ) . Erythrocyte sedimentation rate and C-reactive protein were lowered from 34+/-7 to 19+/-5 mm/h ( P=0.04 ) and from 38+/-11 to 15+/-10 mg/L ( P=0.08 ) , respectively . CONCLUSIONS This is the first study to show that anti-TNF-alpha treatment improves endothelial function in RA . The data suggest that in RA , endothelial dysfunction is part of the disease process and is mediated by TNF-alpha Background — Interleukin-1 increases nitrooxidative stress . We investigated the effects of a human recombinant interleukin-1a receptor antagonist ( anakinra ) on nitrooxidative stress and vascular and left ventricular function . Methods and Results — In an acute , double-blind trial , 23 patients with rheumatoid arthritis were r and omized to receive a single injection of anakinra ( 150 mg SC ) or placebo and , after 48 hours , the alternative treatment . At baseline and 3 hours after the injection , we assessed ( 1 ) coronary flow reserve , aortic distensibility , systolic and diastolic ( Em ) velocity of the mitral annulus , and E to Em ratio ( E/Em ) using echocardiography ; ( 2 ) flow-mediated , endothelium-dependent dilation of the brachial artery ; and ( 3 ) malondialdehyde , nitrotyrosine , interleukin-6 , endothelin-1 , and C-reactive protein . In a chronic , nonr and omized trial , 23 patients received anakinra and 19 received prednisolone for 30 days , after which all indices were reassessed . Compared with baseline , there was a greater reduction in malondialdehyde , nitrotyrosine , interleukin-6 , and endothelin-1 and a greater increase in flow-mediated dilation , coronary flow reserve , aortic distensibility , systolic velocity of mitral annulus , and E/Em after anakinra than after placebo ( malondialdehyde −25 % versus 9 % ; nitrotyrosine −38 % versus −11 % ; interleukin-6 −29 % versus 0.9 % ; endothelin-1 −36 % versus −11 % ; flow-mediated dilation 45 % versus −9 % ; coronary flow reserve 29 % versus 4 % ; and aortic distensibility 45 % versus 2 % ; P<0.05 for all comparisons ) . After 30 days of treatment , the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group ( P<0.05 ) . Conclusions — Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin |
11,794 | 18,226,668 | RESULTS BMD consistently returned toward or to baseline values following DMPA discontinuation in women of all ages . | BACKGROUND While depot medroxyprogesterone acetate ( DMPA ) is a highly effective contraceptive used by millions of women , its use is associated with bone mineral density ( BMD ) loss , raising concerns about long-term risk of osteoporosis and /or fractures . | 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 The association between long-term use of depot-medroxyprogesterone acetate ( DMPA ) and bone mineral density ( BMD ) has been controversial , as seen in three case-control studies in New Zeal and , Thail and , and the United Kingdom . In the present case-controlled study of BMD , a group of 67 Chinese women who had used DMPA from 5 - 15 years was compared with 218 women of the same age range who had not used any steroidal hormones . DMPA users were found to have a significantly lower BMD at lumbar vertebra ( L2 - 4 ) ( 0.93 g/cm2 ) , neck of femur ( 0.69 g/cm2 ) , trochanter ( 0.59 g/cm2 ) , and Ward 's triangle ( 0.58 g/cm2 ) , as compared with the control group , whose corresponding BMD values were 1.03 g/cm2 , 0.83 g/cm2 , 0.71 g/cm2 , and 0.78 g/cm2 , respectively ( p < 0.001 ) . The average percentage of bone loss per year was estimated to be 1.1 % in L2 - 4 , 2.3 % in neck of femur , 2.4 % in trochanter , and 3.5 % in Ward 's triangle . The percentage of bone loss in L2 - 4 was found to be more pronounced with age . This study provided information that the use of DMPA in a Chinese group for > 5 years in associated with bone loss , and a prospect i ve study is needed to confirm these data , which are different from two case-control studies The calcium requirement for prolonged lactation was investigated in a r and omized supplementation study of Gambian mothers consuming a low-calcium diet ( 7.1 mmol/d , or 283 mg/d ) . Sixty women were studied from 10 d to 78 wk of lactation , receiving calcium or placebo for the first 12 mo . The supplement increased average calcium intake by 17.9 mmol/d ( 714 mg/d ) . Supplementation had no effect on breast-milk calcium concentration or on maternal bone mineral content . Urinary calcium output was higher in supplemented than in unsupplemented mothers by 1.18 mmol/d ( 47 mg/d ) , P < or = 0.005 . Longitudinal changes in urinary calcium output and bone mineral content made a substantial contribution to calcium requirements for lactation . This study suggests that , in women with low calcium intakes , there is no direct benefit from increasing calcium intake during lactation , and that physiological mechanisms operate to furnish calcium for breast-milk production BACKGROUND Several studies report an association between depot medroxyprogesterone acetate ( DMPA ) injectable contraception and decreased bone mineral density . Adolescents , who are still gaining bone , may be particularly affected , but there has been little study of the association in adolescent users and none following discontinuation . OBJECTIVE To evaluate bone mineral density changes in adolescents using and discontinuing use of DMPA contraception . DESIGN A population -based prospect i ve cohort study . PARTICIPANTS One hundred seventy adolescent women , aged 14 to 18 years ; 80 baseline DMPA users and 90 age-similar , unexposed comparison women . Sixty-one participants discontinued DMPA use during follow-up . MAIN OUTCOME MEASURE Bone mineral density , measured every 6 months for 24 to 36 months at the hip , spine , and whole body , comparing mean bone mineral density changes in DMPA users and discontinuers with nonusers . RESULTS Among DMPA users , bone mineral density declined significantly relative to nonusers at the hip and spine but not the whole body . Annualized mean percentage changes , adjusted for covariates , were hip , -1.81 % vs -0.19 % ; P<.001 ; spine , -0.97 % vs 1.32 % ; P<.001 , and whole body , 0.73 % vs 0.88 % ; P = .78 for DMPA users vs nonusers , respectively . New users lost bone mineral density more rapidly than prevalent users . Discontinuers experienced significantly increased bone mineral density relative to nonusers at all anatomical sites ; annualized mean percentage changes were hip , 1.34 % vs -0.19 % ; P = .004 ; spine , 2.86 % vs 1.32 % ; P = .004 ; and whole body , 3.56 % vs 0.88 % ; P<.001 . CONCLUSIONS Use of DMPA contraception in adolescents was associated with significant continuous losses of bone mineral density at the hip and spine . However , significant gains postdiscontinuation provide evidence that the loss of bone mass is apparently reversed OBJECTIVE The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception . STUDY DESIGN One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned r and omly to receive monthly injections of estradiol cypionate or placebo . The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 ( n = 69 ) to 24 ( n = 36 ) months . Participants , technicians , and physicians were blinded to estrogen treatment . RESULTS Over the 24-month period , the percentage of change from baseline bone mineral density at the lumbar spine was 2.8 % in the estradiol cypionate group versus -1.8 % in the placebo group ( P < .001 ) . At the femoral neck , the percentage of change from baseline bone mineral density was 4.7 % in the estradiol cypionate group versus -5.1 % in the placebo group ( P < .001 ) . CONCLUSION Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections Several studies indicate that parity and lactation are associated with modest , short-term bone loss , but the long-term effect on osteoporotic fracture risk is uncertain . The authors therefore analyzed data from a population -based case-control study among Swedish postmenopausal women aged 50 - 81 years between October 1993 and February 1995 . Mailed question naires and telephone interviews were used to collect data on 1,328 incident cases with hip fracture and 3,312 r and omly selected controls . In age-adjusted analyses , the risk of hip fracture among all women was reduced by 10 % per child ( 95 % confidence interval ( CI ) : 5 , 14 ) . After multivariate adjustment including body mass index as a covariate , the risk reduction was 5 % per child ( 95 % CI : 0 , 10 ) . Oral contraceptive use modified the association of parity with hip fracture risk . Among never users of oral contraceptives , the risk of hip fracture was reduced by 8 % per child ( 95 % CI : 2 , 13 ) , whereas among ever users of oral contraceptives , the risk was in the opposite direction , with an increase in risk by 19 % per child ( 95 % CI : 0 , 41 ) . After parity was considered , there was no association of duration of lactation period with fracture risk . The authors conclude that parity is modestly associated with a reduced hip fracture risk among women who had not used oral contraceptives previously The primary aim of this prospect i ve 2-year follow-up study was to investigate the effect of depot medroxyprogesterone acetate ( DMPA ) on the maintenance of bone mass in women aged 30 - 45 years . The effects of estrogen or calcium substitution during the second year of follow-up was investigated in seven DMPA users with a high annual bone loss during the first year . The bone mass of 35 users of DMPA and 10 women without hormonal contraception was investigated using peripheral quantitative computed tomography . The baseline cortical and trabecular bone mass ( TBM ) and the annual change was not different in DMPA users and controls . Over 24 months we measured an increase in TBM of 0.6 % and a decrease in cortical bone mass of 0.1 % in exposed women . Some but not all of the DMPA users with a bone loss during the first year could be successfully treated with estradiol or calcium . In conclusion , we did not observe an accelerated bone loss in DMPA users aged 30 - 45 years A cross-sectional study was design ed to determine trabecular bone density in 75 long-term depot-medroxyprogesterone acetate ( DMPA ) users ( > 3 yr ) matched with non-DMPA users by age , body mass index ( 18 - 25 ) , limitation of age ( < 45 yr ) , and body weight ( < 60 kg ) . The long-term DMPA cases were divided into 3 groups according to duration of injectable contraceptive use . Neither cases nor controls had a smoking or chronic alcohol consumption history . Cases and controls were matched by age . Trabecular bone of the femoral neck were assessed by X-ray and interpreted by a single-blinded radiologist . Trabecular bone patterns were grade d according to Singh 's Index . Blood collection for determination of estradiol , prolactin , calcium , phosphorus , and medroxyprogesterone acetate were performed in cases and controls . Venous blood was taken at twelfth week of injection of DMPA and within 5 days after menstrual bleeding cessation in the controls . Mean trabecular bone in the cases was 5.5 + /- 0.6 ( range 4 - 6 ) . It was not statistically different from that in the controls ( mean 5.5 + /- 0.6 , range 2 - 6 ) . No statistically significant difference of serum , calcium , phosphorus , prolactin , and estradiol was seen in the cases when compared to controls at mid follicular phase of normal menstrual cycle . Serum MPA of individual case at twelfth week of injection was 4.1 + /- 1.1 nmol/l . In conclusion , trabecular bone density in long-term DMPA users were not statistically different from normal menstruating women who have not received injectable DMPA The question of differential effects on bone density by two different types of progestogen-only methods for contraception in premenopausal women was addressed . Data from a prospect i ve r and omized clinical trial among 22 premenopausal women , age 32.6 ( range 20 - 45 years ) , who were r and omly assigned to either of two treatments with continuous progestogens for contraception were analyzed ; depot-medroxyprogesterone acetate ( DMPA ) or continuous levonorgestrel treatment with subdermal implants ( Norplant ) , respectively . Forearm bone density ( BMDprox ) increased with 2.94 % ( p = 0.006 ) in women who were prescribed levonorgestrel , which was in contrast to stable values in those prescribed depot-medroxy-progesterone acetate ; group difference at 6 months for BMDprox 3.4 % ( 95 % CI 1.3 , 5.5 ; p = 0.025 ) and BMDdist 4.1 % ( 95 % CI - 1.3 , 9.6 ; p = 0.077 ) . The changes in bone density were consistent with the changes in biochemical indices for bone metabolism ; DMPA users showed signs of increased bone turnover and users of levonorgestrel showed increased bone formation with increased levels of both alkaline phosphatase ( p = 0.004 ) and osteocalcin ( p = 0.007 ) . The findings suggest an increase in bone density during treatment with levonorgestrel and stable values during short-term administration of DMPA , in st and ard clinical doses for contraception Depot medroxyprogesterone acetate ( DMPA ) , an injectable progestogen , is a widely used contraceptive acting primarily by inhibiting secretion of pituitary gonadotrophins , thus producing oestrogen deficiency . Cross‐sectional and prospect i ve studies in pre‐menopausal women have shown DMPA use to be associated with reduced bone density , but bone density increases following discontinuation of the drug . Because fracture rates are low in pre‐menopausal women , the principal concern arising from the effects of DMPA on bone is that there may be residual osteopenia in former users such that their post‐menopausal fracture risk is increased . The present study addresses this question INTRODUCTION This 7-year , prospect i ve , matched-cohort , clinical study evaluated the effects of intramuscular depot medroxyprogesterone acetate ( DMPA ) ( 150 mg/mL ) on bone mineral density ( BMD ) in women aged 25 - 35 years . METHODS Bone mineral density changes in new DMPA-IM users ( n=248 ) were compared with those in women using nonhormonal contraception ( n=360 ) for up to 240 weeks of treatment and 96 weeks of posttreatment follow-up ( in subjects receiving > or=1 dose ) . RESULTS At week 240 of treatment , mean percentage changes from baseline in DMPA-IM vs. nonhormonal subjects were : -5.16 % ( n=21 ) vs. + 0.19 % ( n=65 ) , total hip ( p<.001 ) ; -5.38 % ( n=33 ) vs. + 0.43 % ( n=105 ) , lumbar spine ( p<.001 ) . At week 96 posttreatment , these values were : -0.20 % ( n=25 ) vs. + 0.84 % ( n=43 ) , total hip ( p=.047 ) ; -1.19 % ( n=41 ) vs. + 0.47 % ( n=66 ) , lumbar spine ( p=.017 ) . CONCLUSIONS These results show BMD declines during DMPA-IM use ; following discontinuation , significant increases in BMD occur through 96 weeks posttreatment We performed a prospect i ve study of bone mineral density ( BMD ) in 38 women during their first full-term pregnancy until 12 months postpartum . BMD measurements at lumbar spine [ L2–L4 ( LS ) ] and forearm [ distal 33 % ( RD ) and ultradistal ( RUD ) region of the radius ] were made within 3 months before conception , after delivery , and at 6 and 12 months postpartum . In mid-pregnancy the DXA examination was carried out only at the forearm . Patients were grouped according to duration of lactation as group I , II or III ( 0–1 , 1–6 , 6–12 months respectively ) . During pregnancy there was a significant difference between baseline and delivery ( p < 0.001 ) in the LS , RUD and RD BMD values . In group I there was no statistically significant difference in LS BMD between visits following pregnancy . The RUD BMD loss was recovered by 6 months postpartum ( PP6 ) . Group II showed continuous bone loss from delivery until PP6 at LS and RUD . In group III the LS BMD loss continued throughout the lactation period . The RUD BMD dropped ( 4.9 % ) until PP6 then increased by 3.0 % as measured at 12 months postpartum ( PP12 ) . There was no significant change in RD BMD in any of three groups during lactation . At LS bone loss between delivery and PP12 correlated well with the duration of lactation ( r=−0.727 ; p<0.001 ) . We suggest that calcium needed for fetal skeletal growth during pregnancy was gained from maternal trabecular and cortical sites and that calcium needed for infant growth during lactation was drawn mainly from the maternal trabecular skeleton in our patients . The effect of pregnancy and lactation on the maternal bone mass was spontaneously compensated after weaning DMPA-SC 104 mg/0.65 mL is a new , low-dose subcutaneous ( SC ) formulation of Depo-Provera contraceptive injection ( 150 mg/mL medroxyprogesterone acetate injectable suspension ) that provides efficacy , safety and immediacy of onset equivalent to Depo-Provera intramuscular ( IM ) injection . Two large , open-label , Phase 3 studies assessed the 1-year contraceptive efficacy , safety and patient satisfaction with DMPA-SC administered every 3 months ( 12 - 13 weeks ) . Zero pregnancies were reported in both studies , which included a total of 16,023 woman-cycles of exposure to DMPA-SC and substantial numbers of overweight or obese women . DMPA-SC was well-tolerated and adverse events were similar to those reported previously with Depo-Provera IM . Thus , DMPA-SC offers women a new , highly effective and convenient long-acting contraceptive option STUDY OBJECTIVE To examine the relationship between biochemical markers of bone metabolism and hormonal contraception in adolescents . DESIGN A prospect i ve , observational design . SETTING The study was conducted in four adolescent health clinics in a large metropolitan area . PARTICIPANTS The study population comprised healthy , postmenarcheal adolescent girls aged 12 - 18 initiating either medroxyprogesterone acetate ( n=53 ) or an oral contraceptive ( OC ) containing 20 mug ethinyl estradiol/100 mug levonorgestrel ( n=165 ) and those using no hormonal contraception ( n=152 ) . INTERVENTIONS None . MAIN OUTCOME MEASURES Serum bone specific alkaline phosphatase ( BSAP ) , urinary deoxypyridinoline ( DPD ) , and bone mineral density ( BMD ) at baseline and 12 months . RESULTS At 12 month follow-up , serum BSAP levels were significantly higher ( P < 0.05 ) in the control group ( 40.4 U/L + /- 1.03 SE ) , than in the DMPA group ( 35.2 U/L + /- 1.05 SE ) and the OC group ( 35.5 U/L + /- 1.03 SE ) . There was a trend in urinary DPD levels to be higher ( P=0.08 ) in the control group ( 9.9 nmol/mmol Cr + /- 1.03 SE ) than in the DMPA group ( 9.1 + /- 1.05 SE ) and the OC group ( 8.9 + /- 1.03 SE ) . No relationship was found between the biochemical markers and BMD at the lumbar spine or the femoral neck . CONCLUSIONS Over 12 months , there was evidence of increased bone formation and resorption in the control group when compared to that in the DMPA and OC groups . This finding may indicate a suppression of bone metabolism in girls using DMPA or an OC containing 20 mug ethinyl estradiol/100 mug levonorgestrel Long-term use of the injectable contraceptive depot medroxyprogesterone acetate ( DMPA , Depo-Provera ) is associated with a reduction in bone mineral density ( BMD ) , particularly in the lumbar spine . The cause of DMPA-associated bone loss is not known , but the relative estrogen deficiency induced by DMPA use could be responsible . We have undertaken a r and omized , double-blind controlled trial of oral estrogen replacement therapy in 38 premenopausal women ( mean age 37 ) with a minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD ( T score < or = 0 ) . Nineteen women were allocated to receive conjugated estrogens ( 0.625 mg/d orally ) and 19 to receive a matching placebo . All continued with regular DMPA injections throughout the study . Areal bone density was measured by dual energy x-ray absorptiometry at the lumbar spine , femoral neck , and total body sites every 6 months for 2 yr ; the main outcome measure being the change in areal BMD at the lumbar spine . At baseline , the two groups were well matched for demographic , anthropometric , and biochemical variables , and for BMD . Twenty-seven subjects completed at least 18 months in the study , and 26 the full 2 yr , with similar numbers dropping out from each group ( mainly for personal reasons ) . In the estrogen-treated group , mean lumbar spine BMD increased 1 % , whereas in the placebo group it fell 2.6 % , over 2 yr . The between group differences were 2.0 % at 12 months ( P = 0.058 ) , 3.2 % at 18 months ( P < 0.01 ) , and 3.5 % at 24 months ( P < 0.002 ) . Differences of lesser statistical magnitude were seen at the femoral neck ( between group differences at 2 yr : 2.7 % , P = 0.24 ) , Ward 's triangle ( 5.0 % , P = 0.055 ) , greater trochanter ( 3.6 % , P = 0.056 ) , total body ( 1.3 % , P = 0.046 ) , legs ( 1.3 % , P = 0.065 ) , and trunk ( 2.0 % , P = 0.029 ) . There were no major adverse events . These data support the view that the likely cause of DMPA-associated bone loss is estrogen deficiency and demonstrate that it can be arrested by estrogen replacement therapy BACKGROUND A clinical study compared efficacy and safety of depot medroxyprogesterone acetate ( DMPA ) with leuprolide for endometriosis-associated pain . METHODS This multicentre , 18 month , evaluator-blinded , comparator-controlled trial r and omized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA ( DMPA-SC 104 ) every 3 months or leuprolide ( 3.75 mg monthly or 11.25 mg every 3 months ) , with 12 months post-treatment follow-up . Endpoints included patient response to treatment in five signs/symptoms ( dysmenorrhoea , dyspareunia , pelvic pain , pelvic tenderness , in duration ) and changes in bone mineral density ( BMD ) and productivity at 6 and 18 months . RESULTS DMPA-SC 104 and leuprolide produced equivalent ( P < 0.02 ) reductions in at least four pain categories and significant ( P < 0.001 ) improvements in composite score at months 6 and 18 . At month 6 , reductions in total hip and lumbar spine BMD were significantly less ( P < 0.001 ) with DMPA-SC 104 versus leuprolide . BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group . Total productivity also significantly ( P < or = 0.05 ) improved in both groups at 6 and 18 months . CONCLUSIONS DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline OBJECTIVE To compare longitudinal changes in bone mineral density ( BMD ) among first-time depot medroxyprogesterone acetate ( DMPA ) users to women using no hormonal contraception , and evaluate user characteristics associated with that BMD change . DESIGN Prospect i ve longitudinal study . SETTING Healthy volunteers in an academic research environment . PATIENT(S ) Women , aged 18 to 35 , choosing DMPA for contraception ( n = 178 ) and women using no hormonal contraception ( n = 145 ) . MAIN OUTCOME MEASURE(S ) Hip and spine BMD measured , at three-month intervals for 24 months , by dual energy x-ray absorptiometry . RESULT ( S ) Mean hip BMD declined 2.8 % ( SE = 0.034 ) 12 months following DMPA initiation and 5.8 % ( SE = 0.096 ) after 24 months . Mean spine ( L1-L3 ) BMD declined 3.5 % ( SE = 0.022 ) and 5.7 % ( SE = 0.034 ) , respectively , after one and two years of DMPA use . Mean hip and spine BMD of control participants changed less than 0.9 % over the same period . Among DMPA users , body mass index ( BMI ) change was inversely associated with BMD change at the hip , but not at the spine . Calcium intake , physical activity , and smoking did not influence BMD change in either group . CONCLUSION ( S ) Hip and spine BMD declined after one DMPA injection and this decline continued with each subsequent injection for 24 months . With the exception of increasing BMI among DMPA users , no user characteristics offered protection against DMPA-related BMD loss Although adolescent women are actively acquiring bone , there has been little study of the possible effects of depot medroxyprogesterone acetate ( DMPA ) injectable contraception use on bone density in adolescents . We conducted a cross-sectional evaluation of the association between DMPA use and bone mineral density in adolescent women , ages 14 - 18 years . Of 174 study participants , 81 were DMPA users ( range , 1 - 13 injections , median = 3 ) and 93 were not . Mean bone density at all anatomic sites ( hip , spine and whole body ) was lower for DMPA users than nonusers , but differences were not statistically significant ( e.g. , hip , 0.940 vs. 0.970 g/cm2 , p = 0.10 ; spine , 0.970 vs. 0.992 g/cm2 , p = 0.19 ) . Duration of DMPA use showed a trend toward lower spine bone density ( p-value for trend = 0.06 ) . This study did not find a strong association between DMPA use and bone density . Further prospect i ve evaluation of bone density changes with DMPA use and after DMPA discontinuation are needed in this age group OBJECTIVE The purpose of this study was to determine the rate of early postmenopausal bone loss in women who had used depot medroxyprogesterone acetate contraception through to menopause . STUDY DESIGN Bone mineral density at the lumbar spine and femoral neck was assessed prospect ively over 3 years in 15 women who reached a natural menopause and who did not undergo hormone replacement therapy and in 16 long-term users of depot medroxyprogesterone acetate who discontinued depot medroxyprogesterone acetate only on reaching menopause . Of the latter , 5 women subsequently underwent hormone replacement therapy . RESULTS Early menopausal bone loss was rapid in the control group ( 6 % from both sites over 3 years ) , but the users of depot medroxyprogesterone acetate ( who did not take hormone replacement therapy ) showed little change in bone mineral density . Between-group differences were statistically significant at years 2 and 3 at both sites ( P < .03-<.002 ) . In the users of depot medroxyprogesterone acetate who underwent hormone replacement therapy , bone mineral density increased significantly ( P < .03 ) at the lumbar spine and was stable at the femoral neck . CONCLUSION Women who use depot medroxyprogesterone acetate through to menopause have attenuated rates of bone loss from the lumbar spine and femoral neck , presumably because they have already lost the estrogen-sensitive component of bone STUDY OBJECTIVE To examine bone mineral density ( BMD ) on a semi-annual basis among control subjects and adolescent females receiving depot medroxyprogesterone acetate ( DMPA ) injection or oral contraceptives . DESIGN Non-r and omized prospect i ve study . SETTING Teenage pregnancy prevention intervention clinic . PARTICIPANTS Adolescent females who were new users of DMPA injection ( N=58 , age 12 - 21 ) or the oral contraceptive pill ( N=71 , age 11 - 19 ) and normal menstruating girls ( N=19 , age 15 - 18 ) . INTERVENTIONS Baseline and 6-monthly measures of lumbar vertebral BMD using dual-energy X-ray absorptiometry over a 2-year period . MAIN OUTCOME MEASURES comparison of percent change on BMD over time between DMPA users , pill users , and normal menstruating girls . RESULTS There was no difference on group characteristics at baseline except for the ethnicity between the controls and the DMPA group . There was a statistically significant decrease in BMD between DMPA users and controls at 6 months ( -3.02 % change , P=0.014 ) 12 months ( -3.38 % change , P=0.001 ) 18 months ( -4.81 % change , P<0.001 ) and 24 months ( -6.81 % change , P=0.010 ) . There was no statistical difference between pill users and controls . CONCLUSION There is a relationship between DMPA use and a decrease in BMD compared to normal menstruating controls that seems to persist up to 24 months 1 . The influence of pregnancy , lactation and weaning on bone mineral density in healthy women was investigated during a 2 year prospect i ve study of 59 pregnant and lactating women from the 18th week of gestation . 2 . Bone mineral density was measured by dual energy X-ray absorptiometry at the non-dominant radius ultra distally and more proximally in the 18th and 37th weeks of gestation , and 0 , 3 , 6 , 12 and 18 months after delivery . Measurements of bone mineral density of the lumbar spine , the proximal femur and the whole body were performed at all date s after delivery . 3 . Reappearance of menstruation after delivery averaged 6.1 months ; mean lactating period was 8.7 months . During pregnancy and lactation bone mineral density tended to decrease , but different measuring sites showed different patterns of bone mineral density changes . The reduction in the ultra distal radius during pregnancy amounted to 2 % , and no further changes were observed here during lactation . After delivery , reduction in mean bone mineral density was most pronounced in the spine ( 5.2 % in 3 months ) , but the fall in bone mass tended to revert after resumption of menstruation . Bone mineral density was still reduced by 3.3 % after 12 months in women with menstruation resumption later than 8 months after delivery . No significant reduction was observed 18 months after delivery . No association with calcium intake , weight changes or initial bone mineral density was observed . High calcium intake did not protect against bone mineral loss in the spine and the femur . 4 . Thus it can be concluded that bone loss during pregnancy and lactation took place mainly from the trabecular skeleton . Resumption of menstruation tended to result in a regain of bone mass towards baseline Whether nulliparity increases fracture risk is unclear from prior studies , which are limited by small sample s or lack of measured bone mineral density . No study has evaluated whether the effect of parity differs by skeletal site . We prospect ively analyzed the relationship of parity to the risk of incident nontraumatic hip , spine , and wrist fractures in 9704 women aged 65 years or older participating in the Study of Osteoporotic Fractures to determine if parity reduces postmenopausal fracture risk , and if so , if this risk reduction is ( 1 ) greater at weight-bearing skeletal sites and ( 2 ) independent of bone mineral density . Parity was ascertained by self-report . Incident hip and wrist fractures were determined by physician adjudication of radiology reports ( mean follow-up , 9.8 years ) and spine fractures by morphometric criteria on serial radiographs . The relationship of parity to hip and wrist fracture was assessed by proportional hazards models . Spine fracture risk was evaluated by logistic regression . Compared with parous women , nulliparous women ( n = 1835 , 19 % ) had an increased risk of hip and spine , but not wrist , fractures . In multivariate models , parity remained a significant predictor only for hip fracture . Nulliparous women had a 44 % increased risk of hip fractures independent of hip bone mineral density ( hazards ratio , 1.44 ; 95 % CI , 1.17 - 1.78 ) . Among parous women , each additional birth reduced hip fracture risk by 9 % ( p = 0.03 ) . Additionally , there were no differences in mean total hip , spine , or radial bone mineral density values between nulliparous and parous women after multivariate adjustment . In conclusion , childbearing reduces hip fracture risk by means that may be independent of hip bone mineral density OBJECTIVE To compare the effect of depot medroxypro‐gesterone acetate ( DMPA ) and two types of oral contraceptives ( OC ) on bone mineral density ( BMD ) among women 18–33 years of age with those not using hormonal contraception . METHODS Data from 155 women were analyzed . Depot medroxyprogesterone acetate was administered to 33 women ; 63 women who chose oral contraception were r and omly assigned to receive either a norethindrone‐containing pill ( n = 28 ) or a desogestrel‐containing pill ( n = 35 ) . Fifty‐nine women who did not use hormonal contraception served as controls . Lumbar spine BMD was determined using dual‐energy x‐ray absorptiometry at baseline and after 12 months of contraceptive use . We analyzed method ‐related percent change in BMD while controlling for body mass index , calcium intake , exercise , and smoking . We had approximately 90 % power to detect a 2.5 % difference between any two groups . RESULTS Users of DMPA experienced a mean BMD loss of 2.74 % over 12 months compared with controls who sustained a 0.37 % loss ( P = .01 ) . Users of OCs generally demonstrated a gain ( 2.33 % for norethindrone‐containing pills , 0.33 % for desogestrel‐containing pills ) , which was different from controls among users of norethindrone‐containing pills ( P = .01 ) , but not among users of desogestrel‐containing pills ( P = .99 ) . Observed changes in BMD among DMPA users differed from women who used either type of pill ( P < .002 ) . CONCLUSION Depot medroxyprogesterone acetate has an adverse effect on BMD , in comparison with OCs or non‐hormonal methods , when used for 12 months . Results must be interpreted cautiously until it is determined whether these effects endure or are reversible The bone density ( BD ) of 72 women using depot-medroxyprogesterone acetate ( DMPA ) for at least 1 year was compared with that of 64 women who were not users of hormonal contraceptives . The BD of lumbar spine , femoral neck , Ward 's triangle , and trochanter was measured by dual energy X-ray absorptiometry ( DEXA-LUNAR DPX ) . Estradiol ( E2 ) concentrations were measured by radioimmunoassay ( RIA ) . The mean age of DMPA users and nonusers was 31.8 and 31.1 years , respectively . Mean E , was 55.7 pg/mL for users and 149.9 pg/mL for controls ( p < 0.001 ) . The BD was significantly lower for DMPA users than for controls in all sites ( p < 0.01 ) . In addition , young adult T-scores in the lumbar spine were significantly lower among DMPA users than in controls ( p < 0.01 ) . Differences were maintained in a sub sample of 47 women per group paired by age and body mass index ( BMI ) . Multiple regression analysis showed that older age , lower BMI , and longer amenorrhea were associated with lower BD in the femoral neck , whereas lower BMI and use of DMPA were associated with lower BD in the lumbar spine OBJECTIVE : To measure the effect of 24 months of depot medroxyprogesterone acetate use on bone mineral density compared with oral contraception ( pills ) and nonhormonal contraception . METHODS : Women aged 18–33 years self-selected oral contraception , depot medroxyprogesterone acetate , or nonhormonal contraception ( controls ) . Those selecting pills were r and omized to formulations containing either 35 & mgr;g ethinyl estradiol and norethindrone or 30 & mgr;g ethinyl estradiol and desogestrel . Controls were frequency matched on age and race/ethnicity to hormonal contraception users . Dual-energy X-ray absorptiometry of the lumbar spine ( L1–L4 ) was performed at baseline , 12 months , and 24 months . Percent change in bone mineral density was analyzed by using analysis of covariance , adjusting for age , race/ethnicity , weight-bearing exercise , calcium intake , smoking status , and body mass index . RESULTS : Of the 191 women making up the final sample , 86 used pills , 47 used depot medroxyprogesterone acetate , and 58 used nonhormonal contraception . Women using depot medroxyprogesterone acetate for 24 months experienced , on average , a 5.7 % loss in bone mineral density , with a 3.2 % loss occurring between months 12 and 24 . On average , users of desogestrel pills experienced a 2.6 % loss in bone mineral density after 24 months . Bonferroni-adjusted pairwise comparisons demonstrated that bone mineral density changes from baseline to 24 months among depot medroxyprogesterone acetate users differed significantly from changes experienced by either of the pill groups or the control group . Changes in bone mineral density among users of either pill did not significantly differ from each other or from controls . CONCLUSION : Loss of bone mineral density associated with depot medroxyprogesterone acetate use appears to be linear during the first 2 years of use . Shifts in bone mineral density among pill users were not significant when compared with controls . LEVEL OF EVIDENCE : Background Depot medroxyprogesterone acetate ( DMPA ) injectable contraception may decrease bone density and increase the risk for osteoporosis in later life . Prospect i ve data are scarce , especially of the effects of DMPA discontinuation on bone . Methods Between 1994 and 1999 , we conducted a population -based prospect i ve cohort study among women enrollees of a Washington State health maintenance organization . We enrolled 457 nonpregnant women , ages 18–39 years ( 183 DMPA users and 274 non-users ) . Bone density was measured by dual-energy x-ray absorptiometry every 6 months for 3 years . Results Bone density decreased notably among DMPA-exposed women at the spine ( adjusted mean bone density was −0.0053 gm/cm2 for DMPA users compared with + 0.0023 gm/cm2 for non-users for each 6-month interval ) and total hip ( −0.0060 compared with −0.0002 gm/cm2 ) . This represents an annualized mean rate of change at the spine of −0.87 % compared with + 0.40 % and , at the hip , −1.12 % compared with −0.05 % . Discontinuers of this method ( N = 110 ) showed sizable increases in bone density over comparison women ( for each 6-month interval , adjusted mean spine bone density was + 0.0067 gm/cm2 compared with + 0.0023 gm/cm2 , respectively ; adjusted mean hip bone density was + 0.0035 compared with −0.0002 gm/cm2 ) . Estimated annualized mean rates of change were + 1.41 % compared with + 1.03 % at the spine and + 0.40 % compared with −0.05 % at the hip . After 30 months , mean bone density for discontinuers was similar to that of non-users . Conclusions In this study , DMPA use was strongly associated with bone density loss . Substantial postdiscontinuation recovery of bone provides evidence that the effects may be largely reversible |
11,795 | 16,235,283 | There was no evidence that vitamin A in a single dose was associated with a reduced risk of mortality among children with measles .
Although we found no overall significant reduction in mortality with vitamin A therapy for children with measles there was evidence that two doses were associated with a reduced risk of mortality and pneumonia-specific mortality in children under the age of two years . | BACKGROUND Measles is a major cause of childhood morbidity and mortality .
Vitamin A deficiency is a recognized risk factor for severe measles infections .
The World Health Organization ( WHO ) recommends administration of an oral dose of vitamin A ( 200,000 international units ( IU ) , or 100,000 IU in infants ) each day for two days to children with measles when they live in areas where vitamin A deficiency may be present .
OBJECTIVES To determine whether vitamin A therapy , commenced after measles has been diagnosed , is beneficial in preventing mortality , pneumonia and other secondary complications in children . | OBJECTIVES --To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation . MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost A prospect i ve study was conducted in slum children to determine the incidence of post-measles corneal disease and to clarify its relationship with nutritional status . A total of 318 cases of measles were identified over a period of 15 mo ; maximum incidence was observed for children between 1 - 2 yr . Most of the children showed weight loss and serum proteins decrease during the acute stage of measles . Corneal lesions were observed in 3 % of the children , and the lesions responded well to treatment . Serum vitamin A and RBP levels were significantly depressed during the acute stage of measles but were restored to normal 8 wk after recovery . There were no significant differences in the serum levels for those with and without eye lesions , which suggests that these lesions may not be mediated simply through the effect of infection on serum concentration of vitamin A cross-sectional study , a follow-up study , and an intervention trial were carried out to investigate the association between mild vitamin A deficiency and the occurrence of diarrhea and respiratory diseases . Cross-sectional analysis was performed among 1,772 children , aged 1 - 8 years , in the Sakon Nakhon province of northeastern Thail and . Children with a history of diarrhea or respiratory disease had lower levels of serum retinol and retinol-binding protein . Adjusted for age , sex , nutritional status , and level of urbanization , logistic regression using data for 877 children showed a negative association between serum retinol and both diarrhea and respiratory diseases . A follow-up three months later ( n = 146 children ) showed that children with deficient serum retinol ( less than 0.35 mumol/liter ) had a fourfold greater risk of respiratory disease ( p less than 0.01 ) . No relation was found for diarrhea . An intervention trial ( n = 166 children aged 1 - 5 years ) showed that , during 2 months of follow-up after administration of oral vitamin A ( 200,000 IU ) , the control group ( aged 3 - 5 years ) had a higher incidence of respiratory disease ( 2.9 times ) as well as diarrhea ( 3.1 times ) . Between 2 and 4 months , a significantly ( p less than 0.025 ) higher incidence of respiratory diseases ( 2.5 times ) could be observed in children aged 1 - 2 years . This study supports earlier reports on a greater risk of respiratory diseases and of diarrhea in mild vitamin A deficiency . Supplementation reduced the incidence of both diarrhea and respiratory disease for a period of at least 2 months Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results . To resolve the question , a r and omised , double-masked , placebo-controlled community trial of 28,630 children aged 6 - 72 months was carried out in rural Nepal , an area representative of the Gangetic flood plain of South Asia . R and omisation was carried out by administrative ward ; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents . After 12 months , the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 ( 95 % confidence interval 0.56 - 0.88 ) , equivalent to a 30 % reduction in mortality . The trial , which had been planned to last 2 years , was discontinued . The reduction in mortality was present in both sexes ( relative risk for boys 0.77 ; for girls 0.65 ) , at all ages ( range of relative risks 0.83 - 0.50 ) , and throughout the year ( 0.76 - 0.67 ) . The reduction in mortality risk was not affected by acute nutritional status , as measured by arm circumference . Thus , periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries |
11,796 | 21,765,384 | The frequency-specific analysis of the postoperative ABG showed no advantage for the small prosthesis in the high frequencies .
There was no difference in postoperative change of bone conduction in the 0.6- and 0.4-mm groups . | OBJECTIVE To analyze the influence of stapes prosthesis diameter on postoperative hearing results after stapedotomy without interposition in otosclerotic patients . | Two hundred ears with otosclerosis have been operated upon using a 0.4-mm diameter Teflon platinum piston in 100 ears and a 0.6-mm diameter Teflon piston in the other 100 ears . The postoperative air-bone gap , calculated as the difference between the postoperative air and bone conduction levels , was smaller in the 0.6 mm group for all frequencies except at 2000 Hz , the differences were statistically insignificant except at 4000 Hz . The mean postoperative air-bone gap was 8.6 dB and 7.4 dB for the 0.4 and 0.6 mm groups , respectively , which is statistically insignificant . We found no postoperative loss of bone conduction exceeding 15 dB , there was a deterioration of more than 10 dB in three ears , one in the 0.4 mm group and two in the 0.6 mm group . According to our results , we conclude that the 0.4 mm and the 0.6 mm Teflon prostheses produce the same hearing improvement in stapes surgery for otosclerosis Tight fixation of stapes prostheses yields better functional results because sound transmission from the incus to the prosthesis is improved . Background : The optimal prosthesis to use for otosclerosis surgery is still a matter of debate . It has been proposed that using prostheses made of Nitinol , a shape-memory metal , produces better functional results with less variability and reduced risk for middle and inner ear damage . This is thought to be because heat activation rather than manual crimping of the prosthesis loop forms a tighter fixation . Methods : Functional results of two groups were compared 1 year after surgery . In one group were 75 cases of stapedotomy performed using Nitinol prostheses . Results were analyzed prospect ively and compared with 75 retrospectively analyzed matched controls with conventional stapes prostheses . Crimping quality was measured in 23 patients by intraoperative laser Doppler interferometry ( LDI ) . Causality was assessed by correlating results of intraoperative LDI and postoperative pure-tone thresholds . Results : Nitinol and conventional prostheses yielded postoperative air-bone gaps ( ABGs ) of 8.0 and 11.6 dB with 71 and 43 % ABG closure within 10 dB , respectively . Intraoperatively , sound transmission was improved by 2.5 dB with the Nitinol prostheses as compared with conventional prostheses . These differences were statistically significant . Intraoperative fixation quality was positively correlated to functional outcome , but results were not statistically significant . Conclusion : Tight fixation , as provided by Nitinol prostheses leads to improved functional results because of better sound transmission properties at the incus-prosthesis interface . The improvement in ABG closure is in the range of 3 dB pure-tone average and more pronounced at higher frequencies . Nitinol prostheses provide an effective treatment option in otosclerosis surgery Objectives : This is the first clinical trial to evaluate the suitability of a new titanium stapes prosthesis , which we developed jointly with the Kurz Company ( Dußlingen ) This study compares hearing results after stapedotomy by 0.6 mm and 0.8 mm teflon pistons . Retrospective analysis studied 100 patients r and omly selected who underwent stapedotomy for otosclerosis with insertion of 0.8 mm teflon piston prosthesis and 100 patients with 0.6 mm teflon piston prosthesis . Air-conduction hearing level in both groups were measured before and after the procedure and the gain of the air conduction between the 2 groups at different frequencies were compared statistically . The group with the 0.8 mm prosthesis had better results that were statistically significant and more pronounced at lower frequencies The early and long-term hearing results of 1,681 primary otosclerosis operations performed by the same surgeon , Jean Marquet , were review ed retrospectively and analyzed with very strict statistical st and ards . Significantly better short- and long-term results were achieved with the stapedotomy technique compared to total stapedectomy , mainly at the higher frequencies ( 4 and 8 kHz ) important for speech discrimination . Whatever technique was used to open the footplate ( micropick , microdrill , or laser ) , no statistical audiometric difference could be found . The results were equal whether or not the stapedial tendon was preserved . Perioperative problems like pronounced oozing , difficult anatomic relationships , and accidental perilymph aspiration could affect hearing at higher frequencies . The calibrated hole technique was equally as good as conventional oval window sealing in sealing of the fenestra to prevent fistula . The stapedotomy technique was found the safest , having fewer complications This study reports the evaluation of hearing results after implantation of a Teflon piston of a different diameter in cases of otosclerosis requiring stapedotomy . By r and om selection , a Teflon piston with a shaft diameter of 0.3 mm was inserted in 34 cases and a piston with a shaft diameter of 0.4 mm in 26 cases . A retrospective analysis of the pre- and postsurgery audiological results of these two patient groups was carried out by microcomputer . A repeated statistical measures analysis of variance was used to test and estimate the air-conduction frequency-specific differences between the two prostheses with respect to changes in pre- and postoperative healing . The results of this comparative study of the two Teflon pistons with different diameters indicate statistically a greater hearing gain for the 0.4-mm prosthesis , especially in the lower frequencies Over the last 10 years , lasers have evolved to become an integral part of stapes surgery . Argon , KTP , and CO2 lasers have all been tested for their improved accuracy and safety in the middle ear . Because of the difference in optical properties between visible light ( argon , KTP ) and infrared ( CO2 ) lasers , discussion s have evolved around which laser is better and safer . In an effort to clarify the issues , a prospect i ve comparison was made of 100 consecutive primary stapedotomies by using either the CO2 or KTP laser From 1975 to 1992 , a total of 1459 primary stapedoplasty operations ( i.e. , stapedectomy , stapedotomy with tendon section , and stapedotomy with tendon preservation ) were performed in 1323 subjects at the Ear , Nose , and Throat Department of the University of Verona . Pure-tone audiometry was carried out in all subjects who were operated on and who underwent 6-month and 10-year follow-ups . To evaluate the influence of stapedius tendon preservation on functional outcome , we r and omly selected subgroups of patients using the three different stapedoplasty techniques and tested them by multiple-frequency tympanometry , psychoacoustic tuning curves , and speech discrimination in noise . Finally , to assess the effect of prosthesis diameter on middle ear transfer function , we used the electrocochleographic technique and examined the threshold and latency of cochlear nerve compound action potentials recorded during surgery from the round window . The results of this study show that the best auditory performance in otosclerotic subjects is achieved by performing a stapedotomy of 0.7 mm diameter , using a 0.6 wire-Teflon piston , and preserving the stapedius tendon Thirty-four ears with conductive hearing loss due to otosclerosis were operated upon using the laser stapedotomy technique . Audiological results were compared with the results of 316 non-laser stapedotomies . The post-operative air-bone gap , calculated as the difference between the post-operative air and bone conduction levels , was smaller with the laser stapedotomy group . Also , the bone conduction showed significant improvement with the use of laser . Significant sensorineural hearing loss was not found in any of the laser-treated patients . According to our results , we concluded that laser is of benefit in stapes surgery for improving the hearing results and minimizing the inner ear trauma BACKGROUND The first hearing results with a new stapes prosthesis with clip function ( Soft-CliP(R ) piston ) are presented . PATIENTS AND METHODS This new prosthesis was used in 15 patients ( mean age 45.2 years ; range 21 - 63 years ) undergoing routine stapes surgery . Soft-CliP(R ) piston prostheses with a shaft diameter of 0.4 mm and a length ranging from 4.25 mm to 5.5 mm were used . Postoperative audiological testing and measurement of the air-bone gap were performed after an average of 47.3 days and compared with the preoperative values . RESULTS The median observed postoperative air-bone gap ( ABG ) was 8.33 dB + /-4.16 dB. All patients had less than 20 dB ABG and in 53.3 % of cases was less than 10 dB. The operating time showed a clear difference between the left ( 66.5 min + /-37.79 min ) and right ears ( 47.2 min + /-11.08 min ) . DISCUSSION This new prosthesis design greatly facilitates a very difficult step in stapes surgery , the prosthesis fixation to the incus . The first postoperative hearing results are very promising but long-term results in a larger group of patients are still pending |
11,797 | 27,609,363 | We conclude that aerobic exercise performed in the fasted state induces higher fat oxidation than exercise performed in the fed state | This study aim ed to verify the effect of aerobic exercise performed in the fasted v. fed states on fat and carbohydrate metabolism in adults . | Overweight and obesity affects more than 66 % of the adult population and is associated with a variety of chronic diseases . Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies . Guidelines of the National Heart , Lung , and Blood Institute ( NHLBI ) encourage a 10 % reduction in weight , although considerable literature indicates reduction in health risk with 3 % to 5 % reduction in weight . Physical activity ( PA ) is recommended as a component of weight management for prevention of weight gain , for weight loss , and for prevention of weight regain after weight loss . In 2001 , the American College of Sports Medicine ( ACSM ) published a Position St and that recommended a minimum of 150 min wk(-1 ) of moderate-intensity PA for overweight and obese adults to improve health ; however , 200 - 300 min wk(-1 ) was recommended for long-term weight loss . More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss . To this end , we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain , for weight loss , and prevention of weight regain . Evidence supports moderate-intensity PA between 150 and 250 min wk(-1 ) to be effective to prevent weight gain . Moderate-intensity PA between 150 and 250 min wk(-1 ) will provide only modest weight loss . Greater amounts of PA ( > 250 min wk(-1 ) ) have been associated with clinical ly significant weight loss . Moderate-intensity PA between 150 and 250 min wk(-1 ) will improve weight loss in studies that use moderate diet restriction but not severe diet restriction . Cross-sectional and prospect i ve studies indicate that after weight loss , weight maintenance is improved with PA > 250 min wk(-1 ) . However , no evidence from well- design ed r and omized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss . Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk . Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk . There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain OBJECTIVE Fat oxidation during exercise depends on nutritional state , and exercise performed in the post-absorptive state oxidizes more fat than that performed in the postpr and ial state . However , the effects of exercise on energy metabolism continue during the post-exercise period , and the difference in fat oxidation during exercise may be compensated for during the post-exercise period . The present study compared the effects of an acute exercise bout in the post-absorptive or postpr and ial state on 24 h fat oxidation . METHODS Twelve young male athletes stayed twice in a room-size metabolic chamber for 24 h indirect calorimetry in a r and omized repeated-measure design . Before or after breakfast , i.e. in the post-absorptive or postpr and ial state , subjects exercised at 50 % VO(2)max for 60 min . RESULTS During the 60 min of exercise , energy expenditure in the two exercise trials were equivalent , but exercise in the post-absorptive state was performed with lower RQ compared with that in the postpr and ial state ( P<0.01 ) . The time of exercise relative to breakfast did not affect 24 h energy expenditure ( P>0.5 ) . However , accumulated 24 h fat oxidation was higher ( P<0.05 ) and that of carbohydrate oxidation was lower ( P<0.05 ) when exercise was performed in the post-absorptive state . CONCLUSIONS Compared with exercise performed in the postpr and ial state , exercise performed in the post-absorptive state oxidized more fat and saved more carbohydrate in the body , without affecting 24 h energy expenditure The glycaemic index ( GI ) concept was originally introduced to classify different sources of carbohydrate (CHO)-rich foods , usually having an energy content of > 80 % from CHO , to their effect on post-meal glycaemia . It was assumed to apply to foods that primarily deliver available CHO , causing hyperglycaemia . Low-GI foods were classified as being digested and absorbed slowly and high-GI foods as being rapidly digested and absorbed , result ing in different glycaemic responses . Low-GI foods were found to induce benefits on certain risk factors for CVD and diabetes . Accordingly it has been proposed that GI classification of foods and drinks could be useful to help consumers make ' healthy food choices ' within specific food groups . Classification of foods according to their impact on blood glucose responses requires a st and ardised way of measuring such responses . The present review discusses the most relevant method ological considerations and highlights specific recommendations regarding number of subjects , sex , subject status , inclusion and exclusion criteria , pre-test conditions , CHO test dose , blood sampling procedures , sampling times , test r and omisation and calculation of glycaemic response area under the curve . All together , these technical recommendations will help to implement or reinforce measurement of GI in laboratories and help to ensure quality of results . Since there is current international interest in alternative ways of expressing glycaemic responses to foods , some of these methods are discussed The purpose of this study was to determine the effects of a pre-exercise meal on the plasma human growth hormone ( hGH ) response and fat oxidation during walking . Subjects ( n=8 ) were r and omly provided with either 1 g/kg body weight of glucose in 200 mL water ( CHO ) or 200 mL water alone ( CON ) 30 min prior to exercise and subsequently walked on a treadmill at 50 % of VO2max for 60 min . Plasma hGH concentrations were significantly higher in subjects who received CHO compared to those who received CON at 15 and 30 min . The fat oxidation rate in the CHO was significantly lower than the CON while walking for 5~15 , 25~35 and 45~55 min . Plasma FFA levels were also significantly lower in the CHO compared to the CON at 30 , 45 and 60 min . Plasma glucose levels in the CHO were significantly lower while plasma insulin levels were significantly higher than in the CON at 15 and 30 min . Therefore , the results of this study suggest that the elevation of plasma hGH levels due to the intake of a pre-exercise meal may not be strongly related to fat oxidation and plasma free fatty acid ( FFA ) levels during low-intensity exercise The present study was undertaken to examine the effects of glucose ingestion before exercise on liver glucose output and muscle glucose uptake during exercise . On two occasions , at least 1 wk apart , six trained men ( peak pulmonary O2 uptake = 5.11 + /- 0.17 l/min ) ingested 400 ml of a solution containing either 75 g glucose [ carbohydrate ( CHO ) ] or a sweet placebo [ control ( Con ) ] 30 min before 60 min of exercise at 71 + /- 1 % peak pulmonary O2 uptake . Glucose kinetics ( rates of appearance and disappearance ) were measured by a primed continuous infusion of [6,6 - 2H2]glucose . Liver glucose output was derived from total glucose appearance and the appearance of ingested glucose from the gut . After glucose ingestion , plasma glucose increased to 6.4 + /- 0.4 mmol/l immediately before exercise , fell to 4.2 + /- 0.5 mmol/l after 20 min of exercise , and then increased to a higher value than in the Con group ( 5.4 + /- 0.3 vs. 4.7 + /- 0.1 mmol/l ; P < 0.05 ) after 60 min of exercise . In the CHO group , plasma insulin was higher immediately before exercise ( P < 0.05 ) and , despite falling during exercise , remained higher than in the Con group after 60 min of exercise ( 57.0 + /- 11.4 vs. 24.8 + /- 1.7 pmol/l ; P < 0.05 ) . The rapid fall in plasma glucose in the CHO group was the result of a higher muscle glucose uptake with the onset of exercise ( P < 0.05 ) , which could not be matched by the glucose rate of appearance . Liver glucose output was decreased by glucose ingestion , and although it increased during the early stages of exercise in the CHO group , it did not rise above the basal values and was reduced by 62 % over the 60 min of exercise compared with the Con group . In summary , preexercise glucose ingestion results in increased muscle glucose uptake and reduced liver glucose output during exercise BACKGROUND Obesity is a major health problem due , in part , to physical inactivity . The amount of activity needed to prevent weight gain is unknown . OBJECTIVE To determine the effects of different amounts and intensities of exercise training . DESIGN R and omized controlled trial ( February 1999-July 2002 ) . SETTING AND PARTICIPANTS Sedentary , overweight men and women ( aged 40 - 65 years ) with mild to moderate dyslipidemia were recruited from Durham , NC , and surrounding communities . INTERVENTIONS Eight-month exercise program with 3 groups : ( 1 ) high amount/vigorous intensity ( calorically equivalent to approximately 20 miles [ 32.0 km ] of jogging per week at 65%-80 % peak oxygen consumption ) ; ( 2 ) low amount/vigorous intensity ( equivalent to approximately 12 miles [ 19.2 km ] of jogging per week at 65%-80 % ) , and ( 3 ) low amount/moderate intensity ( equivalent to approximately 12 miles [ 19.2 km ] of walking per week at 40%-55 % ) . Subjects were counseled not to change their diet and were encouraged to maintain body weight . MAIN OUTCOME MEASURES Body weight , body composition ( via skinfolds ) , and waist circumference . RESULTS Of 302 subjects screened , 182 met criteria and were r and omized and 120 completed the study . There was a significant ( P<.05 ) dose-response relationship between amount of exercise and amount of weight loss and fat mass loss . The high-amount/vigorous-intensity group lost significantly more body mass ( in mean [ SD ] kilograms ) and fat mass ( in mean [ SD ] kilograms ) ( -2.9 [ 2.8 ] and -4.8 [ 3.0 ] , respectively ) than the low-amount/moderate-intensity group ( -0.9 [ 1.8 ] and -2.0 [ 2.6 ] , respectively ) , the low-amount/vigorous-intensity group ( -0.6 [ 2.0 ] and -2.5 [ 3.4 ] , respectively ) , and the controls ( + 1.0 [ 2.1 ] and + 0.4 [ 3.0 ] , respectively ) . Both low-amount groups had significantly greater improvements than controls but were not different from each other . Compared with controls , all exercise groups significantly decreased abdominal , minimal waist , and hip circumference measurements . There were no significant changes in dietary intake for any group . CONCLUSIONS In nondieting , overweight subjects , the controls gained weight , both low-amount exercise groups lost weight and fat , and the high-amount group lost more of each in a dose-response manner . These findings strongly suggest that , absent changes in diet , a higher amount of activity is necessary for weight maintenance and that the positive caloric imbalance observed in the overweight controls is small and can be reversed by a modest amount of exercise . Most individuals can accomplish this by walking 30 minutes every day The oxidation of glucose and fructose ingested during moderate exercise performed on a cycle ergometer ( 120 min , 52 % VO2max ) was compared in ten young males fasted ( n = 5 ) or fed ( n = 5 ) before exercise . The subjects ingested r and omly 1.33 g/kg body weight ( approximately 96 + /- 9 g ) of either enriched 13C-glucose ( G ) , 13C-fructose ( F ) , or water only ( W ) ; the solutions were evenly distributed over the exercise period . The fasted subjects began the three exercises with a lower blood glucose ( P less than or equal to 0.05 for F only ) and insulin ( P less than or equal to 0.05 ) levels and a higher free fatty acid ( FFA ) concentration ( P less than or equal to 0.05 ) than the fed ones . Throughout the exercise period , blood glucose level was maintained in fasted as well as in fed group for G and F ingestions , while it decreased ( P less than or equal to 0.05 at the 100th min in fasted subjects ) with water ingestion . Insulin level was similar in both fed and fasted conditions with F and W ingestions and lower than G trials for the fed subjects . For the three ingestions , FFA was lower ( P less than or equal to 0.05 ) in the fasted than in the fed group over the exercise period . Over the 2-h period of exercise , a greater ( P less than or equal to 0.05 ) amount of exogenous F was oxidized in the fasted ( 49 + /- 6 g ) than in the fed ( 36 + /- 5 g ) group , which represent 31 % and 20 % of the total carbohydrate energy supply , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS Skeletal muscle insulin resistance entails dysregulation of both glucose and fatty acid metabolism . This study examined whether a combined intervention of physical activity and weight loss influences fasting rates of fat oxidation and insulin-stimulated glucose disposal . Obese ( BMI > 30 kg/m(2 ) ) volunteers ( 9 men and 16 women ) without diabetes , aged 39 + /- 4 years , completed 16 weeks of moderate-intensity physical activity combined with caloric reduction . Body composition was determined by dual-energy X-ray absorptiometry and computed tomography . Glucose disposal rates ( R(d ) ) were measured during euglycemic hyperinsulinemia ( 40 mU x m(-2 ) x min(-1 ) ) , and substrate oxidation was determined via indirect calorimetry . Fat mass and regional fat depots were reduced and VO(2max ) improved by 19 % , from 38.8 + /- 1.2 to 46.0 + /- 1.0 ml x kg fat-free mass (FFM)(-1 ) x min(-1 ) ( P < 0.05 ) . Insulin sensitivity improved 49 + /- 10 % ( 6.70 + /- 0.40 to 9.51 + /- 0.51 mg x min(-1 ) x kg FFM(-1 ) ; P < 0.05 ) . Rates of fat oxidation following an overnight fast increased ( 1.16 + /- 0.06 to 1.36 + /- 0.05 mg x min(-1 ) x kg FFM(-1 ) ; P < 0.05 ) , and the proportion of energy derived from fat increased from 38 to 52 % . The strongest predictor of the improved insulin sensitivity was enhanced fasting rates of fat oxidation , accounting for 52 % of the variance . In conclusion , exercise combined with weight loss enhances postabsorptive fat oxidation , which appears to be a key aspect of the improvement in insulin sensitivity in obesity PURPOSE To determine whether eating a breakfast cereal with a moderate glycemic index could alter substrate utilization and improve exercise duration . METHODS Six active women ( age , 24 + /- 2 yr ; weight , 62.2 + /- 2.6 kg ; VO(2peak ) , 46.6 + /- 3.8 mL x kg(-1 ) x min(-1 ) ) ate 75 g of available carbohydrate in the form of regular whole grain rolled oats ( RO ) mixed with 300 mL of water or water alone ( CON ) . The trials were performed in r and om order and the meal or water was ingested 45 min before performing cycling exercise to exhaustion ( 60 % of VO(2peak ) ) . Blood sample s were drawn for glucose , glucose kinetics , free fatty acids ( FFA ) , glycerol , insulin , epinephrine ( EPI ) , and norepinephrine ( NE ) determination . A muscle biopsy was obtained from the vastus lateralis muscle before the trial and immediately after exercise for glycogen determination . Glucose kinetics ( Ra ) were determined using a [ 6,6-(2)H ] glucose tracer . RESULTS Compared with CON , plasma FFA and glycerol levels were suppressed ( P < 0.05 ) during the first 120 min of exercise for the RO trial . Respiratory exchange ratios ( RER ) were also higher ( P < 0.05 ) for the first 120 min of exercise for the RO trial . At exhaustion , glucose , insulin , FFA , glycerol , EPI , NE , RER , and muscle glycogen were not different between trials . Glucose Ra was greater ( P < 0.05 ) during the RO trial compared with CON ( 2.36 + /- 0.22 and 1.92 + /- 0.27 mg x kg(-1 ) x min(-1 ) , respectively ) . Exercise duration was 5 % longer during RO , but the mean times were not significantly different ( 253.6 + /- 6 and 242.0 + /- 15 min , respectively ) . CONCLUSIONS Increased hepatic glucose output before fatigue provides some evidence of glucose sparing after the breakfast cereal trial . However , exercise duration was not significantly altered , possibly because of the sustained suppression of lipid metabolism and increased carbohydrate utilization throughout much of the exercise period Both stable isotope methodology and fluorescence microscopy were applied to define the use of intramuscular triglyceride ( IMTG ) stores as a substrate source during exercise on a whole-body as well as on a fibre type-specific intramyocellular level in trained male cyclists . Following an overnight fast , eight subjects were studied at rest , during 120 min of moderate intensity exercise ( 60 % maximal oxygen uptake capacity ( VO2,max ) ) and 120 min of post-exercise recovery . Continuous infusions of [U-13C]palmitate and [6,6 - 2H2]glucose were administered at rest and during subsequent exercise to quantify whole-body plasma free fatty acid ( FFA ) and glucose oxidation rates and the contribution of other fat sources ( sum of muscle- plus lipoprotein-derived TG ) and muscle glycogen to total energy expenditure . Fibre type-specific intramyocellular lipid content was determined in muscle biopsy sample s collected before , immediately after and 2 h after exercise . At rest , fat oxidation provided 66 + /- 5 % of total energy expenditure , with FFA and other fat sources contributing 48 + /- 6 and 17 + /- 3 % , respectively . FFA oxidation rates increased during exercise , and correlated well with the change in plasma FFA concentrations . Both the use of other fat sources and muscle glycogen declined with the duration of exercise , whereas plasma glucose production and utilisation increased ( P < 0.001 ) . On average , FFA , other fat sources , plasma glucose and muscle glycogen contributed 28 + /- 3 , 15 + /- 2 , 12 + /- 1 and 45 + /- 4 % to total energy expenditure during exercise , respectively . Fluorescence microscopy revealed a 62 + /- 7 % net decline in muscle lipid content following exercise in the type I fibres only , with no subsequent change during recovery . We conclude that IMTG stores form an important substrate source during moderate intensity exercise in endurance-trained male athletes following an overnight fast , with the oxidation rate of muscle- plus lipoprotein-derived TG being decreased with the duration of exercise The effects were compared of exercise in the fasted state and exercise with a high rate of carbohydrate intake on intramyocellular triglyceride ( IMTG ) and glycogen content of human muscle . Using a r and omized crossover study design , nine young healthy volunteers participated in two experimental sessions with an interval of 3 weeks . In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75 % ) , followed by 4 h of controlled recovery . On one occasion they exercised after an overnight fast ( F ) , and on the other ( CHO ) they received carbohydrates before ( approximately 150 g ) and during ( 1 g ( kg bw)(-1 ) h(-1 ) ) exercise . In both conditions , subjects ingested 5 g carbohydrates per kg body weight during recovery . Fibre type-specific relative IMTG content was determined by Oil red O staining in needle biopsies from m. vastus lateralis before , immediately after and 4 h after exercise . During F but not during CHO , the exercise bout decreased IMTG content in type I fibres from 18 + /- 2 % to 6 + /- 2 % ( P = 0.007 ) area lipid staining . Conversely , during recovery , IMTG in type I fibres decreased from 15 + /- 2 % to 10 + /- 2 % in CHO , but did not change in F. Neither exercise nor recovery changed IMTG in type IIa fibres in any experimental condition . Exercise-induced net glycogen breakdown was similar in F and CHO . However , compared with CHO ( 11.0 + /- 7.8 mmol kg(-1 ) h(-1 ) ) , mean rate of postexercise muscle glycogen re synthesis was 3-fold greater in F ( 32.9 + /- 2.7 mmol kg(-1 ) h(-1 ) , P = 0.01 ) . Furthermore , oral glucose loading during recovery increased plasma insulin markedly more in F ( + 46.80 microU ml(-1 ) ) than in CHO ( + 14.63 microU ml(-1 ) , P = 0.02 ) . We conclude that IMTG breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres and that this breakdown is prevented in the CHO-fed state . Furthermore , facilitated glucose-induced insulin secretion may contribute to enhanced muscle glycogen re synthesis following exercise in the fasted state To compare the effectiveness of four dietary preparations for stabilizing resting and exercise measurements , seven male recreational exercisers ( 27 + /- 4 y ) participated in four dietary preparations , each repeated in successive weeks : ( 1 ) 24-h r and om diet including an overnight fast ( RAN ) ; ( 2 ) 24-h r and om diet , including fast , followed by a st and ard meal 3 h before testing ( RANM ) ; ( 3 ) 24-h prescribed diet including an overnight fast ( PRES ) ; and ( 4 ) 24-h prescribed diet , including fast , followed by a st and ard meal ( PRESM ) . After each preparation , metabolic rate ( VO2 ) and respiratory exchange ratio ( RER ) were measured at rest and in association with moderate treadmill exercise . Plasma was analyzed for glucose , cholesterol , and high-density lipoprotein (HDL)-cholesterol . Repeated measures analyses of variance ( ANOVAs ) followed by Tukey posthoc tests indicated that resting VO2 , RER , and blood parameters were not different between the two trials on the same diet . Exercise RER , however , was slightly different in trial 1 than in trial 2 for all preparations except PRESM . Combining both trials , resting VO2 and exercise RER were higher when a pretesting meal was administered . Plasma values were not different for the four dietary preparations . These results suggest that a st and ard overnight fast appears to be adequate for establishing representative and reproducible rest and exercise values for the parameters measured , except possibly for exercise RER reliability PURPOSE AND METHODS Seven subjects exercised to exhaustion on a bicycle ergometer at a workload corresponding to an intensity of 70 % maximal oxygen uptake ( VO2max ) . On one occasion ( FED ) , subjects consumed a preexercise carbohydrate ( CHO ) containing breakfast ( 100 g CHO ) 3 h before exercise . On the other occasion ( FASTED ) , subjects exercised after an overnight fast . Exercise time to fatigue was significantly longer ( P < 0.05 ) when subjects consumed the breakfast ( 136+/-14 min ) compared with when they exercised in the fasted state ( 109+/-12 min ) . RESULTS Pre- and post-exercise muscle glycogen concentrations , respiratory exchange ratio , carbohydrate and fat oxidation , and lactate and insulin concentrations were not significantly different between the two trials . Insulin concentrations decreased significantly ( P < 0.05 ) from 4.7+/-0.05 microIU.mL(-1 ) to 2.8+/-0.4 microIU.mL(-1 ) in FED and from 6.6+/-0.6 microIU.mL(-1 ) to 3.7+/-0.6 microIU.mL(-1 ) in FASTED subjects and free fatty acid concentrations ( FFA ) increased significantly ( P < 0.05 ) from 0.09+/-0.02 mmol . L(-1 ) to 1.4+/-0.6 mmol . L(-1 ) in FED and from 0.17+/-0.02 mmol . L(- ) to 0.74+/-0.27 mmol . L(-1 ) in FASTED subjects over the duration of the trials . CONCLUSIONS In conclusion , the important finding of this study is the increased time to fatigue when subjects ingested the CHO meal with no negative effects ascribed to increased insulin concentrations and decreased FFA concentrations after CHO ingestion Objective : To determine the plasma glucose and insulin responses of various doses of glucose , sucrose , fructose and white bread in normal human subjects . Design : Plasma glucose and insulin were measured before and at various times after 8 subjects ate 13 different test meals in r and omized order on separate days after an overnight fast . Test meals consisted of 500 ml of tea or water to which was added either nothing , 25 , 50 , or 100 g of glucose or sucrose , 25 or 50 g fructose , 50 g glucose plus 50 g fructose , or a 25 , 50 or 100 g carbohydrate portion of white bread . The glycaemic ( GI ) and insulinaemic index ( II ) values of the sugars were calculated by expressing the incremental areas under the plasma glucose and insulin curves ( AUC ) after glucose , sucrose and fructose as a percentage of the respective AUC after white bread containing the same amount of carbohydrate . Setting : University teaching hospital clinical nutrition centre . Subjects : Lean , normal subjects ( 4 male , 4 female ) 21–33 y of age . Results : Plasma insulin responses increased nearly linearly as carbohydrate intake increased from 0 to 100 g , but glycaemic responses increased by only 68 % and 38 % as carbohydrate intake increased from 25 to 50 g and 50 to 100 g , respectively . The GI and II values of glucose , 149±16 and 147±18 , respectively , were significantly greater than those of bread ( 100 ; P<0.05 ) , while the values for fructose , 16±4 and 22±3 were significantly less than those of bread ( P<0.001 ) . GI values did not differ significantly from II values . Conclusions : It is concluded that , in normal subjects , as carbohydrate intake is increased from 0 to 100 g , plasma insulin responses increase at a greater rate than plasma glucose responses . The insulinaemic responses elicited by glucose , sucrose or fructose are similar to those that would be expected from a starchy food with the same glycaemic index . Descriptors |
11,798 | 28,185,757 | Evidence supports mutational testing for EGFR signaling pathway genes , since they provide clinical ly actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC .
Mutations in several of the biomarkers have clear prognostic value . | OBJECTIVES To develop evidence -based guideline recommendations through a systematic review of the literature to establish st and ard molecular biomarker testing of colorectal cancer ( CRC ) tissues to guide epidermal growth factor receptor ( EGFR ) therapies and conventional chemotherapy regimens . | Purpose : Mutations in PIK3CA [ the gene encoding the p110α catalytic subunit of phosphatidylinositide-3-kinase ( PI3 K ) ] play an important role in colorectal carcinogenesis . Experimental evidence suggests that PIK3CA exon 9 and exon 20 mutations trigger different biologic effects , and that concomitant mutations in both exons 9 and 20 synergistically enhance tumorigenic effects . Thus , we hypothesized that PIK3CA exon 9 and exon 20 mutations might have differential effects on clinical outcome in colorectal cancer , and that concomitant PIK3CA exon 9 and 20 mutations might confer aggressive tumor behavior . Experimental Design : We sequenced PIK3CA by pyrosequencing in 1,170 rectal and colon cancers in two prospect i ve cohort studies , and found 189 ( 16 % ) PIK3CA mutated tumors . Mortality HR according to PIK3CA status was computed using Cox proportional hazards model , adjusting for clinical and molecular features , including microsatellite instability , CpG isl and methylator phenotype , LINE-1 methylation , and BRAF and KRAS mutations . Results : Compared with PIK3CA wild-type cases , patients with concomitant PIK3CA mutations in exons 9 and 20 experienced significantly worse cancer-specific survival [ log-rank P = 0.031 ; multivariate HR = 3.51 ; 95 % confidence interval ( CI ) : 1.28–9.62 ] and overall survival ( log-rank P = 0.0008 ; multivariate HR = 2.68 ; 95 % CI : 1.24–5.77 ) . PIK3CA mutation in either exon 9 or 20 alone was not significantly associated with patient survival . No significant interaction of PIK3CA mutation with BRAF or KRAS mutation was observed in survival analysis . Conclusion : Coexistence of PIK3CA ( the PI3 K p110α subunit ) exon 9 and 20 mutations , but not PIK3CA mutation in either exon 9 or 20 alone , is associated with poor prognosis of colorectal cancer patients . Clin Cancer Res ; 18(8 ) ; 2257–68 . © 2012 AACR CONTEXT The fraction of malignant cells in tumor tissue su bmi tted for tests of genetic alterations is a critical variable in testing accuracy . That fraction is currently determined by pathologist visual estimation of the percentage of malignant cells . Inaccuracy could lead to a false-negative test result . OBJECTIVE To describe a prospect i ve , multi-institutional study to determine pathologist estimation accuracy . DESIGN Ten ×20 magnification images of hematoxylin-eosin-stained colon tissue specimens were sent as an educational component of the College of American Pathologists KRAS-B 2011 Survey . Data from 194 labs were analyzed and compared to a criterion st and ard with comprehensive manual nuclear counts . RESULTS Survey responses indicated low interlaboratory precision of pathologist estimation , but mean estimates were fairly accurate . A total of 5 of the 10 cases assessed showed more than 10 % of respondents overestimating in a manner that could lead to false-negative test results . CONCLUSIONS The significance of estimation errors result ing in molecular testing failures with implication s for patient care is unknown , but the current study suggests false-negative test results may occur Lynch syndrome ( LS ) is characterised by the development of colorectal cancer , endometrial cancer and various other cancers , and is caused by a mutation in one of the mismatch repair genes : MLH1 , MSH2 , MSH6 or PMS2 . In 2007 , a group of European experts ( the Mallorca group ) published guidelines for the clinical management of LS . Since then substantial new information has become available necessitating an up date of the guidelines . In 2011 and 2012 workshops were organised in Palma de Mallorca . A total of 35 specialists from 13 countries participated in the meetings . The first step was to formulate important clinical questions . Then a systematic literature search was performed using the Pubmed data base and manual search es of relevant articles . During the workshops the outcome of the literature search was discussed in detail . The guidelines described in this paper may be helpful for the appropriate management of families with LS . Prospect i ve controlled studies should be undertaken to improve further the care of these families Purpose : Cetuximab improves survival in patients with K-ras wild-type advanced colorectal cancer . We examined the predictive and prognostic significance of additional biomarkers in this setting , in particular BRAF , PIK3CA , and PTEN . Experimental Design : Available colorectal tumor sample s were analyzed from the CO.17 study . BRAF mutations were identified in tumor-derived DNA by direct sequencing and PIK3CA mutations were identified using a high-resolution melting screen with confirmation by sequencing . PTEN expression by immunohistochemistry ( IHC ) was performed on tissue microarrays . For each biomarker , prognostic and predictive effects were examined using a Cox model with tests for treatment – biomarker interaction . Results : A total of 572 patients with pretreated colorectal cancer were r and omly assigned to receive cetuximab or best supportive care ( BSC ) . Of 401 patients assessed for BRAF status , 13 ( 3.2 % ) had mutations . Of 407 patients assessed for PIK3CA status , 61 ( 15 % ) had mutations . Of 205 patients assessed for PTEN , 148 ( 72 % ) were negative for IHC expression . None of BRAF , PIK3CA , or PTEN was prognostic for overall or progression-free survival in the BSC arm . None was predictive of benefit from cetuximab , either in the whole study population or the K-ras wild-type subset . In the K-ras wild-type subgroup , the overall survival adjusted HR according to BRAF mutation status was 1.39 ( interaction P = 0.69 ) , PIK3CA mutation status HR = 0.79 ( interaction P = 0.63 ) , and PTEN expression HR = 0.75 ( interaction P = 0.61 ) . Conclusions : In chemotherapy-refractory colorectal cancer , neither PIK3CA mutation status nor PTEN expression were prognostic , nor were they predictive of benefit from cetuximab . Evaluation of predictive significance of BRAF mutations requires a larger sample size . Clin Cancer Res ; 20(3 ) ; 744–53 . © 2013 AACR BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . Background : To test the prognostic value of tumour protein and genetic markers in colorectal cancer ( CRC ) and examine whether deficient mismatch repair ( dMMR ) tumours had a distinct profile relative to proficient mismatch repair ( pMMR ) tumours . Methods : This prospect i ve multicentric study involved 251 stage I – III CRC patients . Analysed biomarkers were EGFR ( binding assay ) , VEGFA , thymidylate synthase ( TS ) , thymidine phosphorylase ( TP ) and dihydropyrimidine dehydrogenase ( DPD ) expressions , MMR status , mutations of KRAS ( codons 12–13 ) , BRAF ( V600E ) , PIK3CA ( exons 9 and 20 ) , APC ( exon 15 ) and P53 ( exons 4–9 ) , CpG isl and methylation phenotype status , ploidy , S-phase , LOH . Results : The only significant predictor of relapse-free survival ( RFS ) was tumour staging . Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated ( P=0.005 ) , BRAF wt ( P=0.009 ) and pMMR tumours ( P=0.036 ) . Deficient mismatch repair tumours significantly demonstrated higher TS ( median 3.1 vs 1.4 ) and TP ( median 5.8 vs 3.5 ) expression relative to pMMR ( P<0.001 ) and show higher DPD expression ( median 14.9 vs 7.9 , P=0.027 ) and EGFR content ( median 69 vs 38 , P=0.037 ) relative to pMMR . Conclusions : Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy BACKGROUND Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor ( EGFR ) therapy . Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy . METHODS In this prospect ive-retrospective analysis , we assessed the efficacy and safety of panitumumab plus oxaliplatin , fluorouracil , and leucovorin ( FOLFOX4 ) as compared with FOLFOX4 alone , according to RAS ( KRAS or NRAS ) or BRAF mutation status . A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following : KRAS exon 3 or 4 ; NRAS exon 2 , 3 , or 4 ; or BRAF exon 15 . The overall rate of ascertainment of RAS status was 90 % . RESULTS Among 512 patients without RAS mutations , progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone ( hazard ratio for progression or death with combination therapy , 0.72 ; 95 % confidence interval [ CI ] , 0.58 to 0.90 ; P=0.004 ) . Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group ( hazard ratio for death , 0.78 ; 95 % CI , 0.62 to 0.99 ; P=0.04 ) . A total of 108 patients ( 17 % ) with nonmutated KRAS exon 2 had other RAS mutations . These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment , which was consistent with the findings in patients with KRAS mutations in exon 2 . BRAF mutations were a negative prognostic factor . No new safety signals were identified . CONCLUSIONS Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4 . In patients who had metastatic colorectal cancer without RAS mutations , improvements in overall survival were observed with panitumumab-FOLFOX4 therapy . ( Funded by Amgen and others ; PRIME Clinical Trials.gov number , NCT00364013 . ) Loss of phosphatase and tensin homologue ( PTEN ) expression may be prognostic in colorectal cancer ( CRC ) and may have a correlation with vascular endothelial growth factor ( VEGF ) expression via hypoxia‐inducible factor 1 ( HIF‐1 ) alpha , and the PI3K/mTOR pathways . We therefore have explored the prognostic association of PTEN loss and the potential that PTEN loss may be predictive of outcome with bevacizumab . Patients enrolled in the AGITG MAX trial , a r and omized Phase III trial of capecitabine ( C ) + /− bevacizumab ( B ) ( + /− mitomycin C [ M ] ) with available tissues were analyzed for PTEN expression ( loss vs. no loss ) as assessed using a Taqman ® copy number assay ( CNA ) . Of the original 471 patients enrolled , tissues from 302 ( 64.1 % ) patients were analyzed . PTEN loss was observed in 38.7 % of patients . There was no relationship between PTEN loss and KRAS or BRAF mutation . PTEN status was not prognostic for progression‐free survival ( PFS ) or overall survival ( OS ) in multivariate analyses adjusting for other baseline factors ; loss versus no loss PFS hazard ratio ( HR ) 0.9 ( 0.7–1.16 ) , OS HR 1.04 ( 0.79–1.38 ) . PTEN was not prognostic when assessed by KRAS and BRAF status . By using the comparison of C versus CB+CBM , PTEN status was not significantly predictive of the effectiveness of B for PFS or OS . PTEN status was not prognostic for survival in advanced colorectal cancer , irrespective of KRAS or BRAF status . PTEN status did not significantly predict different benefit with bevacizumb therapy BACKGROUND Somatic mutations in PIK3CA ( phosphatidylinositol-4,5-bisphosphonate 3-kinase [ PI3 K ] , catalytic subunit alpha gene ) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies , including colorectal cancer . METHODS We examined associations of PIK3CA oncogene mutation with relapse , survival , and treatment efficacy in 627 stage III colon carcinoma case subjects within a r and omized adjuvant chemotherapy trial ( 5-fluorouracil and leucovorin [ FU/LV ] vs irinotecan [ CPT11 ] , fluorouracil and leucovorin [ IFL ] ; Cancer and Leukemia Group B 89803 [ Alliance ] ) . We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing . Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation , adjusting for clinical features and status of routine st and ard molecular pathology features , including KRAS and BRAF mutations and microsatellite instability ( mismatch repair deficiency ) . All statistical tests were two-sided . RESULTS Compared with PIK3CA wild-type cases , overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free , disease-free , or overall survival ( log-rank P > .70 ; P > .40 in multivariable regression models ) . There was no statistically significant interaction between PIK3CA and KRAS ( or BRAF ) mutation status in survival analysis ( P(interaction ) > .18 ) . PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy ( P(interaction ) > .16 ) . CONCLUSIONS Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis . PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy AIMS The aim of this study is to evaluate if mismatch repair ( MMR ) defective colorectal cancer has a different response to adjuvant 5-fluorouracil ( 5-FU ) chemotherapy in a cohort of patients prospect ively followed during 5 years . METHODS The cohort included 754 surgically treated patients with colorectal cancer . MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis . Median follow-up was 49.2 months ( range 1 - 73 ) . At inclusion , 505 patients were diagnosed as TNM II or III stage , analysis of the efficacy of adjuvant chemotherapy was made on this population . Adjuvant chemotherapy was applied to 248 patients ( 98.2 % 5-FU based ) . RESULTS MMR deficiency was found in 76 patients ( 10.1 % ) . No differences were found in overall survival ( log-rank p=0.3 ) or disease-free survival ( log-rank p=0.3 ) regarding MMR status . Adjuvant chemotherapy improves survival in patients in the II or III stage , but this improvement is only evident in patients with MMR-competent tumours ( log-rank p=0.00001 ) . Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy ( log-rank p=0.7 ) . A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy ( Hazard ratio 2.04 ; 95 % confidence interval : 1.42 - 2.93 ) . CONCLUSION In a cohort of colorectal cancer patients , those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy PURPOSE Aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) protect against colorectal cancer ( CRC ) and are associated with reduced disease recurrence and improved outcome after primary treatment . However , toxicities of NSAIDs have limited their use as antineoplastic therapy . Recent data have suggested that the benefit of aspirin after CRC diagnosis is limited to patients with PIK3CA-mutant cancers . We sought to determine the predictive utility of PIK3CA mutation for benefit from both cyclooxygenase-2 inhibition and aspirin . METHODS We performed molecular analysis of tumors from 896 participants in the Vioxx in Colorectal Cancer Therapy : Definition of Optimal Regime ( VICTOR ) trial , a large r and omized trial comparing rofecoxib with placebo after primary CRC resection . We compared relapse-free survival and overall survival between rofecoxib therapy and placebo and between the use and nonuse of low-dose aspirin , according to tumor PIK3CA mutation status . RESULTS We found no evidence of a greater benefit from rofecoxib treatment compared with placebo in patients whose tumors had PIK3CA mutations ( multivariate adjusted hazard ratio [ HR ] , 1.2 ; 95 % CI , 0.53 to 2.72 ; P = .66 ; (P)INTERACTION = .47 ) compared with patients with PIK3CA wild-type cancers ( HR , 0.87 ; 95 % CI , 0.64 to 1.16 ; P = .34 ) . In contrast , regular aspirin use after CRC diagnosis was associated with a reduced rate of CRC recurrence in patients with PIK3CA-mutant cancers ( HR , 0.11 ; 95 % CI , 0.001 to 0.832 ; P = .027 ; (P)INTERACTION = .024 ) but not in patients lacking tumor PIK3CA mutation ( HR , 0.92 ; 95 % CI , 0.60 to 1.42 ; P = .71 ) . CONCLUSION Although tumor PIK3CA mutation does not predict benefit from rofecoxib treatment , it merits further evaluation as a predictive biomarker for aspirin therapy . Our findings are concordant with recent data and support the prospect i ve investigation of adjuvant aspirin in PIK3CA-mutant CRC BACKGROUND Epidemiologic evidence indicates that aspirin use is associated with reduced risks of colon cancer and possibly several other cancers , including prostate and breast cancers . Recent results from the Women 's Health Study r and omized trial indicate that long-term use of low-dose aspirin ( 100 mg every other day ) does not substantially reduce cancer risk . However , the potential effect of long-term daily use of higher doses of aspirin on cancer incidence remains uncertain . METHODS We examined associations between long-term daily use of adult-strength aspirin ( > or = 325 mg/day ) and both overall cancer incidence and incidence of 10 types of cancer among 69,810 men and 76,303 women participating in the Cancer Prevention Study II Nutrition Cohort , a relatively elderly population . Aspirin use was reported at enrollment in 1992 - 1993 and up date d in 1997 , 1999 , and 2001 . Multivariable Cox proportional hazards regression was used to calculate rate ratios ( RRs ) . RESULTS During follow-up through June 2003 , 10,931 men and 7196 women were diagnosed with cancer . Long-term ( > or = 5 years ) daily use of adult-strength aspirin , compared with no use , was associated with lower overall cancer incidence in men ( multivariable-adjusted RR = 0.84 , 95 % confidence interval [ CI ] = 0.76 to 0.93 ) and non-statistically significantly lower overall cancer incidence in women ( multivariable-adjusted RR = 0.86 , 95 % CI = 0.73 to 1.03 ) . Overall cancer incidence per 100,000 person-years ( st and ardized to the age distributions of men and women in the study ) with long-term daily aspirin use and no aspirin use was 1858 and 2163 , respectively , among men and 1083 and 1169 , respectively , among women . Long-term daily aspirin use was associated with lower incidence of colorectal cancer ( RR = 0.68 , 95 % CI = 0.52 to 0.90 among men and women combined ) and prostate cancer ( RR = 0.81 , 95 % CI = 0.70 to 0.94 ) and a non-statistically significant lower risk of female breast cancer ( RR = 0.83 , 95 % CI = 0.63 to 1.10 ) . CONCLUSIONS Long-term daily use of adult-strength aspirin may be associated with modestly reduced overall cancer incidence in population s among whom colorectal , prostate , and breast cancers are common PURPOSE The phase III CRYSTAL study demonstrated that addition of cetuximab to fluorouracil , leucovorin , and irinotecan ( FOLFIRI ) significantly improved overall survival , progression-free survival , and objective response in the first-line treatment of patients with KRAS codon 12/13 ( exon 2 ) wild-type metastatic colorectal cancer ( mCRC ) . Outcome was reassessed in subgroups defined by extended RAS mutation testing . PATIENTS AND METHODS Existing DNA sample s from KRAS exon 2 wild-type tumors from CRYSTAL study patients were reanalyzed for other RAS mutations in four additional KRAS codons ( exons 3 and 4 ) and six NRAS codons ( exons 2 , 3 , and 4 ) using beads , emulsion , amplification , and magnetics technology . No tissue microdissection was performed . A ≥ 5 % mutant allele cutoff was used to call mutations . RESULTS Mutation status was evaluable in 430 ( 64.6 % ) of 666 patients with KRAS exon 2 wild-type tumors . Other RAS mutations were detected in 63 ( 14.7 % ) of 430 patients . In those with RAS wild-type tumors , a significant benefit across all efficacy end points was associated with the addition of cetuximab to FOLFIRI . In patients with other RAS tumor mutations , no difference in efficacy outcomes between treatment groups was seen . The safety profile in RAS subgroups was similar and in line with expectations . CONCLUSION In the first-line treatment of mCRC , patients with RAS wild-type tumors derived a significant benefit from the addition of cetuximab to FOLFIRI ; patients with RAS tumor mutations did not . Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy , thereby allowing the further tailoring of cetuximab administration to maximize patient benefit Abstract Background . Recent data have suggested that regular aspirin use improves overall and cancer-specific survival in the subset of colorectal cancer ( CRC ) patients harboring PIK3CA mutations . However , the number of PIK3CA-mutated CRC patients examined in these studies was modest . Our collaborative study aims to vali date the association between regular aspirin use and survival in patients with PIK3CA-mutated CRC . Patients and methods . Patients with PIK3CA-mutated CRC were identified at Moffitt Cancer Center ( MCC ) in the United States and Royal Melbourne Hospital ( RMH ) in Australia . Prospect i ve clinicopathological data and survival data were available . At MCC , PIK3CA mutations were identified by targeted exome sequencing using the Illumina GAIIx Next Generation Sequencing platform . At RMH , Sanger sequencing was utilized . Multivariate survival analyses were conducted using Cox logistic regression . Results . From a cohort of 1487 CRC patients , 185 patients harbored a PIK3CA mutation . Median age of patients with PIK3CA-mutated tumors was 72 years ( range : 34–92 ) and median follow up was 54 months . Forty-nine ( 26 % ) patients used aspirin regularly . Regular aspirin use was not associated with improved overall survival ( multivariate HR 0.96 , p = 0.86 ) . There was a trend towards improved cancer-specific survival ( multivariate HR 0.60 , p = 0.14 ) , but this was not significant . Conclusions . Despite examining a large number of patients , we did not confirm that regular aspirin use was associated with statistically significant improvements in survival in PIK3CA-mutated CRC patients . Prospect i ve evaluation of this relationship is warranted PURPOSE PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis . However , little is known about the prognostic role of PIK3CA mutation in colon cancer . PATIENTS AND METHODS Using 450 resectable colon cancers ( stage I to III ) in two independent prospect i ve cohorts , we detected PIK3CA mutation in 82 tumors ( 18 % ) by pyrosequencing . Cox proportional hazards models were used to calculate hazard ratios ( HRs ) of colon cancer-specific and overall mortalities , adjusted for patient characteristics and tumoral molecular features , including the CpG isl and methylation phenotype , microsatellite instability ( MSI ) , LINE-1 hypomethylation , and p53 , CIMP , KRAS and BRAF mutation . RESULTS Compared with patients with PIK3CA wild-type tumors , those with PIK3CA-mutated tumors experienced an increase in colon cancer-specific mortality according to univariate analysis ( HR = 1.64 ; 95 % CI , 0.95 to 2.86 ) , which persisted after adjusting for other known or potential risk factors for cancer recurrence ( including MSI ; multivariate HR = 2.23 ; 95 % CI , 1.21 to 4.11 ) . The effect of PIK3CA mutation on cancer survival seemed to differ according to KRAS mutational status . Among patients with KRAS wild-type tumors , the presence of PIK3CA mutation was associated with a significant increase in colon cancer-specific mortality ( HR = 3.80 ; 95 % CI , 1.56 to 9.27 ) . In contrast , PIK3CA mutation conferred no significant effect on mortality among patients with KRAS-mutated tumors ( HR = 1.25 ; 95 % CI , 0.52 to 2.96 ) . CONCLUSION Among patients who undergo a curative resection of colon cancer , PIK3CA mutation is associated with shorter cancer-specific survival . The adverse effect of PIK3CA mutation may be potentially limited to patients with KRAS wild-type tumors Importance The prognostic value of BRAF and KRAS mutations in patients who have undergone resection for colon cancer and have been treated with combination leucovorin , fluorouracil , and oxaliplatin (FOLFOX)-based adjuvant chemotherapy is controversial , possibly owing to a lack of stratification on mismatch repair status . Objective To examine the prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with adjuvant FOLFOX with or without cetuximab . Design , Setting , and Participants This study included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated between December 2005 and November 2009 in the PETACC-8 phase III r and omized trial . Mismatch repair , BRAF V600E , and KRAS exon 2 mutational status were determined on prospect ively collected tumor blocks from 2559 patients enrolled in the PETACC-8 trial . The data were analyzed in April 2015 . Intervention Patients were r and omly assigned to receive 6 months of FOLFOX4 or FOLFOX4 plus cetuximab after surgical resection for stage III colon cancer . Main Outcomes and Measures Associations between these biomarkers and disease-free survival ( DFS ) and overall survival ( OS ) were analyzed with Cox proportional hazards models . Multivariate models were adjusted for covariates ( age , sex , tumor grade , T/N stage , tumor location , Eastern Cooperative Oncology Group performance status ) . Results Among the 2559 patients enrolled in the PETACC-8 trial ( 42.9 % female ; median [ range ] age , 60.0 [ 19.0 - 75.0 ] years ) , microsatellite instability ( MSI ) phenotype , KRAS , and BRAF V600E mutations were detected in , respectively , 9.9 % ( 177 of 1791 ) , 33.1 % ( 588 of 1776 ) , and 9.0 % ( 148 of 1643 ) of cases . In multivariate analysis , MSI ( hazard ratio [ HR ] for DFS : 1.10 [ 95 % CI , 0.73 - 1.64 ] , P = .67 ; HR for OS : 1.02 [ 95 % CI , 0.61 - 1.69 ] , P = .94 ) and BRAF V600E mutation ( HR for DFS : 1.22 [ 95 % CI , 0.81 - 1.85 ] , P = .34 ; HR for OS : 1.13 [ 95 % CI , 0.64 - 2.00 ] , P = .66 ) were not prognostic , whereas KRAS mutation was significantly associated with shorter DFS ( HR , 1.55 [ 95 % CI , 1.23 - 1.95 ] ; P < .001 ) and OS ( HR , 1.56 [ 95 % CI , 1.12 - 2.15 ] ; P = .008 ) . The subgroup analysis showed in patients with microsatellite-stable tumors that both KRAS ( HR for DFS : 1.64 [ 95 % CI , 1.29 - 2.08 ] , P < .001 ; HR for OS : 1.71 [ 95 % CI , 1.21 - 2.41 ] , P = .002 ) and BRAF V600E mutation ( HR for DFS : 1.74 [ 95 % CI , 1.14 - 2.69 ] , P = .01 ; HR for OS : 1.84 [ 95 % CI , 1.01 - 3.36 ] , P = .046 ) were independently associated with worse clinical outcomes . In patients with MSI tumors , KRAS status was not prognostic , whereas BRAF V600E mutation was associated with significantly longer DFS ( HR , 0.23 [ 95 % CI , 0.06 - 0.92 ] ; P = .04 ) but not OS ( HR , 0.19 [ 95 % CI , 0.03 - 1.24 ] ; P = .08 ) . Conclusions and Relevance BRAF V600E and KRAS mutations were significantly associated with shorter DFS and OS in patients with microsatellite-stable tumors but not in patients with MSI tumors . Future trials in the adjuvant setting will have to take into account mismatch repair , BRAF , and KRAS status for stratification . Trial Registration EudraCT 2005 - 003463 - 23 OBJECTIVE To establish evidence -based recommendations for the molecular analysis of lung cancers that are required to guide EGFR- and ALK-directed therapies , addressing which patients and sample s should be tested , and when and how testing should be performed . PARTICIPANTS Three cochairs without conflicts of interest were selected , one from each of the 3 sponsoring professional societies : College of American Pathologists , International Association for the Study of Lung Cancer , and Association for Molecular Pathology . Writing and advisory panels were constituted from additional experts from these societies . EVIDENCE Three unbiased literature search es of electronic data bases were performed to capture published articles from January 2004 through February 2012 , yielding 1533 articles whose abstract s were screened to identify 521 pertinent articles that were then review ed in detail for their relevance to the recommendations . EVIDENCE was formally grade d for each recommendation . CONSENSUS PROCESS Initial recommendations were formulated by the cochairs and panel members at a public meeting . Each guideline section was assigned to at least 2 panelists . Drafts were circulated to the writing panel ( version 1 ) , advisory panel ( version 2 ) , and the public ( version 3 ) before su bmi ssion ( version 4 ) . CONCLUSIONS The 37 guideline items address 14 subjects , including 15 recommendations ( evidence grade A/B ) . The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor ( EGFR ) or anaplastic lymphoma kinase ( ALK ) inhibitor , respectively , in all patients with advanced-stage adenocarcinoma , regardless of sex , race , smoking history , or other clinical risk factors , and to prioritize EGFR and ALK testing over other molecular predictive tests . As scientific discoveries and clinical practice outpace the completion of r and omized clinical trials , evidence -based guidelines developed by expert practitioners are vital for communicating emerging clinical st and ards . Already , new treatments targeting genetic alterations in other , less common driver oncogenes are being evaluated in lung cancer , and testing for these may be addressed in future versions of these guidelines BACKGROUND Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors . We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer . METHODS Tumor specimens were collected from patients with colon cancer who were enrolled in r and omized trials of fluorouracil-based adjuvant chemotherapy . Microsatellite instability was assessed with the use of mononucleotide and dinucleotide markers . RESULTS Of 570 tissue specimens , 95 ( 16.7 percent ) exhibited high-frequency microsatellite instability . Among 287 patients who did not receive adjuvant therapy , those with tumors displaying high-frequency microsatellite instability had a better five-year rate of overall survival than patients with tumors exhibiting microsatellite stability or low-frequency instability ( hazard ratio for death , 0.31 [ 95 percent confidence interval , 0.14 to 0.72 ] ; P=0.004 ) . Among patients who received adjuvant chemotherapy , high-frequency microsatellite instability was not correlated with increased overall survival ( hazard ratio for death , 1.07 [ 95 percent confidence interval , 0.62 to 1.86 ] ; P=0.80 ) . The benefit of treatment differed significantly according to the microsatellite-instability status ( P=0.01 ) . Adjuvant chemotherapy improved overall survival among patients with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability , according to a multivariate analysis adjusted for stage and grade ( hazard ratio for death , 0.72 [ 95 percent confidence interval , 0.53 to 0.99 ] ; P=0.04 ) . By contrast , there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability . CONCLUSIONS Fluorouracil-based adjuvant chemotherapy benefited patients with stage II or stage III colon cancer with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability but not those with tumors exhibiting high-frequency microsatellite instability BACKGROUND & AIMS Long-term data on the risk of colorectal cancer according to dose , duration , and consistency of aspirin therapy are limited . METHODS We conducted a prospect i ve study of 47,363 male health professionals who were ages 40 - 75 years at enrollment in 1986 . Biennially , we collected data on aspirin use , other risk factors , and diagnoses of colorectal cancer . We confirmed all reports of colorectal cancer through 2004 by review of medical records . RESULTS During 18 years of follow-up , we documented 975 cases of colorectal cancer over 761,757 person-years . After adjustment for risk factors , men who regularly used aspirin ( > /=2 times per week ) had a multivariate relative risk ( RR ) for colorectal cancer of 0.79 ( 95 % confidence interval , [ CI ] , 0.69 - 0.90 ) compared with nonregular users . However , significant risk reduction required at least 6 - 10 years of use ( P for trend = .008 ) and was no longer evident within 4 years of discontinuing use ( multivariate RR , 1.00 ; CI , 0.72 - 1.39 ) . The benefit appeared related to increasing cumulative average dose : compared with men who denied any aspirin use , the multivariate RRs for cancer were 0.94 ( CI , 0.75 - 1.18 ) for men who used 0.5 - 1.5 st and ard aspirin tablets per week , 0.80 ( CI , 0.63 - 1.01 ) for 2 - 5 aspirin tablets per week , 0.72 ( CI , 0.56 - 0.92 ) for 6 - 14 aspirin tablets per week , and 0.30 ( CI , 0.11 - 0.81 ) for > 14 aspirin tablets per week ( P for trend = .004 ) . CONCLUSIONS Regular , long-term aspirin use reduces risk of colorectal cancer among men . However , the benefit of aspirin necessitates at least 6 years of consistent use , with maximal risk reduction at doses greater than 14 tablets per week . The potential hazards associated with long-term use of such doses should be carefully considered AIMS Patients with metastatic colorectal carcinoma ( mCRC ) carrying activating mutations of the KRAS gene do not benefit from treatment with anti-EGF receptor monoclonal antibodies . Therefore , KRAS mutation testing of mCRC patients is m and atory in the clinical setting to aid in the choice of appropriate therapy . MATERIAL S & METHODS We developed a cost-effective approach for the determination of KRAS mutations in codons 12 and 13 in clinical practice based on a sensitive PCR/sequencing technique and the commercially available real-time PCR-based Therascreen kit ( DxS Ltd ) . RESULTS & CONCLUSION The PCR/sequencing test was able to detect 10 % mutant DNA in a background of wild-type DNA . By using this assay , we determined the mutational status of KRAS in 527 out of 540 ( 97.6 % ) formalin-fixed paraffin-embedded tissues from mCRC patients . PCR/sequencing was not conclusive in 13 cases , in which low-intensity peaks suggestive of potential mutations were identified . The DxS assay , which showed a sensitivity of 1 % , identified mutations in 11 out of 13 inconclusive cases . Interestingly , five of these 11 cases showed high levels of DNA fragmentation . No significant difference was found in the ability of PCR/sequencing and DxS to identify KRAS mutations within 160 cases with more than 30 % tumor cells . However , in 24 sample s with less than 30 % tumor cells , DxS showed an higher sensitivity . In conclusion , our findings suggest that PCR/sequencing can be used for mutational analysis of the majority of tumor sample s that have more than 30 % tumor cell content , whereas more sensitive and expensive tests should be reserved for inconclusive cases and for sample s with a low amount of tumor cells |
11,799 | 29,354,065 | Conclusion : Compared to no exercise or other types of exercise with low-to-moderate intensity , Tai Chi seems a good choice for coronary disease rehabilitation in improving cardiorespiratory fitness . | Background : Tai Chi that originated in China as a martial art is an aerobic exercise with low-to-moderate intensity and may play a role in cardiac rehabilitation .
Aim : To systematic ally review the effect of Tai Chi on cardiorespiratory fitness for coronary disease rehabilitation . | Background —Tai Chi Chuan ( TTC ) exercise has beneficial effects on the components of physical condition and can produce a substantial reduction in the risk of multiple falls . Previous studies have shown that short term TCC exercise did not improve the scores in the single leg stance test with eyes closed and the sit and reach test . There has apparently been no research into the effects of TCC on total body rotation flexibility and heart rate responses at rest and after a three minute step test . Methods —In this cross sectional study , 28 male TCC practitioners with an average age of 67.5 years old and 13.2 years of TCC exercise experience were recruited to form the TCC group . Another 30 sedentary men aged 66.2 were selected to serve as the control group . Measurements included resting heart rate , left and right single leg stance with eyes closed , modified sit and reach test , total body rotation test ( left and right ) , and a three minute step test . Results —Compared with the sedentary group , the TCC group had significantly better scores in resting heart rate , three minute step test heart rate , modified sit and reach , total body rotation test on both right and left side ( p<0.01 ) , and both right and left leg st and ing with eyes closed ( p<0.05 ) . According to the American Fitness St and ards , the TCC group attained the 90th percentile rank for sit and reach and total body rotation test , right and left . Conclusion —Long term regular TCC exercise has favourable effects on the promotion of balance control , flexibility , and cardiovascular fitness in older adults BACKGROUND Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results . Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis . We therefore conducted a prospect i ve study of the effect of exercise training on endothelial function in patients with coronary artery disease . METHODS We r and omly assigned 19 patients with coronary endothelial dysfunction , indicated by abnormal acetylcholine-induced vasoconstriction , to an exercise-training group ( 10 patients ) or a control group ( 9 patients ) . To reduce confounding , patients with coronary risk factors that could be influenced by exercise training ( such as diabetes , hypertension , hypercholesterolemia , and smoking ) were excluded . In an initial study and after four weeks , the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine ( 0.072 , 0.72 , and 7.2 microg per minute ) were assessed . The mean peak flow velocity was measured by Doppler velocimetry , and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography . RESULTS In the initial study , the two groups had similar vasoconstrictive responses to acetylcholine . After four weeks of exercise training , coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent ( from a mean [ + /-SE ] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks ; P<0.05 for the comparison with the change in the control group ) . In the exercise-training group , the increases in mean peak flow velocity in response to 0.072 , 0.72 , and 7.2 microg of acetylcholine per minute were 12+/-7 , 36+/-11 , and 78+/-16 percent , respectively , in the initial study . After four weeks of exercise , the increases in response to acetylcholine were 27+/-7 , 73+/-19 , and 142+/-28 percent ( P<0.01 for the comparison with the control group ) . Coronary blood-flow reserve ( the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity ) increased by 29 percent after four weeks of exercise ( from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks ; P<0.01 for the comparison with the control group ) . CONCLUSIONS Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease INTRODUCTION In patients with cardiac diseases , lifestyle changes such as an increase in physical activity are recommended to prevent further cardiac events . In Germany this is possible by attending outpatient heart groups . A problem inherent in these programs is the lack of adherence since more than two thirds of patients stop attending cardiac rehabilitation programs after six months . An alternative to the conventional implementation of heart groups is Tai Chi , which was found to improve adherence to cardiac rehabilitation programs in international studies . METHODS Patients were r and omly assigned to a conventional heart group or a heart group with Tai Chi exercises . At the beginning of the study , a medical history was taken and physical and instrumental tests were carried out , including an assessment of anxiety/depression ( HADS question naire ) and physical well-being ( SD-12 ) . Follow-up tests were performed every three months . RESULTS Patients were 62.6 ± 8.5 years old , the mean BMI was 28.6 ± 62 kg/m(2 ) , and the proportion of women was 29.8 % . The groups were different in terms of age ( conventional heart group : 65.0 ± 7.5 ; Tai Chi group : 59.9 ± 8.9 years ) . Therefore , age-adjusted analyses were performed in addition to the planned analyses . Regarding the primary endpoint of the study , there was no difference between the groups . After twelve months , 50 % of subjects were active in the Tai Chi group and 48 % in the conventional heart group ( odds ratio 0.92 , p = 0.891 ) . After adjustment for age by logistic regression , the odds ratio was 0.47 ( p = 0.285 ) . Furthermore , both the participation period in weeks ( Tai Chi group : 43.3 ± 26.0 ; conventional group : 45.5 ± 24.2 , p = 0.766 ) and the participation rate ( Tai Chi group : 66.8 ± 19.2 % Tai Chi , conventional group : 76.3 ± 16.5 % , p = 0.074 ) did not differ between the two groups . A further analysis showed a non-significant trend for improvement of anxiety , depression and physical well-being in the Tai Chi group compared with the conventional group . CONCLUSION The insight gained in international studies regarding a better adherence to Tai Chi-guided prevention programs was not transferable to heart group participants from Germany . However , there was a trend regarding a better mental condition in the Tai Chi group PURPOSE This study prospect ively evaluated the training effect of a 1-yr Tai Chi Chuan ( TCC ) program for low-risk patients with coronary artery bypass surgery ( CABS ) after a postoperative outpatient ( phase II ) cardiac rehabilitation program . METHODS Twenty patients with mean age of 56.5+/-7.4 yr completed this study . The TCC group included nine men who practice d classical Yang TCC with an exercise intensity of 48 - 57 % heart rate range ( HRR ) . The control group included 11 men whom were recommended to do a home-based self-adjusted exercise program with similar intensity of phase II cardiac rehabilitation . Grade d exercise tests were performed before and after 1 yr of training for all subjects . RESULTS Mean attendance of the TCC group was 3.8+/-1.5 times weekly in contrast to 1.7+/-1.1 times for the control group . During the follow-up examination , the TCC group increased 10.3 % in VO2peak ( from 26.2+/-4.4 to 28.9+/-5.0 mL x kg(-1 ) min(-1 ) , P<0.01 ) and increased 11.9 % in peak work rate ( from 135+/-26 W to 151+/-28 W , P<0.01 ) . However , the control group showed slight decrease in VO2peak from 26.0+/-3.9 to 25.6+/-4.6 mL x kg(-1 ) x min(-1 ) and in peak work rate from 131+/-23 W to 128+/-32 W. At the ventilatory threshold , the TCC group also showed significant increase in VO2 and work rate ( P<0.05 ) . The control group did not significantly change in these variables . CONCLUSIONS The study demonstrated that a 1-yr TCC program for low-risk patients with CABS could favorably enhance cardiorespiratory function BACKGROUND Patients with a recent myocardial infa rct ion ( MI ) present a reduction in functional capacity expressed as a decrease in peak oxygen consumption ( Vo2 peak ) . The impact of a Tai Chi Chuan ( TCC ) cardiac rehabilitation program for patients recovering from recent MI has yet to be assessed . Our goal is to evaluate functional capacity after a TCC-based cardiac rehabilitation program in patients with recent MI . METHODS A single-blind r and omized clinical trial was conducted . The research ers who performed the tests were blinded to group allocation . Between the 14th and 21st days after hospital discharge , all patients performed a cardiopulmonary exercise testing and a laboratory blood workup . Mean age was similar ( 56±9 years in the TCC group and 60±9 years in the control group ) . Patients allocated to the intervention group performed 3 weekly sessions of TCC Beijin style for 12 weeks ( n=31 ) . The control group participated in 3 weekly sessions of full-body stretching exercises ( n=30 ) . RESULTS After the 12-week study period , participants in the TCC group experienced a significant 14 % increase in Vo2 peak from baseline ( 21.6 ± 5.2 to 24.6 ± 5.2 mL/kg per minute ) , whereas control participants had a nonsignificant 5 % decline in Vo2 peak ( 20.4 ± 5.1 to 19.4 ± 4.4 mL/kg per minute ) . There was a significant difference between the 2 groups ( P<.0001 ) . CONCLUSIONS Tai Chi Chuan practice was associated with an increase in Vo2 peak in patients with a recent MI and may constitute an effective form of cardiac rehabilitation in this patient population Tai chi -- moving for better balance , a falls-prevention program developed from a r and omized controlled trial for community-based use , was evaluated with the re- aim framework in 6 community centers . The program had a 100 % adoption rate and 87 % reach into the target older adult population . All centers implemented the intervention with good fidelity , and participants showed significant improvements in health-related outcome measures . This evidence -based tai chi program is practical to disseminate and can be effectively implemented and maintained in community setting |
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